Osmosis High-Yield Notes Pathology Volume 2

NOTES
NOTES
ACUTE CORONARY SYNDROMES
GENERALLY, WHAT ARE THEY?

PATHOLOGY & CAUSES TREATMENT
▪ Signs and symptoms caused by decreased MEDICATIONS
blood flow in the coronary arteries to the ▪ Oxygen as needed
extent that the muscle cannot function ▪ Pain control with nitrates and/or morphine
properly, or even dies
▪ Antiplatelets
▪ Acute coronary syndromes are almost
▪ Anticoagulants
always due to atherosclerosis
▪ Nitrates: decreases preload by vasodilation
▪ Beta blockers: reduces cardiac demand by
SIGNS & SYMPTOMS decreasing heart rate, BP and contractility
(first-line choice: metoprolol)
▪ See individual disorders ▪ Statins: HMG-CoA reductase inhibitor
that reduces production of cholesterol to
improve lipid profile
DIAGNOSIS
OTHER INTERVENTIONS
▪ See individual disorders
▪ Hospital admission with continuous
monitoring
▪ Reestablish blood flow via catheterization /
revascularization
▪ Lifestyle changes: improve diet (reduce
intake of saturated fat), smoking cessation,
control blood pressure, strict management
of diabetes mellitus, increase exercise,
weight loss, improve lipid profile
Figure 1.1 Illustration depicting ST depression and ST elevation seen in myocardial infarctions.
OSMOSIS.ORG 1
MYOCARDIAL INFARCTION (MI)
osms.it/myocardial-infarction
COMPLICATIONS
PATHOLOGY & CAUSES ▪ Heart failure: heart muscle fails to
compensate for damage; risk related to
▪ Death of heart muscle cells due to lack of size/territory of infarct and individual’s
oxygen-rich blood flow baseline cardiac function
▪ Plaque buildup (fat, cholesterol, proteins, ▪ Cardiac arrhythmia: may be seen
calcium, white blood cells) takes years to within minutes after MI or years later. If
form in lumen undiagnosed MI, may be cause of death
▪ Blood platelets adhere to plaque and ▪ Left ventricular (LV) failure and pulmonary
enhance clotting process, creating edema: happens after left ventricular
blockage infarction, free wall rupture, ventricular
▪ Necrosis of myocardial cells follows series septal defect, papillary muscle rupture with
of events mitral regurgitation
▫ < 24 hrs: early coagulative necrosis, cell ▪ Postinfarction pericarditis, papillary muscle
debris in blood, edema, wavy fibers and rupture (might lead to acute, severe mitral
hemorrhage regurgitation), interventricular septal
▫ 1–3 days: extensive necrosis, tissue has rupture, ventricular pseudoaneurysm
acute inflammation with neutrophils formation, ventricular free wall rupture
▫ 3–14 days: macrophages and (might lead to ventricular free wall rupture
granulation tissue in margins leading to pericardial tamponade/ventricular
▫ > 14 days: contracted scar forms pseudoaneurysm), true ventricular
aneurysm, Dressler syndrome
TYPES
MNEMONIC: DARTH VADER
ST segment elevation myocardial infarction
(STEMI) Complications of MI
▪ Coronary artery completely blocked; full Death
thickness of myocardial wall involved Arrythmia
▪ ECG shows ST elevation, possible Q waves Rupture (free ventricular wall/
ventricular septum/papillary
Non-ST segment elevation MI (NSTEMI) muscles)
▪ Coronary artery not completely blocked, Tamponade
subendocardium may be especially Heart failure (acute or chronic)
vulnerable to ischemia
Valve disease
▪ ECG shows ST depression
Aneurysm of ventricles
Dressler's syndrome
RISK FACTORS thromboEmbolism (mural
▪ Modifiable risk factors: older age, smoking, thrombus)
high blood pressure, diabetes mellitus, high Recurrence/ mitral
cholesterol, low levels of physical activity, Regurgitation
obesity, excessive alcohol use, illegal drug
use (e.g., cocaine, amphetamines), chronic
stress
▪ Non-modifiable risk factors: family history,
biological male
2 OSMOSIS.ORG
Chapter 1 Acute Coronary Syndromes
SIGNS & SYMPTOMS TREATMENT

▪ Acute chest pain lasting > 20 min, ▪ STEMI first priority: emergent reperfusion
radiating to arm/jaw via percutaneous coronary intervention (e.g.
▪ Uncomfortable chest/back/neck/ catheterization)/thrombolysis
jaw/stomach pain, dyspnea, fatigue, ▫ Very time sensitive
diaphoresis, and/or nausea ▪ NSTEMI: reperfusion via percutaneous
▪ Feeling of fullness/indigestion coronary intervention (not thrombolysis)
▫ Less time sensitive than in STEMI
DIAGNOSIS MEDICATIONS
LAB RESULTS ▪ Heparin, aspirin + clopidogrel, beta
blockers, ACE inhibitors, statins
▪ Usually detected with diagnostic laboratory
work for cardiac enzymes ▪ Control symptoms with morphine and
nitroglycerin
▫ Troponin I, troponin T most specific,
sensitive markers: rise apparent within
2–4 hrs, peaking ~24 hrs
▫ CK-MB can detect reinfarction after
initial MI: levels increased 4 hrs after
infarction, peak at 24 hrs, return to
normal after 48 hrs
OTHER DIAGNOSTICS
ECG
▪ Can confirm diagnosis; time sensitive, not
accurate after 6 hours
▪ < 30 min: ST segment elevation
▫ Only seen in STEMIs Figure 1.3 Gross pathology of a ruptured
▫ ST depression/no ST segment deviation papillary muscle, a serious complication of
would be seen in NSTEMIs myocardial infarction.
▪ < 24 hrs: T wave inversion
▪ > 24 hrs: Q waves appear
Figure 1.4 Histological appearance of the

myocardium following a myocardial infarct.
Figure 1.2 A pathology pot containing a heart
exhibiting an anterior myocardial infarction,
usually the result of left anterior descending
artery disease.
OSMOSIS.ORG 3
PRINZMETAL'S ANGINA
osms.it/prinzmetals-angina

▪ AKA vasospastic angina/variant angina MEDICATIONS
Calcium channel blockers
CAUSES
▪ Coronary artery vasospasms; occur Vasodilators
spontaneously even at rest ▪ Increases coronary blood flow to heart
▪ Vasospasms: constriction of the smooth
muscle surrounding the artery, reducing
blood flow through the vessel
▫ Cause of vasospasms not
well understood; likely due to
vasoconstrictors such as platelet
thromboxane A2
▫ Coronary artery vasospasms cause
ischemia throughout all of the heart
layers
SIGNS & SYMPTOMS

▪ Same as stable angina, except pain may
occur at rest
▪ Pain described as pressure, squeezing,
burning, or tightness; can radiate to the
either/both arms, jaw, shoulders, and back;
lasts less than 20 minutes
▪ Other symptoms: Levine’s sign (a clenched
fist held over the chest), dyspnea,
diaphoresis, fatigue, nausea, and epigastric
pain
DIAGNOSIS
DIAGNOSTIC IMAGING
▪ Transient ST segment elevation
▪ Illustrates transmural ischemia
4 OSMOSIS.ORG
Chapter 1 Acute Coronary Syndromes
UNSTABLE ANGINA
osms.it/unstable-angina
PATHOLOGY & CAUSES DIAGNOSIS

▪ Episodic chest pain that either LAB RESULTS
▫ Is new in onset ▪ Serial troponins measured for individuals
▫ Occurs at rest unpredictably with unstable angina to rule out myocardial
▫ Rapidly worsens over time infarction
▫ Occurs within 48 hrs after acute MI ▪ Troponin released after injury to myocytes
is a marker for myocardial injury
▪ Usually caused by ruptured atherosclerotic
plaque → formation of thrombosis on top
of plaque → almost complete blockage in OTHER DIAGNOSTICS
blood vessel → ischemia → pain
ECG
▪ Medical emergency: high risk of
progression to MI ▪ Can present with ST segment depression
▫ Angina: myocytes still alive ▫ May also present with T wave
inversions
▫ Myocardial infarction: death of
myocytes ▫ Illustrates subendocardial ischemia

▪ Unstable angina, NSTEMIs are
▪ Same as stable angina, except pain may
indistinguishable at initial evaluation
occur at rest
▫ Elevated troponins indicating myocardial
▪ Pain described as pressure, squeezing,
infarction not detectable for hours
burning, or tightness; can radiate to the
either/both arms, jaw, shoulders, and back; ▫ Initial management identical
lasts less than 20 minutes
▪ Other symptoms: Levine’s sign (a clenched MEDICATIONS
fist held over the chest), dyspnea,
diaphoresis, fatigue, nausea, and epigastric Clopidogrel
pain
Low-molecular-weight-heparin (LMWH)
▪ Prevents clot formation
Enoxaparin
▪ Drug of choice based on empirical evidence
OSMOSIS.ORG 5
NOTES
NOTES
ACYANOTIC DEFECTS

Eisenmenger syndrome
PATHOLOGY & CAUSES ▪ At rest: asymptomatic
▪ Heart defects presenting without cyanosis ▪ With exertion: cyanosis, palpitations
(blue-tinged skin) dyspnea, chest pain, syncope
▪ Caused by fetal heart malformation, can
lead to heart failure DIAGNOSIS
▪ ASD, PDA, and VSD
▫ All three cause left-to right shunt → DIAGNOSTIC IMAGING
oxygenated blood flows redundantly ▪ Heart imaging to identify defect type
through pulmonary circulation →
becomes Eisenmenger syndrome over
time TREATMENT
SURGERY
SIGNS & SYMPTOMS ▪ Rarely
▪ Sometimes asymptomatic, but can lead to
heart failure, Eisenmenger syndrome MNEMONIC: P(C)AV
Heart failure Acyanotic defects
▪ Infants: poor feeding/failure to thrive, Patent ductus arteriosus
fluid retention, pulmonary congestion, (Coarctation of the aorta): no
hepatomegaly, respiratory distress, shunt
elevated jugular venous pressure Atrial septal defect
Ventricular septal defect
6 OSMOSIS.ORG
Chapter 2 Acyanotic Defects
Figure 2.1 Illustration of blood flow through a ventricular septal defect.
ATRIAL SEPTAL DEFECT (ASD)

osms.it/atrial-septal-defect
PATHOLOGY & CAUSES

▪ A hole in the heart wall dividing left/right
atria (left-to-right shunt)
▪ Blood passes through pulmonary
circulation redundantly
SIGNS & SYMPTOMS

▪ Fixed, split S2 and pulmonic ejection
murmur (louder with age)
▪ Infants and children
▫ Respiratory infections
▫ Failure to thrive
▪ Adults (before 40) Figure 2.2 CT scan in the axial plane showing
▫ Palpitations, exercise intolerance, an atrial septal defect. Note the faint contrast
dyspnea, fatigue plume as blood flows from the high pressure
left system to the low pressure right system.
RA; right atrium. LA; left atrium. RV; right
ventricle. LV; left ventricle.
OSMOSIS.ORG 7
DIAGNOSIS
DIAGNOSTIC IMAGING
Chest X-ray
▪ Right heart dilation
▪ Prominent pulmonary vascularity
Transesophageal echocardiography
▪ Visualize size & location accurately
SURGERY
Figure 2.3 Intraoperative view of multiple,
Right heart catheterization pinhole atrial septal defects.
▪ Increased oxygen saturation in:
▫ Right atrium
▫ Right ventricle TREATMENT
▫ Pulmonary artery
SURGERY
▪ Percutaneous surgical closure
▪ Adults: surgery in cases of
▫ Right ventricular enlargement,
paradoxical embolism, right-to-left
shunt
Figure 2.4 Illustration depecting blood shunting from left to right atrium in atrial septal defect.
8 OSMOSIS.ORG
COARCTATION OF THE AORTA

(CoA)
osms.it/coarctation-of-the-aorta
compared to lower extremities
PATHOLOGY & CAUSES ▪ Secondary hypertension
▪ Severe heart failure, shock if/when PDA
▪ Narrowed segment of aorta
closes
▪ Upstream issues
▪ Other symptoms may more apparent with
▫ Blood flow increases into aortic age
branches before coarctation → blood
▫ Chest pain, cold extremities, claudication
flow, pressure increases in upper
on exertion
extremities, head
▫ Left ventricular impulse palpable,
▪ Downstream issues
sustained
▫ Decreased blood flow, decreased
▫ Pulsations felt in intercostal spaces
pressure in lower extremities
▫ Kidneys receive less blood → activate Adults
renin-angiotensin-aldosterone system ▪ Hypertension (most common)
(RAAS) → secondary hypertension ▪ Hypotension in lower extremities
▪ Preductal coarctation ▪ Bilateral lower extremity claudication
▫ Associated with Turner syndrome, PDA ▪ Dyspnea on exertion
▫ May go unnoticed unless severe. ▪ Delayed/weak femoral pulses
Presents as postductal coarctation
▪ Postductal coarctation
▫ Distal to ligamentum arteriosum DIAGNOSIS
▫ Presents in adulthood
▫ Blood pressure higher upstream, lower DIAGNOSTIC IMAGING
downstream Angiogram
▫ Autoregulatory vasoconstriction/ ▪ Visualize narrowing in aorta, anatomy &
vasodilation preserves regional blood severity
flow
Chest X-ray
▪ Rib notching: 3-sign (narrowed aorta
SIGNS & SYMPTOMS resembles notch of number 3 due to
prestenotic of aortic arch & postenotic of
▪ Depends on presence/severity of PDA descending aorta dilatation)
▪ Systolic murmur
▫ Systole: diamond-shaped murmur Echocardiograph
▫ Diastole: high-pitched decrescendo ▪ Visualize location, size, blood turbulance
murmur
OTHER DIAGNOSTICS
Infants
▪ Lower extremity cyanosis ECG
▪ Absent or delayed femoral pulse ▪ Left ventricular hypertrophy, left atrial
▪ Failure to thrive/poor feeding enlargement
▪ Blood pressure higher in upper extremities
OSMOSIS.ORG 9
TREATMENT
MEDICATIONS
Prostaglandin E
▪ Increases flow to lower extremities
SURGERY
▪ Resection with end-to-end anastomosis
▫ If unfeasible, bypass graft across area of
coarctation
▪ Long-segment coarctation: subclavian
aortoplasty Figure 2.5 Illustration showing narrowing of
▪ Prosthetic patch aortoplasty (rarely) aorta lumen.
▪ Balloon angioplasty with possible stent
Figure 2.7 A chest radiograph demonstrating

the figure of three sign seen in coarctation of
the aorta.
Figure 2.6 CT scan in the sagittal plane
demonstrating coarctation of the aorta.
10 OSMOSIS.ORG
PATENT DUCTUS ARTERIOSUS

(PDA)
osms.it/patent-ductus-arteriosus

▪ Ductus arteriosus remains open after birth DIAGNOSTIC IMAGING
▪ Left-to-right shunt between atria
Echocardiograph
▪ Sometimes presents with congenital
▪ 2D suprasternal echocardiogram
defects (congenital rubella syndrome)
Chest X-ray
CAUSES ▪ Normal/cardiomegaly
Congenital rubella
▪ Mother-fetal transmission of rubella in first
OTHER DIAGNOSTICS
trimester → cytopathic damage to blood ECG
vessels, ischemia to organs
▪ Left ventricular hypertrophy, left atrial
▪ Prematurity enlargement
▪ Perinatal distress, hypoxia
TREATMENT
SIGNS & SYMPTOMS
▪ Small asymptomatic PDA: monitor
Depend on size of PDA
▪ Smaller
MEDICATIONS
▫ Usually asymptomatic
▫ Neonates: holosystolic “machine-line” Neonates (10–14 days)
murmur on auscultation ▪ Close PDA using prostaglandin inhibitor
▫ Infants, children, adults: continuous
murmur Symptomatic moderate/large PDA
▪ Moderate ▪ During heart failure
▫ Exercise intolerance ▫ Digoxin, furosemide
▫ Continuous murmur
▫ Wide systemic pulse pressure SURGERY
▫ Displaced ventricular apex Symptomatic moderate/large PDA
▪ Larger ▪ Closure recommended for symptoms of
▫ Infants: leads to heart failure left-to-right shunting, left-sided volume
▫ Children: shortness of breath, overload, reversible pulmonary arterial
fatigability, Eisenmenger syndrome hypertension
▫ Children < 5kg/11lbs: surgical ligation
▫ > 5kg/11lbs (including adolescents/
adults): percutaneous occlusion, surgical
ligation for large PDA
OSMOSIS.ORG 11
Figure 2.8 Illustration depicting location of a patent ductus arteriosus.
Figure 2.9 Volume-rendered CT scan of the

heart and great vessels showing a patent
ductus arteriosus.
12 OSMOSIS.ORG
VENTRICULAR SEPTAL DEFECT

(VSD)
osms.it/ventricular-septal-defect

▪ Left-to-right shunt between ventricles DIAGNOSTIC IMAGING
▪ Most common congenital heart disease
Chest X-ray
▪ Left-to-right shunt between ventricles
▪ Unreliable; may indicate left atrial
▪ Often presents with other defects (e.g. enlargement, right ventricular hypertrophy,
tetralogy of Fallot) left ventricular hypertrophy, or pulmonary
Size of defect artery enlargement
▪ Small: restrictive Echocardiogram
▫ Normal pressure maintained between ▪ Determines location and size
ventricles
▪ Moderate or large: non-restrictive MRI
▫ No pressure difference between ▪ Use if echo does not diagnose
ventricles
SURGERY
Cardiac catheterization
SIGNS & SYMPTOMS ▪ Used if echo and MRI did not diagnose, but
individual still has pulmonary hypertension
▪ Asymptomatic in utero
▪ Holosystolic murmur (loud, high-pitched)
located at lower left sternal border OTHER INTERVENTIONS
Size of defect ECG

▪ Small: asymptomatic, murmur ▪ Left ventricular hypertrophy
▪ Moderate–large: sweating, poor feeding/ ▫ May see right ventricular hypertrophy;
failure to thrive, respiratory infections. left, right atrial enlargement (may see
Murmur plus thrill, and diastolic rumble in Katz–Wachtel phenomenon)
mitral area
▫ Signs of congestive heart failure
(dyspnea, persistent cough, pulmonary
vascular resistance)
▫ Eisenmenger’s syndrome
OSMOSIS.ORG 13
TREATMENT
▪ Most small VSDs close on their own
SURGERY
▪ Repair larger shunts by age 2 to prevent
pulmonary hypertension
Surgical repair
▪ Patch closure over ventricular septal defect
(preferred treatment)
Transcatheter closure
▪ Mesh to close VSD (higher risk)
Hybrid procedure
Figure 2.10 View of the right side of the heart
showing multiple ventricular septal defects.
Figure 2.11 Doppler ultrasound scan demonstrating flow of blood across the interventricular
septum in a VSD.
14 OSMOSIS.ORG
NOTES
NOTES
ANEURYSMS & DISSECTION
ANEURYSMS
osms.it/aneuryms
TYPES
PATHOLOGY & CAUSES
True aneurysms
▪ Abnormal dilations in blood vessel; 1.5x ▪ All layers of blood vessel wall dilate
larger than normal vessel diameter (> 3.0 ▫ Fusiform aneurysms: blood vessel walls
cm in aortic and thoracic) dilate symmetrically
▪ Frequently occurs in areas of high blood ▫ Saccular (berry) aneurysms:
pressure: aorta, femoral, iliac, popliteal, asymmetrical ballooning of blood vessel
and cerebral arteries; can occur in veins walls due to increased blood pressure
(uncommon). Pressure on blood vessel on one side of blood vessel wall
walls increases with diameter of vessel
lumen (LaPlace’s law) Pseudoaneurysms
▪ 60% of true aortic aneurysms occur in ▪ Small hole in blood vessel wall → blood
abdominal aorta, 40% in thoracic aorta; leaks out, pools; resembles fusiform/
most between renal artery branch and saccular aneurysm
aortic bifurcation due to less collagen in this
area of aorta CAUSES
Locations Ischemia
▪ Can occur in any blood vessel; particularly ▪ Ischemia of arteries with vasa vasorum:
life-threatening in the following locations hyaline arteriolosclerosis decreases blood
▪ Abdominal aortic aneurysm (AAA) to large artery walls; decreases smooth
▫ Localized in abdominal aorta (diameter muscle in arterial tunica media
> 3cm/1.12in or > 50% larger than ▪ Ischemia of arteries without vasa vasorum:
normal) plaque from atherosclerosis blocks blood
▫ Caused by atherosclerosis, infection, vessel walls from receiving oxygen
trauma, arteritis, cystic medial necrosis
Infection
▪ Thoracic aortic aneurysm
▪ Tertiary syphilis: causes inflammation of
▫ Localized in thoracic aorta. Less
tunica intima of vasa vasorum, decreasing
common than abdominal aortic
blood to arterial wall in thoracic artery
aneurysm
(endarteritis obliterans)
▪ Cerebral aneurysms
▪ Mycotic aneurysms: secondary infection in
▫ Located in brain; particularly threatening intracranial arteries/visceral arteries/arteries
in circle of Willis of extremities (bacteria enters vessel wall,
weakening it)
▫ Pathogens include: Bacteroides fragilis,
Pseudomonas aeruginosa, Salmonella
OSMOSIS.ORG 15
Figure 3.1 Illustration depicting differences between types of aneurysms.
species, Aspergillus, Candida, aorta, inferior vena cava/duodenum,

Mucor (also an infective endocarditis respectively)
complication) ▪ Thoracic aortic aneurysm
Genetic ▫ Dissection, rupture (bleeding into
thoracic cavity)
▪ Connective tissue disorders: Marfan’s
syndrome, Ehlers-Danlos syndrome ▪ Cerebral aneurysm
▫ Rupture (leads to hemorrhagic stroke or
subarachnoid hemorrhage)
RISK FACTORS ▫ If large, aneurysm can place pressure
▪ White biologically-male individuals on surrounding cerebral tissue, causing
of European descent, advanced age, neurological symptoms
smoking, hyperlipidemia, hypertension,
family history, Ehlers-Danlos syndrome,
Marfan syndrome, syphilis, cystic medial SIGNS & SYMPTOMS
degeneration, bicuspid aortic valve
▪ Asymptomatic until rupture: severe pain
COMPLICATIONS in specific location (abdomen, chest, lower
▪ High mortality rates back, groin), pulsating mass, hypotension,
syncope
▪ Rupture: internal exsanguination; increased
intracranial pressure (if in brain) ▪ Abdominal aortic aneurysm
▪ Compression to surrounding structures: ▫ On rupture: pain in abdomen/back,
superior vena cava syndrome, aortic pulsating sensation in abdomen, low
insufficiency blood pressure, syncope
▪ Thrombosis/emboli: stagnant blood in extra ▫ Large aneurysms felt by pushing on
lumen space abdomen
▪ Abdominal aortic aneurysm
▫ Rupture (bleeding can be retroperitoneal
or into abdominal cavity), acute aortic
occlusion, aortocaval/aortoduodenal
fistulae (connections between
16 OSMOSIS.ORG
Chapter 3 Aneurysms & Dissection
▪ Repair methods
DIAGNOSIS ▫ Surgical clipping: aneurysm clipped at
base
DIAGNOSTIC IMAGING
▫ Endovascular coiling: platinum wires
Ultrasound promote blood clotting, decrease blood
▪ Confirms presence, location, size; monitors flow through aneurysm
growth ▫ Endovascular stenting: wire stent
inside aneurysm allows blood to bypass
CT scan aneurysm
▪ Accurately measures; used pre-surgery
CTA scan OTHER INTERVENTIONS

▪ CT scan + injecting contrast dye shows ▪ Goals, initially
blood flow; used for surgery ▫ Prevent aneurysm rupture with regular
ultrasound monitoring
▪ Goals for individuals receiving surgery for
OTHER DIAGNOSTICS
aneurysm
ECG ▫ Maintain tissue perfusion, motor and
▪ Rules out myocardial infarction sensory function, prevent complications,
i.e. infection/thrombosis
▪ Goals for post-operative individuals
TREATMENT ▫ Maintain blood pressure/perfusion,
especially renal perfusion
MEDICATIONS ▫ Monitor urine output, peripheral
▪ Pharmaceutical treatments for blood pulses, capillary refill, skin temperature,
pressure management abdominal girth, intra abdominal
pressure, limb sensation and movement
▪ Monitor stent/graft patency
SURGERY
▪ Indications: aneurysms > 5cm/1.96in,
0.5cm/0.2in growth in six months,
individual symptomatic
Figure 3.2 Illustration depicting Laplace’s law. Increasing diameter increases pressure on the
walls of blood vessel. Similar to how a balloon becomes easier to fill with air as it inflates.
OSMOSIS.ORG 17
Figure 3.3 A CT scan of the head in the left Figure 3.5 A CT scan of the chest in the
parasagittal plane demonstrating a saccular coronal plane demonstrating a massive
aneurysm of the internal carotid artery. thoracic aortic aneurysm involving the
ascending aorta. The aortic valve is faintly
visible.
Figure 3.4 Abdominal CT scan in the axial plane demonstrating a ruptured abdominal aortic
aneurysm.
18 OSMOSIS.ORG
Chapter 3 Aneurysms & Dissection
AORTIC DISSECTION
osms.it/aortic_dissection
▪ Blood flow tears tunica media/tunica
PATHOLOGY & CAUSES externa → severe internal bleeding →
death
PATHOLOGY ▪ Blood flow tears tunica intima again, return
▪ Tearing/widening of artery’s internal layer, to true lumen (not severe)
followed by blood entering vessel wall,
▪ Obstruction of arterial branches off aorta,
causing pain
leading to ischemia of individual organs
▫ Typically affects aorta
▪ Blood tunnels, creates false lumen that
▪ Tear forms in tunica intima of aorta → extends to aortic branch → obstruction
high pressure blood flows between tunica
intima/tunica media → layer separation →
false lumen → dilate aorta SIGNS & SYMPTOMS
▪ Most aneurysms develop in first 10 cm of
aorta ▪ Sudden, intense, tearing chest pain
▪ Can present acutely/chronically radiating to back, nausea, vomiting,
diaphoresis
TYPES ▪ Chronic dissections painless
▪ Decreased peripheral pulses, asymmetric
Stanford classification pulses
▪ Type A: dissection involves ascending aorta ▪ Hypertension/hypotension depending on
and/or aortic arch, sometimes descending location of dissection
aorta ▪ Diastolic decrescendo murmur: ascending
▪ Type B: dissection involves descending aortic dissections → aortic regurgitation
aorta/aortic arch without involvement of ▪ Neurological deficits: stroke, hemiplegia,
ascending aorta syncope
CAUSES
▪ Weakness in vessel wall due to chronic
hypertension, blood vessel coarctation,
connective tissue disorders, aneurysms
RISK FACTORS
▪ Pregnancy, previous open heart surgery,
vasculitis, trauma, family history of aortic
dissection, Turner’s syndrome, cocaine use
▪ Cystic medial necrosis: familial inherited
disorder causing degenerative breakdown
of collagen, elastin, smooth muscle; wall
weakens, predisposing individual to
aneurysm/dissection
COMPLICATIONS
▪ Pericardial tamponade: most common Figure 3.6 Gross pathology of an aortic
cause of death dissection.
OSMOSIS.ORG 19
OTHER DIAGNOSTICS
DIAGNOSIS
ECG
DIAGNOSTIC IMAGING ▪ Helps rule out alternative diagnostic
possibilities, e.g. myocardial infarction
Chest X-ray
▪ Widening of mediastinum consistent with
dissection, but inadequate as sole evidence TREATMENT
for diagnosis
Transesophageal echocardiogram
MEDICATIONS
▪ Stanford Type B: lower heart rate, blood
▪ Best for hemodynamically-unstable
pressure
individuals
▫ First line: beta-blockers
▪ High sensitivity for identifying dissection,
complications like aortic regurgitation, ▫ Second line: calcium channel blockers
cardiac tamponade, involvement of ▫ Pain management for acute dissection
coronary arteries
CT angiography SURGERY
▪ Best for hemodynamically-stable ▪ Stanford type A: medical emergency,
individuals surgical repair indicated
▪ High sensitivity for identifying dissection, ▪ Stanford Type B: surgical repair indicated
can provide anatomic information useful when dissection acute, complications arise,
in planning surgical repair; visualize/locate medication ineffective
dissection
Figure 3.7 Abdominal CT scan in the axial plane demonstrating an aortic dissection of the
descending aorta. Note the media, dissected from the wall of the aorta, demarcating the true
and the false lumen.
20 OSMOSIS.ORG
NOTES
NOTES
BRADYCARDIA & HEART BLOCK

PATHOLOGY & CAUSES SIGNS & SYMPTOMS
▪ Delay or complete blockage in the electrical ▪ If symptomatic, may present as
conduction system of the heart → abnormal lightheadedness, headache, syncope,
heart rhythm; primarily, bradycardia palpitations, Stokes–Adams attacks,
fatigue, dyspnoea etc.
CAUSES
▪ Can be caused by defect in DIAGNOSIS
▫ Atrioventricular node
▫ Bundle branches ▪ ECG-based; see individual disorders
▫ Sinoatrial node
▪ Idiopathic or secondary to
▫ Myocardial ischemia
TREATMENT
▫ Fibrosis
▪ May not require treatment
▫ Infections
▫ Congenital heart disease
MEDICATIONS
▫ Cardiomyopathies
▪ E.g. atropine
▫ Iatrogenic (e.g. medication, post-
surgery)
OTHER INTERVENTIONS
COMPLICATIONS ▪ Transcutaneous pacing
▪ May progress to fatal arrhythmias, heart ▪ Pacemaker implantation
failure, and/or sudden cardiac death
OSMOSIS.ORG 21
ATRIOVENTRICULAR BLOCK
osms.it/atrioventricular-block

▪ Blockage/delay in electrical signal ▪ Presence/severity depends on ventricular
stimulating contraction between atria, rate
ventricles ▫ Lightheadedness, syncope, fatigue,
dyspnea
TYPES
▪ First degree atrioventricular (AV) block DIAGNOSIS
▪ Second degree atrioventricular block
▫ Type I/Mobitz I/Wenckebach OTHER DIAGNOSTICS
▫ Type II/Mobitz II
ECG
▪ Third degree atrioventricular block/complete
heart block ▪ First-degree AV block
▫ Signal delayed; continues to ventricles
▫ PR interval > 200ms due to delayed
CAUSES ventricular contraction
Congenital heart disease ▪ Second degree AV block
▫ Type I/Mobitz I/Wenckebach: PR
Heart damage interval lengthens with each beat until
▪ Infiltrative/dilated cardiomyopathies, blocked completely (e.g. progressive PR
muscular dystrophy, lyme disease, intervals : 200ms → 260ms → 300ms
myocardial ischemia, myocarditis, → dropped beat; no QRS). Ventricular
endocarditis with abscess, hyperkalemia, escape beat: if ventricle does not receive
high vagal tone signal from atrioventricular node after
short time, latent pacemaker cells within
Iatrogenic causes bundle of His/ventricle kick in, begin
▪ Medication (beta blockers, calcium channel pacing heart at slower than normal rate
blockers, cardiac glycosides), post-cardiac (~20–50bpm)
surgery, post-catheter ablation, post- ▫ Type II/Mobitz II: prolonged PR interval
transcatheter aortic valve implantation (> 200ms). Block commonly in bundle
Lev’s disease/Lenegre-Lev syndrome of His → QRS usually wide (> 110ms),
intermittent dropped beats (no QRS).
▪ Idiopathic fibrosis and calcification of
Happens randomly; no progressive
heart’s electrical conduction system, most
lengthening of PR interval; every second
common in elderly
P wave blocked, may progress to third
degree AV block
COMPLICATIONS ▪ Third degree AV block/complete heart block
▪ Heart failure secondary to bradycardia; ▫ Signal completely blocked every time
third degree AV block risk for sudden ▫ Eg. ventricles contract at lower rate
cardiac death than atria (ventricular pacemaker cells
establish rate)
▫ No association between P waves, QRS
complexes
22 OSMOSIS.ORG
Chapter 4 Bradycardia & Heart Block
MNEMONIC
TREATMENT AV blocks
If the R is far from P, then you
▪ Depends on type/severity
have a First Degree.
▫ For all: identify electrolyte imbalances/
Longer, longer, longer,
medication-induced causes
drop! Then you have a
▪ No treatment: Wenckebach.
▫ First degree AV block, asymptomatic If some P’s don’t get through,
type I second degree then you have Mobitz II.
If P’s and Q’s don’t agree, then
MEDICATIONS you have a Third Degree.
▪ Atropine: second degree, third degree
OTHER INTERVENTIONS
Permanent pacemaker
▪ Asymptomatic: type II second degree, third
degree
▪ Symptomatic: type I & II second degree,
third degree
Transcutaneous pacing
▪ Symptomatic: type I & II second degree,
third degree
Figure 4.1 ECG (lead II) demonstrating first degree atrioventricular block.
Figure 4.2 ECG (lead V1) demonstrating Mobitz I (Wenckebach) second degree atrioventiricular
block.
OSMOSIS.ORG 23
Figure 4.3 ECG (lead V1) demonstrating Mobitz II second degree atrioventricular block.
Figure 4.4 ECG (lead V1) demonstrating third degree (complete) atrioventricular block.
BUNDLE BRANCH BLOCK

osms.it/bundle-branch-block
from complete heart block and may lead to
PATHOLOGY & CAUSES ventricular asystole
▪ Electrical signal for contraction of left/right Intermittent bundle branch block
ventricle completely blocked or delayed ▪ Occasional block, unrelated to heart rate
Rate-related bundle branch block

TYPES
▪ Block occurs when heart rate is relatively
▪ Either right or left bundle branch blocks can
fast, temporarily resolves once heart rate
be complete or incomplete
slows down
▫ Complete: total blockage of signal
transmission
▫ Incomplete: slowed signal transmission CAUSES
▪ Fibrosis/scarring, formed acutely/chronically
Right bundle branch block (RBBB)
▪ Signal blocked in right bundle branch Acute
▫ Left ventricle contracts first → signal ▪ Ischemia, myocardial infarction, myocarditis
carried to right side via Purkinje fibers → ▪ Sudden increase in right ventricular
right ventricle contracts pressure → pulmonary embolism
▪ Iatrogenic: right heart catheterization/
Left bundle branch block (LBBB) ethanol ablation of basal ventricular septum
▪ Signal blocked in left bundle branch
▫ Right ventricle contracts → left ventricle Chronic
contracts ▪ Gradual remodelling of heart muscle
▫ Hypertension, coronary artery disease,
Bilateral bundle branch block cardiomyopathies
▪ Caused by disease involving both right/left ▫ Pulmonary hypertension
bundle branches; on ECG, indistinguishable
▫ Congenital heart disease
24 OSMOSIS.ORG
RISK FACTORS ▪ LBBB only

▪ Increasing age, associated with underlying ▫ Negative V1, positive V6 (away from V1
or advancing heart disease towards V6)
▫ V1: QS, or “little r”-rS complex. W shape
▫ V6: large, notched R wave. M shape
SIGNS & SYMPTOMS ▪ RBBB only
RBBB ▫ Positive V1,negative V6
▪ Asymptomatic; wide splitting on ▫ V1: large terminal R wave. M shape
auscultation ▫ V6: slurred S wave, W shape
LBBB
▪ Asymptomatic; reversed splitting on TREATMENT
auscultation
▪ No treatment
DIAGNOSIS
MNEMONIC: WiLLiaM
OTHER DIAGNOSTICS MaRRoW
ECG ECG of Left BBB
▪ LBBB and RBBB W-shape in V1 Left BBB
▫ Lead II (limb lead) shows long QRS Left BBB has V6 M-shape
complex > 120ms (normal: 80–120ms)
▫ Longer QRS complex because ECG of Right BBB
depolarization starts on time but ends M-shape in V1 Right BBB
later due to depolarization delay in one Right BBB has V6 W-shape
ventricle
Figure 4.5 Illustration depicting mnemonic “WiLLiaM MaRRoW.”
OSMOSIS.ORG 25
Figure 4.6 ECG demonstrating left bundle branch block.
Figure 4.7 ECG demonstrating right bundle branch block.
26 OSMOSIS.ORG
Figure 4.8 Illustration depicting wide QRS in bundle branch block.
Figure 4.9 Illustration depicting M-shape and W-shape in bundle branch blocks.
OSMOSIS.ORG 27
SICK SINUS SYNDROME
osms.it/sick-sinus-syndrome

▪ Malfunction in sinoatrial node (SA node) ▪ Stokes–Adams attacks (fainting due to
characterized by persistent spontaneous asystole/ventricular fibrillation), syncope,
sinus bradycardia, alternating sinus palpitations, chest pain, dyspnea, fatigue,
bradycardia and tachyarrhythmia headache, nausea
(sometimes called tachycardia-bradycardia ▪ Variable ECG findings
syndrome)
CAUSES DIAGNOSIS
▪ Disorders causing scarring/degeneration/
damage to SA node
DIAGNOSTIC IMAGING
▫ Sarcoidosis, amyloidosis, ECG
hemochromatosis, Chagas disease,
cardiomyopathies
OTHER DIAGNOSTICS
▪ Can be caused/worsened by certain
medications ▪ Tilt table testing
▫ Digoxin, calcium channel blockers, beta ▪ Holter monitor
blockers, anti-arrhythmics
▪ Congenital
TREATMENT
▫ Mutations of SCN5A gene encoding
alpha subunit of sodium ion channel OTHER INTERVENTIONS
RISK FACTORS Pacemaker implantation

▪ Elderly ▪ For hemodynamically stable individuals,
tachycardia can be treated with medication;
▪ Coronary artery disease
can be combined with pacemaker in some
▪ High blood pressure cases
▪ Aortic, mitral valve diseases ▪ For hemodynamically unstable individuals,
definitive therapy requires pacemaker
COMPLICATIONS implantation; medication plays limited role
▪ Sinus arrest, sinus node exit block, sinus
bradycardia
▫ May be associated with tachycardia
(characterized by long pause after
tachycardia), e.g. atrial tachycardia, atrial
fibrillation
▫ Associated with azygos continuation of
interrupted inferior vena cava
28 OSMOSIS.ORG
NOTES
NOTES
CARDIAC TUMORS

▪ Abnormal cell growth forms mass in heart ▪ Asymptomatic
▫ Incidental finding on echocardiogram,
TYPES MRI, CT scan
▪ Dyspnea
Primary ▫ Most common symptom
▪ Rare ▫ Can progress to orthopnea, paroxysmal
▫ Adults: myxoma nocturnal dyspnea
▫ Children: rhabdomyoma ▪ “Tumor plop” sound upon auscultation with
left atrial myxoma
Secondary
▪ Syncope, presyncope, dizziness, chest pain/
▪ More common than primary tightness
▪ Metastases from cancer in other areas (lung
cancer, lymphoma, breast cancer, leukemia,
melanoma, hepatocellular carcinoma, colon DIAGNOSIS
cancer)
▫ Lymphogenous/hematogenous DIAGNOSTIC IMAGING
dissemination ▪ MRI, CT scan, ultrasound
▫ Incidental finding
COMPLICATIONS ▫ See individual disorders
▪ Impaired left ventricular structure, filling, ▪ 2D echocardiogram preferred procedure
ejection caused by tumor
▪ Arrhythmias: tumor disrupts normal nodal/
LAB RESULTS
septal electrical conduction
▪ Histology conducted on biopsy via surgical
▪ Heart failure: tumor obstructs inflow/
excision/fine needle aspiration
outflow
▪ Recurrence of tumor after excision (if tumor
not completely removed)
▪ Embolism, sudden cardiac death,
TREATMENT
myocardial infarction
SURGERY
▪ Symptomatic: surgical resection
OTHER INTERVENTIONS
▪ Asymptomatic: monitor
OSMOSIS.ORG 29
ATRIAL MYXOMA
osms.it/atrial-myxoma

▪ A benign heart tumor ▪ Asymptomatic: incidental finding on
▪ Most common primary cardiac tumor in echocardiogram, MRI, CT scan
adults ▪ Dyspnea: most common symptom
▪ Arises in heart’s mesenchymal connective ▫ Can progress to orthopnea, paroxysmal
tissue nocturnal dyspnea
▪ Most common in left atrium, may cause ▪ “Tumor plop” sound upon auscultation with
syncope left atrial myxoma
▫ Tumor in left atrium → obstructs mitral ▪ Syncope, presyncope, dizziness, chest pain/
valve tightness
▪ Histology
▫ Pedunculated (attached to tissue stalk)
▫ Gelatinous due to abundance of ground
DIAGNOSIS
substance
LAB RESULTS
RISK FACTORS Histology
▪ Age 40–60 ▪ Stellate myxoma cells in myxoid stroma of
▪ More common in biological females glycosaminoglycans
▫ Less pronounced in familial atrial
myxoma TREATMENT
▪ Genetic disease
SURGERY
▪ Symptomatic: resection
OTHER INTERVENTIONS
Figure 5.1 Surgically excised atrial myxoma. A

small piece of myocardium marks the point of
attachment.
30 OSMOSIS.ORG
Chapter 5 Cardiac Tumors
Figure 5.2 Histological appearance of a

myxoma with abundant mucoid matrix (pink
background) and scanty, bland spindle cells
with low mitotic activity.
Figure 5.3 A sagittal CT scan demonstrating

a myxoma in the left atrium.
RHABDOMYOMA
osms.it/rhabdomyoma
▪ Associated with nevoid basal cell
PATHOLOGY & CAUSES carcinoma syndrome
▪ Genetic disease
▪ Benign tumor of striated muscle
▪ Most common primary cardiac tumor in
infants/children DIAGNOSIS
▪ Arises in ventricles
▪ Presents congenitally DIAGNOSTIC IMAGING
▪ Benign hamartoma (abnormal tissue
MRI, CT scan, ultrasound
formation)
▪ Incidental finding
▪ Association between rhabdomyoma/
tuberous sclerosis about 30–50% Ultrasound, MRI
▪ Often regresses spontaneously ▪ Visualize tumor
▪ Shrink with age
LAB RESULTS
RISK FACTORS
▪ More common in children Histology
▪ More common in biological males (2.4:1 ▪ Hamartomatous growths surrounded in a
male-female ratio) glycogen-rich eosinophilic cytoplasm
▪ Average presentation age is four years old
OSMOSIS.ORG 31
SIGNS & SYMPTOMS
▪ Usually present at birth
▪ Tender, painful, benign, slow-growing
nodules
▫ Common in neck/mouth/larynx, may
cause breathing difficulties
TREATMENT
SURGERY Figure 5.4 A surgically excised
▪ Symptomatic: surgical resection rhabdomyoma.
OTHER INTERVENTIONS
Figure 5.5 Histological appearance of a rhabdomyoma composed of plump, pink skeletal muscle
cells.
32 OSMOSIS.ORG
NOTES
NOTES
CARDIOMYOPATHY
GENERALLY, WHAT IS IT?

▪ Broad term, describes any issue resulting DIAGNOSTIC IMAGING
from disease of myocardium ▪ Chest X-ray
▪ Primary cardiomyopathy: issue develops of ▪ Echocardiogram/cardiac MRI
its own accord
▪ Secondary cardiomyopathy: issue develops OTHER DIAGNOSTICS
as compensation for another underlying
▪ ECG
disease
RISK FACTORS TREATMENT

▪ Positive family history
MEDICATIONS
COMPLICATIONS ▪ See individual diseases
▫ Heart failure, arrhythmias, sudden
cardiac death SURGERY
▪ Implantable cardioverter-defibrillator (ICD)
▪ Heart transplant
SIGNS & SYMPTOMS
▪ Can be asymptomatic OTHER INTERVENTIONS
▪ Heart failure signs, symptoms ▪ Lifestyle changes
▪ Heart murmurs
OSMOSIS.ORG 33
DILATED CARDIOMYOPATHY
osms.it/dilated-cm
▫ Related to pregnancy-associated
PATHOLOGY & CAUSES hypertension
▫ Half of individuals recover following
▪ Dilation of all four chambers of heart pregnancy
▪ Most common type of cardiomyopathy
▫ New sarcomeres added in series, Sarcoidosis
creates larger chambers with relatively ▪ Growth of granulomas in heart → dilation
weak walls, less muscle for contraction
→ low systolic function
RISK FACTORS
▫ Chambers stretch → valves stretch →
▪ Alcoholism, past family history of diseases
blood regurgitates back into atria
implicated in DMD
CAUSES COMPLICATIONS
▪ Primary dilated cardiomyopathy most often
▪ Systolic heart failure
idiopathic
▫ Valve regurgitation: as chambers
Genetic mutations/conditions stretch, so do valves
▪ Duchenne muscular dystrophy (DMD), ▪ Arrhythmias: stretching muscle irritates
hemochromatosis conduction system
Myocarditis
▪ Can progress from myocarditis to dilated MNEMONIC: ID BIG MAPS
cardiomyopathy Causes of Dilated
Cardiomyopathy
Infection
Idiopathic
▪ Coxsackievirus B: leads to myocarditis,
Drugs/Doxorubicin (and
heart muscle inflammation
cocaine)
▪ Chagas disease: protozoal infection
Beriberi (wet)
Linked to alcoholism Infection
▪ Alcohol, metabolites have direct toxic effect Genetic
on heart muscle Myocarditis
Alcoholism
Linked to certain drugs
Peripartum cardiomyopathy
▪ Chemotherapy: doxorubicin, daunorubicin
Sarcoidosis
▪ Cocaine
Wet beriberi
▪ Beriberi: illness caused by thiamine (vitamin
B1) deficiency
▪ Wet beriberi: affects heart; ↓ thiamine
levels impair myocardium energy
production
Peripartum cardiomyopathy
▪ Can develop in third trimester of pregnancy/
weeks after delivery
34 OSMOSIS.ORG
Chapter 6 Cardiomyopathy

▪ Fatigue, dyspnea MEDICATIONS
▪ Lateral displaced point of maximum ▪ Angiotensin-converting-enzyme (ACE)
impulse (PMI) inhibitor, angiotensin receptor blocker, beta
▪ Chest pain on exertion blocker
▪ Holosystolic murmur (mitral valve ▫ Slows disease progression
regurgitation during systole)
▪ S3 sound (blood rushing into, slamming SURGERY
into dilated ventricular wall during diastole) ▪ Heart transplant (extreme cases)
DIAGNOSIS OTHER INTERVENTIONS

▪ Left ventricular assist device (LVAD):
DIAGNOSTIC IMAGING mechanical pump assists heart in delivering
blood to body
X-ray
▪ Cardiomegaly, pulmonary edema, pleural
effusion
OTHER DIAGNOSTICS
ECG
▪ Shows ventricular dilation, reduced ejection
fraction

enlargement of the heart due to dilated
cardiomyopathy. The heart occupies more
than half the width of the chest.
Figure 6.1 Gross pathology of dilated
cardiomyopathy. Note the large ventricles
and thin ventricular walls.
OSMOSIS.ORG 35
HYPERTROPHIC CARDIOMYOPATHY
(HCM)
osms.it/hypertrophic-cm
COMPLICATIONS
PATHOLOGY & CAUSES ▪ Arrhythmias, sudden cardiac death
▪ Myocardium becomes thick, heavy,
hypercontractile RISK FACTORS
▪ Myocytes become disorganized, new ▪ Positive family history of HCM/conditions
sarcomeres added in parallel to existing known to be associated with HCM (e.g.
ones Friedreich’s ataxia)
▪ Left ventricle most often affected
▫ Muscle growth asymmetrical →
interventricular septum grows larger
SIGNS & SYMPTOMS
relative to free wall
▪ Many individuals asymptomatic
▪ Hypertrophy → walls taking up more
space, ↓ blood fills ventricle ▪ Auscultation: crescendo-decrescendo
murmur
▫ Walls become stiff, less compliant →
less filling → low stroke volume → ▫ ↑ intensity with ↓ venous return
dysfunction in diastolic filling of left (Valsalva, standing), ↓ in intensity with ↑
ventricle → diastolic heart failure venous return (handgrip, squatting)
▪ Arrhythmias: larger muscles require more ▪ Symptoms arise as complications arise
oxygen, coupled with heart having difficulty ▫ Dyspnea: left ventricle stiffening, atrium
delivering blood to tissues → ischemia → increasing back pressure into lungs →
arrhythmias interstitial lung congestion
▫ Fatigue
CAUSES ▫ Exertional chest pain: ischemia
▫ Syncope with exertion: brain receiving
Genetic missense mutation, inherited as low oxygen
autosomal dominant trait ▫ Palpitations: ischemia, arrhythmias
▪ Different genetic mutations affect different ▫ Sudden cardiac death
sarcomere proteins ▪ May exhibit bifid pulse: two pulses felt
▪ Friedreich’s ataxia: autosomal recessive ▫ Mitral valve moves toward outflow tract
neurodegenerative disease → ↑ obstruction mid-systole
Hypertrophic obstructive cardiomyopathy
(subtype)
▪ Interventricular septum growth blocks left
ventricular outflow tract during systole
→ blood must flow quickly through small
opening, ↓ pressure in this area ( Venturi
effect) → low pressure pulls anterior leaflet
of mitral valve toward septum → further
mitral valve obstruction towards septum →
further obstruction overall
36 OSMOSIS.ORG
Disopyramide
DIAGNOSIS ▪ Can be used for its negative inotropic
properties
DIAGNOSTIC IMAGING
Digoxin contraindicated
Echocardiography/cardiac MRI
▪ ↑ force of contraction, can ↑ obstruction
▪ Enlarged heart chambers/↓ ejection fraction
Chest X-ray SURGERY

▪ ↑ ratio of distance between heart, thoracic ▪ Implantable cardioverter-defibrillator
cage
Surgical septal myectomy
LAB RESULTS ▪ Involves removing portion of
interventricular septum, ↓ obstruction
Genetic testing
Septal ablation
▪ Cardiomegaly-implicated gene mutations
▪ Chemical myomectomy to partially ablate
septum
OTHER DIAGNOSTICS
Heart transplant
ECG ▪ If unresponsive to all other forms of
▪ Detectable electrical changes, such as left treatment
ventricular hypertrophy
OTHER INTERVENTIONS
TREATMENT Lifestyle change
▪ Cessation of high-intensity athletics
MEDICATIONS
Beta blockers
▪ ↓ heart rate, contractile force
Calcium channel blockers

▪ If beta blockers not tolerated
▪ Slows down heart rate
Figure 6.4 The histological appearance of

the myocardium in a case of hypertrophic
cardiomyopathy. There is complete myocyte
disarray. The myocytes display bizarre forms
with side to side branching and are arranged
in a whorled configuration.
Figure 6.3 Gross pathology of hypertrophic

cardiomyopathy. The myocardium has
become so enlarged that both ventricles are
almost entirely obliterated.
OSMOSIS.ORG 37
Figure 6.5 Illustration showing the Venturi effect: low blood pressure pulls the anterior
leaflet of the mitral valve towards the septum, creating an obstruction. Blood can’t get
through the small opening, leading to a crescendo-descrescendo heart murmur.
RESTRICTIVE CARDIOMYOPATHY
osms.it/restrictive-cm
heart tissue
PATHOLOGY & CAUSES
Endocardial fibroelastosis
▪ Cardiomyopathy: heart wall is rigid, has ▪ Fibrosis develops in endocardium (inner
difficulty stretching, pumping lining of heart) and subendocardium (layer
▪ Ventricles restrict filling, ↓ cardiac output underneath endocardium)
Loffler syndrome
CAUSES ▪ Eosinophils accumulate in lung tissue
▪ Infiltrative diseases, storage diseases, ▪ Loeffler endocarditis/Loeffler
endomyocardial diseases. endomyocarditis: eosinophils also
Amyloidosis accumulate in endocardial layer of heart
tissue → inflammation, endocardial fibrosis
▪ Amyloids are misfolded proteins →
→ restrict heart tissue
insoluble → deposit in tissues, organs →
organs less compliant Hemochromatosis
▪ Familial amyloid cardiomyopathy ▫ Iron deposits in heart tissue, contributes
▪ Mutant transthyretin (TTR) protein; to restricted tissue
misfolded deposits preferentially in heart
tissue Other causes
▪ Senile cardiac amyloidosis; TTR protein/ ▪ Heart tissue radiation
wild type TTR deposits in heart over time ▫ Radiation generates reactive oxygen
species → inflammation over time
Sarcoidosis → myocardial fibrosis → tissue stiff,
▪ Immune cell collections form granulomas in
38 OSMOSIS.ORG
restrictive
COMPLICATIONS
▪ Can → diastolic heart failure
▫ Stiff ventricles → cannot stretch → less
filling → low cardiac output → heart
failure
MNEMONIC: LASHER
Causes of Restrictive
cardiomyopathy Figure 6.6 Histological appearance of the
myocardium in a case of cardiac amyloidosis;
Loffler syndrome
a cause of restrictive cardiomyopathy. Cardiac
Amyloidosis myocytes (dark purple) are surrounded by
Sarcoidosis amyloid deposits (light pink).
Hemochromatosis
Endocardial fibroelastosis
post-Radiation TREATMENT
MEDICATIONS
SIGNS & SYMPTOMS Loop diuretics
▪ ↓ systemic, pulmonary congestion
▪ Auscultation: stiff ventricle → S4 heart
sound Beta-blocker, calcium channel blocker, an-
▪ Presents as congestive heart failure: giotensin converting enzyme inhibitors
dyspnea; paroxysmal nocturnal dyspnea; ▪ Slows heart rate, ↑ ventricular-filling time
orthopnea; crackles; intraalveolar
hemorrhage; fatigue; inability to exercise;
appetite loss; abdomen swelling; swelling SURGERY
of feet, ankles; uneven/rapid pulse; chest ▪ Heart transplant
pain; low urine output; nocturia
DIAGNOSIS
OTHER DIAGNOSTICS
ECG
▪ Low-amplitude signals: peak to nadir
measurement of QRS complex being <
5mm (limb leads)/< 10mm (precordial
leads). Low voltage produced due to loss of
viable myocardium
▪ Small QRS complexes: QRS complexes
represent ventricular contraction, restricted
tissue → weaker contraction
OSMOSIS.ORG 39
40 OSMOSIS.ORG
NOTES
NOTES
CORONARY ARTERY DISEASE
STABLE ANGINA PECTORIS

osms.it/stable-angina
mass secondary to concentric hypertrophy,
PATHOLOGY & CAUSES and an increased afterload due to the fixed
obstruction to left ventricular outflow
▪ Episodic chest pain because of inadequate
oxygen supply to the heart, most often due Genetic hypertrophic cardiomyopathy
to obstruction in the coronary arteries ▪ Cardiac hypertrophy leads to increased
▪ Most common type of angina oxygen demand of heart muscle. In times
▫ Angina pectoris refers to a specific of high exertion, the heart cannot supply
type of chest pain caused by lack of enough oxygen and ischemia results
blood flow to the heart muscle. Pain
often presents as pressure, fullness, RISK FACTORS
squeezing pain in the center of the chest
▪ Smoking, hypertension, diabetes,
▫ In angina → ischemia in the dyslipidemia (high LDL, low HDL, and high
subendocardium → triggers release of triglycerides), obesity, family history of
adenosine and bradykinin → pain coronary artery disease
CAUSES Protective factors

▪ Modest alcohol consumption (~one drink/
Atherosclerosis day), healthy diet (e.g., lots of vegetables,
▪ Causes plaque buildup in vessel; blood flow grains, and nuts), and regular exercise
to heart muscle limited
▫ As plaque becomes larger and blocks
more flow, pain arises with lower levels SIGNS & SYMPTOMS
of exertion
▪ Chest pain coinciding with increased
Tachyarrhythmias exertion or stress. Pain described as
▪ Increased heart rate increases heart’s pressure, squeezing, burning, or tightness;
demand for oxygen that cannot be can radiate to the either/both arms, jaw,
delivered, thus causing pain shoulders, and back
▫ Pain usually lasts less than 20 minutes
Pulmonary hypertension
▪ Other symptoms: Levine’s sign (a clenched
▪ Left main coronary artery can become fist held over the chest), dyspnea,
compressed by enlarged pulmonary artery diaphoresis, fatigue, nausea, and epigastric
trunk, leading to reduced perfusion and pain
pain
▫ Angina equivalent: These “other
Increased myocardial oxygen demand symptoms” felt without chest pain
during periods of coronary ischemia
▪ Consequence of increased left ventricular
(more common in diabetics, biologically-
female individuals, elderly)
OSMOSIS.ORG 41
DIAGNOSIS TREATMENT
▪ Primarily based on signs/symptoms; MEDICATIONS
“clinical diagnosis”
Sublingual nitroglycerin
▪ The classic regimen for stable angina; as
OTHER DIAGNOSTICS needed, daily aspirin, beta blockers and
Electrocardiogram (ECG) statin
▪ Stable angina can present with ST segment Nitrates and Vasodilator
depression ▪ Nitrates treat immediate pain
▫ May also present with T wave ▪ Vasodilator causes venodilation, which
inversions decreases preload, reducing oxygen
▫ Illustrates subendocardial ischemia demand of the heart
▫ Dynamic ECG changes: changes in ECG ▪ Nitroglycerin
are seen for duration of symptoms, but ▫ Used to treat immediate pain on as-
can reduce in intensity or disappear needed basis
when symptoms abate (e.g. individual
▪ Isosorbide mononitrate
may start with 2mm ST depressions
with no chest pain, but then get 4mm ▫ Used for prevention
ST depressions during an episode of
Beta blockers
unstable angina at rest, which revert to
2mm ST depressions once episode is ▪ Reduce myocardial oxygen demand by
concluded) reducing heart rate and contractility
▪ Other tests may be required to obtain more ▪ First line medication for stable angina
specific information Statins
▪ Preventative. Lowers low density
lipoproteins, improves dyslipidemia
Aspirin
▪ Preventative. Prevents thrombosis by
blocking platelet activation, reduces chance
of stable angina → unstable angina
42 OSMOSIS.ORG
NOTES
NOTES
CYANOTIC DEFECTS

▪ Heart defects with cyanotic presentation: DIAGNOSTIC IMAGING
blue discoloration of skin/mucous ▪ Prenatal ultrasound
membranes, typically seen at fingertips, ▪ Echocardiography
lips, extremities
▪ Chest X-ray
▪ Develop in utero
▪ Persistent truncus arteriosus, hypoplastic
left heart syndrome, transposition of great OTHER DIAGNOSTICS
vessels can lead to heart failure ▪ ECG
▪ Persistent truncus arteriosus, tetralogy of
Fallot can lead to Eisenmenger syndrome
TREATMENT
SIGNS & SYMPTOMS MEDICATIONS

▪ Cyanosis
▪ See individual disorders SURGERY
▪ Definitive treatment
OTHER INTERVENTIONS
▪ Lifestyle changes
Figure 8.1 Illustration depicting blood flow in hypoplastic left heart syndrome.
OSMOSIS.ORG 43
HYPOPLASTIC LEFT HEART
SYNDROME
osms.it/hypoplastic-left-heart-syndrome

▪ Congenital underdevelopment of left heart ▪ Respiratory distress, poor feeding/failure to
thrive, left-sided heart failure
CAUSES
▪ Unknown: primary congenital heart defect DIAGNOSIS
may reduce flow through left ventricle/
left outflow tract, affect other heart DIAGNOSTIC IMAGING
malformations
▪ Underdeveloped left ventricle, ascending Prenatal ultrasound
aorta
Chest X-ray
▫ Aortic/mitral valves may also be
affected, narrow, or absent (atresia) ▪ Cardiomegaly
▪ If untreated: left-sided heart failure →
cardiogenic shock → death OTHER DIAGNOSTICS
Atrial septal defect (ASD) and Patent duc- ECG
tus arteriosus (PDA) ▪ Right ventricular hypertrophy
▪ ASD/PDA required for post-natal survival in ▪ After birth
hypoplastic left heart syndrome
▪ With ASD, PDA: right heart function
present but impaired; sometimes TREATMENT
asymptomatic at birth
▫ Oxygenated blood in left atrium flows MEDICATIONS
into right atrium through ASD → ▪ Prostaglandin E1 keeps ductus arteriosus
pulmonary artery → PDA → aorta → open until surgery can be performed
body
▫ Within one day: ductus arteriosus
begins closing → cyanosis
SURGERY
▪ Surgical repair/heart transplant based on
▪ Without ASD, PDA: heart not capable of
complexity
sustaining life outside womb
▫ Right heart functions normally →
oxygenated blood enters left atrium →
flow backs up due to small mitral valve,
small left ventricle → high pressure in
left atrium, blood circulated ineffectively
by left ventricle
44 OSMOSIS.ORG
Chapter 8 Cyanotic Defects
PERSISTENT TRUNCUS
ARTERIOSUS
osms.it/truncus_arteriosus
associated with genetic disorders
PATHOLOGY & CAUSES (DiGeorge syndrome)
▪ Truncus arteriosus fails to divide into aorta/

pulmonary artery COMPLICATIONS
▪ Single giant artery branching off from ▪ Cardiomegaly
right, left ventricles which splits into aorta, ▪ Pulmonary hypertension, can progress to
pulmonary artery permanent lung damage
▪ Oxygenated, deoxygenated blood mix ▪ Respiratory problems
▪ Deoxygenated blood mixes into systemic ▪ Arrhythmia
circulation → cyanosis ▪ Valve regurgitation
CAUSES
▪ Associated with DiGeorge
SIGNS & SYMPTOMS
syndrome/22q11.2 deletion syndrome
▪ Difficulty breathing, pounding heart,
(abnormal tissue formation during
weak pulse, poor feeding/failure to thrive,
development)
lethargy
▪ Before birth, deoxygenated blood sent to
▪ With physical exertion (severity varies)
mother, oxygenated blood arrives from
mother ▫ Dizziness, fatigue, palpitations, dyspnea
▫ Fetal heart sends blood through ▪ Impaired growth
foramen ovale ▪ Auscultation
▫ Oxygenated, deoxygenated blood mix ▫ Loud systolic murmur along left sternal
in truncus arteriosus. Both circulations border due to increased flow through
get same amount of oxygenated, mitral valve
deoxygenated blood ▫ Constant ejection click before S2
▫ Otherwise normal fetal development (closure of aortic, pulmonic valves)
▪ After birth, the baby relies on own lungs → ▫ Diastolic flow murmur at apex when
foramen ovale closes pulmonary blood flow increases
▫ Deoxygenated, oxygenated blood still
mixed → cyanosis
▫ Excess blood shunted to pulmonary DIAGNOSIS
circuit, as pressure in pulmonary circuit
is less than pressure of systemic circuit DIAGNOSTIC IMAGING
X-ray
RISK FACTORS ▪ Shows heart size, lung abnormalities,
▪ Combination of genes, maternal possible presence of excess fluid in lungs
environment
▪ Smoking, excessive alcohol intake, Echocardiogram
teratogenic medications during pregnancy; ▪ Single large vessel arising from left, right
gestational diabetes; viral illness during ventricles
pregnancy (e.g. German measles); ▪ Abnormalities of valves between large
OSMOSIS.ORG 45
vessel and ventricle it arises from Inotropic agents
▪ May show abnormal blood movement ▪ Strengthens cardiac contractions (e.g.
between right, left ventricle, and volume of Digoxin, treats congestive heart failure,
blood flow to lungs slows down heart rate, increases force of
contractions)
OTHER DIAGNOSTICS Prophylaxis
▪ Newborn pulse oximetry screening ▪ Antibiotics during dental/other surgical
▫ Low oxygen saturation procedures to avoid infections
▫ Diagnose before symptoms develop
ECG SURGERY
▪ Atrial enlargement (notching of P waves/P ▪ Goal: restore normal blood flow through
mitrale) heart
▪ Ventricular hypertrophy ▪ Procedures vary depending on individual
anatomy
▪ Abnormal T waves
▫ Close hole between right/left ventricles
▪ Right axis deviation
▫ Separate large vessel into pulmonary
artery, aorta
TREATMENT ▫ Reconstruct single large vessel into
new, complete aorta
▪ In rare cases, babies may survive into ▫ Implant new tube, valve to connect right
adulthood without surgical repair ventricle with upper part of pulmonary
artery, creating new, complete
pulmonary artery
MEDICATIONS
Diuretics OTHER INTERVENTIONS
▪ Gets rid of excess fluid (e.g. chlorothiazide) ▪ Lifestyle: possible limitation on intense
physical activity
▪ Lifelong monitoring
Figure 8.2 llustration depicting blood flow through the heart in persistent truncus arteriosus.
46 OSMOSIS.ORG
Figure 8.3 Gross pathology of a persistent truncus arteriosus. Both the left and right ventricles
pump blood to both the aorta and pulmonary artery through a quadricuspid truncus valve.
Figure 8.4 Gross pathology of a persistent

truncus arteriosus. Both the left and right
ventricles pump blood to both the aorta and
pulmonary artery through a quadricuspid
truncus valve.
OSMOSIS.ORG 47
TETRALOGY OF FALLOT
osms.it/tetralogy-of-fallot

▪ Combination of four congenital heart ▪ Depend upon severity of stenosis
abnormalities ▪ Less severe right ventricular outflow
▪ Right ventricular outflow tract stenosis obstruction often asymptomatic
(pulmonic stenosis): obstructs pulmonary ▪ Cyanosis around lips, fingernails (“blue
circulation baby syndrome” )
▪ Right ventricular hypertrophy: ▪ Poor feeding/failure to thrive
compensates for right ventricular outflow ▪ Harsh holosystolic murmur at left upper
tract stenosis sternal border → sounds like pulmonary
▪ Ventricular septal defect (VSD): hole in wall stenosis
between ventricles. High pressure in right ▫ Right ventricular heave
ventricle → blood shunts from right to left
▪ Older infants, children
→ deoxygenated blood to body
▫ Clubbed fingers, toes after a few
▪ Aorta overrides ventricular septal defect:
months
aorta in abnormal position. Variable
presentations ▫ Exertional dyspnea
▫ Hypercyanotic episode (tet spell): on
exertion, infant’s oxygen demands
CAUSES increase → sudden decrease in oxygen
▪ Arises during cardiovascular development saturation → cyanosis
▪ Most common cause of cyanotic congenital
heart defects
▪ Four abnormalities together cause DIAGNOSIS
▫ Mixing oxygenated, deoxygenated
blood DIAGNOSTIC IMAGING
▫ Narrowed vessels/valves that increase Echocardiography
cardiac workload
▪ Pre/postnatal
▪ Severity of stenosis affects blood flow,
changing pressure differentials Chest X-ray
▫ Mild stenosis: left-right shunt → ▪ “Boot-shaped” heart
oxygenated blood simply goes through
pulmonary circulation again
▫ Severe stenosis: right-left shunt → MNEMONIC: PROVe
deoxygenated blood enters body Components of tetralogy of
circulation → less oxygen to tissues Fallot
▪ Leads to pulmonic regurgitation: blood Pulmonary infundibular
flows backwards into RV, right heart stenosis
overloads, can cause right-sided heart Right ventricle hypertrophy
failure
Overriding aorta
▪ Associated with alcohol exposure in utero,
Ventricular septal defect
maternal age 40+ years, poor nutrition or
viral illness during pregnancy (e.g. rubella),
Down syndrome or DiGeorge syndrome,
positive family history of tetralogy of Fallot
48 OSMOSIS.ORG
OTHER DIAGNOSTICS
ECG
▪ Right ventricular hypertrophy, right atrial
enlargement
TREATMENT
MEDICATIONS
Prostaglandin E1 analogs (alprostadil)
▪ Severe cases Figure 8.5 Digital clubbing in an adult with
▪ Keep ductus arteriosus open → improve tetralogy of Fallot.
cyanosis until surgery
OTHER INTERVENTIONS
▪ Treat tet spell
▫ Infants squat to reduce cyanosis: kinks
femoral arteries → increases vascular
resistance → increases systemic
pressure → increases pressure in left
ventricle to greater than pressure in
right ventricle → reverse shunt to left-
right → resolve cyanosis
SURGERY
Figure 8.6 A chest radiograph of an infant
▪ Cardiac repair surgery (first year of life) demonstrating the classic boot-shaped heart
▫ VSD patch closure (only oxygenated seen in tetralogy of Fallot.
blood flows from left ventricle into aorta)
▫ Right ventricular outflow tract enlarged
Figure 8.7 Illustration depicting blood flow through a heart with Tetralogy of Fallot.
OSMOSIS.ORG 49
TOTAL ANOMALOUS PULMONARY
VENOUS RETURN
osms.it/anomalous-pulmonary-venous

▪ Congenital heart defect characterized by ▪ Severity of symptoms depend upon
anomalous connection of the pulmonary presence/degree of obstruction
veins and the heart ▪ Cyanosis, tachypnea, tachycardia, dyspnea,
▪ Occurs during first eight weeks of fetal failure to thrive, recurrent respiratory
development; cause unknown infections
▪ In case of infradiaphragmatic variant: liver
TYPES enlargement
Supracardiac variant
▪ Most common DIAGNOSIS
▪ Pulmonary veins open into brachiocephalic
veins/superior vena cava (SVC) DIAGNOSTIC IMAGING
Cardiac variant Chest X-ray

▪ Pulmonary veins open into coronary sinus/ ▫ Snowman sign (figure of 8): dilated
right atrium SVC, pulmonary vein, brachiocephalic
artery formshead; dilated right atrium
Infradiaphragmatic variant forms snowman’s body
▪ Pulmonary veins open into portal/hepatic
Echocardiography
veins
▪ Right ventricular and pulmonary artery
Mixed variant volume loading
▪ Oxygenated blood travels through ▪ Might show left atrium with no connecting
pulmonary veins to right atrium/veins → veins
blood does not leave pulmonary circulation
→ no systemic circulation LAB RESULTS
▪ Incompatible with life unless foramen ▪ Assess oxygenation and acid-base status:
ovale/patent ductus arteriosus present decreased values
→ oxygenated and deoxygenated blood
mix → established connection between
pulmonary and systemic circulation OTHER DIAGNOSTICS
▪ Anomalous connections often accompanied
ECG
by pulmonary vein obstruction →
pulmonary venous hypertension, severe ▪ Right ventricular hypertrophy
cyanosis Auscultation
▪ Systolic ejection murmur
COMPLICATIONS ▪ Increased pulmonary component of S2
▪ Recurrent pulmonary vein stenosis ▪ Split S2
▪ S3 gallop
50 OSMOSIS.ORG
▫ If present, pulmonary venous

TREATMENT obstruction must be identified and
treated promptly
SURGERY
▪ Surgery to establish blood flow from the
right atrium to left atrium OTHER INTERVENTIONS
▪ Cardiac catheterization
TRANSPOSITION OF THE
GREAT VESSELS (TGA)
osms.it/transposition_of_great_vessels
RISK FACTORS
PATHOLOGY & CAUSES ▪ During pregnancy: diabetes, rubella, poor
nutrition, consumption of alcohol, > 40
▪ Abnormal development causes aorta to years old
arise from right ventricle, pulmonary artery
to arise from left ventricle
▪ Transposition creates two small circuits of SIGNS & SYMPTOMS
blood flow rather than one large
▫ Right side: right ventricle → aorta → ▪ In utero: asymptomatic
body → right atrium → right ventricle ▪ d-TGA:
(blood never oxygenated)
▫ Cyanosis, unchanged with supplemental
▫ Left side: left ventricle → pulmonary oxygen (less severe if VSD present)
artery → lungs → pulmonary veins →
▫ Tachypnea
left atrium → left ventricle (blood never
deoxygenated) ▫ Acidosis
▪ After birth → lungs used for oxygen → ▪ l-TGA:
foramen ovale, ductus arteriosus close ▫ Asymptomatic
→ no exchange between two circuits →
cyanosis, death
▪ Sometimes, foramen ovale or ductus DIAGNOSIS
arteriosus stay open, or baby has
ventricular septal defect (VSD); allows DIAGNOSTIC IMAGING
blood to circulate
Echocardiogram
▪ Different levels of severity of transposition
▪ Evaluate heart function, structure
of the great arteries (TGA)
▫ d-TGA: dextro-TGA/complete TGA Chest X-ray
(dextro = aorta on right) ▪ Classic triad
▫ l-TGA: levo-TGA/congenitally corrected ▫ Heart appears as egg on its side/“egg
TGA (levo = aorta on left). Ventricles, on a string” appearance
valves switched. Great vessels in normal ▫ Lung congestion
orientation, but connected to wrong
ventricle. Normal blood flow circuits ▫ Cardiomegaly
preserved Angiogram
▪ Pre-surgery
OSMOSIS.ORG 51
SURGERY
TREATMENT ▪ Balloon atrial septostomy: short-term
solution. Hole created in atrial septum
MEDICATIONS
▪ Surgically switch great vessels
▪ Prostaglandin E: short-term solution. Keeps
ductus arteriosus open ▫ Five year survival rate > 80%
▫ No treatment: one year survival rate
10%
Figure 8.8 Chest radiograph in both a lateral (L) and frontal (R) view, demonstrating the “egg on
a string” sign of transposition of the great vessels.
52 OSMOSIS.ORG
Figure 8.9 Illustration depicting blood flow through a heart with dextro transposition of the great
arteries.
Figure 8.10 Illustration depicting blood flow through a heart with levo transposition of the great
arteries.
OSMOSIS.ORG 53
54 OSMOSIS.ORG
NOTES
NOTES
HEART FAILURE

▪ Normal preload, ↓ contractility (inotropy;
PATHOLOGY & CAUSES force of contraction) → inadequate
emptying of ventricles during systole →
▪ A complex clinical syndrome characterized ↓ EF ≤ 40 (HFrEF); often also have some
by the heart’s inability to effectively fill and/ degree of diastolic dysfunction
or eject (pump) blood
▪ Stroke volume (SV): volume (mL) of blood HF with preserved ejection fraction
pumped by heart per contraction (HFpEF)
▪ Cardiac output (CO): volume of blood ▪ Diastolic HF; “filling dysfunction”
pumped by heart per minute (L/min) ▪ Causes: restrictive cardiomyopathy (e.g.
▫ CO = SV X heart rate amyloidosis, sarcoidosis), valve disease,
hypertension
▪ Preload: amount of blood in left ventricle
before contraction ▪ Ventricles noncompliant and unable to
fill during diastole → ↑ filling pressures ↓
▪ Afterload: stress on the ventricular wall
preload, normal contractility → ↓ SV →
during systole
preserved EF ≥ 50 (HFpEF)
▫ ↑ systemic resistance, ↑ blood viscosity,
aortic valve stenosis, ventricular dilation
→ ↑ afterload TYPES
▪ Inotropy: cardiac contractility ▪ Biventricular heart failure
▪ Ejection fraction (EF): % of blood leaving ▫ Left, right failure; systolic/diastolic
heart during each contraction ▪ Cor pulmonale
▫ Heart failure secondary to any cause of
▫E=
( stroke volume
end diastolic volume ) x100
pulmonary arterial hypertension
▪ Left-sided heart failure
▫ Impaired ability of the left ventricle
▪ Frank–Starling mechanism: loading to maintain adequate cardiac output
ventricle with blood during diastole, without an increase in left-sided filling
stretching out cardiac muscles → more pressures
forceful contraction; ↑ SV during systole ▪ Right-sided heart failure
Heart failure (HF) with reduced ejection ▫ Impaired ability of the right ventricle to
fraction (HFrEF) deliver of blood flow to the pulmonary
▪ Systolic HF; “pump dysfunction” circulation and ↑ right atrial pressure
▪ Causes: ↓ contractility/force of contraction ▪ Classification based on structure and
(e.g. myocardial infarction, myocarditis), symptoms
↓ blood supply to the heart (e.g. ▫ ACC/AHA HF Stages, NYHA Classes
coronary artery disease), ↑ afterload (see table)
(e.g. hypertension), impaired mechanical
function (e.g. valve disease)
OSMOSIS.ORG 55
RISK FACTORS ▪ Arrhythmias
▪ Cardiac disorders: ischemic heart disease, ▪ End organ damage: due to lack of perfusion
valvular heart disease, hypertension, LV ▪ Liver damage (congestive hepatopathy)
hypertrophy, peripartum cardiomyopathy, ▪ Exacerbation
myocarditis, congenital heart disease,
▫ See mnemonic
chronic tachyarrhythmias
▫ Certain drugs may exacerbate HF;
▪ Other chronic diseases: hypertension,
e.g. NSAIDs, excessive doses of beta
diabetes, obesity, chronic lung disease,
blockers, calcium channel blockers,
infiltrative diseases (e.g. amyloidosis)
cyclophosphamide
▪ Toxins: cigarette smoking, ethanol,
cardiotoxic medications (e.g. doxorubicin,
amphotericin B); illicit drugs (e.g. MNEMONIC: FAILURE
amphetamines, cocaine)
Exacerbation of Heart failure
▪ High-output states: thyrotoxicosis, anemia
Forgot medication
▪ ↑ age
Arrhythmia/Anemia
Ischemia/Infarction/Infection
COMPLICATIONS Lifestyle (e.g. too much salt)
▪ Cardiogenic shock Upregulation of CO (e.g.
▪ Biventricular heart failure pregnancy, hyperthyroidism)
▫ Left/right-sided HF precursor/ Renal failure
complication of each other Embolism (e.g. pulmonary)
56 OSMOSIS.ORG
Chapter 9 Heart Failure
OTHER DIAGNOSTICS
SIGNS & SYMPTOMS ▪ History and physical examination
identifying characteristic symptoms,
▪ High filling pressures: pulmonary edema, evidence of fluid retention and/or
dyspnea, orthopnea, exercise intolerance, hypoperfusion and functional impairment
paroxysmal nocturnal dyspnea (PND), due to cardiac dysfunction
basilar crackles, tachypnea, jugular venous
distention (JVD), hypoxemia, fatigue, ECG
peripheral edema, hepatomegaly, S3 ▪ Identifies contributing rhythm disturbances
▪ Low cardiac output: tachycardia,
hypotension, cool extremities, ↓ pulse
pressure, ↓ urine output, ↓ appetite
DIAGNOSIS
DIAGNOSTIC IMAGING
Chest X-ray
▪ Detects cardiomegaly, chamber and vessel
enlargement, pulmonary congestion,
presence of pericardial and pleural
effusions
Doppler echocardiography
▪ Evaluates hemodynamics related to in
valvular and biventricular function
Right heart (pulmonary artery) catheter-

ization TREATMENT
▪ Measures CO (cardiac index), filling
pressures, pulmonary capillary wedge MEDICATIONS
pressure (PCWP) ▪ Individualized in accordance with New
MRI York Heart Association (NYHA) class, EF,
comorbidities
▪ Visualizes ventricular volumes, mass,
presence of myocardial remodeling ▪ Angiotensin converting enzyme (ACE)
inhibitor or angiotensin II receptor blockers
(ARB)
LAB RESULTS ▪ Beta-blocker (carvedilol, bisoprolol,
▪ ↑ B-type natriuretic peptide (BNP) and/or metoprolol ER)
N-terminal pro-BNP ▪ Aldosterone agonist
▪ ↑ serum creatinine and blood urea nitrogen ▪ Mineralocorticoid receptor antagonist
(BUN) indicates glomerular filtration rate ↓ (HFpEF)
GFR due to hypoperfusion
▪ Acute decompensation
▪ ↑ serum total bilirubin and aminotransferase
▫ See mnemonic
indicates congestive hepatopathy from
right-sided HF
▪ ↑ serum lactate if cardiogenic shock
▪ Exercise testing: six-minute walk test
and/or a cardiopulmonary exercise test
measuring oxygen uptake (Vo2) evaluates
exercise capacity
OSMOSIS.ORG 57
MNEMONIC: POND OTHER INTERVENTIONS
Acute decompensation ▪ Lifestyle modifications
Position (upright) +/- positive ▫ Low dietary salt, exercise as tolerated,
pressure ventilation (e.g. smoking cessation, minimize alcohol
BiPAP) intake
Oxygen ▪ Ventricular assist device (VAD)
Nitrates ▪ Implanted defibrillator
Diuretics ▪ Biventricular pacemaker for
resynchronization
SURGERY
▫ Considered in NYHA class of III or
IV despite maximized medical and
resynchronization therapy
COR PULMONALE
osms.it/cor_pulmonale
▪ Recent surgery, hypercoagulable states (↑
PATHOLOGY & CAUSES risk of pulmonary embolism)
▪ Right ventricular hypertrophy, dilation,

and/or dysfunction due to pulmonary COMPLICATIONS
hypertension secondary to pulmonary ▪ RV failure
disease (e.g. chronic obstructive pulmonary ▪ Liver dysfunction
disease (COPD), pulmonary fibrosis),
upper airway obstruction (e.g. obstructive
sleep apnea, obesity-hypoventilation SIGNS & SYMPTOMS
syndrome), or chest wall irregularities (e.g.
kyphoscoliosis) ▪ Dyspnea, chest pain, peripheral edema,
▪ Acute cor pulmonale develops in the jugular venous distension, hepatomegaly
setting of a sudden volume and/or pressure
overload in the right side of the heart; e.g.
massive pulmonary embolism DIAGNOSIS
▪ ↑ pulmonary vascular resistance → ↑
pulmonary circuit afterload → ↑ right DIAGNOSTIC IMAGING
ventricular workload → right ventricular
hypertrophy or dilatation → impaired right Chest X-ray
ventricular function and failure → ↑ right ▪ Visualizes right ventricular hypertrophy,
atrial pressure → fluid back-up into venous distended pulmonary vasculature,
circulation → peripheral edema pulmonary edema
Echocardiography
RISK FACTORS ▪ Detects structural and functional changes
▪ Presence of parenchymal or vascular lung of right ventricle; estimates right ventricular
disease, chronic airway obstruction systolic pressures
▪ Smoking
58 OSMOSIS.ORG
MRI SURGERY
▪ Visualizes right ventricular hypertrophy, ▪ Heart-lung transplant for resistant cor
right atrial enlargement, tricuspid valve pulmonale
dysfunction regurgitation, retrograde flow
Cardiac catheterization OTHER INTERVENTIONS

▪ ↑ elevated central venous pressure, ↑ ▪ Treat underlying disease process
right ventricular, end-diastolic pressure, ▪ Lifestyle
evidence of underlying pulmonary disease ▫ Low dietary salt, exercise as tolerated,
smoking cessation
TREATMENT
MEDICATIONS
▪ Supplemental oxygen
▪ Loop diuretic
DIASTOLIC HEART FAILURE

osms.it/diastolic-heart-failure

▪ A clinical syndrome characterized by failure ▪ Fatigue, dyspnea, orthopnea, exercise
of the heart to pump sufficient blood to intolerance, pulmonary rales, JVD
meet the metabolic needs of the body due
to ↓ ventricular filling
▪ HF with preserved ejection fraction DIAGNOSIS
(HFpEF)
▪ Filling dysfunction DIAGNOSTIC IMAGING
▫ Stiff, non-compliant ventricle → ↓ Chest X-ray
ventricular relaxation → ↑ end diastolic
▪ Cardiomegaly; pulmonary vascular
pressure → ↑ resistance to filling →
congestion; enlargement of right atrium,
↓ preload → EF ≥ 50, ↓ SV, ↓ CO →
ventricle, and pulmonary arteries
pulmonary congestion
Doppler echocardiography
RISK FACTORS ▪ Altered mitral flow velocity, ↑ LVEDP, LV
▪ ↑ age, restrictive cardiomyopathy (e.g. hypertrophy with concentric remodeling,
amyloidosis, sarcoidosis); hypertrophic LA enlargement, ↑ pulmonary artery
cardiomyopathy, long-standing systolic pressure (PASP)
hypertension, valve disease (especially
aortic stenosis), CAD, diabetes, obesity LAB RESULTS
▪ ↑ BNP/NT-proBNP
COMPLICATIONS
▪ Arrhythmias, pulmonary embolism,
pulmonary hypertension, right ventricular
failure
OSMOSIS.ORG 59
OTHER INTERVENTIONS
TREATMENT ▪ Manage contributing factors and associated
conditions
MEDICATIONS
▪ Lifestyle modifications
Alleviation of symptoms ▫ Smoking cessation, ↓ sodium intake,
▪ Diuretics; antihypertensives weight management, ↓ alcohol intake
▫ Beta blockers, ACE inhibitors, ARBs,
aldosterone antagonists
LEFT HEART FAILURE

osms.it/left-heart-failure
RISK FACTORS
PATHOLOGY & CAUSES ▪ Coronary artery disease, infiltrative disease
(e.g. amyloidosis, hemochromatosis) →
▪ A clinical syndrome due to an alteration cardiomyopathy
of structure and/or function of the left
▪ Hypertension, aortic stenosis → ↑ afterload
ventricle (LV) resulting in ↓ cardiac output,
pulmonary congestion, and ↓ peripheral ▪ Mitral or aortic regurgitation → ↑ preload
perfusion ▪ Exposure to toxins → myocardial damage
▪ Categorized according to left ventricular ▪ Arrhythmias → ↓ filling, ↓ ineffective
ejection fraction (LVEF) contractions
▫ Systolic HF: ↓ LVEF ≤40 percent (HFrEF) ▪ age > 60
▫ Diastolic HF: preserved LVEF (HFpEF) ▪ Obesity
▪ ↓ cardiac output → backup of blood into ▪ Diabetes mellitus/metabolic syndrome
left atrium → pulmonary circulation →
↑ pressure in pulmonary capillaries → COMPLICATIONS
pulmonary edema → ↓ gas exchange,
▪ Pulmonary edema, pulmonary hemorrhage
dyspnea
(congested capillaries burst), pleural
▪ Neurohormonal compensatory mechanisms effusion, renal insufficiency
▫ RAAS and adrenergic activation
→ renal salt and water retention +
vasoconstriction → ↑ contractility, ↑ SIGNS & SYMPTOMS
circulating volume → ↑ CO, ↑ organ
perfusion ▪ Exertional dyspnea, orthopnea; (PND),
▫ Adverse effects of compensation: ↑ pulmonary edema (frothy, pink-tinged
afterload, ↑ LV workload, LV remodeling sputum), bibasilar rales, cough, nocturia,
▫ Natriuretic peptide secretion occurs in restlessness, confusion. S3/S4
response to compensatory mechanisms
and atrial stretch → diuresis, natriuresis,
partial RAAS inhibition
60 OSMOSIS.ORG
Echocardiography
▪ LV hypertrophy with eccentric remodeling,
↑ LVEDP, LA enlargement, ↑ PASP
OTHER DIAGNOSTICS
▪ ECG
▫ Identifies contributing rhythm
disturbances
TREATMENT
Figure 9.1 The gross pathological appearance MEDICATIONS
of pulmonary edema. Exerting pressure on ▪ Diuretics, beta blockers, ACE inhibitors,
the lung parenchyma causes frothy white ARBs, ARNI, hydralazine/nitrate
fluid to exude from it. combination, aldosterone antagonists
▫ See mnemonic
DIAGNOSIS
LAB RESULTS MNEMONIC: POND
▪ ↑ BNP/NT-proBNP Acute decompensation
Position (upright) +/- positive
pressure ventilation (e.g.
DIAGNOSTIC IMAGING BiPAP)
Chest X-ray Oxygen
▪ Cardiomegaly, pulmonary vascular Nitrates
congestion, enlargement of right atrium, Diuretics
ventricle, and pulmonary arteries
MEDICATIONS
▪ Diuretics, beta blockers, ACE inhibitors,
ARBs, ARNI, hydralazine/nitrate
combination, aldosterone antagonists
▫ See mnemonic
SURGERY
OTHER INTERVENTIONS
▪ Manage contributing factors and associated
conditions
▪ Lifestyle modifications: smoking cessation,
↓ sodium intake, weight management, ↓
Figure 9.2 A plain chest X-ray image alcohol intake
demonstrating pulmonary edema. The ▪ Cardiac rehabilitation
vessels at the hila are prominent and there
▪ Implantable cardioverter-defibrillator (ICD)
are numerous Kerley B lines.
▪ Ventricular assist device
OSMOSIS.ORG 61
pulmonary edema. There is flocculent fluid
within the alveolar spaces.
Figure 9.4 Pitting edema in an individual with

left-sided heart failure.
RIGHT HEART FAILURE

osms.it/right-heart-failure
COMPLICATIONS
PATHOLOGY & CAUSES ▪ Eventual failure of left side of heart
▪ Tricuspid regurgitation
▪ A clinical syndrome due to an alteration
of structure and/or function of the right ▪ Congestive hepatopathy
ventricle (RV) leading to suboptimal ▪ Cardiac cachexia
delivery of blood flow to the pulmonary ▫ Nausea, vomiting, anorexia, and diffuse
circulation and/or elevated venous abdominal pain due to abdominal
pressures venous congestion → weight loss
▪ ↑ venous pressure → systolic volume
overload
▪ ↑ RV workload (most often due to SIGNS & SYMPTOMS
pulmonary congestion secondary to LV
failure) → RV hypertrophy → ↓ pumping ▪ JVD, hepatojugular reflux, fatigue (related
ability to poor gas exchange), exercise intolerance,
peripheral edema, hepatosplenomegaly,
ascites, S3/S4
CAUSES
▪ Left-sided heart failure, associated
pulmonary edema (most common cause), DIAGNOSIS
right ventricular infarction, bacterial
endocarditis, pulmonic valve stenosis, DIAGNOSTIC IMAGING
cardiomyopathy
Chest X-ray
▪ Cardiomegaly, pulmonary vascular
congestion; enlargement of right atrium,
ventricle, pulmonary arteries
62 OSMOSIS.ORG
Echocardiography
▪ Evaluates RV size and function; detects
hemodynamic alterations
MRI
▪ Myocardial tissue, ventricular volume,
muscle damage
Right heart catheterization

▪ ↑ pressure in heart chambers and lungs
LAB RESULTS
▪ ↑ BNP/NT-proBNP
▪ ↑ serum total bilirubin and aminotransferase
indicates congestive hepatopathy
OTHER DIAGNOSTICS Figure 9.5 A distended external jugular vein

▪ Clinical presentation: right heart (EJV) in an individual with right heart failure.
dysfunction, rule out left heart dysfunction
ECG
▪ Identifies contributing rhythm disturbances
TREATMENT
MEDICATIONS
▪ Loop diuretics
▫ Fluid management
▪ Vasopressors
▫ Circulatory support
OTHER INTERVENTIONS
▪ Treat underlying condition
MNEMONIC: LMNOP
Treatment for Right heart
failure
Lasix
Morphine
Nitrites
Oxygen
VassoPressors
OSMOSIS.ORG 63
NOTES
NOTES
HEART VALVE DISEASE

▪ Wear and tear, external factors, varies by ▪ Auscultation → echocardiogram,
type transesophageal echocardiogram,
▪ Older age, smoking, hypertension, catheterization
hyperlipidemia, diabetes mellitus,
connective tissue disorders, endocarditis,
heart attack TREATMENT
▪ Lifestyle changes, pharmacotherapeutics,
SIGNS & SYMPTOMS surgical intervention
▪ Normally, heart valves keep blood moving

by opening for forward flow and closing to
prevent backflow; symptoms evidence of
flow alterations
▪ Murmurs, altered heart sounds
▪ Sometimes asymptomatic
▪ Advanced disease → heart failure
▪ Left ventricular failure symptoms
▪ Forward effects
▫ Decreased perfusion to body tissues
(e.g. decreased perfusion to brain
= syncope; decreased perfusion to
coronary arteries = chest pain, angina)
▪ Backward effects
▫ Blood backs up to left atrium, into
pulmonary circulation (e.g. pulmonary
edema, dyspnea, fatigue, paroxysmal
nocturnal dyspnea)
▪ Right ventricular failure symptoms
▪ Backup of blood to venous circulation (e.g.
peripheral edema, hepatosplenomegaly) Figure 10.1 Illustration of phonocardiograms
from normal and abnormal heart sounds.
64 OSMOSIS.ORG
Chapter 10 Heart Valve Disease
AORTIC INSUFFICIENCY
osms.it/aortic-insufficiency
COMPLICATIONS
PATHOLOGY & CAUSES
Heart failure
▪ Widening/insufficiency of aortic valve ▪ High blood volume left ventricle → left
▪ Doesn’t close fully, blood flows backwards ventricle compensates, adding sarcomeres
during diastole in series → eccentric left ventricular
▪ AKA aortic regurgitation hypertrophy → left ventricular dysfunction
→ heart failure
CAUSES
Aortic root dilation
SIGNS & SYMPTOMS
▪ Root dilates, pulls apart leaflets
Abnormal heart sounds
▫ Most root dilations idiopathic; some
▪ Early decrescendo diastolic murmur, usually
caused by aortic dissection, aneurysm,
heard at left lower sternal border/apex
Marfan syndrome, Ehlers-Danlos
syndrome, syphilis, ankylosing ▪ Systolic flow murmur may develop in
spondylitis, rheumatoid arthritis, chronic aortic regurgitation; increased
systemic lupus erythematosus blood flow through valve during systole,
regardless of stenosis
▫ Valvular damage: infective endocarditis,
rheumatic fever, bicuspid aortic valve Wide pulse pressure
▫ Inflammation → fibrosis → valve can’t ▪ Increased systolic blood pressure (SBP) and
seal decreased diastolic blood pressure (DBP) =
hyperdynamic circulation
Acute aortic regurgitation (medical emer-
gency) ▪ Calculation for pulse pressure (PP)
▪ Infective endocarditis, trauma, aortic ▫ SBP - DBP = PP
dissection ▪ Hill’s sign
▫ Acute aortic regurgitation presents ▫ Exaggerated difference in SBP when
with sudden cardiovascular collapse, comparing upper, lower limbs
pulmonary edema ▪ Bounding pulses
▫ Chronic aortic regurgitation presents ▫ Evidence of wide PP
less urgently, signs of heart failure ▫ Corrigan pulse (water-hammer pulses):
bounding pulse, blood hammers against
RISK FACTORS arterial walls
▪ Hypertension, syphilis, genetic disorders Other signs
(Marfan’s syndrome, Ehlers-Danlos ▪ de Musset’s sign
syndrome)
▫ Head bobs in time with heartbeat
▪ Quincke’s sign
▫ Light compression of capillary bed leads
to visible pulsations in fingers
OSMOSIS.ORG 65
▪ Traub’s sign OTHER DIAGNOSTICS
▫ Pistol shot sound head over femoral
Electrocardiogram
arteries
▪ Shows non-specific features of left
▪ Duroziez’s sign
▫ Systolic, diastolic bruit over femoral
artery when partially compressed
▪ Landolfi’s sign TREATMENT
▫ Diastolic pupil dilation
▪ Goal: improve cardiac output, decrease
Acute aortic regurgitation regurgitant flow volume
▪ Severe dyspnea, chest pain, hypotension =
left ventricular failure, cardiogenic shock
MEDICATIONS
▪ Vasodilators to reduce afterload
DIAGNOSIS
SURGERY
DIAGNOSTIC IMAGING
▪ Surgical valve replacement
Echocardiography ▪ Surgical replacement once ejection fraction
▪ Using Doppler flow, observe regurgitation < 55%
jet through aortic valve during diastole
Chest X-ray
▪ Nonspecific, may observe cardiomegaly
AORTIC STENOSIS
osms.it/aortic-stenosis
COMPLICATIONS
PATHOLOGY & CAUSES
▪ Heart failure, microangiopathic hemolytic
anemia (red blood cells damaged as they
▪ Stiffening, thickening/calcification of aortic
squeeze through small valve opening),
valve (no longer opens fully during systole)
Heyde’s syndrome
▪ Valve opening narrows → pressure
gradient increases across valve
SIGNS & SYMPTOMS
CAUSES
Asymptomatic
Mechanical stress
▪ Due to slow progression; abnormal heart
▪ Damaged endothelial cells over time → sounds heard on auscultation
fibrosis and calcification → stiff valve does
▫ Ejection click
not open fully
▫ Harsh, systolic, crescendo-decrescendo
Rheumatic heart disease systolic murmur at upper sternal border,
▪ Repeated inflammation, repair → fibrosis radiating to carotids
→ commissural fusion
Advanced state aortic stenosis
▪ Classic triad: angina, syncope, exertional
dyspnea
66 OSMOSIS.ORG
▪ Additional heart sounds: soft, single

S2/paradoxical S2 split; crescendo- TREATMENT
decrescendo systolic murmur peaks later
(the later the peak, the more severe the MEDICATIONS
stenosis); S4 ▪ Venodilators, calcium channel blockers,
▪ Pulsus parvus et tardus (pulse weak, administer beta blockers with caution
delayed)
▪ Narrowed pulse pressure SURGERY
▪ Surgical valve replacement if necessary
MNEMONIC: SAD
Characteristics of Aortic
OTHER INTERVENTIONS
stenosis ▪ If mild, no exercise restrictions; if severe,
reduced physical activity
Syncope
Angina
Dyspnea
DIAGNOSIS
DIAGNOSTIC IMAGING
Transthoracic echocardiogram (TTE)
▪ Observe small aortic orifice during systole,
increased pressure gradient across valve,
left ventricular hypertrophy, calcification of
aortic valve Figure 10.2 Gross pathology of severe aortic
stenosis as a consequence of previous
Cardiac catheterization
rheumatic heart disease. The valve leaflets
▪ Useful for surgical planning are stiffened and fused resulting in a
narrowed lumen.
OTHER DIAGNOSTICS
Electrocardiogram
▪ Shows non-specific features of left
Figure 10.3 Gross pathology of a nodular

bicuspid aortic valve.
OSMOSIS.ORG 67
MITRAL INSUFFICIENCY
osms.it/mitral-insufficieny
▫ Associated with connective tissue
PATHOLOGY & CAUSES disorders (e.g. Marfan syndrome,
Ehlers–Danlos Syndrome)
▪ Mitral valve prolapses (falls back into ▫ Causes larger valve leaflet area,
atrium) elongation of chordae tendineae →
▪ Most common valvular condition mitral valve more prone to rupture
▪ AKA mitral regurgitation (rupture usually happens to chordae
tendineae on posterior leaflet, leaflet
folds up into left atrium)
CAUSES
▫ Doesn’t always cause mitral
Myxomatous degeneration regurgitation but often does since blood
▪ Leaflets, connective tissue, surrounding will leak backwards into left atrium if
tissue weakened → mitral valve prolapse leaflets don’t form perfect seal
68 OSMOSIS.ORG
Damage to papillary muscles ▪ Atrial fibrillation

▪ Caused by heart attacks ▫ Left atrium dilates → muscle walls
▫ Papillary muscle dies → can’t anchor stretch, pacemaker cells irritated
chordae tendineae → mitral valve flops ▪ Thrombus formation, embolism
back → blood leaks back into left atrium ▫ Atrial fibrillation → blood stagnates,
pools → increased risk of thrombus
Left-sided heart failure formation, blood clots → goes to
▪ Left sided heart failure → left ventricle systemic circulation
dilates → stretches mitral valve annulus ▪ Dysphagia
(ring) → blood leaks back into left atrium →
▫ E.g. difficulty swallowing solid foods;
ventricular dilation
dilated atrium compresses neighboring
Rheumatic fever esophagus
▪ Inflammatory disease affecting heart tissue,
leading to chronic rheumatic heart disease
▪ Chronic inflammation → leaflet fibrosis →
SIGNS & SYMPTOMS
leaflets cannot form complete seal → blood
leaks through ▪ Clinical manifestations of heart failure (e.g.
fatigue, swelling, rapid heartbeat)
Mitral regurgitation ▪ Holosystolic murmur
▪ Can also cause left-sided heart failure ▫ Lasts for duration of systole
▪ Regurgitant flow back into left atrium →
increased preload → increased workload
on left atrium, ventricle → left eccentric DIAGNOSIS
hypertrophy (new sarcomeres added in
series to existing ones) → left sided heart DIAGNOSTIC IMAGING
failure
Transthoracic echocardiography (TTE) or
transesophageal echocardiogram (TEE)
RISK FACTORS ▪ Enlarged left atria/ventricle
▪ Intravenous (IV) drug use (increases ▪ Rupture/tear/elongation of mitral valve
likelihood of infective endocarditis) chordae
▪ Congenital bicuspid aortic valve (baby born ▪ Regurgitation (seen as retrograde blood
with aortic valve that has only two instead flow on Doppler imaging)
of three leaflets)
▪ Systolic bowing of mitral leaflet (>2mm
▪ Diabetes, high blood pressure, smoking beyond annular plane)
▪ May reveal leaflet thickening, flail leaflet,
COMPLICATIONS annular dilation
▪ Pulmonary congestion, edema
Chest X-ray
▫ Constant elevation in blood volume,
pressure in left atrium causes dilation ▪ May demonstrate cardiomegaly secondary
→ blood backs up into pulmonary to left atrial/ventricular dilation
circulation
▪ Pulmonary hypertension OTHER DIAGNOSTICS
▫ Extra blood volume, pressure in left
ECG
atrium backs up into lung causing higher
pressure in pulmonary circulation ▪ Abnormal findings often observed in MVP
▪ Right-sided heart failure ▫ Early repolarization in inferior leads
▫ Backup of blood in left atrium, lungs ▫ ST depression, QTc prolongation
→ pulmonary hypertension → right ▫ Premature ventricular contractions
ventricular hypertrophy → right-sided ▪ Not conclusive; result can be normal in
heart failure people who have mild mitral valve disease
OSMOSIS.ORG 69
▫ Reshape valve tissue to create tighter
TREATMENT seal
▫ Repair tears to increase support at base
MEDICATIONS of valve
▪ Lower high blood pressure (e.g. diuretics)
▫ Replace with prosthetic valve
▪ Lower cholesterol (e.g. statins)
▪ Prevent arrhythmias (e.g. amiodarone)
▪ Prevent clots with blood thinners/
anticoagulants (e.g. heparin, warfarin)
▪ Treat heart failure (e.g. digoxin to increase
contractility)
SURGERY
Replacing/repairing valve
▪ Severe mitral regurgitation or stenosis =
valve repair or surgical replacement of valve
▫ Separate fused valve flaps
Figure 10.4 Illustration depicting differences

in mitral valve shape between mitral valve
insuffiency (regurgitation) and mitral stenosis.
MITRAL STENOSIS
osms.it/mitral-stenosis
▪ Diabetes, high blood pressure, smoking
PATHOLOGY & CAUSES
▪ Narrowing of mitral valve COMPLICATIONS
▪ Rheumatic fever: inflammation → leaflets ▪ Pulmonary congestion, edema
fuse together (commissural fusion) → ▫ Constant elevation in blood volume,
prevents seal formation pressure in left atrium → left atrium
▫ Normal mitral valve opening dilates → blood backs up into
(4–6cm2/1.6–2.4in2) narrows to pulmonary circulation
2cm2/0.8in2 ▪ Pulmonary hypertension
▫ Smaller opening → harder for blood ▫ Extra blood volume, pressure in left
to flow from left atrium to ventricle atrium backs up into lung → higher
→ blood backs up in atrium → higher pressure in pulmonary circulation
pressure in left atrium ▪ Right-sided heart failure
▫ Backup of blood in left atrium, lungs
RISK FACTORS → pulmonary hypertension → right
ventricular hypertrophy → right-sided
▪ IV drug use
heart failure
▫ Increases likelihood of infective
▪ Atrial fibrillation
endocarditis
▫ Left atrium dilates → muscle walls
▪ Congenital bicuspid aortic valve
70 OSMOSIS.ORG
stretch, pacemaker cells irritated OTHER DIAGNOSTICS

▪ Thrombus formation, embolism
ECG
▫ Atrial fibrillation → blood stagnates,
▪ Reveals abnormal electrical activity
pools → increased risk of thrombus
depending on severity
formation, blood clots entering systemic
circulation ▫ Not conclusive; result can be normal
in people who have mild mitral valve
▪ Dysphagia
disease
▫ Dilated atrium compresses neighboring
esophagus
TREATMENT
▪ Lower high blood pressure (e.g. metoprolol,
▪ Clinical manifestations of heart failure
lisinopril, diuretics)
▪ “Snap” sound after S2 (closure of aortic,
▪ Lower cholesterol (e.g. statins)
pulmonic valves)
▪ Prevent arrhythmias (e.g. amiodarone)
▫ Higher pressure flowing through fibrotic
valve makes “snap” sound when valve ▪ Prevent clots with blood thinners/
opens anticoagulants (e.g. heparin, warfarin)
▫ Diastolic rumble following “snap” as ▪ Treat heart failure (e.g. digoxin to increase
blood forced through smaller opening contractility)
▪ Dyspnea/difficulty breathing
▫ Pulmonary congestion, pulmonary SURGERY
edema ▪ Replacing/repairing valve: severe mitral
regurgitation or stenosis = valve repair or
surgical replacement of valve
DIAGNOSIS ▫ Separate fused valve flaps
▫ Reshape valve tissue to create tighter
DIAGNOSTIC IMAGING seal
Echocardiography ▫ Repair tears to increase support at base
of valve
▪ Shows abnormal blood flow, narrowed/
insufficient valve ▫ Replace with prosthetic valve
Transesophageal echocardiogram (TEE)

▪ Enlarged left ventricle
▪ Enlarged left/right atria
▪ Possible rupture/tear of mitral valve
chordae
▪ Possible regurgitation
Stress test (echocardiography)

▪ Measure blood pressure pre-, post-test
▪ Record how long individual able to carry
out test
Chest X-ray
▪ Shows heart size, lung condition Figure 10.5 Gross pathology of a stenotic
mitral valve, viewed from the left atrium.
OSMOSIS.ORG 71
MITRAL VALVE PROLAPSE
osms.it/mitral-valve-prolapse
against closed airway), click comes
PATHOLOGY & CAUSES sooner, longer murmur
▫ Standing reduces venous return →
▪ Floppy mitral valve
less blood in ventricle → ventricle is
▪ Cusps of valve flop into atrium during slightly smaller → less room for leaflets
systole. → leaflet forced out earlier during
▪ Myxomatous degeneration from connective contraction
tissue disease (e.g. Ehler–Danlos, Marfan ▪ Individual may report palpitations
syndromes)
▪ Familial mitral valve prolapse
▫ Autosomal dominant: variable DIAGNOSIS
penetrance and expression
DIAGNOSTIC IMAGING
RISK FACTORS Chest X-ray
▪ Age ▪ May demonstrate cardiomegaly secondary
▪ Hypertension to left atrial/ventricular dilation
▪ History of rheumatic fever
Transthoracic echocardiography (TTE) or
▪ Connective tissue disorders
transesophageal echocardiogram (TEE)
▪ Enlarged left atria/ventricle
COMPLICATIONS ▪ Rupture/tear/elongation of mitral valve
▪ Heart failure, arrhythmias, systemic emboli, chordae
cardioembolic stroke, chordal rupture, ▪ Regurgitation (seen as retrograde blood
sudden death flow on Doppler imaging)
▪ Systolic bowing of mitral leaflet (> 2mm
SIGNS & SYMPTOMS beyond annular plane)
▪ May reveal leaflet thickening, flail leaflet,
annular dilation
▪ Usually asymptomatic
▪ Classic heart murmur: midsystolic click
followed by systolic murmur OTHER DIAGNOSTICS
▪ Murmur: blood leaks backward from left Physical examination
ventricle into left atrium
▪ Crescendo murmur in late systole heard
▪ Click: leaflet folding into atrium, suddenly over apex
stopped by chordae tendineae
▪ Mid-systolic click (due to rapid tensing of
▫ When an individual squats, click comes chordae tendineae)
later, shorter murmur
▫ Squatting increases venous return → ECG)
fills left ventricle with more blood → left ▪ Abnormal findings often observed in MVP
ventricle gets slightly larger → leaflets ▫ Early repolarization in inferior leads
have more space → ventricle contracts, ▫ ST depression, QTc prolongation
gets smaller → takes slightly longer for
▫ Premature ventricular contractions
leaflet to be forced into atrium
▪ Not conclusive; result can be normal in
▫ When individual stands/performs
people who have mild mitral valve disease
Valsalva maneuver (forceful exhalation
72 OSMOSIS.ORG
TREATMENT
MEDICATIONS
▪ If palpitations present
▫ Beta blockers; avoid smoking, caffeine
SURGERY
▪ Severe prolapse
▫ Valve repair/replacement (esp. when left
ventricular systolic function impaired)
Figure 10.6 Gross pathology of a mitral valve
prolapse (anterior superior leaflet) viewed
from the left atrium.
PULMONARY INSUFFICIENCY
osms.it/pulmonic-insufficiency

▪ Pulmonary valve doesn’t close fully → ▪ Abnormal heart sounds
blood leaks back into right ventricle ▫ Crescendo-decrescendo murmur: blood
▪ AKA pulmonic regurgitation flows through narrow pulmonary valve,
▪ Blood backflow increases right ventricular causes turbulence that gets louder as
blood volume → right ventricle needs to more blood flows/quieter as blood flow
work harder during systole → eccentric slows, blood leaks back from pulmonary
ventricular hypertrophy → heart failure artery into right ventricle, causes
murmur that starts loud, quietens
▪ Signs of right-sided heart failure may
CAUSES be present (e.g. fatigue, swelling, rapid
▪ Congenital malformation of the leaflets heartbeat)
common
▫ Tetralogy of Fallot (TOF), Noonan’s
syndrome, congenital rubella DIAGNOSIS
▪ Infective endocarditis, rheumatic heart
disease, systemic disease (e.g. carcinoid DIAGNOSTIC IMAGING
disease)
Echocardiogram
▪ Regurgitation seen on Doppler
COMPLICATIONS
▪ Right-sided heart failure Chest X-ray
▫ Ventricles cannot compensate for ▪ May show enlarged right ventricle
increased workload
▪ Microangiopathic hemolytic anemia
▫ Shearing damage to red blood cells
forced through smaller valve, leading to
hemoglobinuria
OSMOSIS.ORG 73
TREATMENT
SURGERY
▪ Valve replacement if symptomatic
Figure 10.7 Illustration depicting decrescendo

murmur as blood flows back into the right
ventricle.
PULMONARY STENOSIS
osms.it/pulmonic-stenosis

▪ Pulmonary valve doesn’t open fully; harder ▪ Initially asymptomatic
for right ventricle to pump blood to lungs ▪ Diastolic crescendo-decrescendo murmur:
▪ Mechanical stress over time abnormal heart sound caused by turbulent
▫ Damages endothelial cells around blood flow through pulmonary valve
valves → fibrosis, calcification → that does not close properly; starts loud,
hardens valve, makes it more difficult to quietens
open fully ▪ Ejection click: valve resists, then finally
▪ Eccentric right ventricular hypertrophy: snaps open
right ventricle must compensate for larger ▪ Appears often as right-sided heart failure
amount of blood volume due to backflow of
blood
DIAGNOSIS
CAUSES DIAGNOSTIC IMAGING
▪ Congenital malformation of leaflets
▫ Associated with tetralogy of Fallot, Echocardiogram
Noonan’s syndrome, congenital rubella ▪ Thickened leaflets, hard to see location of
▪ Systemic disease (e.g. carcinoid disease) stenosis

▪ History of rheumatic heart disease, heart
surgery, or infective endocarditis ▪ Balloon valvuloplasty
▪ Valve replacement if symptomatic right-
COMPLICATIONS sided heart failure
▪ Right-sided heart failure
▫ Right ventricle cannot compensate for
increased force required to push blood
through valve
74 OSMOSIS.ORG
Figure 10.8 Illustration depicting hypertrophy

of right ventricle due to increased blood
pressure in the right ventricle.
TRICUSPID INSUFFICIENCY
osms.it/tricuspid-insufficiency
▪ Infective endocarditis
PATHOLOGY & CAUSES ▪ Trauma
▫ Catheter insertion
▪ Cusps of valve prolapse during systole →
blood backs up into right atrium. ▫ Endocardial pacemaker insertion
▪ AKA tricuspid regurgitation ▫ Blunt chest trauma
CAUSES RISK FACTORS

▪ Rheumatic heart disease ▪ Disease processes may cause pulmonary
hypertension
▫ Most common cause
▪ IV drug abuse
▫ Autoimmune reaction involving valve
leaflets → chronic inflammation →
leaflet fibrosis → valve unable to form COMPLICATIONS
seal ▪ Heart failure
▪ Myocardial infarction ▫ Increased ventricular preload →
▫ Papillary muscles malfunction → eccentric ventricular hypertrophy →
destroyed papillary muscles can’t anchor right ventricular failure
chordae tendineae → blood flows from ▪ Ventricular hypertrophy
right ventricle to right atrium ▫ Structural change in heart → annulus
▪ Pulmonary hypertension stretches → more blood leakage →
▫ Increase in right ventricular pressure → worsens regurgitation
dilates tricuspid valve → blood flows
backward
▪ Congenital causes
▫ Leaflets are displaced → difficult to form
seal (e.g. Ebstein anomaly)
▪ Carcinoid syndrome
▫ Fibrous tissue deposited on valves
▪ Myxomatous valve degeneration
OSMOSIS.ORG 75
SIGNS & SYMPTOMS DIAGNOSIS
▪ Holosystolic murmur DIAGNOSTIC IMAGING
▫ Movement of blood heard throughout
Echocardiogram with Doppler
systole
▪ Shows backflow
▪ Carvallo’s sign
▫ Murmur gets louder with inspiration X-ray
due to negative pressure in chest, more ▪ Shows right ventricular enlargement
blood backs up into heart
▪ S3, S4
▪ Signs of right-sided heart failure TREATMENT
SURGERY
▪ Surgical repair/replacement if symptomatic
TRICUSPID STENOSIS
osms.it/tricuspid-stenosis

▪ Valve unable to open completely during ▪ Ejection click
diastole. ▫ Fibrotic valve makes distinctive snap
▪ Valve leaflets fuse (commissural fusion) → ▪ Diastolic rumble
narrowing of tricuspid valve → impaired ▫ As blood is forced through small valve
blood flow from right atrium to right opening
ventricle
▪ Increased ventricular preload → right
ventricular failure → signs of congestion in
CAUSES venous system
▪ Rheumatic heart disease ▫ Jugular venous distention (JVD)
▫ Most common cause may cause some individuals to feel
▫ Can occur with mitral regurgitation, uncomfortable fluttering in neck
aortic valve disease
▪ Congenital atresia, stenosis
DIAGNOSIS
▪ Pacemaker-induced fibrosis
▪ Cardiac tumors DIAGNOSTIC IMAGING
▪ Infective endocarditis
Echocardiography
▪ Assess degree of leaflet damage, flow
COMPLICATIONS across valve
▪ Increased right atrial volume, pressure →
atrial dilation → blood backs up into venous
circulation OTHER DIAGNOSTICS
▪ Dilation of right atrium → muscle walls Cardiac catheterization
stretch → pacemaker cells become irritable
▪ Measure pressure in right side of heart
→ increases risk of atrial flutter, fibrillation
76 OSMOSIS.ORG
TREATMENT
SURGERY
▪ Balloon valvuloplasty, valve repair/
replacement
Figure 10.9 Illustration depicting differences between tricuspid valve regurgitation and tricuspid
valve stenosis.
OSMOSIS.ORG 77
78 OSMOSIS.ORG
NOTES
NOTES
HYPERTENSION & HYPOTENSION

▪ Changes of blood pressure above (hyper-) OTHER DIAGNOSTICS
or below (hypo-) normal (120/80mmHg) ▪ Blood pressure cuff (sphygmomanometer)
or arterial catheter
CAUSES
▪ Mostly idiopathic, but can include various
causes: impaired regulatory pathways
TREATMENT
(hormonal/neurologic disorders), heart
▪ Hypotension: generally requires no
disease, kidney disease, medications etc.
treatment
▪ Hypertension: treated according to degree,
SIGNS & SYMPTOMS treat underlying cause if present
▪ Can be asymptomatic/include symptoms MEDICATIONS

according to underlying cause, degree of ▪ Hypertension: beta blockers, diuretics, ACE
change in blood pressure inhibitors, calcium channel blockers, etc.
▫ Hypertension: range from headache,
dyspnea, to blurred vision, oliguria,
seizures
▫ Hypotension: range from fatigue, pallor
to syncope
Figure 11.1 Illustration depicting endothelial damage caused by hypertension.
OSMOSIS.ORG 79
HYPERTENSION
osms.it/hypertension
glomerular filtration rate → ↓ secretion of
PATHOLOGY & CAUSES sodium + water → ↑ volume → ↑ blood
pressure
▪ Condition in which blood pressure is
▪ Preeclampsia/eclampsia in pregnancy:
regulated maladaptively, elevating blood
mechanism unknown
pressure over 140/90mmHg
▪ Coarctation of the aorta: low pressure
▪ Isolated systolic hypertension: systolic
past coarctation → low renal perfusion →
blood pressure is elevated, diastolic is not
activation of renin angiotensin-aldosterone
▪ Isolated diastolic hypertension: diastolic system (RAAS) → secondary hypertension
blood pressure is elevated, systolic is not
▪ Cushing’s syndrome: combination of
several pathophysiological mechanisms
CAUSES (e.g. elevated cortisol) that regulate plasma
volume, cardiac output, peripheral vascular
Primary/essential hypertension resistance
▪ Most cases (90%) ▪ Chronic kidney disease: fluid overload,
sodium retention
Secondary hypertension
▪ Known etiology, often reversible
▪ Renovascular hypertension: anything
MNEMONIC: RHNECCK
partially obstructing blood flow to
kidneys (e.g. atherosclerosis, vasculitis, Causes of Secondary
fibromuscular dysplasia). hypertension
▫ Decreased blood flow to kidneys → Renovascular hypertension
kidneys secrete renin → renin converts 1° Hyperaldosteronism
angiotensinogen to angiotensin I → NSAIDs
angiotensin converting enzyme converts Pre-Eclampsia / Eclampsia
angiotensin I to angiotensin II (active) → Coarctation of the aorta
angiotensin II effects:
Cushing’s syndrome
▫ Vasoconstriction: directly increases
Kidney Disease (chronic)
blood pressure
▫ Stimulation of sodium reabsorption:
increases water reabsorption RISK FACTORS
▫ Stimulation of adrenal cortex to release
aldosterone from adrenal cortex → Primary hypertension
aldosterone increases reabsorption of ▪ Risk increases with age, biological male,
sodium + water → increased volume → obesity, stress, sedentary lifestyle, family
high blood pressure history of hypertension
▪ Primary hyperaldosteronism: increased ▪ Race (in decreasing order of risk): African
aldosterone → increased reabsorption of descent > white European descent > Asian
sodium + water → increased volume → descent
increased blood pressure ▪ Diet: excessive sodium, alcohol intake
▪ Nonsteroidal anti-inflammatory drugs ▪ Abnormal lipid panel (high low-density
(NSAIDs) → inhibit cyclooxygenase in lipoproteins, low high-density lipoproteins,
kidneys → ↓ production of PGE-2 (renal high triglycerides)
vasodilator) → vasoconstriction of afferent
arterioles in kidneys → ↓ renal blood flow,
80 OSMOSIS.ORG
Chapter 11 Hypertension & Hypotension
Secondary hypertension
▪ Atherosclerosis: Elderly biological males
SIGNS & SYMPTOMS
▫ Atherosclerosis → renal stenosis → less ▪ Vast majority of cases asymptomatic
blood flow to renal arteries → activation
▪ May experience headache, dyspnea
of RAAS → renovascular hypertension
▪ Renal bruit in secondary hypertension due
to renal artery stenosis
COMPLICATIONS ▪ Hypertensive retinopathy
▪ Increased risk of atherosclerosis,
arteriosclerosis
▪ Arteriolar rarefaction: loss of arterioles DIAGNOSIS
▪ Coronary artery disease, left ventricular
hypertrophy, atrial fibrillation, stroke, OTHER DIAGNOSTICS
hypertensive nephropathy, retinopathy, ▪ Non-invasive/invasive blood pressure
aortic dissection, aneurysms monitoring
▫ High blood pressure: at least 2 separate
measurements with blood pressure
> 140/90mmHg
Figure 11.2 Illustration depicting stages of hypertension.
OSMOSIS.ORG 81
TREATMENT
▪ Reduce BP <140/90mmHg with lifestyle
modification first, then medical treatment
MEDICATIONS
Monotherapy/together
▪ Thiazide-type diuretics: reduce blood
volume by increasing excretion of sodium,
water
▪ Angiotensin-converting enzyme (ACE)
inhibitors: block ACE from converting
angiotensin I to angiotensin II → blocks
RAAS → dilates arteries, decreases blood
Figure 11.3 Retinal photograph volume
demonstrating changes of hypertensive ▫ Lower levels of angiotensin II →
retinopathy (AV nipping and tortuous vasodilation
vessels). ▪ Dihydropyridine calcium channel blockers:
disrupt movement of calcium through
calcium channels in blood vessel walls →
vasodilation
Other agents
▪ Angiotensin II receptor blockers (ARBs):
prevents the vasoconstrictive effects of
angiotensin II by blocking its receptors →
lowering blood pressure
▫ Used when individuals get a cough from
ACE inhibitors
▪ Beta receptor blockers: decrease
contractility, heart rate
Figure 11.4 Histological appearance of ▪ Alpha-2 agonist: stimulates alpha-2
renal artery hyalinosis; a manifestation of receptors → decreases sympathetic activity
hypertensive renal disease. → decreased blood pressure, heart rate
▪ Renin inhibitor: aliskiren
▫ Lower levels of angiotensin I
▪ Hydralazine: elicits direct vasodilation
of vascular smooth muscle, useful in
pregnancy
OTHER INTERVENTIONS
▪ Low sodium diet, exercise, quit smoking,
limit alcohol, maintain healthy weight
82 OSMOSIS.ORG
Chapter 11 Hypertension & Hypotension
HYPERTENSIVE EMERGENCY
osms.it/hypertensive-emergency

▪ Elevated blood pressure > 180/120mmHg OTHER DIAGNOSTICS
with signs of acute end organ damage ▪ Sphygmomanometer
(e.g. encephalopathy, stroke, papilledema, ▫ Blood pressure > 180/120mmHg
myocardial infarction, heart failure,
▪ Evaluation to identify at-risk target organ
microangiopathic hemolytic anemia, etc.)
▫ Electrocardiography (heart)
▪ Complication of poorly managed
hypertension ▫ Chest X-ray (heart, lungs)
▫ Urinalysis (kidneys)
▫ Serum electrolytes, serum creatinine
RISK FACTORS (kidneys)
▪ Kidney failure, renovascular hypertension,
▫ Cardiac enzymes (heart)
stimulant abuse, medication non-adherence
▫ CT scan of brain (if brain suspected →
▪ More common in young adults, particularly
neurologic symptoms, retinopathy)
those of African descent
▫ Contrast-enhanced CT scan of chest (if
aortic dissection suspected)
COMPLICATIONS
▪ Neurological complications (stroke,
seizures), myocardial infarction, kidney TREATMENT
failure, permanent blindness, pulmonary
edema ▪ Treatment varies case-by-case, dependent
on affected organ
SIGNS & SYMPTOMS

MEDICATIONS
▪ Blood pressure > 180/120mmHg, signs of ▪ Unwise to lower blood pressure too quickly/
end-organ damage too much, as this can lower cerebral
perfusion excessively
▫ Blurred vision, altered mental state,
chest pain, headache, nausea, ▫ Most cases: mean arterial pressure
vomiting, numbness in extremities, (MAP) should be reduced using
oliguria, seizure, dyspnea, weakness, intravenous medication 10–20 % in first
papilledema hour, then 5–15% over the following
23 hrs. Specific medications used
dependent on case
OTHER INTERVENTIONS
▪ Exceptions to most cases: acute phase
ischemic stroke (not lowered unless specific
conditions met)
▫ Acute aortic dissection (rapid lowering),
intracerebral hypertension (variable)
OSMOSIS.ORG 83
HYPOTENSION
osms.it/hypotension

▪ Condition in which arterial blood pressure ▪ Lightheadedness, fatigue, pallor, confusion
drops below 90/60mmHg ▪ Significant hypotension → syncope
▪ Physiological in some cases (professional
athletes); considered pathologic if
symptomatic DIAGNOSIS
▪ Not a distinctive disease, but a
manifestation of various conditions OTHER DIAGNOSTICS
▪ Orthostatic hypotension: hypotension ▪ Evaluation of blood pressure with
caused by standing up from a sitting/lying sphygmomanometer/arterial catheter
position ▫ Systolic blood pressure < 90mmHg
▫ Diastolic blood pressure < 60mmHg
CAUSES ▫ Mean arterial pressure < 65mmHg
▪ Orthostatic hypotension
Hypovolemia
▫ Drop in 20mmHg of systolic
▪ Fluid loss (hemorrhage, diarrhea, vomiting), pressure/10mmHg of diastolic pressure
low fluid intake (starvation, oligodipsia), when standing up from a sitting/lying
endocrine disorders, anemia position
Heart disease
▪ Cardiomyopathies, heart valve disease (e.g. TREATMENT
mitral stenosis), congestive heart failure,
myocardial infarction, arrhythmias
▪ Asymptomatic hypotension does not
Medications require treatment
▪ Most commonly cause orthostatic ▪ Treat underlying cause
hypotension
▪ Excessive use of diuretics, alpha/beta
blockers, nitrate preparations, calcium
channel blockers, angiotensin II (AT1)
receptor blockers, antidepressants
Neurological disorders
▪ Spinal cord injury resulting in ↓ sympathetic
output or ↑ parasympathetic output
▪ Dysautonomia (intrinsic autonomic system
dysfunction), Parkinson’s disease
COMPLICATIONS
▪ Ischemia
▪ If severe, can lead to shock
84 OSMOSIS.ORG
NOTES
NOTES
INFECTIONS & INFLAMMATION
OF THE HEART

▪ Heart infections, inflammation (may affect ▪ See individual disorders
epicardium, myocardium, endocardium)
▪ May include: infective endocarditis,
Libman-Sacks endocarditis, myocarditis, DIAGNOSIS
rheumatic fever
▪ May cause/be caused by/coexist with other ▪ See individual disorders
infections
TREATMENT
COMPLICATIONS
▪ Heart failure, arrhythmias, fibrosis ▪ See individual disorders
▪ Infective, Libman–Sacks endocarditis can
cause
▫ Damage to heart valves: dysrhythmias,
valve dysfunction
▫ Invasion of myocardium: heart failure,
heart block, sepsis
▫ Vegetation can embolize to extremities:
infarction/ischemia causing stroke,
pulmonary edema, glomerulonephritis
OSMOSIS.ORG 85
INFECTIVE ENDOCARDITIS
osms.it/endocarditis
▪ Found on skin
PATHOLOGY & CAUSES ▪ Infects damaged, healthy valves
▪ Large vegetations: can destroy valve
▪ Infection of endocardium, usually with
bacteria, may include heart valve ▪ Most commonly contracted from IV drug
use
▪ Valves have small blood vessels → damage
to valve, vessels → microbes in blood Staphylococcus epidermidis
escape into valvular tissue/microbes enter
▪ Infects prosthetic material (e.g. prosthetic
small vessels → infection
heart valves)
▪ Valve endothelial lining damaged
▪ Enters body during valve surgery/infected
▪ Microbes enter body via: dental/surgical IV catheter: sticks around valve/catheter
procedures, injection with infected needle/
▪ Nosocomial infection (infection in hospital)
infected substance, wound/abscess
▪ Gut flora
▪ Vegetation: fibrin, leukocytes, microbes
attach to thrombosis → abnormal growth ▫ Enterococcus faecalis
→ potential embolism ▫ Streptococcus bovis
▪ Often affects left side heart valves ▪ Severe colorectal disease (e.g. colorectal
▫ Predisposing conditions: mitral valve cancer/ulcerative colitis): bacteria migrate
prolapse, bicuspid aortic valves into bloodstream
Coxiella burnetii
TYPES ▪ Exposure to infected animals (e.g. cows,
▪ Classified by microbial cause sheep, goats)
▫ Acute bacterial endocarditis: infection of ▪ Q fever → months/years later, endocarditis
normal valves, rapid progression ▪ Affects those at high risk:
▫ Subacute bacterial endocarditis: immunocompromised, pregnant individuals,
indolent infection of abnormal valves pre-existing heart valve defect
(e.g. S. viridans) ▪ Diagnosis difficult
▫ Endocarditis in IV drug users:
Methicillin-resistant Staphylococcus Candida albicans
aureus (MRSA), Pseudomonas, Candida ▪ Fungal endocarditis
▫ Prosthetic valve endocarditis: ▪ Connected with IV drug use
Staphylococcus epidermidis within 60
Culture-negative endocarditis
days of replacement; after 60 days,
resembles native valve endocarditis ▪ Cannot be linked to bacteria using blood
cultures
▪ Aortic vascular infection, persistent low
CAUSES fever, rash
Viridans streptococci (most common) ▪ Often caused by Coxiella burnetii
▪ Low virulence HACEK organisms
▪ Found in mouth ▪ Haemophilus, Aggregatibacter,
▪ Attacks previously damaged valves Cardiobacterium, Eikenella, Kingella
▪ Small vegetations: don’t destroy valve ▪ Gram-negative bacteria
Staphylococcus aureus ▪ Normal flora of mouth, throat
▪ High virulence
86 OSMOSIS.ORG
Chapter 12 Infections & Inflammation of the Heart
Nonbacterial thrombotic endocarditis

▪ Damage in valve exposes collagen, tissue
DIAGNOSIS
factor → platelets, fibrin adhere → form tiny
thrombosis → mitral valve regurgitation
DIAGNOSTIC IMAGING
▫ Bacteremia → bacterial attach to Chest X-ray
thrombi → bacterial endocarditis ▪ Enlarged heart, possible pulmonary
congestion
RISK FACTORS
Echocardiogram
▪ Valvular problems
▪ Inflamed heart muscle walls, dilation
▫ Mitral valve prolapse
▫ Bicuspid aortic valves
▫ Prosthetic valves
LAB RESULTS
▪ Elevated troponin, creatine kinase levels
▫ Valves affected: mitral > aortic, tricuspid
(due to heart muscle damage)
▪ Congenital cardiac defects
▪ Damage to valves due to rheumatic heart Cardiac muscle biopsy
disease ▪ Definitive diagnosis
▪ IV drug use (esp. tricuspid valve) ▪ Risky procedure, performed only if test
▪ Chronic hemodialysis results would change treatment plan
▪ Poor dentition
OTHER DIAGNOSTICS
SIGNS & SYMPTOMS ECG
▪ Sinus tachycardia (increased heart rate)
▪ Anorexia, weight loss, fatigue ▪ T-wave inversions
▪ See mnemonic below ▪ “Saddle-shaped” ST segment elevations
MNEMONIC: FROM JANE TREATMENT

Signs & Symptoms
Fever ▪ Viral: improves slowly over time
Roth spots: antigen-antibody ▪ Arrhythmias resolve as inflammation
complex deposits in eyes improves
Osler nodes: painful antigen-
antibody complex deposits in MEDICATIONS
pads of digits
▪ Antibiotics
Murmur: turbulent blood flow
▪ Signs of heart failure: managed with
past damaged heart valve
medication, fluid balance
Janeway lesions: erythematous
lesions due to emboli; small,
painless, flat SURGERY
Anemia ▪ Heart transplant in severe cases (e.g.
Nail-bed hemorrhage (splinter Chagas, giant cell myocarditis)
hemorrhages): deposition of
emboli
Emboli: vegetations detach
from valve, deposit
elsewhere (nail beds,
kidneys, spleen, central
nervous system)
OSMOSIS.ORG 87
Figure 12.2 Bacterial vegetations on the
mitral valve in endocarditis.
Figure 12.1 Janeway lesions are hemorrhagic

macules or nodules that may appear on the
palms of the hands or soles of the feet in
cases of infective endocarditis.
Figure 12.3 Roth spots seen in the retina.
88 OSMOSIS.ORG
LIBMAN–SACKS ENDOCARDITIS
osms.it/endocarditis

▪ Autoimmune endocarditis associated ▪ Must exclude infective endocarditis (may
with systemic lupus erythematosus (SLE), coexist)
advanced malignancy, rheumatoid arthritis
▪ AKA nonbacterial thrombotic endocarditis/ DIAGNOSTIC IMAGING
verrucous endocarditis
Transesophageal echocardiogram (TEE)
CAUSES ▪ Small, warty, vegetations on both atrial and
▪ Antigen-antibody complexes settle in ventricular sides of valves
endocardium ▪ Regurgitation, valve insufficiency
▫ Arises on valves /chordae tendineae,
most often mitral valve LAB RESULTS
▫ Arises even on atrial/ventricular ▪ CRP, WBC levels, and antiphospholipid/
endocardium anticardiolipin antibody level may aid in
▫ Sterile vegetations: aortic valves differentiation
COMPLICATIONS TREATMENT
▪ Damage to heart valves
▪ Invasion of myocardium ▪ Treat underlying SLE
▪ Vegetations may embolize
▪ In rare cases, may cause secondary MEDICATIONS
infective endocarditis
Anticoagulants
▪ E.g. heparin, direct thrombin, Xa inhibitors
SIGNS & SYMPTOMS ▪ Address embolic risk
▪ Regurgitant murmurs
▫ Bilateral vegetations on valve leaflets
▪ Clinical manifestations indicate systemic
emboli
▫ Kidney: flank pain, hematuria
▫ Skin: rash, digital ischemia
▫ Cardiac/central nervous system (CNS):
chest pain, stroke
OSMOSIS.ORG 89
MYOCARDITIS
osms.it/myocarditis
RISK FACTORS
PATHOLOGY & CAUSES ▪ Viruses that cause flu-like illnesses, HIV/
AIDS, Lyme disease, strep, staph infections,
▪ Inflammation of/damage to myocardium parasites
▪ Swelling impairs myocardial contraction →
less blood pumped out of heart with each
heartbeat COMPLICATIONS
▪ Heart failure, fibrosis, arrhythmias
CAUSES
Coxsackieviruses A & B infections
SIGNS & SYMPTOMS
▪ Viral infections → lymphocytic myocarditis:
▪ Clinical manifestations of heart failure (e.g.
B, T cells, water invade interstitial space
fatigue, shortness of breath, hepatomegaly,
▪ Common in North America edema)
Trypanosoma cruzii ▪ Acute heart failure → cardiogenic shock
▪ Single-cell protozoan → Chagas disease ▪ Arrhythmias (e.g. ventricular fibrillation,
▪ Amastigotes within heart muscle cells ventricular tachycardia) → sudden cardiac
(intracellular stage of trypanosomes) → death
necrosis of heart muscle cells ▪ Fever
▪ Common in South America ▪ Positional chest pain, related to
pericarditis: better/worse depending on
Trichinella body’s position
▪ Intestinal roundworm may move into heart
→ myocarditis
DIAGNOSIS
Borrelia burgdorferi
▪ Lyme disease bacterium DIAGNOSTIC IMAGING
Toxoplasma gondii Chest X-ray
▪ Single cell parasite harbored by cats ▪ Enlarged heart, possible pulmonary
congestion
Systemic lupus erythematosus (SLE)
▪ Non-infectious myocarditis Echocardiogram
▪ Immune system attacks myocardium ▪ Inflamed heart muscle walls, dilation
Drug-associated/hypersensitivity
LAB RESULTS
▪ Adverse drug reaction inflames heart
▪ Elevated troponin, creatine kinase levels
▪ Eosinophils enters blood vessels in
(due to heart muscle damage)
myocarditis
Cardiac muscle biopsy
Giant cell
▪ Definitive diagnosis
▪ Inflammation of heart from unknown cause
▪ Risky procedure, performed only if test
▪ Macrophages fuse to form single giant cell
results would change treatment plan
90 OSMOSIS.ORG
OTHER DIAGNOSTICS
TREATMENT
ECG
▪ Sinus tachycardia (increased heart rate) ▪ Viral: improves slowly over time
▪ T-wave inversions ▪ Arrhythmias resolve as inflammation
▪ “Saddle-shaped” ST segment elevations improves
MEDICATIONS
MNEMONIC: BCD ST3G ▪ Antibiotics
Common Causes of ▪ Signs of heart failure: managed with
Myocarditis medication, fluid balance
Borrelia burgdorferi
Coxsackieviruses A and B SURGERY
Drug-associated ▪ Heart transplant in severe cases (e.g.
Chagas, giant cell myocarditis)
Systemic lupus
erythematosus
Trypanosoma cruzi
Trichinella
Toxoplasma gondii
Giant cell
Figure 12.4 Histological appearance of

myocardium in viral myocarditis.
OSMOSIS.ORG 91
RHEUMATIC FEVER
osms.it/rheumatic-heart-disease
TYPES
PATHOLOGY & CAUSES ▪ When only a subset of symptoms present,
classified as the following
▪ Autoimmune inflammatory disease caused
by complication of streptococcal infection Pediatric Autoimmune Neuropsychiatric
▪ Develops after streptococcal pharyngitis Disorders Associated with Streptococcal
(strep throat) from Group A beta hemolytic Infections (PANDAS)
streptococcus ▪ Neuropsychiatric symptoms
Poststreptococcal reactive arthritis

CAUSES
▪ Joint symptoms
Molecular mimicry
▪ Antibodies against streptococcal M-protein RISK FACTORS
cross-reacts with proteins on myocardium, ▪ Small number of individuals with strep
heart valves, joints, skin, brain → cytokine- throat develop rheumatic fever, more
mediated inflammatory response likely in children/those in areas of poverty,
▪ Inflammation results in widespread crowding
pathology ▪ Rheumatic fever primarily affects children
5–7 years old, 20 days after infection
Pancarditis
▪ One third of cases asymptomatic
▪ Inflammation of endometrium, myometrium,
pericardium (three layers of heart tissue)
▪ Myometrium: Aschoff bodies SIGNS & SYMPTOMS
(microscopically viewed nodules caused by
inflammation) → leads to fibroid necrosis
Acute rheumatic fever
▫ Characteristic feature of pancarditis
▪ Following symptoms develop 2–4 weeks
▫ Anitschkow cells (enlarged after streptococcal pharyngitis
macrophages inside Aschoff bodies),
▪ Fever
caterpillar-like nuclei
▪ Migratory polyarthritis of joints: temporary
▪ Pericardium: pericarditis causes pain,
inflammation, swelling, joint pain
friction rub due to visceral pericardium
rubbing against parietal pericardium ▪ Erythema marginatum: non-itchy, reddish
rash, rings on arms/trunk
Chronic rheumatic heart disease ▪ Subcutaneous nodules: firm collagen lumps
▪ Repeated exposure to group A beta- under skin
hemolytic streptococcus → immune attacks ▫ Reaction to hypersensitivity
on tissues (esp. heart tissue) ▫ Painless
▪ Valves (typically mitral valve, sometimes ▫ Back of wrist, outside elbow, front of
aortic) develop scar tissue → leaflets knee
thicken, fuse → commissural fusion ▪ Pancarditis (inflammation of three layers of
▫ Stenosis AKA “fish-mouth”/“buttonhole” heart)
stenosis ▪ Dyspnea, sharp chest pain
▫ Regurgitation (blood flows backward) ▪ Friction rub heard on auscultation due to
▪ Chordae tendineae attached to valves pericarditis
thicken ▪ Impaired ability of heart to contract
92 OSMOSIS.ORG
(myocarditis) → heart failure, death ▪ Minor criteria

▪ Sydenham’s chorea: rapid, jerky ▫ Signs/symptoms: fever
movements of face, arms from damage to (>38.5°C/101.3°F), arthralgia
basal ganglia ▫ Laboratory evidence: increased
▫ Autoimmune reaction on basal ganglia acute phase reactants (↑ erythrocyte
of brain sedimentation rate, ↑ C-reactive protein,
▫ Appears late (three months after ↑ leukocytosis)
infection) ▫ Electrocardiograph: prolonged PR
interval
Chronic rheumatic heart disease ▪ Evidence of recent infection
▪ Symptoms dependent on type of ▫ Positive throat culture
damage to heart: aortic stenosis, aortic
▫ Positive rapid antigen detection test
regurgitation, mitral stenosis, mitral
regurgitation, pulmonic regurgitation ▫ Elevated antistreptolysin O titre (ASO)
▪ Exception: Sydenham’s chorea/pancarditis
PANDAS independently may indicate rheumatic fever
▪ Pediatric, abrupt onset, episodic course of ▪ Electrocardiogram changes
symptoms
▪ Neurologic abnormalities: motoric Chronic rheumatic heart disease
hyperactivity (fidgeting), choreiform ▪ Previous repeated cases of rheumatic fever
movements in stressed postures (sudden, ▪ Diagnosis depends on damage done to
jerky movements), frank chorea (rapid, heart: aortic stenosis, aortic regurgitation,
irregular, jerks, movements continuous mitral stenosis, mitral regurgitation,
while awake but improve with sleep) pulmonic regurgitation
▪ Obsessive-compulsive disorder/tic disorder
Poststreptococcal reactive arthritis

▪ Arthritis occurring after a streptococcal
infection
DIAGNOSIS
OTHER DIAGNOSTICS
Jones criteria for acute rheumatic fever
▪ Evidence of previous group A
streptococcus infection plus two major Figure 12.5 Anitschkow cells (enlarged
criteria/one major plus two minor criteria macrophageswith linear nucleoli) in an
Aschoff body (a granuloma) in a case of
rheumatic myocarditis.
MNEMONIC: JONES
Major criteria
Joints: polyarthritis
myOcarditis: O = vaguely
heart-shaped
Nodules: subcutaneous
Erythema marginatum
Sydenham’s chorea
OSMOSIS.ORG 93
Rheumatic heart disease
TREATMENT
▪ Prevent repeated attacks/acute rheumatic
MEDICATIONS fever, streptococcal infections
▪ History of acute rheumatic fever:
Rheumatic fever prophylactic treatment for extended period
▪ Goals of treatment: control, eradicate (benzathine penicillin G/oral penicillin V, 10
streptococcus, prevent complications, years to life)
relieve joint pain, relieve fever
▫ Antibiotics: penicillin G
▫ Anti-inflammatory agents: aspirin,
non-steroidal anti-inflammatory drugs
(NSAIDs), steroids
▫ Antipyretics: NSAIDs
▫ Rest
OTHER INTERVENTIONS
Rheumatic fever
▪ Maintain dental health
▪ Strict long-term, prophylaxis: history of
bacterial endocarditis, heart transplant,
artificial heart valve, other congenital defect
Figure 12.6 Massive cardiomegaly secondary

to aortic and mitral valve disease in a severe
case of rheumatic fever.
Figure 12.7 Gross pathology of acute rheumatic endocarditis; there is a line of acute inflammation
(valvulitis) along the closure line of the mitral valve.
94 OSMOSIS.ORG
NOTES
NOTES
LYMPHATIC DYSFUNCTION
LYMPHEDEMA
osms.it/lymphedema
PATHOLOGY & CAUSES

▪ Lymphatic system becomes obstructed,
causing protein-rich fluid buildup in tissues
▪ When flow is blocked, lymph gets backed
up → drainage stops → fluid accumulates
▪ Inflammatory reaction: macrophages
release inflammatory molecules →
damages nearby cells → scarring, fibrosis
(connective tissues thicken/scar tissue
forms) → hardening
CAUSES
▪ Filariasis: most common cause in low-
income countries
▫ Infection with nematode parasites (e.g.
Wuchereria bancrofti)
▫ Nematode enters lymphatic system,
causes fibrosis, creates a blockage
▪ Cancer, associated treatment: most Figure 13.1 Gross lymphedema of the left leg.
common cause in high-income countries
▫ Removal of lymph nodes most common
cancer treatment-related cause (e.g. STAGING
axillary lymph nodes removed during
▪ Stage 0: latent stage. Damage to
mastectomy)
lymphatics but enough lymph still removed.
▪ Lymphedema praecox/primary Lymphedema not present
lymphedema: congenital, results from
▪ Stage 1: spontaneously reversible. Tissue in
lymphatic system not developing correctly
pitting stage. Affected area normal/almost
< 35 years old
normal size in morning, progressively
▪ Lymphedema tarda/primary lymphedema: worsens throughout day
> 35 years old, associated with genetic
▪ Stage 2: spontaneously irreversible. Tissue
disorders (e.g. Turner syndrome)
spongy, non-pitting (bounces back when
pressed). Fibrosis starts to develop → limbs
RISK FACTORS harden, increase in size
▪ Older age, obesity, rheumatoid/psoriatic ▪ Stage 3: lymphostatic elephantiasis.
arthritis, Turner syndrome, smoking, cancer/ Swelling irreversible, limbs large, hard from
associated treatment (esp. breast cancer) fibrosis
OSMOSIS.ORG 95
COMPLICATIONS
▪ Recurrent cellulitis, limb swelling (esp.
TREATMENT
lower limbs), erythema, pain
▪ No cure, no medication
▪ Depends on severity, limb fibrosis
SIGNS & SYMPTOMS
SURGERY
▪ Chronic swelling , one limb larger than ▪ Goal: improve drainage/reduce fluid load
other
▪ Usually lower limbs; impairs movement
OTHER INTERVENTIONS
▪ Fatigue, fever, chills, weakness
▪ Therapeutic exercises, self care
▪ More likely to occur with superimposed
▪ Kinesio tape: applied to skin to channel
bacterial/fungal skin infection
lymph, reduce swelling
▪ Regional edema: begins as soft, pitting
▪ Aquatic therapy
edema → progresses into chronic fibrosis
without treatment Manual lymphatic drainage (MLD)
▪ Pneumatic pumps: substitute for MLD
DIAGNOSIS Compression
▪ Multilayer compression bandage: stop fluid
DIAGNOSTIC IMAGING accumulation
Lymphoscintigraphy ▪ Compression massages help lymph flow
▪ Nuclear imaging to assess lymphatic flow ▪ Compression garments
▫ Radiotracer injected into affected limb
→ able to visualize dermal backflow,
absent/delayed radiotracer movement,
absent/delayed lymph node visualization
MRI
▪ Shows severity, distribution of edema,
lymphatic channels can be depicted after
intracutaneous contrast injection
MR venogram
▪ Helps differentiate lymphatic channels from
superficial veins
CT scan
▪ Assists in localization (subfascial,
epifascial), characteristics (skin thickening,
honeycomb pattern of edema)
Ultrasound
▪ May be used to reveal blockages
Figure 13.2 A plain X-ray of the forearm

showing edema of the subcutaneous tissues.
The subcutaneous fat shows characteristic
streaky densities.
96 OSMOSIS.ORG
NOTES
NOTES
PERICARDIAL DISEASE

▪ Disorders affecting pericardium DIAGNOSTIC IMAGING
▪ Pericardial cavity: space between visceral, ▪ Echocardiogram
parietal layer, normally filled with 15–50ml ▪ X-ray
of plasma filtrate
OTHER DIAGNOSTICS
CAUSES ▪ ECG
▪ Infections: mostly viral; bacterial, fungal rare
▪ Malignancy, mediastinal radiation
▪ Dressler’s syndrome TREATMENT
▪ Trauma
▪ Pericardiocentesis, pericardiectomy
▪ Drugs, toxins
▪ Metabolic disease (e.g. uremic syndrome,
myxedema, ovarian hyperstimulation MNEMONIC: CARDIAC
syndrome), connective tissue disease
RIND
▪ Immune-mediated disorders
Causes of Pericarditis
Collagen vascular disease
COMPLICATIONS Aortic aneurysm
▪ Heart failure, circulatory problems, Radiation
problems breathing
Drugs
Infections
SIGNS & SYMPTOMS Acute renal failure
Cardiac infarction
▪ See individual diseases Rheumatic fever
Injury
Neoplasms
Dressler’s syndrome
OSMOSIS.ORG 97
ACUTE PERICARDITIS
osms.it/acute-pericarditis
COMPLICATIONS
PATHOLOGY & CAUSES ▪ Constrictive pericarditis, pericardial
effusion, cardiac tamponade
▪ Pericardial inflammation, myopericarditis
▪ Most common pericardial disorder
SIGNS & SYMPTOMS
CAUSES
▪ Idiopathic, viral (e.g. Coxsackie B), ▪ Fever, sharp chest pain worsened with
uremic syndrome (toxic to pericardium), deep breathing, symptoms improve with
Dressler’s syndrome, autoimmune (e.g. sitting up and leaning forward
rheumatoid arthritis, scleroderma, systemic ▪ Pericardial friction rub heard on
lupus erythematosus), cancer, radiation, auscultation, like two pieces of leather
medications (e.g. penicillin, anticonvulsants) rubbing together, loudest on left sternal
border
RISK FACTORS
▪ Surgery, cancer, autoimmune
disease, connective tissue disorders,
immunosuppression
98 OSMOSIS.ORG
Chapter 14 Pericardial Disease
DIAGNOSIS TREATMENT
DIAGNOSTIC IMAGING ▪ Targeted at etiology
X-ray
▪ “Water bottle sign,” liquid collects at the MEDICATIONS
bottom if effusion present ▪ Treat pain, inflammation
▫ Non-steroidal anti-inflammatory drug
Echocardiography (NSAID) + colchicine
▪ Performed to exclude pericardial effusion ▫ Glucocorticoids if NSAID
contraindicated
OTHER INTERVENTIONS ▫ Colchicine important if rheumatoid
▪ Clinical presentation suggestive of arthritis, Dressler syndrome involved
pericardial effusion
SURGERY
ECG
▪ Pericardiotomy if high recurrence
▪ ST elevation, PR depression, voltage
changes, flattened, inverted T wave
OTHER INTERVENTIONS
▪ Rest
MNEMONIC: PSPPS
Acute pericarditis ECG
PericarditiS
PR depression in Precordial
leads
ST elevation
Figure 14.2 Illustration depicting sclerosing

of pericardial tissues in cross-section of heart
wall.

the globular cardiac silhouette seen in a case
of pericardial effusions secondary to acute
pericarditis. This is also known as the water
bottle sign.
OSMOSIS.ORG 99
Figure 14.4 Histology photomicrograph
demonstrating acute pericarditis. The
mesothelial cells of the pericardium are
surrounded by neutrophils and there is no
fibrosis, indicating an acute inflammatory
reponse.
Figure 14.3 Gross pathology of acute

fibrinous pericarditis. The yellow fibrinous
exudate is clearly visible on the external
surface of the heart.
CARDIAC TAMPONADE
osms.it/cardiac-tamponade
RISK FACTORS
PATHOLOGY & CAUSES ▪ Individuals with malignancy, tuberculous,
purulent pericarditis ≥ those with idiopathic
▪ Buildup of fluid in pericardium, constricts pericarditis
heart
▪ Individuals with fibrinolytic therapy,
▪ Tamponade = pressure obstructing flow myocardial infarction
▪ Heart unable to pump normally → blood
flow through chambers obstructed →
cardiac output decreases → hypotension SIGNS & SYMPTOMS
→ lower tissue perfusion → heart rate
increases ▪ Pulsus paradoxus due to ventricular
interdependence
CAUSES ▪ Beck’s triad (see mnemonic)
▪ Acute onset: trauma, myocardial infarction, ▪ Tachycardia, coughing, dyspnea, weakness,
aortic dissection, pericardial effusion myocardial ischemia
▪ Slow onset: cancer, chronic inflammation,
uremic pericarditis, hypothyroidism,
connective tissue disease
100 OSMOSIS.ORG
MNEMONIC: 3Ds
Beck’s triad (Signs &
Symptoms)
Distant heart sounds
Distended jugular veins
Decreased arterial pressure
DIAGNOSIS
DIAGNOSTIC IMAGING
Figure 14.5 A CT scan in the axial plane
Echocardiography demonstrating a large pericardial effusion,
▪ Excess pericardial fluid, heart “swinging” separating the pericardium from the heart
inside pericardial cavity itself and increasing the intrapericardial
pressure, leading to cardiac tamponade.
SURGERY
▪ Cardiac catheterization → pressure in all TREATMENT
four chambers equal
MEDICATIONS
OTHER INTERVENTIONS ▪ IV fluids
▪ Clinical presentation
ECG OTHER INTERVENTIONS

▪ Tachycardia, low QRS complex voltage, Pericardiocentesis
electrical alternans (QRS complexes have
▪ Needle inserted into pericardium to drain
different heights)
excess fluid
Figure 14.6 Illustration depicting fluid build up around pericardium, putting pressure on
the heart walls and decreasing stroke volume.
OSMOSIS.ORG 101
CONSTRICTIVE PERICARDITIS
osms.it/constrictive-pericarditis
PATHOLOGY & CAUSES ▪ Edema: part of fluid overload; ascites,

hepatosplenomegaly (HSM), cachexia
▪ Formation of thick, fibrotic pericardium → (signs of hepatopathy); dyspnea
compresses heart (consequence of low cardiac output)
▪ Fibroblasts accumulate between pericardial ▪ Clinical manifestations of pleural effusion
layers → collagen deposits → creates scars
→ layers become adherent, lose elasticity
▪ Heart filling difficult due to stiffness of DIAGNOSIS
pericardium
▫ Ventricular interdependence: lowered DIAGNOSTIC IMAGING
heart wall compliance, decreased
X-ray
transpulmonary venous pressure → left
ventricular filling decreases → lower ▪ Pericardial calcifications
volume in left heart → right bends Echocardiogram
septum towards left to increase volume
▪ Stiff serous pericardium restricts heart’s
▫ Maximal volume diminished, continues movement
to decrease with disease progression
▪ Volume overload, hepatopathy, decreased CT scan
cardiac output ▪ Anatomical variations, thickness,
distribution of scarring
CAUSES
▪ Idiopathic, viral, radiation, myocardial LAB RESULTS
infarction, collagen disorders, tuberculosis
Plasma brain natriuretic peptide (BNP)
▪ Differentiate between tamponade, cirrhosis,
RISK FACTORS restrictive cardiomyopathy
▪ Acute pericarditis
▪ Cardiac surgery, radiation, connective tissue
disorders, bacterial (purulent) infections
OTHER INTERVENTIONS
Invasive hemodynamic monitoring
COMPLICATIONS ▪ Increased pressure in right atrium,
▪ Heart failure, arrhythmias, cardiac Kussmaul’s sign
tamponade

▪ Elevated jugular venous pressure (JVP) MEDICATIONS
▪ Kussmaul’s sign: paradoxical inspiratory ▪ Diuretics, NSAIDs, corticosteroids
JVP
▪ Pericardial knock: heard before S3 on SURGERY
auscultation
▪ Pericardiectomy (for progressive disease)
102 OSMOSIS.ORG
Figure 14.7 A chest radiograph

demonstrating pericardial calcification
secondary to a chronic pericarditis.
DRESSLER'S SYNDROME
osms.it/dresslers-syndrome

▪ Secondary pericarditis, rare DIAGNOSTIC IMAGING
▪ AKA postmyocardial infarction syndrome
Echocardiogram
▪ May or may not involve pericardial effusion
▪ Evaluate ventricular contractility; effusion,
▪ ≥ two weeks after myocardial infarction signs of tamponade
(MI), immune-mediated response to injury
→ antimyocardial antibodies respond Chest X-ray
to cardiac antigens → immune complex ▪ Cardiac effusion
deposits in pericardium, pleura
LAB RESULTS
SIGNS & SYMPTOMS ▪ Complete blood count (CBC), CRP,
erythrocyte sedimentation rate (ESR);
▪ Unusual fatigue after cardiac surgery/MI troponin studies show leukocytosis, ↑ CRP,
▪ Persistent fever, tachycardia, pulsus ↑ ESR; anti-heart antibody titer
paradoxus
▪ Manifestations of pericarditis: friction rub, OTHER INTERVENTIONS
symptoms improve in sitting position
▪ Pleural effusion signs: pleuritic pain ECG
▪ Changes same as acute pericarditis
▪ ST segment elevation, PR depression
OSMOSIS.ORG 103
TREATMENT
MEDICATIONS
▪ Colchicine recommended after cardiac
surgery as preventative measure
▪ High dose aspirin, NSAIDs, corticosteroids
PERICARDIAL EFFUSION
osms.it/pericardial-effusion

▪ Abnormal accumulation of inflammatory DIAGNOSTIC IMAGING
fluid, immune cells → diffuse into
interstitium → fluid pools in pericardial X-ray
space → pericardial dilation → pressure ▪ Silhouette pools to bottom of heart, gives
on heart, vena cava → decreased cardiac classic “water bottle” sign
filling → cardiac tamponade → decreased
cardiac output Echocardiogram
▪ Types of effusion: serous, serosanguinous, ▪ Pericardial effusion makes heart looks like
chylous it’s dancing within pericardium, “swinging
heart”
CAUSES
LAB RESULTS
▪ Aortic dissection, heart failure,
hypoalbuminemia, lymphatic obstruction, ▪ Elevated markers of inflammation:
malignancy, radiation, renal failure, trauma, C-reactive protein (CRP)
autoimmune disease, acute pericarditis
(viral, bacterial, tuberculous, idiopathic in OTHER INTERVENTIONS
origin), myxedema, some drugs, iatrogenic,
idiopathic ECG
▪ Low QRS complex voltage, electrical
alternans, sinus tachycardia
COMPLICATIONS
▪ Cardiac tamponade
▪ Constrictive pericarditis TREATMENT
MEDICATIONS
SIGNS & SYMPTOMS ▪ Relieve pain, treat underlying cause of
inflammation
▪ Clinical presentation nonspecific, related
to underlying cause, reflecting impaired
cardiac function SURGERY
▪ Diminished heart sounds ▪ Pericardiocentesis
▪ Jugular vein distention
▪ Tachycardia, dyspnea, decreased blood
pressure, lightheadedness
104 OSMOSIS.ORG
NOTES
NOTES
PERIPHERAL ARTERY
DISEASE

certain drugs)
PATHOLOGY & CAUSES ▪ Intermittent arterial constriction → ↓
diameter → ↓ blood flow
▪ Narrowing of the arteries in peripheral,
non-coronary arterial circulation
▪ Vessels of the lower extremities are most RISK FACTORS
commonly affected ▪ Smoking
▪ ↓ blood flow → arterial insufficiency → ▪ High blood pressure
tissue ischemia ▪ Diabetes
▫ ↓ gas and nutrient exchange → tissue ▪ Hyperlipidemia
loss, ulcer formation → poor healing ▪ Metabolic syndrome
▫ Embolus formation → acute limb ▪ Age > 60
ischemia → tissue loss
▪ Obesity
▫ Ischemic cells release adenosine →
▪ ↑ risk in black people of African descent
adenosine signals nerves → sensation
of pain
▫ Claudication: pain caused by poor COMPLICATIONS
circulation; occurs when oxygen ▪ ↑ risk of developing coronary artery
demand is greater than oxygen supply cerebrovascular disease
▪ Location of pain is dependent upon artery ▪ Tissue necrosis
implicated ▪ Amputation
▫ Lower aorta or iliac artery = pain in hips ▪ Pain
and buttocks
▫ Iliac or common femoral artery = pain in
thigh SIGNS & SYMPTOMS
▫ Superficial femoral artery = pain in
upper ⅔ of calf ▪ Often asymptomatic until significant
▫ Popliteal artery = pain in lower ⅓ of calf occlusion develops
▫ Tibial or peroneal artery = pain in foot ▪ Intermittent claudication
▫ Muscle pain due to ↑ oxygen demand
and ↓ supply
TYPES
▪ Rest pain
Occlusive (most common) ▫ Pain or burning sensation in forefoot
▪ Usually caused by blockage due to and toes when legs elevated, pain
atherosclerosis relieved when legs are lowered (gravity
▪ Buildup of plaque → narrowed artery → ↓ assisting blood flow)
blood flow ▪ ↓ lower peripheral pulses (e.g. pedal, tibial)
▪ Leg/foot ulcers that do not heal normally
Functional ▫ Have classic punched out appearance
▪ Caused by a defect in the normal ▫ Often form on toe joints, malleoli, shin,
mechanisms that dilate and constrict base of heel, pressure points
arteries (e.g. inherited defects, injuries,
OSMOSIS.ORG 105
▫ Painful
▫ Slow healing → ↑ risk of infection
DIAGNOSIS
▪ Cutaneous color changes DIAGNOSTIC IMAGING
▫ Elevation pallor: foot turns pale when
raised due to circulation having to work Doppler ultrasound
against gravity as well as narrowed ▪ ↓ blood flow
artery
▫ Dependent rubor: foot turns red when
OTHER DIAGNOSTICS
lowered as gravity works increases
perfusion Auscultation
▪ Skin: cool, dry, shiny, hairless ▪ Bruit (whooshing sound) heard on
▪ Nails: brittle, hypertrophic, ridged auscultation of suspected artery
▪ Signs of acute limb ischemia ▫ Usually pulse of leg’s iliac artery
▫ See mnemonic ▫ Whooshing sound due arterial
narrowing
MNEMONIC: 5Ps Ankle-brachial index (ABI)

Signs of acute limb ischemia ▪ ABI < 0.9: peripheral artery disease
Pain ▪ ABI of 0.4–0.9: claudication
Pallor ▪ ABI of 0.2–0.4: rest pain
Pulselessness ▪ ABI of 0–0.4: tissue loss, ulcers, gangrene
Paresthesia
Paralysis (a surgical
emergency)
TREATMENT
MEDICATIONS
▪ Antiplatelet therapy
SURGERY
▪ Angioplasty, stent insertion
▪ Endarterectomy
▪ Bypass surgery to restore blood flow by
diverting it around blockage
▪ Amputation
OTHER INTERVENTIONS
▪ Modify risk factors; e.g. smoking cessation,
Figure 15.1 An arterial ulcer on the dorsum healthy eating habits, exercising regularly,
of the foot; a consequence of peripheral managing diabetes
vascular disease. Note the punched out
▪ Wound care
appearance.
106 OSMOSIS.ORG
Chapter 15 Peripheral Artery Disease
Figure 15.2 Illustration depicting the Ankle-branchial index.
ARTERIOLOSCLEROSIS
osms.it/arteriolosclerosis
membrane becomes “leaky” → serum
PATHOLOGY & CAUSES proteins move into endothelial cells and
build up into tunica media
▪ Arteriosclerosis: a general term for
diseases where the artery wall becomes Hyperplastic arteriolosclerosis
thicker, harder, and less elastic ▪ Smooth muscle cell hyperplasia → very
▫ Arteriolosclerosis: a disease of the small small lumen → ↓ blood flow → tissue
arteries and arterioles characterized by hypoxia
stiffening and thickening of the vessel ▫ Malignant hypertension → smooth
wall due to high blood pressure or muscle cells lining arteriole exposed to
diabetes, manifested primarily in the plasma proteins → concentric layers of
kidneys smooth muscle cell proliferation (“onion-
skinning”)
TYPES
RISK FACTORS
Hyaline arteriolosclerosis
▪ Diabetes mellitus
▪ Accumulation of proteins and pink hyaline
▪ Chronic hypertension
material → ↑ thickness and stiffening of
vessel wall → ↓ compliance → ↓ blood flow ▪ Malignant hypertension
→ tissue hypoxia
▫ Sustained high-pressure in vessels → COMPLICATIONS
serum proteins pushed into blood vessel ▪ Arteriolonephrosclerosis
walls → protein build-up in tunica media ▪ Formation of intraluminal thrombi
▫ Chronic high blood glucose → ▪ Chronic renal failure
endothelial cells become glycosylated
→ endothelial dysfunction → basement
OSMOSIS.ORG 107
▪ Clinical manifestations of chronic kidney LAB RESULTS
disease ▪ Signs of arteriolonephrosclerosis
▫ Anemia (fatigue, activity intolerance, ▪ ↑ blood urea nitrogen
pallor) ▪ ↑ creatinine
▫ Fluid and electrolyte imbalance (edema, ▪ ↓ hemoglobin
muscle weakness, palpitations)
▪ ↓ hematocrit
▫ Uremia (anorexia, mental status
▪ Proteinuria
changes)
▪ Oliguria
▫ Renal osteodystrophy
TREATMENT
OTHER INTERVENTIONS
▪ Management of diabetes and hypertension;
support renal function
ATHEROSCLEROSIS
osms.it/atherosclerosis
RISK FACTORS
PATHOLOGY & CAUSES ▪ Family history of coronary heart disease
▪ Smoking
▪ Arteriosclerosis: a general term for
diseases where the artery wall becomes ▪ Hypertension
thicker, harder, and less elastic ▪ Dyslipidemia; especially low HDL
▫ Atherosclerosis: atheromatous plaques ▪ Metabolic syndrome
on the tunica intima of large and ▪ Males ≥ 45; females 55 ≥ or premature
medium vessels menopause without hormone replacement
▪ Damage to endothelium → low-density therapy
lipoproteins enter endothelial wall → LDL
oxidation → uptake of LDL by macrophages COMPLICATONS
→ foam cell formation → cytokine and
▪ Cardiovascular and coronary heart disease
growth factor release from foam cells →
formation of thrombogenic fatty streak → ▫ Myocardial infarction, heart failure,
platelets release platelet-derived growth death
factor → migration of smooth muscle cells ▪ Cerebrovascular disease
from vascular media to intima → fibrous ▫ Transient ischemic attack, stroke
cap → atherosclerotic plaque → chronic ▪ Peripheral artery disease
inflammation ▫ Leg ulcers, amputation
▪ Calcium deposits into plaque → stiffening ▪ Aortic aneurysm
of arteries
108 OSMOSIS.ORG
Chapter 15 Peripheral Artery Disease
SIGNS & SYMPTOMS

▪ Symptoms vary according to extent and
location of blockage
▪ Carotid artery
▫ Weakness, difficulty speaking, dizziness,
difficulty walking, blurred vision,
numbness of face/arms/legs, severe
headaches
▪ Peripheral arteries
▫ Claudication, presence of ulcers
▪ Coronary arteries
▫ Angina
▪ Cerebral arteries
▫ Auscultation of bruit, neurological
complaints (e.g. visual changes, facial
paresis)
DIAGNOSIS
▪ History and presence of clinical
manifestations indicating occlusive disease
DIAGNOSTIC IMAGING Figure 15.3 The abdominal aorta at post

mortem showing moderate atherosclerosis.
Angiography
▪ Vascular calcifications, stenosis, occlusion,
collateral circulation
TREATMENT
Ultrasound
▪ Luminal stenosis, atheromatous ▪ Goal: reduce risk of complications with
calcification (hyperechoic foci producing an management risk factors; e.g. lipids, blood
acoustic shadow) glucose, hypertension
Magnetic resonance angiography
▪ Thickened arterial wall, heterogeneous MEDICATIONS
signal within vessel wall (lipid rich necrotic ▪ Antiplatelets
core, plaque, fibrous cap) ▪ Antilipemic agents
▪ Antihypertensives
LAB RESULTS
▪ hs-CRP (high-sensitivity C-reactive protein) SURGERY
test ▪ Complications: stents, bypass grafts,
▫ ↑ CRP indicates “silent atherosclerosis” angioplasty, carotid endarterectomy (CEA)
before cardiovascular event
▪ Fasting lipid profile
OSMOSIS.ORG 109
Figure 15.4 An atherosclerotic artery. Note
how the plaque protrudes into the lumen. It
is composed primarily of cholesterol with an
outer rim of foamy macrophages.
110 OSMOSIS.ORG
NOTES
NOTES
PRE–EXCITATION DISORDERS

▪ Heart rhythm disturbances due to ▪ Acute termination of preexicitation-
accessory pathway in conduction system associated arrhythmias
that allows depolarization to bypass ▪ Chronic prevention of preexicitation-
atrioventricular node and spread from atria associated arrhythmias
to ventricles
▪ Accessory pathways can promote
arrhythmias by two mechanisms
MEDICATIONS
▪ Acute termination
▫ Acting as one limb of a reentrant circuit,
with atrioventricular node acting as the ▫ Adenosine: short acting; causes
other transient heart block (↓ rate of diastolic
depolarization, ↓ HR)
▫ Bypassing physiologic atrioventricular
nodal delay → impulses reaching ▫ Diltiazem (Class IV): calcium channel
ventricle not regulated → very rapid blocker (↓ AV node conduction → ↓ HR)
ventricular responses in atrial arrhythmia ▪ Chronic prevention
setting such as atrial fibrillation, atrial ▫ Amiodarone (Class III): slows
flutter conduction rate (↑ AP duration, ↑ QT
▪ If ventricular rate becomes too high → interval)
ventricles don’t have time to fill → low ▫ Procainamide (Class 1A): slows
cardiac output → shock conduction velocity (↑ AP duration,
↑ ventricular refractory period, ↑ QT
interval)
SIGNS & SYMPTOMS
OTHER INTERVENTIONS
▪ Tachyarrhythmias → palpitations,
chest discomfort, breath shortness,
lightheadedness, syncope ▫ Vagal maneuver (carotid sinus massage/
Valsalva maneuver) → activates vagus
nerve
DIAGNOSIS ▫ Electrical cardioversion (if
pharmacological treatment ineffective/
▪ See individual disorders fast heart rate is poorly tolerated)
▪ Chronic prevention
▫ Radiofrequency catheter ablation
(definitive treatment)
OSMOSIS.ORG 111
AV REENTRANT TACHYCARDIA
(AVRT)
osms.it/av-reentrant-tachycardia

▪ Arrhythmia due to accessory pathway MEDICATIONS
between atria and ventricles that allows ▪ Acute termination
electrical signal to move backwards ▫ Adenosine, Diltiazem (Class III)
Orthodromic atrioventricular reentrant ▪ Chronic prevention
tachycardia (AVRT) ▫ Amiodarone (Class III), Procainamide
▪ Signal moves downward through (Class 1A)
atrioventricular node → ventricles contract
→ upward through accessory pathway OTHER INTERVENTIONS
→ atria contract → moves back down ▪ Acute termination
atrioventricular node → etc.
▫ Vagal maneuver
Antidromic atrioventricular reentrant ▫ Electrical cardioversion (if
tachycardia (AVRT) pharmacological treatment ineffective/
▪ Signal moves downward through fast heart rate is poorly tolerated)
accessory pathway → ventricles contract ▪ Chronic prevention
→ upwards through atrioventricular node ▫ Radiofrequency catheter ablation
→ atria contract → moves back down the
accessory pathway → etc.
SIGNS & SYMPTOMS

▪ Tachyarrhythmias → palpitations,
chest discomfort, breath shortness,
lightheadedness, syncope
DIAGNOSIS
OTHER DIAGNOSTICS
ECG
▪ Orthodromic AVRT
▫ Regular, narrow-complex tachycardia,
P waves are typically retrograde in
morphology and come after QRS
complex
▪ Delta wave is not seen
▪ Antidromic AVRT
▫ Regular, wide-complex tachycardia, P
waves often not visible
112 OSMOSIS.ORG
Chapter 16 Pre-excitation Disorders
Figure 16.1 An electrocardiogram demonstrating othodromic AVRT. Note the narrow QRS
complexes and absence of a discernible P wave.
Figure 16.2 An ECG demonstrating orthodromic AVRT with regular, narrow-complex

tachycardia with retrograde P waves visible just after the QRS complexes, most visible in leads II
and V4-V6.
OSMOSIS.ORG 113
Figure 16.3 An ECG demonstrating antidromic AVRT. There is a regular, wide complex
tachycardia that is usually indistinguishable from VT.
WOLFF–PARKINSON–WHITE
SYNDROME
osms.it/wolff-parkinson-white-syndrome
PATHOLOGY & CAUSES ▪ Most common type of ventricular

preexcitation syndrome
▪ Congenital accessory pathway conducts ▫ 0.1% of individuals have Wolff–
electrical signals between atria and Parkinson–White pattern, a small
ventricles → preexcitation, predisposes proportion of them develops syndrome
individuals to clinically significant
arrhythmias up to sudden cardiac death
▫ Though “bundle of Kent” is a common SIGNS & SYMPTOMS
eponym for congenital accessory
pathway, several different pathways ▪ Tachyarrhythmias → palpitations,
can occur, most commonly direct chest discomfort, breath shortness,
atrioventricular connections, but also lightheadedness, syncope
atriofascicular, nodofascicular, atrio-
Hisian, etc.
▫ Wolff–Parkinson–White pattern: benign
asymptomatic form, solely described
by compatible electrocardiographic
changes
114 OSMOSIS.ORG
Chapter 16 Pre-excitation Disorders
DIAGNOSIS TREATMENT
OTHER DIAGNOSTICS MEDICATIONS
ECG
▫ Adenosine, Diltiazem (Class III)
▪ Short PR interval (< 120ms)
▪ Delta wave
▫ Amiodarone (Class III), Procainamide
▫ Slurred upstroke of QRS
(Class 1A)
▪ Widening of the QRS complex (> 110ms)
▪ Secondary ST segment, T wave changes
OTHER INTERVENTIONS
▫ Vagal maneuver
▫ Electrical cardioversion (if
pharmacological treatment ineffective/
fast heart rate is poorly tolerated)
▫ Radiofrequency catheter ablation
Figure 16.4 ECG pattern in Wolff–Parkinson–White syndrome.
OSMOSIS.ORG 115
Figure 16.5 An ECG of an individual with Wolff–Parkinson–White syndrome (sinus rhythm).
Delta waves are most visible in the V leads.
Figure 16.6 An ECG demonstrating “pre-excited a-fib” or atrial fibrillation in a person with
Wolff–Parkinson–White. It’s an irregularly irregular wide-complex rhythm with no discernible P
waves.
116 OSMOSIS.ORG
NOTES
NOTES
PREMATURE CONTRACTION

▪ Alcohol use
PATHOLOGY & CAUSES ▪ Heart dilation: cardiomyopathies, cor
pulmonale
▪ Depolarizing potential from anywhere in
heart other than sinoatrial (SA) node → ▪ Heart scarring: after myocardial infarction,
contraction earlier than normal in cardiac myocarditis
cycle
▪ Triggered activity COMPLICATIONS
▫ Cells triggered by preceding action ▪ Rarely atrial/ventricular fibrillation
potential after repolarization
▫ Cause: reperfusion therapy after
myocardial infarction/digoxin toxicity SIGNS & SYMPTOMS
▪ Ectopic focus
▫ Cells irritated by electrolyte imbalances,
drugs, ischemic damage → increased ▪ In case of frequent premature contractions:
sympathetic activity → enhanced lightheadedness, palpitations
automaticity → early depolarization
▪ Reentrant loop
▫ Tissue unable to depolarize (e.g. scar
DIAGNOSIS
tissue, amyloid) → no signal conduction
→ depolarizing wave obstructed →
OTHER DIAGNOSTICS
depolarizing wave circles tissue → ▪ ECG
abnormal electrical circuit ▪ Holter monitor
▪ ZIO patch
CAUSES
▪ Often idiopathic TREATMENT
▪ Electrolyte imbalances (hypokalemia,
hypercalcemia, hypomagnesemia) ▪ See individual disorders
▪ Recreational/prescription drugs
(methamphetamines, cocaine, digoxin
intoxication)
OSMOSIS.ORG 117
PREMATURE ATRIAL
CONTRACTION (PAC)
osms.it/premature-atrial-contraction
▪ Noncompensatory pause
PATHOLOGY & CAUSES ▫ Premature impulse enters sinoatrial (SA)
node → shortens cycle
▪ Contraction of atria earlier than normal in
▫ Distinct from compensatory pause:
cardiac cycle
premature ventricular contraction →
▪ Atrial bigeminy: premature atrial premature impulse does not reach
contraction consistently occurs after each SA node → if AV node still refractory,
normal cardiac cycle pauses → lengthens cycle
▪ Atrial trigeminy: premature atrial ▪ Normal QRS
contraction consistently occurs after every
▫ Premature impulse reaches AV node in
two normal cardiac cycles
refractory → blocked premature atrial
contraction → QRS nonexistent
CAUSES ▪ Ashman phenomenon
▪ Heart structural disorders, intoxication, ▫ R-R interval prolongs → increases
electrolyte imbalances refractory period of right bundle branch
→ abnormal conduction of subsequent
COMPLICATIONS impulse → right bundle branch block on
ECG
▪ Atrial fibrillation
▪ Holter monitor
▫ 24h, detect premature contractions
SIGNS & SYMPTOMS
TREATMENT
▪ In case of frequent premature contractions:
lightheadedness, palpitations ▪ Typically requires no treatment
▪ If symptomatic: beta blockers/calcium
OTHER DIAGNOSTICS channel blockers
▪ Electrolyte replacement
ECG
▪ Early, abnormal P wave
▫ Ectopic focus in bottom of atria → SURGERY
negative P wave ▪ If triggering atrial fibrillation:
▫ Ectopic focus closer to atrioventricular radiofrequency catheter ablation
(AV) node → PR interval shorter
▫ P wave, T wave overlap
118 OSMOSIS.ORG
Chapter 17 Premature Contraction
Figure 17.1 Illustration depecting abnormal P wave in atrial bigeminy and trigeminy.
Figure 17.2 Illustration comparing normal ECG tracing vs ECG tracing with premature atrial
contraction.
OSMOSIS.ORG 119
PREMATURE VENTRICULAR
CONTRACTION (PVC)
osms.it/premature-ventricular-contraction
RISK FACTORS
PATHOLOGY & CAUSES ▪ Hypertension, smoking, exercise, stress,
people of African descent (+30% risk),
▪ Contraction of ventricles earlier than normal biological male
in cardiac cycle
▪ Ectopic focus
▫ Latent pacemakers: AV node, bundle of
COMPLICATIONS
His/Purkinje fibers take over SA node’s ▪ Ventricular tachycardia, ventricular
function of pacemaker fibrillation, increased risk for sudden cardiac
death
▫ Irritated cardiac muscle cells → early
depolarization
▪ Triggered activity SIGNS & SYMPTOMS
▫ Ventricular repolarization → ventricle
cells triggered by preceding action ▪ Can be asymptomatic
potential
▪ Lightheadedness, palpitations
▫ Cause: reperfusion therapy after
myocardial infarction/digoxin toxicity
▪ Reentrant loop DIAGNOSIS
▫ Tissue unable to depolarize (e.g. scar
tissue, amyloid) → no signal conduction OTHER DIAGNOSTICS
→ depolarizing wave obstructed →
depolarizing wave circles tissue → ECG
abnormal electrical circuit ▪ Wide, bizarre QRS: signal goes through
▪ Ventricular bigeminy: premature ventricular ventricular muscle, not normal conduction
contraction consistently comes after each pathway → conduction is slower than
normal cardiac cycle normal
▪ Ventricular trigeminy: premature ventricular ▪ Ectopic impulse in right ventricle
contraction consistently comes after every ▫ Left bundle branch block pattern of QRS
two normal cardiac cycles complex
▫ V1: large negative complex, dominating
S wave
CAUSES
▪ Ectopic impulse in left ventricle
▪ Heart structural disorders, intoxication,
electrolyte imbalances ▫ Right bundle branch block pattern of
QRS complex
▫ V1: large positive complex, dominating
R wave
120 OSMOSIS.ORG
Chapter 17 Premature Contraction
▪ Abnormal ST segments: deviation from

isoelectric baseline in opposite direction TREATMENT
from QRS complex
▪ Typically requires no treatment
▪ Inverted T waves in leads, QRS complex
predominantly positive
▪ Nonexistent P wave: covered by wide QRS MEDICATIONS
complex ▪ If symptomatic: venodilators, calcium
▫ QRS followed by compensatory pause channel blockers, administer beta blockers
▪ Ventricular fusion beat: premature QRS with caution
complex occurs during PR segment,
combines with normal depolarization wave SURGERY
▪ R-on-T phenomenon: premature QRS ▪ If triggering ventricular arrhythmias:
complex occurs at/near T wave apex radiofrequency catheter ablation to destroy
▪ Holter monitor ectopic focus/replacement if necessary
OTHER INTERVENTIONS
▪ If mild, no exercise restrictions; if severe,
reduced physical activity
Figure 17.3 Illustration comparing premature ventricular contractions that occur during a P wave,
during a PR segment, and during a T wave.
Figure 17.4 Illustration comparing ventricular bigeminy and trigeminy.
OSMOSIS.ORG 121
NOTES
NOTES
SHOCK
SHOCK
osms.it/shock
creatinine concentration (non-specific,
PATHOLOGY & CAUSES i.e. seen in all forms of shock)
▫ Abnormal potassium levels
▪ Global inadequate tissue perfusion
▫ Metabolic acidosis/alkalosis
▫ Extremely low blood pressure (BP) →
▫ Hematocrit, serum albumin
end-organ failure concentration → reduction in plasma
volume increases concentration
TYPES
Cardiogenic Shock
▪ Hypovolemic shock, cardiogenic shock,
obstructive shock, distributive shock ▪ General clinical manifestations
▫ Hypotension, manifestations of
Hypovolemic Shock pulmonary edema
▪ General clinical manifestations ▪ Subtypes of cardiogenic shock
▫ Reduced preload with suspected cause ▫ Myopathic: find specific cause via ECG/
▪ Variable presentation based on etiology of lab values/chest radiograph
fluid loss ▫ Arrhythmogenic: caused by arrythmia
▪ Hemorrhage, evidence of trauma
Obstructive Shock
▫ Internal bleeding into thoracic/peritoneal/
retroperitoneal space ▪ General clinical manifestations
▪ Nonhemorrhagic fluid loss ▫ Low preload; obstruction of blood flow
outside the heart
▫ Decreased tissue perfusion
▫ Cardiac tamponade, pulmonary
▫ Elevated blood urea nitrogen, serum
embolism, tension pneumothorax
Figure 18.1 Illustration summarizing the causes and effects of hypovolemic, cardiogenic, and
distributive shock.
122 OSMOSIS.ORG
Chapter 18 Shock
Distributive Shock RISK FACTORS

▪ General clinical manifestations ▪ Dependent upon type
▫ Hypotension without reduced preload, ▪ Septic shock most common in United
fluid overload States, followed by cardiogenic,
▪ Subtypes of distributive shock hypovolemic, other forms of distributive/
▫ Septic: caused by infection obstructive shock
▫ Anaphylactic: allergic reaction → ▪ Hypovolemic shock from gastrointestinal
respiratory distress, vomiting, abdominal (GI) losses/dehydration most common in
pain, chest pain, dysrhythmia, collapse low-income countries
▫ Neurogenic: pain at site of spinal
fracture, evidence of spinal injury (loss STAGING
of sensation, paralysis, loss of reflexes)
Initial
▫ Endocrine: adrenal crisis (nonspecific
symptoms, eg. anorexia, nausea, ▪ Cellular, not clinically apparent
vomiting, abdominal pain, fatigue,
Compensatory
lethargy, weakness, fever, confusion,
coma); confirmation of adrenal ▪ Neural, hormonal, biochemical
insufficiency compensation to maintain homeostasis;
inadequate perfusion → autonomic nervous
system attempts to compensate
▫ Sympathetic nervous system
OSMOSIS.ORG 123
vasoconstriction, ↑ contractility ▪ Preserved/hyperdynamic left ventricle =
▫ Release of catecholamines, vasopressin, distributive shock
angiotensin II → ↑ vasoconstriction, ▪ Point-of-care ultrasond
↑ retention water, sodium → ↑ SVR, ↑ ▫ Examination of heart → cause of
blood volume → ↑ BP → ↑ perfusion cardiogenic shock, obstructive shock
Progressive Focused assessment and sonography for
▪ Compensation fails, requires aggressive trauma (FAST)
interventions to prevent multiple organ ▪ Fast ultrasound examination for
dysfunction syndrome hemopericardium, intra-abdominal
bleeding; rule out/in hypovolemic shock
Irreversible
▪ Decreased perfusion (vasoconstriction,
decreased cardiac output) → anaerobic Hemodynamic monitoring
metabolism; profound hypotension, ▪ Via central venous catheters
hypoxemia, organ failure; recovery unlikely ▪ Elevated central venous pressure, low
mixed venous oxygen saturation =
cardiogenic shock
SIGNS & SYMPTOMS
▪ Altered mental state, decreased peripheral LAB RESULTS
pulse, tachycardia, hypotension
Elevated serum lactate
▪ Varies by type and subtype of shock (see
▪ Early indicator, reflective of poor tissue
table below)
perfusion
Renal, liver function tests

DIAGNOSIS ▪ Elevated blood urea nitrogen (BUN),
creatinine, transaminases indicate end-
DIAGNOSTIC IMAGING organ damage
Chest radiography ▫ May help point to cause (acute hepatitis,
▪ Clear in hypovolemic/obstructive shock chronic cirrhosis)
from pulmonary embolism Coagulation studies, D-dimer level
▪ Pneumonia ▪ Elevated fibrin split products, elevated
▫ Septic shock D-dimer level, low fibrinogen level = severe
▪ Pneumothorax shock
▫ Obstructive shock
Cardiac enzymes, natriuretic peptides
▪ Pulmonary edema
▪ Elevated troponin, creatine phosphokinase,
▫ Cardiogenic shock/ARDS
N-terminal pro-brain natriuretic peptide,
Pulmonary artery catheterization brain natriuretic peptide = cardiogenic
shock due to ischemia/pulmonary embolism
▪ Hemodynamic measurements can be
helpful Complete blood count, differential
▪ Measure cardiac output, systemic vascular ▪ High hematocrit
resistance, pulmonary artery occlusion
▫ Hemoconcentration from non-
pressure, right atrial pressure, mixed
hemorrhagic hypovolemic shock
venous oxyhemoglobin saturation
▪ Anemia, bleeding
▪ Rarely necessary to identify etiology of
shock ▫ Hemorrhagic shock
▪ Elevated eosinophil
Ultrasound/echocardiography ▫ Allergy, anaphylactic shock
▪ Allows visualization of altered cardiac ▪ Leukocytosis
function ▫ Septic shock, not specific; more common
124 OSMOSIS.ORG
Chapter 18 Shock
in septic shock, may also occur in other OTHER DIAGNOSTICS

types of shock as sign of poor prognosis
History & physical
Coagulation studies, D-dimer level ▪ Low blood pressure, tachycardia,
▪ Elevated prothrombin time, international tachypnea, signs of poor end-organ
normalized ratio, activated partial perfusion (low urine output, confusion, loss
thromboplastin time of consciousness), weak pulse, cool skin,
▫ Septic shock, other issues (e.g. sepsis, metabolic acidosis, hyperlactatemia
systemic inflammatory response
Shock index
syndrome); elevated D-dimer levels
common in septic shock ▪ Heart rate divided by systolic pressure
▫ Normal range 0.5–0.8
Peripheral O2 sat via pulse oximetry ▫ If index higher, increased suspicion of
▪ Hypoxemia underlying state of shock
▫ Obstructive, cardiogenic shock ▫ Most useful for isolated hypotension/
tachycardia
Urinalysis
▪ Infection, septic shock ECG
▪ Arrhythmia, ST segment changes
Material gram stain from infection sites consistent with ischemia
▪ Septic shock ▪ Low-voltage ECG
Blood culture ▫ Pericardial effusion
▪ identifies causative microbe in case of ▪ Arrhythmia
septic shock; directs targeted antibiotic ▫ Arrhythmogenic cardiogenic shock
therapy ▪ Ischemia
▫ Myopathic cardiogenic shock
OSMOSIS.ORG 125
MNEMONIC: ABCDE
Treatment for shock
TREATMENT
Airway: ensure clear airway,
▪ See chart for a detailed summary of
possibly intubate
treatments for different forms of shock
Breathing: assist individual
in breathing, mechanical
ventilation/sedation OTHER INTERVENTIONS
Circulation: administer fluids
Surviving sepsis campaign guidelines
(e.g. isotonic crystalloid)
▪ End resuscitation when urine output 0.5ml/
Delivery of oxygen: monitor
kg/hr, central venous pressure (CVP) 8–12
lactate levels
mmHg, mean arterial pressure (MAP)
Endpoint resuscitation (specific 65–90mmHg, central venous oxygen
to septic shock) concentration > 70%, normalize lactate
levels
▫ CVP 8–12mmHg (recent literature
shows CVP poorly predicts fluid
responsiveness, poor marker of
adequate resuscitation)
126 OSMOSIS.ORG
NOTES
NOTES
SUDDEN CARDIAC DEATH

▪ Abrupt cessation of cardiac activity (cardiac MEDICATIONS
arrest) in someone asymptomatic up until ▪ According to Advanced Cardiac Life
moment of arrest Support protocols
SIGNS & SYMPTOMS OTHER INTERVENTIONS

Cardiopulmonary resuscitation (CPR)
▪ Asymptomatic
▪ Maintains blood flow by mimicking
pumping motion heart makes during a
DIAGNOSIS medical emergency
▪ Made based on lack of pulse
BRUGADA SYNDROME
osms.it/brugada-syndrome
▪ 20% associated with SCN5A gene
PATHOLOGY & CAUSES mutation which encodes for sodium ion
channel in cell membranes of heart muscle
▪ Condition with characteristic abnormal cells
electrocardiogram findings → increases
risk of sudden cardiac death in healthy
individuals RISK FACTORS
▪ Mixture of normal, abnormal sodium ▪ Biological males, more common in Asia
channels within adjacent myocardial tissue than North America, Europe
can set up heterogenous refractory periods
necessary for development of reentrant COMPLICATIONS
rhythms → ventricular tachycardia/
▪ Ventricular fibrillation, high risk of sudden
fibrillation
cardiac death
CAUSES
▪ Inherited
▫ Autosomal dominant, variable
expression
OSMOSIS.ORG 127
▪ Type I
SIGNS & SYMPTOMS ▫ Right bundle branch block pattern
▪ Brugada pattern ▫ Gradually descending ST elevations, at
least 2mm (0.2mV) in leads V1–V3
▫ ECG findings, no symptoms
▫ Negative T- wave in leads V1–V3
▪ Brugada syndrome
▪ Type II
▫ ECG findings, symptoms of sustained
ventricular tachycardia (palpitations, ▫ Class IV antiarrhythmic can convert to a
syncope, dyspnea, lightheadedness) Type I Brugada pattern—often needed
for diagnosis
▫ Saddle-back pattern with at least 2mm
J point elevation, 1mm ST elevation
DIAGNOSIS (positive/biphasic T wave)
LAB RESULTS
Genetic testing
TREATMENT
▪ Confirms diagnosis
▪ Brugada pattern: none
OTHER DIAGNOSTICS SURGERY

ECG
Implanted cardiac defibrillator (ICD)
▪ Type I/II Brugada electrocardiogram pattern
▪ Brugada syndrome
▫ May present simultaneously, may be
induced by certain drugs (e.g. calcium
channel blockers), or may resurface due
to unknown triggers
Figure 19.1 ECG (lead V1) demonstrating Brugada waveforms type I (left) and type II (right).
128 OSMOSIS.ORG
Chapter 19 Sudden Cardiac Death
Figure 19.2 Calcium channel blockers can increase the chance of developing Brugada syndrome.
The condition is typically associated with right bundle branch block, which makes the heart
susceptible to developing a reentrant rhythm, which in turn causes ventricular tachycardia and
sometimes ventricular fibrillation.
PULSELESS ELECTRICAL
ACTIVITY
osms.it/pulseless-electrical-activity
MNEMONIC: 6Ts & 6Hs
PATHOLOGY & CAUSES Obstruction to blood flow
Tablets/toxins (drug overdose)
▪ Pulseless, despite electrical activity (evident
on ECG) typically resulting in pulse Cardiac Tamponade
▪ Heart does not contract in spite of electrical Tension pneumothorax
activity/does not generate enough cardiac Thrombosis (myocardial
output to cause pulse infarction)
▪ Survival ~20% Thrombosis (pulmonary
embolism)
Trauma (hypovolemia - blood
CAUSES loss)
▪ Abrupt drop in preload
Hypovolemia
▪ Abrupt pump failure
Hypoxia
Hydrogen ions (acidosis)
Hyperkalemia/hypokalemia
Hypoglycemia
Hypothermia
OSMOSIS.ORG 129
▪ Loss of consciousness MEDICATIONS
▪ Breathing stops ▪ If cause unclear medicine used similar to
asystole
▫ Intravenous/intraosseous line,
DIAGNOSIS administer epinephrine 1mg/3–5
minutes
OTHER DIAGNOSTICS
▪ Absence of pulse
ECG
▪ Organized/semi-organized electrical activity
VENTRICULAR FIBRILLATION
osms.it/ventricular-fibrillation
▪ Electrolyte imbalances: hypokalemia,
PATHOLOGY & CAUSES hyperkalemia
▪ Ischemia to ventricular muscle
▪ Ventricular electrical activity disorganized
▪ Scar tissue from previous myocardial
to point that coordinated contraction is
infarction
impossible
▪ Anatomical reentry
▪ Rapid, irregular electrical activity prevents
▪ Electrocution/external electrical stimulation,
ventricles from contracting in sync →
such as in unsynchronized cardioversion
cardiac output falls to zero
▪ If heart tissue stimulated during T wave
▪ Often due to tissue heterogeneity: heart
upslope (in an electrocardiogram), can
cells stressed/damaged, tissues of different
induce fibrillation
areas structurally, electrically different
▪ Mechanism: tissue heterogeneity in
cardiac electrical system → asynchronous SIGNS & SYMPTOMS
depolarization & contraction → inadequate
blood pumped → oxygen deprivation →
▪ Chest pains, dizziness, nausea, rapid pulse,
death
dyspnea
▪ Functional reentry: arrhythmia causes
different areas of heart to depolarize &
contract out of sync → heart non-functional
DIAGNOSIS
CAUSES OTHER DIAGNOSTICS
▪ Medications causing long QT syndrome ▪ Pulse check: no pulse
▪ Illicit drugs (e.g. methamphetamine,
cocaine) ECG
▪ Congenital arrhythmogenic syndromes (e.g. ▪ Absence of PQRST waves; instead, fine,
Brugada, hypertrophic cardiomyopathy, coarse fibrillatory waves
arrhythmogenic right ventricular dysplasia, ▪ Electrocardiogram appears chaotic
Wolff-Parkinson-White syndrome, ▪ Undulating baseline
congenital long QT syndrome)
130 OSMOSIS.ORG
Chapter 19 Sudden Cardiac Death
OTHER INTERVENTIONS
TREATMENT
Cardiopulmonary Resuscitation (CPR)
SURGERY
Defibrillation
ICD ▪ High energy shock depolarizes large
▪ Used when cause is unpreventable enough portion of tissue (critical mass) that
▪ Surgically implanted sinus node can take control
▪ Constantly monitors electrocardiogram
Electrophysiology study
▪ ICD recognizes ventricular fibrillation,
▪ If individual has had previous MI/has
delivers responsive defibrillating shock
survived cardiac arrest in whom signs are
▪ Doesn’t fix underlying condition; treats not apparent after routine, non-invasive
symptom, improves survival testing
▪ Primary prevention ▫ Evaluate for possible ventricular
▫ Individuals with heart failure at risk of tachycardia ablation
ventricular tachycardia/fibrillation
▪ Secondary prevention Revascularization
▫ Cardiac arrest survivors for whom ▪ If ventricular fibrillation occurs in setting of
triggers cannot be treated/prevented myocardial infarction
▫ Cardiac catheterization
▫ CABG
Figure 19.3 Histological appearance of fatal ventricular fibrillation demonstrating broken

myocardial fibers and squared-off nuclei.
OSMOSIS.ORG 131
Figure 19.4 ECG demonstrating ventricular fibrillation.
132 OSMOSIS.ORG
NOTES
NOTES
SUPRAVENTRICULAR
TACHYCARDIA

▪ Abnormally fast heart rhythms due to LAB RESULTS
inappropriate electrical activity in upper ▪ Electrolytes, thyroid stimulating hormone
portion of heart, atria/atrioventricular (AV) levels
node
▪ Ventricles contract > 100 beats per minute,
OTHER DIAGNOSTICS
pathology originates above ventricles
▪ ECG
▫ Ventricles protected by gating at AV
node
TREATMENT
CAUSES
▪ Reentry conductive loops ▪ See individual disorders
▪ Increased automaticity
▪ Triggered activity MEDICATIONS
▪ Calcium channel blockers, beta blockers,
RISK FACTORS anticoagulants
▪ Cardiac: coronary artery disease, heart
failure SURGERY
▪ Non-cardiac: chronic obstructive pulmonary ▪ Catheter ablation
disease (COPD), pulmonary embolism,
alcohol abuse, hyperthyroidism
SIGNS & SYMPTOMS

▪ Palpitations, chest pain, anxiety, dyspnea,
syncope, lightheadedness
OSMOSIS.ORG 133
ATRIAL FIBRILLATION
osms.it/atrial-fibrillation

▪ Rapid, irregular (no discernible rhythm) ▪ May be asymptomatic
heart rate ▪ Dyspnea, fatigue, palpitations,
▪ Progression lightheadedness, weakness, chest pain,
▫ Paroxysmal: intermittent rhythm, hemodynamic shock
may revert back to sinus rhythm
spontaneously
▫ Persistent: > seven days, requires DIAGNOSIS
intervention to convert back to sinus
rhythm LAB RESULTS
▫ Permanent: long-standing atrial ▪ Thyroid stimulating hormone (TSH) levels:
fibrillation, cardioversion unsuccessful exclude hyperthyroidism

▪ Disorganized waves of atrial depolarization, Transthoracic echocardiogram
exact mechanisms not well understood
▪ Evaluate atrial, ventricular size; valvular
▫ Regular impulses of sinus node disease; left ventricular function; pericardial
overwhelmed by rapid electrical disease
discharges from various sources
(automatic foci, multiple reentry Transesophageal echocardiogram
phenomena) ▪ Evaluate for atrial thrombi
▫ Arise from left more than right atrium
OTHER DIAGNOSTICS
RISK FACTORS
▪ Old age: affects 4% 60–70, 14% > 80 ECG
▪ Obesity, diabetes mellitus, excessive ▪ Absent P waves
alcohol consumption, genetic predisposition ▪ Irregularly timed QRS complexes (irregular
▪ Cardiovascular disease: heart failure, R-R intervals)
hypertension, coronary artery disease, ▪ No sawtooth wave in atrial fibrillation
non-rheumatic mitral regurgitation, mitral
valve prolapse, rheumatic heart disease,
damaged atrial myocytes
▪ Increased catecholamine levels
▪ Lung disease
▪ Hyperthyroidism
COMPLICATIONS
▪ Thromboembolic events, heart failure,
hypotensive shock
134 OSMOSIS.ORG
Chapter 20 Supraventricular Tachycardia
OTHER INTERVENTIONS
TREATMENT
Rhythm control
MEDICATIONS ▪ Restore sinus rhythm via cardioversion
Anticoagulation Electrical cardioversion
▪ E.g. warfarin, dabigatran, apixaban, ▪ Defibrillator for synchronization
rivaroxaban
▪ CHA2DS2-VASc/CHADS2 score Catheter ablation
▫ Estimate risk of stroke in non-rheumatic ▪ Destruction of heart regions responsible for
atrial fibrillation; higher score = greater abnormal impulses
risk of stroke
▫ Score 0 (biological male)/1 (biological
female): low risk, no anticoagulation
recommended
▫ Score 1 (biological male): moderate risk,
consider anticoagulation
▫ Score ≥ 2: high risk, anticoagulation
recommended
▫ See table of scores
Rate control
▪ < 100 beats per minute
▪ Beta blockers (preferably β1 selective)
▪ Non-dihydropyridine calcium channel
blockers (e.g. diltiazem, verapamil)
▪ Digoxin
Chemical cardioversion
▪ Administer antiarrhythmic medication
▪ Class Ic antiarrhythmics
▪ Class III antiarrhythmics
▪ Maintenance of sinus rhythm after
cardioversion
▫ Class Ic antiarrhythmics
▫ Class III antiarrhythmics
OSMOSIS.ORG 135
Figure 20.1 An ECG demonstrating atrial fibrillation.
ATRIAL FLUTTER
osms.it/atrial-flutter
▪ Isthmus-independent
PATHOLOGY & CAUSES
▪ Reentrant circuit develops in either atrium
▪ Atria depolarize regularly at very high rates ▪ Associated with variety of reentry loops
(200–350bpm), appear to flutter (common after incomplete atrial ablation
procedures, right atrial surgical scars)
TYPES
CAUSES
Typical atrial flutter (AKA Type 1 flutter) ▪ Reentrant electrical signal from either
▪ More common atrium
▪ Single reentrant circuit, right atrium ▪ Reentrant signal loops back on itself
▪ Isthmus-dependent: reentry circuit crosses → overrides normal sinus rhythm →
cavotricuspid isthmus establishes endless loop of stimulation
▪ Circles tricuspid annulus (ring), usually ▪ Underlying disease (e.g. heart failure,
counterclockwise (viewed from below) valvular disease, hypertension, pulmonary
▪ Cavotricuspid isthmus tissue propagates disease) → heart cells less electrically
signal slower than surrounding tissue stable → alters refractory periods →
→ circuit loops → slows propagation → increased risk of reentrant circuits
surrounding tissue exits refractory period ▪ Reentrant circuits initiated by premature
atrial contraction (PAC) → partial premature
Atypical atrial flutter (AKA Type 2 flutter) contraction, normal tissue relaxes → wave
▪ Less common of stimulation propagates → normal tissue
136 OSMOSIS.ORG
contracts, premature tissue recovers →

chance of reentrant circuit, stimulation DIAGNOSIS
wave doubles back on itself
DIAGNOSTIC IMAGING
RISK FACTORS Echocardiogram
▪ Diseases that change atrial heart cell ▪ Evaluate size of right, left atria, ventricles
properties → differing electrophysiological ▪ Detect pericardial/valvular heart disease
properties in adjacent areas → reentry ▪ Decreased ejection fraction (% of blood
circuit pumped by heart per contraction)
▪ Ischemia, fibrosis, previous myocardial
infarction, heart failure, high blood pressure,
diabetes, valvular heart disease, obstructive LAB RESULTS
sleep apnea ▪ Serum electrolytes
▪ Renal function
COMPLICATIONS ▪ Thyroid stimulating hormone (TSH) levels:
exclude hyperthyroidism
▪ Heart failure, thromboembolic events, atrial
fibrillation
OTHER INTERVENTIONS
SIGNS & SYMPTOMS ECG
▪ Typical P waves absent
▪ Palpitations, tachycardia, fatigue ▪ Typical atrial flutter: P waves, saw tooth
▪ Pain/tightness/discomfort in chest shape (F waves) localised to leads II, III, aVF
▪ Heart failure ▪ Atypical atrial flutter: atrial activity
▫ Exercise intolerance (sawtooth waves/otherwise) may occur
anywhere, dependent on reentrant circuit
▫ Difficulty breathing at night/while lying
location
flat
▪ Ventricular rate usually 1/2 atrial flutter rate
▫ Edema of legs, abdomen
(even ratios 2:1, 4:1 more common than
odd, 3:1, 5:1)
▪ 1:1 atrial: catecholamine excess, presence
of accessory bypass tract/class 1A, 1C
antiarrhythmic drug therapy
Figure 20.2 An electrocardiogram demonstrating atrial flutter with a 3:1 AV nodal block. The atrial
trace demonstrates a characteristic sawtooth pattern.
OSMOSIS.ORG 137
Figure 20.3 An electrocardiogram demonstrating atrial flutter with a 3:1 AV nodal block. The
atrial trace demonstrates a characteristic sawtooth pattern.
SURGERY
TREATMENT
Radiofrequency catheter ablation
MEDICATIONS ▪ Cavotricuspid isthmus no longer able to
▪ Anticoagulants (reduce chance of clot carry electrical signal, prevents reentry
formation), beta blockers/calcium channel
blockers (control rates of ventricles)
OTHER INTERVENTIONS
Electrical cardioversion
▪ Depolarize atrial tissue, resynchronize
contraction
138 OSMOSIS.ORG
ATRIOVENTRICULAR NODAL
REENTRANT TACHYCARDIA
(AVNRT)
osms.it/av-nodal-reentrant-tachycardia
RISK FACTORS
PATHOLOGY & CAUSES
▪ Biologically-female individuals → 75%
of cases, emotional stress → alcohol use
▪ Heart rate disturbance due to accessory
disorder, hyperthyroidism, electrolyte
pathway in/near AV node
disturbances
▪ Electric conduction splits into two
pathways → forms loop
▫ Alpha pathway: slow conduction, short SIGNS & SYMPTOMS
refractory period
▫ Beta pathway: fast conduction, long ▪ Palpitations, transient chest pain, bouts
refractory period of transient tachycardia, transient
hypotension, (pre)syncope
TYPES
Slow-fast/“typical” AVNRT DIAGNOSIS
▪ Anterograde conduction to ventricles via
slow pathway (alpha) LAB RESULTS
▪ Retrograde to atria conduction via fast ▪ Thyroid function
pathway (beta) ▪ Serum electrolytes
▪ Depolarization down both pathways →
reaches end of beta pathway first → signal
splits
OTHER DIAGNOSTICS
▫ Travels to ventricles → contraction ECG
▫ Travels up alpha pathway → meets slow ▪ Tachycardia 140–280bpm
signal → signals cancel each other out ▪ Absent P waves
▪ Depolarization wave from premature beat ▪ P waves immediately before/after QRS
reaches AV node → refractory fast (beta) complex
pathway → signal initially down alpha
▪ P waves inverted/retrograde
pathway only → splits
▪ R’ waves (small secondary R waves)
▫ Travels to ventricles → contraction
▫ Travels up beta pathway → signal
travels down alpha pathway, beta TREATMENT
pathway comes out of refractory period
→ signal reaches end of alpha pathway MEDICATIONS
→splits back up beta pathway
▪ Adenosine, beta blockers, calcium channel
Fast-slow/”atypical” AVNRT blockers to slow AV node conduction
▪ Anterograde conduction via fast pathway,
retrograde conduction via slow pathway
OSMOSIS.ORG 139
OTHER INTERVENTIONS Slow AV node conduction
▪ Vagal maneuver (carotid sinus massage/
Radiofrequency catheter ablation
Valsalva maneuver) → activates vagus
▪ Definitive treatment nerve
▪ Ablation of slow alpha pathway
Figure 20.4 Illustration depicting path of electrical conduction in AV node during slow-fast
AVNRT.
Figure 20.5 An ECG demonstrating typical (slow-fast) AVNRT. R waves are best seen in lead
V1.
140 OSMOSIS.ORG
NOTES
NOTES
VASCULAR COMPRESSION
SYNDROMES

▪ Range of congenital/acquired anatomical DIAGNOSTIC IMAGING
compressions of vasculature/by vascular ▪ X-ray, CT scan, ultrasound
structure
▪ Acquired
OTHER DIAGNOSTICS
▫ Rapid changes in weight → changes to
▪ Physical exam
fat pad cushioning between vasculature,
other structures → compression
▪ Vasculature squeezed between two TREATMENT
structures → ischemia (artery)/vascular
engorgement (vein) SURGERY
▪ Vasculature compresses, obstructs another ▪ See individual disorders
structure → obstruction
OTHER INTERVENTIONS
SIGNS & SYMPTOMS ▪ Weight gain/loss
▪ Vascular obstruction → ischemia

▫ Pain, nausea, vomiting, weakness, cold,
pulseless extremity
▪ Organ obstruction
▫ Pain, nausea, vomiting, weight loss
OSMOSIS.ORG 141
NUTCRACKER SYNDROME
osms.it/nutcracker-syndrome

▪ Left renal vein squeezed between superior ▪ Left flank pain
mesenteric artery, abdominal aorta ▪ Hematuria
▪ Three unpaired arteries ▪ Nausea, vomiting (compression of
▫ Celiac, superior mesenteric, inferior splanchnic veins)
mesenteric ▪ Individuals who are biologically male
▪ Aortomesenteric angle ▫ Scrotal mass → varicocele
▫ Between aorta, superior mesenteric (engorgement of testicular veins)
artery
▪ Aortomesenteric angle reduced → arteries
pinch left renal vein → prevents blood DIAGNOSIS
return to heart → blood backs up in left
kidney → renal hypertension → small DIAGNOSTIC IMAGING
breaks in renal blood vessels → blood in
urine Ultrasound, Doppler, CT scan, MRI, conven-
tional angiography
▪ Aortomesenteric angle may decrease to 6º
▪ Left renal vein stenosis, reduced
▪ Blood may back up in left testicle
aortomesenteric angle
▪ Reduced blood flow through left renal vein
CAUSES on Doppler
▪ Young people: reduction of aortomesenteric ▪ Collateral circulation
angle due to normal growth ▪ Dilated testicular veins → varicocele
▪ Adults: extreme weight loss due to severe
illness (e.g. HIV/AIDS, cancer, anorexia
nervosa), compressing tumors (e.g. TREATMENT
pancreatic)
SURGERY
COMPLICATIONS ▪ For tumors
▪ Varicocele ▫ Move vein, place stent
▫ Left testicular vein drains into left renal
vein → blood backs up into left testicle OTHER INTERVENTIONS
▪ Ovarian vein syndrome ▪ Weight gain
▫ Dilated ovarian vein compresses ureter ▫ Increase mesenteric fat pad → widen
→ abdominal/back/pelvic pain aortomesenteric angle → relieve
▪ Renal vein thrombosis compression
142 OSMOSIS.ORG
Chapter 21 Vascular Compression Syndromes
Figure 21.1 An illustration demonstrating the pathophysiology and sequelae of

nutcracker syndrome.
SUPERIOR MESENTERIC ARTERY

SYNDROME
osms.it/superior-mesenteric-artery-syndrome
▪ Post-scoliosis surgery
PATHOLOGY & CAUSES
▪ Congenital anatomic abnormalities
▪ Vascular structures compressing another ▫ Ligament of Treitz too short
structure ▫ Superior mesenteric artery branches off
▪ Distal third of transverse section of aorta further down
duodenum compresses between abdominal
aorta, superior mesenteric artery COMPLICATIONS
▪ Three unpaired arteries ▪ Small bowel obstruction
▫ Celiac, superior mesenteric, inferior ▪ Severe malnutrition, wasting → increases
mesenteric compression, worsens condition
▪ Mesenteric fat pad thins out → reduces
aortomesenteric angle → aorta,
superior mesenteric artery pinch down
on transverse duodenum → intestinal
obstruction
CAUSES
▪ Extreme weight loss
▫ Illness/intentional
OSMOSIS.ORG 143
▪ Gradual/quick onset; may be intermittent SURGERY
▪ Early satiety; bilious emesis; weight ▪ E.g. ligament of Treitz → allow duodenum
loss; abdominal distention; burping; to move freely
hypersensitive abdomen; reflux, heartburn
▪ Relieved when in left lateral decubitus OTHER INTERVENTIONS
(knee-to-chest) position/prone position;
▪ Management
with Hayes maneuver (apply pressure
below umbilicus towards head, spine) ▫ Nasogastric tube to decompress
stomach, early duodenum; fluids,
electrolytes
▪ Weight gain (regrow mesenteric fat pad);
DIAGNOSIS may require feeding tube past obstruction
DIAGNOSTIC IMAGING
Abdominal X-ray
▪ Dilated fluid/gas-filled stomach, proximal
duodenum
CT scan with oral contrast/MRI

▪ Vascular compression of third part of
duodenum, reduced aortomesenteric
angle, collapsed small bowel distal to SMA
crossing
Abdominal ultrasound
▪ Dilated proximal duodenum, stomach
OTHER DIAGNOSTICS
▪ High-pitched bowel sounds Figure 21.2 An abdominal CT scan in
▪ Succussion splash the axial plane demonstrating superior
▫ Sloshing sound of built-up gas, fluid in mesenteric artery compression syndrome.
distended digestive tract upstream of The third part of the duodenum (outlined) is
obstruction compressed between the superior mesenteric
artery and the aorta.
144 OSMOSIS.ORG
NOTES
NOTES
VASCULAR MALFORMATIONS

▪ Developmental malformations of the DIAGNOSTIC IMAGING
vascular system ▪ Imaging studies usually not needed
SIGNS & SYMPTOMS OTHER DIAGNOSTICS

▪ History
▪ Usually asymptomatic ▪ Physical examination
▪ Large malformations can cause obstruction
/impair organ functions
▪ Diverts away high volume of blood → heart
TREATMENT
compensates → high-output heart failure
▪ Generally no need for treatment unless
formations bleed/cause other problems
SURGERY
▪ Surgical/laser therapy considered for skin
malformations
Figure 22.1 Illustration depicting changing pressure between normal arteries and veins.
OSMOSIS.ORG 145
ARTERIOVENOUS MALFORMATION
osms.it/arteriovenous-malformation
Brain
PATHOLOGY & CAUSES
▪ Epilepsy, neurological deficits, abnormal
sensations (numbness, tingling, pain)
▪ Abnormal capillary bed formation between
artery and vein ▪ Sudden onset, severe headache indicates
subarachnoid hemorrhage
▪ Capillary bed does not form, leaving
arteries connected directly to veins → ▪ Difficulty with movement coordination,
tangling → nidus muscle weakness, paralysis, vertigo
▪ Arteriovenous fistula: single artery to single ▪ Apraxia (physical difficulties performing
vein direct connection actions upon command, though command
is understood)
▪ No capillaries → arteries, veins subjected
to high pressures → arteries dilate → veins Lungs
thicken (fibrosis) ▪ Asymptomatic 1/3 of time
▪ AVM expands over time → compresses ▪ Dyspnea, cough, clubbing, cyanosis,
surrounding tissues → decreases blood hemoptysis, chest pain
flow
▪ Platypnea (shortness of breath in upright
▫ Can cause bruit (whooshing noise heard position, relieved by lying down)
on auscultation)
▪ Orthodeoxia (decrease in oxygen saturation
▫ Noise can get loud enough that person by ≥ 2% when rising from lying down to
with the bruit can hear it, causing standing)
psychological stress, hearing issues and
sleep issues Spine
▪ Muscle weakness, paralysis
CAUSES
Pediatric
▪ Possibly congenital/genetic
▪ May present with
▪ Osler–Weber–Rendu disease/hereditary
▫ Heart failure, macrocephaly, prominent
hemorrhagic telangiectasia connected to
scalp veins
AVM
RISK FACTORS DIAGNOSIS

▪ Biological male, 10–30 years old, genetic
conditions (e.g. Osler-Weber-Rendu) DIAGNOSTIC IMAGING
Angiography
COMPLICATIONS ▪ Functional anatomy of AVM
▪ Ischemia at site, high output heart failure, ▫ Feeding arteries: stenosis
rupture, haemorrhage
▫ Sharp twisting of veins (ectasia)
▫ Arterial and venous dilatation
SIGNS & SYMPTOMS CT scan/MRI
▪ Anatomy of AVM
▪ Most are asymptomatic
▫ Irregular/bulbous masses in brain/
▪ Depend upon location
brainstem
▪ Presence of bruit on auscultation
146 OSMOSIS.ORG
Chapter 22 Vascular Malformations
OTHER DIAGNOSTICS
▪ Bruit
TREATMENT
▪ Treat all arteriovenous malformations
SURGERY
Radiosurgery
▪ Radiation beams target AVM to close
vessels
Endovascular embolization
▪ Catheter placed to obstruct vessels
Figure 22.2 CT scan of the head in the
axial plane demonstrating an arteriovenous
malformation in the left parietal lobe.
CAVERNOUS HEMANGIOMA
osms.it/cavernous-hemangioma
RISK FACTORS
PATHOLOGY & CAUSES ▪ Von Hippel–Lindau disease
▪ Benign tumor formed from tangle of
unencapsulated, dilated, thin-walled blood COMPLICATIONS
vessels ▪ Rupture → hemorrhage
▪ Spherical caverns form from dilatation of ▪ Obstructive jaundice, clotting disorders
vessels separated by fibrous connective ▪ Intravascular thrombosis
tissue ▪ Dystrophic calcifications
▪ Characteristic “mulberry” presentation
TYPES SIGNS & SYMPTOMS

Cerebral cavernous malformations ▪ Usually asymptomatic
Liver cavernous hemangioma Brain

▪ Sometimes found in people with previous ▪ Brain tissue compression → seizures,
pregnancies → high estrogen levels hemorrhages
thought to be a factor ▪ Stroke, speaking difficulties, memory/
attention difficulties
Ocular cavernous hemangioma
▪ Headaches, balance issues
CAUSES Liver
▪ Genetic mutations ▪ Pain in right upper quadrant
▫ CCM1, CCM2, CCM3 ▪ Gastrointestinal issues: nausea, vomiting,
loss of appetite, early fullness after eating
OSMOSIS.ORG 147
Eyes
▪ Double/decreased vision, proptosis
TREATMENT
▪ Monitoring usually sufficient
DIAGNOSIS
MEDICATIONS
DIAGNOSTIC IMAGING ▪ Facial hemangioma growth slowed with
steroids
MRI
▫ Administered orally/injected at site
▪ Seen as popcorn/mulberry shape →
pathognomonic Sclerotherapy
▪ Hepatic cavernous hemangiomas best ▪ Close tumor’s blood supply → tumor
diagnosed with shrinks
▫ Ultrasound
▫ IV contrast CT scan SURGERY
▪ Can be mistaken for metastatic tumors ▪ Prevent damage to healthy tissues
Figure 22.4 A cavernous hemangioma from

the liver, composed of large vascular spaces
Figure 22.3 Abdominal CT scan in the axial with thin walls. No normal liver is present.
plane showing a hemangioma of the liver.
148 OSMOSIS.ORG
HEMANGIOMA
osms.it/hemangioma
black, crusted, sometimes painful
PATHOLOGY & CAUSES ulceration
▫ > five hemangiomas → ultrasound for
▪ Hemangioma/infantile hemangioma (IH): hepatic hemangioma
benign vascular skin tumor
▪ Deeper hemangiomas: bluish lesions,
▫ Originates from endothelial cells lining poorly defined
blood vessels
▫ Can proliferate into bigger tumors
▪ Most frequent tumors of infancy
▫ Some have superficial capillary
▪ Develop a few days after parturition counterparts visible over/surrounding
▫ If IH appears to be present at birth → affected area
not IH ▫ Slower development
▪ Compound hemangiomas: deep IH +
RISK FACTORS superficial IH
▪ Intrauterine hypoxia
Localised hypoxia
▪
DIAGNOSIS
▪ Biological females more at risk
▪ Premature underweight infants DIAGNOSTIC IMAGING
▪ Usually no need for imaging
COMPLICATIONS
Doppler ultrasound
▪ Usually none
▪ High vessel density and high peak arterial
▪ Easily infected, start bleeding
Doppler shift, may show peripheral feeding
▪ Possible ulceration → infection vessels
▪ Usually psychosocial: mostly appear on
highly visible areas (face, neck, etc.) MRI
▪ Multiple IH in newborns can indicate liver ▪ Multiple high signal intensity lobules (due
hemangiomas to cavernous/cystic spaces containing
stagnant blood); often heterogeneous
SIGNS & SYMPTOMS LAB RESULTS

▪ Usually no need for biopsy unless history
▪ Appear in first weeks of life
unclear; used to confirm diagnosis
▪ Tumors can grow for ≤ six months after
birth
▪ Most regress over time, around five years OTHER DIAGNOSTICS
old
History and physical exam
▫ Can leave marks: fibroadipose tissue,
▪ History of onset, age, growth pattern,
changes in pigmentations, scars
duration, treatment
▪ Resemble red/white patch, blemish; can be
found all over body
▪ Superficial lesions: bright red, flat/raised
from the skin → papules AKA “strawberry
hemangiomas”
▫ Exposed areas: if grazed, can produce
OSMOSIS.ORG 149
TREATMENT
▪ Most do not require treatment, regress in a
few years
▪ Exceptions
▫ Functional issues: feeding (laryngeal
hemangiomas), obscuring vision
▫ Bleeding
▫ Hepatic/cardiac complications
▫ Permanent scars causing disfigurement
Figure 22.5 A capillary hemangioma on the
MEDICATIONS abdomen of an infant.
▪ Beta blockers, oral corticosteroids
▪ Antiangiogenic therapies
▫ Usually intravenous: interferon-alfa 2a,
2b, vincristine
SURGERY
▪ Rarely, surgery/laser therapy

capillary hemangioma showing multiple small
vascular spaces containing red blood cells.
LYMPHANGIOMA
osms.it/lymphangioma
layer; fluid-filled cavities; indistinct margins
PATHOLOGY & CAUSES ▪ One/more cysts ≥ 2cm3/0.8in3 in size
▪ Tends to develop in deep soft tissues;
▪ Benign lymphatic malformations
propensity for rapid growth, local invasion
▪ Composition: lymphatic channels/cysts of muscle, bone, underlying tissue
▪ May present at birth/develop during first
few years of life Lymphangioma circumscriptum
(microcystic)
TYPES ▪ AKA simple/capillary lymphangioma
▪ Composition: capillary-sized endothelial-
Cystic hygroma (macrocystic) lined lymphatic networks
▪ AKA cavernous lymphangiomas ▪ One/more cysts < 2cm3/0.8in3 in size
▪ Composition: cystic masses, dilated ▪ Tend to develop in superficial tissues
lymphatic networks with thin endothelial
150 OSMOSIS.ORG
Mixed
▪ Contains variously-sized cysts
DIAGNOSIS
DIAGNOSTIC IMAGING
CAUSES
▪ Failure to form communication between MRI
lymphatic, venous circulation (e.g. jugular ▪ Multiloculated fluid-filled cystic lesions;
lymph sac, internal jugular vein) during fetal identifies lesion’s extent
development
Ultrasound
▪ May be sporadic/associated with genetic
▪ Prenatal cystic mass detection; ↑ nuchal
mutations (e.g. VEGFR3 germline mutation)
translucency (hypoechoic space)
RISK FACTORS Histopathology

▪ Chromosomal anomalies ▪ Cystically dilated channels lined with flat
▫ Turner syndrome, Down syndrome, endothelial cells, filled with lymphatic fluid;
Noonan syndrome (cystic hygroma) deeper vessels are large, contain smooth
muscle
COMPLICATIONS
▪ Lymphedema, recurrent cellulitis TREATMENT
▪ Disfigurement
▪ Lesion recurrence SURGERY
▪ Fetal hydrops, fetal death, obstructed labor, ▪ Resection
chylous pleural effusion, chylopericardium,
airway compression (cystic hygroma) OTHER INTERVENTIONS
▪ Image-guided percutaneous chemoablation
SIGNS & SYMPTOMS ▪ Sclerotherapy
Cystic hygroma
▪ Large (up to 15cm/5.9in), poorly-defined
soft, fluctuant mass
▫ Commonly located in deeper layers of
cervicofacial region, axilla, lateral chest
wall
▫ Covered with normal skin
Lymphangioma circumscriptum
▪ Slightly elevated lesion
▫ Commonly located in head (oral cavity),
trunk, proximal extremities, axillary
region
▫ May appear as translucent/hemorrhagic
vesicles
▫ Overlying skin may be reddish-purple
color secondary to small hemorrhages,
thrombus formation/may contain wart-
like lesions Figure 22.7 CT scan in the coronal plane
demonstrating a large cystic hygroma on the
left side of the neck.
OSMOSIS.ORG 151
a lymphangioma composed of dilated
lymphatic spaces, lined by simple
endothelium.
152 OSMOSIS.ORG
NOTES
NOTES
VASCULAR STEAL SYNDROMES

▪ AKA steal syndrome DIAGNOSTIC IMAGING
▫ Occlusion → blood follows path of least ▪ Incidental finding
resistance → abnormal blood flow
CT angiography
▪ Hemodynamics
▪ Blood flow/occlusion
▫ Length, width of vessel
▪ Obstruction/narrowing of vessel → Doppler ultrasound
increased resistance → blood follows ▪ Retrograde blood flow
path of least resistance → area distal to
obstruction/narrowing receives less blood,
others receive more blood LAB RESULTS
▪ Atherosclerosis, elevated troponin
TYPES
▪ Coronary steal syndrome OTHER DIAGNOSTICS
▫ Coronary arteries ▪ Nuclear stress test
▪ Subclavian steal syndrome ▪ ECG alterations
▫ Subclavian artery ▪ Heart catheterization
CAUSES TREATMENT
▪ Narrowing/obstruction of vessel
▪ Atherosclerosis/structural abnormalities MEDICATIONS
▪ Pharmacological treatment; see individual
disorders
SIGNS & SYMPTOMS
▪ See individual disorders SURGERY
▪ Revascularization of ischemic area
▫ Endovascular methods, bypass surgery,
percutaneous transluminal angioplasty
OSMOSIS.ORG 153
CORONARY STEAL SYNDROME
osms.it/coronary-steal-syndrome
▪ Drugs
PATHOLOGY & CAUSES
▫ Dipyridamole, nitroprusside, isoflurane
(inhaled anesthetic), vasodilators
▪ Narrowed/obstructed coronary vessel
+ vasodilator alters cardiac circulation ▪ Coronary arteriovenous fistula between
→ blood shunted away from area distal coronary artery, cardiac chamber
to narrowing/obstruction exacerbating
ischemia COMPLICATIONS
▪ AKA cardiac steal syndrome ▪ Recurrent myocardial infarction (MI),
▪ Artery narrowing/obstruction → dilation of ischemia
distal arteries to compensate for decreased
blood flow → addition of vasodilator →
dilation of resistance vessels → blood SIGNS & SYMPTOMS
supplying ischemic zone shunted away to
areas of least resistance → more ischemia ▪ Cerebrovascular
▪ Narrowing of coronary arteries + ▫ Presyncope/syncope, vertigo, vision loss,
vasodilator (e.g. dipyridamole, adenosine) memory loss, weak pulse
→ blood flows to non-obstructed vessels ▪ Chest pain
→ exacerbating ischemia ▪ Unequal pulses in upper extremities
▫ Dipyridamole: antiplatelet, vasodilator ▪ Blood pressure differences between arms
→ all coronary vessels dilate when in
individual with partial obstruction of
coronary artery DIAGNOSIS
▫ Vasodilator may steal blood from
deprived region distal to obstruction OTHER DIAGNOSTICS
▪ Dilation of resistance vessels → blood ▪ Cardiac stress test
shunted away from coronary vessels ▫ Vasodilator produces ischemic ECG
changes (with/without exercise)
CAUSES ▪ Coronary angiography
▪ Coronary artery bypass grafting surgery
(CABG)
▫ Rare TREATMENT
▫ Due to left internal mammary artery
(LIMA) graft SURGERY
▫ Retrograde flow from LIMA to left ▪ Balloon angioplasty, stent insertion,
subclavian artery coronary bypass
154 OSMOSIS.ORG
Chapter 23 Vascular Steal Syndromes
SUBCLAVIAN STEAL SYNDROME

osms.it/subclavian-steal-syndrome
RISK FACTORS
PATHOLOGY & CAUSES ▪ Smoking, diabetes, obesity, lack of exercise,
unhealthy diet, family history
▪ Stenosis/occlusion in subclavian artery →
▪ More common in individuals who are
reversal of blood flow in vertebral artery
biologically male
▪ Occlusion/narrowing in subclavian artery
→ blood drawn away from head, flows
retrogradely to supply oxygen to upper COMPLICATIONS
extremities (e.g. blood to brain stolen to ▪ Upper limb ischemia, neurological problems
supply left upper limb)
▫ More often on left than right due to
anatomical location of left subclavian
artery
▪ Narrowing of subclavian artery → short
low resistance pathway becomes high
resistance
▪ Blood flows up right brachiocephalic →
right subclavian → right vertebral artery
→ basilar artery, left vertebral joins →
blockage of left vertebral upstream →
blood from right vertebral artery enters left
vertebral → left subclavian → flows back to
left arm
▪ Rare condition
CAUSES
▪ Atherosclerosis (most common)
▫ Narrowing, hardening of arteries due to
plaque buildup
▪ Takayasu disease (least common)
▫ Chronic inflammation of aorta, large
vessels
▪ Giant cell arteritis
▪ Blalock Taussig shunt
▫ Surgical procedure to increase blood
flow to lungs; tube placed between
subclavian, pulmonary arteries
▪ Thoracic aortic dissection
▪ Thoracic outlet compression
▪ Interrupted aortic arch Figure 23.1 An illustration depicting the flow
▪ Congenital aortic coarctation of blood in subclavian steal syndrome. Blood
flows around the blockage in the proximal
subclavian artery, reversing flow in the
internal carotid and “stealing” the blood from
the brain.
OSMOSIS.ORG 155
SIGNS & SYMPTOMS
▪ Asymptomatic
▪ Numbness of arm, extends to fingertips
(most frequent)
▪ Vertebrobasilar artery insufficiency
▫ Presyncope/syncope, neurologic deficits
▪ Upper extremity claudication
▪ Tingling sensation/numbness in face
▪ Decreased blood pressure on affected side
▪ Transient hemiparesis (weakness) of
affected side
▪ Blood pressure (BP) in left arm < BP in right
arm
▪ Pulse in left arm < pulse in right arm
DIAGNOSIS
DIAGNOSTIC IMAGING
▪ CT angiography
▪ Doppler ultrasound scan
TREATMENT
SURGERY
▪ Balloon stenting, angioplasty
▪ Endarterectomy
156 OSMOSIS.ORG
NOTES
NOTES
VASCULAR TUMORS

▪ Abnormal growths of blood/lymph vessels DIAGNOSTIC IMAGING
▪ Can be benign/malignant, can occur ▪ Visual identification, imaging studies (MRI,
anywhere in body CT scan, ultrasound with Doppler, biopsy)
▪ Vascular tumors are rare, but most ▫ Determine location, tumor size, extent of
commonly found in neonates (e.g. spread
hemangiomas), HIV-positive individuals
(e.g. Kaposi’s sarcoma)
LAB RESULTS
▪ Biopsy for definitive diagnosis
COMPLICATIONS
▪ Metastasis
▪ Complications from chemo/radiation TREATMENT
therapy
▪ Depends on type, location, severity,
malignancy; see individual disorders
SIGNS & SYMPTOMS
ANGIOSARCOMA
osms.it/angiosarcoma
CAUSES
PATHOLOGY & CAUSES ▪ Most likely due to lymphedema (fluid
buildup causing sweeling), radiation
▪ Rare blood vessel malignancy involving exposure, carcinogens
blood vessel endothelial lining
▪ Aggressive, rapidly proliferating → poor
prognosis RISK FACTORS
▪ Can occur anywhere; usually occurs in sun- ▪ Biologically male (twice as likely), elderly,
exposed areas (head, neck, breast) sun-exposure, radiation therapy, chronic
post-mastectomy lymphedema, frequent
▫ Cutaneous angiosarcomas (occur
exposure to vinyl chloride monomer gas in
beneath skin’s surface) most common
PVC manufacturing/arsenic insecticides
▪ Can affect liver blood vessels
▫ High-grade: aggressive, fast-growing
OSMOSIS.ORG 157
▫ Low-grade: less aggressive, slow-
growing DIAGNOSIS
LAB RESULTS
COMPLICATIONS ▪ Biopsy, usually diagnosed late after the
▪ High chance of metastasis, poor prognosis. disease has spread
Better prognosis for individuals with
smaller tumors with clearly delineated
margins. Low grade breast angiosarcoma TREATMENT
has better prognosis than tumors with
poorly-defined borders MEDICATIONS
▪ Chemotherapy
SIGNS & SYMPTOMS
SURGERY
▪ Lesion resembling non-healing bruise/ ▪ Difficult to resect due to delay in diagnosis
wound
▪ Violet color OTHER INTERVENTIONS
▪ Soft, visible, tactile lump/swelling ▪ Radiation
▪ Can form irregular vascular channels that
disrupt tissue planes
▪ Fatigue
▪ Bone pain
▪ Anemia
Figure 24.1 A surgically excised

angiosarcoma.

an angiosarcoma composed of malignant
endothelial cells with vascular spaces
containing red blood cells.
158 OSMOSIS.ORG
Chapter 24 Vascular Tumors
GLOMUS TUMOR
osms.it/glomus-tumor

▪ Benign tumor arising from modified smooth SURGERY
muscle cells of skin’s thermoregulatory ▪ Resection
glomus bodies
▪ Derives from small vessels/arteriovenous
anastomoses in glomus bodies
▪ Malignancy, metastasis rare
▪ Etiology includes loss-of-function
mutation of protein glomulin in familial
glomangiomas
RISK FACTORS
▪ Adults: 20–40 years old
▪ Most lesions solitary, localized
▪ Autosomal dominant inheritance pattern
COMPLICATIONS
▪ Good prognosis, low recurrence rate after
resection
▪ Malignant glomus tumors rare, have good
prognosis when treated with wide excision Figure 24.3 Homogenous enhancement of
▪ Metastasis associated with poor prognosis a glomus tumor of the nail bed at the ulnar
aspect of the left index finger.
SIGNS & SYMPTOMS

▪ Painful, small, red-blue growths
▫ Pain associated with solitary lesions
▫ Younger individuals: multiple tumors,
usually asymptomatic
▪ Usually found on distal extremities
▪ Paroxysmal pain depending on
temperature, pressure changes
▫ Cold, pressure worsens pain
DIAGNOSIS Figure 24.4 Histological appearance of a

glomus tumor.
OTHER DIAGNOSTICS
▪ Visual inspection
▪ Occasional imaging
OSMOSIS.ORG 159
KAPOSI SARCOMA
osms.it/kaposi
STAGING
PATHOLOGY & CAUSES
AIDS-related Kaposi’s sarcoma
▪ Malignant vascular tumor/lesions of blood ▪ Takes three factors into account
vessel endothelial cells ▪ Extent/severity of tumor
▪ Due to human herpesvirus 8 ▫ T0: localized tumor
▪ Virus penetrates cells, causing ▫ T1: widespread, multiple lesions that
uncontrollable replication spread to other organs
▪ May involve visceral organs ▪ CD4 cell count (immune status)
▪ Progression, severity of tumor depends on ▫ I0: CD4 count above 150 cells/mm3
underlying factor
▫ I1: CD4 count less than 150 cells/mm3
▫ Genetic: usually seen in older Eastern
▪ Presence/absence of systemic illness
European males; tumor localized to skin
▫ S0: no systemic illness/opportunistic
▫ AIDs: tumor spreads (see staging
infections, and/or B symptoms. B
below)
symptoms: systemic fever symptoms,
▫ Organ transplant recipients: tumor
night sweats, weight loss, diarrhea
spreads
▫ S1: presence of systemic illness,
opportunistic infections, and/or B
TYPES symptoms
AIDS-related
▪ Most common malignancy in AIDS COMPLICATIONS
▪ Lymphedema
Immunocompromised & iatrogenic-related ▪ Bleeding
Classic/sporadic ▪ Infection
▪ Long term hyperpigmentation
Endemic (African) ▪ Prognosis depends on individual’s immune
▪ Burkitt’s lymphoma due to Epstein-Barr status, viral load (amount of HIV virus in
virus blood)
RISK FACTORS
▪ Immunocompromised individuals
SIGNS & SYMPTOMS
▫ AIDS ▪ Most common symptoms affect skin, also
▫ Kaposi’s sarcoma associated human affect mouth, GI tract, respiratory tract
herpesvirus-8 (HHV-8) ▫ Progresses from flat lesion →
▫ Organ transplant plaque → ulcerating nodule
▪ Biologically male ▫ Purple, red lesion similar to bruise that
▪ Eastern European does not blanch
▪ Higher risk: biologically-male individuals ▫ Lesion starts off flat, may become
engaging in same-sex sexual acts (“MSM“) raised, more painful
160 OSMOSIS.ORG
Chapter 24 Vascular Tumors
▫ Lesions in other tissues (e.g. mouth, MEDICATIONS

nose, throat, lymph nodes, lungs, ▪ HIV/AIDS management with antivirals
gastrointestinal tract); Commonly found ▫ Control HIV/AIDS → lesions shrink
in mucous membranes (esp. hard palate)
▪ Removal of drugs (e.g. corticosteroids)
▪ Pulmonary symptoms: pulmonary Kaposi’s allows immune system to recover
sarcoma
▫ Treatment more difficult in
▫ Coughing (possibly bloody cough) immunocompromised individuals
▫ Dyspnea ▪ Chemotherapy
DIAGNOSIS SURGERY
▪ Surgically remove affected skin
DIAGNOSTIC IMAGING
▪ Bronchoscopy/endoscopy OTHER INTERVENTIONS
▪ Cryotherapy → freeze affected skin
LAB RESULTS ▪ Radiation
▪ Biopsy
TREATMENT
▪ Depends on
▫ Severity of immunosuppression
▫ Number, location of tumors
▫ Symptoms
Figure 24.5 Kaposi sarcoma of the gingiva

in a HIV positive individual. The tumor has
replaced the gingiva of the upper right side of
the jaw. There is overlying oral candidiasis.
Figure 24.6 A Kaposi sarcoma composed

of spindle cells which form slits filled with
erythrocytes.
OSMOSIS.ORG 161
NOTES
NOTES
VASCULITIS

▪ Inflammation of blood vessels LAB RESULTS
▪ Vasculitides categorized by blood vessel ▪ C-reactive protein (CRP), erythrocyte
size: small, medium, large sedimentation rate (ESR), complete blood
count (CBC), various autoantibodies
CAUSES ▪ Biopsy vessel segment
Damaged endothelium
▪ Damaged endothelium → exposed TREATMENT
collagen, tissue → increased blood
coagulation → weakened, damaged blood MEDICATIONS
vessel walls → aneurysms → vessel wall
Reduce inflammatory response
heals, stiffens as fibrin deposits
▪ Corticosteroids/immunosuppressive drugs
Autoimmune disease
▪ Direct method: body mistakes endothelial
layer of blood vessel for foreign pathogen
→ attacks
▫ Molecular mimicry: immune system
white blood cells (WBCs) mistake
normal antigens of endothelial cells for
foreign invaders (e.g. bacteria)
▫ Medium, large-vessel vasculitides
▪ Indirect method: immune system attacks
healthy cells near vascular endothelium →
damages endothelial cells
▫ Small-vessel vasculitides (exception:
Henoch-Schönlein purpura)
SIGNS & SYMPTOMS

▪ Inflammatory response symptoms: fever,
weight loss, malaise, fatigue
▪ Ischemia
▫ Blood cells clump to exposed collagen
inside blood vessels → blood clots →
restricted blood flow
▫ Fibrin deposits in vessel wall → wall
thickens, bulges into vessel → stenosis
→ restricted blood flow
162 OSMOSIS.ORG
Chapter 25 Vasculitis
OSMOSIS.ORG 163
BEHCET'S DISEASE
osms.it/behcets-disease

▪ Autoimmune multisystem vasculitis MEDICATIONS
affecting any sized vessel, arterial/venous ▪ Skin creams, mouth rinses, eye drops
▪ Corticosteroids: (e.g. prednisone) control
RISK FACTORS inflammation
▪ Individuals who are 20–30 years old, of ▪ Medications: (e.g. azathioprine,
Middle Eastern/Asian descent, biologically cyclosporine, or cyclophosphamide)
male suppress immune system
▪ Medications: (e.g. interferon alfa-2b) alter
immune system response
COMPLICATIONS
▪ Blindness from untreated uveitis
(inflammation in eyes)
SIGNS & SYMPTOMS

▪ Recurrent, painful, sterile oral/genital ulcers
(pathergy)
▪ Skin papules indistinguishable from acne
▪ Uveitis, optic neuritis, conjunctivitis iritis
▪ Neurologic involvement
(meningoencephalitis, intracranial HTN,
stroke, headache)
▪ Arthritis (knees, ankles)
▪ Fever, weight loss
DIAGNOSIS
OTHER DIAGNOSTICS
Clinical presentation
▪ Recurrent oral ulcers (three in one year) + Figure 25.1 Mucosal ulcer in an individual
two of following with Behcet’s disease.
▪ Recurrent genital ulcers
▪ Eye lesions, uveitis
▪ Skin lesions
▪ Positive pathergy test
▪ ≥ 2mm papule 24–48 hours after oblique
insertion 5mm into skin with 20-gauge
needle, often performed on forearm
164 OSMOSIS.ORG
BUERGER'S DISEASE
osms.it/buergers
LAB RESULTS
PATHOLOGY & CAUSES
Biopsy
▪ Nonatherosclerotic, segmental, ▪ Definitive; rarely (healing a concern)
inflammatory disease affecting small-, ▪ Histopathologically, acute-phase lesions
medium-sized veins, arteries of extremities show highly cellular, inflammatory
→ inflammatory occlusive thrombus → thrombus with minimal inflammation of
distal extremity ischemia, digit ulcers/ blood vessel
gangrene → autoamputation
▪ AKA thromboangiitis obliterans
▪ Associated with use of tobacco products TREATMENT
RISK FACTORS ▪ Immediate smoking cessation

▪ Individuals < 45 years old, who are
biologically male, use tobacco
▪ Chronic anaerobic periodontal infection (⅔
of people with Buerger disease)
SIGNS & SYMPTOMS

▪ Ulceration of digits
▪ Ischemic claudication: cold, painful,
cyanotic distal extremities
▪ Subcutaneous nodules, superficial
thrombophlebitis
▪ Paresthesias of extremities
▪ Raynaud phenomenon
Figure 25.2 A volume rendered CT
DIAGNOSIS angiogram demonstrating obliteration
of the right femoral artery secondary to
thromboangiitis obliterans. There is also
DIAGNOSTIC IMAGING
stenosis of the femoral artery on the left.
Angiogram
▪ Lack of atherosclerosis
▪ Collateralization, segments of diseased
vessel interspersed: smoking →
atherosclerosis + Buerger disease
simultaneously
OSMOSIS.ORG 165
CHURG–STRAUSS SYNDROME
osms.it/churg-strauss-syndrome

▪ Small, medium vessel granulomatous DIAGNOSTIC IMAGING
vasculitis involving many organ systems
(cardiac, gastrointestinal, respiratory, Chest X-ray
skin, renal, neurologic) in individuals with ▪ Transient, patchy, symmetrical opacities,
allergy-related respiratory conditions (esp. often in hilar/peripheral distribution
asthma) ▪ Pulmonary hemorrhage
▪ AKA eosinophilic granulomatosis with ▪ Bilateral nodular disease without cavitation
polyangiitis (EGPA), allergic granulomatosis
▪ P-ANCA reacting with neutrophilic High-resolution CT scan
myeloperoxidase ▪ Peribronchial, septal thickening
▪ Etiology unknown ▪ Widely scattered indistinct opacities
Pulmonary function test

RISK FACTORS ▪ Obstructive pattern consistent with asthma
▪ Age 30–50; asthma/nasal issues
Bronchoalveolar lavage
▪ High % of eosinophils
SIGNS & SYMPTOMS
LAB RESULTS
▪ Allergies
▪ Eosinophilia > 1500/microL, > 10% on
▫ Asthma, chronic rhinosinusitis, usually differential leukocyte count
precedes vasculitic phase by 8–10 years
▪ P-ANCA/MPO-ANCA antibodies
▪ Neurological
▪ Acute phase reactants: ↑ ESR, CRP
▫ Peripheral neuropathy (usually
mononeuritis multiplex) Lung/skin biopsy
▫ Subarachnoid, cerebral hemorrhage, ▪ Definitive
cerebral infarction, cranial nerve palsies
▪ Skin
▫ Palpable purpura, subcutaneous TREATMENT
nodules
▪ Cardiac ▪ Prognosis poor (five year survival, 25%
without treatment; 50% with treatment)
▫ Damage → heart failure, arrhythmias
▫ Accounts ½ deaths
▪ Other organ systems (renal, MEDICATIONS
gastrointestinal) → symptoms similar to ▪ Corticosteroids, immunosuppressive drugs
medium-vessel vasculitides
166 OSMOSIS.ORG

vasculitis in Churg-Strauss syndrome. The
background is composed almost entirely of
eosinophils.
GIANT CELL ARTERITIS

osms.it/giant-cell-arteritis

▪ Chronic vasculitis of large-, medium-sized ▪ New-onset headache (most common):
vessels temporal branch of carotid artery
▪ AKA temporal arteritis ▪ Jaw claudication (pain when chewing)
▪ Cranial branches of arteries originating ▪ Transient unilateral vision loss (amaurosis
from aortic arch fugax): ophthalmic artery
▫ Temporal branch of carotid artery ▪ Carotid bruits, decreased pulses in arms,
▪ Aorta, carotids also affected aortic regurgitation
▪ Most common systemic vasculitis ▪ Tender, palpable nodules, absent temporal
pulse
▪ Increased risk of aortic dissection, aortic
CAUSES aneurysm
▪ Unknown: possibly genetic, environmental,
autoimmune-related
MNEMONIC: TEMPORAL
RISK FACTORS Characteristics of Temporal
▪ Almost always in individuals ≥ 50 (Giant cell) arteritis
▪ More common in individuals who are Temporal artery tenderness
biologically female ESR >100
▪ Strong association with polymyalgia Multinucleated giant cells
rheumatica (40–50% of GCA individuals) Pain
Onset >50 years old
COMPLICATIONS polymyalgia Rheumatica
▪ Irreversible blindness (if untreated) association
Amaurosis fugax
Lost vision
OSMOSIS.ORG 167
DIAGNOSIS
LAB RESULTS
▪ Extremely elevated ESR (> 100mm/hr), ↑
IL-6 associated with active disease
Temporal artery biopsy

▪ Tightly packed monocytes/macrophages,
as if one giant cell, in internal elastic lamina;
segmental pattern; 90% sensitivity
TREATMENT Figure 25.4 A histology photomicrograph

demonstrating giant cell arteritis. The
external elastic lamina to the right has been
▪ Corticosteroids
completely destroyed by granulomatous
inflammation.
GRANULOMATOSIS WITH
POLYANGIITIS
osms.it/granulomatosis-with-polyangiitis
MNEMONIC: 3Cs
PATHOLOGY & CAUSES “C” drawn from upper
respiratory tract to lungs,
▪ Small-vessel vasculitis involving kidneys (all involved)
nasopharynx, lungs, kidneys
C-anca
▪ AKA Wegener’s granulomatosis
Corticosteroids/
▪ Granulomatous disease of respiratory tract cyclophosphamide
→ systemic necrotizing vasculitis (treatment)
▪ B-cells release cytoplasmic antineutrophil
cytoplasmic antibodies (c-ANCA) →
binds to proteinase 3 (neutrophil granule)
in neutrophils → neutrophils release SIGNS & SYMPTOMS
free radicals → free radicals damage
neighboring endothelial cells → vasculitis ▪ Chronic pain: oral ulcers, bloody nasal
▪ Triad mucus, chronic sinusitis, saddle nose (nose
▫ Focal, necrotizing vasculitis caves in/curls)
▫ Necrotizing granulomas in upper airway, ▪ Hemoptysis, dyspnea, cough, pleuritic
lungs chest pain (inflammation of lung vessels)
▫ Necrotizing glomerulonephritis (renal ▪ Decreased urine production, hypertension,
vasculitis) hematuria, red cell casts, proteinuria
(glomerular inflammation)
RISK FACTORS
▪ Middle aged individuals who are
biologically male
168 OSMOSIS.ORG
DIAGNOSIS TREATMENT
DIAGNOSTIC IMAGING ▪ Relapse common if c-ANCA still present
Abnormal chest X-ray

▪ Nodules, fixed infiltrates, cavities, bronchial
MEDICATIONS
stenosis ▪ Corticosteroids, cyclophosphamide/
rituximab
LAB RESULTS
▪ c-ANCA in 90%, thrombocytopenia
▪ Abnormal urinary sediment; microscopic
hematuria (with/without red cell casts)
Open lung biopsy

▪ Confirm diagnosis; granulomatous
inflammation of artery/perivascular area
OTHER DIAGNOSTICS
Nasal/oral inflammation
▪ Oral ulcers; painful/painless
▪ Purulent bloody nasal discharge
▪ Chronic sinusitis, saddle nose/destructive
sinonasal disease
Figure 25.5 Illustration demonstrating the effects of granulomatosis with polyangiitis.
OSMOSIS.ORG 169
HENOCH–SCHÖNLEIN PURPURA
osms.it/henoch-schonlein-purpura

▪ Small vessel vasculitis secondary to IgA ▪ Self-resolving, may reoccur
immune complex deposition.
▪ Elevated IgA in blood targets self- MEDICATIONS
endothelial cells: molecular mimicry
▪ Steroids, only if severe
▪ Most common systemic vasculitis of
childhood
▪ Frequently follows upper respiratory
infection
▪ Associated with Berger disease (IgA
nephropathy)
▪ Unknown cause; immune-mediated
vasculitis triggered by infections/
immunizations
▪ Self-limited disease
▪ Tetrad
▫ Palpable purpura, without coagulopathy/
thrombocytopenia; mainly lower
extremities
▫ Arthritis/arthralgias
▫ Renal disease
▫ Abdominal pain
SIGNS & SYMPTOMS

▪ Palpable purpura of buttocks, legs (skin
discolouration, as if blood collected under
skin surface); abdominal pain; arthritis/ Figure 25.6 The clinical appearance of
arthralgias; hematuria, decreased kidney Henoch-Schönlein purpura.
function (associated with IgA nephropathy)
DIAGNOSIS
LAB RESULTS
Biopsy
▪ Definitive, not necessary
170 OSMOSIS.ORG
KAWASAKI DISEASE
osms.it/kawasaki-disease

▪ Coronary arteries: inflammation → DIAGNOSTIC IMAGING
aneurysms
Chest X-ray
▪ AKA mucocutaneous lymph node
syndrome ▪ Cardiomegaly
▪ Most common type of vasculitis in children Echocardiography
▪ Usually self-limited ▪ Coronary artery aneurysms, pericardial
effusions, decreased contractility
RISK FACTORS
▪ Infants, children < five years old, Asian LAB RESULTS
descent, biologically male ▪ ↑ CRP, ESR, platelet count (reactive
thrombocytosis)
COMPLICATIONS
▪ Coronary artery aneurysm OTHER DIAGNOSTICS
▪ Decreased myocardial contractility → heart ▪ Four of five CRASH symptoms, high fever
failure lasting five days
▪ Myocardial infarction (MI)
ECG
▪ Arrhythmias
▪ Arrhythmias, abnormal Q waves, prolonged
▪ Peripheral artery occlusion
PR, QT intervals
SIGNS & SYMPTOMS

MNEMONIC: CRASH &
BURN
Signs & Symptoms
Conjunctivitis: bilateral,
nonexudative
Polymorphous Rash:
desquamating
Cervical lymphAdenopathy
Strawberry tongue: cracked
red lips, oral mucositis
Hand-foot erythema/
desquamation: edema,
erythema
Fever: “burn”
Figure 25.7 A coronary angiogram
demonstrating a massive right coronary
artery aneurysm.
OSMOSIS.ORG 171
TREATMENT
MEDICATIONS
▪ Intravenous immunoglobulin (IVIG)
▪ Aspirin
MICROSCOPIC POLYANGIITIS
osms.it/microscopic-polyangiitis

▪ Necrotizing vasculitis: kidney, lung vessels LAB RESULTS
▪ No granulomas present ▪ p-ANCA/MPO-ANCA levels; elevated ESR,
▪ Associated with perinuclear anti-neutrophil CRP, anemia, increased creatinine
cytoplasmic antibodies (p-ANCA)/MPO- ▪ Protein, red blood cells (RBCs)
ANCA
▪ Pauci-immune glomerulonephritis (minimal
immunofluorescent staining for IgG) TREATMENT
▪ Older adults
▪ Relapse common

▪ Corticosteroids, cyclophosphamide
▪ Similar to granulomatosis with polyangiitis,
without nasopharyngeal involvement
▪ Fever, weight loss, fatigue, myalgia,
arthralgias
▪ Cough, dyspnea, hemoptysis, pleuritic
chest pain
▪ Decreased urine output, hematuria, red cell
casts, proteinuria
▪ Skin lesions (especially lower extremities):
purpura → focal necrosis → ulceration
172 OSMOSIS.ORG
POLYARTERITIS NODOSA
osms.it/polyarteritis-nodosa

▪ Immune system forms antibody antigen DIAGNOSTIC IMAGING
complex (sometimes associated with
hepatitis B) → deposits in vessel Mesenteric angiogram
wall → immune reaction → invasion ▪ “String of beads” pattern along artery,
of polymorphonuclear leukocytes → spasms
segmental, transmural inflammation of
muscular arteries → necrosis of three artery LAB RESULTS
layers (tunica intima, media, adventitia) →
▪ HBV, HCV serologies, Cr, muscle enzymes,
fibrosis as walls heal (fibrinoid necrosis)
urinalysis
→ fibrosed vessel wall weakens, prone
to aneurysms → fibrotic aneurysms (hard Biopsy
bulges) develop
▪ Different stages of inflammation in different
vessels OTHER DIAGNOSTICS
Physical exam
RISK FACTORS ▪ Vascular lesions, motor weakness (due to
▪ Individuals > 40 years old, biologically male ischemia)
▪ Active hepatitis B (HBV)/hepatitis C (HCV)
infection
▪ HIV
TREATMENT
▪ Prescription/illicit drug exposure, MEDICATIONS
amphetamines
▪ Corticosteroids
▪ Cyclophosphamide: supplement
SIGNS & SYMPTOMS corticosteroids in moderate to severe cases
▪ Systemic: fever, fatigue, weight loss,

arthralgia
▪ End organ ischemic damage
▪ Renal arteries: HTN
▪ Mesenteric artery: mesenteric ischemia,
severe abdominal pain, gastrointestinal
bleeding
▪ Mononeuropathy multiplex: motor, sensory
deficits occur in > one nerve throughout
body
▪ Skin arteries: skin lesions (e.g. ulcers,
erythematous nodules resembling
erythema nodosum, purpura, livedo
reticularis)
OSMOSIS.ORG 173
Figure 25.8 Illustration showing polyarteritis nodosa’s characteristic “string of beads” pattern
running along the artery.
TAKAYASU ARTERITIS
osms.it/takayasus-arteritis

▪ Segmental, patchy granulomatous ▪ Inflammation
vasculitis of aortic arch, major branches ▫ Aortic branches, upper extremities:
▪ Stenosis, thrombosis, aneurysm weak/absent pulse
▫ Aortic branch, head: neurological
CAUSES symptoms (e.g. headaches, syncope,
stroke)
▪ Unknown; possibly bacterial (e.g.
spirochetes, Mycobacterium tuberculosis, ▫ Coronary arteries: angina
streptococcal) ▫ Renal arteries: HTN
▪ Genetic ▪ Visual disturbances: ocular vessels/retinal
hemorrhage
▪ Constitutional symptoms: fever, night
RISK FACTORS sweats, arthralgias, malaise, fatigue
▪ Individuals of Asian descent, < 40 years
▪ Ischemia in areas of stenosis
old, biologically female
COMPLICATIONS DIAGNOSIS
▪ Limb ischemia; aortic aneurysm;
aortic regurgitation; stroke; secondary DIAGNOSTIC IMAGING
hypertension (HTN) due to renal artery
stenosis CT angiography (CTA), magnetic resonance
angiography (MRA)
▪ Luminal narrowing/occlusion of major aortic
branches
▪ Vessel wall thickening
▪ Aortic valve disease (e.g. regurgitation,
174 OSMOSIS.ORG
stenosis)
▪ Aneurysmal dilation/pseudoaneurysm
formation
Ultrasound
▪ Homogeneous and circumferential
thickening of arterial wall (contrast to
atherosclerotic plaque: non-homogeneous,
calcified, irregular walls)
▪ Vascular occlusion due to intimal
thickening/secondary thrombus formation
▪ Loss of pulsatility of vessel
LAB RESULTS
▪ ↑ ESR
TREATMENT
MEDICATIONS
▪ Corticosteroids
▪ Treat HTN
Figure 25.9 An angiogram demonstrating
SURGERY multiple stenosis of the aortic arch vessels, a
feature of Takayasu arteritis.
▪ Angioplasty (when no acute inflammation);
bypass grafting if severe
OSMOSIS.ORG 175
NOTES
NOTES
VENOUS DYSFUNCTION

▪ Localized hyperpigmentation/skin
PATHOLOGY & CAUSES discoloration
▪ Hard, cord-like veins/prominent dilated
▪ Venous system defects affecting blood flow
tortuous veins
from lower extremities
CAUSES DIAGNOSIS
▪ Blood clot partially/completely blocking
way/venous valves failing to pump blood DIAGNOSTIC IMAGING
against gravity Doppler ultrasound
Virchow’s triad ▪ Assess vein diameter, thrombi, valve status,
▪ Hypercoagulability, increased clot formation blood flow (anterograde vs. retrograde)
▫ Factor V Leiden thrombophilia Venography
▫ Protein C and protein C deficiencies ▪ X-ray, contrast medium injected into vein
▪ Venous stasis from prolonged ▪ Assess status of vein network, detect
immobilization (e.g. bed rest) thrombi
▪ Damage to endothelial lining
LAB RESULTS
RISK FACTORS ▪ D-Dimer: High sensitivity (~100%) and
▪ Prolonged immobility, hereditary clotting negative predictive value (~100%) for
dysfunctions, high estrogen levels, obesity detection of venous thromboembolism
▪ One venous dysfunction can lead to
another
TREATMENT
MNEMONIC: PHD MEDICATIONS
Virchow's Triad ▪ Acute manifestation: unfractionated
Prolonged immobilization heparin/low-molecular-weight heparins
(stasis) ▪ Long-term management: oral
Hypercoagulability anticoagulants (e.g. warfarin)
Damage to endothelium ▪ Prior DVT
▫ Long term anticoagulation therapy,
antiplatelet treatment, parenteral
anticoagulants
SIGNS & SYMPTOMS
▪ Localized pain, usually lower extremities
SURGERY
▪ Vein transplant/repair/removal
▪ Edema
▪ Pruritus
176 OSMOSIS.ORG
Chapter 26 Venous Dysfunction
OTHER INTERVENTIONS
▪ Preventative: calf exercises, compression
stockings/devices, raise affected areas to
decrease swelling
CHRONIC VENOUS INSUFFICIENCY

(CVI)
osms.it/chronic-venous-insufficiency
(hemosiderin deposits)
PATHOLOGY & CAUSES ▪ Pruritus, stasis dermatitis
▪ Painless, wet ulcers, particularly on medial
▪ Veins cannot push blood back to heart,
malleolus
resulting in blood pooling in leg
▪ Edema
▪ Atrophie blanche: hypopigmented atrophic
CAUSES areas with telangiectasia (clusters of red/
▪ Develops from varicosities, DVT, phlebitis purple capillaries), red dots
▫ Varicose veins affect superficial veins,
but blood sometimes rerouted to
collateral veins deep in leg, preventing DIAGNOSIS
blood stagnation
▪ When deep veins carry more blood than DIAGNOSTIC IMAGING
normal
Doppler ultrasound imaging
▫ Deep veins stretch over time, blood
pools ▪ Most common diagnostic
▫ Blood flow stagnation in lower ▪ Modified vein diameter (increased = acute
extremities causes inflammatory thrombus, decreased = chronic thrombus)
reaction in vessels, tissue, causing ▪ Absent color flow: vein completely
fibrosis, venous stasis ulcers occluded
▪ Increased flow in surrounding superficial
veins
RISK FACTORS
▪ Biological females, inactive standing/sitting Venography
for long periods, aging, family history, ▪ Most effective, but invasive and cost-
ligamentous laxity, obesity, smoking, low- prohibitive
extremity trauma, prior venous thrombosis,
arteriovenous shunt, pregnancy
TREATMENT
SIGNS & SYMPTOMS SURGERY
▪ Vein transplant/repair/removal
▪ Calf/ankle pain (most common symptom)
▪ Worse with prolonged standing/sitting,
improves with leg elevation, movement OTHER INTERVENTIONS
▪ Brown hyperpigmentation of skin ▪ Preventative: calf exercises, compression
decrease swelling
OSMOSIS.ORG 177
Figure 26.1 The clinical appearance of mild
CVI. Hemosiderin deposition is clearly visible.
Figure 26.2 Illustration of varicose veins that have developed into a case of CVI.
178 OSMOSIS.ORG
DEEP VEIN THROMBOSIS (DVT)

osms.it/deep-vein-thrombosis

▪ Blood clotting in deep leg veins (iliofemoral, ▪ 50% asymptomatic due to venous collateral
popliteal, femoral veins) channels
▪ Arterial clots usually due to artery wall ▪ Localized inflammation around clot
damage; venous clots don’t require vein ▪ High venous pressure engorges visible
damage superficial veins
▪ Valves inside veins can lower blood ▪ If PE occurs: sudden dyspnea, chest pain
oxygen levels → venous stasis-associated ▫ Fatal if enough lung tissue affected
hypoxemia can activate reactive oxygen
species, other hypoxia-inducible factors →
tissue factor released into blood
DIAGNOSIS
▫ Tissue factor activation → prothrombin
turns into thrombin → fibrin fibers form DIAGNOSTIC IMAGING
net → traps red blood cells, white blood
cells, platelets → venous thrombus Doppler ultrasound imaging
▪ Most common diagnostic
CAUSES ▪ Modified vein diameter
▪ Virchow’s triad ▫ Increased: acute thrombus
▪ Antiphospholipid syndrome ▫ Decreased: chronic thrombus
▪ Prolonged immobilization (bed rest, ▪ Absent colour flow: vein completely
orthopedic casts, long-distance air travel) occluded
▪ Genetic ▪ Increased flow in surrounding superficial
▫ Antithrombin, protein C, S deficiencies veins
Venography
RISK FACTORS ▪ Most effective, but invasive/cost-prohibitive
▪ Pregnancy, oral contraceptives, old age,
major surgery (e.g.orthopedic surgery), LAB RESULTS
malignancy, obesity, trauma, heart failure
▪ D-dimers → rule out DVT
▫ Increased level: plasmin dissolves
COMPLICATIONS thrombus
▪ Pulmonary embolism (PE) most common
▫ Can cause pulmonary infarction, death OTHER DIAGNOSTICS
▪ Post-thrombotic syndrome
▫ Develops in 50% of individuals with Wells’ score
DVT ▪ Higher score indicates increased chance of
▪ Extreme cases: phlegmasia cerulea dolens DVT (Scale of -2 to 9 points)
(blue, painful, swollen leg, possible venous ▫ High score = high chance: > 2 points
gangrene) ▫ Moderate score = moderate chance:
1–2 points
▫ Low score = low chance: < 1 point
OSMOSIS.ORG 179
TREATMENT
MEDICATIONS
▪ Acute manifestation: unfractionated
heparin/low-molecular-weight heparins
▪ Long-term management: oral
anticoagulants (e.g. warfarin)
▪ Prior DVT: long term anticoagulation
therapy, antiplatelet treatment, parenteral
anticoagulants
OTHER INTERVENTIONS
▪ Preventative: calf exercises, compression
decrease swelling
Figure 26.4 Clinical appearance of a deep

Figure 26.3 An IVC filter, used to prevent vein thrombosis of the right leg. The lower
embolization of the deep vein thrombus into leg is erythematous and swollen.
the pulmonary vasculature.
180 OSMOSIS.ORG
THROMBOPHLEBITIS
osms.it/thrombophlebitis
COMPLICATIONS
PATHOLOGY & CAUSES ▪ DVT, superficial thrombophlebitis,
pulmonary embolism
▪ Vein inflammation caused by clot in deep
leg veins
▪ Increased coagulability (Virchow’s triad) SIGNS & SYMPTOMS
▪ Potential locations
▫ Upper limbs (usually at site of IV ▪ Pain, inflammation/swelling, hard, cord-like
cannula) veins
▫ Lower limbs (coupled with varicose ▪ Sometimes asymptomatic, can be revealed
veins) by applying pressure
▫ Periprostatic venous plexus in biological ▫ Hoffman’s sign (forced dorsiflexion on
males foot creates soreness behind knee); not
▫ Pelvic venous plexus in biological 100% accurate
females
▫ Large veins of cranium, dural sinuses
▫ Portal vein DIAGNOSIS
DIAGNOSITC IMAGING
TYPES
Venous duplex ultrasound
Migrating thrombophlebitis
▪ Thrombosed veins thickened, poorly
▪ Occurs in several different locations, usually compressible
in pancreatic carcinomas due to pro-
▪ Completely occluded vein = hypoechoic
clotting factors secreted by tumoral cells
(low level echoes)
Superficial thrombophlebitis ▪ No internal flow present distal to clot
▪ Thrombus develops in vein near skin’s
Imaging studies
surface
▪ Thrombus detection (e.g. CT venography
▫ Mondor’s syndrome: thrombophlebitis
(CTV) with contrast, magnetic resonance
of subcutaneous veins of breast/arm /
(MR) venography)
penis; presents as lump
▪ Blood coagulation tests (e.g. elevated
Suppurative (septic) thrombophlebitis D-dimers)
▪ Infection from IV cannula; possible
purulence LAB RESULTS
Blood coagulation tests
CAUSES
▪ Elevated D-dimers
▪ Most commonly: needle/catheter
▪ Prolonged immobilization: bed rest,
orthopedic casts, long-distance air travel OTHER DIAGNOSTICS
▪ High estrogen: pregnancy, estrogen ▪ Inspection of affected area
replacement therapy, oral contraceptives ▫ Pulse (weak/absent)
▪ Hereditary clotting disorders: protein D/C ▫ Blood pressure (high)
deficiencies/factor V Leiden mutations ▫ Temperature (high)
▪ Vasculitis, Behcet’s disease
OSMOSIS.ORG 181
OTHER INTERVENTIONS
TREATMENT ▪ Preventative: calf exercises, compression
MEDICATIONS decrease swelling
▪ Acute manifestation: unfractionated
heparin/low-molecular-weight heparins
▪ Long-term management: oral
anticoagulants
Figure 26.5 Illustration showing blood clots discovered via imaging studies.
Figure 26.6 Illustration showing a surgically-implanted filter in the inferior vena cava preventing
a pulmonary embolism.
182 OSMOSIS.ORG
VARICOSE VEINS
osms.it/varicose-veins

▪ Enlarged, twisted superficial veins (most ▪ Twisted superficial veins
commonly in leg) ▪ Edema, pain (usually in evening)
▪ Downward gravitational pull causes walls ▪ Pruritus in affected area/stasis dermatitis
of veins to stretch over time, blood leaks because of undrained waste in leg
backwards → extra blood volume twists ▪ Prolonged bleeding, slowed healing in
veins → veins become varicose injuries to adjacent areas
▪ Blood sometimes rerouted to collateral ▪ Restless legs syndrome
veins deep in leg
TYPES DIAGNOSIS
Varicocele DIAGNOSTIC IMAGING
▪ Abnormal enlargement of pampiniform
venous plexus in scrotum Doppler ultrasound
▪ Mechanism same as varicose veins ▪ Used to discover subcutaneous varicosities,
assess saphenofemoral junction
▪ Most common in left testicle
▪ If blood reflux spotted during Valsalva
▫ Left testicular vein brings blood to
manoeuvre → valve incompetence
left renal vein at 90º angle → difficult
→ blood backs up → vein becomes ▪ Reflux > 1s → surgical intervention
varicose → loops back and forth on itself
▫ “Bag of worms” appearance OTHER DIAGNOSTICS
Trendelenburg test
CAUSES ▪ Person laid back on flat surface, leg raised
▪ Obesity, pregnancy, standing for long above heart, blood will flow towards heart
periods of time, menopause → compress upper thigh with tourniquet
▫ Pelvic vein reflux (PVR): ovarian vein (not too tightly) → lower leg onto flat
reflux, internal iliac vein reflux surface → person stands, refilling times
▪ Hyperhomocysteinemia destroying assessed
structural proteins in vessels ▫ Normal: superficial saphenous vein fills
▪ Chronic alcohol use < 30–35s
▫ Faster filling → valvular incompetence
COMPLICATIONS below compressed area → deep/
communicating veins
▪ Chronic venous insufficiency
▫ Slower filling → tourniquet released → if
▪ Venous ulcers
filling sudden → incompetent superficial
▫ Can develop into carcinomas, sarcomas veins
over time (rare)
▪ Superficial thrombophlebitis
OSMOSIS.ORG 183
TREATMENT
SURGERY
▪ Radiofrequency/laser ablation
▪ Sclerotherapy
▪ Ambulatory phlebectomy: removal of
surface vein through slits in skin
OTHER INTERVENTIONS
▪ Preventative: compression stockings/
devices, avoid prolonged standing
Figure 26.7 An X-ray image demonstrating

varicose veins of the left leg.
Figure 26.8 Illustration of a varicocele in the left testicle.
184 OSMOSIS.ORG
NOTES
NOTES
VENTRICULAR TACHYCARDIA

COMPLICATIONS
PATHOLOGY & CAUSES ▪ Sustained VT may result in sudden cardiac
death due to insufficient blood perfusion/
▪ Depolarization wavefronts originate in rapid ventricular fibrillation
ventricles → ventricles pump > 100 beats
per minute ↓ stroke volume
▪ Premature ventricular contractions (PVCs): SIGNS & SYMPTOMS
single instance of ventricle contracting
prematurely ▪ Chest pain, syncope, dizziness, shortness
▫ ≥ three PVCs consecutively defined as of breath, palpitations
ventricular tachycardia (VT)
TYPES DIAGNOSIS
Monomorphic VT LAB RESULTS
▪ Ventricular contractions have typical, ▪ Serum electrolytes
uniform shape ▪ Toxicology studies (therapeutic/recreational
▪ Typical for reentrant circuits drug use)
▫ Depolarizations begin from same spot, ▫ E.g. digoxin, tricyclic antidepressants,
for focal VT because one area of cells in methamphetamine, cocaine
ventricle is responsible
▫ Often caused by reentry around scar OTHER DIAGNOSTICS
in ventricular wall; e.g. from previous
myocardial infarction (MI) ECG
▪ Determines cardiac rhythm
Polymorphic VT
▪ > One QRS complex morphology type
▫ Includes Torsades de pointes TREATMENT
▪ Shape of contractions from each beat
changes as signal begins in different areas MEDICATIONS
of ventricle ▪ Pharmacotherapy
▪ May occur when pacemaker cells stressed, ▫ Depending on cause
increasing automaticity rates, including
from severe hypoxia
SURGERY
▪ Implanted devices
RISK FACTORS
▪ Ventricular muscle ischemia, structural
heart disease, coronary artery disease OTHER INTERVENTIONS
(CAD), electrolyte abnormalities ▪ Cardioversion, pacing
▪ Correct underlying cause
OSMOSIS.ORG 185
Figure 27.1 Illustration depicting ECG of monomorphic ventricular tachycardia.
Figure 27.2 Illustration depicting focal ventrical tachycardia.
186 OSMOSIS.ORG
Chapter 27 Ventricular Tachycardia
LONG QT SYNDROME (LQTS)

osms.it/long-qt-syndrome
Acquired
PATHOLOGY & CAUSES ▪ Usually caused by certain drugs (e.g. anti-
infectives, psychotropics, antiarrhythmics,
▪ Cardiac rhythm disorder characterized by antineoplastics, bronchodilators, gastric
prolonged ventricular repolarization motility agents)
▪ Characterized by abnormally long QT ▫ Common mechanism involves blockage
interval of rapidly activating potassium channels
▫ QT interval: total time from ventricular (IKr) current in potassium channel
depolarization (QRS complex) to encoded by KCNH2 gene
complete repolarization (T wave);
measured from beginning of QRS to end
of T wave RISK FACTORS
▫ QTc (corrected) accounts for changes ▪ Electrolyte imbalances (e.g. hypokalemia,
in heart rate: QTc = QT interval ÷ √RR hypomagnesemia, hypocalcemia)
interval (in sec); AKA Bazett formula ▪ Underlying heart disease (e.g. HF,
▫ Adult normal = 420 ± 20 msec hypertrophic left ventricle, history of
myocardial infarction)
▪ Results in ↑ risk of polymorphic ventricular
arrhythmias (TdP), which can deteriorate ▪ Bradyarrhythmias
into ventricular fibrillation ▪ Biological females > biological males
▪ ↑ age
TYPES ▪ Inherited genetic mutation
▪ Postpartum period
Inherited ▫ Related to physiologic stress, altered
▪ Caused by mutations in genes associated sleep patterns
with cardiac potassium, sodium channels ▪ Anorexia nervosa
▪ Triggered by exertion, emotional events,
stress, postpartum events, noise
COMPLICATIONS
▪ ≥ 13 types identified; associated with
mutations in genes encoding myocyte ion ▪ Malignant arrhythmias (TdP, VF), syncope,
channels seizures, sudden death
▪ KCNQ1, KCNH2, KCNE1, KCNE2 affect
potassium channels → ↓ outward
potassium current
SIGNS & SYMPTOMS
▪ SCN5A affects sodium channels → ↑ ▪ Palpitations, lightheadedness, hypotension
inward sodium current
▫ Two distinct LQT phenotypes due to
mutant alleles in same locus: DIAGNOSIS
▫ Romano–Ward syndrome: autosomal
dominant; LQTS without hearing loss LAB RESULTS
▫ Jervell and Lange–Nielsen syndrome: ▪ Serum electrolytes
autosomal recessive; LQTS with ▫ Hypokalemia, hypomagnesemia,
congenital sensorineural hearing loss hypocalcemia may be present
OSMOSIS.ORG 187
12-lead ECG Congenital LQTS
▪ Prolonged QTc (> 470msec in males, ▪ Left cervicothoracic sympathectomy (LCTS),
> 480msec in females); presence of left cardiac sympathetic denervation;
tachyarrhythmias (TdP); altered T-wave implantable cardioverter-defibrillator (ICD);
morphology pacemaker
Bicycle/treadmill stress test Acquired LQTS

▪ Presence of exercise-associated ▪ Pacemaker → if bradycardia triggers
arrhythmias arrhythmia
Catecholamine drug testing

▪ Differentiates etiology OTHER INTERVENTIONS
▫ Provocative testing with catecholamine; Acquired LQTS
e.g. epinephrine ▪ Address underlying cause; e.g. correct
▫ Measure effect on QT interval electrolyte abnormalities, discontinue
offending drug; temporary transvenous
Clinical/family history, physical examination
overdrive pacing, electrical cardioversion/
▪ With compatible findings defibrillation
Genetic testing Lifestyle modifications
Schwartz score ▪ Avoidance of triggering drugs, avoidance
adrenergic stimuli; e.g. strenuous exercise,
▪ Diagnosis of congenital LQTS by scoring
emotional stress
QTc, clinical factors, individual history
▪ Scoring: probability of congenital LQTS
▫ ≤ 1: low
▫ 1.5–3: intermediate
▫ ≥ 3.5: high
TREATMENT
MEDICATIONS
Congenital LQTS
▪ Beta-blockers: blunt adrenergic response
▪ Mexiletine: for sodium-channel mutations
▪ Flecainide: if SCN5A mutation
Acquired LQTS
▪ Magnesium sulfate: treatment, prevention
of recurrence of long QT-related ventricular
ectopic beats
▪ Isoproterenol: increase sinus rate, decrease
QT interval
▪ Lidocaine/phenytoin: shorten duration of
the action potential
188 OSMOSIS.ORG
Figure 27.3 ECG trace demonstrating long-QT syndrome.
OSMOSIS.ORG 189
Figure 27.4 ECG trace demonstrating long-QT syndrome.
TORSADES DES POINTES (TdP)

osms.it/torsades-de-pointes
MNEMONIC: TO4SADE
PATHOLOGY & CAUSES Drugs that may induce QT
prolongation
▪ Literally means “twisting of the points”
Thiazides
▪ The peaks of QRS complex “twist” around
O4 - Oanzapine, Opioids,
isoelectric line on electrocardiogram
Quinidine, Quinolones
▪ Lengthening QT interval → early
Sotalol/SSRIs
afterdepolarizations (EADs) → premature
ventricular depolarizations → polymorphic Antihistamines/antipsychotics
VT (TdP) AntiDepressants like TCAs
▫ May resolve spontaneously Erythromycin (Macrolide
▫ Transmural reentry/abnormal antibiotics
automaticity may perpetuate TdP
▫ May degenerate into ventricular
fibrillation SIGNS & SYMPTOMS
RISK FACTORS ▪ Palpitations, lightheadedness, syncope
▪ LQTS, drugs associated with LQTS
▪ Bradycardia
DIAGNOSIS
▪ Electrolyte imbalance
▪ Biologically female LAB RESULTS
▪ Anorexia nervosa ▪ Serum electrolytes
▫ Hypokalemia, hypomagnesemia,
COMPLICATIONS hypocalcemia may be present
▪ Ventricular fibrillation, seizures, sudden
cardiac death
190 OSMOSIS.ORG

▪ 12-lead ECG ▪ Left cardio-thoracic sympathectomy
▫ Ventricular rate: 150–300 beats per
minute OTHER INTERVENTIONS
▫ RR interval: irregular ▪ Treat underlying cause; e.g. correct
▫ P wave, PR interval: absent electrolyte abnormalities, discontinue
▫ QRS duration: > 0.12 seconds; changes offending drug
amplitude, shape, direction ▪ Temporary pacing, permanent dual
chamber pacemaker, implantable
cardioverter-defibrillator (ICD)
TREATMENT
MEDICATIONS
▪ For acquired LQTS/other causes of TdP
▫ Magnesium sulfate, isoproterenol,
lidocaine, phenytoin
▪ For congenital LQTS
▫ Beta-blockers, mexiletine
Figure 27.5 ECG demonstrating torsades de pointes.
OSMOSIS.ORG 191
VENTRICULAR TACHYCARDIA
osms.it/ventricular-tachycardia
RISK FACTORS
PATHOLOGY & CAUSES ▪ ↑ age
▪ Cardiac disease
▪ Ventricular arrhythmia originating in
ectopic ventricular pacemaker, resulting in ▫ Post-MI, cardiomyopathy, valve disease,
≥ three premature ventricular complexes HF
(PVCs) occurring at ≥ 100 beats/min ▪ Electrolyte imbalance
▪ Dysrhythmia may be sustained (> 30 ▪ Cardiac ion channelopathies resulting in
seconds)/nonsustained (< 30 seconds)/ long QT syndromes
paroxysmal ▪ Infiltrative disease; e.g. amyloidosis
▪ Abnormally fast ventricular contractions ▪ Pericardial inflammation
→ ↓ ability for ventricles to fill → ↓ ▪ Blunt chest trauma
cardiac output → ↓ perfusion → impaired ▪ Drugs; e.g. cocaine
hemodynamics
COMPLICATIONS
TYPES
▪ Cardiac ischemia, infarction
Non-reentrant/focal ventricular tachycardia ▪ May degenerate into ventricular fibrillation
▪ Triggered by abnormal automaticity of ▪ Sudden cardiac death
specific area of ventricle
▫ Ventricular pacemaker cells fire at high
rate, preventing pacemaker cells in SA SIGNS & SYMPTOMS
node from firing → heart rate driven by
ventricular pacemakers ▪ Chest pain
▫ May be caused by certain medications, ▪ Shortness of breath
illicit drugs (e.g. methamphetamine, ▪ Dizziness
cocaine), electrolyte imbalances, ▪ Syncope
myocardial ischemia in ventricles ▪ Pallor
Reentrant ventricular tachycardia ▪ Blood pressure: normal/↓
▪ More common than focal VT
▪ Reentry: perpetual electrical signal that
occurs due to changes in refractory period
DIAGNOSIS
length, rate of signal conduction
LAB RESULTS
▫ Cardiomyocytes can be altered when
▪ Serum electrolytes
stressed/irritated by external stimuli;
e.g. medications/illicit drugs: change ▫ Hypokalemia, hypomagnesemia,
conduction speed, refractory period hypocalcemia may be present
▫ Dead cells in myocardial tissue create
scar tissue → conduction signals go OTHER DIAGNOSTICS
around scar → perpetual signal, AKA
reentry ECG
▪ Rate: >100 beats per minute, irregular
▪ P waves: may be absent
▫ If present, atrioventricular dissociation
common (hallmark of VT)
192 OSMOSIS.ORG
▫ May be positive/upright or negative/

inverted in Lead II
▪ PR interval: none
▪ QRS complex: wide ( > 0.12 seconds); ≥
3 consecutive; distorted shape: may be
monomorphic/polymorphic
▪ T-waves: large; polarity may be opposite
of major QRS deflection; may be difficult to
distinguish
TREATMENT
MEDICATIONS
▫ Beta blockers, amiodarone,
nondihydropyridine calcium channel
blockers
OTHER INTERVENTIONS
▪ Acute treatment
▫ Cardioversion
▪ Drug cardioversion
▫ Procainamide, lidocaine, amiodarone
frequently used
▪ Electrical cardioversion
▫ Primary treatment for VT associated
with hemodynamic instability/when
drug cardioversion not immediately
available
▪ Radiofrequency catheter ablation
▪ ICD
OSMOSIS.ORG 193
NOTES
NOTES
BILIARY TRACT DISEASES

Magnetic resonance
PATHOLOGY & CAUSES cholangiopancreatography (MRCP)
▪ MRI for detailed images of hepatobiliary,
▪ Diverse spectrum of diseases affecting pancreatic systems
biliary system (gallbladder, bile ducts, liver)
▪ Bile stored in gallbladder → stasis/chemical Endoscopic retrograde cholangiopancrea-
constituents change → precipitate to tography (ERCP)
solid stone → travel down biliary tract → ▪ Down esophagus, stomach, duodenum,
obstruction → decreased bile drainage → ducts → contrast medium injected into
symptoms ducts → X-ray shows narrow areas/
blockages
▫ Complications: pancreatitis (most
SIGNS & SYMPTOMS common); intraluminal/intraductal
bleeding, hematomas; perforation;
▪ Symptoms vary, based on location infection (cholangitis, cholecystitis);
▫ Pain, jaundice, infection, inflammatory cardiopulmonary complications (cardiac
response, sepsis arrhythmia, hypoxemia, aspiration)
▪ Right upper quadrant (RUQ) epigastric pain
▪ Jaundice LAB RESULTS
▪ Nausea, vomiting ▪ See table
▪ Fever, chills → sepsis
TREATMENT
DIAGNOSIS
MEDICATIONS
DIAGNOSTIC IMAGING ▪ Antibiotics
CT scan/ultrasound
▪ Locations of stones, gallbladder wall SURGERY
thickening/inflammation ▪ Cholecystectomy
X-ray
OTHER INTERVENTIONS
▪ Pigmented gallbladder stones (radiopaque)
▪ Sepsis management, biliary drainage,
ERCP
194 OSMOSIS.ORG
Chapter 28 Biliary Tract Diseases
ASCENDING CHOLANGITIS
osms.it/ascending-cholangitis
▪ Common bacteria: E. coli, Klebsiella,
PATHOLOGY & CAUSES Enterobacter, Enterococcus
▪ Medical emergency
▪ Acute infection of bile duct caused
by intestinal bacteria ascending from
duodenum RISK FACTORS
▪ Bacterial infection of bile duct ▪ Gallstones (most common)
superimposed on obstruction of biliary tree; ▪ Stenosis of bile duct due to neoplasm/injury
due to choledocholithiasis from laparoscopic procedure
▪ Gallstones form in gallbladder → slip out
→ travel through cystic bile duct, lodge
in common bile duct → obstruction of
normal bile flow → bacteria ascend from
duodenum to bile duct → infect stagnant
bile, surrounding tissue
OSMOSIS.ORG 195
COMPLICATIONS LAB RESULTS
▪ Sepsis, septic shock ▪ Assess infection, jaundice
▫ High pressure on bile duct → ▫ Increased WBC
obstruction → cells lining ducts widen ▫ Increased serum C-reactive protein
→ bacteria, bile enter bloodstream (CRP)
▪ Multiorgan failure ▫ Elevated LFTs: ALP, GGT, ALT, AST

▪ Charcot’s triad MEDICATIONS
▫ RUQ pain, jaundice, fever/chills ▪ Antibiotics + IV fluids
▪ Reynold’s pentad
▫ Charcot’s triad + hypotension/shock, SURGERY
altered consciousness
▪ Cholecystectomy
▫ Associated with significant morbidity,
▫ Avoid future complications
mortality
OTHER INTERVENTIONS
DIAGNOSIS ▪ ERCP
▫ Removes gallstones
DIAGNOSTIC IMAGING ▪ Shockwave lithotripsy
Ultrasound, ERCP ▫ High frequency sound waves break
▪ Biliary dilation down stone
▪ Bile duct wall thickening ▪ Stent
▪ Evidence of etiology (stricture/stone/stent) ▫ Widen bile ducts in areas of stricture
Figure 28.1 The pathophysiology of ascending cholangitis.
196 OSMOSIS.ORG
BILIARY COLIC
osms.it/biliary-colic

▪ AKA “gallbladder attack” ▪ Pain
▪ Gallstones lodged in bile ducts → ▫ Severe right upper quandrant pain;
temporary severe abdominal pain radiates to right shoulder/shoulder
▪ After meal, gallbladder contracts → blades
gallstone ejected into cystic duct, lodged ▫ Intensity increases for 15 minutes,
→ gallbladder contracts against lodged plateaus for few hours (< six), subsides
stone → severe abdominal pain ▫ Starts hours after meal/at night/laying
▪ Pain subsides when gallstone dislodged flat
▪ Nausea, vomiting, anorexia
CAUSES
▪ Gallstones
DIAGNOSIS
▪ Narrow bile duct
▪ Pancreatitis ▪ Recurrent symptoms
▪ Duodenitis
▪ Esophageal spasms DIAGNOSTIC IMAGING
RISK FACTORS Ultrasound

▪ More common in individuals who are ▪ Confirmation of obstruction
biologically female X-ray, CT scan, MRI
▪ Obesity
▪ Pregnancy
▪ Age ≥ 40 TREATMENT
SURGERY
COMPLICATIONS
▪ Cholecystectomy
▪ Acute cholecystitis
▫ Gallbladder removal
▫ Inflammation of gallbladder wall
▫ Definitive
▫ Gallstone doesn’t dislodge from cystic
duct
OTHER INTERVENTIONS
▪ Pain, symptom management
OSMOSIS.ORG 197
CHOLECYSTITIS (ACUTE)
osms.it/acute-cholecystitis
Acalculous cholecystitis
PATHOLOGY & CAUSES ▪ Acute inflammation of gallbladder without
gallstones/cystic duct obstruction; high
▪ Stone lodged in cystic duct/common bile morbidity, mortality rate
duct → acute inflammation → pain
▪ 5–10% of acute cholecystitis cases
▫ 90% of acute cholecystitis resolves
▪ Rare, difficult to diagnose
within month as stone dislodges
▪ Multifactorial etiology
▪ Fatty meal → small intestine
cholecystokinin (CCK) signals gallbladder ▪ Often occurs in critically ill individuals/
to secrete bile → gallbladder contracts following major surgery
→ stone lodged in cystic duct → blocks ▪ Pathogenesis
bile flow → irritates mucosa → mucosa ▫ Gallbladder ischemia, reperfusion injury
secretes mucus, inflammatory enzymes → ▫ Bacterial invasion of ischemic tissue
inflammation, distention, pressure
▪ Cholesterol stones
COMPLICATIONS
▫ More potent ability to stimulate
▪ Biliary peritonitis (from rupture)
inflammation compared to pigment
gallstones ▪ Gallbladder ischemia → rupture → sepsis
▪ Possible progressions ▪ Acalculous cholecystitis
▫ Stone ejected out of cystic duct →
cholecystitis subsides, symptoms
subside
▫ Stone remains in place → pressure
builds → pushes down on blood vessels
supplying gallbladder → ischemia →
gangrenous cell death → gallbladder
walls weaken → perforation/rupture →
bacteria seeds to bloodstream → sepsis
→ medical emergency
▫ Stone lodged in common bile duct →
blocks flow of bile out of liver
▪ Bacterial growth (cholangitis)
▫ Cholelithiasis → stone descends to
cystic duct → cholecystitis → stone
descends from cystic duct, lodges in
common bile duct → choledolithiasis →
secondary infection due to obstruction
→ cholangitis Figure 28.2 A CT scan in the coronal plane
▫ Most commonly E. coli, Enterococci, demonstrating a thickened, oedematous
Bacterioides fragilis, Clostridium gallbladder, indicative of acute cholecystitis.
198 OSMOSIS.ORG
Diffusion-weighted MRI
SIGNS & SYMPTOMS ▪ Differentiate between acute, chronic
cholecystitis
▪ Midepigastric pain → dull right upper
quadrant pain radiates to right scapula/ Ultrasound
shoulders (esp. after a meal in chronic ▪ Gallstones/sludge
cholecystitis)
▫ Gallbladder wall thickening, distention
▪ Hypoactive bowel sounds; nausea,
▫ Air in gallbladder wall (gangrenous
vomiting, anorexia; jaundice; low grade
cholecystitis)
fever
▫ Pericholecystic fluid from perforation/
▪ Blumberg’s sign/rebound tenderness
exudate
▫ RUQ pain when pressure rapidly
released from abdomen; peritonitis
(secondary to gallbladder perforation/ LAB RESULTS
rupture) ▪ Elevated ALP
▪ Positive Murphy’s sign ▫ Concentrated in liver, bile ducts
▫ Sudden cessation of inhalation due to ▫ Bile backs up, pressure in ducts increase
pain when inflamed gallbladder reaches → cells damaged, die → ALP released
examiner’s fingers ▪ Elevated leukocyte count
▫ Examiner asks individual to exhale →
places hand below right costal margin
in midclavicular line → individual TREATMENT
instructed to breathe in → cessation due
to pain MEDICATIONS
▫ Differentiates cholecystitis from other ▪ Antimicrobials
causes of right upper quadrant pain
SURGERY
▪ Cholecystectomy
DIAGNOSIS
DIAGNOSTIC IMAGING
Cholescintigraphy/hepatic iminodiacetic
acid (HIDA) scan
▪ Radioactive tracer injected into individual
→ marked HIDA taken up by hepatocytes,
excreted in bile → drains down hepatic
ducts
▪ Location of blockage
OSMOSIS.ORG 199
CHOLECYSTITIS (CHRONIC)
osms.it/chronic-cholecystitis
COMPLICATIONS
PATHOLOGY & CAUSES ▪ Biliary peritonitis (from rupture)
▪ Gallbladder ischemia → rupture → sepsis
▪ Obstruction of cystic duct (not infection) →
inflammation of gallbladder wall ▪ Porcelain gallbladder (chronic cholecystitis)
▪ Constant state of inflammation due to ▫ Chronic state of inflammation →
gallstones repeatedly blocking ducts epithelial fibrosis, calcification
▫ Changes gallbladder mucosa → deep ▫ Bluish discoloration of gallbladder;
grooves (Rokatansky–Aschoff sinus) becomes hard, brittle
▫ Pain esp. after meal; gallbladder ▫ Bile stasis → calcium carbonate bile
attempts to secrete bile to small salts to precipitate out → deposit into
intestine for digestion walls
▪ Fatty meal → small intestine ▫ Increased risk of gallbladder cancer
cholecystokinin (CCK) signals gallbladder ▪ Acalculous cholecystitis
to secrete bile → gallbladder contracts
→ stone lodged in cystic duct → blocks
bile flow → irritates mucosa → mucosa SIGNS & SYMPTOMS
secretes mucus, inflammatory enzymes →
inflammation, distention, pressure ▪ Midepigastric pain → dull right upper
▪ Cholesterol stones quadrant pain radiates to right scapula/
▫ More potent ability to stimulate shoulders (esp. after a meal in chronic
inflammation compared to pigment cholecystitis)
gallstones ▪ Hypoactive bowel sounds; nausea,
▪ Possible progressions vomiting, anorexia; jaundice; low grade
fever
▫ Stone ejected out of cystic duct →
cholecystitis subsides, symptoms ▪ Blumberg’s sign/rebound tenderness
subside ▫ Right upper quadrant pain when
▫ Stone remains in place → pressure pressure rapidly released from
builds → pushes down on blood vessels abdomen; peritonitis (secondary to
supplying gallbladder → ischemia → gallbladder perforation/rupture)
gangrenous cell death → gallbladder ▪ Positive Murphy’s sign
walls weaken → perforation/rupture → ▫ Sudden cessation of inhalation due to
bacteria seeds to bloodstream → sepsis pain when inflamed gallbladder reaches
→ medical emergency examiner’s fingers
▫ Stone lodged in common bile duct → ▫ Examiner asks individual to exhale →
blocks flow of bile out of liver places hand below right costal margin
▪ Bacterial growth (cholangitis) in midclavicular line → individual
▫ Cholelithiasis → stone descends to instructed to breathe in → cessation due
cystic duct → cholecystitis → stone to pain
descends from cystic duct, lodges in ▫ Differentiates cholecystitis from other
common bile duct → choledolithiasis → causes of right upper quadrant pain
secondary infection due to obstruction
→ cholangitis
▫ Most commonly E. coli, Enterococci,
Bacterioides fragilis, Clostridium
200 OSMOSIS.ORG
DIAGNOSIS
DIAGNOSTIC IMAGING
Cholescintigraphy/hepatic iminodiacetic
acid (HIDA) scan
▪ Radioactive tracer injected into individual
→ marked HIDA taken up by hepatocytes,
excreted in bile → drains down hepatic
ducts
▪ Location of blockage
Diffusion-weighted MRI
▪ Differentiate between acute, chronic
cholecystitis
Ultrasound
▪ Gallstones/sludge Figure 28.3 Endoscopic retrograde
cholangiopancreatography demonstrating
▫ Gallbladder wall thickening, distention
gallstones in the cystic duct.
▫ Air in gallbladder wall (gangrenous
cholecystitis)
▫ Pericholecystic fluid from perforation/
exudate
LAB RESULTS
▪ Elevated ALP: concentrated in liver, bile
ducts
▫ Bile backs up, pressure in ducts increase
→ cells damaged, die → ALP released
▪ Elevated leukocyte count
TREATMENT Figure 28.4 Histological appearance of

cholestasis in the liver. There is build up of
MEDICATIONS bile pigment in the hepatic parenchyma.
▪ Antimicrobials
SURGERY
▪ Cholecystectomy
OSMOSIS.ORG 201
202 OSMOSIS.ORG
GALLSTONE
osms.it/gallstone
PATHOLOGY & CAUSES

▪ Solid stones inside gallbladder composed
of bile components
▪ Form based on imbalance of chemical
constituents → precipitate out to form solid
stone
TYPES
▪ Categorized by location
(choledocholithiasis, cholelithiasis) or major
composition (cholesterol, bilirubin stones)
Choledocholithiasis
▪ Gallstones in common bile duct →
obstruction of outflow tract Figure 28.5 Cholesterol gallstones.
▫ Stasis, infection (primary cause)
▫ Affects liver function; may cause liver
damage ▪ Radiopaque (visible on X-ray)
▪ Can be caused by excessive extravascular
Cholelithiasis
hemolysis
▪ Gallstones in gallbladder
▫ Extravascular hemolysis →
▫ Primary cause: imbalance of bile macrophages consume RBCs →
components increased unconjugated bilirubin
▫ Bile flow out of liver not obstructed; liver production → too much unconjugated
function not affected bilirubin for liver to conjugate →
unconjugated bilirubin binds to calcium
Cholesterol stones
instead of bile salts → precipitate out to
▪ Most common, 80% form black pigmented stones
▪ Composed primarily of cholesterol ▪ Brown pigmented gallstone: gallbladder/
▪ Cholesterol precipitation out of bile: biliary tract infection
supersaturation; inadequate salts/acids/ ▫ Stones enter common bile duct
phospholipids; gallbladder stasis
▫ Brown pigment due to unconjugated/
▪ Radiolucent (not visible on X-ray) hydrolyzed bilirubin, phospholipids:
infectious organism brings hydrolytic
Bilirubin stones (pigmented stones)
enzymes → hydrolysis of conjugated
▪ Composed primarily of unconjugated bilirubin, phospholipids → combine with
bilirubin calcium ions → precipitate out to form
▫ Formed from nonbacterial, stones
nonenzymatic hydrolysis of conjugated ▫ Common infections: E. coli, Ascaris
bilirubin lumbricoides, Clonorchis sinensis
▪ Occurs when too much bilirubin in bile (trematode endemic to China, Korea,
▪ Combines with calcium → solid calcium Vietnam)
bilirubinate ▫ Commonly seen in Asian populations
OSMOSIS.ORG 203
RISK FACTORS
▪ More common in individuals who
DIAGNOSIS
are biologically female, who use oral
contraceptive
DIAGNOSTIC IMAGING
▫ ↑ estrogen → ↑ cholesterol in bile + bile Ultrasound, CT scan, X-ray, ERCP
hypomotility → ↑ risk of gallstones ▪ Visualize stones
▪ Obesity
▪ Rapid weight loss
LAB RESULTS
▫ Imbalance in bile composition → ↑ risk
▪ Elevated bilirubin levels
of calcium-bilirubin precipitation
▪ Liver function tests (LFTs)
▪ Total parenteral nutrition (prolonged)
▫ Elevated gamma-glutamyl transferase
(GGT), alkaline phosphatase (ALP),
COMPLICATIONS alanine aminotransferase (ALT),
▪ Cholecystitis (inflammation of gallbladder) aspartate transaminase (AST)
▪ Ascending cholangitis
▪ Blockage of common, pancreatic bile ducts
▪ Gallbladder cancer: history of gallstones →
↑ risk of gallbladder cancer
SIGNS & SYMPTOMS

▪ May be asymptomatic
▪ Sudden, intense abdominal epigastric/
substernal pain; radiates to right shoulder/
shoulder blades
▪ Nausea/vomiting; jaundice; abdominal
tenderness, distension; fever, chills;
flatulence, belching
▪ See mnemonic for summary
Figure 28.6 Abdominal ultrasound

MNEMONIC: 6 Fs demonstrating cholelithiasis. The gallstones
Typical clinical presentation cast an acoustic shadow.
of an individual with
gallstones
Fat TREATMENT
Female
Fertile ▪ Necessary only if symptomatic
Forty
Fatty food intolerance MEDICATIONS
Flatulence ▪ Bile salts
▫ Dissolve cholesterol stones
204 OSMOSIS.ORG
SURGERY
▪ Cholecystectomy
OTHER INTERVENTIONS
▪ Pain management
▪ Shock wave therapy (lithotripsy)
▫ High-frequency sound waves fragment
stones
Figure 28.7 Numerous gallstones, of mixed-

type, in a cholecystectomy specimen. The
wall of the gallbladder is thickened and
fibrotic, consistent with long-standing
disease.
PRIMARY SCLEROSING
CHOLANGITIS (PSC)
osms.it/primary-sclerosing-cholangitis
COMPLICATIONS
PATHOLOGY & CAUSES ▪ Portal hypertension
▫ Fibrosis builds around bile ducts →
▪ Autoimmune disorder in which T-cells
constricts portal veins → ↑ pressure
attack, destroy bile duct epithelial cells
in genetically predisposed individuals ▪ Hepatosplenomegaly
exposed to environmental stimuli ▫ Portal hypertension → backup of fluid,
▫ HLA-B8, HLA-DR3, HLA-DRw52a enlargement of spleen, liver
▪ Associated with ulcerative colitis, Crohn’s ▪ Cirrhosis
disease ▫ Recurrent cycle of inflammation, healing
▪ Sclerosis, inflammation of intra-, → tissue scarring → fibrosis
extrahepatic ducts ▪ ↑ risk of cholangiocarcinoma, gallbladder
▪ Cells around bile ducts inflamed, die → cancer, hepatocellular carcinoma
fibrose
▪ Death of epithelial cells lining bile ducts
→ bile leaks into interstitial space,
SIGNS & SYMPTOMS
bloodstream
▪ May remit, recur spontaneously
▪ “Beaded” appearance of bile ducts
▪ Jaundice, RUQ pain, weight loss, pruritus
▫ Stenosis of affected ducts, dilation of
(deposition of bile salts, acids in skin),
unaffected ducts
hepatosplenomegaly
▪ Severity depends on bilirubin levels,
▪ Liver failure
encephalopathy, presence/absence of
ascites, serum albumin level, prothrombin ▫ Ascites, muscle atrophy, spider
time angiomas, increased clotting time, dark
urine, pale stool
OSMOSIS.ORG 205
DIAGNOSIS
DIAGNOSTIC IMAGING
MRCP
▪ Intrahepatic and/or extrahepatic bile duct
dilation; multifocal or diffuse strictures
ERCP
▪ Intrahepatic and/or extrahepatic bile duct
dilation; multifocal or diffuse strictures
LAB RESULTS
▪ Liver function tests (LFTs)
▫ Elevated conjugated bilirubin, ALP, GGT
▪ Elevated serum IgM antibody, p-ANCA
(targets antigens in cytoplasm/nucleus of
neutrophils; 80% of individuals with PSC)
Figure 28.8 Cholangiogram demonstrating
▪ Bilirubinuria multiple biliary strictures in a case of primary
▪ Liver biopsy sclerosing cholangitis.
▫ Stage disease, predict prognosis
OTHER DIAGNOSTICS
▪ Histology
▫ “Onion-skin fibrosis”: concentric rings
of fibrosis around bile duct, resembles
onion skin
TREATMENT
▪ No effective treatment
MEDICATIONS
▪ Treat symptoms, manage complications,
not curative (e.g. antibiotics) Figure 28.9 Histological appearance of
▪ Immunosuppressants, chelators, steroids primary sclerosing cholangitis. There is
onion-skin fibrosis of the biliary ducts.
SURGERY
▪ Liver transplant
▫ Advanced liver disease
206 OSMOSIS.ORG
NOTES
NOTES
COLORECTAL POLYP CONDITIONS

Inflammatory polyps
PATHOLOGY & CAUSES ▪ Caused by inflammatory bowel diseases
▫ Crohn’s disease, ulcerative colitis
▪ Colorectal polyps: overgrowths of epithelial
cells lining colon/rectum ▪ Not malignant
▪ Usually benign, can turn malignant
CAUSES
TYPES ▪ Genetic mutations
▪ Inflammatory conditions (e.g. Crohn’s
Adenomatous polyps/colonic adenomas disease)
▪ Gland-like polyps caused by tumor
suppressor gene mutation in adenomatous
RISK FACTORS
polyposis coli (APC)
▪ Family history
▪ Characterized by accelerated division of
epithelial cells → epithelial dysplasia → ▪ Bowel wall injury (e.g. radiation exposure,
polyp formation smoking, inflammatory bowel disease)
▪ No malignant potential by itself; requires ▪ Risk increases with age
mutations in other tumor suppressants (K-
RAS, p53) COMPLICATIONS
▪ Histologic classification ▪ Malignancy
▫ Tubular: pedunculated polyp, protrudes ▫ Depends on degree of dysplasia, size of
out in lumen polyp
▫ Villous: sessile, cauliflower-like
appearance; more often malignant
▫ Tubulovillous: characteristics of tubular, SIGNS & SYMPTOMS
villous polyps
▪ Often asymptomatic
Serrated polyps ▪ If ulcerating
▪ Saw-tooth appearance microscopically ▫ Rectal bleeding, anemia symptoms (e.g.
▪ Contain methylated CpG islands → fatigue)
silencing of DNA-repair genes, others → ▪ If large
more mutations → malignancy
▫ Obstruction → abdominal pain,
▫ Small polyps (most common): AKA constipation
hyperplastic polyps; rarely malignant
▪ Malabsorption → diarrhea
▫ Large polyps: often flat, sessile,
▪ Some polyposis syndromes
malignant
▫ Extracolonic symptoms
Hamartomatous polyps
▪ Mixture of tissues; disorganized mass
containing tissue found at site of polyp
▪ Occur sporadically/in genetically inherited
conditions (Juvenile polyposis, Peutz–
Jeghers syndrome)
OSMOSIS.ORG 207
DIAGNOSIS TREATMENT
DIAGNOSTIC IMAGING SURGERY
CT scan, MRI Polyp removal (polypectomy)
▪ Hyperdense outpouchings of colonic wall
Colonic resection (colectomy)
into lumen; detection of metastases
▪ If multiple polyps associated with polyposis
Endoscopy (colonoscopy) with biopsy syndromes/polyps with high-grade
▪ Type of polyp, malignant potential (degree dysplasia
of dysplasia)
LAB RESULTS
▪ Iron-deficiency anemia → decreased
red blood cell (RBC) count, low mean
corpuscular volume (MCV) levels
▪ Iron-deficiency anemia → low ferritin,
serum iron, transferrin saturation
▪ APC, RAS, etc. mutations
▪ Assess asymptomatic family members for
risk
OTHER DIAGNOSTICS Figure 29.1 The gross pathological

appearance of a sessile colorectal polyp.
Digital rectal examination
▪ Detection of distal rectal polyps; malignant
polyp, hard, irregular; benign polyps, softer,
pliable

villous adenoma, characterised by a surface
composed of long villous projections. Figure 29.3 The histological appearance of
a tubular adenoma composed of compact
glands with variable levels of dysplasia.
208 OSMOSIS.ORG
Chapter 29 Colorectal Polyp Conditions
FAMILIAL ADENOMATOUS
POLYPOSIS (FAP)
osms.it/familial-adenomatous-polyposis
▫ Abdominal mesenchymal desmoid
PATHOLOGY & CAUSES tumors: compress adjacent structures →
obstruction/vascular impairment
▪ Inherited condition; hundreds/thousands
▫ Other potential malignancies:
adenomatous polyps in colon
thyroid, pancreas, brain (glioma), liver
▪ Autosomal dominant inheritance; 100% (hepatoblastoma)
penetrance; de novo mutations may occur

Classic FAP ▪ Usually asymptomatic until malignancy
▪ Most aggressive, frequent; > 100 polyps at ▪ Colonic manifestations
diagnosis; early onset ▫ Palpable abdominal mass;
hematochezia (rectal bleeding); pain
Attenuated FAP (AFAP)
(esp. abdomen); diarrhea
▪ < 100 polyps at diagnosis (oligopolyposis);
later onset
Autosomal recessive FAP DIAGNOSIS

DIAGNOSTIC IMAGING
CAUSES
▪ Germline mutation in APC gene (tumor Endoscopy with biopsy
suppressor) → prevention of apoptosis →
Colonoscopy, flexible sigmoidoscopy:
cell overgrowth → polyps
▪ Detection of ≥ 100 polyps; ~30 polys,
▪ APC gene nonfunctional in FAP; slightly
AFAP
impaired in AFAP
▪ Autosomal recessive FAP Esophagogastroduodenoscopy (EGD)
▫ Mutations of MUTYH gene on ▪ Gastric, duodenal adenomas
chromosome 1
Barium enema (with double contrast)
▪ Filling defects
RISK FACTORS
▪ Family history Abdominal CT scan
COMPLICATIONS into lumen
▪ Malignancy if untreated
▪ Extracolonic manifestations LAB RESULTS
▫ Congenital hypertrophy of retinal ▪ Iron-deficiency anemia
pigment epithelium (CHRPE) ▪ ↓ RBC, ↓ MCV
▫ Fundic gland polyps: sessile polyps in ▪ ↓ ferritin, ↓ serum iron, ↓ transferrin
stomach, usually not malignant saturation
▫ Duodenal adenomas: malignant ▪ APC mutations
potential
OSMOSIS.ORG 209
OTHER DIAGNOSTICS
TREATMENT
Family history
▪ Cancers, gastrointestinal (GI) tract diseases MEDICATIONS
▪ Cyclooxygenase 2 inhibitors, other
Digital rectal examination nonsteroidal anti-inflammatory drugs
▪ Palpable mass (NSAIDs)
▪ Epidermal growth factor receptor inhibitor:
Ophthalmic examination
erlotinib
▪ CHRPE
▪ Chemotherapy, if colon cancer
SURGERY
▪ Frequent endoscopic check-ups to detect
onset of polyposis every 1–2 years
▫ If polyps detected → surgical removal
(colectomy; proctocolectomy)
Figure 29.4 Endoscopic appearannce of

the colon in a case of familial adenomatous
polyposis.
Figure 29.5 A retinal photograph

demonstrating hypertrophy of the retinal
pigment epithelium in a case of familial
adenomatous polyposis.
GARDNER'S SYNDROME (GS)

osms.it/gardners-syndrome
▪ Tumors outside colon
PATHOLOGY & CAUSES ▫ Fibromas, lipomas, epidermoid cysts,
thyroid neoplasms, osteomas, desmoid
▪ Variant of FAP with prominent extracolonic
▪ Extracolonic polyps can arise in stomach,
manifestations
duodenum, spleen, kidneys, liver,
▪ Inherited condition; numerous mesentery, small bowel; CHRPE lesions
adenomatous polyps in colon; extracolonic
polyps, tumors
210 OSMOSIS.ORG
CAUSES ▪ Supernumerary impacted teeth

▪ APC, RAS, TP53 mutation; DCC deletion → ▪ Multiple jaw osteomas, odontomas
furthers carcinogenesis
Digital rectal examination
▪ Autosomal dominant inheritance
▪ Palpable mass
COMPLICATIONS Ophthalmic examination

▪ Malignancy in colon, thyroid, liver, kidneys ▪ CHRPE
ECG
SIGNS & SYMPTOMS ▪ Stomach, duodenum for polyps
▪ Colonic manifestations
▫ Rectal bleeding, diarrhea TREATMENT
▪ Extracolonic manifestations
▪ No cure; palliative treatment
▫ Desmoid tumors (parietal bumps,
bleeding)
▫ Dental problems SURGERY
▫ Epidermoid cysts ▪ Excision of tumors/polyps with wide (8mm)
▫ Epigastric pain, bleeding, jaundice margin
▫ Malnutrition → malaise, lethargy, fatigue ▪ Colectomy
OTHER INTERVENTIONS
DIAGNOSIS ▪ Radiotherapy, if recurrent
DIAGNOSTIC IMAGING
Endoscopy with biopsy
Colonoscopy, flexible sigmoidoscopy

▪ Direct visualization of adenomatous polyps
in colon
Abdominal CT scan
into lumen
Head/dental X-ray
▪ Dental abnormalities
LAB RESULTS
▪ Iron-deficiency anemia
▫ ↓ RBC, ↓ MCV
▫ ↓ ferritin, ↓ serum iron, ↓ transferrin
saturation
▪ Tumoral markers (e.g. carcinoembryonic
antigen)
▪ APC, RAS, TP53 mutations; DCC deletion
OTHER DIAGNOSTICS
Physical examination
OSMOSIS.ORG 211
JUVENILE POLYPOSIS SYNDROME
osms.it/juvenile-polyposis

▪ Numerous benign (AKA juvenile) polyps DIAGNOSTIC IMAGING
along GI tract
Endoscopic studies
▪ Majority non-neoplastic hamartomas
polyps, in colorectum ▪ E.g. endoscopy, colonoscopy,
sigmoidoscopy
▪ Criteria for diagnosis
CAUSES
▫ > five juvenile polyps in colon/rectum
▪ BMPR1A, SMAD4 mutations
▫ Multiple juvenile polyps in other areas of
▪ Autosomal dominant inheritance; GI tract
incomplete penetrance
▫ Family history with any number of
▪ De novo mutations (25%) polyps
▪ Biopsy, cytology
COMPLICATIONS
▪ Increased risk of colorectal/extracolonic LAB RESULTS
adenocarcinoma; intestinal obstruction
▪ Iron-deficiency anemia
SIGNS & SYMPTOMS ▫ ↓ ferritin, ↓ serum iron, ↓ transferrin
saturation
▪ Hematochezia, anemia symptoms; ▪ BMPR1A, SMAD4 mutations
abdominal pain; diarrhea/constipation;
rectal prolapse
TREATMENT
SURGERY
▪ Polypectomy
▪ Surgical colectomy, proctocolectomy
▫ Malignant, ulcerating polyps
Figure 29.6 A juvenile retention polyp with

abundant edematous stroma and dilated
cystic spaces filled with mucin. The spaces
are lined by cuboidal epithelium.
212 OSMOSIS.ORG
PEUTZ–JEGHERS SYNDROME
(PJS)
osms.it/peutz-jeghers

▪ Inherited condition; benign hamartomatous DIAGNOSTIC IMAGING
polyps, in small bowel; also in colon,
stomach Endoscopy, colonoscopy, with biopsy
▪ Associated with hyperpigmented (melanin- Capsule endoscopy
containing) macules on skin, mucosa
Abdominal CT scan
CAUSES ▪ Hyperdense outpouchings of colonic wall
into lumen
▪ IV drug use
▫ Increases likelihood of infective
endocarditis LAB RESULTS
▪ Congenital bicuspid aortic valve ▪ Fecal occult blood test
▪ Diabetes, high blood pressure, smoking ▪ Iron-deficiency anemia
COMPLICATIONS ▫ ↓ ferritin, ↓ serum iron, ↓ transferrin
saturation
▪ Very high risk of extracolonic malignant
transformation ▪ Tumor markers
▫ Breast, ovarian, cervical, testicular, ▫ CEA, CA-19-9, CA-125
pancreatic, thyroid cancer ▪ STK11 (LKB1) mutations
▪ Mild malignant potential of polyps
OTHER DIAGNOSTICS
SIGNS & SYMPTOMS Diagnostic criteria
▪ One of following
▪ GI ▫ ≥ two PJ polyps confirmed histologically
▫ Ulceration → GI bleeding ▫ ≥ one PJ polyp with family history
(hematochezia/melena) → symptoms of ▫ PJS-associated mucocutaneous
anemia pigmentations
▫ Colicky abdominal pain
▫ Intussusception → bowel obstruction, Digital rectal examination
bowel infarction ▪ Palpable mass
▫ Diarrhea, constipation
▪ Pigmented lesions around oral mucosa,
nostrils, perianal area of extremities; fade
TREATMENT
after puberty
SURGERY
▪ Polypectomy
MEDICATIONS
▪ Cyclooxygenase 2 inhibitors (celecoxib)
OSMOSIS.ORG 213
Peutz-Jegher’s polyp. Figure 29.8 Multiple melanotic macules on
the skin and oral mucosa of a young boy with
Peutz-Jegher’s syndrome.
214 OSMOSIS.ORG
NOTES
NOTES
ESOPHAGEAL DISEASE

▪ Pathologies of the esophagus ▪ Individual history/clinical features,
▪ Esophageal motility disorders esophagogastroduodenoscopy (EGD),
▫ Diseases interfering with correct barium swallow X-ray, esophageal
function of esophagus’ various muscular manometry, endoscopic biopsy
components
TREATMENT
CAUSES
▪ Infections, autoimmune disease, anatomical ▪ See individual diseases
defects, irritative processes
SIGNS & SYMPTOMS

▪ Difficulty/pain while swallowing, especially
spasm-type pain
▪ Difficulty with food regurgitation
ACHALASIA
osms.it/achalasia
▪ Affected individual lacks nonadrenergic,
PATHOLOGY & CAUSES noncholinergic, inhibitory ganglion cells
→ imbalanced excitation and relaxation
▪ Esophageal smooth muscle fibres fail → incomplete lower esophageal sphincter
to relax → lower esophageal sphincter relaxation, increased lower esophageal
remains closed/fails to open tone, lack of esophageal peristalsis
▪ AKA esophageal achalasia, achalasia
cardiae, cardiospasm, esophageal
aperistalsis
CAUSES
▪ Likely caused by underlying autoimmune
▪ Progressive degeneration of ganglion cells
process triggered by previous viral
in myenteric plexus within esophageal wall
infection/ genetic predisposition/
→ lower esophageal sphincter fails to relax
neurodegenerative disease/other infective
→ loss of peristalsis in distal esophagus
process
▪ Involves smooth muscle layer of
esophageal, lower esophageal sphincters
OSMOSIS.ORG 215
Primary achalasia (most common) Endoscopic biopsy
▪ No known underlying cause → failure of ▪ Hypertrophic musculature
distal esophageal inhibitory neurons ▪ Absence of specific nerve cells within
myenteric plexus
Secondary achalasia
▪ Esophageal cancer
▪ Chagas disease OTHER DIAGNOSTICS
▫ Protozoan infection due to Trypanosoma Esophageal manometry
cruzi → loss of intramural ganglion ▪ Lower esophageal sphincter fails to relax
cells → aperistalsis, incomplete lower upon wet swallow (< 75% relaxation)
esophageal sphincter relaxation
▪ Lower esophageal pressure
▫ Normal < 26mmHg
SIGNS & SYMPTOMS ▫ Achalasia > 100mmHg
▫ Nutcracker achalasia > 200mmHg
▪ Dysphagia to solids/liquids, odynophagia ▪ Aperistalsis in esophageal body
(rarely), heartburn unresponsive to proton ▪ Relative increase in intraesophageal
pump inhibitor therapy, symptoms worsen pressure vs. intragastric pressure
progressivelys, regurgitation of undigested
food, substernal chest pain, hiccups
▪ Weight loss TREATMENT
▪ Coughing while lying horizontally,
aspiration of food → recurrent pulmonary MEDICATIONS
complications ▪ Calcium channel blockers for mild to
moderate disease
▪ Nitrates effective before dilatation occurs
DIAGNOSIS ▪ Antimuscarinic agents (rarely effective)
DIAGNOSTIC IMAGING ▪ Proton pump inhibitors (after surgery/
pneumatic dilatation) to prevent reflux
Barium swallow X-ray and continuous damage
fluoroscopy
▪ Normal peristalsis not seen SURGERY
▪ Acute tapering at lower esophageal
sphincter Laparoscopic Heller myotomy
▪ Narrowing of gastroesophageal junction ▪ Esophageal dilatation via surgical cleaving
(bird’s beak/rat’s tail appearance) of muscle
▪ Dilated esophagus above narrowing ▪ Only cut through outer muscle layers (those
▪ Air-fluid margin over barium column due to failing to relax), leaving inner mucosal layer
lack of peristalsis intact
Esophageal endoscopy with or without Endoscopic myotomy

endoscopic ultrasound ▪ Peroral endoscopic myotomy, minimally
▪ May appear normal invasive → incision made through
esophageal mucosa, innermost circular
▪ Unusually increased resistance to passage
muscle layer divided and extended through
of endoscope through esophagogastric
lower esophageal sphincter, 2cm/0.8in into
junction
gastric muscle
▪ Retained food in esophagus on upper
endoscopy
216 OSMOSIS.ORG
Chapter 30 Esophageal Disease
OTHER INTERVENTIONS
▪ Eat slowly, chew well, drink plenty of water
with meals, avoid eating near bedtime,
raise head off bed when sleeping with
pillows (promotes emptying of esophagus
with gravity)
▪ Avoid foods that aggravate reflux →
ketchup, citrus, chocolate, caffeine
Botox injection
▪ Paralyze muscle keeping lower esophageal
sphincter shut (causes scarring of sphincter
→ may complicate later myotomy)
Pneumatic dilatation
▪ Muscle fibres stretched/torn by forceful
inflation of balloon placed in lower
esophageal sphincter Figure 30.1 A barium swallow demonstrating
the bird’s beak sign in achalasia. The proximal
▪ Lowers basal lower esophageal tone by
esophagus is dilated.
disruption of muscular ring
BARRETT'S ESOPHAGUS
osms.it/barretts-esophagus
▫ Upright/supine reflux
PATHOLOGY & CAUSES ▫ Significantly more likely to develop
adenocarcinoma
▪ Premalignant condition; metaplasia of cells
lining lower esophagus Short-segment Barrett’s
▪ Normal stratified squamous epithelium → ▪ Distance between z-line and
simple columnar epithelium, goblet cells gastroesophageal junction < 3cm/1.2in
(usually native to lower gastrointestinal ▫ Greater prevalence
tract)
▫ Shorter history of heartburn
▪ Chronic acid exposure → reflux esophagitis
▫ Usually asymptomatic
(chronic irritation) → metaplasia
▫ Predominantly upright reflux
▪ Bile acids → intestinal differentiation →
promotes cancer growth ▫ Less mucosa involved → lower
incidence of dysplasia
TYPES
RISK FACTORS
▪ If z-line and gastroesophageal junction
coincide → intestinal metaplasia at ▪ Bulimia
gastroesophageal junction ▪ Central obesity
▫ Associated with Helicobacter pylori ▪ Previous chemical damage to esophageal
epithelium (e.g. swallowing lye)
Long-segment Barrett’s ▪ Smoking
▪ Distance between z-line and ▪ Hiatal hernia
gastroesophageal junction > 3cm/1.2in
▫ Associated with more severe reflux
OSMOSIS.ORG 217
COMPLICATIONS
▪ Esophageal adenocarcinoma
TREATMENT
MEDICATIONS
SIGNS & SYMPTOMS Proton pump inhibitors
▪ E.g. omeprazole; manage acid reflux
▪ Same as reflux, not (initial) cancerous Chemoprevention
changes ▪ Nondysplastic/low-grade lesion
▪ Frequent, prolonged heartburn, dysphagia, ▫ Aspirin, NSAIDS → inhibition of
hematemesis, epigastric pain, weight loss cyclooxygenase (COX-1 & 2) may
(due to painful eating) protect against progression of disease
DIAGNOSIS SURGERY
Treatment of dysplastic lesions
DIAGNOSTIC IMAGING
▪ Endoscopic mucosal resection, surgical
Esophagogastroduodenoscopy removal of esophagus, radiation therapy,
▪ Fiber optic camera inserted via mouth → systemic chemotherapy
examine and biopsy esophagus, stomach,
duodenum OTHER INTERVENTIONS
Annual endoscopic observation
LAB RESULTS
▪ For nondysplastic/low-grade lesions
Biopsy
Management of acid reflux
▪ Specimen from
▪ Avoid/reduce intake of foods known to
esophagogastroduodenoscopy must
worsen reflux: chocolate, coffee, tea,
contain goblet cells → “intestinal
peppermint, alcohol, fatty/spicy/acidic foods
metaplasia” → marker for progression of
metaplasia to dysplasia → adenocarcinoma Treatment of dysplastic lesions
▪ Immunohistochemical staining assists in ▪ Radiofrequency ablation
diagnosis
▫ Electrical current used to destroy small
▪ Biopsy classification regions of tissue
▫ Nondysplastic ▪ Spray cryotherapy
▫ Low-grade dysplasia ▫ Liquid nitrogen spray applied to small
▫ High-grade dysplasia region of tissue → freezing → tissue
▫ Frank carcinoma death
▪ Photodynamic therapy
OTHER DIAGNOSTICS ▫ Chemical photosensitizer → cytotoxicity
when stimulated by certain frequency
Screening of light
▪ Biological males, > 60 years old, long
standing reflux, life expectancy > five years
▪ Anyone with diagnosis of Barrett’s
esophagus
Esophageal pH studies
▪ Establish efficacy of proton pump inhibitor
treatment
218 OSMOSIS.ORG
Figure 30.2 Histological appearance of the squamocolumnar junction in a case of Barrett’s

esophagus. The underlying glandular epithelium contains goblet cells, indicating intestinal
metaplasia.
BOERHAAVE SYNDROME
osms.it/boerhaave-syndrome
▫ Chemical mediastinitis → mediastinal
PATHOLOGY & CAUSES necrosis → rupture of overlying pleura
→ contamination of pleural cavity →
▪ Rupture through esophagus caused by pleural effusion
increased intraesophageal pressure and ▫ Effort rupture of cervical esophagus →
negative intrathoracic pressure localized cervical perforation
▪ Vomiting / retching → unrelaxed ▫ Spread of contamination slow due
esophagus, closed glottis → increase to attachments of esophagus to
in esophageal pressure, slight drop in prevertebral fascia
intrathoracic pressure → spontaneous
▪ Usually occurs in anatomically normal
rupture of esophageal wall →
esophagi
contamination of mediastinum with gastric
contents → chemical mediastinitis
▫ Tears commonly occur at left RISK FACTORS
posterolateral aspect (distal esophagus), ▪ Caustic ingestion, pill/medication
just above esophageal hiatus of esophagitis, eosinophilic esophagitis,
diaphragm Barrett’s esophagus, infectious ulcers,
▫ Can be fatal without treatment → sepsis stricture dilatation
OSMOSIS.ORG 219
▪ Barium sulfate common contrast material,
SIGNS & SYMPTOMS but spillage into mediastinal and pleural
spaces → inflammatory response →
▪ Severe vomiting → profound retrosternal fibrosis
chest pain (may radiate to left shoulder) or
abdominal pain Endoscopy avoided
▫ Followed by painful swallowing ▪ May extend tear, introduce air into
(odynophagia), tachypnea, dyspnea, mediastinum
cyanosis, fever, shock
▪ Mackler’s triad: chest pain, vomiting, LAB RESULTS
subcutaneous emphysema
▪ Hemoglobin and hematocrit
▪ Hamman’s sign: crunching/rasping sound,
▪ Assess severity of initial bleeding
synchronous with heartbeat:
▪ Pleural effusion fluid may be high in
▫ Heard over precordium, left lateral
amylase (saliva), low pH
position
▪ Leukocytosis
▫ Caused by mediastinal emphysema
▪ Cervical perforation: neck pain, difficulty
swallowing (dysphagia), difficulty
speaking (dysphonia), tenderness of
sternocleidomastoid
▪ Intra-abdominal perforation: epigastric
pain (may radiate to left shoulder), back
pain, inability to lie supine, acute abdomen
pain
DIAGNOSIS
▪ Non-specific symptoms → diagnostic delay,
poor outcome
▪ Physical examination often unhelpful;
history important
DIAGNOSTIC IMAGING
Chest X-ray
▪ Early: free mediastinal air
▪ Hours to days later: pleural effusion,
pneumothorax, widened mediastinum, Figure 30.3 A contrast swallow in an
subcutaneous emphysema individual with Boerhaave’s syndrome. The
Chest CT scan contrast has leaked into and accumulated in
the thoracic cavity.
▪ Esophageal wall edema/thickening,
extraesophageal air, periesophageal fluid,
mediastinal widening, pneumothorax
Fluoroscopy
▪ Water soluble contrast (gastrografin)
esophagram → location and extent of
extravasation of contrast
220 OSMOSIS.ORG
SURGERY
TREATMENT ▪ Debride infected/necrotic tissue, repair
defect/resection of defect/diversion
MEDICATIONS
▪ IV proton pump inhibitor → reduce acidity,
irritation OTHER INTERVENTIONS
▪ Prophylactic antibiotic therapy ▪ Parenteral/enteral ( jejunostomy/PEG tube)
nutritional support
DIFFUSE ESOPHAGEAL SPASM

osms.it/esophageal-spasm

▪ Esophageal motility disorder characterized DIAGNOSTIC IMAGING
by repetitive, non-peristaltic, spontaneous
contractions of the distal esophageal Barium swallow x-ray (upper GI)
smooth muscle ▪ “Corkscrew” appearance is characteristic
▪ Sphincter function = normal
Endoscopy
▪ Exclude heart disease, mechanical
CAUSES intraluminal obstruction
▪ Cause relatively unknown
▪ Uncontrolled brain signals and extremely OTHER DIAGNOSTICS
hot/cold beverages can trigger disease
24-hour esophageal manometry
COMPLICATIONS ▪ Shows uncoordinated esophageal
contractions of normal amplitude
▪ Leads to difficulty swallowing, impaired
advancement of food and/or regurgitation
TREATMENT
SIGNS & SYMPTOMS
▪ No cure
▪ Intermittent dysphagia
▪ Atypical chest pain that mimics cardiac MEDICATIONS
chest pain; may radiate to jaw, arms, back ▪ Nitrates, calcium channel blockers, and/
▪ Food regurgitation relatively uncommon or botulinum toxin injections to lower
esophageal muscle; used to decrease
spasms
▪ Antidepressants, anti-anxiety medications
SURGERY
▪ Surgical esophagomyotomy rarely
considered
OSMOSIS.ORG 221
GASTROESOPHAGEAL REFLUX
DISEASE (GERD)
osms.it/gastroesophageal-reflux
▫ Often felt shortly after eating meals
PATHOLOGY & CAUSES (worse after large meals/when lying
down)
▪ AKA acid reflux ▪ Halitosis, tooth decay
▪ Failure of lower esophageal sphincter →
poor closure/inappropriate relaxation (poor
tone) of lower esophageal sphincter → DIAGNOSIS
stomach contents re-enter esophagus
▪ Commonly associated with decreased ▪ Can be diagnosed based on clinical
esophageal motility, gastric outlet symptoms, history alone
obstruction, hiatal hernia
DIAGNOSTIC IMAGING
RISK FACTORS
▪ Obesity, pregnancy, smoking, hiatal hernia Endoscopy
▪ Medications ▪ Used when therapeutic response poor/
concerning symptoms present (dysphagia,
▫ Antihistamines, calcium channel
anemia, blood in stool, wheezing, weight
blockers, antidepressants, hypnotics,
loss, voice changes)
glucocorticoids
▪ Zollinger–Ellison syndrome, high blood Upper GI series X-rays with barium con-
calcium (increased gastrin production), trast
scleroderma/systemic sclerosis (esophageal ▪ Useful to identify complications
dysmotility)
▪ Early stages of reflux esophagitis: granular
▪ Visceroptosis nodular appearance of mucosa in distal
third of esophagus with numerous ill-
COMPLICATIONS defined 1–3mm lucencies
▪ Esophagitis, esophageal strictures, Barrett’s ▪ Shallow ulcers and erosions
esophagus (premalignant condition), ▫ Collections of barium in distal
esophageal adenocarcinoma, laryngitis, esophagus near gastroesophageal
chronic cough, pulmonary fibrosis, earache, junction
asthma, recurrent pneumonia ▫ Identify stricture (tapered area
of concentric narrowing in distal
esophagus)
SIGNS & SYMPTOMS
▪ Acid taste in mouth, heartburn, retrosternal
LAB RESULTS
chest pain, early satiety, regurgitation, ▪ 24-hour esophageal pH monitoring in
odynophagia, increased salivation, lower esophagus
postprandial nausea and vomiting,
sore throat, sensation of lump in throat,
coughing, wheezing
222 OSMOSIS.ORG
Biopsy
▪ Edema, basal hyperplasia (non-specific
inflammation)
▪ Lymphocytic inflammation (non-specific)
▪ Neutrophilic inflammation (reflux/
Helicobacter gastritis)
▪ Eosinophilic inflammation (usually reflux,
if > 20 eosinophils per high-power field
extending beyond distal esophagus, more
like eosinophilic esophagitis)
▪ Elongation of papillae
▪ Goblet cell intestinal metaplasia
▪ Thinning of squamous cell layer
▪ Dysplasia
▪ Carcinoma Figure 30.4 The histological appearance of
the squamous-lined esophagus in a case of
OTHER DIAGNOSTICS reflux. The papillae become elongated and
▪ Esophageal manometry (excludes motility there is overgrowth of the basal cells (darker
disorder) blue) known as basal cell hyperplasia.
▪ Short term trial of proton-pump inhibitors
TREATMENT
MEDICATIONS
▪ Antacids neutralise acidity of gastric
secretions
▪ H2 receptor blockers decrease acidification
of gastric secretions
▪ Proton pump inhibitors decrease
acidification of gastric secretions
▪ Prokinetics strengthen lower esophageal
sphincter (LES), causing stomach contents
to empty faster
▪ Baclofen (GABAB agonist)
▫ Inhibits transient LES relaxations,
particularly in postprandial period
▫ Modestly effective, but rarely used due
to frequent dosing requirements
Surface agents and alginates

Figure 30.5 A contrast X-ray demonstrating ▪ Sucralfate (aluminium sucrose sulfate)
gastroesophageal reflux. The contrast ▫ Adheres to mucosal surface →
medium was injected percutaneously into promotes healing, protects from peptic
the stomach and has migrated into the injury
esophagus.
▪ Sodium alginate
▫ Polysaccharide derived from seaweed
→ forms a viscous gum that floats
within stomach → reduced postprandial
acid pocket in proximal stomach
OSMOSIS.ORG 223
SURGERY
Nissen fundoplication
▪ Upper part of stomach wrapped around
lower esophageal sphincter → strengthens
sphincter, prevents acid reflux
Transoral incisionless fundoplication

▪ Similar procedure to Nissen fundoplication,
performed transorally with endoscope
LINX reflux management system

▪ Titanium beads with magnetic cores
wrapped around weak native lower
esophageal sphincter → attractive force
between beads closing sphincter → force
of peristaltic wave of caused by swallowing Figure 30.6 An endoscopic view of
can transiently open beads an esophageal stricture, a potential
consequence of severe, long-standing reflux.
OTHER INTERVENTIONS
Lifestyle modifications
▪ Avoid lying down within three hours after
eating, wedge pillow when sleeping to
elevate head, weight loss, avoid certain
foods (coffee, alcohol, chocolate, fatty/
acidic/spicy foods), smoking cessation,
moderate exercise
MALLORY–WEISS SYNDROME
osms.it/mallory-weiss
CAUSES
PATHOLOGY & CAUSES ▪ Vomiting, straining, coughing, seizures,
blunt abdominal injury, nasogastric tube
▪ Severe vomiting → sudden increase placement, gastroscopy
in intra-abdominal pressure → partial
thickness laceration at gastroesophageal
junction → bleeding from mucosa RISK FACTORS
▪ Also called gastroesophageal laceration ▪ Alcoholism, bulimia, food poisoning, hiatal
syndrome hernia, NSAID abuse, biological male sex
▪ Laceration known as “Mallory–Weiss tear”, (80%), hyperemesis gravidarum (severe
involves mucosa and submucosa, not morning sickness in pregnancy)
muscular layer
224 OSMOSIS.ORG

▪ Hematemesis after episode of violent ▪ In absence of comorbidities (esp. portal vein
retching/vomiting hypertension), significant healing occurs in
▪ Melena first 24–48 hours
▪ Bleeding associated symptoms may cease
after 24–48 hours MEDICATIONS
▪ Epigastric, back pain
Supportive (persistent bleeding uncom-
▪ Signs of hemodynamic instability
mon)
▫ Resting tachycardia, hypotension
▪ Acid suppression
▫ IV proton pump inhibitor
DIAGNOSIS ▪ If nausea and vomiting persistent
▫ Antiemetics
DIAGNOSTIC IMAGING
Endoscopy SURGERY
▪ Tears appear as red longitudinal breaks in Endoscopy (for spurting/oozing tears)
mucosa, may be covered by clot
▪ Cauterization, hemoclips (hemostasis of
small defects), endoscopic band ligation
LAB RESULTS (with or without epinephrine injection),
▪ Hemoglobin, hematocrit (assess severity of arterial embolization
initial bleeding)
Figure 30.7 Endoscopic appearance of a

Mallory-Weiss tear.
OSMOSIS.ORG 225
PLUMMER–VINSON SYNDROME
osms.it/plummer-vinson
DIAGNOSTIC IMAGING
PATHOLOGY & CAUSES
Barium esophagography, videofluoroscopy,
▪ Triad of iron deficiency anemia, dysphagia, esophagogastroduodenoscopy
cervical esophageal web ▪ Esophageal web
▪ AKA Paterson–Brown–Kelly syndrome,
sideropenic dysphagia
LAB RESULTS
▪ Premalignant disease
▪ Anemia
▫ Complete blood cell count, peripheral
CAUSES blood smear, iron study
▪ Exact cause unknown, likely connected to
genetic factors, nutritional deficiencies
TREATMENT
RISK FACTORS
MEDICATIONS
▪ Postmenopause
▪ Iron supplementation, folate, vitamin B12
→ correct iron deficiency anemia
COMPLICATIONS
▪ Esophageal/pharyngeal squamous cell SURGERY
carcinoma
▪ Mechanical widening of esophagus
SIGNS & SYMPTOMS

▪ Esophageal signs and symptoms
▫ Esophageal webs, difficult/painful
swallowing, Plummer–Vinson syndrome
at upper end of esophagus, Schatzki
ring lower end of esophagus
▪ Iron deficiency signs and symptoms
▫ Glossitis, cheilosis, angular stomatitis,
koilonychia, splenomegaly, dizziness,
pallor, dyspnea
DIAGNOSIS
▪ Presence of esophageal web in individual
with iron deficiency anemia Figure 30.8 An endoscopic view of an
esophageal web which is usually associated
with Plummer-Vinson syndrome.
226 OSMOSIS.ORG
ZENKER'S DIVERTICULUM
osms.it/zenkers
CT scan with oral contrast
PATHOLOGY & CAUSES
▪ Distinct outpouching visible
▪ Diverticulum (outpouching) of pharyngeal
mucosa through Killian’s triangle (area of
muscular weakness), between transverse
TREATMENT
fibres of cricopharyngeus muscle and
oblique fibres of lower inferior constrictor ▪ Small/asymptomatic diverticula do not
muscle require treatment
▪ AKA pharyngoesophageal diverticulum,
pharyngeal pouch, hypopharyngeal SURGERY
diverticulum ▪ Neck surgery → cricopharyngeal myotomy,
▪ Pseudodiverticulum diverticulopexy
▫ Does not involve all layers of esophageal
wall → contains mucosa, submucosa OTHER INTERVENTIONS
▪ Non-surgical endoscopic technique
CAUSES ▪ Endoscopic stapling
▪ Uncoordinated swallowing, impaired ▪ Endoscopic laser
relaxation and swallowing, impaired
relaxation and spasm of cricopharyngeus
muscle → increased pressures in distal
pharynx → excessive lower pharyngeal
pressures → diverticulum formation
RISK FACTORS
▪ Biological male > 60 years old
SIGNS & SYMPTOMS

▪ Difficulty swallowing, sense of lump in
throat, cervical webs
▪ Food trapping
▫ Regurgitation, cough, halitosis, infection
DIAGNOSIS
DIAGNOSTIC IMAGING
Barium swallow
▪ Distinct outpouching visible
Figure 30.9 A barium swallow
Upper gastrointestinal endoscopy demonstrating a Zenker’s diverticulum,
▪ Pouch visualized outlined on the right of the image.
OSMOSIS.ORG 227
NOTES
NOTES
GASTRIC DISEASE

▪ Diseases affecting gastric mucosa, gastric MEDICATIONS
outlet, etc. ▪ Proton pump inhibitor (PPI)
▪ Inflammation due to infection; ulceration ▪ Correct fluid, electrolyte deficits
▪ Discontinue nonsteroidal anti-inflammatory
drugs (NSAIDs)
SIGNS & SYMPTOMS
▪ May be asymptomatic SURGERY
▪ Epigastric pain, nausea, vomiting ▪ Endoscopic ligation/coagulation
▪ Anemia; fecal, urinary incontinence; ulcers; ▪ Surgical repair
bleeding
OTHER INTERVENTIONS
▪ Dietary modification; exercise
DIAGNOSIS ▪ Avoid smoking
DIAGNOSTIC IMAGING
▪ Endoscopy
LAB RESULTS
▪ Biopsy
228 OSMOSIS.ORG
Chapter 31 Gastric Disease
CYCLIC VOMITING SYNDROME

osms.it/cyclic-vomiting
▪ Autonomic: lethargy, pallor, excessive
PATHOLOGY & CAUSES salivation, low grade fever
▪ Neurologic: headache, photophobia,
▪ An uncommon disorder characterized by
phonophobia, vertigo
recurrent episodes of vomiting separated
by asymptomatic periods ▪ Social withdrawal
▪ Median onset age: 5–6 years old
DIAGNOSIS
CAUSES
▪ Cause unknown; triggers may include OTHER DIAGNOSTICS
psychological stress (e.g. interpersonal ▪ History and physical examination
conflict, holidays) or physical stress (e.g. ▫ No identifiable organic cause
infections, exhaustion), certain foods (e.g. ▪ Diagnostic criteria (Rome IV criteria)
cow’s milk, chocolate, cheese, monosodium
▫ ≥ three recurrent, discrete episodes
glutamate) menses
of vomiting in the prior year, with
two episodes in the past six months
RISK FACTORS occurring at least one week apart
▪ Children > adults ▫ Variable intervals between vomiting
▫ In children: mitochondrial DNA deletions episodes and asymptomatic baseline
and polymorphisms ▫ Stereotypical characteristics regarding
▪ Females > males timing of onset, symptoms, and duration
▪ Family history of migraines
▪ Autonomic abnormalities (elevated
sympathetic tone)
TREATMENT
▪ Hypothalamic-pituitary-adrenal activation
OTHER INTERVENTIONS
(Sato variant)
▪ During cyclic vomiting episodes
▪ Chronic cannabis use
▫ IV fluids, antiemetics, sedatives; comfort
care in dark, quiet room
COMPLICATIONS
▪ Erosive esophagitis Prevention
▪ Mallory-Weiss tear ▪ Prophylactic therapy
▪ Dehydration ▫ H1-antagonists (e.g. cyproheptadine)
for children ≤ five years old
▪ Electrolyte imbalance
▫ Tricyclic antidepressants (e.g.
▪ Unintended weight loss
amitriptyline) > years of age
▪ Abortive therapy
SIGNS & SYMPTOMS ▫ Triptans; neurokinin-1 receptor
antagonists
▪ Symptoms tend to develop at night, in the ▪ Avoidance of triggers
early morning hours, or upon awakening
▪ Prodromal period is common
▪ Gastrointestinal: vomiting which may
include bile or blood; retching, abdominal
pain, diarrhea
OSMOSIS.ORG 229
GASTRIC DUMPING SYNDROME
osms.it/gastric-dumping

▪ Iatrogenic post-gastric surgery syndrome; DIAGNOSTIC IMAGING
impaired gastric motility → rapid stomach ▪ Endoscopy
emptying
▪ Surgical intervention → disruption in
LAB RESULTS
gastric anatomy, mucosal function, fundus
tone, antropyloric regulatory mechanisms, ▪ Oral glucose challenge test elicits
duodenal feedback on motility → rapid symptoms
emptying of stomach contents into ▪ Hydrogen breath test after glucose
duodenum ingestion
▪ 50% of individuals undergoing gastric
surgical procedures OTHER DIAGNOSTICS
▪ More common in individuals who are ▪ Gastric emptying study
biologically female ▪ Clinical indices
▫ Sigstad’s diagnostic index: > 7
SIGNS & SYMPTOMS ▫ Visick classification: heart rate
variations after oral glucose challenge
▪ GI: early satiety; abdominal colic; nausea,
vomiting; explosive diarrhea; bloating; TREATMENT
malabsorption
▪ Vasomotor: diaphoresis; palpitations; MEDICATIONS
vertigo
▪ Early dumping syndrome Acarbose
▫ 30–60 minutes post-meal ▪ Interferes with carbohydrate reabsorption
▫ Accelerated stomach emptying →
Octreotide
hyperosmolar contents poured into
small bowel → osmotic activity → bowel ▪ Inhibits insulin release
distention, motility stimulated → GI
symptoms OTHER INTERVENTIONS
▪ Late dumping syndrome
Dietary modification
▫ 60–180 minutes post-meal
▪ Avoid simple sugars, fluid intake during
▫ Accelerated stomach emptying → ↑
meals; low carbohydrate, high protein diet
carbohydrate concentration in proximal
intestine → rapid glucose absorption
→ rapid, sustained insulin response →
hypoglycemia → vasomotor symptoms
230 OSMOSIS.ORG
GASTRITIS
osms.it/gastritis
PATHOLOGY & CAUSES ▪ Infectious

▫ Most common cause (80%)
▪ Inflammation of the lining of the stomach ▫ H. pylori → chronic gastritis → gastric
▪ May occur as a short episode or may be of atrophy → metaplasia → dysplasia →
a long duration cancer (associated with intestinal-type
gastric carcinoma)
▫ Cytotoxin-associated gene A (CagA);
TYPES carcinogenic virulence factor of H. pylori
Acute gastritis ▫ Normal gastrin levels, no hypochloridia,
no anti-parietal cell/anti-intrinsic factor
▪ Inflammation of gastric mucosa; compare to
antibodies (compare to autoimmune
gastropathy (without active inflammation)
atrophic gastritis; hypochloridia, anti-
▪ Gastritis, gastropathy parietal/anti- intrinsic factor antibodies)
▫ Clinically identical, histologically distinct ▫ Gastric ulcers
Atrophic gastritis
▪ AKA chronic gastritis, metaplastic gastritis,
gastric atrophy
▪ Chronic inflammation of gastric mucosa
→ epithelial metaplasia, mucosal atrophy,
gland loss
▫ Metaplasia: reversible change of one
epithelium into another, response to
stress
▫ Intestinal metaplasia: goblet cells
CAUSES
Acute gastritis
▪ Certain medications, alcohol,
corticosteroids, uremia
▪ NSAIDs block cyclooxygenase → ↓
prostaglandin E2, I2 production → ↓
gastric defense mechanisms (mucus, HCO3 Figure 31.1 A high magnification image of
secretion) → mucosal injury Helicobacter organisms within a gastric crypt.
▪ H. pylori infection → gastric mucosa Helicobacter are a common cause of gastritis.
infiltrates antrum, corpus → inflammation
involving neutrophil, mononuclear cells
▪ Alcohol, cigarette smoke, caffeine → ▪ Autoimmune
irritates, erodes stomach mucosa lining ▫ Most common cause in individuals
▪ Extreme physiological stress (e.g. shock, without H. pylori
sepsis, burns) ▫ Inherited autoimmunity against intrinsic
factor, H+/K+ ATPase in parietal cells
Atrophic gastritis → inhibition of gastric acid secretion
▪ Two main causes: infectious and (hypochloridia). ↓ intrinsic factor →
autoimmune
OSMOSIS.ORG 231
cobalamin (B12) malabsorption →
pernicious anemia DIAGNOSIS
▫ Hypochloridia (impaired iron absorption
/G-cell hyperplasia, hypergastrinemia →
LAB RESULTS
↑ neuroendocrine tumor formation) Endoscopic biopsy
▫ ↑ gastric adenocarcinoma, ▪ Distinguish gastropathy from gastritis,
neuroendocrine tumors nonspecific; mucosal erosions, erythema,
▫ Damage limited to gastric fundus, body absence of rugae
▪ Infectious atrophic gastritis
RISK FACTORS ▫ Multifocal atrophy; gastric/duodenal
ulcers; erythematous, nodular mucosa;
Atrophic gastritis thickened rugal folds in early disease,
▪ Infectious loss of rugal folds in late disease;
▫ Household crowding; rural areas; poor damage limited to gastric antrum
sanitation ▪ Autoimmune atrophic gastritis
▪ Autoimmune ▫ Diffuse atrophy, absent rugae, mucosal
▫ Associated with HLA-DR3, B8, other thinning, visible submucosal blood
autoimmune diseases; more common in vessels
biologically-female individuals
H. pylori detection
▪ Serology, stool antigen test, urease breath
SIGNS & SYMPTOMS test, biopsy
▪ Atrophic gastritis
▪ May be asymptomatic ▫ H. pylori curved bacilli (hematoxylin,
▪ Epigastric pain, nausea, vomiting eosin; Giemsa; Warthin-Starry stain);
▪ Mucosal ulcers intraepithelial neutrophil, plasma cell
invasion
▪ Hemorrhage, hematemesis, melena
Other lab results
Autoimmune atrophic gastritis
▪ Autoimmune atrophic gastritis
▪ Iron deficiency anemia
▫ Anti-IF antibodies, anti-parietal cell
▫ Hypochlorhydria → dietary iron in
antibodies
ferric form → ↓ iron absorption → iron
deficiency ▫ ↑ serum gastrin: parietal cell loss →
achlorhydria → unrestricted gastrin
▪ Pernicious anemia (symmetrical neuropathy
secretion
predominantly affecting lower limbs)
▫ ↓ serum pepsinogen: gastric oxyntic
▫ Anti-intrinsic factor (IF) antibodies,
mucosa damaged → ↓ chief cells → ↓
↓ cobalamin (B12) absorption →
serum pepsinogen
depletion of 5-methyl-tetrahydrofolate
→ homocysteine cannot convert ▫ Lymphocytosis, eosinophilia, plasma
into methionine → impaired myelin cell invasion; oxyntic gland destruction;
regeneration → subacute combined metaplasia (intestinal, pyloric,
degeneration of spinal cord posterior pancreatic)
columns
▫ Weakness, paraplegia, paresthesias,
ataxia, loss of position/vibration sense
▫ Spasticity, clonus; atrophic glossitis;
fecal/urinary incontinence; diarrhea;
dementia
232 OSMOSIS.ORG
TREATMENT
MEDICATIONS
Remove offending agents
▪ NSAIDs, acids/alkalis
Eradicate H. pylori
▪ Triple therapy
▫ PPI + clarithromycin + amoxicillin (2
weeks)
▪ Quadruple therapy
▫ PPI + bismuth + metronidazole +
tetracycline (1 week)
Correct vitamin deficiencies

▪ For Autoimmune atrophic gastritis
chronic gastritis. The lamina propria contains
numerous plasma cells.
Figure 31.3 The histological appearance

of intestinal metaplasia, characterized by
the presence of goblet cells in the gastric
mucosa.
OSMOSIS.ORG 233
GASTROPARESIS
osms.it/gastroparesis

▪ Delayed gastric emptying, no mechanical ▪ Chronic nausea, vomiting
obstruction ▪ Early satiety, bloating
▪ Abdominal pain
CAUSES
▪ Most common cause
▫ Idiopathic/diabetes
DIAGNOSIS
▪ Iatrogenic (post-surgical/medication side DIAGNOSTIC IMAGING
effect), post-viral
▪ More common among individuals with Endoscopy, CT scan, MRI
T1DM than T2DM secondary to neuropathy ▪ Exclude mechanical obstruction
Gastric emptying scintigraphy
234 OSMOSIS.ORG
TREATMENT OTHER INTERVENTIONS

▪ Exercise; low fat diet
MEDICATIONS
▪ Metoclopramide (gastrointestinal prokinetic)
▪ Remove medications that may delay gastric
emptying
PEPTIC ULCER
osms.it/peptic-ulcer
PATHOLOGY & CAUSES

▪ Chronic mucosal ulceration of stomach/
duodenum extends into muscularis mucosa.
▪ Most common cause of upper
gastrointestinal bleeding; proximal
duodenum/gastric antrum
▪ Associated with chronic gastritis
▪ ↑ acid secretion, ↓ protective mechanisms
→ mucosal damage → ulceration
RISK FACTORS
▪ H. pylori infection (most common)
▫ ↑ gastric acid secretion, ↓ duodenal
HCO3 secretion
▪ NSAID Figure 31.4 An endoscopic view of the
▫ Particularly low dose aspirin gastric antrum which displays two discrete
corticosteroids ulcers.
▪ Physiologic stress
▫ Cushing’s ulcer (intracranial
hypertension), Curling ulcer (severe SIGNS & SYMPTOMS
burns)
▪ Psychological stress ▪ Up to 70% asymptomatic
▪ Hyperchlorydia ▪ Epigastric burning pain; may mimic
▪ Smoking myocardial infarction
▪ Chronic obstructive pulmonary disease ▫ Usually occurs few hours after meal,
(COPD) worsens at night
▪ Hypergastrinemia (Zollinger-Ellison ▫ Pain characteristically relieved by food/
syndrome) antacids
▪ Pain may radiate to back, chest, left/right
upper abdominal quadrants
▪ Nausea, vomiting, coffee-ground emesis,
bloating, weight loss
OSMOSIS.ORG 235
▪ Surgical emergency
▫ Hematemesis, melena, positive guaiac
test if slow bleed
▫ Acute abdomen; abdominal guarding,
peritonitis
▫ GI obstruction
▪ Gastric outlet obstruction, fistula formation
DIAGNOSIS
DIAGNOSTIC IMAGING
Abdominal CT scan
Barium abdominal radiography
Endoscopy
▪ Diagnostic, therapeutic Figure 31.5 A barium study demonstrating
the bullseye sign in a case of a gastric ulcer.
TREATMENT
MEDICATIONS
▪ Discontinue NSAIDs, avoid smoking
▪ PPI
SURGERY
▪ Endoscopic ligation/coagulation of bleeding
ulcers
236 OSMOSIS.ORG
NOTES
NOTES
GASTROINTESTINAL CANCERS

▪ Grading, TNM staging for treatment
PATHOLOGY & CAUSES ▫ T: characteristic of primary Tumor (e.g.
invasion of nearby tissue)
▪ Tumors arising from cells in gastrointestinal
▫ N: involvement of regional lymph Nodes
(GI) tract
▫ M: Metastasis; spread from primary
▪ Multifactorial etiology; generally result from
tumor to other body parts
aberrant cellular signaling, unregulated
cellular growth
▫ Genetic alterations (e.g. point mutations, LAB RESULTS
amplifications, rearrangements,
deletions) Biopsy
▫ Epigenetic influence (e.g. DNA ▪ Histopathological diagnosis
methylation, chromatin remodeling)
▫ Environmental factors (e.g. exposure to
carcinogens, chronic inflammation)
TREATMENT
▪ Risk increases with age MEDICATIONS
▪ Chemotherapy
SIGNS & SYMPTOMS
SURGERY
▪ Highly variable clinical presentation; see ▪ See individual disorders
individual disorders
▪ Fatigue, anorexia, weight loss
OTHER INTERVENTIONS
▪ Radiation therapy
DIAGNOSIS
DIAGNOSTIC IMAGING
Imaging studies
▪ Localization, staging
OSMOSIS.ORG 237
CARCINOID TUMOR
osms.it/carcinoid-tumor
cells
PATHOLOGY & CAUSES
▫ Commonly located in ileum; may arise
from Meckel’s diverticulum
▪ Uncommon, well-differentiated, slow-
growing neuroendocrine tumor; originates ▫ Potential for lymph node/hepatic
in tubular digestive tract; also found in metastasis
bronchopulmonary system, genitourinary ▪ Appendix
tract ▫ Originates from subepithelial endocrine
▪ Benign/malignant; tendency for liver cells
metastasis ▫ Relatively low potential for metastasis
▪ Carcinoid: tumors of different
Hindgut tumors
morphology, less aggressive than GI tract
adenocarcinomas; low grade (proliferative ▪ Rectum, colon, cecum (most common)
activity); low mitotic rate
COMPLICATIONS
TYPES ▪ Depend on tumor’s location, size, local
▪ Embryonic origin of GI tract (e.g. foregut, biochemical attributes
midgut, hindgut) ▫ Local/distant metastasis
▫ Pain: obstruction, intussusception,
Foregut tumors (e.g. stomach) bowel ischemia, mechanical pressure
▪ Type I from tumor
▫ Most common ▫ Desmoplasia: intense, local reaction
▫ Originates from enterochromaffin-like characterized by overproduction
(ECL) cells of extracellular matrix proteins +
▫ In association with high gastrin levels myofibroblast cell proliferation →
secondary to chronic atrophic gastritis fibrosis, obstruction
▫ Small, usually benign ▫ Carcinoid syndrome: tumor-related
▪ Type II humoral factors (e.g. serotonin,
histamine, etc.) → cutaneous flushing,
▫ Originates from ECL cells
pruritic rash; excessive lacrimation;
▫ In association with high gastrin levels wheezing; diaphoresis
induced by gastrinomas (e.g. Zollinger–
Ellison syndrome) in conjunction with
multiple endocrine neoplasia type 1 SIGNS & SYMPTOMS
(MEN1)
▫ Often large, indolent; low-grade ▪ Often asymptomatic, discovered
malignancy incidentally (e.g. imaging, surgery,
▪ Type III endoscopy)
▫ Not associated with high gastrin levels ▪ Vary according origin site
▫ Large, aggressive; local lymphatic/ ▫ Nonspecific, vague abdominal pain
hepatic metastases; produce serotonin ▫ Loss of appetite, vomiting, diarrhea,
(5-HT) constipation
Midgut tumors ▪ Desmoplasia (with CT scan)
▪ Small bowel (most common)
▫ Originates from intraepithelial endocrine
238 OSMOSIS.ORG
Chapter 32 Gastrointestinal Cancers
DIAGNOSIS TREATMENT
DIAGNOSITC IMAGING MEDICATIONS
▪ Somatostatin analogues suppress tumor
CT scan, MRI, labeled somatostatin recep-
proliferation, decrease symptoms
tor-based diagnostic imaging
▪ Localization, TNM staging
▪ Presence of hepatic lesions SURGERY
▪ Surgical removal of tumor
Endoscopy with biopsy
▪ Tumor visualization
▪ Histopathological analysis, grading
LAB RESULTS
▪ 5-hydroxyindoleacetic acid, chromogranin
Figure 32.2 Gross pathology of carcinoid

tumor of the terminal ileum.

carcinoid tumor of the lung.
MNEMONIC: CARCinoid
Carcinoid syndrome
components
Cutaneous flushing
Asthmatic wheezing
Right-sided valvular heart
lesions
Cramping and diarrhea
OSMOSIS.ORG 239
CHOLANGIOCARCINOMA
osms.it/cholangiocarcinoma
(IDH1)
PATHOLOGY & CAUSES ▪ Risk increases with age
▪ Slightly more common in individuals who
▪ Rare bile duct cancers; arise from epithelial
are biologically male
cells of intrahepatic, extrahepatic bile ducts
(not including gallbladder, ampulla of Vater)
▪ High fatality due to late diagnosis; highly COMPLICATIONS
proliferative ▪ Metastasis
▪ Mostly adenocarcinomas; minority ▫ Liver, lymph nodes, peritoneum, bone,
squamous cell carcinomas etc.
▪ Bowel perforation, bleeding
TYPES
▪ Determined by location (Bismuth–Corlette)
SIGNS & SYMPTOMS
Type I
▪ Located below confluence of left, right ▪ Often asymptomatic initially; malaise,
hepatic ducts weight loss, abdominal pain
▪ Extrahepatic disease (when bile drainage
Type II obstructed)
▪ Located at confluence ▫ Right upper quadrant pain, jaundice,
pruritus, dark urine, clay-colored stools,
Type IIIa weight loss
▪ Occludes common hepatic duct ▪ Intrahepatic disease
Type IIIb ▫ Dull right upper quadrant pain, malaise,
▪ Occludes right/left hepatic duct weight loss
▪ Other findings
Type IV ▫ Hepatomegaly, palpated mass
▪ Multicentric
RISK FACTORS
▪ Primary
▫ Existing liver, gallbladder disease:
primary sclerosing cholangitis (PSC);
chronic liver disease (e.g. viral hepatitis,
cirrhosis)
▪ Congenital abnormalities of biliary tree
▪ Genetic disorders
▫ Lynch syndrome; multiple biliary
papillomatosis
▪ Obesity
▪ Liver fluke infection (undercooked fish) a cholangiocarcinoma. There are normal
▪ Intrahepatic cholangiocarcinomas hepatocytes in the top left of the image, with
▫ Associated with mutations in gene the tumour occupying the bottom right of the
encoding isocitrate dehydrogenase 1 image.
240 OSMOSIS.ORG
DIAGNOSIS
▪ History, physical examination
▫ Consistent with hepatobiliary disease
DIAGNOSTIC IMAGING
MRI, CT scan, PET, etc.
▪ Detailed evaluation of lesion TNM staging
Transabdominal/endoscopic ultrasound
(EUS) with biopsy
▪ Biliary obstruction, dilation of intrahepatic
ducts
▪ Histolopathological analysis, grading

LAB RESULTS
cholangiocarcinoma. This image shows the
▪ Tumor markers tumor edge, with normal hepatocytes on the
▫ Carbohydrate antigen (CA) 19-9; right and tumor on the left. The tumor cells
carcinoembryonic antigen (CEA) form tubular structures and are surrounded
▪ Liver function tests by fibrosis.
▫ Consistent with biliary obstruction,
cholestasis
▫ Elevated transaminases, gamma- TREATMENT
glutamyl transpeptidase, alkaline
phosphatase
MEDICATIONS
▫ Prolonged prothrombin time/elevated
▪ Fluoropyrimidine-based chemoradiotherapy
INR
▪ Chemotherapy
▫ Elevated bilirubin
SURGERY
▪ Resection
OTHER INTERVENTIONS
▪ Radiation
OSMOSIS.ORG 241
COLORECTAL CANCER
osms.it/colorectal-cancer
▪ Black people of African descent
PATHOLOGY & CAUSES
▫ Highest rates in United States
▪ Common malignancy of large bowel/rectum ▪ More common in individuals who are
biologically male
▪ Third most common cancer worldwide
▪ Risk increases with age
▪ Often arises from colonic epithelial tissue
→ adenomatous polyp formation → ▪ Protective factors
adenocarcinoma ▫ Physical activity; regular use of aspirin,
▪ High metastatic potential after penetrating other nonsteroidal anti-inflammatory
muscularis mucosa drugs (NSAIDs)
RISK FACTORS COMPLICATIONS

▪ Hereditary ▪ Iron-deficiency anemia (due to bleeding)
▫ Familial adenomatous polyposis; ▪ Local, distant metastasis
Lynch syndrome, MUTYH-associated ▪ Bowel obstruction
polyposis ▪ Cachexia
▪ Inflammatory bowel disease ▪ Bowel perforation → peritonitis
▪ Lifestyle
▫ Smoking, physical inactivity
▪ Dietary
SIGNS & SYMPTOMS
▫ High alcohol consumption; processed ▪ May be asymptomatic initially
red meat; low consumption of fruits,
▪ Vague constitutional symptoms
vegetables
▫ Fatigue, anorexia, weight loss
▪ Obesity
▪ Change in bowel habits
▪ Diabetes mellitus, insulin resistance
▫ Narrowing of stool, constipation,
▪ Low socioeconomic status
diarrhea
▪ History of abdominal radiation
▪ Rectal bleeding
▪ Lack of screening colonoscopy
▫ Frank/occult
▪ Rectal pain, tenesmus (feeling of
incomplete defecation)
▪ Nausea, vomiting
▫ Bowel obstruction from advanced
malignancy
DIAGNOSIS
DIAGNOSTIC IMAGING
Colonoscopy/flexible sigmoidoscopy;
biopsy, CT colonography
▪ Tumor visualization, histopathological
Figure 32.5 Gross pathology of an exophytic analysis, grading, TNM staging, potential
colorectal carcinoma. for resection
242 OSMOSIS.ORG
TREATMENT
MEDICATIONS
▪ Chemotherapy
SURGERY
▪ Polypectomy with clear margins
▪ Surgical resection
▪ Sessile polyps: colectomy

OTHER INTERVENTIONS
adenocarcinoma of the colon. The tumor is
composed of malignant cells which continue ▪ Chemoradiation therapy
to form glandular structure. The left side of
the image displays normal colonic mucosa.
LAB RESULTS
▪ Tumor marker: CEA
▪ Stool guaiac testing
▫ Positive for occult blood
OTHER DIAGNOSTICS
Digital rectal exam
▪ Palpable mass if distal rectal mass
Figure 32.7 A CT scan in the axial plane Figure 32.8 Positron emission tomography
demonstrating a tumor in the cecum. with high levels of tracer accumulation in the
pelvis (rectal tumor) as well as the liver and
kidneys (metastases).
OSMOSIS.ORG 243
ESOPHAGEAL CANCER
osms.it/esophageal-cancer

▪ Rare malignancy of esophageal epithelium ▪ Asymptomatic initially; dysphagia; pyrosis;
▪ Squamous cell carcinoma (most common)/ retrosternal pain; weight loss
adenocarcinoma ▪ Late symptoms
▪ Commonly diagnosed when disease ▫ Coughing, chest discomfort when
advanced swallowing; hiccups if spread to
▪ Tendency for rapid metastasis diaphragm
CAUSES DIAGNOSIS
▪ Chronic exposure to irritants → metaplasia
→ dysplasia → malignant transformation DIAGNOSTIC IMAGING
EUS guided biopsy, CT scan, PET, integrat-
RISK FACTORS ed fluorodeoxyglucose (FDG)
▪ Smoking
▪ Alcohol (esp. combined with smoking) analysis, grading, TNM staging, potential
▪ Gastroesophageal reflux disease (GERD); for resection
reflux esophagitis, Barrett esophagus
▪ Hiatal hernia Bronchoscopy
▪ More common in individuals who are ▪ In carina identifies potential lung
biologically male involvement
OTHER DIAGNOSTICS
▪ Palpable supraclavicular lymphadenopathy
MNEMONIC: ABCDEF
Esophageal cancer risk
factors
Achalasia
Barret’s esophagus
Corrosive esophagitis
Diverticulitis
Esophageal web
Familial
COMPLICATIONS
▪ Esophageal obstruction; regurgitation Figure 32.9 Endoscopic appearance of an
→ aspiration → aspiration pneumonia; esophageal tumor. The tumor sits at the
metastasis gastroesophageal junction and is viewed
from above.
244 OSMOSIS.ORG
TREATMENT
MEDICATIONS
▪ Chemotherapy
SURGERY
▪ Resection of primary tumor, associated
nodes
OTHER INTERVENTIONS
▪ Radiation
Esophageal stenting
▪ Therapeutically enlarges esophageal lumen,
reduces dysphagia
Figure 32.10 A barium swallow

demonstrating a tumor distorting the normal
outline of the esophagus.
GALLBLADDER CANCER
osms.it/gallbladder-cancer
▫ Cholelithiasis (gallstones), primary
PATHOLOGY & CAUSES sclerosing cholangitis, porcelain
gallbladder, gallbladder polyps, biliary
▪ Uncommon malignancy; most frequently cysts; chronic infection (e.g. Salmonella
diagnosed cancer of biliary tract typhi, Helicobacter bilis)
▪ High fatality rate due to typically late ▪ More common in individuals who are
diagnosis biologically female
▪ Most gallbladder cancers arise within ▪ Obesity
fundus ▪ Cigarette smoking
▪ May obstruct bile flow at common bile duct/ ▪ Occupational exposure to carcinogens:
duodenum textile, oil, paper, chemical industries, radon
(mining)
RISK FACTORS ▪ Genetic predisposition
▪ Chronic gallbladder inflammation
OSMOSIS.ORG 245
COMPLICATIONS
▪ Biliary fistula
▪ Local/nodal/distant metastases
SIGNS & SYMPTOMS

▪ Often asymptomatic in early stages;
malignancy discovered incidentally after
symptoms mimic benign gallbladder
disease
▪ Non-specific symptoms Figure 32.11 Histological appearance of
▫ Malaise, pain, anorexia, nausea, gallbladder adenocarcinoma. The tumor
vomiting, weight loss cells show increased nuclear size, prominent
▪ Clinical manifestations (when bile drainage nucleoli and are forming tubular structures.
obstructed)
▫ Jaundice, dark urine
▪ Palpable gallbladder
TREATMENT
▪ Chemotherapy
DIAGNOSTIC IMAGING
SURGERY
EUS guided/percutaneous biopsy, CT scan,
▪ Simple/radical cholecystectomy
MRI, PET, MRCP
analysis, grading, TNM staging, potential OTHER INTERVENTIONS
for resection ▪ Radiation
LAB RESULTS
▪ Tumor markers: CA 19-9; CEA
▪ Liver function tests
▫ Consistent with biliary obstruction,
cholestasis
▫ Elevated transaminases, gamma-
glutamyl transpeptidase, alkaline
phosphatase
▫ Elevated bilirubin
246 OSMOSIS.ORG
HEPATOBLASTOMA
osms.it/hepatoblastoma

▪ Common primary childhood hepatic DIAGNOSTIC IMAGING
malignancy; arises from primitive hepatic
cells Ultrasound, percutaneous biopsy, CT scan
with/without contrast, MRI
▪ Usually occurs in right lobe of liver
▪ Diagnostic workup for tumor visualization,
▪ Morphologically diverse tumor: composed
histopathological analysis, grading,
of many cell types including embryonal
pretreatment staging system (PRETEXT);
hepatocytes, tissues (e.g. bone, striated
potential for resection
muscle)
▪ Extramedullary hematopoiesis may occur in
sinusoids LAB RESULTS
▪ Usually present during first two years of life ▪ Elevated alpha-fetoprotein (AFP)
▪ Genetic testing
RISK FACTORS
▪ Beckwith Wiedemann syndrome
▪ Trisomies 18, 21
▪ Familial adenomatous polyposis
▪ Type Ia glycogen storage disease
▪ Li–Fraumeni syndrome
biologically male
COMPLICATIONS
▪ Ectopic gonadotropin → precocious
puberty (uncommon)
▪ Fatal hepatic hemorrhage, rupture Figure 32.12 Histological appearance of
a hepatoblastoma, a tumor of immature
▪ Metastasis: commonly lungs
hepatocytes.
SIGNS & SYMPTOMS

TREATMENT
▪ Children
▫ Abdominal mass; discomfort MEDICATIONS
▪ Anorexia, weight loss, precocious puberty ▪ Chemotherapy
SURGERY
▪ Resection
OSMOSIS.ORG 247
HEPATOCELLULAR CARCINOMA
osms.it/hepatocellular-carcinoma

▪ Hepatic malignancy commonly diagnosed ▪ Often no symptoms aside from those of
in presence of chronic liver disease chronic liver disease
▪ Epigastric pain; appetite, weight loss
RISK FACTORS ▪ Palpable abdominal mass; manifestations
▪ Hepatitis B/C infection, coinfection with of decompensated cirrhosis (e.g.
hepatitis D splenomegaly, ascites, jaundice); hepatic
bruit
▪ Hereditary hemochromatosis
▪ Cirrhosis
▪ Smoking; frequent alcohol consumption
▪ Obesity
▪ Alpha-1 antitrypsin deficiency
▪ Gallstones
▪ Chronic exposure to aflatoxin (mycotoxin
found in peanuts, soybeans, corn)
biologically male
COMPLICATIONS
▪ Paraneoplastic syndrome: watery
diarrhea, hypoglycemia, hypercalcemia,
erythrocytosis; cutaneous lesions (e.g.
pemphigus foliaceus)
▪ Extrahepatic metastasis: commonly lymph Figure 32.13 An abdominal CT scan in
nodes, lungs, adrenal gland the axial plane demonstrating a massive
hepatocellular carcinoma.
MNEMONIC: ABC
Hepatocellular carcinoma DIAGNOSIS
etiology
Aflatoxins DIAGNOSTIC IMAGING
Hep B
Cirrhosis Ultrasound with biopsy, CT scan, MDCT,
arteriography, portography, MRI
Hepatocellular carcinoma
analysis, grading, TNM staging, potential
features
for resection
AFP increased: classic marker
Bile-producing: DDx from MRI angiography
cholangiocarcinoma ▪ 3D characterization of lesion, hepatic
Most Common primary liver circulation
tumor
248 OSMOSIS.ORG
LAB RESULTS
▪ Elevated aminotransferases, alkaline
phosphatase, gamma-glutamyl
transpeptidase; hyperbilirubinemia;
hypoalbuminemia
▪ Elevated alpha-fetoprotein (most common
serum marker)
Figure 32.14 Gross pathology of

hepatocellular carcinoma.
TREATMENT
MEDICATIONS
▪ Chemotherapy
▪ Systemic molecularly targeted therapy;
sorafenib, nivolumab
hepatocellular carcinima. The cells show
high nuclear variation, thickened nuclear SURGERY
envelopes and occasional prominent nucleoli. ▪ Partial hepatectomy
The cells also have abundant eosinophilic ▪ Liver transplant
cytoplasm.
OTHER INTERVENTIONS
▪ Radiofrequency ablation
▪ Percutaneous ablation with ethanol/acetic
acid
▪ Transarterial chemoembolization
▪ Cryoablation
▪ Radiation therapy; stereotactic body
radiation therapy
OSMOSIS.ORG 249
ORAL CANCER
osms.it/oral-cancer
COMPLICATIONS
PATHOLOGY & CAUSES ▪ Surgical resection → airway, speech,
mastication, cosmetic complications
▪ Oral cavity malignancy; arises from mucosal
▪ Metastasis
surfaces
▫ Lips, buccal mucosa, anterior tongue,
mouth floor, hard palate, gingiva, SIGNS & SYMPTOMS
retromolar trigone
▫ Most often: squamous cell carcinoma ▪ Asymptomatic initially
▪ May arise from normal mucosa/ ▪ Pain/burning sensation
premalignant lesions (e.g. erythroplakia,
▪ Lump/ulcer visualized, palpated
leukoplakia); undergo malignant
transformation ▪ Hard, fixed lymph nodes

▪ Tobacco (esp. with alcohol)
▪ Alcohol DIAGNOSTIC IMAGING
▪ Human papillomavirus (HPV) infection: CT scan/MRI
oropharynx
▪ Local spread/location of additional primary
▪ Periodontal disease tumors
▪ Chronic oral candidiasis
▪ Betel quid chewing
LAB RESULTS
▪ Immunosuppression
▪ Fine needle biopsy; histopathological
▪ Hepatitis C infection diagnosis
▪ Genetic polymorphisms: cytochrome P450
1A1 (CYPIA 1); glutathione S-transferase
mu 1 (GSTM1); alcohol dehydrogenase 3 OTHER DIAGNOSTICS
genotype → oropharyngeal cancers ▪ Palpation and visualization
▪ More common in individuals who are ▫ Of mucous membranes, oral cavity,
biologically male lymph nodes
▪ Flexible laryngoscopy
▫ Back of throat, vocal cords
MNEMONIC: PATH LAB
Oral cancer risks TREATMENT
Plummer-vinson syndrome
Alcohol MEDICATIONS
Tobacco ▪ Chemotherapy
Human papilloma virus
Leukoplakia SURGERY
Asbestos ▪ Resection
Bad oral hygiene
OTHER INTERVENTIONS
▪ Radiation
250 OSMOSIS.ORG
PANCREATIC CANCER
osms.it/pancreatic-carcinoma

▪ Highly lethal malignancy of exocrine DIAGNOSTIC IMAGING
pancreas
Transabdominal ultrasound
▪ Usually unresectable at presentation
▪ Detects degree of biliary tract dilation,
obstruction
RISK FACTORS
▪ Chronic pancreatitis ERCP
▪ Malignant transformation of pancreatic ▪ Increased visibility of pancreaticobiliary tree
intraductal papillary mucinous neoplasm
MRCP
(IPMN)
▪ Visualization of liver parenchyma, vascular
▪ Genetic mutations (e.g. BRCA-1, BRCA-2,
structures
ATM, PALB2, CDKN2A, MLH1)
▪ Smoking; obesity; sedentary lifestyle Laparoscopy
▪ Determines resectability
COMPLICATIONS
Abdominal CT scan; contrast-enhanced CT
▪ Hypercoagulability with possible venous/ scan, EUS guided/percutaneous biopsy
arterial thromboembolism
▪ Paraneoplastic manifestations analysis, grading, TNM staging
▫ Bullous pemphigoid; nodular fat necrosis
(pancreatic panniculitis)
▪ Metastasis
LAB RESULTS
▪ Tumor marker: CA 9-19
▪ Hyperbilirubinemia (mostly conjugated);
SIGNS & SYMPTOMS elevated alkaline phosphatase
▪ Recent onset of diabetes mellitus OTHER DIAGNOSITCS

▫ Tumor location Cardiac catheterization
▪ Pain ▪ Measure pressure in right side of heart
▫ Epigastric, abdominal, may radiate to
the back, may worsen after eating/when
lying down; asthenia:
TREATMENT
▪ Physical weakness, loss of strength; MEDICATIONS
anorexia, nausea; weight loss; jaundice,
▪ Chemotherapy with/without
dark urine
chemoradiotherapy
▪ Hepatomegaly; right upper quadrant mass;
Courvoisier’s sign (nontender, palpable
gallbladder at right costal margin); cachexia; SURGERY
metastasis: left supraclavicular/periumbilical ▪ Resection (e.g. pancreaticoduodenectomy)
lymphadenopathy, ascites, abdominal mass ▫ Only curative treatment
OSMOSIS.ORG 251
pancreatic adenocarcinoma. The tumor cells
Figure 32.16 Cytological preparation of form acini, small sack like spaces surrounded
a pancreatic fine needle aspirate which by malignant glandular cells.
demonstrates pancreatic adenocarcinoma.
The group on the left is the cancer, with large,
pleomorphic nuclei, which overlap with one
another. Contrast these with the smaller,
regularly spaced pancreatic ductal epithelial
cells on the right.
STOMACH (GASTRIC) CANCER

osms.it/stomach-cancer
common in high-risk populations
PATHOLOGY & CAUSES ▪ Intercellular adhesion molecules →
adherence of tumor cells → arrangement in
▪ Aggressive adenocarcinoma arising from glandular formations
gastric mucosa
RISK FACTORS
TYPES
▪ Primary cause (G-INT)
Diffuse type (G-DIF): undifferentiated ▫ H. pylori infection
▪ Impairment/lack of adhesion molecule ▪ Family history of gastric cancer
E-cadherin ▪ Autoimmune atrophic gastritis
▪ Genetic mutation (germline, somatic, ▪ Lifestyle
epigenetic methylation) of CDH1 gene ▫ Smoking, alcohol consumption
→ inactivation of CDH1 → nonfunctional
▪ Diet
E-cadherin → unregulated division
(impaired tumor suppressor function); ▫ Nitrates, nitrosamines, highly-salted
increased ability to spread, invade adjacent foods; pickled/smoked foods
structures ▪ Obesity
▫ Autosomal dominant inheritance pattern ▪ Risk increases with age
▫ More aggressive than G-INT ▪ More common in individuals who are
biologically male
Intestinal type (G-INT): well-differentiated
▪ Due to environmental factors; more
252 OSMOSIS.ORG
▪ Protective factors
▫ Intake of fruit, vegetables, fiber, folate
DIAGNOSIS
DIAGNOSTIC IMAGING
COMPLICATIONS
▪ Metastasis to liver, peritoneum, lymph Esophagogastroduodenoscopy with biop-
nodes, etc. sy, barium studies, abdominopelvic CT scan
▪ Paraneoplastic manifestations ▪ Tumor visualization, histopathological
analysis, grading, TNM staging, potential
▫ Seborrheic keratoses, polyarteritis
for resection
nodosa, Trousseau’s syndrome
(spontaneous, recurrent, migratory
venous thrombosis) OTHER DIAGNOSTICS
▪ Enlarged supraclavicular, anterior axillary,
periumbilical lymph nodes
▪ Palpable abdominal mass
Figure 32.18 Gross pathology of gastric

carcinoma. The stomach has been pinned
flat. The tumor is found in the antrum.
SIGNS & SYMPTOMS

▪ Asymptomatic initially
▪ Early symptoms
▫ Vague constitutional symptoms (e.g.
malaise, loss of appetite, dyspepsia)
▪ With disease progression
▫ Epigastric pain, nausea, vomiting,
dysphagia, weight loss Figure 32.19 The histological appearance of
▪ If GI bleeding a well-differentiated gastric adenocarcinoma
▫ Anemia, melena, coffee-ground of intestinal type. The tumor is composed of
hematemesis disordered glands, the cells of which have
▪ Pseudoachalasia syndrome (difficulty large, hyperchromatic nuclei.
moving food, liquids from esophagus to
stomach)
▫ If tumor extends to Auerbach’s
plexus/obstruction occurs near
gastroesophageal junction
OSMOSIS.ORG 253
SURGERY
TREATMENT ▪ Resection
MEDICATIONS
OTHER INTERVENTIONS
Chemotherapy ▪ Chemoradiotherapy
▪ G-INT, G-DIF differ in susceptibility to
chemotherapeutic agents
▪ Eradication of H pylori infection
WARTHIN'S TUMOR
osms.it/warthins-tumor

▪ Uncommon benign tumor; arises from ▪ Development of painless nodular mass,
salivary gland usually near mandible angle
▪ AKA papillary cystadenoma
lymphomatosum
▪ May involve submandibular/sublingual/ DIAGNOSIS
parotid gland (most common)
▪ Unilateral/bilateral, slow-growing
OTHER DIAGNOSTICS
▪ Easily palpable tumor
RISK FACTORS Fine needle aspiration

▪ Smoking ▪ Histopathological diagnosis
biologically male
TREATMENT
SURGERY
COMPLICATIONS ▪ Local resection/parotidectomy
▪ Malignant transformation (rare)
254 OSMOSIS.ORG
NOTES
NOTES
INFLAMMATORY BOWEL DISEASE

▪ Immune-mediated inflammatory bowel DIAGNOSTIC IMAGING
conditions ▪ Endoscopy
▪ More common in White people of Jewish
descent LAB RESULTS
▪ Usually presents in young people, 15–35 ▪ Biopsy
▪ Up to 25% of people with inflammatory
bowel disease have affected first-degree
relative TREATMENT
CAUSES MEDICATIONS
▪ Gut microbiome alterations ▪ Anti-inflammatory medications; antibiotics;
▪ “Western” style diet: high processing/ immunosuppressants
sugar/fat content
SURGERY
RISK FACTORS ▪ Surgical resection
▪ Crohn’s disease: smoking
▫ Smoking may be protective for OTHER INTERVENTIONS
Ulcerative colitis ▪ Dietary changes
SIGNS & SYMPTOMS

▪ Chronic diarrhea, frequently bloody/mucous
▪ Abdominal pain
▪ Fever, weight loss, anemia
▪ Extraintestinal manifestations
▫ Arthritis, uveitis
OSMOSIS.ORG 255
CROHN'S DISEASE
osms.it/crohns-disease
CAUSES
PATHOLOGY & CAUSES
▪ Unclear; mycobacterium paratuberculosis,
pseudomonas, listeria implicated
▪ AKA Crohn disease, regional enteritis
▪ Chronic, immune-related disorder →
excessive immune response to unknown SIGNS & SYMPTOMS
trigger → transmural inflammation
anywhere along gastrointestinal (GI) tract, ▪ Unpredictable patterns of flares, remissions
mouth to anus
▪ Abdominal pain; most common in right
▪ Compare to ulcerative colitis lower quadrant (ileal inflammation)
▫ Only affects colon, rectum; superficial ▪ Fatigue, fever, nausea, vomiting
lesions; autoimmune disorder where
▪ Chronic diarrhea; may/may not be bloody
tissue is directly attacked by immune
system ▫ Gross bleeding rare; upon microscopy,
bleeding common
▪ Frameshift mutation in nucleotide-binding
oligomerization domain-containing protein ▪ Malabsorption, weight loss, vitamin
2 (NOD2)/ caspase recruitment domain- deficiencies
containing protein 15(CARD15) ▪ Up to 20% of cases present with
▫ Excessive inflammatory response → inflammatory eye, skin, joint lesions
tissue damage ▫ Uveitis, erythema nodosum, pyoderma
▪ Unknown immune response trigger → T gangrenosum, cholelithiasis (impaired
helper (Th) 1 cells release inflammatory bile reabsorption), arthritis
cytokines ▪ Perianal abscesses, phlegmon, fistulae
▫ Interferon (IFN) gamma, tumor necrosis ▫ Perianal fistulas (up to 30%)
factor (TNF) alpha → inflammatory ▫ Enterovesical fistulae → recurrent UTI,
response → cytokines recruit pneumaturia
macrophages → further inflammatory ▫ Enteroenteric fistulae → asymptomatic
mediators released (proteases, platelet ▫ Enterovaginal fistulae → passage of
activating factor, free radicals) → fecal matter through vagina
further inflammation → healthy tissue
▫ Enterocutaneous fistulae → draining of
destroyed → inflammatory cells invade
bowel contents unto skin
intestinal mucosa → ulcer, granuloma
form → transmural inflammation → ▪ Intestinal obstruction (up to 30%)
intestinal lumen; fistula formation,
narrowing
▪ Fistula, stricture formation
▫ Serosal layer involvement → fistula
▫ Most common: enterovesical,
enterocutaneous, enterovaginal,
enteroenteric fistulae
▪ Scattered inflammation → cobblestone
appearance
▪ Most commonly affects terminal ileum,
colon
Figure 33.1 Pyoderma gangrenosum on the
leg of an individual with Crohn’s disease.
256 OSMOSIS.ORG
Chapter 33 Inflammatory Bowel Disease
MNEMONIC: CHRISTMAS
Features of Crohn’s disease
Cobblestones
High temperature
Reduced lumen
Intestinal fistulae
Skip lesions
Transmural: all layers, may
ulcerate
Figure 33.3 Gross pathology of a resected
Malabsorption
colon involved by Crohn’s disease. The
Abdominal pain severe and prolonged inflammation has led
Submucosal fibrosis to a cobblestone appearance of the colonic
mucosa.
DIAGNOSIS
TREATMENT
DIAGNOSTIC IMAGING
▪ Endoscopy MEDICATIONS
▪ Anti-inflammatory medications →
LAB RESULTS sulfasalazine
▪ Biopsy ▫ For colonic symptom management
▫ Cobblestone appearance, intermittent ▪ Antibiotics → metronidazole
lesion pattern, pseudopolyps, aphthous ▫ Reduce bacterial overgrowth, anti-
ulcers inflammatory effect
▪ Immunosuppressants → prednisone,
azathioprine
OTHER DIAGNOSTICS
▫ Only if no response to antibiotics
▪ Barium enema
▪ Antidiarrheals
▪ Methotrexate, anti-TNF agents
▫ Refractory disease
SURGERY
▪ Surgical removal of affected tissue
▫ High relapse rate
▫ Short bowel syndrome: complication of
resection
OTHER INTERVENTIONS
▪ Nutritional supplementation, support

Crohn’s disease. The lamina propria is
expanded by chronic inflammatory cells and
there is a non-caseating granuloma present.
OSMOSIS.ORG 257
MICROSCOPIC COLITIS
osms.it/microscopic-colitis

▪ Idiopathic chronic inflammation of colon → DIAGNOSTIC IMAGING
watery diarrhea
Endoscopy
▪ Associated with celiac disease,
autoimmune diseases, NSAIDs, smoking ▪ Non-specific findings, normal mucosa
biologically female LAB RESULTS
▪ Unknown trigger → abnormal collagen ▪ Biopsy of colonic mucosa
metabolism → dysfunctional epithelium ▫ Inflammatory changes in lamina propria,
→ alteration in barrier function → mucosal intraepithelial lymphocytic infiltration,
inflammation → decreased sodium dense subepithelial collagenous layer
absorption, increased chloride secretion → ▪ Elevated inflammatory markers
secretory diarrhea (nonspecific)
▫ Erythrocyte sedimentation rate,
TYPES myeloperoxidase
▪ Autoantibodies
Collagenous
▫ Anti-thyroid peroxidase (TPO),
▪ More common in older individuals who are
antinuclear (ANA), antineutrophil
biologically female
cytoplasmic (ANCA), anti
▪ Dense subepithelial collagenous layer; Saccharomyces cerevisiae (ASCA),
increased intraepithelial lymphocytes, rheumatoid factor (RF)
inflammatory infiltrate in lamina propria
Lymphocytic
TREATMENT
▪ Increased intraepithelial lymphocytes,
inflammatory infiltrate in lamina propria MEDICATIONS
▪ Avoid NSAIDs, other medications
SIGNS & SYMPTOMS associated with microscopic colitis
▪ Antidiarrheals
▪ Abdominal pain ▫ Loperamide, bismuth salicylate
▪ Chronic watery diarrhea ▪ Corticosteroids
▪ No weight loss ▫ Budesonide, prednisone
▪ Fecal urgency, incontinence ▪ Bile acid sequestrants
▪ Anemia ▫ Cholestyramine
SURGERY
▪ Surgical resection (ileostomy)
258 OSMOSIS.ORG
Figure 33.4 Histological appearance Figure 33.5 Histological appearance of

of collagenous colitis. The subepithelial lymphocytic colitis. There is an increase in
basement membrane is markedly thickened. the number of intraepithelial lymphocytes
(>20/100 epithelial cells).
PROTEIN LOSING ENTEROPATHY

osms.it/protein-losing-enteropathy

▪ Inflammatory GI conditions → loss of serum ▪ Hyponatremia, peripheral edema, ascites
proteins into GI tract ▪ Serosal effusions (pleural and pericardial)
▪ Mucosal injury → epithelial inflammation, ▫ Dyspnea, cough, chest pain
→ mucosal permeability → protein ▪ Steatorrhea, bloating, flatulence, abdominal
exudates across epithelium → proteins in pain
GI tract degraded into amino acids (AA)
▪ Weight loss, chronic diarrhea
▪ Lymphatic obstruction/venous stasis
→ increased hydrostatic pressure in
lymphatics → lymph leaks into intestinal DIAGNOSIS
lumen → reduced chylomicron reabsorption
→ decrease in fat soluble vitamins → LAB RESULTS
protein deficiency
▪ Consider in individuals with edema,
hypoalbuminemia
CAUSES ▪ Increase in alpha-1 antitrypsin clearance
▪ Inflammatory bowel disease ▪ Exclude other causes of hypoproteinemia
▫ Crohn’s disease, ulcerative colitis ▫ Renal disease → proteinuria
▪ Malabsorptive diseases ▫ Hepatic disease → impaired protein
▫ Tropical sprue, celiac sprue synthesis
▪ Infectious diseases ▫ Malnutrition
▫ C. difficile → pseudomembranous colitis
▪ GI malignancies
TREATMENT
OTHER INTERVENTIONS
▪ Low fat, high protein diet; supplement
medium chain triglycerides (MCT)
OSMOSIS.ORG 259
ULCERATIVE COLITIS
osms.it/ulcerative-colitis
MNEMONIC: ULCERATIONS
PATHOLOGY & CAUSES Features of Ulcerative colitis
Ulcers
▪ Autoimmune disease → superficial ulcer
formation; continuous, circumferential Large intestine
inflammation in colonic, rectal mucosa Carcinoma (risk of)
▪ Most common inflammatory bowel disease; Extraintestinal manifestations
may present at any age Remnants of old ulcers
▪ Compare to Crohn’s disease (pseudopolyps)
▫ Usually affects young people, affects Abscesses in crypts
entire GI tract; causes transmural Toxic megacolon (risk of)
inflammation; patches of inflamed Inflamed, red, granular mucosa
mucosa, cobblestone appearance Originates at rectum
▪ CD8+ cell activation → destruction of cells Neutrophil invasion
in mucosal, submucosal colonic layers
Stool is bloody
▫ Associated with perinuclear anti-
neutrophil cytoplasmic antibodies
(p-ANCAs)
▪ Multifactorial origin SIGNS & SYMPTOMS
▫ Environmental stimuli + excessive
sulfide-producing bacteria + genetic ▪ Acute flares, remissions; gradual onset
predisposition ▫ Risk of relapse related to person’s age at
▪ More common among white people, diagnosis
especially of Eastern European descent ▪ Severity determined by frequency of bowel
▪ More common in young individuals who are movements, degree of inflammation,
biologically female systemic symptoms
▪ Colicky, left lower quadrant pain
CAUSES ▪ Diarrhea; frequently grossly bloody, mucous
▪ Unclear; autoimmune reaction against ▪ Rectal tenesmus, incontinence, urgency,
colonic flora, molecular mimicry, increased bleeding
sulfide production implicated ▫ Tenesmus: Latin teinesmos; to strain
▪ Environmental factors contribute to acute ▪ Fever, fatigue, weight loss, anemia,
flares dehydration
▪ Extraintestinal manifestations
COMPLICATIONS ▫ Arthritis (most common); uveitis;
erythema nodosum; pyoderma
▪ Toxic megacolon, anal fissures, perirectal
gangrenosum; primary sclerosing
abscess
cholangitis; arterial, venous
thromboembolisms
260 OSMOSIS.ORG
DIAGNOSIS
▪ > four weeks active diarrhea +
inflammatory findings on endoscopy +
chronic inflammatory changes on biopsy
▪ Biopsy
▫ Crypt abscesses
LAB RESULTS
▪ Anemia
▪ Elevated inflammatory markers
Figure 33.6 A pancolectomy specimen from
▫ Erythrocyte sedimentation rate (ESR), an individual with ulcerative colitis.
C-reactive protein (CRP)
OTHER DIAGNOSTICS
▪ Clinical diagnosis; exclude other causes of
colitis
▫ Infections (e.g. parasites, Clostridium
difficile), STIs, radiation, medications
TREATMENT
MEDICATIONS
▪ Anti-inflammatory medications
▫ Sulfasalazine, mesalamine
▪ Immunosuppressors
▫ Corticosteroids, azathioprine,
cyclosporine
▪ TNF blocking agent
SURGERY
▪ Colectomy only if disease localized Figure 33.7 Abdominal radiograph
demonstrating toxic megacolon, a
complication of ulcerative colitis.
Figure 33.8 The clinical appearance

of erythema nodosum; a cutaneous
manifestation of inflammatory bowel disease.
OSMOSIS.ORG 261
active ulcerative colitis in a colonic biopsy.
There is active inflammation causing crypt
destruction. Cryptitis and crypt abscesses are
also present.
262 OSMOSIS.ORG
NOTES
NOTES
INTESTINAL DISEASES

▪ Diseases preventing adequate digestive ▪ See individual diseases
system function
▫ Often involve inflammation, stasis,
obstruction, necrosis MNEMONIC: APPENDICITIS
▪ Various structural, functional etiologies Right lower-quadrant pain
common differential
Appendicitis/ Abscess
SIGNS & SYMPTOMS Pelvic inflammatory disease
(PID)/ Period pancreatitis
▪ Abdominal symptoms etiologically- Ectopic/ Endometriosis
dependent Neoplasia
▪ Abdominal pain, distension, constipation, Diverticulitis
bowel-habit change, hematochezia,
Intussusception
nausea, vomiting
Crohn’s Disease/ Cyst (ovarian)
▪ Bulging abdominal mass (in hernia)
IBD
Torsion (ovary)
DIAGNOSIS Irritable Bowel Syndrome
Stones
DIAGNOSTIC IMAGING
▪ CT scan, MRI, ultrasound
OTHER DIAGNOSTICS
▪ Right lower-quadrant pain common
differential (see mnemonic)
OSMOSIS.ORG 263
APPENDICITIS
osms.it/appendicitis

▪ Lumen obstruction → vestigial vermiform ▪ Abdominal pain
appendix inflammation ▫ Often begins in umbilical area →
▪ Located at cecum base (near ileocecal McBurney’s point (abdomen’s right
valve) lower-quadrant; one-third distance from
▪ Obstruction → intraluminal content anterior superior iliac spine, umbilicus)
stasis → ↑ luminal, intramural pressure → progressive inflammation
→ thrombosis, occlusion small vessels, ▫ Rovsing’s sign: left lower-quadrant
lymphatic flow stasis → ischemia, necrosis palpated → right lower-quadrant pain
▪ Excessive multiplication (gut flora) behind ▫ Psoas sign: right leg extended in left-
obstruction → immune system response side position → retrocecal appendix
→ fibropurulent reaction → parietal ▫ Obturator sign: right leg internally
peritoneum irritation rotated in supine position → pelvic
▪ Visceral nerve fiber stimulation → appendix
abdominal pain ▪ Fever, anorexia, nausea, vomiting, diarrhea/
constipation
CAUSES ▪ In case of peritonitis
▪ Obstruction ▫ Rebound tenderness at McBurney’s
▫ Lymphoid hyperplasia (adolescence, point
viral infection), fecalith, foreign body ▫ Abdominal guarding (peritoneal
(e.g. undigested seeds), pinworm irritation)
infection, tumor (benign, malignant)
DIAGNOSIS
RISK FACTORS
▪ 10–30 years old, family history, biologically- DIAGNOSTIC IMAGING
male, cystic fibrosis comorbidity (children)
CT scan with IV contrast
COMPLICATIONS ▪ Increased appendix diameter
▪ Appendix-supplying vessel compression ▪ Increased wall enhancement
→ ischemia → appendix wall necrosis ▪ Severe
→ bacterial invasion (wall) → appendix ▫ Visible abscess, pus spillage
rupture → bacterial invasion (peritoneum)
→ peritonitis Ultrasound (pregnancy, children)
▪ Periappendiceal abscess, subphrenic ▪ Visible, noncompressible, dilated appendix
abscess, pylephlebitis, portal venous ▪ ↑ blood flow in appendix wall
thrombosis, sepsis ▪ Visible appendicolith
▪ Right iliac fossa fluid collection
264 OSMOSIS.ORG
Chapter 34 Intestinal Diseases
LAB RESULTS
▪ Neutrophilic leukocytosis
▫ ↑ with progression
▪ Mildly elevated serum bilirubin
▫ Perforation marker
TREATMENT
MEDICATIONS
▪ Antibiotics
▪ IV fluids, no food/water orally (NPO)
Figure 34.1 Camera view of a laparoscopic
SURGERY appendicectomy being performed. The
appendicectomy has been performed and
▪ Removal (appendectomy)
the stump is visible on the right of the image,
▪ Abscess drainage with the severed appendix reflected laterally.
DIVERTICULITIS
osms.it/diverticulitis

▪ Inflamed diverticula; microperforation of ▪ Left lower-quadrant pain (often sigmoid
diverticulum colon); palpable abdominal mass; diarrhea/
constipation; nausea; vomiting; fever;
urinary urgency/frequency/dysuria (inflamed
CAUSES sigmoid colon → bladder irritation)
▪ Increased intraluminal pressure → erosion
→ inflammation, focal necrosis → micro/
macro perforation DIAGNOSIS
RISK FACTORS DIAGNOSTIC IMAGING
▪ Diverticula present
CT scan with contrast
▪ Inflammation → hyperdense tissue
COMPLICATIONS
▪ Stricture, intestinal obstruction Abdominal X-ray
▪ Diverticulum perforation ▪ Bowel obstruction
▫ Abscess, peritonitis ▪ Bowel perforation
▪ Fistula formation ▫ Free air
▫ Bladder communication
▫ Other organ communication (vagina, LAB RESULTS
skin, other parts of bowel) ▪ Leukocytosis
▫ Vesicoenteric fistula: pneumaturia (air in
urine), fecaluria (stool in urine)
OSMOSIS.ORG 265
TREATMENT
MEDICATIONS
▪ Uncomplicated
▫ Antibiotics, fluids, no food/water orally
(NPO)
SURGERY
▪ Resection
▫ Severe case/recurrence/complication
Figure 34.2 Gross pathology of sigmoid
diverticulosis. Notice how the diverticula
OTHER INTERVENTIONS appear either side of the longitudinal muscle.
▪ High-fiber diet
▫ Prevents recurrence
DIVERTICULOSIS
osms.it/diverticulosis
(some areas) → mucosa/submucosa
PATHOLOGY & CAUSES herniation predisposed → diverticulum
formation
▪ Diverticulum (plural diverticula): ▫ Sigmoid colon: smallest diameter →
outpouching of hollow anatomical structure highest pressure (Laplace’s Law:
wall P∝1/D), most common location
▫ Most frequent in large intestine ▪ Outpouching: tend to form where intestinal
(particularly sigmoid colon) wall-supplying blood vessels (i.e. vasa
▪ Diverticulosis: multiple diverticula present recta) traverse muscle layer
TYPES RISK FACTORS

True diverticulum ▪ Lifestyle: low-fiber diet, constipation; fatty
food, red meat-rich diet; inactivity; smoking
▪ All organ wall layers included (e.g. Meckel’s
diverticulum) ▪ ↑ age ↑ risk
▪ Biologically-male
False (pseudo-) diverticulum ▪ Family history
▪ Only mucosa, submucosa layers included ▪ Obesity
▫ Most common ▪ Connective tissue disorders
▫ Colonic diverticula ▫ Marfan syndrome
▫ Ehlers–Danlos syndrome
CAUSES ▫ Autosomal dominant polycystic kidney
▪ Multifactorial pathogenesis from abnormal disease
colonic motility
▪ Abnormal/exaggerated smooth muscle
contractions → unequal intraluminal
pressure distribution → high pressure
266 OSMOSIS.ORG
COMPLICATIONS
▪ Blood vessel surrounding weakened
TREATMENT
outpouching ruptures → large intestine
blood loss → bloody stool
SURGERY
▪ Resection (if complications develop)
▪ Inflammation (diverticulitis)
▪ Segmental colitis
OTHER INTERVENTIONS
▪ Lifestyle changes
SIGNS & SYMPTOMS ▫ Diet (↑ fiber intake), avoid constipation, ↑
physical activity, smoking cessation
▪ Vague abdominal pain, tenderness, bloating
▪ Occasional cramping
▪ Altered bowel habit (diarrhea/constipation)
▪ Rectal bleeding (hematochezia—fresh
blood in stool)
DIAGNOSIS
▪ Often found incidentally
DIAGNOSTIC IMAGING
X-ray with barium enema
▪ Lower gastrointestinal series
▪ Directly shows pouches
CT scan Figure 34.3 Barium study demonstrating

▪ Visualization of colonic diverticula, multiple diverticula.
thickening of the bowel wall thickening (>
4mm), an increase in soft tissue density
within pericolonic
OTHER DIAGNOSTICS
Colonoscopy, sigmoidoscopy
▪ Visible outpouching
OSMOSIS.ORG 267
FEMORAL HERNIA
osms.it/femoral-hernia
▪ Abdominal contents enter hernia → may
PATHOLOGY & CAUSES precipitate intestinal obstruction
▫ Most common cause worldwide
▪ Intestinal projection across femoral canal
associated with femoral artery, vein; below ▫ Incarcerated/strangulated; severe
inguinal ligament, lateral to pubic tubercle abdominal pain, tenderness, erythema,
fever, nausea, vomiting
CAUSES
▪ Congenital, acquired DIAGNOSIS
▪ Weakness/abnormal fascial opening in
abdominal wall DIAGNOSTIC IMAGING
▪ Usually includes properitoneal fat/omentum
Ultrasound
edge/small bowel loop
▪ Variable echogenicity of tissue; movement
of intra-abdominal structures in an inferior
RISK FACTORS direction through the femoral canal
▪ Biologically-female, congenital disorder
(embryological development → processus CT scan
vaginalis obliteration failure), hernia (family ▪ Visualization of characteristic funnel-
history), obesity, pregnancy, frequent heavy shaped neck; protrusion through femoral
lifting ring
▪ Narrow femoral canal
▫ ↑ incarceration/strangulation risk SURGERY
▪ Compression of femoral vein ▪ Repair
▪ Bowel obstruction ▫ Open/laparoscopic (case-dependent)
▪ Early/elective repair
SIGNS & SYMPTOMS ▫ Uncomplicated, asymptomatic hernia

▪ Urgent repair
▪ Asymptomatic (commonly) ▫ Complicated hernia (may require bowel
resection)
▪ Can manifest intestinal obstruction
symptoms
▫ Bulging mass, pain, discomfort
▫ Supine: may resolve
▫ Valsalva maneuver (coughing/straining):
worsens
268 OSMOSIS.ORG
GALLSTONE ILEUS
osms.it/gallstone-ileus
Effect on intestinal wall
PATHOLOGY & CAUSES
▪ Simple: no blood supply impairment
▪ Gastrointestinal motility (peristalsis) ▪ Strangulated: blood supply cut off to bowel
disruption → impaired bowel content section
propulsion ▪ Closed loop: obstruction occurs at each end
▪ Blockage → progressive intestine dilation of bowel section
blockage-proximal, decompression Type of factor
blockage-distal
▪ Mechanical: obstruction caused by
▪ Gas accumulation (swallowed air, bacterial gallstone, neoplasm, adhesion, stricture,
fermentation) → ↑ bowel distention hematoma, meconium (in cystic fibrosis),
▪ Bowel wall edema → ↓ bowel content medical device migration (PEG tube)
absorption → luminal fluid sequestration ▪ Functional: intestinal musculature
▪ ↑ capillary permeability → transudative fluid paralysis caused by trauma (surgery, blunt
loss from intestinal lumen into peritoneal abdominal trauma), peritonitis, medication
cavity (opiates, anticholinergics)
▪ Emesis → fluid, electrolyte (Na, K, H, Cl)
loss → metabolic alkalosis, hypovolemia
RISK FACTORS
▪ Bowel dilation continues → ↓ intestinal
▪ Surgery; bowel manipulation, anesthesia,
wall tissue perfusion → ischemia, necrosis,
postoperative opioids
bowel perforation
▪ Hernia, neoplasm history, abdominal/pelvic
irradiation, chronic inflammation, abdominal
TYPES trauma
Onset
▪ Acute: factors such as torsion, COMPLICATIONS
intussusception → sudden onset ▪ Fluid/electrolyte/acid-base imbalance;
▪ Chronic: factors such as tumor growth → bowel strangulation, necrosis; perforation;
prolonged onset sepsis
▪ Recurrent: often caused by adhesions →
intermittent obstructions
SIGNS & SYMPTOMS
Extent
▪ Partial: some of intestinal lumen remains ▪ Abdominal distension, cramping pain,
open constipation, nausea, vomiting
▪ Complete: total lumen obstruction ▪ Dehydration: tachycardia, dry mucous
membranes, ↓ urine output
Location ▪ Bowel sounds
▪ Intrinsic: obstruction within bowel ▫ High-pitched “tinkling” sound
wall—e.g. inflammatory stricture, edema, auscultated: acute mechanical bowel
hemorrhage, foreign body (ingested, obstruction
parasite accumulation, large biliary calculus) ▫ Muffled, hypoactive bowel sounds:
▪ Extrinsic: obstruction outside bowel wall— significant bowel distention association
e.g. torsion, compression (hernia) ▪ Abdominal percussion: hyperresonance/
tympany
OSMOSIS.ORG 269
DIAGNOSIS
DIAGNOSTIC IMAGING
X-ray
▪ Small intestine, colon distension
TREATMENT
SURGERY
▪ Surgical intervention: e.g. release
adhesions, complete obstructions, repair
bowel
OTHER INTERVENTIONS
Figure 34.4 A CT scan of the abdomen and
▪ No food/water orally (NPO)
pelvis in the coronal plane demonstrating
▪ Fluid, electrolyte replacement a gallstone in the terminal ileum. If so large
▪ Parenteral feeding → nasogastric that it is unable to pass through the ileocecal
decompression valve, the gallstone will cause small bowel
obstruction.
GASTROENTERITIS
osms.it/viral-gastroenteritis
▪ Viral contact
PATHOLOGY & CAUSES ▫ E.g. daycare center, cruise ship, closed
community outbreak; contaminated
▪ Gastrointestinal tract viral infection (lasts food/water
12 hours–3 days)
▪ Primary transmission
▫ Oral–fecal route
COMPLICATIONS
▪ Severe dehydration → altered mental
▪ Viruses → epithelium damage → osmotic
status, weight loss
diarrhea (> three stools daily), vomiting
CAUSES SIGNS & SYMPTOMS

▪ Children: rotavirus (most common)
▪ Adult: norovirus (most common), astrovirus, ▪ Watery diarrhea; nausea; vomiting;
adenoviruses abdominal cramps, pain; fever; malaise;
dehydration (dry lips, skin turgor,
tachycardia)
RISK FACTORS
▪ ↑ morbidity
▫ Children, elderly, immunocompromised
individuals
270 OSMOSIS.ORG
DIAGNOSIS
LAB RESULTS
▪ Stool sample
▫ Excludes bacterial/parasitic etiology
▪ ↑ C-reactive protein (CRP), ↑ leukocytes
▪ Polymerase chain reaction (PCR)
▫ Stool, vomit: enzyme-linked
immunosorbent assay (ELISA)
performed for rotavirus
TREATMENT
Figure 34.5 A scanning electron micrograph
of a cluster of Norwalk virus capsids. OTHER INTERVENTIONS
▪ Fluid replacement
Prevention
▪ Hygiene practices, rotavirus vaccine
INGUINAL HERNIAS
osms.it/inguinal-hernias
▫ Testicular descent path: covered
PATHOLOGY & CAUSES by three layers of spermatic fascia
(three layers); external spermatic
Direct inguinal hernia fascia (external oblique muscle fascia
▪ Peritoneal sac; projects directly through continuation); cremasteric muscle
inguinal triangle (AKA Hesselbach’s fascia; internal spermatic fascia (internal
triangle) oblique muscle fascia continuation)
▪ Projects medially to inferior epigastric
vessels, lateral to rectus abdominis, pierces CAUSES
parietal peritoneum
▪ Hesselbach’s triangle composition: inguinal Indirect inguinal hernia
ligament (AKA Poupart’s ligament), rectus ▪ Processus vaginalis closure failure (i.e.
abdominis muscle (lateral border), inferior internal inguinal ring and processus
epigastric vessels vaginalis obliteration failure)
▪ Covered by external spermatic fascia
Indirect inguinal hernia RISK FACTORS

▪ Most common hernia Direct inguinal hernia
▪ Intestinal projection through internal ▪ Acquired, affects transversalis fascia
inguinal ring
▫ Chronic intra-abdominal pressure ↑ (e.g.
▫ Location: spermatic cord (biologically- obesity, chronic cough, constipation,
male), round ligament (biologically- heavy lifting—occupational/recreational)
female) exit the abdomen
▪ Abdominal wall musculature atrophy
OSMOSIS.ORG 271
(aging)
▪ Older, biologically-male individuals
DIAGNOSIS
Indirect inguinal hernia DIAGNOSTIC IMAGING
▪ Biologically-male individuals > biologically- Ultrasound
female individuals
▪ Direct inguinal hernia
▫ Biologically male: late right testicle
▫ Variable echogenicity of tissue;
descent
movement of intra-abdominal structures
▫ Biologically female: asymmetric pelvis in an anterior direction through the
Hesselbach triangle
COMPLICATIONS ▪ Indirect inguinal hernia
▫ Visualization through abdominal wall in
Direct inguinal hernia
biologically-female individuals
▪ Incarceration/strangulation potential
CT scan
Indirect inguinal hernia
▪ Direct inguinal hernia
▪ Can form hydrocele
▫ Visualization of a protrusion with
▪ May precipitate intestinal obstruction compressing inguinal canal contents;
▪ Most common cause worldwide inguinal canal pushed into a semicircle
of tissue that resembles a moon
crescent
SIGNS & SYMPTOMS ▪ Indirect inguinal hernia
▫ Identifies occult hernia/complications;
▪ May be asymptomatic hernia neck visualized superolateral to
▪ Bulging mass (indirect inguinal hernia, the inferior epigastric vessels
mass in groin), pain, discomfort
▫ Valsalva maneuver cessation/prone: may
resolve
OTHER DIAGNOSTICS
▪ Indirect inguinal hernia
▪ Valsalva maneuver: worsens projection
▫ History, clinical exam; sufficient for
▫ Coughing/straining
majority of suspected inguinal hernias
Direct inguinal hernia
▪ May precipitate intestinal obstruction
▫ Most common cause worldwide
▫ Incarcerated/strangulated: severe
abdominal pain, tenderness, erythema,
fever, nausea, vomiting
Indirect inguinal hernia

▪ Visible bulge
▫ May be unapparent in biologically-
female individuals
▪ Incarcerated/strangulated
▫ Severe abdominal pain, tenderness,
erythema, fever, nausea, vomiting
Figure 34.6 Intraperitoneal view of an

inguinal hernia during a laparoscopic hernia
repair. The peritoneal cavity extends into the
inginal canal, lateral to the epigastric vessels,
making this an indirect hernia.
272 OSMOSIS.ORG
TREATMENT
SURGERY
Repair
▪ Open/laparoscopic (case-dependent)
▪ Elective repair
▫ Symptomatic hernias
▪ Direct inguinal hernia (asymptomatic)
▫ Monitor, surgical repair preferred
Figure 34.8 A CT scan in the coronal plane

Figure 34.7 Clinical appearance of a hernia demonstrating an indirect inguinal hernia.
in the groin. It is often not possible to The proximal bowel is dilated, indicating a
distinguish between a direct and indirect strangulated hernia causing obstruction.
hernia on clinical examination alone.
INTESTINAL ADHESIONS
osms.it/intestinal-adhesions
▪ Injury prevents enzyme secretion →
PATHOLOGY & CAUSES macrophages, fibroblasts deposit collagen
into adhesion → permanent
▪ Fibrous tissue bands form physical
attachment between intestines → ↓
intestinal motility CAUSES
▪ Formed from scarred, post-trauma tissue ▪ Surgery (most common), inflammation
(cholecystitis, pancreatitis, peritonitis),
▪ Tissue injury → inflammation → fibrin
endometriosis, pelvic inflammatory disease
deposits → fibrin connects parts left (similar
to reconstructive “glue”)
▪ Adhesions extend between tissue if both COMPLICATIONS
parts have been injured, close proximity ▪ Bowel obstruction, intestinal wall volvulus/
▪ Initial fibrous adhesions dissolved by ischemia
fibrinolytic enzymes
OSMOSIS.ORG 273
SIGNS & SYMPTOMS
▪ Abdominal pain, vomiting, bloating,
constipation
DIAGNOSIS
DIAGNOSTIC IMAGING
X-ray
▪ Detect obstruction; small intestine dilation
CT scan, ultrasound Figure 34.9 Intraoperative view of abdominal

▪ Exclude other obstructive causes adhesions.
TREATMENT
SURGERY
▪ Surgical/laparoscopic adhesion excision
INTUSSUSCEPTION
osms.it/intussusception
RISK FACTORS
PATHOLOGY & CAUSES ▪ Most common < 24 months old,
intestinal malrotation history, previous
▪ Condition that occurs when part of intussusception, intussusception in sibling,
intestine folds into adjacent section → biologically male
obstruction
▪ Ileocecal region most commonly affected
▪ May be idiopathic/caused by abnormal
COMPLICATIONS
structure (causes pathological lead point) ▪ Peritonitis, sepsis
→ peristalsis causes one part of bowel
to move ahead of adjacent section →
bowel telescoping → ↑ pressure, impaired SIGNS & SYMPTOMS
venous return → bleeding, bowel ischemia,
infarction ▪ Intermittent abdominal pain (worsens with
peristalsis)
▪ Guarding
CAUSES
▪ Straining efforts, draw knees toward chest
▪ Adults: abnormal growth (e.g. polyp, tumor)
▪ Vomiting
▪ Infants: post-infection lymphoid hyperplasia
(Peyer’s patches), Meckel’s diverticulum ▪ Sausage-like abdominal mass
▪ “Red currant jelly” stool (blood, mucus)
274 OSMOSIS.ORG
DIAGNOSIS TREATMENT
▪ Free telescoped intestine portion → clear
Ultrasound, X-ray, CT scan
obstruction → remove necrotic tissue
▪ Telescoped intestine: visualized as classic
bull’s-eye image
▪ Intestinal obstruction signs OTHER INTERVENTIONS
▪ Reduction by air/hydrostatic contrast
material enema (e.g. saline, barium)
OTHER DIAGNOSTICS
▪ May be felt during digital rectal examination
(children)
IRRITABLE BOWEL SYNDROME

(IBS)
osms.it/IBS
previous gastroenteritis, stress
PATHOLOGY & CAUSES
▪ Chronic functional gastrointestinal system SIGNS & SYMPTOMS
disorder; recurrent abdominal pain,
impaired bowel motility ▪ Impaired bowel motility → diarrhea/
▫ No microscopic, macroscopic constipation
irregularities ▪ Recurrent abdominal pain
▫ Constipation/diarrhea ▫ Bowel movement → improvement
▪ Bloating, nausea, mucus in stool
CAUSES
▪ Pathology not completely understood; likely
multifactorial DIAGNOSIS
▫ Visceral hypersensitivity: altered stimuli
response OTHER DIAGNOSTICS
▫ Fecal flora alterations; bacterial ▪ Based on predominant consistency of stool
overgrowth ▫ Diarrhea predominant, constipation
▫ Food sensitivity: short-chain predominant, mixed stool pattern,
carbohydrates; ↑ water in bowel → unclassified
smooth muscle spasm, diarrhea; ▪ Organic disease exclusion
metabolized by bacteria → gas →
bloating, spasm, pain “Rome IV” diagnostic criteria
▫ Psychosocial influence ▪ Abdominal pain ≥ one day weekly in last
three months, associated with two/more of
▫ Genetic factor
following
▫ Defecation → lessened pain
RISK FACTORS ▫ Change in stool frequency
▪ Biologically-female (region-dependent), ▫ Change in stool consistency
OSMOSIS.ORG 275
OTHER INTERVENTIONS
TREATMENT ▪ Stress management
▪ Diet modification
▪ No definitive cure
▫ Low fermentable oligo-, di-,
monosaccharides/polyols diet (low
MEDICATIONS FODMAPs diet)
▪ Symptom-guided therapy ▫ Avoid gas-producing food (caffeine,
▫ Diarrhea predominant: drugs (e.g. alcohol)
loperamide) ▫ Probiotics
▫ Constipation predominant: fiber ▫ Physical activity
supplementation, adequate fluid intake,
osmotic laxatives
▫ Spasm, pain: antispasmodics
ISCHEMIC COLITIS
osms.it/ischemic-colitis
▫ Hypercoagulable states (e.g. factor V
PATHOLOGY & CAUSES Leiden)
▫ Biologically-female individuals
▪ Inflammatory, ischemic condition; ▫ Impaired perfusion (e.g. aortic surgery,
affects colon, most often splenic flexure, myocardial infarction, hemodialysis)
rectosigmoid junction
▫ Vasculopathy
▪ Sudden blood flow ↓ → insufficient
▫ Certain drugs (e.g. vasopressors)
perfusion, oxygen/nutrient delivery to
bowel → compromised cellular metabolism
→ ischemia, inflammation, infarction, COMPLICATIONS
necrosis → possible perforation ▪ Gangrenous bowel, stricture, pancolitis,
▪ Damaged, gangrenous mucosa promotes colonic perforation, peritonitis, sepsis,
fluid/electrolyte loss → dehydration, shock, shock, metabolic acidosis, multisystem
metabolic acidosis organ failure, reperfusion injury, potentially
fatal
CAUSES
▪ Ischemia causes may be occlusive (embolic, SIGNS & SYMPTOMS
thrombotic)/nonocclusive (↓ mesenteric
circulation → severe hypotension,
▪ Symptomatology may be self-limiting
vasospasm)
▪ Localized abdominal cramping, tenderness
▫ Usually acute, may be chronic disorder
(usually left side)
for marathon runners
▪ Loose, bloody stools, hematochezia
▪ ↓ bowel sounds
RISK FACTORS ▪ Guarding, rebound tenderness
▪ Any cause of ↓ perfusion/mesenteric arterial
▪ Fever
embolism, thrombosis/vasoconstriction
▪ May develop shock signs (e.g. hypotension)
▫ Risk ↑ with age/comorbidities
276 OSMOSIS.ORG
▪ Stool culture
DIAGNOSIS ▪ Identifies infectious etiology
DIAGNOSTIC IMAGING
X-ray/CT scan TREATMENT
▪ Abdominal; visualizes obstruction,
perforation, pneumonitis MEDICATIONS
▫ Thumbprinting: segmented bowel ▪ Antibiotics
edema/thickening pattern ▫ Perforation/infection
▫ Double-halo pattern: mucosa,
muscularis hyperdensity SURGERY
▫ Pneumatosis coli, pneumoperitoneum ▪ Bowel resection
indicates perforation ▫ Necrotic tissue
Colonoscopy
▪ Visualizes ischemia: edema, erythema,
friable mucosa
▪ Single-stripe sign: linear ulcer seen along
longitudinal axis
▪ Submucosal hemorrhage: bluish nodules
▪ Biopsy: transmural fibrosis, mucosal
atrophy
LAB RESULTS
▪ Leukocytosis, thrombocytopenia, ↓
hemoglobin
▪ ↑ serum lactate, lactate dehydrogenase Figure 34.10 The endoscopic appearance of
(LDH), creatine phosphokinase (CPK), the colon in a case of ischemic colitis. There is
amylase indicates tissue damage mucosal edema and patchy erythema.
OSMOSIS.ORG 277
OTHER INTERVENTIONS
▪ Circulatory support
▫ IV fluids, electrolytes
▪ Bowel rest

colon in an individual with ischemic colitis.
There is mucosal necrosis, a sign that the
condition is in its early stages at the time of
biopsy.
NECROTIZING ENTEROCOLITIS
(NEC)
osms.it/necrotizing-enterocolitis
RISK FACTORS
PATHOLOGY & CAUSES ▪ Gestational age < 32 weeks
▪ Low birth weight < 2kg/4.41lbs
▪ Severe intestinal disorder: inflammation,
ischemic necrosis ▪ Dysbiosis-contributing interventions
▫ Terminal ileum, colon (most often ▫ Antibiotics, acid-reducing agents,
affected) feeding bovine milk formula
▪ Multifactorial pathology ▪ Human milk promotes commensal bacteria
growth, supports mucosal integrity
▪ Preterm infants
▪ Infections, gas-forming organism presence
▫ Immature gastrointestinal tract
characterized by ↓ intercellular junction ▪ Underlying conditions
integrity + ↓ mucosal barrier → ▫ Term infants (e.g. fetal growth
triggering event → normal intestinal restriction, perinatal hypoxia, congenital
microbiome dysbiosis → ↑ pathogenic heart disease, gastrointestinal disorders,
bacterial growth → exaggerated sepsis)
immune system response → release of
host cytokines, chemokines → tissue COMPLICATIONS
injury → necrosis
▪ Bowel perforation, ileus, septic shock,
▪ Term infants metabolic acidosis, coagulopathy,
▫ Usually underlying condition adversely respiratory failure
affecting intestinal perfusion ▪ Surgical complications
278 OSMOSIS.ORG
▫ Strictures, short bowel syndrome OTHER DIAGNOSTICS

▪ ↑ impaired neurodevelopmental
Surgery
development risk
▪ Through surgical/postmortem specimens
▪ High mortality rate
▫ Gross examination: gangrenous
necrosis, hemorrhage, subserosal gas
SIGNS & SYMPTOMS collection
▫ Histological examination: edema,
▪ Abrupt feeding tolerance change hemorrhage, transmural necrosis,
▪ Abdominal distension, tenderness bacterial infiltration
▪ Erythema, crepitus, induration may also be
present
TREATMENT
▪ ↑ gastric residuals
▪ Vomiting (often bilious), bilious drainage MEDICATIONS
from enteral feeding tubes ▪ Empirical antimicrobial therapy
▪ Hematochezia
▪ Nonspecific findings
SURGERY
▫ Temperature instability, lethargy, apnea
▪ Exploratory laparotomy, bowel resection
▪ Primary peritoneal drainage (PPD) → ↓
intra-abdominal pressure
OTHER INTERVENTIONS
▪ Address complications (e.g. metabolic
correction/hematologic abnormalities)
▪ Bowel rest with nasogastric intubation
decompression
▪ Supplemental oxygen/mechanical
ventilation
▪ Fluid replacement
▪ Inotropic support
Figure 34.12 Gross pathology of necrotizing ▪ Total parenteral nutrition (TPN)
enterocolitis.
DIAGNOSIS
DIAGNOSTIC IMAGING
Abdominal radiography, ultrasound
▪ Pneumatosis intestinalis,
pneumoperitoneum/hepatobiliary gas
LAB RESULTS
▪ Positive blood culture, ↓ platelets, ↓ red
blood cells, disseminated intravascular
coagulopathy evidence, ↑ serum lactate
OSMOSIS.ORG 279
SMALL BOWEL ISCHEMIA &
INFARCTION
osms.it/ischemia-and-infarction
cardiopulmonary bypass surgery,

PATHOLOGY & CAUSES hemodialysis → ↓ intestinal perfusion)
▪ Coagulative disorders
▪ Serious small bowel condition; reduced
▪ Atherosclerotic occlusive disease
blood flow, subsequent infarction; AKA
mesenteric ischemia ▪ Hypovolemia (e.g. dehydration,
hemorrhage)
▫ Collateral circulation network →
small bowel especially vulnerable to ▪ Bowel strangulation (e.g. volvulus,
widespread ischemic injury incarcerated hernia)
▫ Hypoxia, subsequent reperfusion → ▪ Vasoconstriction medications
tissue injury
▪ ↓ blood flow may be acute/chronic COMPLICATIONS
▫ Acute: sudden ↓ small intestine ▪ Ileus, shock, metabolic acidosis,
perfusion multisystem organ failure, high mortality
▫ Chronic: episodic ↓ digestion
perfusion (often related to mesenteric
atherosclerosis) SIGNS & SYMPTOMS
▪ Insufficient perfusion, oxygen/nutrient
delivery to bowel → compromised cellular ▪ Severe abdominal pain (often postprandial);
metabolism → ischemia, inflammation, nausea, vomiting; distended abdomen;
transmural infarction, necrosis → bacterial guarding, rebound tenderness (develops
transmigration + possible perforation later); ↓ bowel sounds; fever; feculent
▪ Damaged, gangrenous mucosa promotes breath odor; rectal bleeding; may exhibit
fluid/electrolyte loss → dehydration, shock, shock signs (e.g. hypotension)
metabolic acidosis
DIAGNOSIS
CAUSES
▪ Ischemia causes DIAGNOSTIC IMAGING
▫ Occlusive (arterial/venous): embolic,
thrombotic, tumor, volvulus, CT/magnetic resonance (MR) angiography
intussusception, hernia, atherosclerosis ▪ Detects acute mesenteric ischemia
▫ Nonocclusive: severe hypotension, Abdominal X-ray/CT scan
vasospasm → ↓ mesenteric circulation
▪ Dilated bowel loops, bowel wall thickening,
thumbprinting, intestinal pneumatosis, free
RISK FACTORS intraperitoneal air
▪ Any cause of ↓ perfusion/mesenteric arterial
embolism, thrombosis/vasoconstriction LAB RESULTS
▪ Cardiac disorders (e.g. arrhythmia, valvular ▪ Leukocytosis with left shift, ↑ hematocrit
disease → arterial emboli formation (dehydration, hemoconcentration)
from heart; ↓ cardiac output, peripheral
▪ ↑ serum lactate, amylase, alkaline
hypoperfusion)
phosphatase
▪ Procedures (e.g. cardiac catheterization,
280 OSMOSIS.ORG

▪ Laparotomy ▪ Resection
▫ Abdominal exploration
OTHER INTERVENTIONS
TREATMENT ▪ Pain management
▪ Bowel rest with decompression
MEDICATIONS
▪ Antibiotics
▪ Circulatory support
▫ IV fluids, electrolytes, inotropic
medications
VOLVULUS
osms.it/volvulus

▪ Intestinal obstruction ▪ Abdominal tenderness, pain, distension,
▫ Intestinal twisting/looping bilious vomiting, constipation, fever,
auscultation (abnormal bowel sounds,
often decreased), percussion (tympany),
TYPES hematochezia (may indicate bowel
▪ Classified by location ischemia, necrosis)
Sigmoid volvulus (most common)
▪ Usually middle-aged/elderly individuals DIAGNOSIS
▪ Causes include pregnancy, chronic
constipation (e.g. Hirschsprung’s disease), DIAGNOSTIC IMAGING
intestinal adhesions
X-ray
Cecal volvulus ▪ Asses volvulus shape
▪ Causes include impaired abdominal ▫ Bent inner tube sign (“coffee bean” sign)
mesentery development, pregnancy,
chronic constipation Barium enema
▪ May show “bird’s beak” shape (point of
Midgut volvulus
twisted bowel)
▪ Usually infants/young children
▪ Perforation suspected → barium contrast
▪ Caused by anomalous intestinal contraindicated
development (e.g. intestinal malrotation)
CT scan
COMPLICATIONS ▪ Twisted mesentery (“whirlpool” sign)
▪ Mesenteric artery compression → intestinal
wall ischemia, infarction
▪ Intestinal wall perforation, infection (e.g.
diffuse peritonitis)
OSMOSIS.ORG 281
TREATMENT
SURGERY
▪ In case of midgut volvulus/ischemia/
necrosis; surgical resection if necessary
OTHER INTERVENTIONS
▪ IV fluid replacement
▪ Bowel decompression
▫ Sigmoid volvulus: sigmoidoscopy
▫ Cecal volvulus: colonoscopy
Figure 34.13 Abdominal radiograph

demonstrating a massively dilated sigmoid
colon in a case of sigmoid volvulus.
Figure 34.14 3D CT virtual colonoscopy

demonstrating sigmoid volvulus.
282 OSMOSIS.ORG
NOTES
NOTES
LIVER & GALLBLADDER
CONGENITAL CONDITIONS

▪ Inherited metabolic/congenital structural DIAGNOSTIC IMAGING
anomalies, affect hepatobiliary system → ▪ Ultrasound
hyperbilirubinemia ▪ Oral cholecystogram

▪ Kernicterus ▪ Conjugated vs. unconjugated bilirubin, liver
▪ Recurrent cholangitis, cirrhosis function tests
▪ Portal hypertension ▪ Biopsy
▪ Metabolic problems, impaired growth
TREATMENT
SIGNS & SYMPTOMS
▪ Jaundice, dark urine, light stools
▪ Impaired liver function
▪ Neurologic alterations
BILIARY ATRESIA
osms.it/biliary-atresia
TYPES
PATHOLOGY & CAUSES ▪ Biliary atresia only; not accompanied by
other anomalies (most common)
▪ Congenital anomaly of extrahepatic duct
▪ Biliary atresia + laterality malformations
fibrosis, obstruction of bile flow
(left-right axis patterning/malpositioning of
▪ Infections, environmental toxins, immune organs)
dysregulation, genetic mutations →
▫ Dextrocardia, situs inversus, asplenia/
perinatal injury to biliary system
polysplenia, interrupted inferior vena
▪ Bile prevented from entering duodenum cava
→ impaired fat digestion, absorption +
▫ Related CFC1 gene mutation
cholestasis, distension of gallbladder, ducts
▪ Biliary atresia + intestinal atresia,
imperforate anus, kidney anomalies
OSMOSIS.ORG 283
COMPLICATIONS
▪ Liver cirrhosis, portal hypertension, hepatic
encephalopathy
▪ Recurrent cholangitis, cirrhosis
▪ Metabolic problems, impaired growth
(associated with malabsorption)
SIGNS & SYMPTOMS

▪ Neonates asymptomatic at birth; stools
Figure 35.1 Intraoperative photography of
gradually become acholic, clay-colored
extra-hepatic biliary atresia. The underside of
▪ Persistent jaundice the liver displays only connective tissue in the
▫ Skin gradually turns yellow, greenish- gallbladder fossa.
bronze
▪ Dark urine
▫ Increased bilirubin concentration
TREATMENT
▪ Portal hypertension
▫ Splenomegaly, ascites, enlarged MEDICATIONS
abdominal veins
▪ Ursodeoxycholic acid (hydrophilic bile acid)
▪ Impaired liver function → decreased
coagulation factors, bleeding tendencies
▫ Impaired coagulation also related to SURGERY
decreased vitamin K absorption ▪ Type indicated by blood chemistry, imaging,
biopsy
DIAGNOSIS Intraoperative cholangiogram

▪ Gold standard for confirming obstruction,
DIAGNOSTIC IMAGING diagnosis
Ultrasound Hepatoportoenterostomy (Kasai HPE)

▪ Abnormal gallbladder size, shape, ▪ Restores bile flow from liver; may need
contractility; absent common bile duct; subsequent revision
“triangular cord” sign (triangle-shaped
Liver transplant
echogenic density above porta hepatis)
▪ If Kasai procedure unsuccessful
Hepatobiliary scintigraphy
▪ Decreased/absent patency of extrahepatic OTHER INTERVENTIONS
biliary tree
Diet
LAB RESULTS ▪ Fat-soluble vitamin supplements; high
protein diet, medium-chain triglyceride
▪ Increased conjugated serum bilirubin,
supplements
aminotransferases
Liver biopsy
▪ Identifies obstruction-related histological
changes
284 OSMOSIS.ORG
Chapter 35 Liver & Gallbladder Congenital Conditions
CRIGLER–NAJJAR SYNDROME
osms.it/crigler-najjar-syndrome
COMPLICATIONS
PATHOLOGY & CAUSES ▪ Kernicterus (Type I), if not promptly
addressed
▪ Rare inherited metabolic disorder;
nonhemolytic hyperbilirubinemia
▪ Autosomal recessive inheritance pattern SIGNS & SYMPTOMS
▪ AKA congenital nonhemolytic jaundice with
glucuronosyltransferase deficiency ▪ Persistent jaundice in first few days of life
▪ Neurological symptoms as kernicterus
TYPES develops
Type I
▪ Severe jaundice, bilirubin encephalopathy, DIAGNOSIS
possible kernicterus-associated neurologic
impairment LAB RESULTS
Type II Unconjugated hyperbilirubinemia
▪ Lower serum bilirubin concentration; no ▪ Type I: 20–50 mg/dL
neurologic impairment ▪ Type II: < 20 mg/dL
Stool color
CAUSES ▪ Type I: pale yellow, low fecal urobilinogen
▪ Mutation in coding area of UGT gene, (significantly decreased bilirubin
encodes for bilirubin-conjugating enzyme conjugation)
UGT1A1 (bilirubin-uridine diphosphate
▪ Type II: normal
glucuronosyltransferase) → structurally
abnormal enzyme → decreased/absent Normal liver histology, liver function tests
conjugation of bilirubin
RISK FACTORS
▪ Consanguinity
OSMOSIS.ORG 285
OTHER INTERVENTIONS
TREATMENT
Phototherapy
MEDICATIONS ▪ In first years of life; effectiveness decreases
over time
Phenobarbital
▪ Useful in Type II, induces residual UGT Exchange transfusion
activity
Plasmapheresis + albumin infusions
▪ Removes bilirubin tightly bound to serum
SURGERY albumin
Liver transplant
▪ Definitive treatment for Crigler-Najjar
syndrome Type I
DUBIN–JOHNSON SYNDROME
osms.it/dubin-johnson-syndrome

▪ Inherited metabolic disorder; mild, DIAGNOSTIC IMAGING
fluctuating elevations in conjugated
(predominantly), unconjugated bilirubin, no Oral cholecystogram
evidence of hemolysis ▪ Gallbladder may not be visualized
▪ Autosomal inheritance pattern
▪ MRP2 (ABCC) gene mutation → LAB RESULTS
impaired hepatic excretion of non-bile- ▪ Hyperbilirubinemia, normal liver function
salt organic anions, bilirubin into bile via tests
canalicular membrane → cholestasis → ▪ Total urinary coproporphyrin normal;
hyperbilirubinemia majority, coproporphyrin I
Liver biopsy, histological exam

SIGNS & SYMPTOMS ▪ Brown, black discoloration
▫ Pigment accumulates in lysosomes
▪ Mild jaundice; evident during physiological
stress (e.g. illness)/hormonal fluctuations
(e.g. pregnancy, oral contraceptives) TREATMENT
▪ Constitutional
▫ Vague abdominal pains, weakness ▪ None required
▪ Occasional hepatosplenomegaly
286 OSMOSIS.ORG
Chapter 35 Liver & Gallbladder Congenital Conditions
GILBERT'S SYNDROME
osms.it/gilberts-syndrome

▪ Benign, inherited metabolic disorder; ▪ Asymptomatic between episodes, jaundice
recurring unconjugated hyperbilirubinemia, evident during physiological stress
jaundice ▪ Clinical manifestations
▪ Autosomal recessive inheritance pattern ▫ During adolescence, with effects of sex
▪ AKA Meulengracht disease, familial steroids on bilirubin metabolism
nonhemolytic jaundice
▪ Serum bilirubin increases during
physiologic stress (e.g. illness, dehydration, DIAGNOSIS
fasting, overexertion, menses)
▪ Differs from other forms of non-hemolytic ▪ Exclude other causes of unconjugated
hyperbilirubinemia hyperbilirubinemia
▫ Genetic mutation in promoter region
of UGT gene → structurally normal
enzyme → impaired genetic expression
TREATMENT
of hepatic UGT with decreased activity
→ decreased conjugation of bilirubin ▪ None required
ROTOR SYNDROME
osms.it/rotor-syndrome

▪ Rare benign inherited disorder; ▪ Mild jaundice; during physiological
chronic conjugated, unconjugated hormonal fluctuations (e.g. pregnancy, oral
hyperbilirubinemia; no hemolysis contraceptive use)
▪ SLCO1B1, SLCO1B3 gene mutations
(code for transporter proteins 1B1, 1B3
responsible for bilirubin re-uptake by DIAGNOSIS
hepatocytes) → alters bilirubin re-uptake →
increases bilirubin in plasma DIAGNOSTIC IMAGING
Oral cholecystogram
COMPLICATIONS ▪ Normal gallbladder opacification
▪ Impaired 1B1 activity → significant drug
toxicities (e.g. statin-associated myopathy)
LAB RESULTS
▪ Hyperbilirubinemia, normal liver function
tests
OSMOSIS.ORG 287
▪ Total urinary coproporphyrin markedly
increased; majority coproporphyrin I
Liver biopsy, histological exam

▪ Normal
TREATMENT
▪ None required
288 OSMOSIS.ORG
NOTES
NOTES
LIVER DISEASES

(e.g. increase in free calcium)
PATHOLOGY & CAUSES ▪ Decreased hepatic metabolism of
circulating estrogens → hyperestrogenism
▪ Diseases affecting hepatic parenchymal
▫ Spider nevi: vascular lesions, central
tissue or vasculature
arteriole surrounded by smaller vessels
▪ Variable insults
▫ Palmar erythema
▫ Impairment in function of/destruction
▫ Gynecomastia
of liver parenchyma → inflammation →
scarring (cirrhosis) → liver failure ▪ Fetor hepaticus (breath odor due to
increased dimethyl sulfide levels)
▫ Obstruction or restriction of blood flow
through liver → hypertension in portal ▪ Jaundice (cellular necrosis → reduced
circuit producing secondary systemic hepatic ability to metabolize, excrete
effects bilirubin → buildup of unconjugated
bilirubin in the blood)
▫ Diseases caused by anomalies in
absorbing, storing, converting or ▪ Decreased production of coagulation
detoxification → accumulation of factors → easy bruising, bleeding
substances in the liver and other tissues ▪ Hepatic encephalopathy
causing damage ▫ Ammonia, related nitrogenous
substances not cleared from blood →
accumulate in brain → impaired cerebral
SIGNS & SYMPTOMS function
▪ Early stages generally asymptomatic

▪ Non-specific symptoms MNEMONIC: ABCDEFGHIJ
▫ Weakness, weight loss, fatigue Common signs of liver
disease
Portal hypertension Asterixis, Ascites, Ankle
▪ Abdominal distension (ascites) edema, Atrophy of testicles
▪ Splenomegaly Bruising
▪ Esophageal varices → trouble swallowing, Clubbing/ Color change of nails
hematemesis, dark stools (leukonychia)
▪ Caput medusae Dupuytren’s contracture
▫ Dilated periumbilical collateral veins Encephalopathy / palmar
▪ Cruveilhier–Baumgarten murmur Erythema
▫ Venous hum heard in epigastric region Fetor hepaticus
with stethoscope Gynecomastia
Liver cellular dysfunction Hepatomegaly
▪ Decreased hepatic albumin production Increase size of parotids
▫ Decreased osmotic pressure → edema Jaundice
▫ Increase in levels of free circulating
compounds normally bound to albumin
OSMOSIS.ORG 289
▫ Neglect of personal appearance MNEMONIC: 3Cs & 3Cs
▫ Unresponsive, forgetful, trouble Hepatomegaly common
concentrating causes
▫ Changes in sleeping habits Cirrhosis
▫ Psychosis Carcinoma
▫ Asterixis (bilateral asynchronous Cardiac failure
flapping of outstretches, dorsiflexed
hands) Hepatomegaly rare causes
▪ Decreased metabolism of active Cholestasis
compounds → increased sensitivity to Cysts
certain medications
Cellular infiltration
▪ Pruritus
anti-hepatitis B core IgM

DIAGNOSIS
▫ Hepatitis C: hepatitis C antibody,
DIAGNOSTIC IMAGING hepatitis C RNA
▪ CT scan with contrast, MRI, ultrasound, ▫ Hepatitis D & E: IgM, IgG antibodies
radionuclide imaging ▪ Autoimmune panel
▫ Rheumatoid factor (RF), anti-cyclic
citrullinated peptide antibody (CCP),
LAB RESULTS anti-nuclear antibody (ANA), anti-
▪ Complete blood count (CBC) double stranded DNA (anti-dsDNA),
▪ Liver function tests anti-extractable nuclear antigen (anti-
▫ Tests of synthetic function: serum ENA), antineutrophil cytoplasmic
albumin level, international normalized antibody (ANCA)
ratio (INR) ▪ Liver biopsy
▫ Hepatocellular enzymes: aspartate
transaminase (AST), alanine
transaminase (ALT), total bilirubin, direct TREATMENT
bilirubin
▫ Ductal enzymes: alkaline phosphatase ▪ Initially disease-specific; see individual
(ALP), gamma glutamyl transpeptidase disorders
(GGT)
▪ Hepatitis virus serology SURGERY
▫ Hepatitis A: anti-hepatitis A IgM, anti- ▪ Advanced disease → liver transplant
hepatitis A IgG
▫ Hepatitis B: hepatitis B surface antigen,
anti-hepatitis B core/surface antibodies,
290 OSMOSIS.ORG
Chapter 36 Liver Diseases
ALCOHOLIC LIVER DISEASE

osms.it/alcoholic-liver-disease
▪ Large vacuoles coalesce → fatty cysts →
PATHOLOGY & CAUSES irreversible lesions
▪ Macrovesicular steatosis most commonly
▪ Abnormal lipid retention in hepatocytes
associated with alcohol, diabetes, obesity,
(steatosis) → large triglyceride fat vacuoles
corticosteroids
accumulate in liver cells → fatty liver
▪ Severe fatty liver may be accompanied by
▪ Fat content of liver exceeds 5–10% by
inflammation, steatosis → steatohepatitis
weight
▫ Steatohepatitis → hepatocyte
▪ Can be accompanied by progressive
ballooning, necrosis → liver cell death,
inflammation (hepatitis) → steatohepatitis
inflammatory response → hepatic
stellate cell activation → fibrosis →
RISK FACTORS cirrhosis
▪ Glycogen storage diseases, acute fatty liver
during pregnancy, malnutrition, obesity, COMPLICATIONS
HIV, hepatitis C
▪ Hepatocellular carcinoma
Alcohol
▪ Most common cause
SIGNS & SYMPTOMS
▪ Chronic alcohol use → production of toxic
metabolites (e.g. aldehydes)
▪ Fatigue, malaise, dull right-upper-quadrant
▫ Damages mitochondria, cellular pain, mild jaundice (rare), significant
structures → impaired cellular energy damage → hepatomegaly, ascites
mechanisms
▫ Alcohol metabolised to aldehyde hepatic
enzymes (reaction facilitates conversion DIAGNOSIS
of NAD+ → NADH; lower NAD+
concentration → less fatty acid oxidation DIAGNOSTIC IMAGING
→ fatty acids accumulate → steatosis)
Ultrasound
STAGING ▪ Steatosis → bright liver with increased
echogenicity
▪ Stages of intracytoplasmic accumulation of
triglycerides → fatty change ▪ Fibrosis → coarse echo pattern
▪ Cirrhosis → nodules → irregular outline of
Initial stage liver surface
▪ Hepatocytes contain small fat vacuoles
(liposomes) around nucleus (microvesicular CT scan
fatty change) ▪ Lower density than spleen on CT scan
Late stage MRI

▪ Vacuoles enlarge → nucleus pushed to ▪ Fat → bright on T1 and T2-weighted
cell periphery → signet ring appearance images
(macrovesicular fatty change)
▪ Vesicles well-delineated, optically empty LAB RESULTS
▫ Fats dissolve during tissue processing
Liver function tests
▪ Serum aminotransferases normal/
OSMOSIS.ORG 291
moderately elevated
▫ AST usually more elevated than ALT in
TREATMENT
alcoholic fatty liver disease
▪ Hepatic steatosis reversible, non-
▫ GGT often elevated in alcoholic fatty progressive if underlying cause controlled
liver disease (e.g. cease alcohol use)
Secondary causes of steatosis
▪ Hepatitis C virus antibodies
▪ Hepatitis A IgG
▪ Hepatitis B surface antigen, surface
antibody, core antibody
▪ Plasma iron, ferritin, total iron-binding
capacity
Biopsy
▪ Early changes
▫ Accumulation of membrane bound large
droplet steatosis (Large macrovesicular
drops → alcoholic steatosis; small
microvesicular droplets → acute fatty Figure 36.1 A Mallory–Denk body is a feature
liver of pregnancy, tetracycline toxicity, of many liver pathologies including alcoholic
Reye’s syndrome) hepatitis and alcoholic cirrhosis.
▫ Proliferation of smooth endoplasmic
reticulum
▫ Gradual distortion of mitochondria
▪ Steatohepatitis
▫ Presence of neutrophils → alcoholic
steatohepatitis, unusual in chronic viral
hepatitis
▫ Mallory-Denk bodies (clusters of
intracellular cytoskeletal protein
aggregates)
▪ Advanced changes
▫ Fibrosis: accumulation of scar tissue
or extracellular matrix, potentially
reversible if individual stops drinking Figure 36.2 Histological appearance of fatty
alcohol, not true cirrhosis characterized liver. The numerous white spaces represent
by presence of regenerative nodules the accumulation of lipid.
(irreversible)
292 OSMOSIS.ORG
AUTOIMMUNE HEPATITIS
osms.it/autoimmune-hepatitis

▪ Inflammation of the liver tissue caused by LAB RESULTS
autoimmunity ▪ ↑↑ALT, ↑ AST, ↓ albumin, ↑ prothrombin
time
TYPES ▪ Type 1
▪ Type 1: 80% of cases ▫ Antinuclear antibodies (ANAs),
▪ Type 2: most common in young antibodies against smooth muscle
biologically-female individuals proteins, or (ASMAs)
▪ Type 3: different antibodies but presents as ▪ Type 2
Type 1 ▫ Antibodies to the microsomes of the
▪ Type 4: no detectable antibodies liver or kidney (ALKM-1), liver cytosol
antigen (ALC-1)
▪ Type 3
CAUSES ▫ Soluble liver antigen positive
▪ Combination of environmental triggers and
genetic predisposition
TREATMENT
RISK FACTORS
▪ Young biologically-female individuals; MEDICATIONS
presence of HLA-DR3.DR4 Immunosuppressants
▪ Corticosteroids, azathioprine
COMPLICATIONS
▪ Acute liver failure, chronic liver failure, SURGERY
hepatocellular carcinoma, long term
immunosuppression can lead to Liver transplantation
malignancies ▪ If resistant to drug therapies
SIGNS & SYMPTOMS

▪ Wide spectrum of presentation, from
asymptomatic to cirrhosis and liver failure
▪ Common moderate symptoms
▫ Fever, jaundice, and
hepatosplenomegaly
▪ Chronic disease symptoms
▫ Coagulation disturbance, impaired
immunity
▪ Type 2 is associated with other diseases
(Hashimoto’s thyroiditis, Grave’s disease)
OSMOSIS.ORG 293
autoimmune hepatitis. There is an infiltration
of lymphocytes and plasma cells at the
interface between the hepatic lobule and the
portal tract i.e. lymphoplasmacytic interface
hepatitis.
BUDD–CHIARI SYNDROME
osms.it/budd-chiari-syndrome
▪ Trauma
PATHOLOGY & CAUSES ▪ Pregnancy
▪ Contraceptive therapy
▪ Congestive hepatic disease caused by
obstruction of hepatic venous outflow
▪ Usually > one hepatic vein or hepatic COMPLICATIONS
section of vena cava ▪ Cirrhosis and liver failure
▪ Venous congestion leads to ▪ Esophageal, gastric and rectal varices
▫ Ischemia and centrilobular necrosis ▪ Kidney dysfunction (hepatorenal syndrome)
▫ Increased pressure in portal system →
portal hypertension
SIGNS & SYMPTOMS
CAUSES ▪ Can present acutely or chronically
▪ Occlusion (primary)
▪ Classic triad
▫ Thrombosis (most common)
▫ Hepatomegaly
▪ Compression (secondary)
▫ Abdominal pain
▫ Tumor mass, granuloma
▫ Ascites
▪ Jaundice
RISK FACTORS ▪ Fever
▪ Myeloproliferative and hematologic ▪ Other signs and symptoms of portal
disorders (e.g. polycythemia vera) hypertension (e.g. splenomegaly,
▪ Hypocoagulative disorders encephalopathy)
▪ Tumors
▪ Infections (e.g. tuberculosis)
▪ Inflammatory diseases
294 OSMOSIS.ORG
DIAGNOSIS TREATMENT
DIAGNOSTIC IMAGING ▪ Treat the underlying cause
Doppler ultrasound
▪ Thrombus MEDICATIONS
▪ Alteration of hepatic venous outflow ▪ Usually insufficient
▪ ‘Spider web’ formation around the ▪ Anticoagulants
obstruction duto collateral vessels ▪ Diuretics
proliferation
Venography
SURGERY
Liver transplantation
CT scan, MRI
▪ In case of fulminant liver failure
LAB RESULTS Portosystemic shunt

▪ Elevated aminotransferases ▪ Divert the flow away from the obstruction
▪ Liver biopsy ▪ Transjugular intrahepatic portosystemic
shunt (TIPS)
▪ Surgical shunt
OTHER INTERVENTIONS
Thrombolytic therapy
▪ Dissolve clots
▪ Balloon angioplasty
Figure 36.4 An abdominal CT scan in the

axial plane demonstrating hypoperfusion of
the right lobe of the liver secondary to Budd-
Chiari syndrome.
OSMOSIS.ORG 295
CHOLESTATIC LIVER DISEASE
osms.it/cholestatic-liver-disease
malignancy (biliary tree/head of
PATHOLOGY & CAUSES pancreas), strictures, cystic fibrosis
(impaired secretory function of biliary
▪ Cholestasis: decrease in bile flow through epithelium), primary sclerosing
bile ducts into duodenum cholangitis (immune system attacks
▪ Hepatic retention, spillage into systemic bile ducts → inflammation, scar tissue),
circulation of cholesterol, bile salts → biliary atresia (≥ one newborn infant’s
incorporation into biological membranes bile ducts narrow/blocked/absent)
→ altered membrane fluidity → injury to ▫ Complications: prolonged obstruction
biological membranes, impaired function → biliary cirrhosis; subtotal/intermittent
of membrane channels → bile secretion obstruction → ascending cholangitis
impaired in liver (secondary bacterial infection of biliary
▪ No bile reaches small intestine → intestinal tree) → sepsis, if untreated
malabsorption → nutritional deficiencies of
fat soluble vitamins (A, D, E, K)
SIGNS & SYMPTOMS
CAUSES
▪ Jaundice
Hepatocellular cholestasis ▫ Individual components of bile enter
▪ Impaired secretion of bile by hepatocytes serum (e.g. conjugated bilirubin)
▫ Intracellular accumulation of bile ▪ Pain
acids → ↓ regulation of bile synthesis ▫ Right upper quadrant (RUQ) pain,
→ ↓ total bile production/secretion radiates to right shoulder, minutes to
→ accumulation of bile components hours in duration (often after fatty meal)
(e.g. conjugated bilirubin) → diffuse/ ▪ Pruritus
exocytose into interstitium → diffuse
▫ Systemic accumulation of bile salts/
into blood
endogenous opioids/lysophosphatidic
Elevated levels of estrogen acid
▪ Breakdown of cholesterol → cholic acid ▪ Skin xanthomas
(bile acid) ▫ Focal accumulations of cholesterol
▪ ↑ estrogen → inhibition of export pump → (common in obstructive jaundice)
estrogen-induced cholestasis ▪ Pale stools/dark urine
▪ Risk factors ▫ Absence of bile in gut → conjugated
▫ Oral contraceptives (increase estrogen bilirubin (water soluble) not excreted
exposure), pregnancy (pregnancy- with bile, excreted via kidneys
induced cholestasis), anabolic steroids
(similar in structure to estrogen)
▪ Extrahepatic cholestasis
▫ Physical obstruction blocks bile flow
▫ Ductal obstruction → bile accumulates
in liver → ↑ pressure in bile ducts → bile
leaks through tight junctions between
hepatocytes → enters serum, interstitial
space
▫ Causes: cholelithiasis (gallstones),
296 OSMOSIS.ORG
DIAGNOSIS TREATMENT
LAB RESULTS MEDICATIONS
▪ Associated vitamin deficiency
Liver function tests (LFTs)
▫ Fat-soluble vitamin supplementation
▪ Elevated membrane-bound enzymes
▪ Children
(sensitive to hepatocyte damage) → ↑
serum alkaline phosphatase (ALP), gamma- ▫ Ursodeoxycholic acid → increased bile
glutamyl transpeptidase (GGT) formation
Histology
SURGERY
▪ Individual hepatocytes take on brownish-
▪ Extrahepatic obstruction
green stippled appearance (due to
trapped bile), canalicular bile plugs form ▫ Surgical correction of obstruction
between individual hepatocytes/bile ducts (e.g. cholecystectomy; if gallstone
(excreted bile cannot travel further due to obstructing common bile duct, removal
obstruction) of gallbladder)
▫ Under sufficient pressure, canalicular
plugs may rupture → spillage of bile into OTHER INTERVENTIONS
surrounding tissue → hepatic necrosis ▪ Pregnancy-induced cholestasis
▫ Early delivery (around week 36 of
gestation)
CIRRHOSIS
osms.it/cirrhosis
fibrotic material in extracellular matrix
PATHOLOGY & CAUSES ▪ Fibrotic cascade → formation of fibrous
septa → separation of hepatocyte nodules
▪ Hepatic parenchyma replaced by scar → distortion of liver architecture →
tissue → scar tissue blocks portal flow of decrease blood flow throughout → splenic
blood through liver → raised blood pressure congestion → hypersplenism, splenic
and disturbance of function sequestration of platelets
▪ Reversible phase → hepatitis/fatty liver ▪ Injured liver cells group together →
(steatosis) often precedes cirrhosis regenerative nodules (clumps of cells
▪ Long term accumulation of liver damage → between fibrotic tissue, collagen) → bumpy
disruption of liver architecture → functional cirrhotic liver
impairment
▪ Develops over months to years
RISK FACTORS
▪ Damage to parenchyma → activation of
▪ Chronic alcohol use, chronic hepatitis C
stellate cells (sit between sinusoids and
infection, chronic hepatitis B (+/- hepatitis
hepatocytes in perisinusoidal space) →
D) infection, autoimmune hepatitis,
secretion of
hereditary hemochromatosis, Wilson
▫ TGF-β1 → production of myofibroblasts disease, alpha 1-antitrypsin deficiency,
→ increased fibrosis, proliferation of medications
connective tissue
▫ TIMP 1 & 2 (matrix metalloproteinase
inhibitors) → prevents breakdown of
OSMOSIS.ORG 297
COMPLICATIONS (ERCP) /magnetic resonance
▪ Portal hypertension, hepatic cholangiopancreatography (MRCP))
encephalopathy, increased blood levels of
Diagnostic paracentesis
estrogens, hepatocellular carcinoma
▪ Determine ascitic fluid origin
▪ Portal hypertension
MNEMONIC: HEPATIC ▪ Suspected spontaneous bacterial peritonitis
Causes of Cirrhosis ▫ Cell count, gram stain, culture
Hemochromatosis (primary) ▫ Serum: ascites albumin gradient (SAAG)
Enzyme deficiency (alpha-1- > 1.1 g/dL → portal HTN
anti-trypsin)
Post hepatic (infection + drug LAB RESULTS
induced) ▪ AST, ALT moderately elevated, AST > ALT
Alcoholic ▪ ALP 2–3x normal
Tyrosinosis ▪ GGT very high in chronic alcoholic liver
Indigenous people in America disease
(galactosemia) ▪ Bilirubin increases as cirrhosis worsens
Cardiac/ Cholestatic (biliary)/ ▪ Albumin decreases as synthetic function
Cancer/ Copper (Wilson’s) declines
▪ Prothrombin time increases as synthetic
function declines
SIGNS & SYMPTOMS ▪ Hyponatremia from inability to excrete free
water (high levels of antidiuretic hormone,
▪ Early stages generally asymptomatic aldosterone)
▫ Liver may be enlarged, shrinks as ▪ Serum biomarkers correlate with degree of
cirrhosis progresses liver damage in variety of liver diseases
▫ Non-specific symptoms: weakness, ▪ A2-macroglobulin, haptoglobin,
weight loss, fatigue apolipoprotein A1, bilirubin, GGT, age,
▪ Portal hypertension biological sex
▪ Liver cellular dysfunction Histology
▪ Nail changes (Muehrcke’s lines, Terry’s ▪ Macroscopic appearance
nails, clubbing)
▫ Surface irregular, consistency firm
▪ Hypertrophic osteoarthropathy
▫ Yellow color (in steatosis)
▪ Dupuytren’s contracture
▫ Nodular
▪ Liver biopsy
DIAGNOSIS ▫ Microscopic appearance of hepatocytes
(regenerating nodules) and fibrosis/
DIAGNOSTIC IMAGING connective tissue deposits between
nodules
Ultrasound ▪ Cause specific abnormalities
▪ Small nodular liver (advanced cirrhosis), ▫ Chronic hepatitis B: infiltration of liver
increased echogenicity, irregular- looking parenchyma with lymphocytes
areas, widening fissures, splenomegaly, ▫ Cardiac cirrhosis: erythrocytes, greater
imaging of blood flow in portal vein amount of fibrosis in tissue surrounding
Endoscopy hepatic vein
▪ Esophagogastroduodenoscopy (EGD) ▫ Primary biliary cholangitis: fibrosis
around bile duct, presence of
▫ Exclude esophageal varices
granulomas, pooling of bile
▪ Imaging of bile ducts (endoscopic
▫ Alcoholic cirrhosis: neutrophilic
retrograde cholangiopancreatography
infiltration
298 OSMOSIS.ORG
OTHER DIAGNOSTICS
Child-Pugh score
▪ Grading of cirrhosis
▫ Class A (5–6 points): one year survival
100%, two year survival 85%
▫ Class B (7–9 points): one year survival
81%, two year survival 57%
▫ Class C (10–15 points): one year
survival 45%, two year survival 35%
Figure 36.5 Gross pathology of micronodular

TREATMENT liver cirrhosis.
MEDICATIONS
▪ Antiviral medication (e.g. interferon)
▫ For hepatitis B, C
▪ Corticosteroids
▫ For autoimmune hepatitis
▪ Diuretics, antibiotics, laxatives, enemas,
thiamine, steroids, acetylcysteine,
pentoxifylline
▫ For decompensation (compensated
cirrhosis—no jaundice, ascites, variceal
bleeding, hepatic encephalopathy;
development of any of above →
decompensated)
Figure 36.6 Histological appearance of liver
cirrhosis (trichrome stain). The blue highlights
OTHER INTERVENTIONS the bands of fibrosis between islands of
▪ Abstain from alcohol hepatocytes.
▫ For alcoholic hepatitis
▪ Chelation therapy (e.g. penicillamine)
▫ For Wilson disease
▪ Dissolve gallstones
▫ Blockage of bile ducts
OSMOSIS.ORG 299
FITZ–HUGH–CURTIS SYNDROME
osms.it/fitz-hugh-curtis-syndrome
▪ Causative organisms
PATHOLOGY & CAUSES ▫ Commonly: Chlamydia trachomatis,
Neisseria gonorrhoeae, Mycobacterium
▪ Pelvic inflammatory disease (PID) → tuberculosis (endemic areas)
inflammation of local structures → anterior
▫ Reported: Trichomonas vaginalis,
liver capsule inflammation (perihepatitis)
Ureaplasma urealyticum, Mycoplasma
→ patchy purulent, fibrinous exudate →
hominis, Bacteroides spp., Gardnerella
adhesions form
vaginalis, E. coli and Streptococcus spp.
CAUSES
RISK FACTORS
▪ Etiology of inflammation poorly understood
▪ Biological females of reproductive age
▪ Thinning of cervical mucus → bacteria
colonizing vagina enters uterus, fallopian
tubes → infection, inflammation → possibly SIGNS & SYMPTOMS
spreads via
▫ Direct intraperitoneal spread from initial ▪ Vomiting, nausea, hiccupping, headaches
pelvic inflammation and infection
▪ Acute onset right upper quadrant
▫ Bacterial seeding via lymphatic abdominal pain; aggravated by breathing,
bloodstream coughing, laughing (pleuritic pain), may
▫ Autoimmune response to PID refer to right shoulder, tenderness to
300 OSMOSIS.ORG
palpation, tenderness to percussion of

overlying ribs TREATMENT
▪ Fever, chills, night sweats, malaise, vaginal
discharge, lower abdominal pain, cervical
MEDICATIONS
motion tenderness ▪ Organism-specific antibiotics
▪ Pain management
▫ Appropriate analgesia
DIAGNOSIS ▫ Laparoscopy for lysis of adhesions for
refractory pain
▪ History of pelvic inflammatory disease
DIAGNOSTIC IMAGING
▪ Typically normal
Abdominal CT scan with contrast

▪ Perihepatic
▫ Subtle enhancement of liver capsule,
inflammatory stranding and fluid along
right paracolic gutter and perihepatic
region, gallbladder wall thickening,
pericholecystic inflammatory change
▪ Pelvic Figure 36.7 A laparoscopic view of intra
▫ Possible tubo-ovarian abscess abdominal adhesions caused by Fitz-Hugh-
Curtis syndrome.
LAB RESULTS
▪ Liver function tests
▫ Typically normal
▪ D-dimer
▫ Markedly raised
▫ Often ordered due to pleuritic chest pain
▪ Endocervical/low vaginal swab
▫ Culture causative organism
OTHER DIAGNOSTICS
Laparoscopy
▪ “Violin string” adhesions of parietal
peritoneum to liver/diaphragm
OSMOSIS.ORG 301
HEMOCHROMATOSIS
osms.it/hemochromatosis

▪ Excessive iron absorption in the intestine → ▪ Initially asymptomatic
iron deposited in organs and tissues → free ▫ Biogically male: symptoms appear
radical generation → cellular damage → around age 50
cell death → tissue fibrosis ▫ Biologically female: eliminate iron
through menstrual bleeding →
TYPES symptoms appear 10-20 years after
menopause
Primary (hereditary: autosomal recessive) ▪ Signs and symptoms of liver disease
▪ Variety of possible mutations (C282Y ▪ Altered glucose homeostasis (hyper/
being the most common) in HFE gene on hypoglycemia)
chromosome 6 regulating iron absorption ▪ Fatigue
from food → most of the iron in the food
▪ Arthralgia
is absorbed by enterocytes in the gut and
pass into the bloodstream → iron overload ▪ Sexual dysfunction
▪ Abdominal pain
Secondary (not genetic) ▪ Cardiac arrhythmias
▪ Multiple blood transfusions → erythrocytes
contain iron bound to the hemoglobin →
heme is released in bloodstream when DIAGNOSIS
erythrocytes die after 120 days
▪ Chronic hemolytic anemias LAB RESULTS
▪ Excessive iron intake (very rare) ▪ High levels of serum iron
▪ Elevated ferritin
COMPLICATIONS ▪ High transferrin saturation
▪ Caused by deposition of iron in tissues ▪ Decreased total iron binding capacity
▫ Liver: cirrhosis, cancer
Liver biopsy
▫ Pancreas: altered endocrine and
▪ Iron can be seen as brown spots inside
exocrine function
hepatocytes → it becomes blue with a
▫ Skin: bronze pigmentation Prussian blue stain
▫ Heart: cardiomyopathy, arrhythmias
▫ Gonads (related to impaired pituitary
OTHER DIAGNOSTICS
function): amenorrhea in biologically-
female individuals, testicular atrophy in ▪ Genetic analysis and screening of family
biologically-male individuals members
▫ Adrenal gland: gland insufficiency
▫ Joints: degenerative joint disease
302 OSMOSIS.ORG
TREATMENT
MEDICATIONS
Deferoxamine
▪ Chelating agent binds iron molecules →
deferoxamine excreted by kidneys → urine
excretion → decreases iron load
SURGERY
▪ Advanced liver damage → transplantation
Figure 36.8 Iron deposition (hemosiderosis)
in the liver parenchyma in a case
hemochromatosis. There is associated OTHER INTERVENTIONS
hepatocyte damage. ▪ Phlebotomy
▪ Dietary changes to reduce iron absorption
Figure 36.9 Prussian blue stain on a liver

biopsy highlights iron deposits in a case of
hemochromatosis.
OSMOSIS.ORG 303
HEPATITIS B
osms.it/hepatitis

▪ Infection of the liver caused by hepatitis B LAB RESULTS
virus (HBV) ▪ HBV virions found in blood serum, proves
▪ DNA virus from the hepadna group viral replication
▪ Incubation is 1–6 months, long term carrier ▪ ↑ ALT, ↑ AST
state established after, transmitted through ▪ ↑ CRP, ↑ ESR, ↑ WBC
blood or semen ▪ HBsAg (surface antigen); present in acute
▪ Immune system attacks infected infection then cleared in recovery; if present
hepatocytes over six months → chronic infection; used
to create vaccine
RISK FACTORS ▪ Anti-HBc IgM (core antigen); present in
▪ Intravenous drug users, unprotected active infection for six months; if present
sexual intercourse, blood transfusions; longer individual is carrier; used for
hemodialysis screening because present most of the time
▪ Anti-HBc IgG develop after IgM, lifelong
secretion indicates individual is immune
COMPLICATIONS ▪ Anti-HBe secreted core antigen, appears
▪ Liver cirrhosis, hepatocellular carcinoma during viral replication, indicates active
infection
▪ Bilirubin normal to increased
SIGNS & SYMPTOMS
▪ General infection OTHER DIAGNOSTICS
▫ Low grade fever, malaise, lethargy, ▪ Physical exams shows hepatomegaly
anorexia
▪ Liver related
▫ Fatty stool, dark urine, jaundice,
TREATMENT
hepatomegaly, scleral icterus, pruritus,
right upper quadrant tenderness
MEDICATIONS
▪ Interferon alpha, nucleoside reverse
transcriptase inhibitors (NRTI)
▪ Post exposure prophylaxis available with
HBV immunoglobulins
▪ Vaccine available
304 OSMOSIS.ORG
HEPATITIS C
osms.it/hepatitis

▪ Viral hepatitis caused by hepatitis C virus LAB RESULTS
(HCV) ▪ Enzyme-linked immunosorbent assay
▪ RNA virus from the class of flaviviridae (ELISA) used to detect antibodies in
▪ Incubation is 6–7 weeks, lifelong infectious chronic cases, may be false negative in
carrier state immunosuppressed
▪ Virus mutates often to bypass the host ▪ Specific hepatitis C antigens immunoassay
immune system ▪ HCV RNA test with PCR
▪ Minority of individuals develop acute ▪ ↑ ALT
hepatitis symptoms, due to this majority ▪ ↑ CRP, ↑ ESR, ↑ WBC
progress to chronic infection
OTHER DIAGNOSTICS
RISK FACTORS ▪ Physical exam shows enlarged liver
▪ Intravenous drug use, sexual contact, from
mother to child in neonatal period (vertical
transmission); chronic hemodialysis TREATMENT
COMPLICATIONS MEDICATIONS
▪ Cirrhosis, hepatocellular carcinoma, renal ▪ Interferon alfa, ribavirin
dysfunction (HCV immune complexes ▪ Screen for HBV, HIV and HAV; vaccinate
involved in pathogenesis) against HBV and HAV if tests are negative
▪ No HCV vaccine available

▪ Liver transplant in case of liver failure
▪ General infection
▫ Low grade fever, malaise, lethargy,
anorexia
▪ Liver related
▫ Fatty stool, dark urine (iron), jaundice,
hepatomegaly, icterus, pruritus
OSMOSIS.ORG 305
HEPATITIS E
osms.it/hepatitis

▪ Viral hepatitis caused by hepatitis E virus LAB RESULTS
(HEV) ▪ Anti - HEV IgM assay in acute infection,
▪ RNA virus from the class hepeviridae PCR in chronic cases
▪ Transmitted via fecal-oral route ▪ ↑ ALT
▪ ↑ CRP, ↑ ESR, ↑ WBC
RISK FACTORS
▪ Consuming contaminated food and water OTHER DIAGNOSTICS
in endemic areas, blood transfusions, from ▪ Physical exam shows enlarged liver
mother to child in neonatal period
▪ Rare but if present then cholestatic
MEDICATIONS
hepatitis, chronic infection in
immunosuppressed individuals, liver failure, ▪ Ribavirin used in immunosuppressed
high mortality rate in pregnant individuals individuals
SURGERY
SIGNS & SYMPTOMS ▪ Liver transplant in case of liver failure
▪ General infection
▫ Low grade fever, malaise, lethargy,
anorexia
▪ Liver related
▫ Fatty stool, dark urine (iron), jaundice,
hepatomegaly, icterus, pruritus
▪ Other
▫ Diarrhea, arthralgia, urticarial rash
306 OSMOSIS.ORG
HEPATOCELLULAR ADENOMA
osms.it/hepatocellular-adenoma

▪ Rare, benign liver tumor DIAGNOSTIC IMAGING
▪ Formed from hepatic epithelial cells, often ▪ Often incidental finding on abdominal
in healthy liver imaging
▫ Enlarged, nonfunctional epithelial cells
Ultrasound
▫ More glycogen, lipids than expected
▪ Solitary well-demarcated heterogeneous
▫ Surrounding tissue highly vascularized mass with variable echogenicity
▫ Bile ducts, portal triads absent
CT scan
CAUSES ▪ Well-marginated isoattenuating hepatic
lesions; fat content → hypoattenuation
▪ Exact mechanisms unknown; associated
with estrogen-based drugs: oral
contraceptives, anabolic steroids LAB RESULTS
▪ Genetic diseases
Histology (definitive)
▫ Glycogen storage disease type I (von
▪ Well-circumscribed nodules
Gierke’s disease): glucose cannot
be generated from glycogen via ▫ Sheets of hepatocytes with bubbly
gluconeogenesis vacuolated cytoplasm
▪ Lack portal tracts/central veins
RISK FACTORS
▪ Diabetes, metabolic syndrome, obesity TREATMENT
COMPLICATIONS SURGERY
▪ Rupture, bleeding; malignant ▪ Surgical resection
transformation (rare)
OTHER INTERVENTIONS
▪ Estrogen-associated
SIGNS & SYMPTOMS ▫ Cessation of estrogen-based medication
→ adenoma regression
▪ Von Gierke’s disease
▪ Abdominal pain (esp. epigastric/RUQ),
▫ Strict dietary management → adenoma
palpable mass
regression
▪ If adenoma ruptures, bleeds
▫ Hypotension, tachycardia, diaphoresis
OSMOSIS.ORG 307
Figure 36.10 Intraoperative photograph of
a large, well-circumscribed hepatocellular
adenoma of the left lobe of the liver. There
is a rim of normal liver surrounding the
adenoma. The right lobe of the liver is just
visible to the left of the image.
NEONATAL HEPATITIS
osms.it/neonatal-hepatitis
COMPLICATIONS
PATHOLOGY & CAUSES ▪ If untreated > six months
▫ Chronic liver disease → hepatic cirrhosis
▪ Inflammation of liver in newborns (usually
→ liver failure
1–2 months after birth)

▪ Viruses (20%)
▫ Infect mother during pregnancy/baby ▪ Jaundice, pruritus, rashes, dark urine,
shortly after birth pale stools, hepatomegaly (due to liver
▫ Rubella; Cytomegalovirus (CMV); inflammation)
hepatitis A,B,C ▪ Decreased intestinal bile flow → impaired
▪ Idiopathic (80%) fat digestion, vitamin absorption → failure
to grow
▫ Unknown origin
▫ Viral
▫ Neonatal cholestasis DIAGNOSIS
▫ Newborn bile production immature → ↓
bile production DIAGNOSTIC IMAGING
▫ Developing liver more sensitive to injury
→ ↓ bile synthesis, flow Ultrasound
▪ Genetic ▪ Check bile ducts for obstruction, correct
development
▫ Alpha 1-antitrypsin deficiency:
malformation → cannot be transported
out of hepatocytes → accumulation
within cells → cell death → hepatitis
308 OSMOSIS.ORG
LAB RESULTS
TREATMENT
Liver biopsy
▪ Multinucleated giant cells MEDICATIONS
▫ Arise from combination of neighboring ▪ Ursodeoxycholic acid
cells (hepatocytes) ▫ Increase bile formation
▫ Signs of cholestatic liver disease
Blood tests
SURGERY
▪ Cirrhotic liver disease/liver failure requires
▪ ↑ serum bilirubin
liver transplant
OTHER INTERVENTIONS
▪ Optimize nutrition/vitamin supplementation
NON-ALCOHOLIC FATTY LIVER

DISEASE
osms.it/non-alcoholic-fatty-liver
NAFL → NASH
PATHOLOGY & CAUSES
▪ Second hit hypothesis
▪ Disease due to fat accumulation in liver, ▫ Initial fatty change benign → oxidative
associated inflammation stress, hormonal imbalances,
mitochondrial abnormalities →
progression
TYPES ▪ Hepatocytic fat vulnerable to degradation
Non-alcoholic fatty liver (NAFL) ▫ Unsaturated fatty acids: ≥ one double
bond, hydrogen atoms vulnerable to
▪ Steatosis without inflammation
initiators (e.g. reactive oxygen species)
Non-alcoholic steatohepatitis (NASH) ▫ Process damages cell lipid membranes
▪ Steatosis with hepatic inflammation, → mitochondrial dysfunction → cell
indistinguishable from alcoholic death → inflammation → steatohepatitis
steatohepatitis (NASH)
Subtype
RISK FACTORS
▪ Liver steatosis without evident secondary
▪ NAFL → NASH
cause (e.g. chronic alcohol use/persistent
viral infection) ▫ Age > 50
▫ Liver large, soft, yellow greasy ▫ BMI ≥ 28kg/m2 (5.7lbs/ft2)
▫ Bloating, hepatocyte necrosis ▫ Diabetes mellitus
▫ Mallory–Denk bodies ▫ Elevated serum aminotransferases
▫ Damage attracts neutrophils → more ▫ Ballooning degeneration, Mallory–Denk
inflammation bodies or fibrosis on biopsy
▫ Inflammation → hepatic stellate cells ▪ NAFL (general)
activate → fibrosis → cirrhosis ▫ Insulin resistance, metabolic syndrome,
▫ ≥ Three of: obesity, hypertension,
OSMOSIS.ORG 309
diabetes, hypertriglyceridemia, Liver biopsy
hyperlipidemia, excessive soft drink ▪ > 5% fat content → NAFL
consumption (high concentration of ▪ Iron deposits
fructose), diet rich in saturated fats,
▪ NAFL
medications (corticosteroids)
▫ Steatosis alone
▫ Steatosis with lobular/portal
COMPLICATIONS inflammation without hepatocyte
▪ Liver cirrhosis, hepatocellular carcinoma ballooning
▫ Steatosis with hepatocyte ballooning
but without inflammation
SIGNS & SYMPTOMS ▪ NASH
▪ Usually asymptomatic ▫ Hepatocyte ballooning degeneration,
hepatic lobular inflammation,
▪ Fatigue, malaise, dull right upper quadrant
apoptotic bodies, mild chronic portal
pain, mild jaundice (rare), significant liver
inflammation, perisinusoidal collagen
damage → hepatomegaly, ascites
deposition → zone 3 accentuation
(chicken wire pattern), portal fibrosis
without perisinusoidal or pericellular
DIAGNOSIS fibrosis, cirrhosis (macronodular
or mixed), Mallory–Denk bodies,
▪ Typically diagnosed as incidental finding on megamitochondria, vacuolated nuclei in
liver function panel periportal hepatocytes
DIAGNOSTIC IMAGING OTHER DIAGNOSTICS

▪ Identify fatty infiltrates ▪ Alcohol consumption > 25 ml/day pure
Ultrasound ethanol excludes diagnosis
▪ Increased echogenicity → bright appearing
liver → diffuse fatty infiltration TREATMENT
CT scan
▪ Decreased hepatic attenuation
OTHER INTERVENTIONS
Dietary changes
MRI
▪ Avoid high fructose-corn syrup, trans-fats
▪ Increased fat signal
▪ Omega 3 fatty acid supplementation →
improvement in liver fat deposition
LAB RESULTS ▪ Coffee and olive oil consumption may be
▪ Destruction of hepatocytes → increase in protective
liver enzymes AST/ALT
▪ Serum ALT > AST level = NAFL Treat insulin resistance
▪ Weight-loss
▪ Insulin sensitizers
Treat hyperlipidemia
▪ Statins
310 OSMOSIS.ORG
PORTAL HYPERTENSION
osms.it/portal-hypertension

▪ Elevation of blood pressure in the portal ▪ GI bleeding (secondary to esophagogastric
venous system above 5mmHg varices) → most life-threatening
complication
CAUSES ▫ Hematemesis
▫ Melena
Prehepatic causes ▪ Jaundice
▪ Portal vein obstruction (e.g. thrombosis) ▪ Ascites
Intrahepatic causes ▪ Periumbilical caput medusae
▪ Cirrhosis (most common of all causes) ▪ Signs and symptoms of encephalopathy
▪ Schistosomiasis ▫ Altered level of consciousness
▪ Sarcoidosis ▫ Lethargy
▫ Hand tremor when the wrist is extended
Posthepatic causes (aka asterixis)
▪ Right-sided heart failure ▫ Seizure, coma and death
▪ Constrictive pericarditis
▪ Budd–Chiari syndrome
DIAGNOSIS
COMPLICATIONS DIAGNOSITC IMAGING
▪ Portosystemic shunts and development of
collateral channels Liver ultrasound
▫ Esophageal varices ▪ Nodules in case of cirrhosis
▫ Hemorrhoids CT scan, MRI
▫ Caput medusae (distension of ▪ Ascites
abdominal wall veins)
▪ Cirrhosis
▪ Increased hydrostatic pressure and
▪ Splenomegaly
hypoalbuminemia → ascites
▪ Vascular alteration such as inferior vena
▪ Splenomegaly (blood drainage backs up to
cava dilatation
spleen due to high pressure portal system)
→ sequestration of blood elements →
anemia, thrombocytopenia, leukopenia LAB RESULTS
▪ Liver disease and blood shunting away ▪ Full blood count
from liver → decreased blood detoxification ▪ Liver enzymes and serology
→ increased ammonia in the blood → ▪ Perform emergent upper GI endoscopy, to
encephalopathy diagnose/treat varices
▪ Spontaneous bacterial peritonitis
OSMOSIS.ORG 311
OTHER DIAGNOSTICS
TREATMENT
Diagnostic paracentesis
▪ Will determine if ascites is due to portal ▪ Prevent and treat the complications
HTN or other etiology
▪ Serum ascites albumin gradient (SAAG) > MEDICATIONS
1.1 mg/dL ▪ Beta-blockers
▫ Portal HTN is likely ▫ → decrease portal venous pressure
▪ IV octreotide
▫ If bleeding, non-selective beta blockers
(prophylaxis), antibiotics (prophylaxis for
spontaneous bacterial peritonitis)
▫ For esophageal varices
▪ Diuretics and sodium restriction
▫ For ascites
SURGERY
▪ Transjugular intrahepatic portosystemic
shunt
▫ Communication between portal vein
and hepatic vein → blood bypasses the
liver circulation → reduced intrahepatic
pressure
▪ Balloon tamponade, sclerotherapy, variceal
ligation/banding
Figure 36.11 Ascites as a consequence of
▫ For esophageal varices
portal hypertension caused by cirrhosis of
the liver.
MNEMONIC: ABCDE
Features of Portal
hypertension
Ascites
Bleeding (haematemesis, piles)
Caput medusae
Diminished liver
Enlarged spleen
Figure 36.12 Barium swallow demonstrating

esophageal varices.
312 OSMOSIS.ORG
Figure 36.13 Endoscopic appearance of

esophageal varices.
PRIMARY BILIARY CIRRHOSIS

osms.it/primary-biliary-cirrhosis
COMPLICATIONS
PATHOLOGY & CAUSES ▪ Osteoporosis, hyperlipidemia, fat soluble
vitamin deficiencies
▪ Autoimmune disease of liver → progressive
destruction of cells lining small intrahepatic
bile ducts → leakage of bile, toxins into SIGNS & SYMPTOMS
liver parenchyma, blood → inflammation,
fibrosis → cirrhosis
▪ Fatigue, pruritus, jaundice, right upper
▪ AKA primary biliary cholangitis quadrant pain
▪ Loss of bone density → fractures
CAUSES ▪ Hypercholesterolemia → xanthelasma,
▪ Failure of immune tolerance against xanthoma
mitochondrial pyruvate dehydrogenase ▪ Liver cirrhosis → ascites, splenomegaly,
complex (PDC-E2), other hepatic proteins esophageal varices, hepatic
→ destruction of cells lining bile ducts → encephalopathy
autoimmunity

▪ Biological female, family history of disease,
DIAGNOSTIC IMAGING
extrahepatic autoimmune disease
▫ Previous infection with environmental Abdominal ultrasound/MRCP/CT scan
gram-negative Novosphingobium ▪ Rule out bile duct obstruction
aromaticivorans → cross-reaction
between bacterial antigens, hepatic
mitochondrial proteins LAB RESULTS
▪ Antimitochondrial antibodies (most
individuals)
OSMOSIS.ORG 313
▪ Other autoantibodies may be present
▫ Antinuclear antibody, anti-
TREATMENT
glycoprotein-210 antibodies, anti-p62
antibodies (suggests more severe
MEDICATIONS
disease → liver failure), anticentromere ▪ Ursodeoxycholic acid
antibodies (correlates with developing ▫ Reduces intestinal absorption of
portal hypertension), anti-np62 and cholesterol → reduces cholestasis,
anti-sp100 improves liver function tests
▪ Elevated IgM, total cholesterol, HDL, GGT, ▪ Cholestyramine
ALP (released from damaged bile ducts), ▫ Bile acid sequestrant → reduces bile
bilirubin = advanced disease acid absorption in gut → relieves itching
due to bile acids in circulation
Liver biopsy (percutaneous/laparoscopic)
▪ Modafinil
▪ Interlobular bile duct destruction, bile duct
▫ For fatigue
inflammation (intraepithelial lymphocytes),
periductal epithelioid granulomas
OTHER INTERVENTIONS
▪ Cease all alcohol intake

of primary biliary cirrhosis. The bile duct
is surrounded by epithelioid macrophages
which in turn are surrounded by a rim of
lymphocytes, indicative of granulomatous
inflammation.
WILSON'S DISEASE
osms.it/wilsons-disease
▪ Reduced copper elimination in the bile
PATHOLOGY & CAUSES ▪ Copper accumulation in hepatocytes → free
radical generation → hepatocyte damage
▪ Autosomal recessive mutation in ATP7B → spilling of free copper into the blood
gene → defect in ATP7B transport protein → copper accumulation in organs and
action in the hepatocyte tissues → free radical generation → tissues
▪ AKA hepatolenticular degeneration damage
▪ Reduced copper incorporation into
apoceruloplasmin and reduction of its
copper-bound form (ceruloplasmin)
314 OSMOSIS.ORG
COMPLICATIONS
▪ Liver: cirrhosis, liver failure
DIAGNOSIS
▪ Brain: movement disorders, dementia, and LAB RESULTS
psychiatric issues
▪ Signs of liver dysfunction (e.g. high liver
▪ Kidney: renal disease enzymes)
▪ Eye: Kayser–Fleischer’s ring, sunflower ▪ Low serum ceruloplasmin
cataract
▪ High 24-hour copper excretion
▪ Blood: hemolytic anemia
TREATMENT
SIGNS & SYMPTOMS
MEDICATIONS
▪ Presents at a young age (< 30 years old)
▪ Chelating agents → make it easier to
▪ Signs and symptoms of cirrhosis and portal excrete copper
hypertension (e.g. hepatosplenomegaly,
▫ Penicillamine (penicillin metabolite
jaundice, ascites, esophageal varices)
without antibiotic properties)
▪ Signs of renal dysfunction
▫ Trientine hydrochloride
▪ Parkinsonian-like movement disorders
▪ Agents that block intestinal absorption of
▫ Tremors copper
▫ Rigidity ▫ Ammonium tetrathiomolybdate
▪ Psychiatric illness ▫ Zinc
▫ Depression
▫ Personality changes
SURGERY
▫ Psychosis
▪ Advanced liver damage → transplantation
▫ Cognitive dysfunctions
▪ Kayser–Fleischer ring
▫ Ring of copper deposition in the cornea
OTHER INTERVENTIONS
(Descemet’s membrane) ▪ Eliminate copper-rich food (e.g.
mushrooms, nuts, shellfish)
▫ Appears to encircle the iris
Figure 36.15 Copper deposition in

Descemet’s membrane of the sclera results in
a Kayser–Fleischer ring.
OSMOSIS.ORG 315
NOTES
NOTES
LOWER GASTROINTESTINAL
CONGENITAL MALFORMATIONS

▪ Lower gastrointestinal tract structural/ DIAGNOSTIC IMAGING
functional anomalies during embryonic ▪ Prenatal ultrasound, MRI, CT scan/
development; present at birth radiography
▪ Malformations from duodenum to anus ▪ Avoid X-ray due to teratogenicity
CAUSES
TREATMENT
▪ Genetic, environmental factors
SURGERY
SIGNS & SYMPTOMS ▪ See individual disorders
▪ At birth: may be asymptomatic

▪ Malformations: relatively benign (nausea,
vomiting, difficulty passing stool) to life
incompatibility
GASTROSCHISIS
osms.it/gastroschisis
CAUSES
PATHOLOGY & CAUSES ▪ Genetic, environmental factors
▪ Extrasomatic protrusion of intestines
through hole in abdominal wall near RISK FACTORS
umbilicus ▪ Mother’s young age
▪ Hernia: affected organs exit cavity ▪ Exposure to teratogenic substances
▪ Week 4 of gestation: lateral folds fail to (alcohol, tobacco)
fuse → hole in abdominal wall → organs
protrude COMPLICATIONS
▪ Most common on right side ▪ Intestinal inflammation due to intrauterine
▪ Usually small intestine exposure to amniotic fluid, malabsorption,
▪ Stomach, liver may also protrude (rare) infarction of intestinal tube due to
compressed blood vessels, infection
316 OSMOSIS.ORG
Chapter 37 Lower Gastrointestinal Congenital Malformations
SIGNS & SYMPTOMS

▪ During fetal life: asymptomatic
▪ At birth: difficulty feeding/passing stool
DIAGNOSIS
DIAGNOSTIC IMAGING
Intrauterine ultrasound, MRI
X-ray, CT scan
▪ Post-op evaluation
LAB RESULTS
▪ Increased maternal serum alpha-
fetoprotein (MSAFP) Figure 37.1 An abdominal X-ray of a newborn
with gastroschisis. The abdominal contents
OTHER DIAGNOSTICS are clearly visible outside the abdominal wall.
▪ Defect visible at birth
TREATMENT
▪ Fatal if untreated
MEDICATIONS
▪ Antibiotics for existing/potential infection
▪ IV fluid/nutrients
SURGERY
▪ Surgical repositioning of organs back into
abdominal cavity, closure of abdominal wall
defect
▪ Usually requires multiple surgeries
OSMOSIS.ORG 317
HIRSCHSPRUNG'S DISEASE
osms.it/hirschsprungs-disease

▪ Myenteric (Auerbach), submucosal DIAGNOSTIC IMAGING
(Meissner) plexuses absent from intestinal ▪ Barium assisted radiography
wall in distal bowel
▪ AKA congenital aganglionic megacolon
LAB RESULTS
▪ Absent plexuses (regulate bowel function)
▪ Rectal suction biopsy
→ intestine muscles permanently
constricted → passing stool difficult,
impossible OTHER DIAGNOSTICS
▪ Digital rectal exam
CAUSES
▪ Failure of neuroblasts to migrate from
neural crest to intestine, form plexuses
TREATMENT
▪ Genetic: RET proto-oncogene, EDNRB, etc. SURGERY
▪ RET proto-oncogene: sporadic/autosomal ▪ Surgical resection of intestine, subsequent
dominant (familial) cases; associated with fusion of remaining healthy tissue (pull-
Down syndrome through technique)
▪ Isolated: sporadic/autosomal dominant
▪ Present within syndrome: Down syndrome,
multiple endocrine neoplasia II, etc.
COMPLICATIONS
▪ Constipation/obstipation, malnutrition,
enterocolitis, intestinal perforation,
megacolon
SIGNS & SYMPTOMS

▪ At birth: asymptomatic
▪ Can be diagnosed in adulthood
▪ First sign: baby’s inability to pass Figure 37.2 Immunohistochemical
meconium, 48 hours postpartum staining for acetylcholinesterase in the
▪ Vomiting, abdominal distension, colics colon of an individual with Hirschprung’s
disease. Ganglia are absent resulting in
overstimulation of nerves and increased
levels of acetylcholinesterase.
318 OSMOSIS.ORG
IMPERFORATE ANUS
osms.it/imperforate-anus

▪ Narrowed anal opening (anal stenosis)/ DIAGNOSTIC IMAGING
complete atresia
MRI, ultrasound, X-ray/CT scan
▪ AKA anal atresia
▪ Determine internal extent of defect, plan
▪ Anus completely closed → colon ends in
corrective surgery
blind pouch in pelvis/opens into other pelvic
structures (bladder, vagina) via fistulae
▪ All pelvic structures open into same OTHER DIAGNOSTICS
channel → persistent cloaca ▪ Physical exam at birth, defect visible
▪ Nerve, muscle tissue of missing parts of
anus, rectum missing/malformed
TREATMENT
CAUSES SURGERY
▪ Mostly unknown genetic cause ▪ Anoplasty if possible, colostomy if not
▪ HLXB9 gene: only when imperforate anus
is present within Currarino syndrome
COMPLICATIONS
▪ Megacolon, intestinal rupture, septic shock,
incontinence/constipation (even after
surgery)
MNEMONIC: VACTERL
Group of malformations with
common, unknown cause
Vertebral anomalies
Anal atresia
Cardiovascular anomalies
Tracheoesophageal fistula
Esophageal atresia
Renal anomalies
Figure 37.3 A lateral X-ray of a neonate
Limb defects
demonstrating an imperforate anus. The
rectum is dilated and the anal canal is absent.
SIGNS & SYMPTOMS

▪ Constipation (if anus narrowed), obstipation
(if anus non-existent)
▪ Vomiting, abdominal distension
OSMOSIS.ORG 319
INTESTINAL ATRESIA
osms.it/intestinal-atresia
CAUSES
PATHOLOGY & CAUSES ▪ Duodenal intestinal atresia
▫ Strongly associated with trisomy 21
▪ Congenital malformation resulting in closed/
(Down syndrome)
absent part of small/large intestine
▪ Non-duodenal intestinal atresias
▪ Different from intestinal stenosis; in
stenosis the passageway exists, and is just ▫ Intrauterine ischemic injury (small part
narrowed of duodenum, entire jejunum, ileum,
colon receive vascularization from
superior mesenteric artery)
TYPES
▪ Named according to affected portion of
intestine: duodenal, jejunal, ileal, colonic
COMPLICATIONS
▪ Distension of stomach and duodenum
▪ Divided into duodenal/non-duodenal
caused by accumulated amniotic fluid
intestinal atresia due to different
which has nowhere to go
mechanism of origin
▪ Polyhydramnios (accumulation of amniotic
▪ Duodenal intestinal atresia is caused by
fluid in amniotic sac)
failure in duodenal vacuolization
▫ Fetus swallows less fluid due to
▫ During fetal development duodenal
intestinal obstruction → more fluid
epithelium proliferates rapidly →
accumulates in amniotic sac
complete duodenal obstruction
(AKA solid phase of vacuolization)→ ▪ Intestinal perforation and
apoptosis of excess cells → formation pneumoperitoneum/meconium peritonitis
of small vacuoles which fuse → re-
establish duodenal passageway (AKA
recanalization phase) SIGNS & SYMPTOMS
▪ Bilious vomiting, abdominal pain,
malnutrition
320 OSMOSIS.ORG
DIAGNOSIS
DIAGNOSTIC IMAGING
Prenatal ultrasound
▪ To assess signs of obstruction; detectable
in the third trimester
▫ Duodenal atresia: dilated fluid-filled
stomach adjacent to dilated duodenum
▫ Non-duodenal intestinal atresia: Dilated
fluid-filled bowel loops
▫ Polyhydramnios
Postnatal X-ray
▪ Duodenal atresia: Double bubble sign
(dilated stomach adjacent to dilated
duodenum) Figure 37.5 A plain abdominal radiograph of
▪ Non-duodenal intestinal atresia: dilated a neonate demonstrating the double bubble
bowel loops with air-fluid levels proximal to sign of duodenal atresia.
the obstruction
OTHER DIAGNOSTICS
▪ Physical examination
▫ Apple peel (spiral) shape of intestines
upon visual examination during surgery
▪ Amniocentesis to determine possible
trisomy 21
TREATMENT
SURGERY
▪ Gastric decompression: removal of fluid
from stomach
▪ IV fluid compensation
▪ Surgical reattachment of functional portions
of intestines
▫ In case of duodenal intestinal atresia →
duodenoduodenostomy
Figure 37.4 A plain abdominal radiograph of

a neonate demonstrating the triple bubble
sign of jejunal atresia.
OSMOSIS.ORG 321
INTESTINAL MALROTATION
osms.it/intestinal-malrotation

▪ Improper rotation of midgut during DIAGNOSTIC IMAGING
embryogenesis
MRI/CT scan/barium-assisted radiography
▪ Rapid midgut growth in restricted space →
herniation into umbilical coelum → rotation ▪ Detect improper organ position
270° around SMA → error occurs = final
anatomy description
▫ Small intestine lodges into left TREATMENT
abdominal cavity → cecum in lower
right quadrant, first two thirds of colon SURGERY
lodge into right side over small intestine ▪ Surgical repositioning of intestines,
▪ Due to error, several organs in incorrect resection of Ladd’s bands to remove
anatomical position duodenal obstruction
▫ Small intestine in right side ▪ Preventive appendectomy
▫ Coecum in epigastrium
▫ Appendix follows coecum
▫ Ladd’s bands span over vertical
duodenum, compressing from outside
▫ Suspensory muscle of duodenum
further right
▫ Mesentery of small intestine narrower
root
COMPLICATIONS
▪ Omphalocele, volvulus (part of intestine
rotates around itself/part of mesenterium
→ blocks passage of intestinal content →
compresses blood vessels → obstructs
blood flow), ileus, ischemic bowel,
malnutrition, hernias
SIGNS & SYMPTOMS

Figure 37.6 An abdominal X-ray with bowel
contrast demonstrating intestinal malrotation.
▪ Colic, bilous regurgitation, abdominal The entire small bowel is situated on the right
distension side of the abdomen.
322 OSMOSIS.ORG
MECKEL'S DIVERTICULUM
osms.it/meckels-diverticulum

▪ Abnormal pouch on antimesenteric side of DIAGNOSTIC IMAGING
ileum
Abdominal ultrasound/CT scan
▪ True diverticulum (contains all three layers
of intestinal wall) ▪ Incidental finding
▪ Early fetal life: nutrients received from yolk Angiography
sac into ileum via omphalomesenteric duct
until it obliterates (week 5–6 of pregnancy)
▪ If omphalomesenteric duct obliterates OTHER DIAGNOSTICS
improperly: Meckel’s diverticulum Meckel’s scan
▪ May contain ectopic epithelia, ▪ In children; technetium-99m procedure,
omphalomesenteric duct lined with detects gastric mucosa in diverticulum
pluripotent cells
Surgery
COMPLICATIONS ▪ Incidental finding
▪ Diverticulitis, ulcers from HCl secretion
if gastric mucosa present, perforation of
diverticulum, food impaction, lithiasis,
TREATMENT
peritonitis, peritoneal adhesions,
intussusception, volvulus, neoplasms SURGERY
▪ Uncomplicated: resection of diverticulum
▪ Complicated: resection of diverticulum,
MNEMONIC intestine
Meckel's Rule of 2s
Symptomatic presentation
before 2 years of age
2% of population
Approximately 2 feet from
ileocecal valve
2 inches in length
2 types of ectopic mucosa
(pancreatic, gastric)
SIGNS & SYMPTOMS

▪ Abdominal pain/distension, melena,
vomiting, constipation
Figure 37.7 Intraoperative photograph of a
Meckel’s diverticulum.
OSMOSIS.ORG 323
demonstrating a Meckel’s diverticulum.
Figure 37.9 Histological appearance of a Meckel’s diverticulum containing ectopic gastric

mucosa.
324 OSMOSIS.ORG
OMPHALOCELE
osms.it/omphalocele

▪ Persistent, pathological, herniation of DIAGNOSTIC IMAGING
intestines into umbilical cord
Intrauterine ultrasound
▪ Midgut herniates through umbilicus → pulls
layer of peritoneum into umbilical cord in MRI
order to properly develop (grow, rotate) due
to insufficient space in abdominal cavity →
returns into abdomen LAB RESULTS
▪ Midgut doesn’t return: omphalocele ▪ Blood test for MSAFP
▪ High mortality rate ▪ Amniocentesis
CAUSES TREATMENT
▪ Associated with: trisomy 13 (Patau SURGERY
syndrome), trisomy 18 (Edward’s ▪ Surgical repositioning of protruding organs
syndrome), trisomy 21 (Down syndrome),
Beckwith–Wiedemann syndrome
RISK FACTORS
▪ Consumption of alcohol/tobacco during
pregnancy, certain medications (SSRIs),
obesity
COMPLICATIONS
▪ Abdominal cavity malformation, volvulus,
ischemic bowel
SIGNS & SYMPTOMS

▪ Intrauterine: asymptomatic
▪ At birth: visible defect
Figure 37.10 An MRI scan in the sagittal plane
demonstrating a large omphalocele. The
abdominal organs are clearly visible outside
the abdominal wall.
OSMOSIS.ORG 325
326 OSMOSIS.ORG
NOTES
NOTES
MALABSORPTION CONDITIONS

▪ Impaired ability of gastrointestinal tract to DIAGNOSTIC IMAGING
absorb nutrients ▪ Abdominal ultrasound, colonoscopy,
▪ Malabsorption may be intestinal biopsy, serological markers
▫ Global → impaired function of intestinal
cells LAB RESULTS
▫ Partial → external agent interferes with ▪ D-xylose test
absorption
▫ Test for carbohydrate malabsorption
▪ Manifestation of underlying illness; may be
▪ Fecal fat testing
congenital/acquired/infectious
▪ Complete blood count (CBC)
▫ Look for for infection, anemia
CAUSES
▪ Defects in absorption process of intestinal
cells (e.g. change to bowel surface area) OTHER DIAGNOSTICS
▪ Impaired nutrient digestion (e.g. altered ▪ Individual history
digestive enzymes) ▫ Pancreatitis
▫ Recent surgeries
▫ Symptoms of vitamin deficiency
SIGNS & SYMPTOMS ▫ Family history
▪ Abdominal distention, pain

▪ Chronic diarrhea, malabsorption, TREATMENT
dehydration
▪ Weight loss ▪ See individual disorders
▪ Clinical manifestations of nutritional
deficiencies (e.g. paresthesias from
cobalamin deficiency)
OSMOSIS.ORG 327
CELIAC DISEASE
osms.it/celiac-disease

▪ Autoimmune disorder of small intestine ▪ Abdominal distention, chronic diarrhea
▪ AKA gluten-sensitive enteropathy/ (steatorrhea)
nontropical sprue ▪ Failure to thrive (children)
▪ Dermatitis herpetiformis
CAUSES ▫ Circulating IgA antibodies attack dermal
▪ Triggered by foods containing gliadin, a papillae → generalized rash
peptide found in foods containing gluten
(e.g. grains: wheat, barley, rye, oats)
▫ Gluten consumption → degradation into
DIAGNOSIS
peptides in small intestine → secretory
IgA binds to gliadin in duodenum → LAB RESULTS
IgA-gliadin complex binds to transferrin ▪ Anti-gliadin IgA/IgG
receptor → IgA-gliadin complex travels ▪ Anti-endomysium IgA
across enterocyte into lamina propria ▪ Anti-tissue transglutaminase IgA
→ tissue transglutaminase deaminates ▫ Tissue transglutaminase: endomysial
gliadin → macrophages uptake, present enzyme released in response to cellular
deaminated gliadin in MHC-2 molecules stress
HLA-DQ 2, 8 → CD4+ activation
▫ More sensitive, specific
→ inflammatory cytokines released
(interferon gamma, tumor necrosis Duodenal biopsy
factor) → damage/destruction of ▪ Showing lymphocytic infiltration, villous
intestinal villi → B cell activation → anti- atrophy, crypt hyperplasia
gliadin, anti-tissue transglutaminase,
antiendomysial antibodies released
→ CD8+ cell activation → tissue TREATMENT
destruction
▪ On microscopy OTHER INTERVENTIONS
▫ Villous atrophy, mucosal inflammation, ▪ Correct nutritional deficiencies related to
intestinal crypt hyperplasia malabsorption
▪ Presence of anti-gliadin, anti-endomysium
IgA = pathognomonic Preventative
▪ Gluten-free diet
RISK FACTORS
▪ Northern European ancestry, genetic MNEMONIC: Grains are
component
BROWn
Grains to avoid with Celiac
disease
Barley
Rye
Oats
Wheat
328 OSMOSIS.ORG
Chapter 38 Malabsorption Conditions
Figure 38.1 Histological appearance of Figure 38.2 Clinical appearance of dermatitis

a duodenal biopsy in an individual with herpetiformis. Individual with celiac disease
celiac disease. There is villous blunting, an are at increased risk of this condition.
expansion of the lamina propria by chronic
inflammatory cells and an increase in crypt
length. A higher magnification would reveal
an increase in lymphocyte count in the
surface epithelium.
LACTOSE INTOLERANCE
osms.it/lactose-intolerance

▪ Decreased ability to digest lactose ▪ Occur after consuming lactose (e.g. milk,
▪ Lactose consumption → lactase deficiency/ cheese)
inactivity → ↑ undigested lactose → ▪ Abdominal pain, cramping in lower
fermentation by colonic flora → gas, quadrants
osmotically active substances produced → ▪ Abdominal distention, flatulence, vomiting,
bloating, diarrhea diarrhea (more common in children)
CAUSES
▪ Most often acquired due to physiologic
DIAGNOSIS
weaning off of milk
▪ Based on above symptoms
RISK FACTORS
LAB RESULTS
▪ Non-European ancestry (most common)
▪ Unabsorbed carbohydrates → high stool
▪ Increases with age
osmotic gap
▪ May be congenital
▪ Bacterial lactose fermentation → acidic
▫ Rare, autosomal recessive disorder stool pH
▪ May be developmental
▫ Most common among premature infants
▪ Underlying intestinal disease
OSMOSIS.ORG 329
Preventative
TREATMENT ▪ Lactose-free diet
OTHER INTERVENTIONS ▫ Compensate with lactase
▪ Optimize calcium, vitamin D intake
SMALL BOWEL BACTERIAL

OVERGROWTH SYNDROME
osms.it/sbbos
▪ Altered mental status after high

PATHOLOGY & CAUSES carbohydrate meal
▪ Failure to thrive (children)
▪ Excessive colonic bacteria colonizing small
intestine
▪ Often occurs secondary to conditions DIAGNOSIS
limiting intestinal motility, gastric acid and
bile secretion and IgA deficiencies LAB RESULTS
▪ Signs/symptoms of vitamin, electrolyte
CAUSES abnormalities
▪ Alteration of factors regulating intestinal ▫ Weakness, ataxia, paresthesias → B12
flora → aerobic bacteria proliferation → deficiency
changes in aerobic microclimate of small ▫ Perioral numbness, feet paresthesias,
intestine → migration of colonic anaerobic muscle cramping → calcium deficiency
bacteria → damage to intestinal surface → ▪ Anemia
maldigestion, malabsorption → symptoms
▫ Macrocytic → B12 deficiency
▫ ↑ bacteria → ↑ carbohydrate metabolism
▫ Microcytic → chronic bleeding
→ ↑ gas production → bloating
▪ Fecal fat testing
▫ ↑ bacteria → bile acid inactivation → ↑
fat in colon → osmotic effect → diarrhea ▪ Lactulose/glucose breath testing
▫ ↑ bacteria → intrinsic factor degradation ▪ Jejunal aspirate, culture
→ impaired B12 absorption → B12 ▫ > 103 colony forming units
deficiency
OTHER DIAGNOSTICS
RISK FACTORS ▪ Individual history
▪ Increases with age ▫ Chronic pancreatitis, intestinal surgery,
GI neuropathy
SIGNS & SYMPTOMS

TREATMENT
▪ Abdominal pain/distention, chronic diarrhea,
flatulence MEDICATIONS
▪ Tympanitic abdomen upon percussion ▪ Antibiotics
330 OSMOSIS.ORG
TROPICAL SPRUE
osms.it/tropical-sprue

▪ Gastrointestinal disease of uncertain DIAGNOSTIC IMAGING
etiology resulting in nutrient malabsorption
Endoscopy
CAUSES Barium swallow

▪ Acute intestinal infection (viral/bacterial/ ▪ Shows intestinal wall thickening
protozoan) → damaged intestinal lining →
inflammation → enteroglucagon secretion LAB RESULTS
→ decreased intestinal motility → increased ▪ Fecal fat test
intestinal transit time → overgrowth
▪ D-xylose test
of Klebsiella, E. coli, Enterobacter →
production of toxic fermentation byproducts ▪ Jejunal biopsy
→ further inflammation → villous atrophy ▫ Shows villous atrophy, inflammation
→ malabsorption → depletion of folate,
B12 → intestinal villi can’t function normally
→ further intestinal injury, megaloblastic TREATMENT
anemia
MEDICATIONS
RISK FACTORS ▪ Antibiotics → reduce bacterial overgrowth
▪ Most common in individuals living in ▪ Replace folate, B12
tropical regions
SIGNS & SYMPTOMS

▪ Diarrhea, weight loss, dehydration,
abdominal pain, fatigue, megaloblastic
anemia
OSMOSIS.ORG 331
WHIPPLE'S DISEASE
osms.it/whipples-disease

▪ Rare, malabsorptive infectious disease ▪ Four cardinal signs
caused by Tropheryma whipplei ▫ Diarrhea, weight loss, abdominal pain,
▪ Pathognomonic finding → lamina propria arthralgias
displays numerous macrophages with ▪ Endocarditis, pericarditis, myocarditis
periodic acid-Schiff (PAS) positive ▪ Skin hyperpigmentation
intracellular material
▪ Pleural disease
CAUSES
▪ Tropheryma whipplei DIAGNOSIS
▫ Gram-positive, non-acid fast, PAS
positive bacillus; ubiquitous in LAB RESULTS
environment ▪ Biopsy
▫ Fecal-oral transmission ▫ Shows copious PAS positive
▪ Readily spreads throughout body, causing macrophages invading lamina propria in
multisystem effects intestine
▫ Evades immune response → allows for ▪ ≥ two positive PCR/PAS tests
accumulation of bacilli in tissues ▪ Immunohistochemistry for T. whipplei
▪ Current hypothesis suggests host ▪ Laboratory findings suggesting chronic
immunodeficiency as predisposing factor inflammation, nutritional deficits

▪ Middle-aged biological males of European
ancestry; exposure to fecal matter (sewage MEDICATIONS
workers, farmers)
▪ Start with IV antibiotics → ceftriaxone/
penicillin G
MNEMONIC: WHIPPLES ▪ Trimethoprim-sulfamethoxazole (1 year)
Features of Whipple’s
disease
Weight loss
Hyperpigmentation of skin
Infection with tropheryma
whippelii
PAS positive granules in
macrophage
Polyarthritis
Lymphadenopathy
Enteric involvement
Steatorrhea
332 OSMOSIS.ORG

duodenum in a case of Whipple’s disease.
The lamina propria is occupied by numerous
foamy macrophages. Electron microscopy
would reveal numerous membrane bound
bacilli.

duodenal biopsy with the special stain DPAS
(diastase periodic acid-Schiff). This stain
highlights diastase resistant mucin within the
foamy macrophages residing in the lamina
propria. The mucin within goblet cells is also
positively stained.
OSMOSIS.ORG 333
NOTES
NOTES
ORAL DISEASE

▪ Infectious, inflammatory diseases; affect DIAGNOSTIC IMAGING
oral cavity, associated structures
X-ray
▪ See individual diseases
RISK FACTORS
▪ Poor oral hygiene, dehydration, CT scan
concomitant illness, malnutrition ▪ Soft tissue inflammation extension

▪ Inflammation MEDICATIONS
▫ Redness, swelling, pain, loss of function, ▪ Nonsteroidal anti-inflammatory drugs
warmth (NSAIDs) for pain
▪ Infection ▫ For inflammation
▫ Fever, malaise, localized pain ▪ Antibiotics, antifungal medications
▫ For infection
APHTHOUS ULCERS
osms.it/aphthous-ulcers
Herpetiform
PATHOLOGY & CAUSES ▪ Coalesce, recur frequently
▪ Painful lesions inside mouth; benign, non-
infectious; AKA canker sores CAUSES
▪ Idiopathic; likely multifactorial; may be part
of TH1 autoimmune response, hormonal
TYPES
factors influence epithelium thickness,
Minor connected to vitamin B12 deficiencies
▪ Small (3–4mm), last 7–10 days, recur 3–4
times/year; if recurrent, > 4 times/year RISK FACTORS
▪ Stress, systemic autoimmune disorders (e.g.
Major
celiac), nutritional deficiencies, stopping
▪ Lesions > 1cm, last 10–30 days smoking, oral cavity trauma (e.g. biting lips,
dentures)
334 OSMOSIS.ORG
Chapter 39 Oral Disease
COMPLICATIONS
▪ Recurrent aphthous stomatitis (Mikulicz
DIAGNOSIS
ulcers), infection; may interfere with eating/
drinking
OTHER DIAGNOSTICS
▪ Recurrence of ulcers
SIGNS & SYMPTOMS

TREATMENT
▪ Round/oval ulcerations in oral mucosa,
white/yellow sharply demarcated center MEDICATIONS
covered with fibrous membrane cap, ▪ Vitamin B12 supplementation
surrounded by red erythematous margins; ▪ Topical analgesics, corticosteroids,
yellowish exudate sucralfate suspension
▪ Inside of cheeks, lips; under tongue; painful ▪ Anti-tumor necrosis factor (TNF)-alpha
swallowing, if in back of throat agents
▫ Recalcitrant, recurrent ulcers
Minor
▪ Small, mildly painful, annoying, round/
oval, disappear within seven days, resolve OTHER INTERVENTIONS
spontaneously, no scarring; more common ▪ Avoid triggers
on non-keratinized epithelium
Major
▪ Larger, painful, recur more often, may scar
Herpetiform
▪ Not herpes virus connected, vesicles
coalesce into patches
Figure 39.1 The clinical appearance of

aphthous ulcers.
OSMOSIS.ORG 335
DENTAL CARIES DISEASE
osms.it/dental-caries

▪ Odontogenic infections; tooth decay caused DIAGNOSTIC IMAGING
by acids produced by bacteria.
Odontogram ( jaw X-ray)
▪ Bacteria → plaque → ↓ pH →
demineralization → caries ▪ Examine depth of lesions
CT scan
CAUSES ▪ If widespread, soft tissue infection
▪ Streptococcus mutans, Streptococcus
sabrinus, Lactobacillus spp.
OTHER DIAGNOSTICS
▫ Metabolically produce acids
RISK FACTORS ▪ Teeth discoloration, changes
▪ Prolonged bottle use (baby bottle tooth
decay), poor oral hygiene, sugar-rich foods,
diabetes mellitus (DM), salivary gland
TREATMENT
disorders (e.g. Sjogren’s), medications that
decrease salivation
MEDICATIONS
▪ Topical/systemic antibiotics
COMPLICATIONS
▪ Hematogenous spread of bacteria to heart
SURGERY
valves, joints, implanted prosthetics ▪ Extraction of infected material, replacement
with fillings
▪ Spread from enamel to tooth pulp, alveolar
bone
▪ Abscesses OTHER INTERVENTIONS
▪ Soft tissue infections in extraoral ▪ Dietary counselling, hygiene improvement
perforation
▪ Deep head, neck infections
▪ Jaw osteomyelitis
▪ Tooth loss
SIGNS & SYMPTOMS

▪ Yellow/black teeth staining, enamel
softening; appearance of pits, cracks
▪ If severe: tooth collapse
▪ If pulp affected: dull pain exacerbated by
cold, soft food
▪ If root caries: lower, where teeth close
together, food difficult to extract; more Figure 39.2 A dental cavity in the tooth of a
difficult to diagnose ten-year-old boy.
336 OSMOSIS.ORG
Figure 39.3 An orthopantomogram

demonstrating dental cavities of the left
mandibular second and third molar teeth.
GINGIVITIS
osms.it/gingivitis
COMPLICATIONS
PATHOLOGY & CAUSES
▪ Periodontitis, tooth loss, receding gums
▪ Type of periodontal disease; inflammation
of gums SIGNS & SYMPTOMS
▪ Pathogenic bacteria tunnel between
microcolonies on tooth to surface in order ▪ Redness, swelling, bleeding after brushing/
to bring in steady supply of food → form flossing
hard mass (dental calculus) → bacterial
▪ May be asymptomatic in early infection
plaque formation → enter gingival sulcus →
gingivitis
▪ Immune response delivers blood to DIAGNOSIS
damaged tissue → provides nutrients for
bacteria → immune response activates DIAGNOSTIC IMAGING
osteoclasts → dissolves bone → tooth
loosening X-ray
▪ Non-infectious systemic factors → gingival ▪ Evaluate bone level, sulcus becomes
overgrowth, inflammation deeper as periodontal pocket expands
▫ Hormonal shifts (e.g. during pregnancy)
▫ Drug-induced (e.g. phenytoin, calcium OTHER DIAGNOSTICS
channel blockers)
▫ Malnutrition-induced (e.g. vitamin C Physical exam
deficiency) ▪ Swollen/bleeding gums, probe gingival
▫ Non-plaque-induced (rare, associated sulcus to determine depth
with genetics, allergy, trauma)
RISK FACTORS
▪ Poor dental hygiene, older age
OSMOSIS.ORG 337
TREATMENT
MEDICATIONS
▪ Antibiotics for severe infections
SURGERY
▪ Removal of infected tissue if severe
Figure 39.4 An individual with a severe

case of gingivitis. The gums are swollen and
hemorrhagic. There is visible plaque covering
the free gingival margin of both maxillary
incisors.
LUDWIG'S ANGINA
osms.it/ludwigs-angina

▪ Bilateral infection of submandibular space ▪ Infection
(sublingual, submylohoid) ▫ Fever, chills, malaise, pain
▪ Stiff neck, dysphagia, individual
CAUSES leans forward to expand airway, no
▪ Spread from infection of 2nd/3rd mandibular lymphadenopathy, bilateral, sudden
molars, pericoronitis, parotitis, peritonsillar aggressive spread, enlarged tongue,
abscess drooling
▪ Mandibular fracture, piercings ▪ Critical symptoms
▪ Causative agents polymicrobial from mouth ▫ Stridor, cyanosis
flora, dominated by Streptococcus viridans; ▪ No abscess formation
staphylococci, bacteroides also common
DIAGNOSIS
RISK FACTORS
▪ DM, hypertension, HIV infection, DIAGNOSTIC IMAGING
immunosuppression
CT scan
COMPLICATIONS ▪ Rule out abscess formation (occurs late in
disease)
▪ Airway obstruction, mediastinitis,
necrotizing cellulitis, sepsis, asphyxia ▪ Chest CT scan
▫ Mediastinitis
338 OSMOSIS.ORG
LAB RESULTS
▪ Blood culture
TREATMENT
MEDICATIONS
OTHER DIAGNOSTICS ▪ Empiric broad-spectrum antibiotics with
▪ Ultrasound-guided needle aspiration beta-lactamase activity
SURGERY
▪ Surgical drainage, if abscess identified on
CT scan
OTHER INTERVENTIONS
Airway management
▪ Fiberoptic nasal intubation, emergent
tracheostomy may be necessary
ORAL CANDIDIASIS
osms.it/oral-candidiasis
COMPLICATIONS
PATHOLOGY & CAUSES
▪ Spread into pharynx, disseminated
candidiasis
▪ Opportunistic infection of oral mucosal
membranes by Candida spp. (e.g. Candida
albicans)
SIGNS & SYMPTOMS
▪ AKA thrush
TYPES ▪ Cottony feeling in mouth; lesions
▪ Pain/tenderness in oral cavity
Pseudomembranous
▪ Painful swallowing (odynophagia)
▪ Whitish plaques on oral mucosa (most
common); can be scraped off to reveal ▪ Decreased sense of taste
erythematous surface ▪ Angular cheilitis
Atrophic (denture stomatitis)

▪ Red lesions without plaques DIAGNOSIS
Hyperplastic (rare) LAB RESULTS
▪ Non-scrapable plaques ▪ Microbiological analysis of scrapings; Gram
stain; KOH preparation; biopsy
RISK FACTORS
▪ Young age, dentures, xerostomia,
antibiotics, DM, malnutrition
▪ Immunosuppression due to corticosteroids,
chemotherapy, HIV/AIDS
OSMOSIS.ORG 339
TREATMENT
MEDICATIONS
▪ Topical antifungal agents (e.g. nystatin
suspension, clotrimazole troches, systemic
fluconazole)
Figure 39.5 Oral candidiasis in a child who

had taken antibiotics.
PAROTITIS
osms.it/parotitis
sympathomimetics)
PATHOLOGY & CAUSES
▪ Parotid gland inflammation COMPLICATIONS
▪ Salivary stasis → seeding of parotid ▪ Spread to deep head, neck structures;
(Stensen) duct by microorganisms → septic jugular thrombophlebitis; septic
infection, inflammation osteomyelitis; sepsis; respiratory
obstruction; facial nerve palsy
CAUSES
▪ Bacterial: S. aureus, most common SIGNS & SYMPTOMS
▪ Viral: mumps, influenza, coxsackie, Epstein–
Barr virus (EBV) ▪ Systemic manifestations
▪ Autoinflammatory: sarcoidosis as part of ▫ Fever, chills
Mikulicz syndrome ▪ Periauricular, mandibular pain, swelling;
trismus, dysphagia; purulent drainage
RISK FACTORS ▪ Viral
▪ Surgery, dehydration, salivary gland ▫ No discharge, prodrome followed by
stones, poor oral hygiene, medications that swelling lasting 5–10 days
decrease salivation (e.g. anticholinergic,
340 OSMOSIS.ORG
DIAGNOSIS
DIAGNOSTIC IMAGING
▪ Sample purulent exudate, ultrasound
guided needle aspiration; culture, Gram
stain
Ultrasound
▪ Increased blood flow through gland,
enlargement, nodules
CT scan
▪ Extension of inflammation to surrounding
tissues
LAB RESULTS
▪ Complete blood count (CBC) Figure 39.6 The clinical appearance of
▪ Increased amylase without underlying parotitis of the left parotid gland. There is a
pancreatitis marked swelling just anterior to the left ear.
▪ Viral shows leukocytosis, increased IgM
against mumps
TREATMENT
MEDICATIONS
▪ Hydration; IV antibiotics
▪ Vaccination
▫ Mumps prevention
PERIODONTITIS
osms.it/periodontitis
→ tooth loosening
PATHOLOGY & CAUSES ▪ Severity based on ligament loss
▪ Porphyromonas gingivalis impairs immune
▪ Inflammation, destruction of supporting
cells, kills bacteria → pathogenic bacteria
structures around teeth, wasting of bone
overgrow
▪ Dysbiosis (disturbed bacterial symbiosis)
▪ Necrotizing ulcerative periodontitis (NUP)
more extreme than in gingivitis
▫ Extreme loss of periodontal attachment,
▪ Orange-complex of bacteria
alveolar bone; associated with
(Fusobacterium nucleatum, Prevotella
immunosuppression (e.g. HIV/AIDS;
intermedia), red-complex of bacteria
chemotherapy, severe malnutrition);
(Tannerella forsythia, Treponema denticola,
may be associated with enteric bacteria,
Porphyromonas gingivalis) → immune
yeast
response → more blood flow to damaged
tissue → provides nutrients for bacteria
→ more damage to gingiva, periodontal
ligament → activated osteoclasts in bone
OSMOSIS.ORG 341
▪ Poor oral hygiene; red-, orange-complex ▪ Clinical exam
bacteria ▫ Probe teeth pockets, test for bleeding,
depth
RISK FACTORS
▪ DM, smoking, Ehler–Danlos syndrome
TREATMENT
▪ Tooth loss, infection spread to soft tissues ▪ Systemic antibiotics (if severe)
of head, neck, sinusitis; hematogenous
dissemination to heart valves (prosthetic/
native), joints, etc.
SURGERY
▪ Removal of infected tissue (if severe)

▪ Prevent plaque formation
▪ Redness, swelling, tender to palpation
▫ Daily brushing, flossing; antimicrobial
▪ Halitosis agents (e.g. mouthwash)
▪ Bleeding during teeth brushing ▪ Scaling, root planing
▪ Teeth loosening ▫ Remove plaque
▪ Periodontal pockets widen ▪ Topical fluoride
DIAGNOSIS
DIAGNOSTIC IMAGING
Panoramic dental X-ray
▪ Bone loss around tooth
SIALADENITIS
osms.it/sialadenitis
inflammation, tissue swelling
PATHOLOGY & CAUSES
▪ Inflammation of salivary glands CAUSES
▫ Parotid (most common), sublingual, ▪ Bacterial: Staphylococcus aureus (most
submandibular; unilateral common), Streptococcus viridans,
Haemophilus influenzae
▪ Decreased flow of saliva → deposits settle
in walls of salivary duct → duct blocked ▪ Viral: mumps, HIV
→ flow of saliva slowed → deposits of
calcium, phosphorous, etc. precipitate → RISK FACTORS
form small concretions (microsialoliths) ▪ Decreased salivary flow (dehydration,
→ grow into sialoliths → stones block illness, anticholinergic medications,
duct → bacteria moves from mouth up, Sjogren’s syndrome)
around blockage, into salivary duct →
342 OSMOSIS.ORG
LAB RESULTS
▪ Lab culture of pus
▫ Gentle compression of gland
OTHER DIAGNOSTICS
TREATMENT
MEDICATIONS
▪ Antibiotics
SURGERY
▪ Surgical gland removal
▫ If disease recurrent
Figure 39.7 An individual holding their
own salivary duct stone following surgical
removal. Salivary duct stones predispose OTHER INTERVENTIONS
individuals to sialadenitis. ▪ Hydration, warm compress, glandular
massage, sialogogues
SIGNS & SYMPTOMS

▪ Acute sialadenitis
▫ Fever, chills, abscess formation
▫ Pain, swelling, redness of skin overlying
affected gland
▫ Less saliva → dry mouth → bad taste
(pus leaking out of affected duct)
▫ Severe: painful to open mouth
▪ Chronic sialadenitis
▫ Less painful, gland enlarges following
meals, no overlying redness of the skin
▫ Associated with conditions linked
to chronic decreased salivary flow
(e.g. Sjogren’s syndrome), due to
inflammation, salivary duct fibrosis,
altering glandular tissue, composition of
saliva Figure 39.8 A submandibular sialogram
demonstrating a salivary duct stone; a risk
factor for sialadenitis.
DIAGNOSIS
DIAGNOSTIC IMAGING
Ultrasound
▪ Abscess, salivary stone, tumor
OSMOSIS.ORG 343
of sialadenitis at low power. The acini are
surrounded by dense fibrosis and display
patchy lymphocytic infiltrates.
344 OSMOSIS.ORG
NOTES
NOTES
PANCREATITIS

▪ Inflammation of pancreas ▪ Upper abdominal pain radiating to back;
nausea; vomiting
TYPES
▪ Acute, chronic DIAGNOSIS
▪ Acute ▪ Abdominal CT scan; ultrasound
▫ Gallstones, alcoholism, direct trauma,
infections (mumps) LAB RESULTS
▪ Chronic ▪ Clinical, lab findings; see individual
▫ Recurrent acute pancreatitis, chronic disorders
alcoholism, cystic fibrosis
RISK FACTORS
TREATMENT
▪ Smoking OTHER INTERVENTIONS
▪ Dietary modifications, symptomatic
treatment
PANCREATIC PSEUDOCYST
osms.it/pancreatic-pseudocyst
hemorrhagic fat necrosis → inflammatory
PATHOLOGY & CAUSES reaction → encapsulation of fluid by fibrous
and granulation tissue
▪ Localized fluid collection of pancreatic
enzymes, necrotic debris and blood
encapsulated by non-epithelialized wall CAUSES
(hence the name pseudocyst) composed of ▪ Arises as complication of acute/chronic
fibrous and granulation tissue pancreatitis/abdominal trauma
▪ Usually take up to 4–6 weeks to develop,
unlike acute fluid collections COMPLICATIONS
▪ Occurs due to disruption of pancreatic ▪ Infection; hemorrhage
duct → accumulation of pancreatic fluid → ▪ Compression of the gastrointestinal/urinary/
OSMOSIS.ORG 345
biliary tract
▪ Rupture → spilling of enzymes and debris
into abdominal cavity → diffuse peritonitis
SIGNS & SYMPTOMS

▪ Abdominal discomfort, indigestion,
anorexia, abdominal mass
DIAGNOSIS
DIAGNOSTIC IMAGING
CT scan
▪ Large cyst cavity of low attenuation
surrounded by well-defined enhancing wall Figure 40.1 A CT scan in the axial plane
within, around pancreas demonstrating a pancreatic pseudocyst.
▪ Calcifications
▪ If present, complications may be visualized
Ultrasound TREATMENT
▪ Visualization of hypoechoic/anechoic cystic
fluid collections ▪ Initially
▫ Bowel rest, total parenteral nutrition
MRI (TPN), observation
▪ Not necessary, but useful for distinguishing
from organized necrosis
SURGERY
▪ If symptoms do not improve
LAB RESULTS ▫ Surgical drainage to establish
connection which drains
Cyst fluid analysis
pseudocystic fluid into small intestine
▪ To distinguish from tumor (cystojejunostomy), stomach
▫ ↓ carcinoembryonic antigen (CEA) (cystogastrostomy), or duodenum
▫ ↑ cmylase (cystoduodenostomy)
▫ ↓ cluid viscosity ▪ Endoscopic drainage
346 OSMOSIS.ORG
Chapter 40 Pancreatitis
PANCREATITIS (ACUTE)
osms.it/acute-pancreatitis
Alcohol
PATHOLOGY & CAUSES ▪ Increases zymogen secretion; decreases
fluid, bicarbonate production → pancreatic
▪ Sudden inflammation of pancreas due juices become thick, viscous → pancreatic
to autodigestion → reversible pancreatic duct blocked
injury.
▪ Stimulates release of inflammatory
cytokines
TYPES ▪ Oxidative metabolism produces free
radicals
Mild
▪ Inflammation, parenchymal edema, Gallstones
peripancreatic fat necrosis ▪ Lodge at Oddi sphincter → pancreatic duct
blocked
Severe
▪ Parenchymal necrosis, hemorrhage Alcohol and gallstones
▪ Pancreatic duct blocked → pancreatic
CAUSES juices back up → pressure increases →
zymogen granules fuse with lysosomes
▪ See mnemonic for summary of causes
→ trypsinogen transforms into activated
trypsin → digestive enzyme activation,
autodigestion
MNEMONIC: I GET
SMASHED RISK FACTORS
Causes of Acute pancreatitis ▪ Biologically male to biologically female, 1:3
Idiopathic ▪ Smoking
Gallstones
Ethanol abuse COMPLICATIONS
Trauma ▪ Most often
Steroids ▫ Acute pseudocyst, intra-abdominal
Mumps infection infection, pancreatic abscess,
Alcohol abuse disseminated intravascular coagulation
Scorpion sting (DIC), internal pancreatic fistula
Hypertriglyceridemia, ▪ Severe manifestations
hypercalcemia ▫ Acute respiratory distress syndrome
Endoscopic retrograde (ARDS), acute renal failure, hemorrhage,
cholangiopancreatography hypotensive shock
Drugs: sulfa drugs, reverse-
transcriptase inhibitors,
protease inhibitors
OSMOSIS.ORG 347
▪ Abdominal pain; loss of appetite; palpable, MEDICATIONS
tender mass ▪ Pain management, hydration, electrolytes
▪ Cullen’s sign ▪ Hyperbaric oxygen therapy, antibiotics
▫ Periumbilical region bruising
▪ Grey Turner’s sign SURGERY
▫ Bruising along flank ▪ Necrosectomy
OTHER INTERVENTIONS
▪ Total restriction of food intake, alcohol
cessation
▪ Endoscopic retrograde
cholangiopancreatography (ERCP)
Figure 40.2 Cullen’s sign. Individual

presented with a four-day history of
abdominal pain following an alcohol binge.
DIAGNOSIS
DIAGNOSTIC IMAGING
CT scan
▪ Visualization of inflammation, necrosis,
abscess, pancreatic pseudocysts
Ultrasound Figure 40.3 A CT scan in the axial plane

▪ Gallstones demonstrating acute pancreatitis. There
is diffuse enlargement of the pancreas
associated with peripancreatic fluid.
LAB RESULTS
▪ Elevated serum amylase, lipase, bilirubin
OTHER DIAGNOSTICS
Histology
▪ Microvascular edema; fat tissue necrosis;
acute inflammation; destruction of
parenchyma, blood vessels; interstitial
hemorrhage
348 OSMOSIS.ORG
Chapter 40 Pancreatitis
PANCREATITIS (CHRONIC)
osms.it/chronic-pancreatitis
MNEMONIC: TIGAR-O
PATHOLOGY & CAUSES Causes of Chronic
pancreatitis
▪ Persistent, chronic inflammation of
Toxins: chronic alcoholism
pancreas due to autodigestion →
irreversible injury of exocrine, endocrine Idiopathic
pancreas Genetic
▪ Fibrosis, calcification Autoimmune
▫ Prolonged inflammation produces Recurrent acute pancreatitis
fibrogenic cytokines, transforming Obstruction: gallstones,
growth factor beta (TGF-beta), platelet- pancreatic head tumor
derived growth factor (PDGF) →
activates myofibroblasts → collagen
production, fibrosis
▫ Early stages: Langerhans islets not
SIGNS & SYMPTOMS
affected
▪ Severe abdominal pain radiates to back;
▫ Advanced: atrophy, fibrosis of islets
nausea; vomiting; steatorrhea; weight loss;
edema due to malabsorption
CAUSES
▪ See mnemonic for summary of causes
▪ Genetic DIAGNOSIS
▫ Hereditary chronic pancreatitis:
DIAGNOSTIC IMAGING
autosomal-dominant disease due to
mutations in cationic trypsinogen gene CT scan
▫ Cystic fibrosis: cystic fibrosis ▪ Visualization of pancreatic ducts dilatation,
transmembrane conductance regulator calcifications, atrophy, pseudocysts
(CFTR) mutation → decreased
bicarbonate secretion → pancreatic duct Ultrasound
plugged, obstructed ▪ Hyperechogenicity (fibrosis), pseudocysts,
▪ Autoimmune pseudoaneurysms, ascites
▫ Distinct form of chronic pancreatitis →
ERCP/magnetic resonance cholangiopan-
manifestation of immunoglobulin G (IgG)
creatography (MRCP)
related disease
▪ Visualization of pancreatic ducts; chain-of-
lakes pattern due to alternating stenosis,
COMPLICATIONS dilation
▪ Pancreatic pseudocyst; ascites; pancreatic
insufficiency; diabetes mellitus; vitamins A,
D, E, K deficiency; pancreatic cancer
LAB RESULTS
▪ Mildly elevated serum amylase, alkaline
phosphatase, bilirubin
OSMOSIS.ORG 349
OTHER DIAGNOSTICS
Histology
▪ Dilatation of pancreatic ducts; acinar cell
atrophy; fibrosis; chronic inflammatory
infiltrate; protein plugs, calcifications
TREATMENT
MEDICATIONS pancreatic fat necrosis in a case of severe
▪ Pain management pancreatitis.
▪ Pancreatic enzyme replacement
SURGERY
Endoscopy, surgery
▪ Resectional/drainage procedures for
pseudocyst, fistula, ascites
OTHER INTERVENTIONS
▪ Alcohol cessation, dietary modifications
(low-fat)
350 OSMOSIS.ORG
NOTES
NOTES
PERITONEAL PATHOLOGY

▪ Conditions affecting peritoneal cavity (e.g. DIAGNOSTIC IMAGING
serosal membrane inflammation, gas)
X-ray
▪ Peritonitis
CAUSES
▫ Supine, upright abdominal films
Peritonitis ▪ Pneumoperitoneum
▪ Spontaneous bacterial peritonitis ▫ Upright chest radiography
▪ Leakage of gastrointestinal (GI) contents ▫ Subdiaphragmatic free gas; cupola sign
▪ Presence of foreign material ▫ Rigler’s sign, football sign
▫ Bile, blood, contrast material ▫ Lateral decubitus X-ray
▪ Endometriosis
CT scan
▪ Peritoneal dialysis
▪ Pneumoperitoneum
Pneumoperitoneum ▫ Small quantities of air
▪ Perforation of anterior duodenal ulcer
▪ Iatrogenic LAB RESULTS
▪ Increased intrathoracic pressure
Paracentesis
▪ Peritonitis
SIGNS & SYMPTOMS ▫ If ascites present
Peritonitis Complete blood count (CBC)

▪ Fever, chills, tachycardia Blood chemistry
▪ Ascites, abdominal distention, abdominal
rigidity, spider angiomata, jaundice
▪ Anorexia, nausea, vomiting, diarrhea TREATMENT
▪ Encephalopathy; delirium, confusion,
cognitive decline MEDICATIONS
▪ Absent bowel sounds, ileus ▪ Systemic antibiotics
Pneumoperitoneum
SURGERY
▪ Abdominal pain, rigidity
▪ Exploratory laparotomy
▪ Absent bowel sounds, ileus
OSMOSIS.ORG 351
PERITONITIS
osms.it/peritonitis

▪ Inflammation of serosal membrane DIAGNOSTIC IMAGING
lining abdominal cavity, organs (AKA
peritoneum). Supine, upright abdominal films
▪ Neutrophilic infiltration, formation of ▪ Subhepatic/subdiaphragmatic free air,
fibrinopurulent exudate abscesses in case of perforated viscus
CAUSES LAB RESULTS

▪ Spontaneous bacterial peritonitis ▪ Leukocytosis, acidosis
▫ Bacterial migration from GI lumen; more Paracentesis
common in people with ascites/cirrhosis
▪ If ascites present
▫ E. coli, Klebsiella, Pseudomonas,
▪ Serum ascites albumin gradient (SAAG)
Proteus, Gram-negatives
▫ > 1.1 in spontaneous bacterial
▪ Leakage of GI contents; most common;
peritonitis
perforated viscera
▪ Neutrophil count > 250 cells/microliter
▫ Proximal GI tract perforation → Gram-
positive bacteria
▫ Distal GI tract perforation → Gram- TREATMENT
negative bacteria
▪ Foreign material MEDICATIONS
▫ Bile, blood, contrast material
Systemic antibiotics
▪ Endometriosis
▪ Third generation cephalosporins/quinolones
SIGNS & SYMPTOMS

▪ Fever, chills, tachycardia
▪ Ascites, abdominal distention, abdominal
rigidity, spider angiomata, jaundice
▪ Anorexia, nausea, vomiting, diarrhea →
hypovolemia, renal failure
▪ Early stages
▫ Dull, poorly localized abdominal pain
▪ Late stages
▫ Severe, localized abdominal pain; acute
abdomen Figure 41.1 The histological appearance
▪ Encephalopathy; delirium, confusion, of tuberculous peritonitis, a rare kind of
cognitive decline peritonitis. There are numerous epithelioid
macrophages and giant cells infiltrating the
peritoneal biopsy.
352 OSMOSIS.ORG
Chapter 41 Peritoneal Pathology
Figure 41.2 An abdominal CT scan with oral

contrast in the axial plane demonstrating
severe peritonitis. There is diffuse peritoneal
thickening and large amounts of radiodense
fluid. On laparotomy this was discovered to
be pus.
PNEUMOPERITONEUM
osms.it/pneumoperitoneum

▪ Abnormal collection of gas within DIAGNOSTIC IMAGING
peritoneal cavity.
CT scan
▪ Small quantities of air
CAUSES
▪ Most common Upright chest radiography
▫ Perforation of anterior duodenal ulcer ▪ Subdiaphragmatic free gas; Cupola sign
secondary to peptic ulcer disease (free intraperitoneal air, well-defined
▪ Iatrogenic superior border formed by diaphragm)
▫ Abdominal surgery; resolves Supine abdominal X-ray
spontaneously
▪ Rigler’s sign (double wall sign): both sides
▪ Increased intrathoracic pressure of abdominal wall visible
(mechanical ventilation, chest
▪ Football sign (massive pneumoperitoneum):
compressions)
ellipsoid shape of abdominal cavity outlined
by gas
SIGNS & SYMPTOMS Lateral decubitus X-ray
▪ Free gas between liver, abdominal wall
▪ Abdominal pain, rigidity
OSMOSIS.ORG 353
TREATMENT
SURGERY
Exploratory laparotomy
▪ Repair perforated viscus

demonstrating air in the peritoneal cavity.
The air has also tracked along an umbilical
hernia.
Figure 41.4 An erect chest radiograph

demonstrating a sub-diaphragmatic air
bubble, diagnostic of pneumoperitoneum.
354 OSMOSIS.ORG
NOTES
NOTES
RECTAL & ANAL PATHOLOGY

▪ Diseases affecting rectum and anal region ▪ History, physical examination
▪ Discomfort during defecation, itching, pain,
bleeding ▪ Change dietary/defecation habits,
pharmacological, surgical
SIGNS & SYMPTOMS
▪ Visible abnormalities
ANAL FISSURE
osms.it/anal-fissure
COMPLICATIONS
PATHOLOGY & CAUSES ▪ Fecal bacteria infection
▪ Anal mucosa linear fissure
▪ Hard bowel movement → anal mucosa SIGNS & SYMPTOMS
stretches → acute fissure → internal anal
sphincter spasms → blood flow reduces → ▪ Midline tear
difficult healing → chronic fissure
▪ Pain during bowel movements → fear of
▪ Midline, anteriorly/posteriorly defecation → constipation → harder stool
→ more pain
RISK FACTORS ▪ Blood on toilet paper/stool
▪ Low fiber diet
Diarrhea
▪
DIAGNOSIS
▪ Previous anal surgery
▪ Anal trauma ▪ History, examination of anal region/rectum
▪ Abnormalities in internal anal sphincter
▪ Sexually transmitted infections (STIs)
▫ Human papillomavirus (HPV), herpes,
chlamydia
▪ Inflammatory bowel disease (IBD)
OSMOSIS.ORG 355
TREATMENT
MEDICATIONS
▪ Stool softeners
▪ Topical nitrates/calcium channel blocker (e.g
diltiazem)
SURGERY
▪ Sphincterotomy
OTHER INTERVENTIONS
▪ Proper anal hygiene Figure 42.1 The clinical appearance of an anal
▪ Warm bath (AKA sitz bath) fissure affecting the posterior anal mucosa.
▪ Muscle relaxation → increase healing
mechanisms
▪ Fiber supplementation
ANAL FISTULA
osms.it/anal-fistula
Extrasphincteric
PATHOLOGY & CAUSES ▪ Rectum/sigmoid colon → levator muscle ani
→ skin
▪ Abnormal communication between anal
canal, perianal skin
▫ Fistula: Latin (pipe, catheter), from findo SIGNS & SYMPTOMS
(cleave, divide, split)
▪ Foreign material in anal crypts → anal ▪ Skin excoriations, pus/serous fluid/feces
glands ducts blocked → anal abscess → draining from skin-opening, bleeding,
pus travels to skin through tract itching, pain, redness, swelling
TYPES
DIAGNOSIS
Intersphincteric
▪ Internal anal sphincter → space between OTHER DIAGNOSTICS
internal, external anal sphincters (AKA ▪ Anal examination → delineate course of
intersphincteric plane) → skin fistula
Transsphincteric (U-shaped fistula)

▪ Internal anal sphincter → intersphincteric TREATMENT
plane → external anal sphincter → skin
SURGERY
Suprasphincteric
▪ Drain infection → eradicate fistulous tract
▪ Internal anal sphincter → puborectalis → preserve anal sphincter function → avoid
muscle → space between puborectalis, recurrences
levator ani muscle → skin
356 OSMOSIS.ORG
Chapter 42 Rectal & Anal Pathology
Figure 42.2 Surgical wound following

removal of an anal fistula.
HEMORRHOID
osms.it/hemorrhoid
COMPLICATIONS
PATHOLOGY & CAUSES
Internal hemorrhoids
▪ Anal cushions hypertrophy due to ▪ Bleeding with bowel movements
supportive tissue deterioration ▪ Prolapsing
▪ Incarceration, strangulation → pain
TYPES ▪ Mucus deposits on perianal tissue →
itching
Internal
▪ Affecting hemorrhoidal venous cushions External hemorrhoids
above dentate line ▪ Bleeding
▫ Grade I: bleed but not prolapse ▪ Acute thrombosis → acute pain
▫ Grade II: prolapse on straining but ▪ Itching
reduce spontaneously ▪ Hygiene difficulties
▫ Grade III: prolapse on straining, require
manual reduction
▫ Grade IV: spontaneous, irreducible SIGNS & SYMPTOMS
prolapse
▪ Itching
External
▪ Bleeding associated with bowel movement
▪ Affecting hemorrhoidal venous cushions → bright red blood on toilet paper
below dentate line
▪ Pain
▪ Mucous discharge
RISK FACTORS ▪ Perianal mass in case of prolapse
▪ Constipation (low fiber diet), strenuous
defecation, diarrhea, prolonged sitting,
aging, increased intra-abdominal pressure,
pregnancy, intra-abdominal mass, ascites,
portal hypertension
OSMOSIS.ORG 357
DIAGNOSIS TREATMENT
DIAGNOSTIC IMAGING MEDICATIONS
▪ Anoscopy for internal hemorrhoids ▪ Stool softeners
▪ Topical, systemic analgesics
OTHER DIAGNOSTICS
▪ Anal, perianal inspection SURGERY
▪ Digital rectal examination ▪ Sclerotherapy, rubber band ligation, infrared
coagulation
OTHER INTERVENTIONS
▪ Increase fiber, fluid intake

of an excised hemorrhoid. There is
fibromuscular hyperplasia and numerous
dilated vascular spaces.
Figure 42.4 External appearance of grade 2

hemorrhoids.
RECTAL PROLAPSE
osms.it/rectal-prolapse

▪ Partial/total slip of rectal tissue through anal ▪ Mass protruding through anus
orifice ▫ After defecation; when sneezing/
coughing; when walking → pain, rectal
RISK FACTORS bleeding, incontinence
▪ Constipation, diarrhea, pregnancy, pelvic
floor damage
COMPLICATIONS
▪ Mucous discharge, bleeding, fecal
incontinence, constipation, rectal ulceration
358 OSMOSIS.ORG
Chapter 42 Rectal & Anal Pathology
DIAGNOSIS TREATMENT
▪ Physical examination ▪ Sutures/mesh slings to anchor rectum to
▫ Prolapse clearly evident posterior wall of pelvis (sacrum)
▫ Open or laparoscopic
▪ Rectosigmoidectomy
▫ Part of rectum and sigmoid pulled
through anus and removed,
reanastomosis of remaining rectum to
colon
▫ Usually reserved for severe prolapse/
non-candidates for open/laparoscopic
procedure
OTHER INTERVENTIONS
▪ High fiber diet, enemas, suppositories (to
avoid constipation/straining)
Figure 42.5 A complete rectal prolapse. ▪ Kegel exercises may help limit progression
OSMOSIS.ORG 359
NOTES
NOTES
UPPER GASTROINTESTINAL

▪ Upper gastrointestinal tract structural/ DIAGNOSTIC IMAGING
functional anomalies during embryonic ▪ Prenatal ultrasound; MRI
development; present at birth ▪ X-ray/CT scan
▫ Avoid if possible due to teratogenicity
CAUSES
TREATMENT
▪ May be asymptomatic/complete
dysfunction of gastrointestinal (GI), life OTHER INTERVENTIONS
incompatibility
▪ Nasogastric intubation
CLEFT LIP & PALATE

osms.it/cleft-lip-and-palate
Combination (CLP, cheilopalatoschisis)
PATHOLOGY & CAUSES ▪ Most severe forms; split alveolar ridge,
uvula (cheilognathopalatoschisis)
▪ Group of congenital malformations in upper
lip, oral cavity roof
▪ Result of improper fusion of facial bones, RISK FACTORS
associated tissues ▪ Other inherited genetic disorders (e.g.
Patau syndrome, Stickler syndrome)
▪ Environmental teratogenic factors
TYPES
(e.g. intrauterine hypoxia, pesticides,
▪ Based on severity anticonvulsant medication, folate
Cleft lip (CL, cheiloschisis) deficiency)
▪ Unilateral, bilateral “hare lip”
COMPLICATIONS
Cleft palate (CP, palatoschisis) ▪ Speech impediments, hearing issues/
▪ Commonly uvula also split recurrent otitis media, difficulty eating
360 OSMOSIS.ORG
Chapter 43 Upper Gastrointestinal Congenital Malformations
OTHER INTERVENTIONS
SIGNS & SYMPTOMS ▪ Temporary prosthetic implants, until
surgery
▪ Velopharyngeal insufficiency
▪ Speech-language therapy
▫ Inability to temporarily stop physical
▪ Folate supplementation during pregnancy
communication between oral, nasal
decreases risk
cavities
▪ Dysphonia
▫ Air leaks to nasal cavity → hypernasal
vocalization
▪ Dysarthria
▫ Abnormal structure increases speech
difficulty → distorted word structure
▪ Nasal cavity infection
▫ Food trapped in nasal cavity →
predisposes infection
DIAGNOSIS
DIAGNOSTIC IMAGING Figure 43.1 A cleft hard palate in an infant.
Prenatal ultrasound
▪ Evaluation of integrity of nares, upper lip,
hard and soft palate
▪ 3D reconstruction and surface rendering
allow for better diagnosis and help parents
prepare psychologically
MRI
▪ Evaluation of associated extra/intracranial
abnormalities
▪ Prenatal MRI aids in confirmation and
characterization/integrity of maxillary arch
CT scan/X-ray
▪ Not typically used; 3D reconstructions can
aid in surgical planning
OTHER DIAGNOSTICS
▪ Clinically evident at birth
TREATMENT
SURGERY Figure 43.2 A child with a unilateral,
▪ Surgical closure of cleft lip by three months incomplete cleft lip.
of age
▪ Timing for surgical closure of palate is
variable; usually done by one year of age
OSMOSIS.ORG 361
CONGENITAL DIAPHRAGMATIC
HERNIA (CDH)
osms.it/congenital-diaphragmatic-hernia
MNEMONIC: 5Bs
PATHOLOGY & CAUSES Bochdalek hernia features
Bochdalek hernia
▪ Protrusion of abdominal viscera into chest
cavity Big
▪ Results from abnormal development of Back and medial, usually left
diaphragm in utero side
▪ High mortality rate Baby
▪ Incomplete diaphragm formation → Bad: associated with
abdominal organs protrude into chest pulmonary hypoplasia
cavity → physical obstruction of heart,
lung formation/function → pulmonary
hypoplasia, surfactant deficiency, DIAGNOSIS
pulmonary hypertension, arrhythmia
DIAGNOSTIC IMAGING
TYPES
Prenatal ultrasound
Bochdalek hernia ▪ Polyhydramnios
▪ Posterolateral diaphragmatic hernia; most ▪ Cardiomediastinal shift with possible
common CDH abnormal cardiac axis
▫ Viscera protrude through posterolateral ▪ Lack of visualization of normal stomach
segment of diaphragm bubble
▫ Left kidney, perinephric fat, stomach, ▪ Absent bowel loops in abdomen; stomach
small intestine and small bowel in thorax
▪ Intrathoracic herniation of liver (seen in
Morgagni hernia
85%, poor prognosis)
▪ Retrosternal, parasternal diaphragmatic
▪ Peristaltic bowel movements in thorax
hernia
▪ Reduced abdominal circumference
▫ Viscera protrude through foramina of
Morgagni (form sternocostal angle) X-ray
▪ indistinct diaphragm, opacification of
CAUSES hemithorax (typically left-sided)
MRI
▪ Helpful in further assessment of pulmonary
SIGNS & SYMPTOMS hypoplasia
▪ Measurement of fetal lung volumes
▪ Dyspnea, tachypnea, central cyanosis,
tachycardia, retractions, nasal flaring,
decreased/absent breath sounds on
affected side, scaphoid abdomen
362 OSMOSIS.ORG
TREATMENT
SURGERY
▪ Surgical repair of hernia
OTHER INTERVENTIONS
▪ Planned delivery after week 37 of gestation
→ immediate intubation, mechanical
ventilation
▪ Inhaled nitric oxide for severe pulmonary
hypertension
▪ Nasogastric, pulmonary intubation
Figure 43.3 A plain X-ray of a newborn

demonstrating visible bowel loops in the
thoracic cavity.
ESOPHAGEAL WEB
osms.it/esophageal-web

▪ Rare narrowing of esophagus due to thin ▪ May be asymptomatic (if small)
membrane of esophageal tissues (mucosa, ▪ Dysphagia: difficulty in swallowing
submucosa) ▪ Odynophagia: painful swallowing
▪ Most commonly appear in lower third of ▪ Retrosternal pain: can be mistaken for
esophagus angina pectoris
▪ Can be congenital/acquired
▪ May occur as solitary disease
DIAGNOSIS
RISK FACTORS
OTHER DIAGNOSTICS
▪ Plummer–Vinson syndrome
▫ Sideropenic dysphagia, iron-deficiency Fluoroscopy/barium swallow
anemia, glossitis, cheilosis, esophageal ▪ Visualized when esophagus is fully
webs distended with contrast
▪ “Jet effect” of contrast being ejected distally
COMPLICATIONS from web
▪ Food impaction, perforation by solid food/
esophageal probe insertion
TREATMENT
OTHER INTERVENTIONS
▪ Endoscopic dilation via inflated balloon
OSMOSIS.ORG 363
HYPERTROPHIC PYLORIC STENOSIS
osms.it/hypertrophic-pyloric-stenosis
Fluoroscopy
PATHOLOGY & CAUSES ▪ Delayed gastric emptying
▪ Elongated pylorus with narrow lumen
▪ Constriction of pylorus due to pyloric
sphincter hypertrophy → gastric outflow ▪ Entrance to pylorus may be beak shaped
obstructed
▪ Autosomal dominant/multifactorial
TREATMENT
RISK FACTORS SURGERY
▪ Firstborn, biologically male, parents had ▪ Pyloromyotomy
hypertrophic pyloric stenosis, macrolide
exposure
OTHER INTERVENTIONS
▪ Rehydration
COMPLICATIONS ▪ Regulate acid-base status, correct
▪ Dehydration, malnourishment, acid-base electrolyte abnormalities
imbalance
SIGNS & SYMPTOMS

▪ Projectile nonbilious vomiting at/soon after
birth
▪ Visible peristalsis
▪ Dehydrated, undernourished
DIAGNOSIS
DIAGNOSTIC IMAGING
X-ray
▪ Distended stomach, minimal intestinal gas
Ultrasound
▪ Modality of choice; but cannot exclude
midgut volvulus
▪ Pyloric muscle thickness Figure 43.4 An abdominal radiograph
demonstrating a grossly dilated stomach,
OTHER DIAGNOSITCS secondary to obstructive pyloric stenosis.
▪ Abdominal olive palpable on physical
examination
364 OSMOSIS.ORG
THYROGLOSSAL DUCT CYST

osms.it/thyroglossal-duct-cyst
OTHER DIAGNOSTICS
PATHOLOGY & CAUSES ▪ Fluctuant mass palpable at a anterior
midline/paramedian location
▪ Benign cyst; epithelium of unclosed
▪ Draining sinus may be visible
thyroglossal duct
▪ Thyroid cells migrate from foramen cecum
downward → leave thyroglossal duct → TREATMENT
thyroid duct stays open → fills with mucus
→ cyst forms SURGERY
▪ Surgical excision (Sistrunk procedure)
COMPLICATIONS
▪ Infection (spread from respiratory system),
inflammation, discharging sinus with skin
(secondary to inflammation/trauma), thyroid
gland malformation (if thyroid cells remain
in thyroglossal duct/cyst), extrathyroid
thyroid carcinoma (from leftover thyroid
cells)
SIGNS & SYMPTOMS

▪ Painless mass in front of neck, moves when Figure 43.5 The clinical appearance of a
swallowing; inflammation, pain; dysphagia; thyroglossal duct cyst. There is a vague,
dyspnea fluctuant swelling in the midline of the neck.
DIAGNOSIS
DIAGNOSTIC IMAGING
Ultrasound
▪ Fluctuant mass filled with anechoic fluid,
thin walled, without vascularity
CT scan
▪ Thin-walled, well-defined homogeneous,
fluid dense lesions, anterior midline/
paramedian location
▪ May demonstrate capsular enhancement
▪ Sternocleidomastoid muscle may be
displaced posteriorly/posterolaterally
Figure 43.6 A CT scan of the head and
▪ May be embedded in infrahyoid muscles neck in the sagittal plane demonstrating a
thyroglossal duct cyst adjacent to the hyoid
bone.
OSMOSIS.ORG 365
TRACHEOESOPHAGEAL FISTULA
osms.it/tracheoesophageal-fistula
COMPLICATIONS
PATHOLOGY & CAUSES ▪ Atresia (due to hydrochloric acid
accumulation), gastroesophageal reflux,
▪ Pathologic communication between dysphagia, frequent respiratory infections
trachea, esophagus
▪ Results from tracheoesophageal ridge
fusion failure SIGNS & SYMPTOMS
▪ Occurs as congenital malformation/surgery
complication (later in life) ▪ Hypersalivation/drooling, choking, vomiting,
▪ VACTERL association; see mnemonic central cyanosis upon feeding
MNEMONIC: VACTERL DIAGNOSIS

Group of malformations with
common, unknown cause DIAGNOSTIC IMAGING
Vertebral anomalies Chest X-ray
Anal atresia ▪ Nasogastric tube coiled in proximal
Cardiovascular anomalies esophagus (usually sufficient for diagnosis)
Tracheoesophageal fistula
Fluoroscopy/Barium swallow
Esophageal atresia
▪ If difficult to diagnose, may require contrast
Renal anomalies
swallow study to visualize contrast passing
Limb defects into tracheobronchial tree
▫ Barium is contrast medium of choice
(ionic iodinated medium can cause
TYPES chemical pneumonitis)
Type A
CT scan
▪ Middle esophageal segment missing
▪ Useful for preoperative planning
Type B
▪ Proximal esophagus communicates with OTHER DIAGNOSTICS
trachea ▪ Inability to pass gastric tube
Type C (most common) ▪ Neonates drool, choke, vomit during first
feeding
▪ Distal esophagus communicates with
trachea, proximal esophagus atresia
Type D TREATMENT
▪ Proximal, distal esophageal segments
communicate with trachea, middle segment SURGERY
atresia ▪ Surgical closing of pathologic
communication, fusion of esophageal buds
Type E (AKA Type H)
▪ Complete esophagus, additional part
communicates with trachea
366 OSMOSIS.ORG
Figure 43.7 An acquired tracheo-esophageal

fistula.
OSMOSIS.ORG 367
NOTES
NOTES
CONGENITAL ANEMIA

▪ Inherited macrocytic-normochromic ▪ See individual disorders
anemias
▫ Diamond–Blackfan anemia
DIAGNOSIS
▫ Fanconi anemia
COMPLICATIONS
▪ Congenital anomalies, ↑ blood malignancy
risk, solid tumor cancers TREATMENT
368 OSMOSIS.ORG
Chapter 44 Congenital Anemia
DIAMOND–BLACKFAN ANEMIA
(DBA)
osms.it/diamond-blackfan-anemia
anemia
PATHOLOGY & CAUSES ▫ No other significant cytopathies evident
▫ Sporadic, unpredictable penetrance →
▪ Autosomal dominant ribosomopathy
high degree of genotypic heterogeneity
resulting in inherited bone-marrow failure
→ variety of possible congenital
syndrome, macrocytic-normochromic
anomalies
anemia, associated congenital anomalies
▪ Genetic mutation → ribosomopathy →
impaired hematopoiesis → red blood
cell aplasia → macrocytic-normochromic
OSMOSIS.ORG 369
COMPLICATIONS no erythroid precursors
▪ Genetic predisposition to malignancies like ▪ Serum erythropoietin, fetal hemoglobin
myelogenous leukemia, myelodysplastic (HbF) increased secondary to stress
syndrome, solid tumors hematopoiesis
▪ Congenital anomalies increase complication ▪ Elevated erythrocyte adenosine deaminase
risk (eADA)
SIGNS & SYMPTOMS OTHER DIAGNOSTICS

▪ Classical physical congenital anomalies
▪ Anemia often present at birth → signs and associated with DBA
symptoms of impaired oxygen-carrying ▪ Genetic testing, family history
capacity (e.g. pallor, tachycardia, apnea,
lethargy)
▪ Low birth weight, evidence of growth
restriction usually present TREATMENT
Congenital anomalies ▪ 25% chance of spontaneous remission
▫ Craniofacial: low-set ears, micrognathia,
high-arched/cleft palate, broad nasal MEDICATIONS
bridge
▫ Neck: short, may be webbed Corticosteroids
▫ Ophthalmological: congenital glaucoma, ▪ Hemoglobin ↑ observed after steroid
cataracts, strabismus therapy initiation
▫ Thumbs: duplex/bifid; flat thenar ▪ Weigh dose, duration of steroid treatment
eminence against adverse effects (e.g. growth
▫ Urogenital: absent/horseshoe kidney disturbances, adrenal suppression,
▫ Cardiac: ventricular/atrial septal defect, immunosuppression, pathological fractures)
coarctation of the aorta
SURGERY
DIAGNOSIS Curative
▪ Allogeneic hematopoietic stem cell
▪ DBA usually diagnosed within first month transplant
of life
OTHER INTERVENTIONS
DIAGNOSTIC IMAGING ▪ Monitor for development of malignancies
▪ Specialist care (e.g. cardiology, nephrology,
Renal imaging/echocardiography
urology)
▪ Find internal congenital anomalies
▪ Family support, genetic counseling
LAB RESULTS Transfusions

▪ Complete blood cell count (CBC) with red ▪ Packed red blood cells
blood cell indices ▫ Maintain Hgb ≥ 8g/dL
▫ ↓ red blood cell count, hemoglobin, ▫ Must be leukocyte poor to decrease
hematocrit transmission of cytomegalovirus
▫ Reticulocytopenia ▫ Monitor for iron overload, hemosiderosis
▫ ↑ mean corpuscular volume (MCV)
▫ Normal mean corpuscular hemoglobin
(MCH), white blood cell, platelet counts
▪ Bone marrow aspirate normal, except few/
370 OSMOSIS.ORG
Chapter 44 Congenital Anemia
FANCONI ANEMIA (FA)

osms.it/fanconi-anemia

▪ Autosomal recessive/X-linked disorder of ▪ Cytopenias develop → clinical
chromosome fragility causing inherited manifestations → increased bruising/
bone marrow failure syndrome, macrocytic- bleeding, frequent infections
normochromic anemia, pancytopenia ▪ Symptomatic anemia related to impaired
oxygen-carrying capacity develops late in
Physical abnormalities disease
▪ Short stature, malformations associated
with the VACTERL-H (vertebral, anal,
cardiac, tracheoesophageal, renal, limb and DIAGNOSIS
hydrocephalus) association
▫ Microcephaly, congenital heart disease, ▪ History, physical examination
imperforate anus, conductive deafness,
hypogenitalia, cafe-au-lait spots
LAB RESULTS
▪ CBC assessment, bone marrow
CAUSES examination
▪ Mutation of several genes responsible for
DNA repair FA testing indicators
▫ Impaired cellular repair of DNA cross- ▪ Evidence of single-/multilineage cytopenias
links → impaired regulation of cell cycle, with no other identified cause
genomic instability → hematopoietic ▫ ↓ absolute neutrophil count, platelet
stem cell loss → macrocytic- count, absolute reticulocyte count,
normochromic anemia → bone marrow hemoglobin
aplasia → pancytopenia ▪ Hypocellular bone marrow (without
▫ Predisposition for development of blood/ evidence of malignancy/other known cause)
solid tumor malignancies ▪ Congenital anomalies
▪ Bone marrow biopsy usually normocellular ▪ Family history: people of Ashkenazi Jewish
at birth descent have ↑ carrier frequency
▪ Macrocytic-normochromic anemia and
other cytopenias develop gradually → FA-specific testing
usually diagnosed within first eight years ▪ Chromosome DEB assay
of life ▫ Laboratory test for chromosomal
breakage performed on leukocytes
COMPLICATIONS (indicates chromosome instability
syndrome; not FA-specific)
▪ Neutropenia: life-threatening infections
▪ Cytometric flow analysis
▪ Thrombocytopenia: bleeding tendencies
▫ Examines cellular growth, division;
▪ Malignancies: e.g. myelogenous leukemia,
cytometry following DNA crosslinking
myelodysplastic syndrome, solid tumors
shows cells unable to repair DNA
▪ Endocrine derangements: hypothalamic- damage, cellular arrest in cell cycle G2
pituitary axis disruption during fetal phase
development
▪ Chromosomal breakage test positive → FA
▪ Congenital anomalies gene sequencing recommended
OSMOSIS.ORG 371
TREATMENT
MEDICATIONS OTHER INTERVENTIONS
▪ Screen, monitor for malignancies
Growth factors
▪ Specialist care (e.g. cardiology, nephrology,
▪ Granulocyte colony-stimulating factor (G-
endocrinology)
CSF)
▪ Family support, genetic counselling
▪ Granulocyte-macrophage-stimulating
factor (GM-CSF) Transfusions
▪ Thrombopoietin mimetics (e.g. romiplostim) ▪ Leukoreduced, irradiated packed red blood
cells
Androgen therapy
▫ Symptomatic anemia
▪ (e.g. oxymetholone) sometimes ↑ blood cell
count ▫ Hemodynamic instability
▪ Platelet transfusions
▫ Platelet count < 10,000/microL
SURGERY
▫ Evidence of severe bruising, bleeding
Bone marrow failure
transplant
372 OSMOSIS.ORG
NOTES
NOTES
DYSPLASTIC & PROLIFERATIVE
DISORDERS

▪ Acquired disorders caused by defective LAB RESULTS
hematopoiesis ▪ Complete blood count (CBC)
▫ Cell line levels
CAUSES ▪ Peripheral blood smear
▪ Mostly idiopathic ▫ Morphology
▪ Gene mutations ▪ Bone marrow aspiration/biopsy
▫ JAK2 gene in most myeloproliferative ▫ Morphology, cellularity (normal, hypo,
disorders hyper), % of blasts
▪ Cytogenetic studies
▫ Chromosomal abnormalities
COMPLICATIONS
▪ Molecular tests
▪ Can progress to serious conditions
▫ Gene mutations
▫ Acute myelogenous leukemia (AML)

OTHER INTERVENTIONS
▪ Can be asymptomatic
▪ Blood transfusion
▪ When symptomatic, depends on cell line
affected ▪ Hematopoietic stem cell transplant
OSMOSIS.ORG 373
ESSENTIAL THROMBOCYTOSIS
osms.it/essential-thrombocytosis

▪ Chronic myeloproliferative neoplasm due to LAB RESULTS
overproduction of megakaryocytes in bone ▪ Platelets > 450 × 103/µL for ≥ two months;
marrow anisocytosis
▪ AKA essential thrombocythemia ▪ ↑ bleeding time
▪ ↑ platelets, abnormally shaped; ↓ platelet
survival Bone marrow aspiration/biopsy
▪ Thromboses; bleeding episodes may occur; ▪ Normal cellularity
other cell lines may be affected
Genetic testing
▪ JAK2 mutation (50%), MPL (5–10%)/
▪ JAK2 mutation
calreticulin
▪ “Spent phase” of myelofibrosis/AML (rarely)
OTHER DIAGNOSTCS
▪ History of thrombosis, bleeding, vasomotor
SIGNS & SYMPTOMS symptoms, first trimester fetal loss
▪ Primary symptomatic manifestations due

to thrombosis → potential ischemia in TREATMENT
various organs, extremities (e.g. stroke,
erythromelalgia) MEDICATIONS
▪ Headache, dizziness, fatigue, vision loss, ▪ Low risk for thrombosis
abdominal pain, nausea ▫ Antiplatelet drugs (aspirin, anagrelide)
▪ Less frequently, paradoxical bleeding ▪ High risk for thrombosis
▫ Epistaxis, bleeding gums, ecchymoses ▫ Hydroxyurea, interferon-alpha
▪ Splenomegaly
SURGERY
▪ In severe conditions
▫ Plateletpheresis (removal of platelets
from blood)
Figure 45.1 A peripheral blood smear from

an individual with essential thrombocytosis.
There are a higher than normal number of
platelets visible.
374 OSMOSIS.ORG
Chapter 45 Dysplastic & Proliferative Disorders
LANGERHANS CELL
HISTIOCYTOSIS (LCH)
osms.it/langerhans-cell-histiocytosis

▪ Rare, proliferative disorder affecting ▪ Lytic bone lesions may be asymptomatic/
Langerhans cells (type of dendritic cells), cause localized pain
myeloid progenitor cells in bone marrow ▪ Skin lesions
▪ AKA histiocytosis X ▫ Brown to purplish papules pustular,
▪ Osteolytic bone lesions infiltrated with purpuric, petechial, vesicular, papulo-
histiocytes; histiocytes, lymphocytes, nodular; eczema-like rash
macrophages, eosinophils infiltrate organs: ▪ Mucous membranes
skin, lymph nodes, bones, lungs, liver, ▫ Gingivitis, mucosal mass/ulcers, loose
spleen, central nervous system (CNS) teeth
Proliferating cells ▪ Lymphadenopathy
▪ Functionally immature ▪ Liver, spleen
▪ Immunohistochemistry ▫ Hepatic lesions, hepatosplenomegaly
▫ CD1a, S100 positive ▪ Lungs
▪ Abundant, foamy cytoplasm ▫ Recurrent spontaneous pneumothorax,
dyspnoea, chest pain
▪ Folded, grooved nuclei
▪ CNS
▪ Birbeck granules, “tennis racket”/rod-
shaped cytoplasmic organelles ▫ Diabetes insipidus, neurological deficits
▪ Systematic symptoms
▫ Fever, lethargy, weight loss
RISK FACTORS
▪ Usually affects children; also present in
adults DIAGNOSIS
▪ Mutations detected; most common (55–
60%) activates BRAF gene DIAGNOSTIC IMAGING
MRI
COMPLICATIONS
▪ CNS involvement
▪ CNS
▫ Pituitary gland → diabetes insipidus,
pons, basal ganglia; cerebellum LAB RESULTS
→ cognitive deficits, neuromotor ▪ Accumulation of inflammatory cells,
dysfunction Langerhans cells (large, mononuclear
▪ Liver, spleen cells with prominent nuclear groove), few
▫ Worse prognosis; sclerosing cholangitis cytoplasmic vacuoles, pale eosinophilic
may require liver transplant cytoplasm
OSMOSIS.ORG 375
TREATMENT
▪ Spontaneous regression can occur
MEDICATIONS
▪ Systemic corticosteroids
▪ Chemotherapeutic agents
▫ Alkylating agents, antimetabolites, vinca
alkaloids
SURGERY
▪ Surgial excision
OTHER INTERVENTIONS
of Langerhans cell histiocytosis. There are
numerous clonal dendritic cells (light pink)
with associated eosinophils (red).
Figure 45.3 An MRI scan of the head in the

sagittal plane demonstrating a subcutaneous
soft-tissue mass, destroying the frontal bone.
The diagnosis was confirmed as Langerhans
histiocytosis on biopsy.
376 OSMOSIS.ORG
LEUKEMOID REACTION
osms.it/leukemoid-reaction
▪ Drugs
PATHOLOGY & CAUSES
▫ Sulfonamides, dapsone,
glucocorticosteroids, granulocyte-colony
▪ Excessive, reactive leukocytosis (WBCs:
stimulating factor (G-CSF)
40,000–100,000/mL), resembling leukemia,
with increase in neutrophil precursors, “left ▪ Asplenia
shift” (e.g. myeloblasts, promyelocytes, ▪ Metabolic
myelocytes) in peripheral blood ▫ Diabetic ketoacidosis, preeclampsia,
▪ Cytoplasmic toxic granulation, Dohle uremia
bodies, blue-gray inclusions in peripheral
cytoplasm of neutrophils
▪ Lymphocytic reaction can occur SIGNS & SYMPTOMS
▪ Fatigue, weakness, high fever
COMPLICATIONS
▪ Severe/chronic infections
▫ Clostridium difficile infection (CDI), DIAGNOSIS
Mycobacterium tuberculosis, Bordetella
pertussis, Epstein–Barr virus (EBV) LAB RESULTS
▪ Sepsis ▪ ↑↑↑ WBCs
▪ Non-infectious inflammation ▪ Rule out blood malignancies
▫ Burns, postoperative state, acute ▫ Mature neutrophil precursors, unlike
asthma attack, acute episodes of gout immature cells in acute leukemia (blasts
▪ Severe hemolysis < 20%); toxic granulation, Döhle bodies
▪ Acute hemorrhage unlike chronic myelogenous leukemia
(CML)
▫ Peritoneal cavity
▫ Serum leukocyte alkaline phosphatase
▪ Tissue necrosis
(LAP) score normal/elevated, unlike CML
▫ Hepatic necrosis, ischemic colitis
▫ Confirm CML by Philadelphia
▪ Metastatic cancer chromosome with BCR/ABL fusion gene
▪ Paraneoplastic syndrome + FISH/PCR
▫ Lung carcinoma, renal cell carcinoma ▫ Bone marrow aspiration/biopsy
TREATMENT
▪ Treatment of underlying condition
OSMOSIS.ORG 377
MYELODYSPLASTIC SYNDROMES
(MDS)
osms.it/myelodysplastic-syndrome
▪ Functional defects in red (RBCs), white
PATHOLOGY & CAUSES blood cells (WBCs), platelets → anemia,
infections, bleeding
▪ Group of malignant hematopoietic stem cell
disorders
▪ Abnormal, ineffective hematopoiesis → SIGNS & SYMPTOMS
peripheral cytopenia
▪ Asymptomatic in early stages
Dysplastic cells
▪ Fatigue (anemia), infections (neutropenia),
▪ Pseudo Pelger–Huët cells
bleeding (thrombocytopenia)
▫ Bilobed neutrophils
▪ Ring sideroblasts
▫ Erythroblasts with granules of iron DIAGNOSIS
accumulated in mitochondria
▪ Megaloblastoid maturation LAB RESULTS
▪ Nuclear budding abnormalities ▪ Low RBCs, WBCs, platelets, normal/mildly
▪ Pawn ball megakaryocytes elevated mean corpuscular volume (MCV),
▫ Discrete nuclear lobes/multinucleation increased red cell distribution width (RDW)
▪ Low reticulocyte count, dysplastic RBCs,
WBCs, normal platelets, 1–20% blasts
CAUSES
▪ Dysplastic cells, increased blasts
▪ Can be idiopathic/secondary to exposure
▪ Chromosomal abnormalities, gene
▫ Toxins, genotoxic drugs,
mutations
immunosuppressive agents,
chemotherapy, radiation therapy (t-
MDS, therapy related MDS) TREATMENT
▪ Genetic defects due to
▫ Epigenetic factors, RNA splicing factors, MEDICATIONS
transcription factors ▪ Tumor necrosis factor (TNF) inhibitors
▫ 5q (5q-) deletion most common (e.g.lenalidomide, thalidomide), DNA
▪ Affects elderly individuals; mean age of methylation inhibitors
onset is 70 years
OTHER INTERVENTIONS
COMPLICATIONS
Allogeneic hematopoietic stem cell trans-
▪ MDS = pre-leukemias, high risk of
plant
conversion to AML
▪ Only curative option, for young individuals
▪ % of blasts (1–20%)
▪ If transplant not an option → blood product
▫ How close individual is to AML (> 20%)
transfusions, infection control (supportive)
▪ Progresses slowly → most succumb to
bleeding, infections before AML
378 OSMOSIS.ORG
Figure 45.4 A neutrophil from a in the

peripheral blood smear of an individual with
myelodysplastic syndrome. The neutrophil
is hypogranulated and has a hypolobated
nucleus, known as a pseudo Pelger–Huët
nucleus.
POLYCYTHEMIA VERA (PCV)

osms.it/polycythemia-vera
RISK FACTORS
PATHOLOGY & CAUSES ▪ Occurs in all ages; median age at diagnosis
60 years
▪ Chronic myeloproliferative neoplastic
▪ Genetic
disease
▫ JAK2V617F mutation (95% of cases)
▪ Hematopoietic stem cell disorder →
erythroid, granulocytic, megakaryocytic
lineages proliferate COMPLICATIONS
▪ Increased ▪ Hypertension, Budd–Chiari syndrome,
▫ RBCs, independent of erythropoietin deep vein thrombosis, arterial thrombosis,
(EPO); platelets; basophils; eosinophils; myocardial infarction (MI), gout (high cell
cell turnover → hyperuricemia turnover, hyperuricemia), PCV → AML
▪ Polycythemia → increased blood viscosity; (rare)
increased total blood volume → abnormal ▪ If untreated
blood flow ▫ Thrombotic, hemorrhagic complications
▪ Abnormal blood flow, defective platelet → death within months
function → vein thrombosis, infarcts,
bleeding
▪ PCV may evolve to “spent phase”
▫ Myelofibrosis, extramedullary
hematopoiesis in liver, spleen
OSMOSIS.ORG 379
SIGNS & SYMPTOMS
▪ Symptoms due to ↑ in RBCs → blood
viscosity
▫ Headache, fatigue, dizziness, dyspnea,
plethora, cyanosis
▪ Symptoms due to ↑ in basophils →
histamine release
▫ Pruritus (intense itching, especially after
hot shower), gastric ulcers
▪ Thrombosis
▫ Deep vein thrombosis, MI, Budd–Chiari
erythromelalgia; a sign of numerous diseases,
syndrome (portal vein thrombosis),
including polycythemia vera.
erythromelalgia (hyperemic
and inflamed extremities due to
microvascular occlusion of vessels)
▪ Bleeding TREATMENT
▫ Bleeding gums, epistaxis, ecchymoses,
GI bleed MEDICATIONS
▪ Hepatosplenomegaly, splenomegaly ▪ Hydroxyurea
▪ Hypertension ▫ ↓ RBC production
▪ Interferon-alpha
▫ ↑ RBC destruction
DIAGNOSIS ▪ Aspirin
▫ ↓ risk of thrombosis
LAB RESULTS
▪ Exclude secondary polycythemia (hypoxia,
renal cell, hepatocellular carcinoma); ↑ EPO OTHER INTERVENTIONS
serum ▪ Phlebotomy
▪ CBC ▫ ↓ hematocrit, hemoglobin
▫ ↑ RBCs, hematocrit, hemoglobin; ↑
platelets/WBCs
▪ ↑ Lactate dehydrogenase
▪ ↓ serum EPO
▪ Bone marrow aspiration/biopsy confirms
diagnosis
▪ Genetic testing
▫ JAK2 mutation

erythromelalgia; a sign of numerous diseases,
including polycythemia vera.
380 OSMOSIS.ORG
PRIMARY MYELOFIBROSIS (PM)

osms.it/myelofibrosis
OTHER INTERVENTIONS
PATHOLOGY & CAUSES
Bone marrow aspiration
▪ Chronic myeloproliferative disease of ▪ Dry tap, no sample (accumulation of
hematopoietic stem cells resulting in bone collagen fibers)
marrow fibrosis
▪ AKA essential thrombocythemia
▪ Overproduction of megakaryocytes in bone
marrow
▪ Increased platelets, abnormally shaped;
decreased platelet survival
▪ Thromboses; bleeding episodes may occur;
other cell lines may be affected
▪ JAK2 mutation (50%), MPL (5–10%)/
calreticulin
▪ “Spent phase” of myelofibrosis/AML (rarely)

SIGNS & SYMPTOMS of the bone marrow in an individual with
myelofibrosis. The fibrosis is seen as fine
▪ May be asymptomatic silver strands upon staining with reticulin.
▪ When symptomatic, thrombosis, potential
ischemia in various organs
▫ Headache, dizziness, fatigue, numbness TREATMENT
in extremities, erythromelalgia, vision
loss, abdominal pain, nausea MEDICATIONS
▪ Less frequently, bleeding ▪ Low risk for thrombosis
▫ Epistaxis, bleeding gums, bruises ▫ Antiplatelet drugs (aspirin, anagrelide)
▪ Splenomegaly ▪ High risk for thrombosis
▫ Hydroxyurea, interferon-alpha
DIAGNOSIS SURGERY
▪ In severe conditions
LAB RESULTS ▫ Plateletpheresis (removal of platelets
▪ ↓ RBCs, platelets from blood)
▪ Leukoerythroblastosis, dacryocytes
Bone marrow biopsy

▪ Hypocellularity, fibrosis
OSMOSIS.ORG 381
382 OSMOSIS.ORG
NOTES
NOTES
HYPERCOAGULABLE DISORDERS

▪ Unregulated activation of coagulation ▪ Family history of thrombophilia, thrombosis
cascade → vascular thrombosis under age of 50 years, thrombosis in
unusual location (e.g. portal veins),
recurrent thromboembolic episodes
CAUSES
▪ Inherited/acquired
▪ Secondary to liver disease, autoimmune LAB RESULTS
systemic disorders, renal failure, ▪ Assays for specific proteins/factors,
acute thrombosis, exposure to toxins, antibodies
anticoagulation therapy ▪ Genetic testing
▪ Venous, arterial thrombosis, obstetric
MEDICATIONS
SIGNS & SYMPTOMS ▪ Anticoagulants/thrombolysis
▫ If symptomatic
▪ Deep vein thrombosis (DVT) → pulmonary ▪ Prophylactic anticoagulation when high risk
embolism (PE) for thrombosis
▫ E.g. perioperatively/in postpartum period
▫ If asymptomatic
OSMOSIS.ORG 383
ANTIPHOSPHOLIPID SYNDROME
(APS)
osms.it/antiphospholipid-syndrome

▪ Acquired autoimmune multisystem ▪ Recurrent venous thromboses
disorder; associated underlying disorders, ▫ DVT → PE → pulmonary hypertension
systemic lupus erythematosus (SLE) ▫ Superficial thrombophlebitis
▪ AKA lupus anticoagulant syndrome ▫ Hepatic/portal vein thrombosis → Budd-
▫ May be idiopathic; may appear after Chiari syndrome, hepatic infarction,
exposure drugs/infectious agents portal hypertension, cirrhosis
▪ Antiphospholipid antibodies (aPL) bind to ▫ Adrenal vein thrombosis → hemorrhagic
targets → induce hypercoagulable state infarction
▪ Pathways ▪ Recurrent arterial thromboses (less
▫ Thromboembolic episodes/pregnancy common)
morbidity ▫ Stroke/transient ischemic attack
▫ Increase in atherosclerosis, fetal loss, ▫ Myocardial infarction
neurological damage; aPL-associated ▫ Bowel infarction
increase in vascular tone ▫ Multiple capillary, arterial thromboses →
▪ Catastrophic APS (rare) renal microangiopathy → renovascular
▫ Widespread thrombosis → multiorgan hypertension
failure
Pregnancy complications LAB RESULTS
▪ Spontaneous abortions; fetal death ▪ ≥ one antiphospholipid antibodies
▪ Premature birth due to ▫ Lupus anticoagulant, AKA lupus
preeclampsia/placental insufficiency antibody
▫ Anticardiolipin antibody
Cutaneous complications
▫ Anti-beta2 glycoprotein I
▪ Livedo reticularis (most common)
▪ ≥ one clinical feature
▫ Obstruction of microvasculature → net-
▫ Vascular thrombosis/pregnancy
like purplish discolouration of skin
morbidity
▪ Cutaneous ulcers
▪ Moderate thrombocytopenia
Ocular complications ▪ Prolonged PT, aPTT
▪ Retinal venous/arterial circulation occlusion; ▫ Not corrected by plasma transfusions
anterior ischemic optic neuropathy ▪ False positive in venereal disease lab test,
rapid plasma reagin test for syphilis
▫ Cardiolipin phospholipid as major
reagent
384 OSMOSIS.ORG
Chapter 46 Hypercoagulable Disorders
TREATMENT
MEDICATIONS
▪ Aspirin/anticoagulants (e.g. warfarin)
▫ To stabilize coagulation pathways
▫ Lifelong systemic therapy with
antiplatelet medications
ANTITHROMBIN III DEFICIENCY

osms.it/antithrombin-III-deficiency

▪ Endogenous serine protease inhibitor in LAB RESULTS
coagulation cascade; inactivates thrombin
(factor IIa), factor Xa. Genetic testing
Functional assay
CAUSES ▪ Reduced plasma antithrombin III activity
▪ Inherited ▪ PT/aPTT/thrombin time
▫ Autosomal dominant gene mutation; ▫ No change + aPTT → diminished
variable penetrance increase following heparin
▪ Acquired
▫ Defective synthesis; liver disease,
therapy with vitamin K antagonists (e.g.
warfarin)
▫ Loss in urine; renal failure/nephrotic TREATMENT
syndrome
▫ Depletion in acute thrombosis/ MEDICATIONS
disseminated intravascular disease (DIC) ▪ Treat deep vein thrombosis / pulmonary
embolism
COMPLICATIONS ▫ Anticoagulants with vitamin K
▪ Venous thromboembolism antagonists/direct oral anticoagulants
▪ Heparin resistance (DOACS)
▪ If ≥ two thromboembolic events occur →
lifelong anticoagulant therapy (e.g. vitamin
SIGNS & SYMPTOMS K antagonists/ DOACs)
▪ Prophylactic antithrombin replacement
▪ Deep vein thrombosis → pulmonary ▫ High-risk thrombophilic situations (e.g.
embolism surgery/pregnancy)
OSMOSIS.ORG 385
FACTOR V LEIDEN (FVL)
osms.it/factor-v-leiden

▪ Inherited thrombophilia LAB RESULTS
▪ Mutant form of coagulation factor V, lacks ▪ Genetic testing
Arg506 cleavage site ▫ FVL mutation (direct analysis of genomic
DNA)
CAUSES ▫ Functional aPC resistance assay
▪ FVL → resistance to degradation by (individual’s plasma mixed with factor
activated protein C (aPC) → unregulated V-deficient plasma)
activation of coagulation cascade
→ hypercoagulable state → venous OTHER DIAGNOSTICS
thromboembolism (VTE) ▪ Family history of thrombophilia
▪ VTE at young age/in unusual location
RISK FACTORS
▪ FVL homozygosity
▪ Coinheritance with other thrombophilia TREATMENT
disorders
MEDICATIONS
▪ Pregnancy (physiologic hypercoagulability)
▪ Anticoagulants/thrombolysis
▪ Oral hormonal contraceptives
▫ Treat for DVT/PE
▫ If ≥ two thromboembolic events →
SIGNS & SYMPTOMS lifelong anticoagulant therapy
▪ Prophylactic anticoagulation
▪ VTE ▫ High risk thrombophilic situations (e.g.
▪ DVT/thrombosis in superficial veins of surgery, pregnancy)
lower extremities/cerebral, portal, hepatic
veins
▪ Possible fetal loss
386 OSMOSIS.ORG
Chapter 46 Hypercoagulable Disorders
PROTEIN C DEFICIENCY
osms.it/protein-c-deficiency

▪ Protein C deficiency → familial LAB RESULTS
thrombophilia
Functional assay
▪ Protein C
▪ Reduced protein C
▫ Vitamin K-dependent inhibitor of factors
V, VIII
▫ Protein C deficiency → unregulated OTHER DIAGNOSTICS
activation of coagulation cascade → ▪ Monitor if recurrent VTE, family history
increased thrombotic risk of VTE, thrombosis in unusual location/at
young age
TYPES
▪ Type I TREATMENT
▫ Reduced protein C levels
▪ Type II MEDICATIONS
▫ Normal protein C levels, reduced ▪ Anticoagulants/thrombolysis
function ▫ Treat deep vein thrombosis/VTE
▪ Prophylactic protein C concentrate
CAUSES ▫ Asymptomatic individuals (e.g.
▪ Autosomal dominant inherited disorder perioperatively/in postpartum period)
▪ Acute thrombosis, disseminated
Warfarin-induced skin necrosis
intravascular coagulation, liver disease,
vitamin K antagonist anticoagulants ▪ Stop warfarin; start vitamin K, heparin,
protein C concentrate/fresh frozen plasma
administration
COMPLICATIONS
▪ Due to treatment
▫ Warfarin-induced thrombotic skin MNEMONIC
necrosis Proteins C & S
C and S inhibit coagulation:
they are Clot Stoppers
SIGNS & SYMPTOMS
▪ Venous thromboembolism (VTE)
▪ In homozygotes, neonatal purpura
fulminans
OSMOSIS.ORG 387
PROTEIN S DEFICIENCY
osms.it/protein-s-deficiency

▪ Deficiency of protein S → familial ▪ VTE
thrombophilia ▪ In homozygotes, neonatal purpura
▪ Protein S fulminans
▫ Cofactor of protein C
▫ Protein S deficiency → decreased
protein C activity → enhanced activity
DIAGNOSIS
of coagulation cascade → increased
thrombotic risk ▪ Monitor if recurrent venous
thromboembolism (VTE), family history of
VTE, thrombosis at young age/in unusual
TYPES location
▪ Type I (classic)
▫ Reduced total protein S, free protein S, LAB RESULTS
protein S function
▪ Protein S assay
▪ Type II (rare)
▫ Normal total, free protein S, reduced
function TREATMENT
▪ Type III
▫ Reduced free protein S, protein S MEDICATIONS
function; normal total protein S ▪ Anticoagulants/thrombolysis
▫ Treat deep vein thrombosis
CAUSES ▪ If asymptomatic, avoid drugs that
▪ Autosomal dominant inherited condition predispose to thrombosis (e.g. oral
contraceptives)
▫ Most individuals heterozygous for
PROS1 gene mutation ▪ Prophylactic anticoagulation (e.g.
preoperatively/in postpartum period)
▪ Pregnancy, oral hormonal contraceptive,
disseminated intravascular coagulation
(DIC), acute thrombosis, HIV infection,
nephrotic syndrome, liver disease
388 OSMOSIS.ORG
NOTES
NOTES
HYPOCOAGULABLE DISORDERS

▪ Acquired, inherited disorders; defects in LAB RESULTS
coagulation cascade ▪ Platelet count
▪ Levels of clotting factors
Prothrombin time (PT)
SIGNS & SYMPTOMS ▪
▪ Partial thromboplastin time (aPTT)
▪ Bleeding ▪ Fibrin degradation products
▪ Thrombosis, only disseminated ▪ Genetic testing
intravascular disease (DIC)
TREATMENT
OTHER INTERVENTIONS
▪ Supportive therapy
DISSEMINATED INTRAVASCULAR
COAGULATION (DIC)
osms.it/disseminated-intravascular-coagulation
CAUSES
PATHOLOGY & CAUSES
▪ Complication of underlying conditions
▪ Acquired, paradoxical process of ▪ Obstetric complications (e.g. preeclampsia,
thrombosis, bleeding obstetric hemorrhage, retained dead fetus)
▪ Release of procoagulants, tissue factors, ▪ Critical illness (individuals in intensive care
bacterial components, enzymes/major unit)
endothelial injury → excessive activation ▪ Malignancy
of coagulation cascade → thrombosis ▫ Mucin-secreting adenocarcinoma (e.g.,
of small/medium blood vessels → lungs, pancreas, stomach, prostate,
activation of fibrinolysis to resolve clots ovaries)
→ fibrin degradation products released ▫ Acute promyelocytic leukemia (APL)
into circulation → interfere with platelet ▪ Infection/sepsis, especially gram-negative
aggregation, clot formation bacteria
▪ Depletion of platelets, fibrin, coagulation ▪ Massive tissue injury due to trauma,
factors → consumption coagulopathy
OSMOSIS.ORG 389
surgery, burn, fracture
▪ Intravascular hemolysis due to blood type
SIGNS & SYMPTOMS
incompatibility
▪ Acute: bleeding episodes (e.g. ecchymoses,
▪ Shock petechiae, purpura, blood oozing from
▪ Snakebites gingival/oral mucosa, sites of trauma,
catheters, intravenous lines)
COMPLICATIONS ▪ Chronic: thromboembolism, tissue hypoxia,
▪ Widespread thrombosis, ischemia, necrosis infarctions
of brain, heart, kidneys, liver, lungs,
adrenals, spleen → organ dysfunction
▪ Microangiopathic hemolytic anemia
DIAGNOSIS
(MAHA)
LAB RESULTS
▪ Paradoxical tendency to life-threatening
bleeding, due to consumption of ▪ ↓ Platelets
procoagulatory factors ▪ ↓ Fibrinogen
▪ ↓ Clotting factors
▪ ↑ Prothrombin time (PT)
MNEMONIC: DIC TEAR ▪ ↑ Partial thromboplastin time (aPTT)
Common causes of DIC ▪ ↑ D-dimers (fibrin degradation product)
Delivery TEAR: obstetric ▪ Schistocytes, damaged red blood cells
complications (RBCs) due to MAHA
Infections: gram negative)/ ▪ Physiologic compensation → lab results
Immunological normal
Cancer: prostate, pancreas, ▫ For chronic (solid tumors, large aortic
lung, stomach aneurysms)
Obstretrical complications
Toxemia of pregnancy TREATMENT
Emboli (amniotic)
Abruptio placentae
MEDICATIONS
▪ Oxygen, IV fluids
Retain fetus products
OTHER INTERVENTIONS
▪ Replace clotting factors with fresh frozen
plasma (FFP), cryoprecipitate, fibrinogen
▪ Platelet transfusions, if platelet count <
30,000
▪ RBC transfusions for severe bleeding
390 OSMOSIS.ORG
Chapter 47 Hypocoagulable Disorders
HEMOPHILIA A
osms.it/hemophilia-a

▪ Most common inherited clotting factor LAB RESULTS
deficiency; classic hemophilia ▪ Normal platelet count
▪ X-linked recessive disorder ▪ Normal prothrombin time (extrinsic
▪ Mutated gene F8 on X chromosome pathway not affected)
▪ Prolonged partial thromboplastin time
CAUSES (intrinsic pathway affected)
▪ Quantitative/qualitative deficiency of factor ▪ Factor VIII clotting assay
VIII → insufficient activation of the intrinsic ▪ Genetic testing
pathway → defect in common coagulation
pathway → increased tendency for
bleeding TREATMENT
MEDICATIONS
RISK FACTORS Desmopressin (DDAVP)
▪ More common in individuals who are ▪ For mild quantitative hemophilia A
biologically male; individuals who are ▫ → stimulates von Willebrand factor
biologically female more likely to be carriers (vWF) release → promotes stabilization
of residual factor VIII
SIGNS & SYMPTOMS

OTHER INTERVENTIONS
▪ Varies according to mutation, factor VIII ▪ Recombinant factor VIII infusions
activity ▪ If severe deficiency, immune system may
▪ Asymptomatic/spontaneous bleeding perceive supplemental factors as foreign
→ production of antibodies (inhibitors) →
▪ < 10% factor VIII
elimination of injected factors/anaphylaxis
▫ Easy bruising
▪ Avoid sports, trauma, medications that
▫ Prolonged bleeding, after injury/surgery promote bleeding
▫ Hematomas (e.g. muscle hematomas, ▪ Local measures
hemophilic pseudotumors)
▫ Treat hemarthrosis, hematomas (e.g.
▫ Gastrointestinal (GI) bleeding resting of affected part, application of
▫ Hematuria ice)
▫ Severe epistaxis
▫ Painful hemarthrosis → progressive
joint irregularity, disability (knee most
common)
▫ Intracerebral hemorrhage
OSMOSIS.ORG 391
Figure 47.2 An MRI scan of the knee
demonstrating hemarthrosis. Individuals
Figure 47.1 An abdominal MRI scan in the with hemophilia are at increased risk of
coronal plane demonstrating a hematoma of hemarthrosis.
the right psoas muscle in an individual with
hemophilia.
HEMOPHILIA B
osms.it/hemophilia-b

▪ Mutated gene F9 on X chromosome LAB RESULTS
▪ AKA Christmas disease ▪ Normal platelet count, prothrombin time
▪ Qualitative/quantitative deficiency of (intrinsic pathway affected)
coagulation factor IX → insufficient ▪ Factor IX clotting assay/genetic mutation
activation of intrinsic coagulation pathway testing
→ impaired hemostasis
▪ Less common
TREATMENT
DDAVP
▪ Spontaneous bleeding, delayed bleeding
after trauma, hemarthrosis, hematomas, ▪ Not helpful in hemophilia B; stimulates
epistaxis, intracranial, GI/genitourinary tract vWF → stabilizes only factor VIII, not IX
bleeding
OTHER INTERVENTIONS
▪ Infusions of recombinant factor IX
392 OSMOSIS.ORG
Chapter 47 Hypocoagulable Disorders
VON WILLEBRAND DISEASE

osms.it/von-willebrand-disease

▪ Most common inherited bleeding disorder LAB RESULTS
of primary hemostasis ▪ Abnormal PFA-100 test
▪ Defective platelet function with normal ▪ ↓ factor VIII activity
platelet count ▪ ↓ vWF
▪ Quantitative/qualitative deficiency of vWF ▪ PTT prolonged
→ impaired platelet aggregation, adhesion,
▪ ↓ platelet aggregation, presence of
dysfunction of factor VIII → deficiency in
ristocetin
coagulation cascade → bleeding tendency
▪ Collagen-binding function reduced
▪ Hemostatic pressure (e.g. surgery/trauma)
▪ Platelet count normal
TYPES
TREATMENT
Type I
▪ Most common MEDICATIONS
▪ Autosomal dominant, partial quantitative ▪ DDAVP
deficiency ▫ Type I, Type II
Type II ▪ Factor VIII/vWF concentrates
▪ Autosomal dominant, qualitative deficiency ▫ After major injury; during operation;
Type III, II not responding to DDAVP
Type III ▪ High-purity vWF concentrates
▪ Autosomal recessive, severe quantitative
deficiency
OTHER INTERVENTIONS
▪ Local measures, tranexamic acid for mild
SIGNS & SYMPTOMS bleeding
▪ Typically asymptomatic
▪ Surgery/trauma provoke clinical
manifestation
▪ Spontaneous mucosal, cutaneous bleeding
(e.g. epistaxis, easy bruising, excessive
bleeding from wounds, bleeding gums)
▪ Menorrhagia
▪ GI bleeding
▪ Internal/joint bleeding (Type III)
OSMOSIS.ORG 393
NOTES
NOTES
LEUKEMIAS

Neoplastic infiltration
PATHOLOGY & CAUSES ▪ Bone marrow
▫ Bone pain
▪ Malignant neoplastic monoclonal
proliferation of hematopoietic blood cells ▪ Thymus
▪ Abnormal blood cells/precursors ▫ Palpable mass, airway compression
accumulate in bone marrow → physical ▪ Liver and spleen
suppression → prevent maturation ▫ Hepatosplenomegaly
▪ Lymph nodes
TYPES ▫ Lymphadenopathy
▪ Meningeal infiltration
Acute
▫ Headaches, vomiting, nerve palsies,
▪ Acute lymphoid leukemia nuchal rigidity
▪ Acute myeloid leukemia
Chronic DIAGNOSIS
▪ Chronic lymphoid leukemia
▪ Chronic myeloid leukemia LAB RESULTS
▪ Blood count
RISK FACTORS ▪ Blood smear
▪ Numerical, structural chromosomal ▪ Bone marrow smear
aberrations ▪ Immunophenotyping
▪ Ionizing radiation, chemotherapy
▪ Benzene exposure
TREATMENT
▪ Infections, bleeding → death ▪ Chemotherapy

▪ Bone marrow transplantation
Cellular maturation absent
▪ Anemia → fatigue, shortness of breath, OTHER INTERVENTIONS
pallor ▪ Radiation therapy
▪ Thrombocytopenia → bruising, petechiae,
epistaxis
▪ Neutropenia → bacterial infections → fever,
pneumonia, sepsis
394 OSMOSIS.ORG
Chapter 48 Leukemias
ACUTE LYMPHOID LEUKEMIA (ALL)

osms.it/acute-lymphoid
PATHOLOGY & CAUSES pneumonia, sepsis
▪ Neoplastic monoclonal proliferation of Neoplastic infiltration

lymphoid stem cells (lymphoblasts) in bone ▪ Bone marrow
marrow ▫ Bone pain
▪ Immature lymphoblasts accumulate in bone ▪ Thymus
marrow → physical suppression → prevent
▫ Palpable mass, airway compression
maturation
▪ Liver and spleen
▫ Hepatosplenomegaly
TYPES
▪ Lymph nodes
B cell acute lymphoblastic leukemia ▫ Lymphadenopathy
(B-ALL) ▪ Meningeal infiltration
▪ Most common (85%) ▫ Headaches, vomiting, nerve palsies,
▪ Origin nuchal rigidity
▫ Pre-B cells of bone marrow
▪ Associated with translocations t(12,21),
t(9,22) DIAGNOSIS
T cell acute lymphoblastic leukemia LAB RESULTS
(T-ALL)
Blood count, smear of peripheral blood
▪ Origin
▪ ↑ lymphoblasts
▫ Pre-T cells in thymus
▪ ↑ white blood cells
▪ Associated with NOTCH1 mutation
Bone marrow smear
RISK FACTORS ▪ Hypercellular bone marrow, lymphoblast
▪ Young age (most common leukemia in domination (> 20%)
children) ▪ T-ALL
▫ B-ALL: peak incidence at three years old ▫ “Starry sky” pattern produced by
▫ T-ALL: peak incidence at 15–20 years phagocytosing macrophages
old ▪ Mitotic figures
▪ Down syndrome (after age five)
Immunophenotyping
▪ Radiation exposure
▪ Terminal deoxynucleotidyl transferase (TdT)
▫ Positive nuclear staining, distinguish
SIGNS & SYMPTOMS from acute myeloid leukemia (AML)
▪ B-ALL
▪ Abrupt onset ▫ Express tumor markers CD10, CD19,
CD20
Cellular maturation absent
▪ T-ALL
▪ Anemia → fatigue, shortness of breath,
▫ Express tumor markers CD1, CD2, CD5,
pallor
CD7, CDH
epistaxis
OSMOSIS.ORG 395
TREATMENT
MEDICATIONS
▪ Aggressive chemotherapy with
prophylactic injections to scrotum,
cerebrospinal fluid (CSF)
▫ 95% complete remission, 75% cure rate
▫ More successful in children > two years
old
▪ If spread to brain
▫ Intrathecal chemotherapy/radiation
therapy
▪ Tyrosine-kinase inhibitors
MNEMONIC: ABCDE
Figure 48.1 A bone marrow film from an
Characteristics of Acute
individual with acute lymphoid leukemia.
leukemias
Acute:
Blasts predominate
Children
Drastic course
Elderly
Few WBC’s (+ Fevers)
ACUTE MYELOID LEUKEMIA (AML)

osms.it/acute-myeloid
Acute megakaryocytic leukemia
PATHOLOGY & CAUSES
▪ Neoplastic monoclonal proliferation of RISK FACTORS
myelogenous stem cells (myeloblasts) in ▪ Adults age; peak at 60
bone marrow ▪ Radiation, chemotherapy
▪ Immature myeloblasts accumulate in ▪ Myeloproliferative disorders
bone marrow → physical suppression → ▪ Down syndrome (before age five)
prevents maturation
COMPLICATIONS
TYPES ▪ Disseminated intravascular coagulation
Acute promyelocytic leukemia (DIC)
▪ Associated with translocation t(15,17)
→ disruption of retinoic acid receptor → SIGNS & SYMPTOMS
promyelocytes accumulate
Acute monocytic leukemia ▪ Abrupt onset
396 OSMOSIS.ORG
Cellular maturation absent SURGERY

▪ Anemia → fatigue, shortness of breath, ▪ Bone marrow transplantation
pallor
epistaxis
pneumonia, sepsis
▪ Symptoms less common in AML than ALL
▪ Bone marrow
▫ Bone pain
▪ Thymus
▫ Palpable mass, airway compression
▪ Liver and spleen
▫ Hepatosplenomegaly
▪ Lymph nodes
▫ Lymphadenopathy
▪ Meningeal infiltration
▫ Headaches, vomiting, nerve palsies, Figure 48.2 The histological appearance of a
nuchal rigidity myeloid sarcoma, also known as a chloroma.
The tumor is an extramedullary manifestation
of acute myeloid leukemia.
▪ Symptoms more common in AML than ALL
▪ Skin
▫ Leukemia cutis
▪ Gums
▫ Swelling (classic)
DIAGNOSIS
LAB RESULTS
Blood count, blood smear
▪ ↑ leukocytes, anemia
Bone marrow smear

▪ ↑ myeloblasts > 20%
▪ Myeloblasts containing Auer rods
(aggregates of myeloperoxidase)
Figure 48.3 A CT scan of the head in the

TREATMENT axial plane demonstrating a myeloid sarcoma,
or chloroma, of the occiput. The tumor is
MEDICATIONS extradural and destroying the overlying bone.
▪ Chemotherapy
▪ All-trans retinoic acid treatment
▫ For promyelocytic leukemia
OSMOSIS.ORG 397
MNEMONIC: ABCDE
Characteristics of Acute
leukemias
Acute:
Blasts predominate
Children
Drastic course
Elderly
Few WBC’s (+ Fevers)
CHRONIC LYMPHOID LEUKEMIA

(CLL)
osms.it/chronic-lymphoid

▪ Neoplastic monoclonal proliferation ▪ Late onset
of mature, functionally abnormal B
lymphocytes in bone marrow, blood Cellular maturation absent
▪ Mature B lymphocytes accumulate in bone ▪ Anemia → fatigue, shortness of breath,
marrow → physical suppression → prevent pallor
maturation ▪ Thrombocytopenia → bruising, petechiae,
epistaxis
CAUSES pneumonia, sepsis
▪ Chromosomal abnormalities
▪ Mutation of proteins involved in tyrosine Neoplastic infiltration
kinase pathway (e.g. Bruton’s tyrosine ▪ Symptoms less common in AML than ALL
kinase) ▪ Bone marrow
▫ Bone pain
RISK FACTORS ▪ Thymus
▪ Adult age; most common leukemia in adults ▫ Palpable mass, airway compression
▪ Family history ▪ Liver and spleen
▪ Agent Orange exposure ▫ Hepatosplenomegaly
▪ Lymph nodes
COMPLICATIONS ▫ Lymphadenopathy
▪ Abnormal Ig secretion ▪ Meningeal infiltration
▫ Hypogammaglobulinemia, autoimmunity ▫ Headaches, vomiting, nerve palsies,
(e.g. autoimmune hemolytic anemia) nuchal rigidity
▪ Richter syndrome
▫ Progresses into aggressive lymphoma
(e.g diffuse large B cell lymphoma)
398 OSMOSIS.ORG
DIAGNOSIS
LAB RESULTS
Blood count, blood smear
▪ Lymphocytosis > 5,000 per mm3
▪ Smudge cells: disruption of fragile cell
membranes of abnormal lymphocytes
Immunophenotyping
▪ CD5, CD20, CD23
OTHER DIAGNOSTICS
Surgery
▪ Lymph node biopsy
▫ ↑ small, round lymphocytes infiltration
▫ Proliferation centers (pathognomic)
Figure 48.4 The gross pathological
appearance of the spleen in a case of chronic
TREATMENT lymphoid leukemia. The lymph nodes at the
hilum of the spleen are also involved.
MEDICATIONS
▪ Chemotherapy
▪ Immunotherapy
SURGERY
▪ Bone marrow transplant
OTHER INTERVENTIONS

of chronic lymphocytic leukemia. There
is a proliferation centre (also known as a
pseudofollicle) composed of malignant
lymphocytes with bigger, larger nuclei. This
proliferation centre is surrounded by small,
darker staining lymphocytes.
Figure 48.6 A CT scan in the coronal

plane demonstrating splenomegaly as a
consequence of chronic lymphoid leukemia.
OSMOSIS.ORG 399
CHRONIC MYELOID LEUKEMIA
(CML)
osms.it/chronic-myeloid
▪ Increasing anemia, thrombocytopenia,
PATHOLOGY & CAUSES basophilia
▪ Bone pain, fever
▪ Neoplastic monoclonal proliferation of
▪ Significant splenomegaly
mature granulocytes/precursors
▪ Mature granulocytes accumulate in bone
marrow → physical suppression → prevent DIAGNOSIS
maturation
▪ Associated with Philadelphia chromosome LAB RESULTS
t(9, 22) → BCR-ABL1 fusion → chimeric
protein with strong tyrosine kinase activity Blood count, blood smear
(> 90% of individuals) ▪ ↑ granulocytes (basophils, eosinophils,
neutrophils)
RISK FACTORS Bone marrow biopsy
▪ Adult age (> 40 years), radiation exposure,
▪ Hypercellularity (cells of myeloid cell line/
benzene exposure
precursors)
▪ Karyotypic analysis
SIGNS & SYMPTOMS ▫ Fluorescent in situ hybridization (FISH),
PCR: BCR-ABL1 gene mapping
▪ Classified by clinical signs, lab results ▪ Mild fibrosis
Chronic phase (85% at time of diagnosis)

▪ Leukocytosis (predominantly neutrophils)
▪ Asymptomatic/non-specific symptoms
▫ Fatigue, weight loss, loss of energy,
fever
Accelerated phase
▪ > 20% basophils in blood/bone marrow
▪ 10–19% myeloblasts in blood/bone marrow
▪ Anemia
▪ Splenomegaly, hepatomegaly,
lymphadenopathy
▪ Recurrent infections Figure 48.7 A bone marrow smear
▪ Bleeding, petechiae, ecchymoses demonstrating a small, hypolobated
▪ Treatment less effective megakaryocyte, typical of chronic
myelogenous leukemia.
Blast crisis
▪ Terminal phase; rapid progression, low
survival rate
▪ > 20% myeloblasts/lymphoblasts in blood/
bone marrow
400 OSMOSIS.ORG
TREATMENT
MEDICATIONS
▪ Tyrosine kinase inhibitors
SURGERY
▪ Bone marrow transplantation
OSMOSIS.ORG 401
NOTES
NOTES
LYMPHOMAS

▪ Metastasis to bone marrow → crowds
PATHOLOGY & CAUSES out normal marrow progenitor cells →
decreases healthy erythrocytes/leukocytes/
▪ Lymphocytic tumors platelets
▪ Nodal lymphomas: develop in lymph nodes
▪ Extranodal lymphomas: develop in/spread
to other organs/tissues SIGNS & SYMPTOMS
▪ Neoplastic B cells do not produce
antibodies ▪ B (systemic) symptoms: fever, night
▪ Attract non-neoplastic inflammatory cells sweats, weight loss, fatigue, loss of
(e.g. T cells) via chemokines appetite, chills
▪ Activate fibroblasts to make collagen,
eosinophils DIAGNOSIS
TYPES DIAGNOSTIC IMAGING
Hodgkin’s lymphomas CT scan, positron emission tomography
▪ Spread contiguously (to nearby lymph (PET) scan
nodes; rarely extranodal) ▪ Stage of lymphoma
▫ Prognosis better for Hodgkin’s:
contiguous spread allows direct, LAB RESULTS
targeted treatment
▪ Reed–Sternberg cells Lymph node biopsy
▪ Confirmation, type
Non-Hodgkin’s lymphomas
▪ Spread non-contiguously
▪ No Reed–Sternberg cells TREATMENT
▪ Depends on extent, stage, category; age,
CAUSES health of individual; coexisting diseases
▪ Genetic mutation in lymphocytes → no
apoptosis → cell divides → becomes
neoplastic cell
MEDICATIONS
▪ Chemotherapy
▪ Possible link between viruses (e.g. HIV,
EBV), lymphomas
SURGERY
COMPLICATIONS ▪ Stem cell transplant
▪ Metastasis to spinal cord → spinal cord
compression → sensory/motor deficits OTHER INTERVENTIONS
402 OSMOSIS.ORG
Chapter 49 Lymphomas
HODGKIN'S LYMPHOMA
osms.it/hodgkins
Histological CHL subtypes
PATHOLOGY & CAUSES ▪ Nodular sclerosis Hodgkin’s lymphoma
▫ Most common; esp. in young adults
▪ B-cell tumors; Reed–Sternberg cells: large
mononuclear, neoplastic cells; two cells ▫ Neoplastic, inflammatory cells
surrounded by collagen from fibroblasts
fused, two nuclei (resemble owl eyes)
forming nodules
▫ Lacunar cells (Reed–Sternberg cells with
TYPES shrunken cytoplasm, nucleus appears as
if in middle of lacuna/lake)
Classical Hodgkin’s lymphoma (CHL)
▫ Good prognosis
▪ More common
▪ Mixed cellularity
▪ Reed–Sternberg cells express CD45/CD20;
not CD15/CD30 ▫ Second most common; more common in
older adults
▪ Histological subtypes: background
inflammatory cells, fibrosis ▫ Prevalent in HIV-positive individuals
▫ Mixed inflammatory background
OSMOSIS.ORG 403
composed of eosinophils, neutrophils,
plasma cells, histiocytes surrounding SIGNS & SYMPTOMS
Reed–Sternberg cells
▪ Painless cervical lymphadenopathy
▪ Lymphocyte-rich
▫ Mediastinal lymphadenopathy: nodular
▫ Reed-Sternberg cells surrounded by
sclerosis subtype
lymphocytes
▪ Cytokine release: fever, drenching night
▫ Best prognosis, caught early
sweats, weight loss
▪ Lymphocyte-depleted
▫ Rarely present with nodular lymphocyte
▫ Rarest; median age: 30–37 years predominant Hodgkin’s lymphoma
▫ No reactive lymphocytes, abundance of ▪ B symptoms
Reed–Sternberg cells
▫ Nodular sclerosis: about 50%
▫ Prevalent in HIV-positive individuals
▫ Mixed cellularity: common
▫ Worst prognosis, advanced stage
▫ Lymphocyte-rich: rare
diagnosis
▫ Lymphocyte-depleted: common
Nodular lymphocyte predominant Hod-
gkin’s lymphoma
▪ More common in individuals who are DIAGNOSIS
biologically male
▪ Abnormal B cells express CD20/CD45; not DIAGNOSTIC IMAGING
CD15/CD30 ▪ CT scan, PET scan
▪ Lymphocyte-predominant cells; no Reed–
Sternberg cells LAB RESULTS
▫ Large groups of lymphocytes form ▪ Lymph node biopsy
nodules around lobulate-nucleated
“popcorn” cells (variant of Reed–
Sternberg cells)
▪ Slow-growing, highly curable
▪ Small risk of transformation to aggressive
non-Hodgkin’s lymphoma
STAGING
▪ Stage 1: limited to one lymph node group/
group of adjacent lymph nodes
▪ Stage 2: ≥ two lymph node regions on
same side as diaphragm
▪ Stage 3: lymph nodes on both sides
(superior, inferior) of diaphragm
▪ Stage 4: lymph nodes superior, inferior to
diaphragm; liver/spleen/lungs/bone marrow
▪ Subdivisions
▫ Category A: no symptoms Figure 49.1 A CT scan of the chest in
▫ Category B: B symptoms present the coronal plane demonstrating a large
mediastinal mass. The mass is a focus of
▫ Category E: organs/tissues beyond
Hodgkin’s lymphoma.
lymph system
404 OSMOSIS.ORG
TREATMENT
MEDICATIONS
Rituximab
▪ For nodular lymphocyte predominant
Hodgkin’s lymphoma
▪ Monoclonal antibody, binds CD20, induces
complement-mediated lysis → apoptosis

Hodgkin’s lymphoma. Reed–Sternberg cells
are pathognomonic of this disease.
Figure 49.3 The gross pathology of a spleen

that has been infiltrated by Hodgkin’s
lymphoma.
NON-HODGKIN'S LYMPHOMA
osms.it/non-hodgkin
▫ Slow growing
PATHOLOGY & CAUSES ▫ Chromosomal translocation: t(14,18)
→ BCL2 gene placed after Ig heavy
▪ B/T cell tumors, no Reed–Sternberg cells chain promoter → overexpression of
BCL2 → inhibition of apoptosis → cell
TYPES proliferation
▫ BCL2 promotes cell viability, blocks
B cell lymphomas apoptosis
▪ More common ▪ Burkitt lymphoma
▪ Neoplastic B cells: CD20 on surface ▫ Highly aggressive
▪ Rate of growth: slow/aggressive/highly ▫ “Starry sky” appearance under
aggressive microscope
B cell lymphoma subtypes ▫ Stars: tingible bodies (macrophages)
with phagocytosed dead neoplastic cells
▪ Diffuse large B cell lymphoma
▫ Sky: dark neoplastic lymphocytes
▫ Aggressive
▫ Chromosomal translocation: t(8,14)
▫ Most common
→ Myc gene moved adjacent to IgH
▪ Follicular lymphoma
OSMOSIS.ORG 405
promoter sequence → upregulation of ▪ Marginal zone lymphoma
Myc gene → Myc gene stimulates cell ▫ Indolent
growth, metabolism → increased cell ▫ Most common type
division
▫ Associated with mucosa-associated
▫ Variant in individuals of African lymphoid tissue (extranodal) in cases of
descent: extranodal involvement of jaw, chronic inflammation of stomach lining
associated with EBV infection (e.g. chronic H. pylori infection)
▫ Variant in individuals of non-African ▫ May occur in lymph nodes (nodal
descent: extranodal involvement of marginal zone lymphoma)/spleen
abdomen (e.g. at ileocecal junction), less (splenic marginal zone lymphoma)
frequently associated with EBV infection
▪ Lymphoplasmacytic lymphoma
▪ Mantle cell lymphoma
▫ Indolent
▫ Aggressive
▫ Bone marrow, lymph nodes, spleen
▫ Chromosomal translocation: t (11,14)
▫ Waldenstrom macroglobulinemia:
→ BCL1 gene moved to Ig promoter
neoplastic cells produce M proteins
→ upregulation of BCL1 gene →
(IgM) in high levels → IgM released into
stimulation of cell growth
406 OSMOSIS.ORG
blood → increases blood viscosity
T cell lymphomas
▪ Adult T cell lymphoma
▫ AKA leukemia: abnormal leukocytes in
bloodstream
▫ Possibly cause: human T-lymphotropic
virus (HTLV)
▫ HTLV infects T cells → becomes
incorporated into T cell DNA → genetic
mutation → adult T cell lymphoma
▪ Mycosis fungoides
▫ T cell lymphoma of of skin, resembles
fungal infection
▫ Neoplastic cells: CD4+ helper T cells
circulate in blood → Sezary syndrome
(erythroderma)
Figure 49.4 A PET scan in the coronal plane
demonstrating gross lymphadenopathy in
SIGNS & SYMPTOMS the axillary, para-aortic and inguinal chains.
The underlying cause is a Non-Hodgkin
lymphoma.
▪ Painless lymphadenopathy
▪ B symptoms: release of cytokines
▪ Extranodal involvement of GI tract: bowel DIAGNOSIS
obstruction
▪ Extranodal involvement of bone marrow: DIAGNOSTIC IMAGING
fatigue, easy bruising, recurrent infections
▪ CT scan, PET scan
▪ Extranodal involvement of spinal cord:
motor/sensory deficits (esp. legs)
LAB RESULTS
▪ Lymph node biopsy
TREATMENT
MEDICATIONS
Rituximab
▪ CD20-positive B cell non-Hodgkin
lymphomas
Figure 49.5 A diffuse large B-cell lymphoma

in a cytology specimen.
OSMOSIS.ORG 407
mantle cell lymphoma at low power. This Figure 49.7 A diffuse large B-cell lymphoma
lymph node has been infiltrated by the in a cytology specimen.
malignant lymphocytes which have a vaguely
nodular architecture.
408 OSMOSIS.ORG
NOTES
NOTES
MACROCYTIC ANEMIA

▪ Bone marrow produces larger than normal LAB RESULTS
erythrocytes AKA red blood cells (RBCs) ▪ Complete blood count
▪ Peripheral blood smear analysis
CAUSES ▪ Blood chemistry
▪ Multifactorial: nutritional deficits, genetics, ▪ Iron studies
substance exposure (e.g. certain drugs, ▪ Genetic testing
alcohol)
TREATMENT
SIGNS & SYMPTOMS
▪ Address underlying causes
▪ Fatigue, dyspnea, weight loss, pallor,
impaired concentration/memory, diarrhea,
onychoschizia (brittle nails)
MEGALOBLASTIC ANEMIA
osms.it/megaloblastic-anemia
B12 deficiency
PATHOLOGY & CAUSES ▪ Insufficient diet (e.g. vegan diet without B12
supplements, alcoholism, systemic/mental
▪ Macrocytic, normochromic anemia illness, food insecurity)
characterized by formation of large RBCs
▪ Malabsorption
▫ Lack of intrinsic factor → pernicious
CAUSES anemia
Cobalamin and/or folate deficiency ▫ Surgical: gastrectomy, bariatric surgery
→ lack of absorptive surface →
▪ Impaired DNA synthesis during
pernicious anemia
erythropoiesis → uncoordinated maturation
of cytoplasm and nuclei in erythroblasts ▫ Pancreatic insufficiency → impaired
(nuclear-cytoplasmic asynchrony) → binding of B12 to intrinsic factor →
abnormally large RBCs (macrocytosis) + pernicious anemia
defective cells with fragile membranes → ▫ Medications that interfere with
RBCs die prematurely → anemia absorption: e.g. biguanides, H2 receptor
blockers, proton-pump inhibitors,
neomycin
OSMOSIS.ORG 409
▫ Fish tapeworm (Diphyllobothrium latum)
→ competes with host for B12 DIAGNOSIS
Folate deficiency LAB RESULTS
▪ Insufficient diet ▪ Peripheral blood cell analysis
▪ Adequate diet but increased requirements ▫ Increased mean corpuscular volume
(e.g. pregnancy, lactation, chronic (MCV)
hemolysis, exfoliative skin disease) ▫ Increased mean corpuscular hemoglobin
▪ Malabsorption (e.g. celiac disease, (MCH)
inflammatory bowel disease, gastric ▫ Normal mean corpuscular hemoglobin
surgery) concentration (MCHC)
▪ Metabolic interference from medications ▫ Hypersegmented neutrophils
(e.g. methotrexate, phenytoin, trimethoprim) ▫ Anisocytosis (different sizes of RBCs)
▪ Alcoholism ▫ Poikilocytosis (abnormally-shaped
Less common causes of macrocytosis RBCs)
▪ Thiamine-responsive megaloblastic ▫ Macroovalocytes (large oval-shaped
anemia syndrome, congenital anemias cells)
(Fanconi anemia, Diamond–Blackfan ▪ Decreased RBC count secondary to
anemia), myelodysplastic syndromes, pure increased hemolytic destruction of
RBC aplasia, lipid abnormalities (e.g. liver defective erythrocytes
disease), thyroid disease, copper deficiency ▪ Decreased reticulocyte count → formation
▪ Impaired DNA synthesis also causes impaired in anemias caused by defective
formation of giant metamyelocytes → DNA synthesis
neutrophils with hypersegmented nuclei ▪ Mild leukopenia and/or thrombocytopenia
caused by defective DNA synthesis
▪ Decreased serum hemoglobin and
SIGNS & SYMPTOMS hematocrit related to decreased number of
circulating RBCs
▪ From decreased number of functional RBCs ▪ Markers of hemolysis
in circulation → decreased RBC oxygen- ▫ Increased lactate dehydrogenase (LDH)
carrying capacity → tissue hypoxia
▫ Increased serum unconjugated bilirubin
▫ Fatigue
▫ Decreased haptoglobin
▫ Activity intolerance
▪ Decreased serum B12 and/or folate levels
▫ Pallor
▪ Increased homocysteine or methylmalonic
▫ Compensatory mechanisms: increased acid are also evidence of B12 deficiency
heart rate, bounding pulse
▪ From increased rate of hemolysis,
destruction of defective cells TREATMENT
▫ Jaundice: hemolysis → increased serum
bilirubin MEDICATIONS
▫ Splenomegaly: increased ▪ Supplementation: increased dietary vitamin
reticuloendothelial activity secondary to B12 and/or folate when indicated
extravascular hemolysis ▫ Parenteral vitamin B12 if pernicious
▪ From neuronal demyelination (if B12 anemia
decreased): numbness, tingling, weakness, ▫ Dietary vitamin B12 found in animal
possible neuropsychiatric symptomatology products
▫ Folate found in both plant, animal
products, esp. dark green leafy
vegetables
410 OSMOSIS.ORG
Chapter 50 Macrocytic Anemia
Figure 50.2 An erythrocyte displaying a

Cabot ring and basophilic stippling. These
features represent disordered erythropoiesis
and are seen in many conditions, including
megaloblastic anemias.
Figure 50.1 A hyperlobated neutrophile in
a peripheral blood smear; a characteristic
feature of megaloblastic anemia.
SIDEROBLASTIC ANEMIA
osms.it/sideroblastic-anemia
Acquired forms
PATHOLOGY & CAUSES ▪ Clonal: myelodysplastic syndromes/
myeloproliferative neoplasms alter
▪ Anemias caused by altered mitochondrial erythrocytes, granulocytes, platelets
function and defects in heme synthesis
▪ Reversible (metabolic): caused by exposure
within erythroid cells
to a substance (e.g. excessive alcohol/drugs
such as isoniazid, chloramphenicol; copper
TYPES deficiency/zinc overload)
Congenital forms Both congenital & acquired

▪ Involve inheritance patterns affecting ▪ Impaired erythropoiesis, hemoglobin
nuclear/mitochondrial genes encoding for synthesis → reduced iron in RBCs +
erythrocyte synthesis—X-linked/autosomal defective RBCs undergo apoptosis within
recessive/mitochondrial inheritance bone marrow + fewer functional RBCs in
patterns circulation → anemia
▫ Syndromic: presents with clinical ▪ Circulating RBC morphology: microcytic/
manifestations of anemia along with dimorphic (normocytic-to-macrocytic)
effects on other organ systems (e.g.
exocrine pancreatic insufficiency,
sensorineural deafness, hepatic/renal
COMPLICATIONS
failure, myopathy) ▪ Systemic effects of heme synthesis defects
include impaired utilization of iron →
▫ Non-syndromic: main features
accumulation in mitochondria → systemic
associated with anemia, iron overload
iron overload → complications from
hemochromatosis (e.g. diabetes, cardiac
OSMOSIS.ORG 411
pathology) Complete blood count
▫ Repeated blood transfusions add to iron ▪ Decreased serum hemoglobin
overload ▪ Decreased RBC count
▪ Anemia-induced acceleration of ▪ Decreased/low reticulocyte count—related
erythropoiesis → erythroid hyperplasia of to ineffective erythropoiesis
bone marrow
▪ Increased risk of infection Iron studies
▪ Acute leukemia develops in some cases ▪ Hemochromatosis
▪ Infection possibly fatal Genetic testing

▪ Presentation variable depending on cause ▪ If sideroblastic anemia acquired, cause is
▪ Clinical manifestations of decreased reversible with treatment
oxygen-carrying capacity of RBCs and
hypoxia (e.g. fatigue, dyspnea, palpitations,
pallor; mild jaundice if hemolysis significant) MEDICATIONS
▪ Erythropoietic hemochromatosis will ▪ X-linked sideroblastic anemia: vitamin B6
manifest as varying degrees of iron (pyridoxine)
overload (e.g. hepatosplenomegaly, cardiac
arrhythmias, heart failure) SURGERY
▪ Reduce organ damage secondary to iron
overload
DIAGNOSIS ▫ Mild anemia: therapeutic phlebotomy
LAB RESULTS
OTHER INTERVENTIONS
Bone marrow aspirate smear ▪ Reduce organ damage secondary to iron
▪ Presence of sideroblasts confirms diagnosis overload
▫ Prussian blue stain reveals iron ring ▫ Mild anemia: therapeutic phlebotomy
around nucleus ▫ Chelation therapy (e.g. deferoxamine)
RBC indices
▪ Low MCH
▪ MCV may be low/normal/high
▫ Acquired sideroblastic anemias often
produce macrocytic erythrocytes
▫ Hereditary sideroblastic anemias
produce microcytic erythrocytes
Blood smear analysis

▪ Anisocytosis
▪ Poikilocytosis
▪ Micro/macrocytosis
▪ Hypochromic erythrocytes
Figure 50.3 An erythrocyte displaying a
▪ Iron-containing inclusions (Pappenheimer
Cabot ring and basophilic stippling. These
bodies) may be present
features represent disordered erythropoiesis
and are seen in many conditions, including
megaloblastic anemias.
412 OSMOSIS.ORG
NOTES
NOTES
METHEMOGLOBINEMIA
METHEMOGLOBINEMIA
osms.it/methemoglobinemia
▪ Industrial chemicals
PATHOLOGY & CAUSES ▫ Aniline dyes, chlorates, bromates,
nitrates
▪ ↑ methemoglobin levels in blood > 10%
▫ Normal methemoglobin level < 1% Congenital methemoglobinemia
▪ Methemoglobin ▪ Recessive gene → enzyme diaphorase I
▫ Hemoglobin form: contains ferric (Fe3+) deficiency → inefficient methemoglobin ↓
iron → ↓ oxygen affinity → accumulation
▫ Overwhelming oxidative stress (in red ▪ Abnormal hemoglobin variants (HbM/HbH)
blood cells) → iron oxidation within → hemoglobin not enzymatic-reduction
heme (Fe2+ → Fe3+) → hemoglobin amenable
converted to methemoglobin ▪ Diaphorase I cofactor deficiency
▫ Oxygen binding → ↑ affinity in ▫ Impaired upstream enzymes →
remaining heme sites that may have insufficient diaphorase I cofactors
been in ferrous (Fe2+) state in heme production → impaired enzymatic
tetramer → left shift in oxygen curve → reduction
overall oxygen to tissue release ability ↓ ▫ Pyruvate kinase deficiency
→ tissue hypoxia ▫ Glucose-6-phosphate dehydrogenase
▪ Healthy cells deficiency
▫ Spontaneous methemoglobin
conversion rapidly ↓ by protective
enzymes SIGNS & SYMPTOMS
▫ Nicotinamide adenine dinucleotide-
reduced (NADH) methemoglobin ▪ Arterial blood may develop bluish/
reductase (diaphorase I) chocolate-brown tinge
▫ Nicotinamide adenine dinucleotide ▪ Healthy individuals
phosphate (NADPH) methemoglobin ▫ Symptoms may only manifest at
reductase methemoglobin levels > 15%
▫ Ascorbic acid ▫ Cyanosis → dyspnea, mental status
▫ Glutathione enzyme system change, headache, fatigue, exercise
intolerance, dizziness
▪ Severe methemoglobinemia (> 50%) →
TYPES seizure, coma, death
Acquired methemoglobinemia
▪ ↑ methemoglobin formation
▪ Drugs
▫ Antibiotics, local anesthetics,
antiemetics
OSMOSIS.ORG 413
DIAGNOSIS TREATMENT
▪ Specific
Co-oximetry
▫ Methylene blue: intravenous reducing
▪ Analyses blood-spectrum absorption → agent → reduces heme group from
methemoglobin peak absorbance at 631nm methemoglobin → hemoglobin
LAB RESULTS OTHER INTERVENTIONS

▪ Arterial blood gas ▪ Supplemental oxygen
▫ Clinical cyanosis in normal arterial PO2 ▪ Vitamin C (ascorbic acid) may improve
presence cyanosis in chronic cases
▪ Enzyme assays
▫ Enzyme assays for specific enzymes
involved in maintaining hemoglobin in
reduced state may be utilized
414 OSMOSIS.ORG
NOTES
NOTES
MICROCYTIC ANEMIA

▪ Inherited/acquired anemias, small LAB RESULTS
erythrocytes, varying hemoglobin content ▪ Complete blood count (CBC), peripheral
blood smear analysis, blood chemistry, iron
studies
SIGNS & SYMPTOMS
▪ Decreased oxygen to tissues → fatigue, TREATMENT
pallor, dyspnea, activity intolerance
OTHER INTERVENTIONS
▪ Nutrient replacement, packed red blood cell
MNEMONIC: Find Those transfusions
Small Cells Last
Microcytic anemias
Fe deficiency
Thalassemia
Sideroblastic
Chronic disease
Lead poisoning
OSMOSIS.ORG 415
IRON-DEFICIENCY ANEMIA
osms.it/iron-deficiency-anemia
COMPLICATIONS
PATHOLOGY & CAUSES ▪ High-output heart failure, angina,
cardiorespiratory failure
▪ Microcytic, hypochromic anemia, small
▪ Infants, young children
erythrocytes, decreased hemoglobin
▫ Impaired growth, development
▪ Insufficient iron → decreased iron for
hemoglobin synthesis → impaired
erythropoiesis → production of microcytic,
hypochromic erythrocytes SIGNS & SYMPTOMS
▫ Insufficient iron to synthesize
Decreased oxygen to tissues
hemoglobin during erythropoiesis (most
common cause of anemia worldwide) ▪ Pallor
▪ Fatigue, activity intolerance, exertional
dyspnea, angina
CAUSES ▪ Compensatory mechanisms
Insufficient intake/absorption ▫ Palpitations, increased pulse, increased
▪ Decreased intake cardiac output, tachypnea, selective
shunting of blood to vital organs (e.g.
▫ Eating disorders (e.g. pica, anorexia,
skin to kidneys)
bulimia); self-imposed dietary
restrictions (e.g. vegan diet); food Effects on epithelial tissues
insecurity
▪ Glossitis
▪ Decreased absorption
▫ Smooth, “beefy red” tongue
▫ Celiac disease, surgical resection of
▪ Cheilosis
gastrointestinal (GI) tract, bariatric
surgery, excessive dietary calcium, ▫ Scaling, fissuring; dryness; lip scaling
tannates, oxalates ▪ Koilonychia
▫ Spoon-shaped, concave nails
Increased need ▪ Esophageal stricture
▪ Increased need ▪ Gastric atrophy
▫ Pregnancy, lactation ▪ Blue sclerae
▪ Increased growth ▪ Pagophagia
▫ Infants, children, adolescents ▫ Obsessive consumption of ice
Increased loss
▪ Overt blood loss
DIAGNOSIS
▫ Hematemesis, trauma-related
hemorrhage, heavy menses, hematuria,
LAB RESULTS
multiple blood donations
▪ ↓ red blood cell count
▪ Occult
▪ Low/normal reticulocytes
▫ GI bleed (e.g. peptic ulcer, tumor);
vascular lesions (e.g. hemorrhoids); ▪ ↓ hemoglobin, hematocrit
hookworm/other helminthic infections ▪ Hypochromic-microcytic erythrocytes
▫ Decreased: mean corpuscular volume
(MCV), mean corpuscular hemoglobin
(MCH), mean corpuscular hemoglobin
concentration (MCHC)
416 OSMOSIS.ORG
Chapter 52 Microcytic Anemias
▫ Blood smear analysis: erythrocytes with

increased central pallor (> ⅓ diameter, TREATMENT
anisocytosis (anisto = unequal),
poikilocytosis (poikilo = irregular), target MEDICATIONS
cells (resemble target; center stain with ▪ PO iron supplements (e.g. ferrous sulfate)
pallor ring, outside stain ring) ▪ Parenteral iron
▪ Iron studies ▫ Severe, persistent anemia
▫ Decreased serum iron, ferritin (stores ▫ Intolerance of PO iron
cellular iron) ▫ Nonadherence to PO supplements/
▫ Decreased transferrin saturation (major dietary changes
iron transport protein)
▫ Increased total iron binding capacity OTHER INTERVENTIONS
▪ Increase dietary iron
OTHER DIAGNOSTICS ▫ Heme iron (e.g. meat) absorbed better
▪ History, physical examination (e.g. than non-heme iron (e.g. eggs, legumes,
colonoscopy for GI bleed) nuts)
▫ Vitamin C increases absorption; calcium
decreases absorption
▪ Blood transfusion
LEAD POISONING-RELATED
ANEMIA
osms.it/lead-poisoning
▪ Exposure to soil/dust contaminated with
PATHOLOGY & CAUSES lead
▪ Breathing industrial emissions containing
▪ Lead exposure, toxicity → anemia lead (e.g. smelters, refineries, battery
▪ Lead absorbed through lungs/skin/GI tract manufacturing, recycling)
▫ Interferes with enzymatic steps in heme ▪ Food/ beverages from lead-glazed ceramics
pathway → decreased hemoglobin
synthesis, microcytosis
▫ Impairs sodium/potassium ATPase in SIGNS & SYMPTOMS
erythrocyte cell membrane → hemolysis
▪ Small, hypochromic red blood cells →
hypoxemia → decreased oxygen to tissues
RISK FACTORS
→ tissue hypoxia → fatigue, dyspnea,
▪ Water contaminated with industrial waste/ activity intolerance
from pipes made of lead/that contain lead
▪ Lead toxicity
solder
▫ Abdominal pain, headache, difficulty
▪ Exposure to leaded paint/paint dust/chips
concentrating, muscle/joint pain,
(esp. children); increased risk in older
confusion, ataxia
homes (built before 1978, lead in paint
since banned)
OSMOSIS.ORG 417
DIAGNOSIS TREATMENT
▪ ↑ serum blood lead level (BLL) ▪ Eliminate exposure
▪ Basophilic stippling ▪ Chelation therapy
▪ ↓ or normal MCV ▫ Dimercaptosuccinic acid (DMSA, AKA
▪ ↓ mean MCH succimer), CaNa2EDTA
▪ Hemolysis
▫ ↑ indirect bilirubin, LDH
▫ ↓ haptoglobin
THALASSEMIA
osms.it/thalassemia
globin chains → absent/ reduced chains
PATHOLOGY & CAUSES ▪ One gene missing: alpha-thalassemia
minima
▪ Thallas = sea; emia = blood
▫ Benign carrier state
▪ Inherited hemoglobinopathies; most
▪ Two genes missing: alpha-thalassemia
common in individuals with Mediterranean,
minor, alpha thalassemia trait
Middle Eastern, Southeast Asian, African
genetic descent ▫ Mild anemia
▪ Hemoglobin synthesis with insufficient ▪ Three genes missing: hemoglobin H (HbH)
globin chains → impaired erythropoiesis, disease
malfunctioning erythrocytes ▫ Mild anemia/may require periodic
▪ Autosomal recessive inheritance; wide transfusions (variable presentation)
range of phenotypes, clinical syndromes ▪ Four genes missing: alpha-thalassemia
▪ Deficient alpha/beta chains → imbalanced major, hydrops fetalis, hemoglobin Barts
beta chain to alpha chain ratio → globin ▫ Incompatible with extrauterine life due
chains aggregate, precipitate in erythroid to inability to form normal hemoglobin;
precursors → unstable hemoglobin death occurs before/shortly after birth
tetramer ▫ Only hemoglobin Barts (Hb Barts) is
▫ Impaired erythropoiesis produced; tetramers of gamma globulin,
▫ Intramedullary hemolysis and apoptosis oxygen not delivered to fetal tissues
▫ Small, hypochromic cells → decreased ▫ Severe anemia during fetal development
oxygen to tissues → hydrops fetalis → heart failure,
hepatomegaly, ascites, death
▫ Production of few microcytic,
hypochromic erythrocytes with rigid, Beta-thalassemia
less deformable membranes →
▪ Genetic mutations of one/both genes →
extravascular hemolysis, phagocytosis
absent/reduced beta chains
by reticuloendothelial macrophages
▪ Mutation in one beta globin chain: beta-
thalassemia minor, thalassemia trait
TYPES ▫ Asymptomatic carrier state/mild anemia
Alpha-thalassemia ▪ Mutation in two beta globin chains:
reduced beta globin production → beta-
▪ Deletion of ≥ one gene(s) encoding alpha
thalassemia intermedia
418 OSMOSIS.ORG
Chapter 52 Microcytic Anemias
▫ Heterogeneous presentation ▪ Chronic hemolysis

▫ May become transfusion-dependent ▫ Jaundice, dark urine,
later in life hepatosplenomegaly
▪ No beta globin chains produced: beta-
thalassemia major
▫ Transfusion dependent DIAGNOSIS
LAB RESULTS
COMPLICATIONS ▪ ↓ serum hemoglobin
▪ Hemolytic, microcytic, hypochromic anemia
▪ Decreased/normal/increased reticulocyte
▫ Chronic tissue hypoxia count → degree of impaired erythropoiesis
▫ Leg ulcers ▪ White blood cells, platelets normal
▫ High output heart failure ▪ Red blood cell indices
▫ Hypermetabolic state → nutritional ▫ Hypochromic-microcytic erythrocytes
deficiencies (children: growth
▫ MCHC increased related to erythrocyte
impairment)
dehydration
▪ Extrameduallary hematopoiesis → bone
▫ Decreased MCV
marrow hyperplasia, bone marrow widens,
structural malformations (e.g. facial ▫ High red cell distribution width (RDW)
irregularity, osteoporosis, premature fusion ▪ Blood smear analysis
of epiphysis in children) ▫ Poikilocytosis (dacrocytes, i.e. teardrop-
▪ Hemolysis → increased bilirubin → shaped cells)
gallstones ▫ Anisocytosis
▪ Iron overload, deposition in tissue ▫ Erythroblasts (nucleated red blood cells)
▫ Myocardium → arrhythmias, restrictive ▫ Target cells
cardiomyopathy, heart failure ▫ Inclusions (precipitated globin chains)
▫ Pancreas, other endocrine glands → ▪ Blood chemistry indicative of hemolysis
endocrinopathies (e.g. diabetes, thyroid ▫ Increased lactate dehydrogenase (LDH)
dysfunction)
▫ Increased indirect (unconjugated)
▫ Liver → cirrhosis, hepatocellular cancer bilirubin
▫ Kidneys → renal insufficiency (metabolic ▫ Decreased haptoglobin
load from high hematopoietic cell
▪ Iron studies
turnover)
▫ Increased serum iron, transferrin
▪ Hydrops fetalis
saturation (TSAT), serum ferritin
▫ Alpha thalassemia major only
▪ Diagnostics to determine organ
▪ Treatment-related complications involvement (e.g. cardiac MRI, thyroid
▫ Transfusions, chelation therapy hormone, glucose levels, bone mineral
density)
▪ Hemoglobin analysis using high-
SIGNS & SYMPTOMS performance liquid chromatography
(HPLC)/hemoglobin electrophoresis, genetic
▪ With exception of alpha-thalassemia major, testing (confirmation)
mild compared to beta-thalassemia
▪ Decreased oxygen to tissues
▫ Systemic: pallor, fatigue, activity
intolerance
▫ Cardiac: altered hemodynamics, e.g.
tachycardia, low blood pressure,
arrhythmias
OSMOSIS.ORG 419
TREATMENT
▪ According to phenotype
MEDICATIONS
▪ Folic acid supplements: support
erythropoiesis
SURGERY
▪ Splenectomy
OTHER INTERVENTIONS
▪ Blood transfusions
▪ Chelation therapy
▪ Allogeneic hematopoietic cell
transplantation (beta-thalassemia major)
▪ Consultation with cardiology, other
specialties: organ involvement
▪ Ongoing monitoring: individuals with high
impairment (e.g. blood, iron studies; liver
studies; growth, development in children)
420 OSMOSIS.ORG
NOTES
NOTES
NORMOCYTIC ANEMIA
(DECREASED PRODUCTION)

▪ Insufficient production of erythrocytes AKA LAB RESULTS
red blood cells (RBCs) ▪ Complete blood count (CBC)
CAUSES ▪ Blood chemistry
▪ Chronic diseases most common cause ▪ Iron studies
(e.g. kidney disease, cancer, rheumatoid ▪ Genetic testing (rarely)
arthritis)
TREATMENT
SIGNS & SYMPTOMS
MEDICATIONS
▪ Variable depending on degree of hypoxia, ▪ Dietary changes
pallor; fatigue; dyspnea; activity intolerance;
cardiorespiratory compromise
OTHER INTERVENTIONS
▪ Supplementation (address iron deficiency)
ANEMIA OF CHRONIC DISEASE

(ACD)
osms.it/anemia-of-chronic-disease
6 (IL6), tumor necrosis factor alpha (TNF
PATHOLOGY & CAUSES alpha), interferon beta (IFN beta), interferon
gamma (IFN gamma)
▪ Deficient RBC production due to chronic ▫ ↑ hepcidin secretion by liver → ↓
diseases (e.g. infection, inflammation, iron absorption from gastrointestinal
malignancy) (GI) tract, ↓ iron sequestration in
reticuloendothelial system → ↓ iron
▪ AKA anemia of chronic inflammation
available for erythropoiesis
▫ ↓ secretion of erythropoietin
CAUSES ▫ Direct inhibition of erythropoiesis
▪ Inflammatory processes in iron homeostasis ▫ ↓ erythrocyte lifespan
▪ Systemic inflammation → ↑ circulation
cytokines, interleukin 1 (IL1), interleukin
OSMOSIS.ORG 421
RISK FACTORS (ESR), C-reactive protein (CRP), IL6
▪ Advanced age, physical trauma ▪ Decreased serum iron levels
▪ High ferritin
Decreased serum transferrin saturation
SIGNS & SYMPTOMS
▪
▪ Decreased total iron binding capacity
▪ Hypoxia, pallor; fatigue; dyspnea; activity ▪ Low serum erythropoietin concentration
intolerance; cardiorespiratory compromise ▪ Decreased reticulocyte count
▪ Variable depending on degree of hypoxia ▪ Bone marrow examination
▫ Increased iron in macrophages (related
to actions of hepcidin), erythroid
DIAGNOSIS precursors
LAB RESULTS
▪ RBCs normochromic, normocytic
▪ Microcytic, hypochromic RBCs (rarely)
TREATMENT
▪ Leukocytosis
MEDICATIONS
▫ Underlying disorder
▪ Supplemental iron
▪ Normal/low mean corpuscular hemoglobin
▫ IV more effective than oral iron for
(MHC), mean corpuscular volume (MCV)
systemic inflammation
▪ Normal mean corpuscular hemoglobin
▪ Erythropoiesis-stimulating agents (e.g.
concentration (MCHC)
epoetin alfa, darbepoetin alpha)
▪ Normal/increased red cell distribution width
▫ For severe anemia
(RDW) normal/increased
▪ Erythrocyte hypoproliferation
▫ Decreased RBC count OTHER INTERVENTIONS
▫ Mild to moderate decrease in ▪ Transfusion of packed RBCs
hemoglobin ▫ For severe anemia
▪ Elevated erythrocyte sedimentation rate
422 OSMOSIS.ORG
Chapter 53 Normocytic Anemia (Decreased Production)
APLASTIC ANEMIA
osms.it/aplastic-anemia
PATHOLOGY & CAUSES infections

▫ Neutropenia-related sepsis common
cause of death
▪ Pancytopenia due to bone marrow
hypoplasia/aplasia ▪ Thrombocytopenia
▪ Idiopathic/inherited/acquired ▫ Mucosal hemorrhage (e.g. gingival,
nares, ecchymosis, petechiae, heavy
menstrual flow, occult blood in stool,
CAUSES intracranial hemorrhage)
▪ Inherited ▪ Anemia
▫ Fanconi anemia; Shwachman–Diamond ▫ Pallor, fatigue, dyspnea, activity
syndrome; familial aplastic anemias; intolerance, cardiorespiratory
reticular dysgenesis compromise
▪ Acquired
▫ Immune processes (e.g. systemic
lupus erythematosus, graft-versus- DIAGNOSIS
host disease, paroxysmal nocturnal
hemoglobinuria) LAB RESULTS
▫ Drugs (e.g. cytotoxic cancer ▪ Prolonged bleeding time
chemotherapy, carbamazepine, ▪ Decreased hemoglobin, hematocrit
phenytoin, indomethacin, sulfonamides, ▪ Absolute neutrophil count decreased
chloramphenicol)
▪ Platelet count decreased
▫ Viruses (e.g. Epstein–Barr, HIV, hepatitis,
▪ Reticulocyte count decreased
herpes)
▫ Normal erythrocyte morphology
▫ Toxic chemicals (e.g., solvents, benzene,
pesticides) ▪ Bone marrow biopsy
▫ Ionizing radiation ▫ Some lymphocytes, plasma cells,
stromal elements (e.g. blastoid cells)
▪ Acquired or idiopathic
▫ No increase in blasts/dysplasia
▫ Insidious onset of bone marrow
hypoplasia/aplasia, hematopoietic cell
loss → ↓ production of cell lineages TREATMENT
(thrombocytes, leukocytes, erythrocytes)
→ peripheral pancytopenia
▪ Treat underlying cause
▫ Discontinue offending drug treatment
COMPLICATIONS ▪ Varies by age, severity of symptoms,
▪ Impairment of blood’s immunity, likelihood of finding donor match
hemostasis, oxygen-carrying capacities
MEDICATIONS
SIGNS & SYMPTOMS ▪ Manage cytopenias
▪ Antimicrobials for infections
▪ Deficient thrombocytes, leukocytes ▫ Medical emergency: fever + low
▫ Shorter lifespan absolute neutrophil count
▪ Neutropenia ▪ Growth factors
▫ Increased frequency/severity of ▫ Granulocyte colony-stimulating factor
OSMOSIS.ORG 423
(G-CSF): frequent/severe infections
▫ Thrombopoietin (TPO) receptor agonists
with immunosuppressive therapy
▫ Hematopoietic growth factors (rarely)
▪ Immunosuppressive therapy (IST)
▫ Consists of antithymocyte globulin
(ATG) + cyclosporin A
▫ Administer glucocorticoid with ATG:
steroid reduces risk of serum sickness;
immunosuppressive properties
▫ Cyclosporin A: immunosuppressive
▫ Eltrombopag (thrombopoietic agent) to Figure 53.1 A bone marrow biopsy from an
increase platelet count individual with aplastic anemia. The bone
marrow spaces contain large amounts of fat
and minimal hematopoietic tissue is present.
OTHER INTERVENTIONS
▪ Hematopoietic stem cell transplant
▫ Curative if effective
▪ Transfusions
▫ Platelets, packed red blood cells
▫ Increased risk of alloimmunization, graft
rejection after bone marrow transplant
424 OSMOSIS.ORG
NOTES
NOTES
NORMOCYTIC ANEMIA
(INCREASED HEMOLYSIS)

▪ Inherited/acquired disorders resulting in LAB RESULTS
premature destruction of normal red blood ▪ Complete blood count (CBC)
cells (RBCs) ▪ Peripheral blood smear analysis
▪ Measure plasma for hemolysis indicators
SIGNS & SYMPTOMS ▫ Bilirubin, lactate dehydrogenase (LDH),
haptoglobin
▪ If hematopoietic compensation insufficient, ▪ Measure specific indicators of hemolysis in
anemic symptoms (e.g. pallor, fatigue, urine
activity intolerance) ▫ Hemoglobin, bilirubin, hemosiderin
▪ Intravascular hemolysis → hemoglobinuria,
iron deficiency
▪ Extravascular hemolysis → jaundice,
TREATMENT
splenomegaly, gallstone formation
AUTOIMMUNE HEMOLYTIC ANEMIA

(AHA)
osms.it/autoimmune-hemolytic-anemia
temperature (37°C/98.6°F)
PATHOLOGY & CAUSES ▪ Predominant autoantibody: IgG (IgA and
IgM may also be involved)
▪ Anemia caused by immune destruction of
▪ Predominant RBC antigen: Rh
red blood cells by autoantibodies against
antigens on RBCs surface ▪ Associated with immune deficiencies,
malignancies, certain drugs
▪ AKA AIHA
▪ Antibody fixes complement + binds to
RBC membrane → antibody-coated RBCS
TYPES destroyed in spleen
Warm AIHA ▫ Usual site of hemolysis: extravascular,
by macrophages in spleen, liver
▪ Most common
▪ “Warm” because optimum temperature for
antibody to react with RBCs = normal body
OSMOSIS.ORG 425
Cold AIHA COMPLICATIONS
▪ “Cold” because optimum temperature ▪ Depend on type/degree of hemolysis
for antibody to react with RBCs = below ▪ Anemia, venous thromboembolism,
normal body temperature (4°C/39.2°F) cholelithiasis, renal insufficiency
▪ Predominant autoantibody: IgM ▪ Older individuals: increased risk of cardiac
▪ Predominant RBC antigen: I, i, P complications
▪ Antibodies activate direct complement
system attack
▪ Usual site of hemolysis: intravascular, SIGNS & SYMPTOMS
complement-mediated
▪ Onset insidious/acute
▪ Paroxysmal cold hemoglobinuria
▪ If hematopoietic compensation insufficient,
▫ Most common in children
anemic signs and symptoms (e.g. pallor,
▫ Caused by Donath–Landsteiner fatigue, activity intolerance)
antibody
▪ If severe anemia/underlying cardiac disease,
▫ Associated with viral (e.g. measles, a hyperdynamic state (e.g. bounding pulses,
varicella) or bacterial (e.g. mycoplasma, tachycardia, pulmonary congestion)
H. influenza) infections
▪ Cold AIHA
▪ Cold agglutinin syndrome
▫ Hemoglobinuria after exposure to cold
▫ Most common in adults > 70 years old temperatures
▫ Primarily biologically-female individuals ▪ Paroxysmal cold hemoglobinuria
▫ Associated with lymphoproliferative ▫ Jaundice, hemoglobinuria, anemia after
disorders, autoimmune disorders, infection; pain in legs, back following
mycoplasma infections exposure to cold
▪ Cold agglutinin syndrome
▫ Anemia, acrocyanosis, or Raynaud’s
phenomenon
DIAGNOSIS
LAB RESULTS
▪ Evidence of hemolysis
▫ Increased lactate dehydrogenase (LDH)
▫ Increased indirect bilirubin
▫ Decreased haptoglobin
▪ Increased mean corpuscular volume (MCV)
▪ Low hemoglobin, hematocrit
▪ Reticulocytosis
▪ Direct antibody (DAT)
RISK FACTORS ▫ Warm: positive for IgG/IgG + C3d
▪ Exposure to cold ▫ Cold: positive for C3d
▪ Administration of offending drug ▪ Partial macrophage phagocytosis →
spherocytosis
▪ Development of associated diagnosis
▫ Infection, malignancy, autoimmune
disorder
426 OSMOSIS.ORG
Chapter 54 Normocytic Anemia (Increased Hemolysis)
TREATMENT
▪ Cold AIHA: often no treatment required
MEDICATIONS
▪ Corticosteroids
▪ Monoclonal antibody: rituximab
▪ Immunosuppressants
SURGERY
▪ Splenectomy (reduces hemolysis)
OTHER INTERVENTIONS
Figure 54.1 A peripheral blood smear from an
▪ Eliminate triggers (e.g. cold, drugs) individual with warm autoimune hemolytic
▪ Correct anemia anemia. There are numerous spherocytes
▫ Folic acid supplements to support present due to degradation of the red cell
erythropoiesis membrane by macrophages.
▫ Blood transfusion
GLUCOSE-6-PHOSPHATE
DEHYDROGENASE DEFICIENCY
osms.it/G6PD
decreased lifespan
PATHOLOGY & CAUSES ▫ Certain drugs (sulfa drugs, antimalarials)
and chemicals (e.g. henna compounds,
▪ Hematological enzymopathy where aniline-based dyes, naphthalene)
deficient glucose-6-phosphate interact with hemoglobin + oxygen
dehydrogenase (G6PD) causes premature → hydrogen peroxide (H2O2), other
hemolysis oxidizing radicals within cell →
▪ Inherited, X-linked mutation of G6PD gene hemoglobin precipitation
▪ Hemolysis can be acute/intermittent/chronic ▪ Infections → possible generation of
(rare) hydrogen peroxide by leukocytes/exposure
▪ Inadequate G6PD, GSH → oxidative stress to neutrophil produced oxidants →
→ build-up of free radicals, peroxides → hemoglobin precipitation
precipitation of hemoglobin → disruption ▪ Ingestion of fava beans (favism)
of cell membrane → increased cellular
rigidity → extravascular hemolysis, W.H.O. Classifications
accelerated removal of damaged RBCs ▪ Based on degree of enzyme deficiency,
by reticuloendothelial system in spleen; resulting hemolysis
intravascular hemolysis may also occur ▪ Class I: G6PD < 10% of normal; chronic
▪ Hemolysis precipitated by sources of hemolytic anemia
oxidative damage that trigger hemolysis. ▪ Class II: G6PD < 10% of normal;
▫ RBCs with deficient G6PD have a intermittent hemolysis when exposed to
OSMOSIS.ORG 427
oxidative stress ▫ Elevated indirect bilirubin
▫ G6PD Mediterranean: majority of ▫ Elevated lactate dehydrogenase (LDH)
RBCs hemolyze in setting of oxidative ▫ Decreased haptoglobin
stress; half-life of G6PD especially short ▪ Reticulocytosis
(measured in hours)
▪ Hemoglobinuria, hemosiderinuria
▪ Class III: G6PD 10–60% of normal;
▪ G6PD assay
intermittent hemolysis when exposed to
trigger ▫ Directly measures G6PD activity
in RBCs; false-negative if testing
▫ G6PD A- : only oldest RBCs hemolyze
done during/immediately after acute
in setting of oxidative stress; G6PD half-
hemolytic episode
life = 13 days (normal = 62 days)
▪ Screening tests
▫ Fluorescent spot test: glucose-
TYPES 6-phosphate + NADP added to
▪ Acute hemolysis hemolysate of individual’s RBCs →
▫ May be mild/severe (life-threatening) fluorescence of NADPH
▪ Kernicterus ▫ Methemoglobin reduction test:
▫ G6PD-related neonatal jaundice → methylene blue measures transfer
kernicterus if not promptly treated of hydrogen ions from NADPH to
▪ Renal failure methemoglobin → indirectly estimates
NADPH generation
▫ Newborn screening: blood analyzed for
RISK FACTORS biochemical, genetic markers of G6PD,
▪ Most common in people of African, Asian, other inherited disorders
Mediterranean descent ▪ Confirmatory test to assay NADPH
formation performed after positive
screening test/as initial test
SIGNS & SYMPTOMS ▫ Spectrophotometric analysis of RBC
hemolysate + glucose-6-phosphate +
▪ Generally asymptomatic until exposed to
NADP measures NADPH generation
oxidative stress
rate
▪ Acute hemolysis
▫ Pallor, jaundice, dark urine
▫ Abdominal/back pain due to increased TREATMENT
splenic activity
▫ Renal insufficiency (severe hemolysis) MEDICATIONS
▪ Favism (potentially fatal acute hemolysis) ▪ Folic acid supplements (support
erythropoiesis)

▪ Eliminate triggers
LAB RESULTS
▪ Manage acute hemolytic episodes
▪ Decreased hemoglobin
▫ Hydration
▪ Heinz bodies
▫ Transfusions
▫ Caused by precipitation of oxidized,
▪ Phototherapy, exchange transfusion
denatured hemoglobin
▫ Neonatal jaundice
▪ Bite cells
▫ Cells have bitten appearance where
macrophages have removed bits of
precipitated hemoglobin from RBC
▪ Blood chemistry demonstrates evidence of
hemolysis
428 OSMOSIS.ORG
HEMOLYTIC DISEASE OF THE

NEWBORN
osms.it/hemolytic-disease-of-the-newborn
▫ Occurs in type O mother with naturally-

PATHOLOGY & CAUSES occurring Anti-A and Anti-B antibodies
+ Type A/Type B fetus
▪ Anemia caused by hemolytic destruction ▫ Can occur in first and all subsequent
of fetal/neonatal erythrocytes by maternal pregnancies
antibodies
▪ AKA alloimmune HDFN/erythroblastosis
fetalis RISK FACTORS
▪ Blood group incompatibility, fetomaternal
hemorrhage
CAUSES
▪ Fetomaternal hemorrhage exposes
maternal circulation to antigens present COMPLICATIONS
on fetal RBCs → maternal sensitization ▪ Anemia, hyperbilirubinemia, kernicterus
→ formation of maternal IgG antibodies ▪ Growth restriction, hydrops fetalis,
against fetal RBCs → IgG antibodies small erythroblastosis fetalis
enough to cross placenta → antibody ▫ Increased immature RBCs in fetal
attachment to fetal cells → agglutination circulation
(clumping) → microcirculatory impairment
→ hemolysis, destruction of RBCs by
macrophages in reticuloendothelial system SIGNS & SYMPTOMS
▫ Involves Rhesus (Rh) blood group/A, B,
AB, O blood groups ▪ Hemolytic disease caused by ABO
▪ Causes of maternal sensitization include incompatibility
normal delivery, spontaneous/induced ▫ Mild to moderate hyperbilirubinemia
abortion, chorionic villus sampling, within first 24h of life
amniocentesis, antenatal hemorrhage, ▫ Mild to moderate anemia
maternal trauma, idiopathic
▪ Hemolytic disease caused by Rh
▫ Small amount (0.1mL) of fetal blood incompatibility (more severe)
needed to induce maternal immune
▫ Hyperbilirubinemia, kernicterus:
response
possible
▪ Rh incompatibility
▫ Symptomatic anemia: pallor, lethargy,
▫ Rh negative mother exposed to Rh tachycardia, tachypnea
positive fetal RBCs → maternal anti-D
▫ Hydrops fetalis: related to severe
antibodies formed
anemia-induced hypoxia; subcutaneous
▫ Usually will not affect first pregnancy edema, pleural/pericardial effusion,
when initial exposure occurs; adversely ascites, signs and symptoms of shock
affects subsequent pregnancies
▪ Antenatal presentation
▫ Decreasing occurrence due to
▫ Intrauterine growth restriction signals
availability of Rh(D) immune globulin
problems with ongoing hemolysis,
prophylaxis
hypoxia
▪ ABO incompatibility
▫ More common, less severe morbidity,
mortality than with Rh incompatibility
OSMOSIS.ORG 429
DIAGNOSIS TREATMENT
▪ Hematopoietic agents (epoetin alfa/
Doppler ultrasound darbepoetin), iron supplements
▪ Antenatal (maternal testing) ▫ Anemia
▪ Notes growth restriction/presence of
hydrops
OTHER INTERVENTIONS
▪ RBC transfusion
LAB RESULTS
▫ Anemia, hydrops fetalis
▪ Antenatal (maternal testing)
▪ Exchange transfusion
▫ Positive indirect antiglobulin test: IAT,
▫ Hyperbilirubinemia, hydrops fetalis
indirect Coombs test; demonstrates IgG
antibodies in maternal serum ▪ Phototherapy
▫ Kleihauer–Betke test: positive if ▫ Hyperbilirubinemia
fetomaternal hemorrhage has occurred ▪ Intravenous immunoglobulin (IVIG)
▫ Percutaneous umbilical blood sampling ▫ Hyperbilirubinemia
(PUBS): measures hemoglobin, ▫ Reduces hemolysis, bilirubin production
hematocrit, identifies fetal blood type ▪ Pericardiocentesis, paracentesis,
▫ Spectrophotometric amniotic fluid thoracentesis
analysis: increased bilirubin if significant ▫ Hydrops fetalis; as indicated for
hemolysis has occurred pericardial effusion, pleural effusion,
▪ Postnatal (neonatal testing) ascites
▫ Blood typing: confirm incompatibility of ▪ Intrauterine RBCl transfusion
maternal, neonatal blood types ▫ Hydrops fetalis if diagnosed antenatally
▫ Positive direct antiglobulin test:
DAT, direct Coombs test; evidence of
maternal antibodies on RBC surface
▫ Positive indirect antiglobulin test:
IAT, indirect Coombs test; evidence of
maternal antibodies in serum
▫ Transcutaneous bilirubin (TcB), serum
bilirubin: increased
▫ CBC: decreased RBCs, reticulocytosis,
decreased hemoglobin and hematocrit
▫ Peripheral blood smear analysis:
evidence of hemolysis; polychromasia,
microspherocytosis (seen in ABO
incompatibility)
430 OSMOSIS.ORG
HEREDITARY SPHEROCYTOSIS
osms.it/hereditary-spherocytosis

▪ Inherited RBC membrane defect causing ▪ Jaundice
destabilization of cellular membrane, ▪ Anemic signs and symptoms (e.g. pallor,
resulting in chronic, premature fatigue, activity intolerance)
extravascular hemolysis ▪ Splenomegaly
▪ Autosomal dominant (75%) or autosomal
recessive (25%)
▪ Mutations of genes encoding for proteins DIAGNOSIS
that secure RBC membrane skeleton
to plasma membrane → membrane LAB RESULTS
destabilization → rigidity, resistance to ▪ Decreased hemoglobin
deformability → hemolysis ▪ Reticulocytosis
▪ Spherocytosis
TYPES ▫ Morphology = sphere-shaped (normal =
biconcave)
Mild (20–30%)
▪ Presence of schistocytes (RBC fragments)
▪ Mild anemia, splenomegaly, jaundice;
▪ Slightly decreased to normal MCV
modest reticulocytosis; normal hemoglobin
▫ Spherocytes: decreased MCV
▪ Adolescents/adults most commonly
diagnosed ▫ Reticulocytes: increased MCV
▪ Elevated mean cell hemoglobin
Moderate (60–70%) concentration (MCHC)
▪ Moderate anemia, reticulocytosis, ▫ Secondary to dehydration, loss of
hyperbilirubinemia cellular membrane
▪ Require occasional transfusions ▪ Elevated red cell distribution width (RDW)
▪ Infants/children most commonly diagnosed ▪ Evidence of hemolysis
▫ Elevated indirect bilirubin
Severe (5%)
▫ Elevated lactate dehydrogenase (LDH)
▪ Marked anemia, hyperbilirubinemia,
splenomegaly ▫ Decreased haptoglobin
▪ Regular transfusions needed ▪ Osmotic fragility test, acidified glycerol lysis
test (AGLT)
▫ Identifies spherocytes which lyse in
RISK FACTORS hypotonic solutions at higher rate than
▪ Most common in people of Northern normal RBCs
European descent ▪ Cryohemolysis test
▫ Uses hypertonic solution, temperature
COMPLICATIONS manipulation to identify spherocytes
▪ Transient aplastic crisis caused by which lyse at higher rate than normal
infections (e.g. parvovirus B19) RBCs
▪ Megaloblastic anemia related to folate ▪ Eosin-5-maleimide (EMA) binding test
deficiency ▫ Flow cytometric test to observe cell
▪ Neonatal icterus; non-immune hydrops membrane protein interaction with
fetalis with fetal death if disease = severe eosin-5-maleimide dye
OSMOSIS.ORG 431
▪ Osmotic gradient ektacytometry
▫ Measures surface area to volume, cell
hydration, membrane deformability
TREATMENT
SURGERY
▪ Splenectomy
OTHER INTERVENTIONS
▪ Phototherapy, exchange transfusions
▫ Neonatal hyperbilirubinemia
▪ Folic acid supplements
▫ Support hematopoiesis
Figure 54.2 A peripheral blood smear
demonstrating sphere shaped erythrocytes in
an individual with hereditary spherocytosis.
The erythrocytes have lost their biconcave
shape.
PAROXYSMAL NOCTURNAL
HEMOGLOBINURIA (PNH)
osms.it/paroxysmal-nocturnal-hemoglobinuria
susceptibility to complement activity
PATHOLOGY & CAUSES → complement-mediated intravascular
hemolysis
▪ Inherited, X-linked hematologic stem cell ▪ Three phenotypes of RBCs categorized
disorder resulting in nocturnal hemolysis, according to amount of GPI-anchored
hemolytic anemia, bone marrow failure, proteins on cell surface
thrombosis
▫ Type I: normal
▫ Type II: decreased
CAUSES ▫ Type III: absent
▪ Mutation of PIGA gene in hematopoietic
stem cells
RISK FACTORS
▫ PIGA required for synthesis of
glycosylphosphatidylinositol (GPI) ▪ Hemolysis in PNH cases increases in
protein on cell surface setting of increased complement activation
▫ GPI anchors glycoproteins on ▫ Infections
erythrocyte surface, protecting cell ▫ Surgery
from lysis by attenuating activity of ▫ Blood transfusions
complement ▫ Strenuous exercise
▪ GPI protein absence or deficiency → ↑ ▫ Excessive alcohol use
432 OSMOSIS.ORG
COMPLICATIONS
▪ Intravascular, extravascular hemolysis →
DIAGNOSIS
anemia
LAB RESULTS
▪ Consequences of hemoglobin-mediated
nitric oxide scavenging ▪ Range from normal to abnormal according
to degree of GPI-anchored protein loss,
▫ Intravascular hemolysis → free
resulting hemolysis
hemoglobin → ↑ consumption of nitric
oxide → smooth muscle dystonia, ▪ RBCs normal morphologically
vasospasm (abdominal pain, esophageal (pancytopenia may be evident in setting of
spasm, erectile dysfunction) bone marrow failure)
▪ Venous, arterial thrombosis ▪ Occasional poikilocytosis, anisocytosis
▫ Multifactorial etiology related to ▪ Normochromic
proinflammatory complement activity, ▪ Normal to extremely decreased serum
decreased availability of nitric oxide with hemoglobin
resulting vasoconstriction, endothelial ▪ Reticulocyte count ranges from normal to
cell activation, associated platelet decreased
aggregation/clot formation ▪ Evidence of hemolysis
▫ Hepatic vein thrombosis (Budd–Chiari ▫ Elevated bilirubin
syndrome) → hepatomegaly, jaundice, ▫ Decreased haptoglobin
ascites, gastric and/or esophageal
▫ Elevated LDH
varices
▪ Direct antiglobulin (DAT/Coombs) positive
▫ Intestinal vein thrombosis → ischemic
colitis ▪ Hemoglobinuria, hemosiderinuria
▫ Cerebral vein thrombosis → headache,
neurologic effects OTHER INTERVENTIONS
▪ Microvascular hemolysis + iron deposits in ▪ Bone marrow examination may indicate
renal tubules → chronic kidney disease hypocellularity
▪ Bone-marrow failure, aplastic anemia ▪ Flow cytometry
related to hematopoietic stem cell injury
▪ Eculizumab treatments associated with
Increased risk of life-threatening neisserial TREATMENT
infections
MEDICATIONS
▪ Eculizumab
SIGNS & SYMPTOMS ▫ Monoclonal antibody, reduces
complement-mediated hemolysis
▪ Variable according to degree of GPI- ▫ Vaccinate against Neisseria meningitidis
anchored protein loss → hemolysis
▪ Iron, folic acid supplements support
▪ Intermittent episodes (paroxysms) of erythropoiesis
hemoglobinuria
▪ Therapeutic anticoagulation and/or
▫ Dark urine thrombolysis, as indicated for thrombosis
▫ Hemolysis during night ▪ Immunosuppressive therapy if aplastic
▪ Clinical manifestations of anemia; e.g. anemia present
pallor, fatigue, exertional dyspnea
SURGERY
transplant
OTHER INTERVENTIONS
▪ Red blood cell transfusions as needed
OSMOSIS.ORG 433
PIRUVATE KINASE DEFICIENCY
osms.it/piruvate-kinase-deficiency
▪ Accelerated hemolysis during pregnancy/
PATHOLOGY & CAUSES with oral contraceptive use
▪ Neonatal icterus/non-immune hydrops
▪ Hematological enzymopathy caused by fetalis
deficient pyruvate kinase, resulting in
▪ Transient aplastic crisis induced by
chronic, premature hemolysis of RBCs,
infections (e.g. parvovirus B19)
hyperactive erythropoiesis
▪ Inherited, autosomal recessive mutation of
(PK-LR) pyruvate kinase-LR (liver-red cell) SIGNS & SYMPTOMS
gene
▫ Homozygous for single PK-LR mutation/ ▪ Variable presentation ranging from
heterozygous for two mutations compensated disease to transfusion-
▪ Hemolysis primarily extravascular (within dependent anemia
spleen); intravascular hemolysis variable ▪ Anemic signs and symptoms
▪ Pyruvate kinase ▫ Pallor, shortness of breath, activity
▫ Tetramer enzyme, catalyzes intolerance
transphosphorylation of ▪ Jaundice, splenomegaly
phosphoenolpyruvate into pyruvate,
ATP during glycolysis
▫ Pyruvate kinase deficiency-related DIAGNOSIS
block in glycolysis → accumulation of
2,3-bisphosphoglycerate (2,3-BPG) → LAB RESULTS
shifts oxyhemoglobin dissociation curve ▪ Decreased RBC count, reticulocytosis
to right → improved oxygen delivery to
▪ Increased serum glycolytic 2,3-BPG
tissues → better tolerance of hemolytic
anemia ▪ Hemoglobinuria, hemosiderinuria
▪ Evidence of hemolytic anemia with one or
both of
CAUSES
▫ Low levels of erythrocytic PK enzymatic
▪ Hemolytic mechanism is unclear; possibly activity
▫ ATP deficiency ▫ PK-LR gene mutation
▫ Apoptosis of erythroid progenitors in ▪ Evidence of hemolysis
spleen (ineffective erythropoiesis)
▫ Elevated lactate dehydrogenase (LDH)
RISK FACTORS ▫ Decreased haptoglobin
▪ Most common in white people of Northern
European descent, Asian people of Chinese
descent, genetically-isolated communities OTHER DIAGNOSTICS
of Swiss/German descent ▪ Clinical evidence of hemolysis
▫ Jaundice, pigmented (bilirubin)
gallstones
COMPLICATIONS
▪ Pigmented gallstone formation
▪ Iron overload-associated organ damage
▪ Megaloblastic anemia related to folate
deficiency
434 OSMOSIS.ORG
OTHER INTERVENTIONS
TREATMENT ▪ RBC transfusions
▫ Often chronic
SURGERY
▪ Chelation therapy
▪ Splenectomy
▫ Reduces iron-related organ damage
▫ Reduces hemolysis
▪ Folic acid supplementation
▪ Allogeneic hematopoietic cell
transplantation ▫ Supports erythropoiesis
▫ May be curative ▪ Phototherapy, exchange transfusion
▫ Treats neonatal jaundice
SICKLE-CELL ANEMIA
osms.it/sickle-cell-anemia
HbSA
PATHOLOGY & CAUSES ▪ Sickle-cell trait/benign carrier state
▫ Heterozygous for HbS + hemoglobin A
▪ Hemolytic anemia caused by sickle-cell
(normal hemoglobin)
disease (SCD)
▪ A group of inherited hemoglobinopathies HbS beta thalassemia
caused by point mutation of beta globin ▪ Heterozygous for HbS + one beta
gene → produces hemoglobin S (HbS) thalassemia gene
▪ RBCs containing HbS tend to polymerize,
deform into sickle/crescent-shaped forms HbSD, HbSE, HbSO
when deoxygenated ▪ Rare
▫ Triggers for deoxygenation: cold, ▪ Heterozygous for HbS + one other
dehydration, insomnia, alcohol abnormal hemoglobin (D, E, or O)
consumption, stressful situations,
overexertion, hormonal changes
COMPLICATIONS
▫ Deoxygenation may be idiopathic
▪ Affect all body systems
▪ Sickled cells less deformable than normal
▪ Hematologic
RBCs
▫ Anemia related to aplastic crisis
▫ Decreased lifespan due to hemolysis
involving temporary arrest of
erythropoiesis
TYPES ▪ Pain
HbSS ▫ Vaso-occlusion, tissue ischemia,
infarction; dactylitis (acute pain in
▪ Sickle-cell disease
small bones of hands/feet especially in
▫ Homozygous for HbS children)
▫ Chronic hemolytic anemia ▪ Increased risk of infection
HbSC ▫ Related to hyposplenism/asplenism,
decreased tissue perfusion
▪ Milder form of sickle-cell disease
▪ Central nervous system
▫ Heterozygous for HbS + abnormal
hemoglobin C ▫ Ischemic/hemorrhagic stroke; transient
ischemic attack, seizures
OSMOSIS.ORG 435
▪ Cardiovascular ▪ Mostly normochromic, normocytic cells;
▫ Myocardial infarction, dysrhythmias, polychromasia may be present secondary
cardiomyopathy, heart failure, venous to reticulocytosis
thromboembolism, leg ulcers, sudden ▪ Sickled cells present in SCD but not sickle-
death cell trait
▪ Respiratory ▪ Canoe-shaped (partially sickled) RBCs
▫ Acute chest syndrome (fever, chest ▪ Howell Jolly bodies
pain, hypoxemia, wheezing, cough, ▫ Related to hyposplenia
respiratory distress), pulmonary ▪ Normal-to-increased mean corpuscular
hypertension, disordered breathing volume (MCV)
during sleep with nocturnal hypoxemia
▪ Target cells
▪ Genitourinary, reproductive
▪ Diagnostic tests to determine organ
▫ Priapism, erectile dysfunction; damage (e.g. urinalysis → hematuria,
pregnancy complications, fetal/neonatal albuminuria from renal papillary damage)
or maternal (e.g. intrauterine growth
▪ Evidence of hemolysis
restriction, fetal death, low birthweight;
preeclampsia, thromboembolic events) ▫ Elevated unconjugated bilirubin
▪ Endocrine ▫ Elevated lactate dehydrogenase (LDH)
▫ Delayed growth, development ▫ Low haptoglobin
▪ Skeletal ▪ Positive solubility test (Sickledex)
▫ Osteoporosis, bone infarction ▪ Hemoglobin electrophoresis provides
definitive diagnosis (90–95% HbS)
▪ Sensory
▫ Proliferative retinopathy, retinal
detachment TREATMENT
▪ Systemic
▫ Multiorgan failure related to ischemia ▪ Prevent/reduce occurrence of crises (e.g.
and/or infarction immunizations to prevent infection, manage
stress, prevent deoxygenation)
SIGNS & SYMPTOMS

MEDICATIONS
▪ Mild to moderate anemia (e.g. fatigue, ▪ Hydroxyurea
activity intolerance, extertional dyspnea) ▫ Increases cell deformability, decreases
▪ Hypersplenism RBC endothelial adhesion, increases
hemoglobin F levels; reduces sickling
▪ Pain from acute vaso-occlusive crisis
▪ L-glutamine
▫ Reduces sickling
DIAGNOSIS ▪ Pain management
▫ Analgesics, adjunctive, non-
▪ Findings variable depending on inheritance pharmacological therapies
pattern, degree of hemolysis
▪ Pain indicates cell sickling, vaso-occlusion SURGERY
▪ Hematopoietic cell transplantation
LAB RESULTS
▪ Vaso-occlusion, hemolysis, splenic OTHER INTERVENTIONS
sequestration → decreased hemoglobin,
hematocrit, RBC count
▪ Folic acid supplements
▪ Reticulocytosis
▪ Manage iron deficiency
▪ Increased white blood cell (WBC) count
436 OSMOSIS.ORG
Figure 54.3 A recoloured scanning electron Figure 54.4 An abdominal CT scan in the
micrograph demonstrating a sickled axial plane demonstrating autosplenectomy
erythrocyte. in an individual with sickle cell disease. The
splenic remnant is densely calcified.
Figure 54.5 A peripheral blood smear

containing sickled erythrocytes in an
individual with sickle cell disease.
OSMOSIS.ORG 437
NOTES
NOTES
PLASMA CELL DYSCRASIAS

▪ Acquired/inherited disorders LAB RESULTS
▫ Impaired platelet function, decreased ▪ Complete blood count (CBC)
platelet count, sequelae ▪ Peripheral blood smear analysis
▪ Accelerated destruction/consumption → ▪ Platelet function tests
decreased platelets
TREATMENT
SIGNS & SYMPTOMS
OTHER INTERVENTIONS
▪ Mucocutaneous bleeding (e.g. epistaxis, ▪ Mitigate complications of deranged platelet
gingival bleeding, petechiae, purpura) function
MONOCLONAL GAMMOPATHY OF
UNDETERMINED SIGNIFICANCE
(MGUS)
osms.it/monoclonal-gammopathy
CAUSES
PATHOLOGY & CAUSES
Genetic mutations
▪ Asymptomatic premalignant plasma cell ▪ t(14,11)
proliferative disorder; M protein < 3g/dL ▫ Translocation between Ig heavy chain
▪ Most common plasma cell dyscrasia gene on chromosome 14, oncogene
▪ M protein (cyclin D1) on chromosome 11
▫ IgM, IgA, IgG of free light chains ▪ t(14,6)
▪ 25% progress to multiple myeloma, early ▫ Translocation between Ig heavy chain
stage gene on chromosome 14, oncogene
cyclin D3 on chromosome 6
▪ Deletion of gene TP53 tumor suppressor
TYPES
locus on chromosome 17
▪ Non-IgM MGUS (IgG, IgA, IgD MGUS)
▪ IgM MGUS
438 OSMOSIS.ORG
Chapter 55 Plasma Cell Dyscrasias
RISK FACTORS
▪ More commons in individuals who are
DIAGNOSIS
biologically male; increased incidence with
age LAB RESULTS
▪ Agent Orange exposure ▪ Monoclonal proteins < 3mg/dL
▪ Plasma cells CD38+, CD56+, CD19-
COMPLICATIONS Bone marrow biopsy

▪ Multiple myeloma (IgA, IgG MGUS), ▪ Mild hypercellularity
Waldenström macroglobulinemia, AL ▫ Plasma cells < 10%
amyloidosis, light chain deposition disease
(IgM MGUS)
▪ Venous thromboembolism (VTE), fractures, TREATMENT
infections
OTHER INTERVENTIONS
▪ No treatment
SIGNS & SYMPTOMS ▪ Regular observation; assess progression
▪ Mostly asymptomatic
▪ Rash, paresthesias, hypoesthesia
MULTIPLE MYELOMA
osms.it/multiple-myeloma
Calcium (elevated)
PATHOLOGY & CAUSES
▪ Increased bone resorption → hypercalcemia
▪ Neoplasm of plasma cells (myeloma cells) Renal disease
in bone marrow ▪ Monoclonal free light chains (к, λ)
▫ Overproduction of M protein ▫ Low molecular mass, filter easily in
▪ M protein renal glomeruli → Bence Jones proteins
▫ IgG, IgA, free light chains in urine, toxic to proximal tubules →
▪ Bone marrow cells, myeloma cells secrete proximal tubular necrosis
cytokines, interleukin 6 (IL6), NF-κB → ▫ Bence Jones, Tamm-Horsfall proteins,
promote proliferation, survival of myeloma albumin form obstructive proteinaceous
cells casts in distal convoluted tubules,
collecting ducts
▫ Hypercalcemia, hypercalciuria →
MNEMONIC: CRAB nephrocalcinosis
Features of Multiple myeloma
Anemia
Calcium elevated
▪ Neutropenia, thrombocytopenia
Renal disease
▪ Bone marrow infiltration by myeloma cells,
Anemia
cytokines → inhibits hematopoiesis
Bone lesions
Bone lesions (osteolytic)
▪ Neoplastic cells secrete cytokines (IL1β,
TNFɑ) → activate osteoclasts → increase
bone resorption → hypercalcemia,
OSMOSIS.ORG 439
pathologic fractures
▪ Axial skeleton (skull, spinal vertebrae, ribs,
SIGNS & SYMPTOMS
pelvic bones), long bones
▪ Hypercalcemia
▪ Pathologic fractures along vertebrae →
▫ Confusion, somnolence, constipation,
spinal cord compression
nausea, thirst
▪ Anemia, neutropenia, thrombocytopenia
TYPES ▫ Fatigue, pallor, fever, infections, bleeding
Smoldering multiple myeloma (SMM) ▪ Bone lesions
▪ Asymptomatic ▫ Pain, pathologic fractures; spinal
cord compression → neuropathies
Symptomatic multiple myeloma (hypoesthesia, paresthesia)
Non-secretory multiple myeloma

▪ Less common (3%) DIAGNOSIS
Genetic mutations X-ray (skeletal survey)

▪ t(14,11) ▪ Multiple rounded lytic bone lesions in skull,
long bones, spine
▫ Translocation between Ig heavy chain
gene on chromosome 14, oncogene CT scan
(cyclin D1) on chromosome 11
▪ Radiodense bone lesions; in advanced
▪ t(14,6) disease, lesions in spleen, lymph nodes,
▫ Translocation between Ig heavy chain lungs, etc.
gene on chromosome 14, oncogene
cyclin D3 on chromosome 6 MRI
▪ Deletion of gene TP53 tumor suppressor ▪ Radiodense lesions in thoracic, lumbar
locus on chromosome 17 vertebrae
Fluorescent in situ hybridization (FISH)

RISK FACTORS ▪ Detection of chromosomal mutations
▪ Alcohol consumption, obesity, radiation (translocations, deletions)
exposure, family history
LAB RESULTS
COMPLICATIONS ▪ Cormocytic, normochromic anemia,
▪ Free light chains deposit in kidneys, heart, thrombocytopenia, leukopenia
other organs → immunoglobulin light chain ▪ Increased monoclonal proteins (free light
amyloidosis (AL amyloidosis) chains, ↑IgG > 3mg/dL, ↑IgA)
▪ Renal failure ▪ Monoclonal protein measurement with
▪ Infection → death densitometer
▫ Most common, urinary tract infections ▪ Calcium blood test
(UTIs); pneumonia ▫ > 2.7mmol/L
▪ Hyperviscosity syndrome ▪ Bence Jones proteins (> 6mg/dL)
▪ Quantification of Bence Jones proteins
▪ Proteinuria greater than 1g/24hr
▪ Myeloma cells CD36+, CD56+, CD138+,
CD319+
440 OSMOSIS.ORG
Bone marrow biopsy

▪ Neoplastic infiltration → hypercellularity (>
30% plasma cells)
▪ Cytology
▫ Plasma cells: 2–3 times larger, eccentric
nuclei, perinuclear halo (prominent Golgi
apparatus)
▫ Other variants: mott cells (multiple
grapelike cytoplasmic inclusions), flame
cells (fiery red cytoplasm)
TREATMENT
Figure 55.1 An X-ray image of the skull
displaying numerous lytic lesions caused
▪ Treatable, incurable
by myelomatous deposits. This radiological
▫ If untreated, survival 5–12 months; with presentation is commonly known as a pepper
treatment, 48% survival for five years pot skull.
MEDICATIONS
▪ Chemotherapy
▫ Bortezomib, lenalidomide–
dexamethasone, melphalan
▪ Immunomodulators
▫ Thalidomide, lenalidomide
▪ Bisphosphonates: prevent bone loss
▪ Antibiotics: infections
▪ Glucocorticoids: hypercalcemia
OTHER INTERVENTIONS
▪ Autologous hematopoietic stem-cell Figure 55.2 A histological section of the
transplantation (ASCT) kidney from an individual with multiple
▪ Allogeneic stem cell transplantation with myeloma. The myeloma cast colors a light
chemotherapy, glucocorticoids pink on PAS stain.
Figure 55.3 An X-ray image of the forearm

demonstrating multiple lytic lesions in an
individual with multiple myeloma.

a plasmacytoma, an aggregate of malignant
plasma cells found in the soft tissues or axial
skeleton.
OSMOSIS.ORG 441
WALDENSTRÖM
MACROGLOBULINEMIA
osms.it/waldenstrom-macroglobulinemia
Hyperviscosity syndrome triad
PATHOLOGY & CAUSES
▪ Retinopathy
▪ Neoplasm of plasma cells, ▫ Stasis + venous congestion, distention,
lymphoplasmacytoid cells; high levels of M hemorrhage of retinal veins → vision
protein as IgM antibodies loss
▪ AKA lymphoplasmacytic lymphoma ▪ Neurologic symptoms
▪ Preceded by MGUS ▫ Venous congestion of cerebral veins →
hypoperfusion → headache, vertigo,
▪ Neoplastic plasma, lymphoplasmacytoid
hearing loss, parestesias, ataxia, stupor
cells infiltrate, crowd out normal
hematopoietic cells → anemia ▪ Mucosal bleeding
▪ High levels of IgM antibodies aggregate ▫ IgM antibodies interfere with
coagulation → gum bleeding, epistaxis,
▫ Hyperviscosity syndrome
rectal bleeding, menorrhagia
▫ Cryoglobulinemia: IgM proteins become
insoluble at reduced temperatures
DIAGNOSIS
CAUSES
▪ Somatic mutations of MYD88, CXCR4 DIAGNOSTIC IMAGING
genes
CT scan
▪ Hepatomegaly, splenomegaly
RISK FACTORS
▪ Autoimmune diseases mediated by
LAB RESULTS
antibodies
▪ Normocytic, normochromic anemia
▪ HIV, hepatitis, rickettsiosis
▪ IgM ≥ 3000mg/dL
▪ Pesticides exposure
▪ Autoimmune hemolysis, raynaud
phenomenon secondary to ▪ If asymptomatic, observation
cryoglobulinemia
▪ Amyloidosis of heart, kidney, liver, lungs, MEDICATIONS
joints ▪ Chemotherapy
▪ Plasmapheresis for hyperviscosity
SIGNS & SYMPTOMS syndrome
▪ Infiltration of neoplastic plasma cells OTHER INTERVENTIONS

▫ Splenomegaly, hepatomegaly, ▪ Rarely autologous stem cell transplantation
lymphadenopathy
▪ Anemia
▫ Weakness, fatigue, weight loss
442 OSMOSIS.ORG
Figure 55.5 A peripheral blood film

demonstrating rouleaux formation. Rouleaux
may be seen in many infections, autoimmune
conditions and plasma cell diseases,
including Waldenstrom macroglobulinemia.
OSMOSIS.ORG 443
NOTES
NOTES
PLATELET DISORDERS

▪ Platelet dysfunction, impaired hemostasis, LAB RESULTS
bleeding ▪ Complete blood count (CBC)
▪ Clotting studies (e.g. bleeding time)
RISK FACTORS ▪ Platelet function tests
▪ Children of parents who are close relatives
(consanguineous)
TREATMENT
COMPLICATIONS ▪ Manage spontaneous/trauma-related
▪ Mild to severe hemorrhage bleeding episodes

▪ Anti-fibrinolytic therapy
▪ Mucocutaneous bleeding ▪ Platelet transfusions
▪ Excessive bruising/bleeding after minor ▪ Avoid antiplatelet medications
trauma ▪ Corticosteroids, immunosuppressants
▪ Immediate, excessive bleeding with
invasive procedures
BERNARD–SOULIER SYNDROME
(BSS)
osms.it/bernard-soulier-syndrome
▪ Platelets lack essential glycoprotein Ib-IX-V
PATHOLOGY & CAUSES complex (GPIb) → impaired hemostasis →
bleeding
▪ Rare, inherited clotting disorder; mild
thrombocytopenia, macrothrombocytopenia
(giant platelets), platelet dysfunction, RISK FACTORS
bleeding ▪ Prevalence in individuals of Mediterranean
descent
CAUSES
(consanguineous)
▪ Autosomal recessive inheritance pattern
444 OSMOSIS.ORG
Chapter 56 Platelet Disorders
▪ Clotting studies
SIGNS & SYMPTOMS ▫ Bleeding time prolonged (PT, aPTT
normal)
▪ Mucocutaneous bleeding
▪ Flow cytometry
▫ Epistaxis; gingival bleeding; petechiae,
purpura (coalesced petechiae); GI ▫ Deficient/absent GPIb-IX-V complex
bleeding; genitourinary bleeding (e.g.
hematuria); menorrhagia OTHER DIAGNOSTICS
▪ Excessive bruising/bleeding after minor ▪ Physical examination
trauma; bruises linger ▫ Purpura
▪ Immediate, excessive bleeding with ▫ Ecchymoses
invasive procedures
▪ Asymptomatic until adulthood
TREATMENT
▪ Avoid antiplatelet medications
LAB RESULTS ▪ Anti-fibrinolytic therapy (e.g. tranexamic
▪ CBC acid)
▫ Low platelet count
OTHER INTERVENTIONS
▫ Giant platelets (accelerated platelet
▪ Platelet transfusions (e.g. prophylaxis
turnover)
before invasive procedures)
▫ HLA matching/leukocyte reduced
platelets reduces risk of allo-antibody
formation
GLANZMANN'S THROMBASTHENIA
(GT)
osms.it/glanzmanns-thrombasthenia
CAUSES
PATHOLOGY & CAUSES ▪ Autosomal recessive inheritance pattern
▪ Rarely, allo-/auto-antibodies to platelet
▪ Inherited bleeding disorder, defect in
αIIbβ3 produced by autoimmune conditions
platelet surface receptor αIIbβ3
(e.g. systemic lupus erythematosus,
▪ Platelet-mediated hemostasis immune thrombocytopenia,
▫ Binding of platelets to exposed myelodysplastic syndrome) during
components of injured endothelium pregnancy/with use of platelet integrin αIIbβ3
through glycoprotein (GP) receptors on antagonists (abciximab, eptifibatide)
platelet surface (e.g. GPIb/IX, GPIa/IIa,
integrin αIIbβ3)
RISK FACTORS
▪ Integrin αIIbβ3 defect → impaired platelet
clot retraction, altered hemostasis ▪ Slightly more common in individuals who
are biologically female
OSMOSIS.ORG 445
▪ Conditions requiring frequent platelet ▪ Flow cytometry
transfusion ▫ Deficient/absent αIIbβ3 platelet receptors
▫ Platelet alloimmunization ▫ Mutation analysis through genomic
DNA sequencing
COMPLICATIONS
▪ Fatal bleeding OTHER DIAGNOSTICS
▫ Risk increases during childbirth ▪ Physical examination
(maternofetal bleeding, primary/ ▫ Purpura
secondary postpartum hemorrhage) ▫ Ecchymoses

▪ Mucocutaneous bleeding ▪ Avoid antiplatelet medications, punctures,
▫ Epistaxis; gingival bleeding; petechiae, invasive procedures
purpura (coalesced petechiae);
gastrointestinal (GI) bleeding;
genitourinary bleeding (e.g. hematuria); MEDICATIONS
menorrhagia ▪ Individuals who are biologically female, of
▪ Excessive bruising/bleeding after minor childbearing age
trauma ▫ Metrorrhagia: oral contraceptives
▪ Immediate, excessive bleeding with (suppress menstrual periods); iron
invasive procedures supplementation; hysterectomy (if
bleeding severe)
▪ Infants
▫ Childbirth: prophylaxis with
▫ Leukocytosis, delayed separation of
recombinant factor VIIa + antifibrinolytic
umbilical cord, purpura, spontaneous
agent
bruising, mucocutaneous bleeding
▪ Rituximab, corticosteroids,
immunosuppressants (e.g.
DIAGNOSIS cyclophosphamide)

▪ CBC ▪ Manage bleeding episodes
▫ Platelet count normal ▫ Compression, fibrin sealants, gelatin
▪ Clotting studies sponges, nasal packing, topical
▫ Bleeding time prolonged (PT, aPTT thrombin, anti-fibrinolytic therapy (e.g.
normal) tranexamic acid), recombinant factor
▪ Light transmission aggregometry (LTA) VIIa
▫ Determines degree of platelet ▪ Platelet transfusions (e.g. prophylaxis
aggregation before invasive procedures)
▫ Decreased or absent in GT ▫ HLA matching/administration of
leukocyte reduced platelets reduces
▪ Platelet function analyzer (PFA)
allo-antibody formation
▫ Measures flow rate as platelets form
▪ Oral hygiene mitigates gingival bleeding
platelet plug within capillary tube
▪ Hematopoietic cell transplantation (if
▫ Formation of platelet plug prolonged in
bleeding severe, recurrent)
GT
446 OSMOSIS.ORG
NOTES
NOTES
PORPHYRIA

Chronic
PATHOLOGY & CAUSES
▪ E.g. porphyria cutanea tarda, erythropoietic
porphyria
▪ Metabolic diseases; accumulation of heme
▪ Skin manifestations
precursors
▪ Photosensitivity
▫ Porphyrin; neurologic/cutaneous
disorders ▫ Pain, discomfort, burning of sunlight-
exposed areas
▪ Mostly hereditary
▪ Vesiculo-erosive manifestations (e.g.
▫ Porphyria cutanea tarda (most common)
erosions, blistering)
▫ Acute intermittent porphyria
▪ Increased skin fragility
▫ Aminolevulinic acid dehydratase
deficiency porphyria (AKA Doss
porphyria) DIAGNOSIS
▫ Hereditary coproporphyria
▫ Variegate porphyria LAB RESULTS
▫ Congenital erythropoietic porphyria ▪ Blood, urine tests
▫ Increased levels of porphobilinogen in
CAUSES urine
▪ Sporadic/inherited enzyme mutations in ▪ Genetic testing
heme production → porphyrin accumulates
in tissues
TREATMENT
RISK FACTORS MEDICATIONS
▪ Smoke, alcohol, hormonal changes, fasting, ▪ Acute intermittent porphyria (AIP)
stress, certain drugs, sunlight exposure,
▫ Hospitalization during acute attack,
lead poisoning
intravenous hemin, etc.
▪ Porphyria cutanea tarda (PCT)
COMPLICATIONS ▫ Phlebotomy, chloroquine/
▪ Paralysis, seizures hydroxychloroquine sulfate, etc.
SIGNS & SYMPTOMS

Acute
▪ Resolve once attack passes (e.g. acute
intermittent porphyria, doss porphyria)
▪ Abdominal pain, vomiting, hypertension,
tachycardia, neurological/psychiatric
symptoms (e.g. seizures, neuropathy,
anxiety, confusion, hallucinations), red urine
OSMOSIS.ORG 447
ACUTE INTERMITTENT
PORPHYRIA (AIP)
osms.it/acute-intermittent-porphyria

▪ Neurovisceral disease ▪ Acute episodes lasting several hours to few
▫ Acute, recurrent attacks of abdominal days
pain + other clinical manifestations ▫ Severe, diffuse abdominal pain
(neuropsychiatric, gastrointestinal, ▫ Palpitations, sweating
urinary) ▫ GI: nausea, vomiting, constipation
▫ Neurological: seizure, peripheral
CAUSES neuropathy (e.g. tingling sensations in
▪ Autosomal dominant mutation of limbs), muscle weakness
hydroxymethylbilane synthase (HBMS) ▫ Psychiatric: irritability, anxiety,
gene → alterated codification of hallucinations
enzyme hydroxymethylbilane synthase ▫ Urinary: dysuria, urinary retention,
(AKA porphobilinogen deaminase/ discolored (reddish, red-brown) urine
uroporphyrinogen I synthase) → impaired
heme production → accumulation of
metabolites: porphobilinogen (PBG), MNEMONIC: 5Ps
aminolevulinic acid (ALA) Features of Acute
intermittent porphyria
RISK FACTORS Pain in the abdomen
▪ Drugs (e.g. barbiturates, antiepileptics, Polyneuropathy
rifampin) Psychological abnormalities
▪ Alcohol Pink urine
▪ Exposure to tobacco smoke Precipitated by drugs:
▪ Hormonal fluctuations (e.g. menstruation) including barbiturates, oral
▪ Dietary changes (e.g. reduced caloric contraceptives, sulfa drugs
intake)
▪ Stress (e.g. illness, psychological stress)
DIAGNOSIS
COMPLICATIONS
▪ Hypertension, kidney failure, neuromuscular LAB RESULTS
respiratory failure, hepatocellular carcinoma ▪ Elevation of heme precursor in urine (PBG)
▪ Genetic testing
448 OSMOSIS.ORG
Chapter 57 Porphyria
TREATMENT
MEDICATIONS
▪ Intravenous hemin
▪ Symptomatic treatment (e.g. antiemetics,
pain medications)
Figure 57.1 The urine of an individual with

porphyria (right).
PORPHYRIA CUTANEA TARDA (PCT)

osms.it/porphyria-cutanea-tarda

▪ Blistering cutaneous lesions of sunlight- ▪ Increased mechanical fragility after sunlight
exposed skin exposure → painful vesicles, blisters on
hands/face (minor trauma)
▪ Increased facial hair growth (e.g.
TYPES
hypertrichosis)
▪ PCT Type I: acquired disease
▪ Hardened yellow skin lesions (e.g.
▪ PCT Type II: autosomal dominant disease scleroderma-like plaques)
▪ Hypermelanosis (brownish skin
CAUSES pigmentation)
▪ Impaired function of uroporphyrinogen ▪ Abnormal urine color
decarboxylase (UROD) enzyme →
porphyrins overproduction, accumulation →
photosensitizing porphyrins in skin damage DIAGNOSIS
proteins, lipids, basement membrane →
cutaneous lesions LAB RESULTS
▪ Elevated porphyrins level (orange-red
RISK FACTORS fluorescence on Wood lamp)
▪ Alcohol ▪ Elevated porphyrins level in stool
▪ Exposure to tobacco smoke ▪ UROD activity in blood cells
▪ Hormonal imbalances Skin biopsy of lesions
▪ Infectious disease (e.g. HIV, hepatitis C) ▪ Subepidermal bullae, inflammation
▪ Hemochromatosis, iron overloading ▪ Immunofluorescence
▫ Immunoglobulins at dermal-epidermal
COMPLICATIONS junctions
▪ Cirrhosis, hepatocellular carcinoma
OSMOSIS.ORG 449
TREATMENT
MEDICATIONS
▪ Low doses of chloroquine/
hydroxychloroquine sulfate
OTHER INTERVENTIONS
▪ Avoid sunlight exposure
▪ Discontinue aggravating substances
(alcohol, estrogen)
▪ Blood removal (e.g. phlebotomy) Figure 57.2 Skin lesions on the dorsum of
▫ Decrease body iron load both hands in a case of porphyria cutanea
▪ Limit iron-rich food tarda.
450 OSMOSIS.ORG
NOTES
NOTES
SPLEEN PATHOLOGY

OTHER DIAGNOSTICS
PATHOLOGY & CAUSES
Enlarged spleen
▪ Injuries/medical procedures/illnesses ▪ Palpable (increased risk of rupture)
▫ Impair splenic function/lead to spleen
removal
TREATMENT
▪ Asplenia → frequent infections Asplenia

▪ Traumatic rupture → shock, referred pain to ▪ Immunization/antibiotic prophylaxis
left shoulder
SURGERY
DIAGNOSIS Splenic rupture
▪ Splenectomy
DIAGNOSTIC IMAGING ▫ If hemodynamically unstable
Ultrasound/CT scan
▪ Splenic rupture, asplenia OTHER INTERVENTIONS
Splenic rupture
LAB RESULTS ▪ Strict bed rest, 1–3 days
▪ Impaired blood filtration ▫ Conservative; if hemodynamically stable
OSMOSIS.ORG 451
ASPLENIA
osms.it/asplenia
▪ Reduced splenic function, less severe
PATHOLOGY & CAUSES
▪ Absence of normal spleen → SIGNS & SYMPTOMS
immunodeficiency
▪ Splenic macrophages loss → inability to ▪ Recurrent infection
clear opsonized bacteria from blood ▪ Sickle cell disease
▪ T-cell independent antibodies deficiency ▫ Enlarged palpable spleen
▪ Increased infection risk, severity from
polysaccharide encapsulated bacteria
▫ Haemophilus influenzae type b, DIAGNOSIS
Streptococcus pneumoniae, Neisseria
meningitidis, Group B streptococcus, DIAGNOSTIC IMAGING
Klebsiella pneumoniae, Salmonella typhi ▪ Abdominal ultrasound, CT scan/MRI
▪ Radionuclide scan
TYPES ▫ Assess for function
Acquired asplenia
▪ Splenectomy LAB RESULTS
▫ Surgical procedure, spleen partially/ ▪ Thrombocytosis (elevated platelet count),
completely removed (following trauma, leukocytosis (elevated white cell count)
cancer, hemoglobinopathies, massive ▪ Howell–Jolly bodies
enlargement) ▫ Erythrocytes containing basophilic DNA
▪ Auto-splenectomy fragments
▫ Underlying disease → focal venous ▪ Target cells
occlusion → repeated infarction → ▫ Erythrocytes with increased ratio of
gradual perivascular fibrosis → loss surface membrane area to volume
of function (e.g. sickle-cell disease,
pneumococcal septicaemia, systemic
lupus erythematosus) TREATMENT
Congenital asplenia (rare) MEDICATIONS
▪ Heterotaxy syndrome (situs ambiguus) →
disruption to splenic development during Antibiotics
embryogenesis → no spleen/formation of ▪ Antibiotic prophylaxis (penicillins)
multiple ineffective spleens → functional ▪ Early antibiotic prescription at first sign of
asplenia infection (common/otherwise)
▪ Isolated congenital asplenia → ribosomal
mutation → failure of spleen development Vaccination
▪ Pneumococcal polysaccharide vaccine
Functional asplenia ▪ Haemophilus influenzae type b vaccine
▪ Splenic tissue present, functionally impaired ▪ Meningococcal conjugate vaccine
(e.g. sickle-cell disease, isolated congenital
▪ Influenza vaccine
asplenia)
Hyposplenism
452 OSMOSIS.ORG
Chapter 58 Spleen Pathology
Figure 58.1 A peripheral blood smear with

erythrocytes containing Howell–Jolly bodies.
Howell-Jolly bodies represent a damaged or Figure 58.2 A peripheral blood smear
absent spleen which has failed to filter these containing target cells; erythrocytes that have
red blood cells. become derformed and damaged, yet have
not been cleared by an absent spleen.
RUPTURED SPLEEN
osms.it/ruptured-spleen
▪ Medications
PATHOLOGY & CAUSES ▫ Anticoagulants
▪ Pregnancy
▪ Splenic rupture → break in splenic
structural integrity → large amount of blood ▪ Enlarged spleens more vulnerable to
leaks into abdomen → shock → death traumatic rupture

Traumatic
▪ Abdominal pain, epigastric tenderness, pain
▪ Significant force to spleen → rupture in left flank
▪ Blunt trauma to abdomen ▪ Kehr’s sign
▪ Penetrating trauma (e.g. gunshots/ ▫ Blood in peritoneal cavity → irritation of
stabwounds) surrounding tissues → pain referred to
tip of left shoulder
Non-traumatic
▪ Hypovolemic shock
▪ Splenomegaly → capsule thins, decreases
structural integrity ▫ Tachycardia, hypotension, tachypnea,
pallor, anxiety
▪ Infectious diseases
▫ Malaria, infectious mononucleosis
▪ Medical procedures DIAGNOSIS
▫ Colonoscopy
▪ Hematological disease DIAGNOSTIC IMAGING
▫ Non-Hodgkin’s lymphoma, acute
Emergency ultrasound
lymphoblastic leukemia
▪ Free blood in peritoneum
▪ Malignancy
▫ Angiosarcoma
OSMOSIS.ORG 453
▪ Free blood in peritoneum
TREATMENT
▪ Spleen → inhomogeneous hypodense SURGERY
regions
Splenectomy
OTHER DIAGNOSTICS ▪ Hemodynamically unstable/emergency/
grade IV, V injury
Procedural
▪ Peritoneal lavage → free blood drawn from OTHER INTERVENTIONS
peritoneum
Strict bed rest, 1–3 days
▪ Conservative (hemodynamically stable)
▪ Follow-up CT scan in seven days
Figure 58.3 An abdominal CT scan in the

axial plane demonstrating a large perisplenic
hematoma. This hematoma has formed as
a result of splenic rupture, most likely as a
Figure 58.4 The gross pathology of a spleen
result of trauma.
ruptured by trauma. The capsule is torn,
revealing the dark red splenic parenchyma.
454 OSMOSIS.ORG
NOTES
NOTES
THROMBOCYTOPENIA

▪ Acquired/inherited disorders: impaired LAB RESULTS
platelet function, decreased platelet count, ▪ Complete blood count (CBC)
sequelae ▪ Peripheral blood smear analysis
▪ Accelerated destruction/consumption → ▪ Platelet function tests
decreased platelets
TREATMENT
▪ Mitigate complications of deranged platelet
▪ Mucocutaneous bleeding (e.g. epistaxis, function
gingival bleeding, petechiae, purpura)
HEPARIN-INDUCED
THROMBOCYTOPENIA (HIT)
osms.it/heparin-induced-thrombocytopenia
▪ Increased consumption of platelets for
PATHOLOGY & CAUSES clotting + removal of antibody-heparin-
PF4 complexes by macrophages
▪ Acquired platelet disorder of reticuloendothelial system →
▫ Accelerated thrombosis in arteries, veins thrombocytopenia
→ consumptive thrombocytopenia. ▫ Thrombocytopenia usually not sufficient
▫ Occurs in individuals exposed to to cause significant bleeding
unfractionated heparin/low molecular ▪ Classified by severity, timing, degree
weight heparin (LMWH) of drop in platelet count drop, antibody
▫ AKA heparin-induced thrombocytopenia mediation
thrombosis (HITT)
▪ Exposure to heparin/LMWH → IgG RISK FACTORS
autoantibodies formed against heparin
▪ 5% individuals exposed to unfractionated/
→ platelet factor 4 (PF4) binds to heparin
LMWH
→ antibody-heparin-PF4 complex →
increased platelet activation → thrombosis ▫ Unfractionated > LMWH
formation in arteries, veins
OSMOSIS.ORG 455
▪ Dose
▫ Prophylactic dose > therapeutic doses >
DIAGNOSIS
intermittent heparin flushes
LAB RESULTS
biologically female HIT antibody testing
▪ HIT immunoassay
▫ ELISA for anti-PF4 antibodies
▫ PF4 antibodies in individual’s serum
▫ Colorimetric change: optical density
(OD), HIT antibody concentration
▫ Higher OD = higher antibody titer = HIT
▪ Functional assay
▫ Serotonin release assay (SRA)
▫ Serotonin release from platelets, ability
of HIT antibodies from individual’s
serum to activate test platelets
▫ Release of serotonin + therapeutic
heparin concentration
▪ Heparin-induced platelet aggregation
(HIPA) assay
▫ Platelet aggregation with no heparin,
low/high heparin concentration
▫ Minimal platelet aggregation with no
heparin, high heparin concentrations;
strong aggregation with low heparin
concentrations
COMPLICATIONS
▪ Venous thromboembolism (VTE) OTHER DIAGNOSTICS
▪ Occlusion of large lower limb arteries by ▪ History of exposure to unfractionated
platelet rich “white clots” → limb ischemia, heparin
necrosis, gangrene, loss of limbs ▪ New venous/arterial thrombosis
▪ Skin necrosis
▪ Organ infarction
▫ Kidney, myocardial infarction; MNEMONIC: 4Ts
cerebrovascular insult Diagnosis of
▪ Adrenal hemorrhage Thrombocytopenia
▫ Adrenal vein thrombosis Thrombocytopenia: CBC, fall in
▪ Heparin-induced anaphylactoid reactions platelet count
Timing: fall in platelet count,
5–10 days after heparin
SIGNS & SYMPTOMS initiation
Thrombosis: venous/arterial
▪ Skin necrosis at injection site thrombosis, sequelae
▪ Acute systemic reaction after IV heparin OTher: no other explanations
bolus
▫ Fever with chills, tachycardia,
hypertension, dyspnea
▪ Limb ischemia, organ infarction
456 OSMOSIS.ORG
Chapter 59 Thrombocytopenia
▫ Transition to warfarin/other outpatient

TREATMENT anticoagulant after stabilization
MEDICATIONS
▪ Immediate discontinuation of heparin SURGERY
▪ Administration of non-heparin Thromboembolectomy
anticoagulant (e.g. fondaparinux, ▪ If severe limb ischemia, high risk for
argatroban) amputation
IDIOPATHIC THROMBOCYTOPENIC
PURPURA (ITP)
osms.it/idiopathic-thrombocytopenic-purpura
malignancy, chronic lymphocytic leukemia

PATHOLOGY & CAUSES ▫ Alter immune homeostasis
▫ Alterations in T cell-mediated
▪ Acquired thrombocytopenia; accelerated
cytotoxicity/suppression of
immune platelet destruction → bleeding
megakaryocyte production, maturation
▪ AKA, immune thrombocytopenic purpura,
autoimmune thrombocytopenic purpura Drug-induced immune thrombocytopenia
▪ B cells produce IgG autoantibodies against (DITP)
platelet glycoproteins (e.g. IIb/IIIa, Ib/ ▪ Triggered by drug-dependent platelet
IX complexes) → platelets coated with antibodies
antibodies recognized as “non-self” by ▪ Quinidine, phenytoin, valproic acid,
splenic macrophages → platelet destruction rifampin, trimethoprim-sulfamethoxazole,
▫ Contributing factors: impaired platelet sulfonamides
production, cell-mediated platelet ▪ Reaction due to drug/metabolites
destruction
Severe ITP
TYPES ▪ Platelet counts < 10,000–20,000/microL;
significant bleeding requires treatment
▪ Classifed by cause, duration, severity
Refractory ITP
Primary ITP
▪ Severe ITP, fails to respond to/relapses after
▪ Idiopathic
splenectomy
Secondary ITP
▪ Caused by systemic condition RISK FACTORS
▪ Viral infections (most common) ▪ Age; genetic/acquired factors
▫ HIV, hepatitis C, cytomegalovirus
▫ Antibodies against viral antigens
cross-react with platelet antigens via
molecular mimicry
▪ Bacterial lipopolysaccharides attach to
platelet surfaces → increase phagocytosis
of platelets
▪ Systemic lupus erythematosus, lymphoid
OSMOSIS.ORG 457
COMPLICATIONS
▪ Potentially severe hemorrhage (uncommon)
TREATMENT
▫ Intracranial bleeding, subarachnoid
MEDICATIONS
hemorrhage, gastrointestinal (GI)
hemorrhage, hematuria, severe Raise platelet count
menorrhagia ▪ High dose glucocorticoids (dexamethasone;
prednisone)
SIGNS & SYMPTOMS ▪ Immune globulin (IVIG)
If no response to above medications

▪ Bruising easily after minor trauma ▪ Rituximab
▪ Mucocutaneous bleeding ▫ Monoclonal antibody reduces antibody-
▫ Petechiae, purpura, epistaxis, gingival dependent cytotoxicity, complement-
bleeding mediated lysis of platelets
▪ Thrombopoietin (TPO) receptor agonists
(e.g. eltrombopag)
DIAGNOSIS
▫ Increases platelet production
by stimulating production of
LAB RESULTS megakaryocytes
▪ CBC
▪ Immunosuppressive agents
▫ Low platelet count
▫ Danazol, azathioprine, cyclosporine
▫ Scarce platelets Medications to avoid
▪ Flow cytometry-based assays ▪ Antiplatelet agents
▫ Drug-dependent platelet antibodies ▫ Aspirin, other nonsteroidal anti-
inflammatory drugs (NSAIDs)
OTHER DIAGNOSTICS
▪ History of drug implicated in DITP SURGERY
▪ If no response to medication
Splenectomy
▪ Reduces platelet destruction
OTHER INTERVENTIONS
▪ Platelet transfusions
▫ Clinically significant bleeding
Figure 59.1 Multiple petechiae present in the

skin of an individual with ITP. The platelet
count was < 5 x 109/L.
458 OSMOSIS.ORG
Chapter 59 Thrombocytopenia
THROMBOTIC
THROMBOCYTOPENIC PURPURA
(TTP)
osms.it/thrombotic-thrombocytopenic
ancestry, diagnosed with systemic lupus

PATHOLOGY & CAUSES erythematosus (SLE)
▪ Sepsis, liver disease, pancreatitis, cardiac
▪ Thrombotic microangiopathy (TMA) surgery
caused by deficient activity of ADAMTS13
▫ Reduce activity of ADAMTS13
protease
▪ Pregnancy
▪ ADAMTS13 breaks von Willebrand factor
(vWF) molecules into smaller multimers, ▫ Decrease in ADAMTS13, increase in
prevents excessive accumulation on vWF, 2nd–3rd trimesters
endothelial surfaces in microvasculature
▪ Excessive vWF on endothelial surfaces → COMPLICATIONS
increased propensity for platelets to attach, ▪ Organ damage
accumulate (esp. in high pressure areas ▫ Renal insufficiency, focal neurologic/
with shearing stress) + endothelial damage mental status anomalies, arrhythmias
→ platelet-rich thrombi in microcirculation
→ tissue ischemia, organ dysfunction,
microangiopathic hemolytic anemia SIGNS & SYMPTOMS
(MAHA), thrombocytopenia
▪ Thrombocytopenia consumptive ▪ Classic TTP pentad
▫ Increased need for platelets from cyclical ▫ Thrombocytopenia, MAHA, renal
clot formation, dissolution dysfunction, neurologic impairment (e.g.
▪ MAHA headache, confusion, seizures, coma),
▫ Red blood cell (RBC) mechanical fever
fragmentation in microthrombi, ▪ Mucocutaneous bleeding
damaged vessels → schistocytes ▫ Petechiae, purpura (coalesced
▪ Organs most affected by TTP in petechiae), epistaxis, gingival bleeding
microcirculation ▪ Intravascular hemolysis → dark urine
▫ Brain, heart, adrenal glands, pancreas, ▪ Lightheadedness, abdominal pain, easy
kidneys bruising, nausea/vomiting
CAUSES
▪ ADAMTS13 deficiency
MNEMONIC: RAFT'N
Common signs of Thrombotic
▫ Acquired inhibitory autoantibody (IgG)
thrombocytopenia purpura
to ADAMTS13; inherited mutation of
ADAMTS13 gene (minority) Renal problems
Anemia: MAHA associated
Fever
RISK FACTORS
Thrombocytopenia
▪ Increased prevalence in individuals
who are biologically female, of African Neurologic dysfunction
OSMOSIS.ORG 459
OTHER DIAGNOSTICS
DIAGNOSIS ▪ ADAMTS13 assay
▫ Gel electrophoresis of VWF multimers
LAB RESULTS
measures degradation by ADAMTS13
▪ CBC
▪ ADAMTS13 inhibitor assay
▫ Decreased platelet count
▫ Autoantibody titer
▫ Increased reticulocyte count
▪ Genetic testing
▫ Decreased hemoglobin, hematocrit
▫ ADAMTS13 gene mutation, if hereditary
▪ Peripheral blood smear analysis TTP suspected
▫ Schistocytes, spherocytes
▪ Hemolysis
▫ Elevated lactate dehydrogenase (LDH) TREATMENT
▫ Reduced haptoglobin
MEDICATIONS
▪ Glucocorticoids
▪ Elevated creatinine
▪ Monoclonal antibody
▫ Renal insufficiency
OTHER INTERVENTIONS
▪ Plasma exchange (PEX)
460 OSMOSIS.ORG
NOTES
NOTES
THYMUS NEOPLASIA

▪ Tumors in thymus (anterior mediastinum) DIAGNOSTIC IMAGING
▪ Chest X-ray, CT scan
TYPES
▪ Classified by cell from which tumors arise LAB RESULTS
▪ Fine needle aspiration/core biopsy
Thymoma, thymic cancers (most common)
▪ Thymic epithelial cells
TREATMENT
Neuroendocrine tumors
▪ Carcinoids MEDICATIONS
Others ▪ Chemotherapy/radiation therapy/both
▪ Thymic hyperplasia, cysts, thymolipoma
SURGERY
COMPLICATIONS ▪ Resection
▪ Bioactive substances → paraneoplastic
syndromes
SIGNS & SYMPTOMS

▪ Can be asymptomatic
▪ Chest pain, cough, dyspnea, paraneoplastic
syndromes
OSMOSIS.ORG 461
THYMOMA
osms.it/thymoma
▪ Fatigue
PATHOLOGY & CAUSES
▪ Compression of mediastinal structures
▪ Rare tumor from epithelial cells (thymus) ▫ Esophagus → dysphagia
▪ Benign/malignant ▫ Airways → cough, dyspnea
▪ Localization ▫ Recurrent laryngeal nerve →
hoarseness
▫ Anterior superior mediastinum (most
frequently) ▫ Superior vena cava (SVC) → SVC
syndrome (face, arms edema; venous
▫ Atypical position (neck, thyroid,
distension in neck, chest, arms)
pulmonary hilum)
▫ Chest pain
▪ Macroscopic characteristics
▫ Lobulated Paraneoplastic syndromes
▫ Firm ▪ Myasthenia gravis (most frequent, 30%)
▫ Gray-white ▫ Muscle weakness
▫ Containing cystic spaces/calcifications/ ▫ Drooping eyelid (ptosis), double vision
hemorrhages (diplopia)
▫ Dysphagia (difficulty swallowing)
TYPES ▪ Pure red cells aplasia
▪ Extension (Masaoka staging systems) ▪ Hypogammaglobulinemia
▪ Graves disease
Type I
▪ Pernicious anemia
▪ Encapsulated (non-invasive)
▪ Systemic lupus erythematosus
Type II ▪ Sjogren syndrome
▪ Invasion through capsula ▪ Dermatomyositis-polymyositis
▪ Cushing syndrome
Type III
▪ Invasion into adjacent organs
DIAGNOSIS
Type IV
▪ Local and distant implantations DIAGNOSTIC IMAGING
(metastases)
Chest X-ray
COMPLICATIONS ▪ Hyperdense mediastinal mass,
calcifications
▪ Mass effect (e.g. cardiac tamponade,
respiratory problems); humoral effects (e.g. CT scan
paraneoplastic syndromes), metastases,
▪ Well-defined attenuation, cystic
recurrences
components, calcifications
MRI, nuclear medicine studies

SIGNS & SYMPTOMS
▪ Asymptomatic; found incidentally during LAB RESULTS
imaging studies ▪ Fine-needle aspiration/core biopsy
▪ Weight loss
462 OSMOSIS.ORG
Chapter 60 Thymus Neoplasia
TREATMENT
MEDICATIONS
▪ Surgical resection of thymus (thymectomy)
OTHER INTERVENTIONS
▪ Pre/post-operative chemotherapy/
radiotherapy (advanced Masaoka stages)
Figure 60.1 A CT scan in the axial plane Figure 60.2 The gross pathology of a
demonstrating a large thymoma occupying thymoma.
the superior and anterior mediastinum.
OSMOSIS.ORG 463
NOTES
NOTES
ADULT PRIMARY BRAIN TUMORS

LAB RESULTS
PATHOLOGY & CAUSES ▪ Biopsy: histopathologic, molecular
examination
▪ Diverse central nervous system cell
neoplasms
▫ Benign/malignant OTHER DIAGNOSTICS
▪ Tumor grades: World Health Organization
(WHO) grading system
RISK FACTORS
▪ Genetic predisposition
▪ Ionizing radiation exposure TREATMENT
▪ Dietary N-nitroso compounds (NOCs)
▪ Dependent on tumor stage, grade
COMPLICATIONS
▪ Mass effect: hydrocephalus, ↑ intracranial MEDICATIONS
pressure, herniation ▪ Steroids
▪ Neurocognition, motor dysfunction, death ▪ Monoclonal antibodies
▫ Avastin
▪ Chemotherapy
SIGNS & SYMPTOMS
▪ Vary depending on tumor type SURGERY
▪ May be asymptomatic; headache; visual, ▪ Resection
hearing deficits; nausea; vomiting; altered
level of consciousness (LOC) OTHER INTERVENTIONS
▪ Radiation
DIAGNOSIS
DIAGNOSTIC IMAGING
CT scan/MRI
▪ Visualizes tumor mass
464 OSMOSIS.ORG
Chapter 61 Adult Primary Brain Tumors
GLIOBLASTOMA MULTIFORME
(GBM)
osms.it/gllioblastoma-multiforme
▪ Proneural
PATHOLOGY & CAUSES ▫ Secondary type gene mutations
▪ Highly malignant, aggressive glial cell ▪ Neural
tumor ▪ ↑ expression of NEFL, GABRA1, SYT1,
▪ Location: usually hemispheric white matter SLC12A5 tumor markers
▫ Mass with grayish periphery, necrosed ▪ Mesenchymal
yellow center, multiple bleeding zones ▫ ↓ NF1 gene, ↑ TNF and NF-κB pathway
▪ World Health Organization (WHO) grade genes expression
IV tumor
CAUSES
TYPES ▪ Genetic alterations
Histology Primary GBM

▪ Giant-cell glioblastoma ▪ Epidermal growth factor receptor (EGFR)
▫ Multinuclear, giant cells gene mutation → overexpression, constant
receptor activation → uncontrolled cell
▪ Gliosarcoma
proliferation
▫ Combined astrocytic, sarcoma-like
▪ Heterozygosity loss commonly affects long
components; squamous/gland-like
arm of chromosome 10
structures → possible differentiation into
other tissue ▪ Phosphatase, tensin homologue (PTEN)
gene mutation → tyrosine phosphatase
▪ Epithelioid glioblastoma
activity loss → overactivated signaling
▫ Eosinophilic cytoplasm in large pathways → ↑ proliferation
epithelioid cells
Secondary GBM
Development-based
▪ IDH1/IDH2 gene mutation →
▪ Correlated with Isocitrate dehydrogenase 2-hydroxyglutarate (2-HG) overproduction
(IDH) gene mutation → impaired DNA methylation due to 2-HG
▪ Primary ▪ TP53 mutation → tumor suppression
▫ Spontaneous development, individuals function lost
aged > 50 ▪ Heterozygosity loss on long arm of
▫ AKA IDH wild-type: no IDH gene chromosomes 13, 19, 22
mutation ▪ Platelet-derived growth factor (PDGF) gene
▪ Secondary mutation with overexpression → ↑ PDGF
▫ Individuals aged < 50 receptor binding → ↑ proliferation
▫ Low-grade astrocytoma (WHO grade II)
▫ Anaplastic astrocytoma (WHO grade III) RISK FACTORS
▪ White, biologically-male individuals of
Subtypes: molecular characteristics
Jewish descent, aged 45–70
▪ Classic
▪ Genetically-inherited diseases
▫ Molecular changes resemble primary
▫ Li–Fraumeni syndrome, tuberous
type
sclerosis, neurofibromatosis
OSMOSIS.ORG 465
▪ Radiation exposure OTHER DIAGNOSTICS
▪ Tobacco use
Histology
▪ Pesticide exposure
▪ Inadequate astrocyte differentiation
▪ Viruses with atypical nuclei, uncontrolled cell
▫ Simian virus 40, Human herpesvirus 6, proliferation with shape/size cell variation
Cytomegalovirus ▪ Immunostaining
▫ Commonly positive glial fibrillary acidic
COMPLICATIONS protein (GFAP)
▪ Extension to ventricular wall
▪ Meningeal gliomatosis
▫ Malignant cell spread to spinal cord via
▪ Recurrence
▪ Multifocality
▪ Mass effect
▫ Obstructive hydrocephalus, ↑
intracranial pressure, herniation
▪ Seizures
▫ Supratentorial glioblastoma
SIGNS & SYMPTOMS

▪ Severe morning headache, attenuates
throughout day → focal symptomatology
▫ Motor (gradual), sensory, vision loss;
aphasia Figure 61.1 An MRI scan of the head in the
coronal plane demonstrating glioblastoma of
▪ Mental changes
the left temporal lobe.
▫ Altered mood, personality; impaired
comprehension, concentration, memory
DIAGNOSIS
DIAGNOSTIC IMAGING
CT scan
▪ Hypodense central area, irregular ring-like
edge enhancements
MRI
▪ T1: hypointense center
▪ T2: hyperintense center, peripheral low- Figure 61.2 The histological appearance
attenuated vasogenic edema of a glioblastoma multiforme. The tumor
is composed of malignant glial cells with
Magnetic resonance spectroscopy (MRS)
marked nuclear pleomorphism. The tumor
▪ ↑ choline, lactate, lipid peaks demonstrates necrosis and is forming
▪ ↓ N-acetylaspartate, myo-inositol peaks microvascular channels.
Positron emission tomography (PET)
▪ ↑ glucose metabolism
466 OSMOSIS.ORG
TREATMENT
MEDICATIONS
▪ Avastin (common)
SURGERY
▪ Total/subtotal tumor resection
OTHER INTERVENTIONS
▪ Adjuvant chemotherapy, radiation therapy
HEMANGIOBLASTOMA
osms.it/hemangioblastoma
COMPLICATIONS
PATHOLOGY & CAUSES ▪ Acute hemorrhage
▫ Intracerebral: brainstem compression/
▪ Benign tumor; vascular cell proliferation,
tonsillar herniation, obstructive
new blood vessel formation
hydrocephalus
▪ Cherry red cystic/solid mass structure in
▫ Spinal: acute quadriplegia
cerebellum, spinal cord, brainstem
▪ Tumor mass effect → ↑ intracranial
▪ WHO grade I tumor
pressure
▪ Local structure compression: neurologic
CAUSES deficits (e.g. oculomotor nerve dysfunction,
motor weakness, sensory deficits)
Sporadic
▪ Paraneoplastic erythrocytosis →
▪ Usually solitaire, cerebellum most
polycythemia
commonly affected
Von Hippel–Lindau (VHL) disease

▪ Gene impairment with HL protein
SIGNS & SYMPTOMS
dysfunction → hypoxia inducing factor
(HIF) build up → ↑ production of angiogenic ▪ Tumor location-dependent
factors, vascular endothelial growth factor ▫ Brainstem: visual, sensory impairment;
(VEGF), platelet-derived growth factor motor weakness
(PDGF), transforming growth factor (TGF) ▫ Cerebellum: ataxia
→ stimulation of angiogenesis ▫ Spinal cord: pain, sensory impairment
▪ Small, multiple lesions ▪ In von Hippel–Lindau disease (VHL)
▪ Common spinal cord affection, retinal ▫ Effect on retina → vision loss
hemangiomas also occurs
RISK FACTORS
▪ Biologically-male individuals, aged 20–50
OSMOSIS.ORG 467
DIAGNOSIS
DIAGNOSTIC IMAGING
MRI
▪ T1 hypointense/T2 hyperintense mass with
defined edges
CT scan
▪ Hypodense mass
Ultrasound
Figure 61.4 The histological appearance of a
▪ Hyperechoic zones amid surrounding tissue hemangioblastoma. The tumor is composed
Angiography of numerous, closely-packed, thin-walled
capillaries with underlying neoplastic stromal
▪ Preoperative tumor visualization
cells.
OTHER DIAGNOSTICS
Histology TREATMENT
▪ Two components
▫ Endothelial: small endothelial cells with MEDICATIONS
sparse cytoplasm ▪ Antiangiogenic treatment
▫ Stromal: cells with eosinophilic ▫ ↓ EDGF production
cytoplasm, numerous vacuoles
SURGERY
▪ Excision
▪ Stereotactic radiosurgery
Figure 61.3 Immunohistochemical staining of

a hemangioblastoma with CD31 highlights
the endothelial component of the tumor (dark
brown).
468 OSMOSIS.ORG
MENINGIOMA
osms.it/meningioma
COMPLICATIONS
PATHOLOGY & CAUSES ▪ Recurrent meningiomas
▪ Tumor arising from dome-shaped ▪ Mass effect
meningeal arachnoid cells with base on ▫ Obstructive hydrocephalus, ↑
meninges intracranial pressure, herniation
▪ Intracranial (usual), spinal (occasional) ▪ Bone abnormalities
▪ WHO grade I, II, III (morphology- ▫ Reactive sclerosis, bone invasion/erosion
dependent) possible (meningioma located on skull
base)
▪ Seizures
CAUSES
Sporadic
▪ TNF-receptor associated factor 7 (TRAF7)
mutation
Genetic predisposition
▪ Long arm of chromosome 22 loss → NF2
tumor suppressor gene impairment
▪ SMARCB1 tumor suppressor gene
mutation
▪ MEN1 tumor suppressor gene mutation
RISK FACTORS
Genetically-inherited diseases
▪ Neurofibromatosis type 2
▫ Intracranial localization (usual), spinal
meninges (occasional)
▫ Associated with multiple meningiomas Figure 61.5 An MRI scan of the head in the
coronal plane demonstrating a meningioma.
▪ Schwannomatosis
▪ Multiple endocrine neoplasia type I (MEN I)
Ionizing radiation SIGNS & SYMPTOMS

▪ Radiation exposure, dental radiographs,
diagnostic CT scan (children) ▪ May be asymptomatic; very slow growth
Other risk factors ▪ Symptoms tumor location-dependent
▪ Obesity Visual impairment
▪ Black, biologically-female individuals of ▪ Sella turcica vicinity
African descent more prone, ↑ incidence in ▫ One-sided papilledema, optic atrophy of
later age other eye (Foster–Kennedy syndrome)
▪ Cavernous sinus meningiomas
▫ Compression of cranial nerves supplying
extraocular muscles → muscles
OSMOSIS.ORG 469
weakness, double vision
▪ Optic nerve meningiomas
DIAGNOSIS
▫ Gradual, monocular, vision loss DIAGNOSTIC IMAGING
Impaired hearing and smell MRI
▪ Cerebellopontine angle meningiomas ▪ T1 hypointense/T2 hyperintense dural-
▫ Sensorineural deafness based mass, dural thickening with tail-like
▪ Olfactory groove meningiomas: anosmia structure (“tail sign”)
Behavioral changes CT scan

▪ Apathy, impaired attention, impulsivity ▪ Isodense mass, brain tissue compression
▪ Usually subfrontal meningiomas
PET
Muscle weakness ▪ ↑ uptake of 18F-Fluorodeoxyglucose
▪ Parasagittal meningiomas
▫ Contralateral leg weakness OTHER DIAGNOSTICS
▪ Foramen magnum meningiomas
▫ Lesion-side arm weakness → ipsilateral Histology
leg progression → contralateral leg ▪ WHO Grade I
affection → contralateral arm weakness ▫ Benign, not classified
▪ Spinal cord meningiomas ▪ WHO grade II
▫ One-sided plegia of extremities, sensory ▫ Atypical, needs to have at least three of
loss on other side (Brown–Séquard ↑ nucleus-cytoplasm ratio, ↑ cellularity,
syndrome) prominent nucleus, unorganized growth,
focal necrosis
▪ WHO grade III
▫ Malignant; ↑ mitotic index with atypical
cells, brain tissue infiltration, multifocal
necrosis
TREATMENT
▪ Monitoring
▫ Lesions small, asymptomatic
SURGERY
Figure 61.6 The histological appearance of ▪ Resection
a meningioma showing a typical whorled
▫ Large symptomatic/asymptomatic
architecture.
tumors
▪ Stereotactic radiosurgery
▫ Hard-to-reach/smaller than 3cm/1.18in
lesions
OTHER INTERVENTIONS
▪ Radiotherapy
▫ Primary management/adjuvant therapy
470 OSMOSIS.ORG
OLIGODENDROGLIOMA
osms.it/olligodendroglioma

▪ A tumor derived from oligodendrocytes ▪ May be asymptomatic; slow tumor growth
▪ Supratentorial in frontal/temporal white ▪ Seizures
matter (usual); spinal cord (occasional) ▫ Focal/secondarily generalized
▪ Genetic alteration combination → ▪ Focal symptomatology
oligodendroglioma grade II development → ▫ Frontal lobe: one-sided muscle
oligodendroglioma grade III progression weakness, impaired sensory perception,
▪ Oligodendroglioma grade III can develop impaired memory
without oligodendroglioma grade II ▫ Temporal lobe: impaired language
TYPES
DIAGNOSIS
WHO classification
▪ Grade II DIAGNOSTIC IMAGING
▫ Low-grade, low mitotic index with
MRI
atypical nuclei
▪ T1 hypointense/T2 hyperintense mass
▪ Grade III
▫ High-grade (anaplastic), ↑ cellular CT scan
density, ↑ mitotic index with atypical ▪ Hypodense, delineated tumor mass with
nuclei, microvascular proliferation calcification present
▪ Oligodendroglioma not-other-specified
(NOS)
LAB RESULTS
▫ Tumors with appropriate histologic
characteristics without 19p-1q ▪ Genetic testing
chromosomes co-deletion or IDH1/IDH2 ▫ IDH gene mutation, 19p-1q detection
gene mutation
OTHER DIAGNOSTICS
CAUSES
Histology
▪ IDH1/IDH2 gene mutation
▪ Needed for diagnosis
▪ 19p-1q chromosomes co-deletion due to
▫ Diffuse infiltrative tumors
unbalanced translocation
▫ Large nuclei with perinuclear halo—
“fried egg” appearance
RISK FACTORS ▫ ↑ capillary branching—“chicken wire”
▪ Biologically-female > biologically-male appearance
individuals, aged 25–45, most commonly
affected
OSMOSIS.ORG 471
TREATMENT
MEDICATIONS
▪ Chemotherapy
SURGERY
▪ Resection
OTHER INTERVENTIONS
Figure 61.7 The histological appearance of an
oligodendroglioma. The tumor is composed
of monomorphic malignant glial cells with
perinuclear halos and visible nucleoli.
472 OSMOSIS.ORG
NOTES
NOTES
AUTONOMIC DISEASES

▪ Autonomic nervous system (ANS) disorders DIAGNOSTIC IMAGING
(dysautonomia) ▪ See individual diseases
▪ Normative autonomic function
▫ Balanced impulses of sympathetic, LAB RESULTS
parasympathetic ANS
▪ Nerve biopsy
▫ One/both components fail → symptoms
▫ Neuropathy detection
▪ Etiology
▫ Genetic, environmental factors
OTHER DIAGNOSTICS
▪ Autonomic function test battery
CAUSES ▫ Monitor heart rate, autonomic functions
▪ Primary for pathological changes
▫ Pure autonomic failure, familial ▪ Valsalva maneuver
dysautonomia, multiple system atrophy,
▫ ↑ intraspinal pressure → neuropathic
postural orthostatic tachycardia
symptom exacerbation
syndrome (POTS)
▪ Quantitative sudomotor axon reflex test
▪ Secondary (neuropathy)
(QSART) test
▫ Alcoholism, diabetes mellitus, trauma,
▫ Electrical current → sweat gland
HIV infection, multiple sclerosis, Lyme
stimulation
disease, Parkinson’s disease, porphyria,
nerve compression (tumor), drug toxicity ▪ Tilt table test
(vincristine) ▫ Individual lies on table → table tilted
upright → detects sudden blood
pressure change
SIGNS & SYMPTOMS
▪ Breadth of autonomic function → wide TREATMENT
symptomatic variation
▪ Common autonomic disease symptoms ▪ Treat underlying cause if possible
▫ ↑↓ heart/respiration rate ▪ Mostly symptomatic treatment
▫ ↑↓ blood pressure
▫ Bowel/bladder/erectile dysfunction
▫ Hypohidrosis/hyperhidrosis
▫ Syncope
OSMOSIS.ORG 473
HORNER'S SYNDROME
osms.it/horners-syndrome

▪ AKA oculosympathetic paresis ▪ Classic triad: ptosis, anhydrosis, miosis
▪ Clinical syndrome ▪ May present with anhidrosis (if 2nd
▫ Damaged sympathetic neural pathways order neurons affected), flushing
to eye, associated structures (impaired vasoconstriction), apparent
▪ Sympathetic innervation to eye enophthalmos (ptosis)
▫ Three neurons comprise pathway
▫ 1st order neurons: in posterolateral MNEMONIC: PAM
hypothalamus, preganglionic fibers
Signs & symptoms of
▫ 2nd order neurons: in ciliospinal center Horner’s syndrome
(Budge’s center) in intermediolateral
Ptosis
segment of spinal column (C8–T2) →
preganglionic fibers travel to superior Anhidrosis
cervical ganglion (SCG) → synapse with Miosis
3rd order neurons
▫ 3rd order neurons: in SCG,
postganglionic fibers follow different
paths upon leaving SCG → flushing,
absent sweating not mandatory signs
▪ Manifests ipsilaterally
CAUSES
▪ Condition manifests following pathway
interruption
▪ Congenital/acquired
▫ Congenital: may present with
heterochromia iridis as eye pigmentation
under sympathetic innervation during
development Figure 62.1 An individual with Horner’s
▪ Classification based on lesion’s level syndrome demonstrating ptosis and miosis of
the left eye.
▫ 1st order neuron lesion: Arnold–Chiari
malformation, cerebrovascular insult,
basal skull tumor
▫ 2nd order neuron lesion: trauma, DIAGNOSIS
cervical rib, Pancoast tumor,
neuroblastoma, aorta dissection DIAGNOSTIC IMAGING
▫ 3rd order neuron lesion: herpes zoster,
internal carotid artery dissection, cluster X-ray
headache ▪ Detects Pancoast tumor, shoulder trauma
MRI
▪ Detects aneurysm, dissection
474 OSMOSIS.ORG
Chapter 62 Autonomic Diseases
LAB RESULTS ▫ Apraclonidine: upregulation of α1

▪ Vanillylmandelic acid (VMA) level receptors (↑ apraclonidine sensitivity) →
▫ Detects neuroblastoma mydriasis occurs
▫ Hydroxyamphetamine: 1st or 2nd order
neuron lesion → mydriasis occurs
OTHER DIAGNOSTICS (postganglionic fibers undamaged); 3rd
▪ Neurological exam order neuron lesion → weaker/absent
▪ Pharmacological diagnostics mydriasis in affected eye
▫ Disorder detection, lesion level
determination
▫ Cocaine drops: norepinephrine missing TREATMENT
from synaptic cleft → absent mydriasis
▪ Treat the underlying cause if possible
ORTHOSTATIC HYPOTENSION (OH)

osms.it/orthostatic-hypotension

▪ Sudden, sustained systolic blood pressure ▪ Pale skin, vertigo, blurred vision, nausea,
(> 20mmHg)/diastolic blood pressure (> heart palpitations
10mmHg) drop within three minutes upon
standing/ tilting head upright ≥ 60°
▪ Delayed/lowered lower-body DIAGNOSIS
vasoconstriction
▪ Lower-body blood accumulation LAB RESULTS
while seated/supine → lower-body ▪ Measure blood pressure
vasoconstriction delayed upon standing → ▫ Confirm sudden drop
↓ cardiac output → ↓ cerebral perfusion →
dizziness, blurred vision, syncope
OTHER DIAGNOSTICS
▪ Tilt table test
CAUSES ▫ Provokes OH episode
▪ Neuropathy impairs vasoconstriction
▪ Baroreceptor reflex impairment (α1
blockers inhibit vasoconstriction) TREATMENT
▪ Hypovolemia (absolute/relative);
atherosclerosis; diabetes mellitus; MEDICATION
Addison’s disease; Parkinson’s disease; ▪ Corticosteroids
anorexia nervosa; alcohol, THC intoxication; ▪ Antihypotensives
medication (MAOI) ▪ Supplemental measures (caffeine)
▪ Occurs in elderly/postpartum individuals
OTHER INTERVENTIONS
COMPLICATIONS ▪ Increase blood pressure via increased fluid/
▪ Postural orthostatic tachycardia syndrome salt intake
(compensatory mechanism for chronic ↓ ▪ Treating underlying cause
cardiac output), syncope, injury (falling)
OSMOSIS.ORG 475
NOTES
NOTES
BALANCE DISORDERS

▪ Disorders of inner ear (vestibular portion) DIAGNOSTIC IMAGING
→ disequilibrium (balance loss) ▪ CT scan, MRI

▪ Inner ear infections, injuries; genetic ▪ Audiometric test
disorders, others ▪ Neurologic examination
▪ Clinical manifestation
SIGNS & SYMPTOMS
▪ Vertigo TREATMENT
▫ Spinning sensation of oneself/
surroundings MEDICATIONS
▪ Hearing loss, tinnitus ▪ Antibiotics (causitive)
▪ Antihistamines, antiemetics,
anticholinergics (symptomatic)
SURGERY
▪ Causative treatment
OTHER INTERVENTIONS
▪ Vestibular rehabilitation therapy
476 OSMOSIS.ORG
Chapter 63 Balance Disorders
LABYRINTHITIS
osms.it/labyrinthitis

▪ Inner ear (labyrinth) inflation OTHER DIAGNOSTICS
▪ Damage of auditory, vestibular-end organs ▪ Head, neck examination
responsible for hearing, retaining balance ▫ Nystagmus
(rotational, linear-motion sensation) ▪ Neurologic examination
▫ Positive Romberg’s test: inability to
CAUSES maintain postural control
▪ Viral infection (rubella virus, ▫ Abnormal tandem gait: inability to walk
cytomegalovirus, mumps virus) in straight line with one foot in front of
▪ Bacterial infection other (heel-to-toe)
▫ Streptococcus pneumoniae, ▪ Head impulse, Nystagmus, and Test of
Haemophilus influenzae, Neisseria skew (HiNTs) examination
meningitidis; most commonly meningitis/ ▫ Positive head-thrust test: inability to
otitis media complication maintain visual fixation when head
▪ Head injury, stress, allergy, medication turned rapidly toward side of lesion by
examiner
▫ Negative test of skew
RISK FACTORS
▫ Direction-changing nystagmus
▪ Upper respiratory tract infection
▪ Permanent hearing loss
MEDICATIONS
▪ Inflammation
SIGNS & SYMPTOMS ▫ Corticosteroids
▪ Bacterial infection
▪ Severe vertigo (oneself/surroundings seem ▫ Antibiotics
spinning), associated symptoms
▪ Symptomatic treatment
▪ Fatigue, nausea, vomiting
▫ Antihistamines, antiemetics,
▪ Rotational motion signalization impairment anticholinergics
→ nystagmus
▪ Tinnitus, hearing loss
▪ Gait impairment
OTHER INTERVENTIONS
▪ Self-limiting
▫ Recovery in 1–6 weeks
▫ Head, eye movement, postural change,
walking exercise
OSMOSIS.ORG 477
MENIERE'S DISEASE
osms.it/menieres-disease

▪ Idiopathic inner-ear disorder OTHER DIAGNOSTICS
▫ Vertigo, progressive hearing loss ▪ Diagnostic criteria
▫ Two/more unprovoked vertigo episodes
CAUSES (each last > 20 minutes)
▪ Exact cause unknown ▫ Audiometrically-confirmed sensorineural
hearing loss in affected ear on at least
▫ Likely abnormal fluid, ion homeostasis in
one occasion before/during/after vertigo
inner ear (endolymphatic hydrops)
episode
▪ Possibly due to endolymphatic sac/
▫ Tinnitus/fullness feeling in ear
duct blockage, viral infection, vestibular
aqueduct hypoplasia, vascular constriction
TREATMENT
RISK FACTORS
▪ Children MEDICATIONS
▫ Congenital inner-ear malformations ▪ Symptomatic treatment
▪ Family history (10% familial) ▫ Antihistamines, antiemetics,
anticholinergics

▪ Symptoms do not improve
▪ Spontaneous vertigo episodes (last 20
minutes–24 hours), associated symptoms ▫ Surgical decompression of
(fatigue, nausea, vomiting); tinnitus, endolymphatic sac
progressive hearing loss
▪ Less common OTHER INTERVENTIONS
▫ Drop attack (sudden fall with preserved ▪ Sodium restriction, diuretics may alleviate
consciousness) symptoms (unknown efficacy)
478 OSMOSIS.ORG
SCHWANNOMA
osms.it/schwannoma
OTHER DIAGNOSTICS
PATHOLOGY & CAUSES
▪ Neurologic examination
▪ Benign nerve-sheath Schwann cell tumor ▫ Cranial nerve deficit
▪ Involves any peripheral nerve ▪ Audiometry
▫ Most commonly affects head, neck ▫ Confirms sensorineural hearing loss
nerves; vestibular nerve (vestibular
schwannoma)
▪ Associated with neurofibromatosis type II
TREATMENT
(presents with bilateral schwannomas)
SURGERY
▫ Caused by loss-of-function mutation
▪ Excision
in neurofibromin 2 (NF2) gene that
encodes tumor-suppressor protein
merlin (schwannomin) OTHER INTERVENTIONS
RISK FACTORS ▫ Stereotactic radiosurgery, stereotactic
▪ Childhood radiation treatment radiotherapy, proton beam therapy
COMPLICATIONS
▪ Very rarely become malignant
(neurofibrosarcoma degeneration)
▪ Left untreated
▫ Brainstem compression, cerebellar tonsil
herniation, hydrocephalus
SIGNS & SYMPTOMS

▪ Cochlear nerve involvement → hearing Figure 63.1 The histological appearance of a
loss, tinnitus Schwannoma demonstrating characteristic
▪ Vestibular nerve involvement → walking Antoni A and Antoni B areas.
disequilibrium
▪ Trigeminal nerve involvement → facial
paresthesia, hypoesthesia, pain
▪ Facial nerve involvement → facial paresis,
gustatory disturbances; xerophthalmia,
paroxysmal lacrimation, xerostomia
DIAGNOSIS
DIAGNOSTIC IMAGING
MRI Figure 63.2 The gross pathology of an
▪ Mass detection excised schwannoma.
OSMOSIS.ORG 479
VERTIGO
osms.it/vertigo

▪ Sensation that oneself/surroundings are ▪ Peripheral vertigo
spinning ▫ Mild–moderate disequilibrium (dizziness,
▫ Symptom, not disease lightheadedness)
▪ Labyrinth, vestibular nerve, vestibular ▫ Spinning sensation; fatigue, nausea,
centers (in brainstem) damage/dysfunction vomiting; hearing loss, tinnitus, fullness,
ear pain
CAUSES ▪ Central vertigo
▪ Peripheral vertigo ▫ Severe disequilibrium
▫ Calcified otoliths in posterior ▫ Less prominent spinning sensation,
semicircular canal (canalithiasis) → nausea than peripheral vertigo
benign paroxysmal positional vertigo ▫ May be accompanied by neurologic
(most common) deficits, nystagmus
▫ Labyrinthitis, Ménière disease, herpes
zoster oticus
▪ Central vertigo
DIAGNOSIS
▫ Vestibular migraine; brainstem ischemia; DIAGNOSTIC IMAGING
cerebellar infarction, hemorrhage;
multiple sclerosis MRI/CT scan
▪ Suspected central vertigo
▫ Central nervous system abnormalities
MNEMONIC: VOMITS
Causes of vertigo
OTHER INTERVENTIONS
Vestibulitis: labyrinthitis or
vestibular neuronitis Vestibular system function tests
Ototoxic drugs ▪ Differentiate vertigo from other dizziness
Meniere’s disease causes
Injury ▪ Electronystagmography
Tumor ▪ Dix–Hallpike maneuver
Spin: benign paroxysmal ▫ Individual sits, head rotated 45° towards
positional vertigo ear being tested → individual lowered to
supine past bed’s end, extends neck 20°
below horizontal → vertigo, nystagmus
reproduced → test positive
▪ Head-thrust test
▫ Individual fixates on target while head
is rotated quickly → catch-up saccades,
nystagmus → test positive
480 OSMOSIS.ORG
▪ Rotation test
▫ Individual accelerates, decelerates in
TREATMENT
rotating chair → analyze postrotatory
nystagmus → test positive
MEDICATIONS
▪ Vestibular migraines (underlying cause)
▪ Caloric reflex test
▫ Anticonvulsants, beta blockers
▫ Cold/warm water/air irrigation into
external auditory canal ▪ Symptomatic treatment
▫ Antihistamines, antiemetics,
Audiometry anticholinergics, benzodiazepines
▪ Assess hearing loss
OTHER INTERVENTIONS
OSMOSIS.ORG 481
NOTES
NOTES
BRAIN ISCHEMIA

▪ Impaired brain function due to lack of blood DIAGNOSTIC IMAGING
CT scan
TYPES ▪ Visualize trauma, bleeding, skull fracture
Focal ischemia MRI
▪ Occlusion of blood vessel → ↓ perfusion → ▪ Visualize hypointense, hyperintense blood
affected regions damaged clot
▪ ↓ oxygen → ischemic stroke
▪ Blood vessel rupture → hemorrhagic stroke; MR/CT angiography
bleeding inside parenchyma/between brain ▪ Visualize occlusions, aneurysms
membranes
Global ischemia TREATMENT

▪ Cardiac arrest → whole brain
hypoperfusion → brain damage MEDICATIONS
▪ Antiplatelet medications (e.g. aspirin/
CAUSES clopidogrel)
▪ Atherosclerotic plaque/thrombosis/emboli ▪ IV tissue plasminogen activator (tPA)
▪ Hypertension ▪ Mannitol, other osmotic diuretics
▪ Blood vessel malformation ▫ ↑ intracranial pressure treatment
▪ Cardiac arrest, tachycardia, congenital
heart problems SURGERY
▪ Tumors ▪ Evacuation of blood clot
▪ ↑ intracranial pressure treatment
SIGNS & SYMPTOMS

OTHER INTERVENTIONS
▪ Altered consciousness; weakness; ▪ Manage conditions that worsen prognosis
problems with vision, hearing, swallowing; (e.g. hyperglycemia, fever)
dizziness, vertigo
▪ See mnemonic for common symptoms
MNEMONIC: FAST
Common stroke symptoms
Facial drooping
Arm weakness
Speech difficulties
Time: reminder to call
emergency services
482 OSMOSIS.ORG
Chapter 64 Brain Ischemia
EPIDURAL HEMATOMA
osms.it/epidural_hematoma
▫ Spontaneous spinal hematoma (very
PATHOLOGY & CAUSES rare)
▪ Systemic lupus erythematosus
▪ Nervous tissue compression due to
accumulation of blood in epidural space ▫ Vasculitis, associated with immune
system reaction
▪ Head trauma → skull fracture → damage
of blood vessels through dura mater → ▪ Coagulopathies, bleeding diathesis, sickle
extradural blood accumulation → rapid, cell anemia
limited expansion of hematoma due to tight
dura adherence at cranial sutures → brain COMPLICATIONS
tissue compression → neurological decline ▪ ↑ intracranial pressure
▪ Supratentorial herniation → compression of
TYPES arteries → ischemic stroke
▪ Infratentorial herniation → brainstem
Intracranial compression → heart, respiratory arrest
▪ Frontal injuries ▪ Paralysis/sensory loss
▫ Anterior ethmoidal artery ▪ Seizures
▪ Temporoparietal (most common)
▫ Middle meningeal artery
▪ Occipital SIGNS & SYMPTOMS
▫ Transverse, sigmoid sinus
▪ Vertex ▪ Initial loss of consciousness, lucid state
if blood slowly accumulating; delayed
▫ Superior sagittal sinus
neurological deterioration consequence of
Spinal enlarging hematoma compression
▪ Venous plexus of lumbar, thoracic regions ▪ Intracranial epidural hematoma
▫ Broken skull with hematoma
▫ Otorrhea/rhinorrhea
CAUSES
▫ Altered consciousness
▪ Neurosurgical procedures complication
▪ ↑ intracranial pressure
▪ Trauma
▫ Headache
Intracranial epidural hematoma ▫ Nausea with vomiting
▪ Head trauma → pterion skull fracture (most ▫ Cushing reflex (↑ blood pressure, ↓ heart
common) rate, irregular breathing)
▪ Blood vessel malformations ▫ Focal signs (weakness of extremities on
opposite side; dilated pupil on injured
Spinal epidural hematoma side due to compression of CN III)
▪ Trauma (e.g. lumbar puncture/epidural ▪ Spinal epidural hematoma
anesthesia)
▫ Radicular back pain (resembles pain
from herniated discus)
RISK FACTORS ▫ Sensory defects
▪ More common in individuals who are ▫ Urinary, fecal incontinence
biologically male, between 2–60 years
▪ Pregnancy
OSMOSIS.ORG 483
MRI
▪ T2-WI: acutely
▫ Hypointense blood clot due to
deoxyhemoglobin
▪ T1, T2-WI: in following weeks
▫ Deoxy → methemoglobin; hyperintense
blood clot
▪ T1-WI: months later
▫ Methemoglobin → hemosiderin;
hypointense mass
TREATMENT
MEDICATIONS
▪ Mannitol, other osmotic diuretics
▫ ↑ urine excretion, ↓ intracranial pressure
Figure 64.1 A CT scan of the head in the ▪ Anticoagulation reversal
axial plane demonstrating a large epidural ▫ Individuals undergoing surgery, on
hematoma with a classical biconvex shape. anticoagulation therapy
SURGERY
DIAGNOSIS ▪ Craniotomy
▫ Evacuation of blood mass
DIAGNOSTIC IMAGING ▪ Embolization/ligation of damaged blood
vessel
X-ray
▪ Trephination (burr-hole)
▪ Skull fracture
▫ In acute EDH, if neurosurgical procedure
CT scan delayed
▪ Hematoma: typically presents as a ▪ Laminectomy
biconvex, relatively heterogeneous, high ▫ ↓ blood in spinal epidural hematoma
density mass in the space between skull,
brain; does not cross sutures
OTHER INTERVENTIONS
▪ Swirl sign: bleeding into blood clot, diverse
hypoattenuated foci ▪ Observation, nonoperative management
▪ Assess hematoma volume ▫ Awake, conscious individuals
▪ Skull fracture ▫ If hematoma volume < 30cm3, thickness
< 15mm, midline shift < 5mm
484 OSMOSIS.ORG
INTRACEREBRAL HEMORRHAGE
osms.it/intracerebral-hemorrhage
▪ Posttraumatic
PATHOLOGY & CAUSES ▪ Coagulopathies
▪ Condition characterized by blood vessels ▪ Sickle cell disease
rupture → intraparenchymal blood
accumulation RISK FACTORS
▪ Blood vessel trauma, rupture → creates ▪ Individuals who are biologically male of
pool of blood → tissue, surrounding Asian descent
blood vessel compression → hypoxia in ▪ Black individuals who are biologically male
downstream tissue → damage due to of African descent
compression, oxygen lack
▪ Heavy alcohol use; amphetamines, cocaine
abuse, antithrombotic medications; ↓
CAUSES LDL, cholesterol, triglycerides; previous
cerebrovascular insult
Hypertension
▪ Most common
COMPLICATIONS
▪ Leads to
▪ Hemorrhage enlargement
▫ Atherosclerosis in large arteries
▫ In hemorrhage border
▫ Hyaline arteriolosclerosis → focal
▫ Poor prognosis
arterioles necrosis → small wall ruptures
→ subclinical microbleeds ▪ Intraventricular, subarachnoid expansion
▫ Charcot–Bouchard aneurysms ▪ Hydrocephalus
(microaneurysms)
▪ Basal ganglia; thalamus; midbrain; pons;
cerebellum primarily affected
SIGNS & SYMPTOMS
Vascular abnormalities ▪ Begin slowly, worsen gradually
▪ Cerebral amyloid angiopathy ▪ Enlargement of hematoma within few
▫ Deposition of amyloid in blood vessel hours, ↑ intracranial pressure
walls → vessels more prone to rupture ▫ Altered consciousness, headache,
▫ Lobar localization: parietal, occipital nausea, vomiting, unequal pupil size
lobes ▪ Fever
▫ Blood vessels: leptomeningeal, cerebral
Area of brain affected
cortical arterioles
▪ Anterior/middle cerebral artery: numbness,
▪ Arteriovenous malformations
sudden muscle weakness
▫ Usually affect children
▪ Posterior cerebral artery: impaired vision
▪ Aneurysm, vasculitis, vascular tumours (e.g.
▪ Broca’s area: slurred speech
hemangioma)
▪ Wernicke’s area: difficulty understanding
Other causes speech
▪ Secondary to ischemic stroke
Focal neurological signs
▫ Blood flow blockage → reperfusion
▪ Basal ganglia manifestation: loss of
→ ↑ chance of blood vessel rupture →
contralateral sensory, motor functions;
bleeding into dead tissue (hemorrhagic
homonymous hemianopsia
conversion)
▪ Thalamus: contralateral loss of
OSMOSIS.ORG 485
sensory, motor functions; homonymous MR angiography
hemianopsia; aphasia if dominant/neglect if ▪ Vasculitis, arteriovenous malformations,
nondominant; narrowed pupils unreactive other blood vessel pathology
to light
▪ Lobar manifestation: homonymous
hemianopsia; if frontal region, contralateral
LAB RESULTS
leg plegia/paresis; seizures ▪ Prothrombin time (PT), activated partial
thromboplastin time (aPTT), platelet count
▪ Pons: coma within few minutes of
hemorrhage; quadriplegia, miosis/deafness; ▫ If cause for bleeding diathesis unclear
speaking difficulties when awake
▪ Cerebellum: ataxia; same side face
weakness; loss of face, body sensory
TREATMENT
function; occipital headache, neck stiffness
MEDICATIONS
▪ Vitamin K, unactivated prothrombin
DIAGNOSIS ▫ With anticoagulant usage
▪ Protamine sulfate
DIAGNOSTIC IMAGING ▫ For heparin users
▪ Antipyretics
CT scan
▫ Fever reduction
▪ Hyperdense blood mass acutely; isodense,
ring enhancement appearance in ▪ Osmotic diuretics (e.g. mannitol)
subsequent weeks; hypodense chronically ▫ Regulation of ↑ ICP
▪ Trauma ▪ Saline
▫ Multifocal bleedings ▫ Fluid replacement
▪ Coagulum retracts, edema develops ▪ Nicardipine/nitroprusside/enalapril/
▫ Confused with hemorrhagic infarction nitroglycerin
▫ Hypertension
CT angiography ▪ Phenytoin/levetiracetam
▪ Spot sign: unifocal/multifocal enhancement ▫ Seizures
of contrast; ↑ risk of hematoma expansion
MRI (T2-WI) SURGERY

▪ Hyperacute (first 24 hours) ▪ Ventriculostomy
▫ Hyperintense center of mass ▫ Regulation of ↑ intracranial pressure
▫ Hypointense periphery, border ▪ If hemorrhage > 3cm/1.2in/lobar of young
▪ Subacute persons/brainstem compression
▫ Hypointense in > three days: ▫ Craniotomy with clot removal
intracellular methemoglobin ▫ Stereotactic aspiration
▫ Hyperintense in > seven days: ▫ Endoscopic evacuation
lysis of red blood cells; extracellular
methemoglobin
▫ Chronic: hypointense; after two weeks
486 OSMOSIS.ORG

axial plane demonstrating a right-sided,
periventricular, intracerebral hemorrhage.
ISCHEMIC STROKE
osms.it/ischemic-stroke
few minutes of stroke
PATHOLOGY & CAUSES ▫ Blood flow < 10ml/100g tissue/minute
▪ Decreased blood supply in specific brain ▪ Ischemic penumbra
area due to blood vessel obstruction → ▫ Periphery of affected region preserved
hypoperfusion, tissue hypoxia, infarction due to collateral circulation; chance of
▪ ↓ blood flow → lack of oxygen, glucose in survival if blood restored quickly
brain → ↓ adenosine triphosphate (ATP) ▫ Blood flow < 25ml/100g tissue/minute
production, electrochemical gradient → cell ▫ Infarction zone spreads if blood supply
death not restored quickly
Two mechanisms of cell death

▪ Sodium buildup: water follows sodium →
TYPES
cell swelling, death Five subtypes (TOAST classification)
▪ Calcium buildup: creates oxygen radicals ▪ Large artery atherosclerosis
→ damages mitochondrial, lysosomal
▪ Small artery strokes
lipid membrane → seeping of degradative
enzymes, apoptosis-inducing factors → cell ▪ Cardioembolic infarction
death ▫ Formation of emboli in heart → lodging
in brain arteries
Two zones ▪ Other determined pathology
▪ Ischemic core ▪ Undetermined pathology
▫ Brain tissue dies from ischemia within
OSMOSIS.ORG 487
CAUSES Moyamoya disease
▪ Progressive stenosis of cerebral arteries →
Thrombosis
ischemia
▪ May lead to obstruction inside blood vessel
▪ Narrowing of blood vessel due to Dissection of artery wall
atherosclerotic plaque → gradual ↓ blood
flow RISK FACTORS
▪ Damage to atherosclerotic fibrous cap ▪ Age (esp. > 55)
→ platelet, clotting cascade activation →
thrombus formation with sudden stop of
biologically male
blood flow
▪ More common in black individuals of
Embolism African descent
▪ Four classes based on emboli origin ▪ Migraine headaches with aura
▫ Cardiac emboli: atrial fibrillation, ▪ Genetics; specific gene loci associated with
rheumatic valve disease, infective stroke subtypes
endocarditis, dilated cardiomyopathies, ▫ ABO loci: all subtypes
left atrial myxoma ▫ HDAC9: large vessel stroke
▫ Possible cardiac/aortic emboli: ▫ PITX2, ZFHX3: cardioembolic stroke
calcification of mitral valve annulus,
▪ Hematologic disorders
patent foramen ovale, atheroma in
ascending/arch of aorta, atrial septal ▫ Multiple myeloma, sickle cell disease,
aneurysm polycythemia vera; esp. in younger
individuals
▫ Arterial emboli: detachment of blood
clot (e.g. atherosclerotic plaque in bigger ▪ Hypertension, diabetes mellitus,
upstream artery) → emboli travels heart diseases, dyslipidemia,
through blood → lodges in smaller hyperhomocysteinemia, smoking, physical
downstream artery inactivity, cocaine abuse
▫ Cryptogenic: unknown origin of emboli
COMPLICATIONS
Lacunar infarct ▪ Blood reaches infarcted regions through
▪ Affects small blood vessels of distal collateral blood vessel/dissolution of
vertebral, basilar artery, middle cerebral occlusive embolus/thrombus; first week
artery, circle of Willis
▫ Lipohyalinosis: buildup of hyaline in Hemorrhagic transformation
arterioles wall → hypertrophy of tunica ▪ Ischemia → impaired cellular, metabolic
media → progressive narrowing of functions of affected region; ↑ permeability
arterioles until blood flow stops of damaged blood vessels → resolved
▫ Microatheromatoma: narrowing of cause of ischemia → restored blood flow →
blood vessel due to debris accumulation blood extravasation
within wall ▪ Gray matter more commonly affected;
large number of collateral vessels worsen
Hypoperfusion reperfusion injury
▪ Lack of blood reaching brain due heart ▪ Massive cerebral infarction; hyperglycemia;
failure, ↓ cardiac output ↓ cholesterol, LDL, IV recombinant tissue
▪ Most vulnerable plasminogen activator (rtPA): higher risk of
▫ Spaces between supply of two arteries hemorrhagic transformation
(watershed regions)
Cerebral edema
Inflammation of blood vessel wall ▪ ↑ intracranial pressure with possible
▪ E.g. Takayasu/giant cell arteritis herniation
▫ Cytotoxic: defective ATP pump, swelling
of brain cellular elements due to water
488 OSMOSIS.ORG
accumulation difficulties; facial weakness; hand

▫ Vasogenic: ↑ permeability of blood-brain weakness, clumsiness (clumsy hand
barrier → ↑ extracellular fluid volume syndrome)
due to ↑ passing of proteins, other
macromolecules Anterior cerebral artery
▪ Contralateral hemiparesis (esp. leg, face),
Liquefactive necrosis sensory deficit; inability to understand,
▪ First 48 hours: edema, paleness of affected produce speech (left hemisphere); impaired
region judgment; incontinency
▪ 2–10 days: affected area gelatinous;
Middle cerebral artery
noticeable border between healthy,
damaged tissue ▪ Contralateral paresis (esp. face, arm),
sensory deficit; inability to understand,
▪ 3–21 days: liquefaction of tissue; fluid-filled
produce speech (left hemisphere);
cavity
hemispatial neglect (right hemisphere);
Seizures homonymous hemianopsia; deviation of
eye to damaged side
▪ Brain injury → ↑ irritability of nervous tissue
with neuronal discharges Posterior cerebellar artery
Deep vein thrombosis ▪ Homonymous hemianopsia
▪ Esp. immobilized individuals ▪ Cortical blindness (bilateral lesion)
▪ Midbrain
Pneumonia ▫ Oculomotor, trochlear palsy → dilated
▪ Swallowing mechanism impairment → pupil
aspiration pneumonia ▪ Thalamus
▪ Intubation/ventilatory support → ↑ risk for ▫ Sensory loss, impaired memory, altered
pneumonia consciousness
Dysphagia ▪ Posterior cerebellar artery syndrome (PICA)
▪ Due to damage of cortex, subcortical ▫ AKA “Wallenberg” syndrome
structures responsible for swallowing ▫ Dizziness, nystagmus; speech,
swallowing difficulties
Dementia ▫ Ipsilateral: facial sensory loss, Horner’s
▪ Altered memory, cognition, behavior due to sign, ataxia
brain damage ▫ Contralateral: loss of pain, temperature
sensation in limbs
SIGNS & SYMPTOMS Basilar, vertebral arteries

▪ Dizziness; gait, vision disorders; dysarthria,
Thrombosis dysphagia
▪ Neurological defects ▪ Locked-in syndrome
▫ Thrombosis/embolism of basilar artery
Embolism
▫ Plegia of head, body muscles, except
▪ Sudden start of symptoms; maximum
eye; only blinking, vertical eye
defects
movement possible
Lacunar stroke
▪ Contralateral, mostly motor/sensory
defects; four syndromes
DIAGNOSIS
▫ Pure motor stroke: internal capsule
DIAGNOSTIC IMAGING
lesion
▪ If applicable
▫ Pure sensory stroke: thalamus lesion
▫ Ataxic hemiparesis Noncontrast CT scan
▫ Dysarthria: speech, swallowing ▪ First few hours
OSMOSIS.ORG 489
▫ Affected tissue appears normal
▪ Later
▫ Loss of differentiation between white,
grey matter
▫ Hypodense parenchyma with sulcal
effacement
▫ Loss of insular ribbon sign
CT perfusion
▪ Detection of core, ischemic penumbra
CT angiography
▪ Find thrombus, embolus in blood vessel/
intra-arterial thrombolysis
MRI
▪ T1, T2 weighted imaging (see table)
▪ Diffusion-weighted imaging
▫ Shows ischemic stroke early;
differentiation from acute, chronic
▪ Fluid-attenuated inversion recovery (FLAIR) axial plane demonstrating a large ischemic
sequence stroke in territory of the middle cerebral
▫ Hyperintense signal within 12 hours artery. The scan was performed three days
after the onset of symptoms.
Transcranial Doppler ultrasound
▪ Visualization of occlusion in middle cerebral
artery/intracranial carotid/vertebrobasilar
artery TREATMENT
Conventional angiography MEDICATIONS
▪ Visualize occlusion; for confirmation of CTA, ▪ Establishment of blood flow in ischemic
MRA findings penumbra
▫ Thrombolytic enzymes: rtPA;
LAB RESULTS alteplase given within 4.5 hours; after
▪ Blood tests hemorrhagic stroke ruled out
▫ ↑ cardiac markers in heart disease ▫ Antiplatelet therapy: aspirin (325mg
▫ ↑ erythrocytes in polycythemia vera orally within 48 hours); other drugs (e.g.
clopidogrel/aggrenox)
▫ Toxicology screening (individual
suspected of sympathomimetics abuse) ▪ Hypertension treatment
▫ ↑ blood glucose level ▫ IV labetalol/nicardipine: only if systolic
pressure > 220, diastolic > 120
mmHg; except in individuals with vital
OTHER DIAGNOSTICS indications for lowering blood pressure
▪ Symptoms, neurological changes scoring (acute myocardial infarction, kidney
▪ Based on National Institute of Health stroke failure, dissection of aorta)
scale (NIHSS) ▪ Cerebral edema management
▫ Antipyretic: if temperature ≥ 40°C/
ECG 100.4ºF
▪ Detection of myocardial ischemia/atrial ▫ IV insulin: hyperglycemia; keep glucose
fibrillation between 140–180 mg/dl (7.8–10
mmol/L)
490 OSMOSIS.ORG
▪ Prevention OTHER INTERVENTIONS

▫ Anticoagulant medications: emboli ▪ Cerebral edema management
prevention (e.g. warfarin, aspirin) ▫ Hyperbaric oxygen therapy: ↑ pure
oxygen supply in damaged regions
SURGERY ▫ Fluid management: isotonic saline
▪ Establishment of blood flow in ischemic without dextrose
penumbra ▪ Protection of airwaves, prevention of
▫ Mechanical embolus removal in cerebral aspiration
ischemia (MERCI) retriever ▫ Head elevation by 30%, nothing by
▫ Penumbra system (aspiration, mouth/nil per os (NPO) status
extraction) ▪ Prevention
▫ Solitaire revascularization device, Trevo ▫ Control risk factors (for atherosclerosis):
(stent-retriever systems) e.g. smoking, hypertension, diabetes,
▪ Cerebral edema management aspirin use; carotid endarterectomy
▫ Craniectomy ▫ Lifestyle alteration: exercising,
appropriate diet
PSYCHOTHERAPY
▪ If applicable
▪ Type of psychotherapy (e.g. group
therapy, exposure therapy) with goal of
psychotherapy
OSMOSIS.ORG 491
SACCULAR ANEURYSM
osms.it/saccular-aneurysm
disease (ADPKD), bacterial endocarditis,
PATHOLOGY & CAUSES fibromuscular dysplasia
▪ Familial predisposition; smoking; alcohol,
▪ Asymmetrical ballooning of blood vessel cocaine use; hypertension; trauma
wall
▪ Bifurcation of arteries common place esp.
on circle of Willis due to weakness of wall, COMPLICATIONS
turbulent blood flow ▪ Warning leaks
▫ Anterior communicating (most ▫ May precede aneurysm rupture; strong
common); posterior communicating; headaches, photophobia, nausea/
middle cerebral; internal carotid; basilar vomiting
artery tip ▪ Rupture → subarachnoid hemorrhage
▫ Apex of aneurysm/atheromatous plaque
TYPES edge
▫ ↑ risk in smokers, individuals with
Type A migraines, elderly, affection of posterior
▪ Blood vessel wall with endothelium, linear circulation, larger size
smooth muscle ▪ Ischemia
▫ Thrombus forms within aneurysm →
Type B
detachment of small particles (emboli)
▪ Disorganization of smooth muscle, → emboli lodges → ischemia of
thickening of wall downstream tissue
Type C ▪ Multiple aneurysms
▪ Hypocellular wall with thickening of intima/
luminal thrombosis
SIGNS & SYMPTOMS
Type D
▪ Hypocellular wall coated with thin ▪ May be asymptomatic if small
thrombosis layer ▪ Mass effect symptoms due to size
▫ Anterior communicating artery: both leg
CAUSES weakness with positive Babinski sign
▪ Inborn defect of arteries, lack of external ▫ Posterior communicating, internal
lamina, tunica media → hemodynamic carotid artery: headaches with palsy of
stress over years → gradual ballooning oculomotor nerve
of blood vessel wall, thickening of intima, ▫ Left middle cerebral artery: inability to
adventitia understand, produce speech
▫ Right middle cerebral artery:
contralateral field vision loss
RISK FACTORS
biologically female, > 50 years (due to
estrogen deficiency)
▪ Diseases associated with aneurysm
▫ Ehler–Danlos syndrome,
pseudoxanthoma elasticum, lupus,
autosomal dominant polycystic kidney
492 OSMOSIS.ORG
DIAGNOSIS TREATMENT
▪ Endovascular management
CT/MR angiography
▫ Aneurysmal coiling with thrombosis →
▪ Detect aneurysms > 2mm
endothelialization across aneurysm neck
→ prevents rebleeding, regrowth
▫ In development: stent-assisted, balloon-
assisted coiling; disruptors, flow
diverters
▪ Surgical clipping
OTHER INTERVENTIONS
▪ Regular monitoring with CTA/MRA
▪ Avoid smoking, alcohol, drugs, excessive
strain
SUBARACHNOID HEMORRHAGE
(SAH)
osms.it/subarachnoid-hemorrhage
▪ Smoking; hypertension; alcohol, cocaine
PATHOLOGY & CAUSES abuse
▪ Diseases associated with saccular
▪ Bleeding into space between pia mater,
aneurysm (e.g. blood vessel disorders,
arachnoid membrane
Ehlers–Danlos syndrome, Marfan
▪ Injury/spontaneous event → rupture of syndrome, polycystic kidney disease)
blood vessel in subarachnoid space →
▪ Sickle cell disease
release of blood into cerebrospinal fluid
(CSF) → rapid ↑ intracranial pressure ▪ Coagulopathies
▪ Traumatic: head injury (e.g. bridging vein ▪ Vasospasm
tear) ▫ Delayed ischemia; 4–11 days after SAH
▪ Spontaneous: arterial origin (more ▫ Blood clot lysis → release of
common) spasmogenic substances (e.g.
▫ Rupture of saccular “berry” aneurysms endothelin), ↓ production of nitric oxide
(e.g. anterior half of circle of Willis) → vasospasm due to smooth muscle
contraction → brain ischemia
▫ Arteriovenous blood vessel
malformations ▪ Hydrocephalus
▫ Clogging of CSF drainage
▪ Rebleeding
RISK FACTORS
▫ May occur two weeks after SAH
biologically female, elderly ▫ ↑ tendency in individuals with
OSMOSIS.ORG 493
hypertension, anxiety, seizures post- ▫ ↑ intracranial pressure → abducens
SAH nerve paralysis → eye pointing out →
▫ Associated with ↑ mortality, neurological diplopia
damage
▪ Sympathetic hyperactivity due to ↑
intracranial pressure, SAH (“sympathetic DIAGNOSIS
surge”) → sudden, life-threatening ↑ of
blood pressure due to vasoconstriction DIAGNOSTIC IMAGING
▪ ↑ plasma adrenaline levels due to Noncontrast CT scan
sympathetic hyperactivity → arrhythmias
▪ Fisher scale grading
▪ Over-action of sympathetic nervous
▫ Group 1: no hemorrhage
system → pulmonary vasoconstriction
→ ↑ capillary permeability, pressure → ▫ Group 2: blood depositions < 1mm,
neurogenic pulmonary edema without blood clots
▪ Hyponatremia ▫ Group 3: blood depositions > 1mm, with
localized clots
▪ Meningitis (irritation from presence of
blood) ▫ Group 4: diffuse/lack of subarachnoid
hemorrhage with extension to
▪ Seizures
ventricles, brain parenchyma
▪ Hydrocephalus
SIGNS & SYMPTOMS ▫ “Mickey Mouse” ventricular system
appearance
▪ Area of brain
MRI
▫ Anterior/middle cerebral artery:
▪ Visualize arteriovenous malformations (not
numbness, sudden muscle weakness
detected by angiography)
▫ Broca’s area: slurred speech
▫ Wernicke’s area: difficulty Digital-subtraction cerebral/CT/MR angiog-
understanding speech raphy
▪ ↑ intracranial pressure ▪ Visualize aneurysm
▫ Thunderclap headache: “worst ever”
headache; may be only symptom LAB RESULTS
▫ Nausea, vomiting ▪ Identify hematologic abnormalities
▪ Altered consciousness; coma, confusion, ▪ PT, aPTT: identify coagulopathies
seizures ▪ ↑ troponin, if heart abnormalities present
▪ Meningeal irritation: bleeding into
subarachnoid space filled with CSF →
blood degradation → irritation of meninges, OTHER DIAGNOSTICS
development of aseptic meningitis ▪ Lumbar puncture
▫ Neck pain, stiffness ▫ ↑ erythrocytes in all three samples
▫ Positive meningeal signs: Kernig’s (pain ▫ CSF centrifugation: yellow coloration
generated by knee extension from 90º); due to erythrocytes breakage, release
Brudzinski’s (forced neck flexion → of heme (“xanthochromia”); positive 3–4
spontaneous knee, hip flexion) weeks after SAH
▫ Photophobia ▪ Physical examination
▪ Focal neurological signs ▫ Characteristic neurological presentation;
▫ Posterior communicating artery fever; tachycardia; fundoscopy (optic
aneurysm rupture/brain herniation due disc swelling, retinal hemorrhages)
to ↑ intracranial pressure → oculomotor
ECG
nerve paralysis → ipsilateral ptosis; eye
pointed down, out; mydriasis, loss of ▪ ↑ QRS, QT intervals; ↓ PR intervals; U
pupillary light reflex waves; dysrhythmias
494 OSMOSIS.ORG
TREATMENT
MEDICATIONS
▪ Antihypertensive therapy: beta-blockers;
hydralazine, calcium channel blockers; ACE
inhibitors
▪ Intracranial pressure treatment: osmotic,
loop diuretics
▪ Prior all procedures: IV midazolam (initial
treatment)
▪ Vasoconstriction treatment: calcium
channel blocker (e.g. nimodipine),
recombinant tissue plasminogen activator
▪ Seizure treatment: phenytoin/phenobarbital
Figure 64.4 A CT scan of thea head in the
▪ Pulmonary edema treatment: diuretics, sagittal plane demonstrating high signal in
dobutamine the sulci of the frontal lobe, consistent with a
subarachnoid hemorrhage.
SURGERY
▪ Aneurysm treatment: endovascular coiling
(with aneurysm obliteration), craniotomy
(with aneurysm neck clipping, coiling)
▪ Vasoconstriction: aspiration/irrigation of
blood clot during clipping process, CSF
drainage, transluminal balloon angioplasty
▪ Hydrocephalus: temporary/serial lumbar
puncture for CSF drainage, permanent
ventricular shunt, ventriculostomy
OTHER INTERVENTIONS
▪ Vital sign stabilization
▪ Intubation if comatose, heart monitoring
(initial treatment)
▪ Keep blood pressure < 140mmHg to avoid
rebleeding
OSMOSIS.ORG 495
SUBDURAL HEMATOMA (SDH)
osms.it/subdural-hematoma
PATHOLOGY & CAUSES of brain on surrounding structures →

bridging veins tear
▪ Shaken baby syndrome
▪ Intracranial bleeding with blood
accumulation between dura mater, ▪ Spontaneous
arachnoid membrane ▫ Vascular malformations
▪ Head trauma → tearing of venous ▪ Neurosurgical procedure complication
blood vessels/small cortical arteries →
blood accumulation → limited blood RISK FACTORS
mass expansion due to adherent dural
▪ Brain atrophy elderly
attachments → brain tissue compression
▫ ↑ bridging veins stretch
▪ Infants, alcohol abusers
TYPES
▫ Thinner wall of bridging veins
Acute ▪ Epilepsy, anticoagulant drugs,
▪ Slow blood outflow into subdural space thrombocytopenia
due to low pressure in bridging veins
Subacute
COMPLICATIONS
▪ Liquefaction of granulation tissue in chronic
▪ Combination of fluid, clotted blood
subdural hematoma (subdural hygroma)
Chronic → ↑ protein → expansion of mass due to
▪ Caused by minor trauma/inflammation water drawn by osmotic pressure → mass
effect brain injuries
▪ More common in elderly
▪ ↑ intracranial pressure → supratentorial,
▪ Head trauma with small bleeding, dural
infratentorial herniation of brain
border cell damage → inflammation,
unsuccessful attempt to repair border ▪ Progressive dementia in chronic subdural
cells with formation of granulation hematoma
tissue → encapsulation; development
of blood vessels within new membrane
→ erythrocytes, plasma exudation from
SIGNS & SYMPTOMS
leaky capillaries to encapsulated space →
recurrent bleeding with expansion ▪ Loss of consciousness after trauma/in
ensuing days due to hematoma expansion
▪ Bleeding characteristics
CAUSES
▫ Hemispheric: most common
▪ Head trauma (most common)
▫ Interhemispheric: altered consciousness,
▪ Acceleration-deceleration (coup- headache, hemiparesis
contrecoup injury)
▪ Physical examination
▪ cceleration of body → sudden stop with
▫ Broken basilar skull: periorbital
forwarding momentum carrying brain →
ecchymosis (raccoon eyes),
impacts front of skull → backward brain
retroauricular ecchymosis (Battle’s sign)
movement → impacts back of skull →
bridging veins tear ▫ CSF rhinorrhea/otorrhea
▪ Intracranial hypotension ▪ Acute subdural hematoma
▫ ↓ CSF due to lumbar puncture/ ▫ Neurological presentation in 48–72
lumboperitoneal shunt → ↑ traction hours
496 OSMOSIS.ORG
▫ May be comatose/awake
▫ Sudden, severe headache with nausea,
vomiting; unequal pupils; difficulties in
speech, swallowing; palsies of cranial
nerves
▪ Subacute
▫ Presents 2–14 days
▪ Chronic
▫ Present 14 days after injury
▫ Impaired cognitive skills, altered
consciousness, headaches, contralateral/
ipsilateral hemiparesis (depends on
hematoma location), hemianopsia, optic
disc swelling
DIAGNOSIS
DIAGNOSTIC IMAGING
CT scan
▪ Acute: crescent-shape hyperdense blood
demonstrating a large, right-sided, subdural
collection
hematoma. The hematoma has a classical
▪ Subacute/chronic: isodense/hypodense crescentic shape.
crescentic mass
MRI
TREATMENT
▪ T2-WI (acutely): hypointense blood clot
due to deoxyhemoglobin
MEDICATIONS
▪ T1, T2-WI (in following weeks): bright
▪ Diuretics
appearance; deoxy → methemoglobin
▫ ↓ intracranial pressure
▪ T1-WI (months later): hypointense clot due
to hemosiderin remains ▪ Vitamin K/factor VIII inhibitor activity
bypassing agent (FEIBA)/frozen plasma
MR/CT angiography ▫ Anticoagulation reverse; ↓ risk of
▪ Spontaneous SDH hematoma enlargement; individuals
undergoing surgery
SURGERY
▪ If clot thickness > 10mm, midline shift >
5mm, intracranial pressure > 20mmHg
▫ Burr hole, craniotomy, decompressive
craniectomy, blood vessel ligation
OTHER INTERVENTIONS
▪ Nonsurgical treatment based on Glasgow
coma score (GCS); clot thickness (<
10mm); neurological examination; stable/
deteriorated condition; comorbidities,
associated injuries; age
OSMOSIS.ORG 497
TRANSIENT ISCHEMIC ATTACK
(TIA)
osms.it/transient-ischemic-attack
▫ If nondominant hemisphere affected
PATHOLOGY & CAUSES ▪ Distal vertebral artery
▪ Short-lasting neurological dysfunction ▫ Dizziness, difficulty speaking, double
due to transient focal ischemia, without vision
infarction ▪ Mid-basilar artery
▪ Blood vessel occlusion/stenosis → ↓ blood ▫ Dizziness, paresis affecting both legs/
flow in affected region → neurological arms
dysfunction
Embolic TIA (> one hour)
▪ Anterior cerebral circulation
CAUSES ▫ Symptoms depend on blood vessel
▪ Adults: thrombosis, hypoperfusion, emboli lodged
▪ Children: congenital heart defects with ▫ Middle cerebral artery: contralateral
thrombosis, coagulopathies, idiopathic hemiplegia; aphasia if dominant
progressive arteriopathy of childhood hemisphere; hemispatial neglect if
(Moyamoya disease) nondominant
▫ Branches of middle cerebral artery:
RISK FACTORS numbness/motor function loss; face,
▪ More common in black individuals of arm, leg
African descent who are biologically male; ↑ ▫ Ophthalmic artery: amaurosis fugax;
risk with age transient monocular/binocular vision loss
▪ Family history, hypertension, diabetes, ▪ Posterior cerebral circulation
obesity, obstructive sleep apnea, ↑ low- ▫ Dizziness, focal hearing loss, speech
density lipoprotein (LDL), ↓ high-density difficulties, double vision, hemi/
lipoprotein (HDL), atherosclerosis, cocaine quadrantanopia, face/body numbness
abuse, smoking ▫ Basilar artery: thalamus, subthalamus,
medial midbrain, reticular activating
COMPLICATIONS system → stupor/coma
▪ Recurrent TIA
▪ Ischemic stroke DIAGNOSIS
DIAGNOSTIC IMAGING
SIGNS & SYMPTOMS
CT/MR/conventional catheter angiography
▪ Duration: few minutes to one hour ▪ Occlusion within blood vessel
↓ flow in large arteries (few minutes) Diffusion-weighted MRI
▪ Numbness/paresis ▪ Ischemic regions corresponding to
▫ Face, cheek, tongue, arm, hand, leg neurologic symptomatology
▪ Aphasia ▪ Changes seen within first few hours of
▫ If dominant hemisphere affected symptoms
▪ Hemispatial neglect
498 OSMOSIS.ORG
Perfusion-weighted MRI
▪ ↓ tissue blood flow
TREATMENT
Neck Doppler ultrasound MEDICATIONS
▪ Evaluate carotid stenosis ▪ Antiplatelet (noncardioembolic TIA)
▫ Aspirin/extended-release dipyridamole/
aspirin + clopidogrel
LAB RESULTS
▪ Anticoagulation
▪ Hypoglycemia, hyponatremia,
thrombocytosis: rule out conditions that ▫ Atrial fibrillation: low-molecular-weight
mimic TIA heparin
▫ Heart thrombus: in acute myocardial
infarction/rheumatic mitral valve;
OTHER DIAGNOSTICS warfarin + direct acting oral
▪ See mnemonic anticoagulants (e.g. apixaban)
▫ ABCD2 score: evaluate risk for possible ▪ Diuretics, angiotensin-converting enzyme
ischemic stroke (can occur two days (ACE) inhibitors
after TIA) ▫ Blood pressure control
▪ Statins
MNEMONIC: ABCD2 ▫ Cholesterol management
Evaluating ischemic stroke
risk SURGERY
Age ▪ Same side carotid stenosis/TIA
Blood pressure ▫ Carotid endarterectomy
Clinical features
Duration of symptoms OTHER INTERVENTIONS
Diabetes ▪ Mediterranean diet
OSMOSIS.ORG 499
NOTES
NOTES
CEREBRAL CORTEX NERVOUS
SYSTEM INFECTIONS

▪ Infection, inflammatory disorders of central DIAGNOSTIC IMAGING
nervous system (CNS), surrounding tissues
Brain CT scan/MRI
▪ With contrast: bright ring with dark
CAUSES center indicates brain abscess; underlying
▪ Bacteria (most common), viruses, fungi, sinusitis, thickening of superior ophthalmic
parasites, prions, aberrant immune vein, irregular filling defects indicate
responses, reactions to medications cavernous sinus thrombosis; fluid
collections in epidural space indicate
RISK FACTORS epidural abscesses
▪ Immunocompromised individuals (e.g. HIV, ▪ Focal/diffuse diffusion-restriction, cerebellar
diabetes, chemotherapy, corticosteroid use) atrophy indicates Creutzfeldt–Jakob disease
(CJD)

▪ Lumbar puncture (if not contraindicated)
▪ Fever
▫ Culture, biochemical analysis of fluid
▪ Headache
▪ Blood cultures
▪ Focal neurological symptoms
▪ Altered level of consciousness
TREATMENT
MEDICATIONS
▪ Empiric antibiotic therapy followed by
targeted therapy once cause identified
▪ Corticosteroids to manage inflammation/
cerebral edema
500 OSMOSIS.ORG
Chapter 65 Cerebral Cortex Nervous System Infections
BRAIN ABSCESS
osms.it/brain-abscess

▪ Localized focal necrosis of brain tissue with ▪ Classic triad (20% of cases)
inflammation, usually caused by bacterial ▫ Fever, progressively worsening focal
infection neurology, headache
▪ Rare (de novo within brain; primary ▫ Increased intracranial pressure (ICP)
infection typically arises elsewhere, spreads while supine → worse headache
to brain) early morning, at night/increased ICP
stimulates medullary center, area
Sources of infection postrema → morning vomiting
▪ Direct implantation ▪ Mental status change, seizures, nausea,
▫ Traumatic inoculation (e.g. head trauma vomiting, papilledema
→ skull fracture with broken skin →
bacterial contamination)
▫ Iatrogenic: contamination through DIAGNOSIS
invasive procedures
▪ Local extension from adjacent foci of DIAGNOSTIC IMAGING
infection
MRI/CT scan with contrast
▫ Ear infection, dental abscess, paranasal
sinusitis, mastoiditis, epidural abscess ▪ Initial immature lesions without capsule:
difficult to distinguish from space-
▪ Hematogenous spread
occupying lesions/infarcts
▫ Distant sources of infection (e.g. organ
▪ 4–5 days after initial infection: formation
infection)
of capsule around necrotic focus → ring-
▫ Congenital heart disease with right-to- enhancing appearance
left shunt → loss of pulmonary filtration
▫ Intravenous contrast material cannot
of microorganisms → abscesses in
pass through capsule → accumulation
distribution of middle cerebral artery
around lesion → bright ring with dark
▪ Common causative bacterial organisms center
(abscesses often polymicrobial)
▫ Staphylococcus aureus, Streptococcus,
Bacteroides, Enterobacteriaceae, LAB RESULTS
Pseudomonas ▪ Lumbar puncture
▪ Immunocompromised hosts may develop ▫ If intracranial pressure not significantly
viral/fungal abscesses, commonly raised
caused by poliovirus, Toxoplasma gondii, ▫ ↑ white cell count, ↑ protein
Cryptococcus neoformans concentration, normal glucose content
▪ Abscess aspirate
RISK FACTORS ▫ Sample obtained via imaging-guided
▪ Right-to-left cardiac shunts, bronchiectasis, aspirate/during surgical drainage;
immunosuppression culture of causative organism → specific
treatment
COMPLICATIONS
▪ Ischemia/necrosis of pituitary → pituitary
insufficiency → Addisonian crisis
OSMOSIS.ORG 501
TREATMENT
MEDICATIONS
▪ Targeted antibiotic therapy
▫ Penetration through abscess wall
poor, typically accompanies surgical
management
▪ Hyperbaric oxygen therapy
▫ Reduces intracranial pressure,
bacteriostatic, enhances oxidative
immune function
▪ Corticosteroids in complicated cases with
pituitary insufficiency
SURGERY Figure 65.1 A CT scan of the head in the

▪ Drainage axial plane demonstrating a abscess in the
left frontal lobe. This example developed five
▪ Removal of any foreign material
weeks following a repair of a depressed skull
fracture.
CAVERNOUS SINUS THROMBOSIS

osms.it/cavernous-sinus-thrombosis
RISK FACTORS
PATHOLOGY & CAUSES ▪ Immunosuppression (e.g. uncontrolled
diabetes, corticosteroid use, cancer,
Cavernous sinuses chemotherapy)
▪ Irregularly shaped, trabeculated, blood filled ▪ Thrombophilia
cavities, acts as venous channel between
▪ Obesity
endosteum, dura mater at base of skull
▪ Severe dehydration
▪ Numerous important structures pass
through cavernous sinuses
▫ Internal carotid artery COMPLICATIONS
▫ Cranial nerves III, IV, V (branches V1, ▪ Dural venous, cavernous system valveless
V2), VI → communication with dural sinuses,
▪ Drain into internal jugular vein cerebral, emissary veins → meningitis, dural
empyema, brain abscess
Infection ▪ Spread via jugular vein to pulmonary
▪ Infection → formation of blood clot within vasculature → septic emboli, pulmonary
cavernous sinus abscesses, pneumonia
▪ Infection often arises via contiguous spread ▪ Carotid artery narrowing → stroke
from nearby infection (e.g. nasal furuncle, ▪ Ischemia/direct infectious spread →
sphenoidal/ethmoidal sinusitis/dental hypopituitarism
infection)
▫ Commonly associated organisms:
Staphylococcus aureus, Streptococcus
502 OSMOSIS.ORG
MRI
SIGNS & SYMPTOMS ▪ T1, T2: absent flow void, abnormal signal
characteristics of affect cavernous sinus
▪ Local compression, inflammation of cranial
nerves (III–VI) → several partial/complete ▪ Contrast venogram: deformity of internal
cranial neuropathies carotid artery in cavernous sinus, signal
hyperintensity in thrombosed vascular
▫ Diplopia, limited eye abduction, non-
sinuses
reactive pupil, numbness/paresthesia
around eyes, nose, forehead, facial pain
▪ Decreased drainage from facial vein, TREATMENT
superior, inferior ophthalmic veins →
periorbital edema, chemosis (conjunctival MEDICATIONS
swelling), proptosis, headache
▪ Broad spectrum empiric antibiotic therapy
until primary agent, source identified
DIAGNOSIS
SURGERY
DIAGNOSTIC IMAGING ▪ Sinus drainage (e.g. drainage,
sphenoidotomy if primary infection arises
CT scan from sphenoidal sinuses)
▪ Non-contrast: high-density thrombus in
cavernous sinus
▪ With contrast: underlying sinusitis,
thickening of superior ophthalmic vein,
irregular filling defects in cavernous sinus
CREUTZFELDT–JAKOB DISEASE
osms.it/creutzfeldt-Jakob-disease
→ holes form where nerves died →
PATHOLOGY & CAUSES sponge-like appearance on microscopy
▪ Universally fatal prionopathy; spongiform

encephalopathy → rapidly progressive TYPES
dementia ▪ Sporadic (sCJD)
▪ Native prions play role in long-term ▫ Majority (> 85%) of cases occur
memory, neuronal repair spontaneously
▪ Infectious prions composed entirely of ▪ Familial (fCJD)
protein, folded in structurally abstract ▫ Minority (< 10%) transferred via
conformations; able to pass on “misfolded” autosomal dominant inheritance
conformation ▪ Variant (vCJD)
▫ Infectious prions propagate by inducing ▫ Bovine-to-human transmission of
misfolding of native host prion proteins bovine spongiform encephalopathy
→ formation of new infectious prions
▪ Iatrogenic (iCJD)
▫ Malformed prion proteins extremely
▫ Exposure to brain/spinal tissue from
stable (resistant to denaturation by
infected individual (e.g. cadaveric human
enzymes) → accumulation in infected
pituitary hormone)
neuronal tissue → formation of amyloid
sheets → eventual tissue damage, death
OSMOSIS.ORG 503
RISK FACTORS
▪ Exposure to harvested human brain
TREATMENT
products (e.g. corneal grafts, dural grafts,
human growth hormone), ingestion of
MEDICATIONS
infected bovine products, cannibalism ▪ Sedatives/antidepressants/antipsychotics
▫ Palliative, relief of psychiatric symptoms
▪ Benzodiazepines/antiepileptics
COMPLICATIONS
▫ Palliative, relief of movement disorders
▪ Progressive neurodegeneration →
(e.g. myoclonic jerks)
dysphagia → aspiration pneumonia
common
SIGNS & SYMPTOMS

▪ Rapidly progressive dementia: memory
loss, personality change, hallucinations
▪ Movement disorders: myoclonus, ataxia,
rigid posture
▪ Psychiatric: anxiety, depression, psychosis
DIAGNOSIS
DIAGNOSTIC IMAGING Figure 65.2 A section of the brain
demonstrating a prion plaque. This individual
MRI displayed the symptoms of variant CJD.
▪ Diffusion-weighted MRI
▫ Focal/diffuse diffusion-restriction
involving cerebral cortex/basal ganglia
▪ Fluid-attenuated inversion recovery
(FLAIR)/T2-weighted
▫ Hyperintense signal changes in basal
ganglia, thalamus, cortex
▪ Cerebellar atrophy
LAB RESULTS
▪ Cerebrospinal fluid (CSF)
▫ Elevated concentration of 14-3-3
protein
▪ Tissue biopsy
▫ Prion deposits in brain (definitive
diagnosis) skeletal muscle, tonsils,
spleen; classical histological appearance
→ spongiform change in gray matter
OTHER DIAGNOSTICS
▪ Electroencephalography (EEG)
▫ Generalized periodic sharp wave pattern
504 OSMOSIS.ORG
ENCEPHALITIS
osms.it/encephalitis

▪ Acute inflammatory brain disease due ▪ Fever, chills, malaise
to direct invasion/pathogen-initiated ▪ Meningeal involvement → meningism
immune response → inflammation of brain ▫ Nuchal rigidity (inability to flex neck
parenchyma (often with meningitis) forward passively due to increased
▫ Peripheral nerves conduits to brain muscle tone, stiffness), headache,
parenchyma for viral infection—rabies, photosensitivity
herpes simplex virus (HSV) ▪ Parenchymal involvement → focal
▫ Hematogenous spread → transfer of neurological signs, seizures, altered mental
infections from distant sites state
CAUSES
DIAGNOSIS
▪ Viral (most common): HSV-1 (most
common), arbovirus (e.g. West Nile virus),
DIAGNOSTIC IMAGING
enterovirus (e.g. Polio), varicella zoster
virus (VSV), Epstein Barr virus (EBV), HIV, Brain CT scan (with/without contrast)
influenza ▪ Complete prior to lumbar puncture to
▪ Bacterial: Listeria monocytogenes, exclude significantly increased ICP,
mycobacteria, spirochetes (e.g. syphilis) obstructive hydrocephalus, mass effect
▪ Parasites: protozoa (e.g. Toxoplasma),
malaria Brain MRI
▪ Fungi: cryptococcus ▪ Increased T2 signal intensity in
▪ Non-infectious, autoimmune: acute frontotemporal region → viral (HSV)
disseminated encephalomyelitis, anti-N- encephalitis
methyl-D-aspartate (NMDA) receptor
encephalitis, T-cell lymphoma LAB RESULTS
Blood tests
RISK FACTORS
▪ Blood, CSF cultures
▪ Immunosuppression
▫ Bacterial pathogens
▪ Travel to low-income nations
▪ Blood glucose
▪ Exposure to disease vectors in endemic
▫ Comparison with CSF glucose; exclude
areas
confusion due to hypoglycemia
▪ Toxoplasma serology
COMPLICATIONS
▪ Seizures, syndrome of inappropriate CSF
secretion of antidiuretic hormone (SIADH), ▪ CSF chemistry
increased ICP, coma ▫ Lymphocytosis (> 5WBC/mL) with
normal glucose → viral encephalitis
▪ CSF polymerase chain reaction (PCR)
▫ Diagnosis of specific viral cause
▪ Specific antibody testing for EBV, arbovirus
OSMOSIS.ORG 505
Tissue analysis
▪ Tzanck smear (from base) of suspicious skin
lesions → identify presence of VZV/HSV
▪ Brain biopsy (definitive diagnosis)
▫ Cowdry type A inclusions (HSV, VZV,
CMV)
▫ Hemorrhagic necrosis in temporal,
orbitofrontal lobes (HSV)
OTHER DIAGNOSTICS
▪ EEG
▫ Temporal lobe discharges → viral (HSV)
encephalitis
TREATMENT
Figure 65.3 An MRI scan of the head
MEDICATIONS demonstrating increased signal in the left
▪ Viral encephalitis temporal lobe. HSV encephalitis was later
▫ HSV encephalitis: acyclovir confirmed by PCR of the cerebrospinal fluid.
▫ CMV encephalitis: ganciclovir/foscarnet
▫ Most viral infections lack specific
antiviral agent
▪ Bacterial encephalitis
▫ Targeted antibiotics
Figure 65.4 A histological section of the

brain demonstrating a lymphocytic infiltrate
in an individual with encephalitis.
506 OSMOSIS.ORG
EPIDURAL ABSCESS
osms.it/epidural-abscess
▪ Loose association between dura, vertebral
PATHOLOGY & CAUSES bodies → extension of spinal epidural
abscess to multiple spinal levels →
▪ Collection of pus, infectious material in extensive neurological findings
epidural space of CNS
▪ Typically caused by Staphylococcus aureus,
enteric gram-negative bacilli (e.g. E. coli),
TYPES coagulase-negative Staphylococci reaching
dural space
Intracranial epidural abscess ▫ Direct extension of local infection;
▪ Dura mater (tough outermost layer of vertebral osteomyelitis, psoas abscess,
meninges) directly in contact with skull soft-tissue infection
▪ Puss, granulation tissue accumulate ▫ Hematogenous seeding from distant
between dura mater, cranial bone infection
▪ Dura adheres tightly to skull → limits ▫ Iatrogenic spread due to invasive
expansion → dangerously increases ICP procedures
▪ Typically caused by Staphylococci/ ▪ Risk factors: old age, invasive spinal
Streptococci reaching dural space procedures, immunocompromised states,
▫ Direct extension from local infection (e.g. intravenous drug use, most common in
ear/paranasal sinuses) → osteomyelitis thoracolumbar area (epidural space larger,
→ abscess formation contains more fat tissue)
▫ Hematogenous seeding from distant ▪ Complications: recurrent sepsis, spinal cord
infection injury → bladder dysfunction
▫ Iatrogenic spread due to invasive
procedures
▪ Risk factors: prior craniotomy, head injury, SIGNS & SYMPTOMS
sinusitis, otitis media, mastoiditis
▪ Complications: seizures, increased ICP → ▪ Fever, malaise
uncal/tonsillar herniation, hemorrhage into ▪ Cranial epidural abscess
abscess, septic shock ▫ Pain/tenderness over abscess site, pus
draining from ear/sinuses, neck stiffness,
Spinal epidural abscess headache, nausea, vomiting
▪ Spinal epidural space ▪ Spinal epidural abscess (staging follows
▫ Outermost space within spinal canal clinical progression)
(formed by vertebrae, lying outside dura ▫ Back pain, tenderness, fever
mater) ▫ Radicular pain, reflex abnormalities
▫ Contains lymphatics, spinal nerve roots, ▫ Sensory abnormalities, motor weakness,
connective tissue, fat, vasculature loss of bowel/bladder control
▪ Collection of pus/inflammatory granulation ▫ Paralysis (progresses to irreversible
tissue between dura mater, vertebral paralysis without rapid surgical
column → spinal epidural abscess → intervention)
physical compression, inflammation of
surrounding tissues, spinal cord → local
ischemia
OSMOSIS.ORG 507
DIAGNOSIS
DIAGNOSTIC IMAGING
▪ Fluid collections in epidural space
MRI with contrast

▪ Homogeneous enhancement of abnormal
area, liquid abscess surrounded by
inflammatory tissue showing varying
degrees of peripheral enhancement
X-ray
▪ Osteomyelitis, vertebral collapse
LAB RESULTS
▪ Blood cultures
▫ May culture causative organism
▪ Lumbar puncture contraindicated
▫ Risk of spreading infection to
subarachnoid space
▪ CT-guided aspirates/surgically-obtained
fluid
▫ Culture causative organism Figure 65.5 A histological section of the
brain demonstrating a lymphocytic infiltrate
in an individual with encephalitis.
TREATMENT
MEDICATIONS
▪ Initial empirical antibiotic therapy, broad-
spectrum coverage for gram-positive,
gram-negative organisms
▫ Vancomycin (Gram-positive coverage),
third-generation cephalosporins (Gram-
positive, Gram-negative)
▪ Targeted antibiotics specific to isolated
organisms
SURGERY
▪ Intracranial
▫ Craniotomy → removal of infected bone,
surgical decompression
▪ Spinal
▫ Decompressive laminectomy (CT-
guided drainage)
508 OSMOSIS.ORG
MENINGITIS
osms.it/meningitis
PATHOLOGY & CAUSES

▪ Inflammation of meninges surrounding
brain, spinal cord
CAUSES
Bacteria, viruses, fungi, parasites, non-
infectious causes
▪ Non-infectious: e.g. medications,
autoimmune disease, malignancy
▪ “Aseptic meningitis”
Figure 65.6 A sample of cerebrospinal
▫ Don’t culture on typical bacterial media
fluid taken from an individual with bacterial
(e.g. viruses, fungi, parasites, non-
meningitis.
infectious causes)
▪ Acute illness
▫ Onset: hours, days Microbial spread to CNS
▫ Likely viral/bacterial causes ▪ Hematogenous spread (from distant site of
▪ Chronic meningitis infection)
▫ Onset: weeks, months ▪ Retrograde transport along cranial/
▫ Likely mycobacteria, fungi, Lyme peripheral nerves (viral illness)
disease, parasitic causes ▪ Contiguous spread from local infections of
▪ Pyogenic meningitis sinuses, ears, overlying bone
▫ Most likely bug by age group ▫ Infectious agents colonize nasopharynx/
▫ Mnemonic: Explaining Big Hot Neck respiratory tract
Stiffness (in order from birth to death) ▫ Preceding viral infection → breakdown
of normal nasal mucosal barrier →
colonizing bacteria enter bloodstream →
MNEMONIC: Explaining Big seeding of subarachnoid space in areas
Hot Neck Stiffness where blood-brain barrier vulnerable
(e.g. choroid plexus)
Causative microorganisms in
meningitis by age group ▪ Traumatic inoculation
E. coli, Group B streptococcus Other sources of inflammation
(infants)
▪ Significant inflammation not directly due to
Haemophilus influenzae (older bacterial action
infants, kids)
▪ Presence of bacterial antigens (e.g. cell
Neisseria meningitidis (young wall products) in CNS → recognition by
adults) astrocytes, microglia → cytokine release →
Streptococcus pneumoniae inflammation
(elderly) ▪ Inflammation → increased blood-brain
barrier permeability → vasogenic cerebral
edema
OSMOSIS.ORG 509
▪ Extravasation of white blood cells, plasma COMPLICATIONS
into CSF → interstitial edema ▪ Cerebral edema, cerebral herniation,
▪ Immune cell activity (e.g. further cytokine deafness, epilepsy, hydrocephalus,
release, oxidative burst) → inflammation of cognitive deficits
walls of blood vessels → cerebral vasculitis
→ decreased blood flow → cytotoxic
edema SIGNS & SYMPTOMS
▪ Collectively edema subtypes → raised
intracranial pressure ▪ Neonates, children
▪ Administration of antibiotics → greater ▫ Fever, lethargy, irritability, vomiting, poor
amounts of bacterial antigens (from feeding
dead bacteria) enter CSF → worsening ▪ Adults
inflammation (initially) ▫ Classic triad (< 50% of cases): sudden
onset headache, fever, nuchal rigidity
RISK FACTORS ▫ Photophobia, phonophobia (discomfort
▪ Immunocompromised individuals, with loud sounds), confusion, vomiting,
unvaccinated individuals (S. pneumoniae, papilledema
H. influenzae Type B) ▫ Brudziński’s sign: passive neck flexion
▪ Penetrating head trauma → pain, involuntary flexion of hips,
knees
▪ Anatomical meningeal defects (CSF leaks)
▫ Kernig’s sign: resistance to knee
▪ Contact with colonized/infected individuals
extension when hip flexed to 90º
510 OSMOSIS.ORG
▫ Jolt accentuation of headache:

headache worsens if individual asked to DIAGNOSIS
“jolt” head from side to side in horizontal
plane LAB RESULTS
▪ Meningococcal meningitis ▪ Lumbar puncture
▫ Petechial rash; non-blanching ▫ Gram stain; bacterial culture,
when pressure applied; trunk, lower susceptibility; WBC count, differential;
extremities RBC count; glucose, protein
concentration
▫ Acid-fast bacilli stain in TB endemic
areas/if suspected exposure
▫ HSV/enterovirus PCR
▪ Preemptive treatment to any close

TREATMENT contacts of individuals with meningococcal
meningitis is a single dose of ceftriaxone/
MEDICATIONS rifampin
Prevention Acute bacterial meningitis
▪ Immunization with meningococcal, mumps, ▪ Empiric antibiotic therapy based on age
pneumococcal, Hib vaccines
▫ If immediate lumbar puncture
performed, obtain sample prior to
antibiotics
OSMOSIS.ORG 511
▫ < one week: penicillin (e.g. ampicillin)
+ third-generation cephalosporin (e.g.
cefotaxime)/aminoglycoside
▫ 1 week–3 months: third-generation
cephalosporin + vancomycin
▫ > three months: vancomycin
▫ Targeted antibiotic therapy
▫ Corticosteroids: inflammation, cerebral
edema (dexamethasone)
Aseptic meningitis
▪ HSV, VZV meningitis: acyclovir
▪ Fungal meningitis (cryptococcal
meningitis): amphotericin B, flucytosine
Figure 65.7 The brain of an individual at post

mortem following death from meningitis.
Removal of the dura mater reveals pus
surrounding the brain.
Figure 65.8 Post mortem histology of the brain and meninges of an individual who died from
acute bacterial meningitis. The zoomed in area demonstrates numerous neutrophils infiltrating
the meninges.
512 OSMOSIS.ORG
NOTES
NOTES
CEREBROSPINAL
MALFORMATIONS

▪ Disorders affecting normative central ▪ Developmental milestones
nervous system (CNS) development/ ▫ Not met
function ▪ Motor dysfunction
▪ Varying severity, intensity ▫ Ataxia, paresis, unsteady gait, speech
impairment, poor coordination
CAUSES ▪ Dysautonomia
▪ Primary ▪ Intellectual disability
▫ Genetic mutation/idiopathic ▫ Learning/memory issues
▪ Secondary ▪ Dementia
▫ E.g. trauma, infection, neoplasm,
environmental factors
DIAGNOSIS
▪ Cerebral ischemia, delivery trauma, ▪ CT scan, MRI
premature birth, teratogenic substance
exposure (prenatal)
▪ Supportive structure (bone, connective OTHER DIAGNOSTICS
tissue) malformation → physically obstructs ▪ Neurological exam
CNS development
TREATMENT
▪ Mostly supportive
SURGERY
▪ In some cases; see individual disorders
OSMOSIS.ORG 513
ARNOLD–CHIARI MALFORMATION
osms.it/arnold-chiari-malformation

▪ Insufficient posterior fossa growth → ▪ Nausea, vertigo, nystagmus, unsteady gait
developmental cerebellum, brainstem, ▪ Lumbosacral/thoracic myelomeningocele
craniocervical junction malformation presence
▪ Affects cerebellar structure, position ▪ Medulla oblongata compression →
▪ AKA Chiari malformation type II (types I, III, dysautonomia (↓ ↑ heart/breathing rate,
IV—no specific name) neurogenic bladder, sleep apnea, pupillary
▪ Chiari malformations: similar presentations, dilation, etc.)
different mechanism development ▪ Paralysis/dysesthesia below spinal
▪ Accompanying findings: aqueductal compression
stenosis, upward cerebellar displacement, ▪ Valsalva maneuver → symptoms worsen
cerebellar dysplasia (increased intracranial pressure)
▪ Cerebellar tonsil protrusion through
foramen magnum
▪ Associations: lumbosacral DIAGNOSIS
myelomeningocele, Pierre Robin syndrome,
neurofibromatosis type I, Noonan syndrome DIAGNOSTIC IMAGING
▪ Commonly accompanies spina bifida CT scan, MRI
▪ Findings include presence of
RISK FACTORS myelomeningocele, cerebellar tissue
▪ Hydrocephalus (congenital/acquired) (downward displacement) through foramen
▪ Ehlers–Danlos syndrome, Marfan syndrome magnum, small fourth ventricle, tectal
→ craniocervical joint instability → beaking, atlas assimilation
cerebellar tonsil displacement
▪ Posterior cranial fossa malformation OTHER DIAGNOSTICS
(agenesia, craniosynostosis, osteopetrosis) ▪ Neurological exam
▪ Posterior cranial fossa pathology (tumor,
abscess, cyst, hematoma)
TREATMENT
▪ Aqueductal stenosis → impaired CSF flow
▪ Open neural tube defect closure
→ non-communicating hydrocephalus →
lateral, third ventricle dilatation ▪ Shunt placement (relieves hydrocephalus)
▪ Fourth ventricle obstruction → non- ▪ Bone removal (↓ brain structure pressure)
communicating hydrocephalus → aqueduct
dilatation; lateral, third ventricles OTHER INTERVENTIONS
▪ Brainstem, spinal cord compression ▪ Address complications: neurogenic
▪ Syringomyelia (hydrocephalus → bowel, bladder; neonatal feeding difficulty;
distention, dilation of spinal cord’s central respiratory failure, apnea
canal)
514 OSMOSIS.ORG
Chapter 66 Cerebrospinal Malformations
Figure 66.1 An MRI scan of the head in

the sagittal plane of an individual with an
Arnold-Chiari malformation. There is a small
posterior fossa and partial descent of the
brainstem and the cerebellar tonsils through
the foramen magnum.
CEREBRAL PALSY (CP)

osms.it/cerebral-palsy
CAUSES
PATHOLOGY & CAUSES ▪ Primary: genetic (autosomal recessive
glutamate decarboxylase-1 deficiency)
▪ Wide disorder group; non-progressive
▪ Secondary: preterm birth (most common
cerebral lesions impair motor, postural
cause), CNS injury, intrauterine growth
function/muscle tone
restriction, intrauterine infection,
▪ Most common motor disorder, 2.1 per 1000 antepartum hemorrhage, severe placental
babies affected, ages 0–3 years pathology, multiple pregnancy
▪ Varying severity, complexity
▪ Often accompanied by mental function
impairment, epilepsy
RISK FACTORS
▪ Prenatal/perinatal
▫ CNS trauma (pregnancy/birth)
MNEMONIC: PALSY ▫ Cerebrovascular insult (infarction,
Main characteristcs of CP thrombosis, hypoxic-ischemic injury)
Paresis ▫ CNS infection
Ataxia ▫ Radiation exposure
Lagging motor development ▫ Methylmercury/alcohol (prenatal
exposure)
Spasticity
▫ Maternal smoking/obesity
Young
▫ Infections during pregnancy
OSMOSIS.ORG 515
▪ Postnatal
▫ Stroke, CNS trauma, hypoxia (drowning),
SIGNS & SYMPTOMS
sepsis/meningitis, kernicterus
▪ Motor symptoms (type-dependent)
▫ Paresis, ataxia, spasticity, irregular
posture, orthopedic contracture,
scoliosis, seizure, neurogenic bladder/
bowel, impaired vision/speech, difficulty
feeding/swallowing
DIAGNOSIS TREATMENT
DIAGNOSTIC IMAGING ▪ No definitive treatment
CT scan, MRI
▪ Type-dependent MEDICATIONS
▫ Hypoxic-ischemic lesions (e.g. ▪ Benzodiazepines → myorelaxation, anxiety
periventricular leukomalacia/basal relief
ganglia lesions); cortical malformation; ▪ Spasmolytics → muscle-spasticity relief
hydrocephalus ▪ Anticonvulsants → seizure treatment,
prevention
Ultrasound ▪ Pain medication
▪ In young infants with open anterior
fontanelle
SURGERY
▪ Posture correction
OTHER DIAGNOSTICS
▪ Neurological exam
▪ Diagnostic tests
OTHER INTERVENTIONS
▪ Physical, occupational, speech therapy
▫ Differentiate from other motor
dysfunction disorders (e.g metabolic ▪ Posture correction
disorders, stroke, hydrocephalus, ▫ Braces/other orthotic devices
hematomas)
516 OSMOSIS.ORG
DANDY–WALKER SYNDROME
(DWS)
osms.it/dandy-Walker-malformation
CAUSES
PATHOLOGY & CAUSES ▪ Genetic, environmental factors
▫ Meckel syndrome
▪ Neurodevelopmental disorders; affect
cerebellar vermis, fourth ventricle ▫ Chromosomal aneuploidy (e.g. 45X,
triploidy)
▪ Classical triad
▫ Rubella infection/warfarin exposure
▫ Vermis hypoplasia/agenesis, cystic
during pregnancy
dilatation (fourth ventricle), posterior
fossa enlargement ▫ Maternal alcohol consumption
▪ Accompanying disorders (wide range) ▫ Congenital heart defect
▫ Cortical dysplasia, syringomyelia, ▫ Neural tube defect
schizencephaly, corpus callosum ▫ Holoprosencephaly
dysgenesis, cleft palate, etc.
▪ Associated with posterior fossa COMPLICATIONS
malformations–hemangiomas– ▪ Foramina (Magendie, Luschka) atresia →
arterial anomalies–cardiac defects– hydrocephalus
eye abnormalities–sternal cleft and
supraumbilical raphe syndrome (PHACES)
SIGNS & SYMPTOMS
MNEMONIC: DWS ▪ Macrocephaly, developmental milestones
Components of DWS not met (mental, motor), impaired motor
Dilated 4th ventricle coordination, unsteady gait, seizure, lower
Water on the brain limb spasticity, eye/ear involvement (rarely)
Small vermis
OSMOSIS.ORG 517
DIAGNOSIS TREATMENT
DIAGNOSTIC IMAGING ▪ No definitive treatment
MRI, prenatal ultrasound

▪ Characteristic findings SURGERY
▫ Cerebellar vermis agenesis/hypoplasia, Ventricular-peritoneal shunt
cystic dilatation (fourth ventricle), ▪ Manages hydrocephalus
posterior fossa enlargement;
hydrocephalus, absent corpus callosum
may also be present OTHER INTERVENTIONS
▪ Physical, occupational therapy
LAB RESULTS
▪ Amniocentesis

sagittal plane demonstrating a Dandy-Walker
malformation in a one-year-old boy. There is
accompanying gross hydrocephalus.
518 OSMOSIS.ORG
NORMAL PRESSURE
HYDROCEPHALUS (NPH)
osms.it/normal-pressure-hydrocephalus
OTHER DIAGNOSTICS
PATHOLOGY & CAUSES ▪ High-volume lumbar puncture/lumbar drain
trial
▪ Cerebrospinal fluid (CSF) accumulation →
▫ Improved functionality with CSF removal
progressive lateral ventricle enlargement
▪ AKA Hakim’s syndrome
▪ Intracranial pressure (ICP) not normal
(name is misnomer) TREATMENT
CAUSES SURGERY
▪ Slight–moderate elevation → classical ↑ ICP ▪ In some situations
symptoms (nausea, vomiting, photophobia,
neck pain, stiffness) not evident Ventriculoperitoneal shunt
▪ ↑ CSF → ↑ ICP → lateral ventricle dilation ▪ ↑ ICP relief
→ pressure on corona radiata
▫ Urinary incontinence), brainstem
structure (magnetic gait), periventricular
limbic system (dementia)
▪ Idiopathic/secondary
▫ Cerebrovascular insult, meningitis,
trauma, tumor
RISK FACTORS
▪ Prevalence largest among elderly (common
onset approx. 60 years old)
SIGNS & SYMPTOMS

▪ Unsteady gait
▫ Described as magnetic or “glue-footed”
▪ Urinary incontinence
▪ Cognitive impairment
sagittal plane demonstrating hydrocephalus.
There is a prominent flow void in the sylvian
DIAGNOSIS aqueduct, suggesting a normal-pressure
hydrocephalus.
DIAGNOSTIC IMAGING
MRI/CT scan
▪ Ventriculomegaly, enlarged Sylvian fissures,
enlarged sulci with no cortical atrophy
OSMOSIS.ORG 519
RETT SYNDROME
osms.it/rett-syndrome
RISK FACTORS
PATHOLOGY & CAUSES ▪ Young, individuals who are biologically
female
▪ Rare neurological disorder, impairs motor
▪ Extraordinarily, individuals who are
function (eating, walking, talking, breathing)
biologically male with Klinefelter syndrome
▪ AKA cerebroatrophic hyperammonemia (XXY), otherwise fatal for biologically-male
▪ Associated with prolonged QT syndrome (XY) individuals
▪ X-linked autosomal dominant MeCP2 gene ▪ Growth failure
mutation (spontaneous) ▪ Seizure
▪ MeCP2 protein involved in forming ▪ Fractures (related to ↓ bone mineralization)
neuronal connections, when only one gene
▪ Cardiac abnormalities; e.g. prolonged QTc
is mutated, the other one can compensate
interval
to a degree
▪ Autonomic nervous system dysfunction
▪ Sleep disturbances
▪ Behavioral issues; e.g. clapping, “pill-rolling”
(due to extrapyramidal motor defects)
520 OSMOSIS.ORG

▪ Manifests after six months old → later, ▪ No definitive treatment
divided into four stages
MEDICATIONS
DIAGNOSIS ▪ SSRI (behavioral issues)

▪ Genetic test ▪ Occupational, speech, physical therapy
▫ MeCP2 mutation ▪ Nutritional support for fracture reduction
OTHER DIAGNOSTICS
▪ Clinically diagnosed (characteristic findings)
▫ Loss of acquired purposeful hand skills,
spoken language
▫ Gait abnormalities
▫ Stereotypic hand movements
SEPTO-OPTIC DYSPLASIA (SOD)

osms.it/septo-optic-dysplasia

▪ Congenital malformation triad ▪ Nystagmus
▫ Underdeveloped optic nerve, ▪ Visual impairment
hypopituitarism, absent septum ▪ Intellectual impairment
pellucidum ▪ Seizure
▪ AKA de Morsier syndrome ▪ Growth hormone deficiency → short
▪ Most individuals have two of three stature, hypoglycemia, micropenis (if
components, some present with all three biologically-male)
▪ May also have encephalomalacia, ▪ Vasopressin deficiency → diabetes
schizencephaly, ectopic pituitary tissue insipidus
▪ Hyperprolactinemia
CAUSES ▪ Hyperbilirubinemia → jaundice
▪ Genetic
▫ Spontaneous/inherited HESX1, OTX2,
SOX2, PAX6 mutation DIAGNOSIS
▪ In utero sodium valproate, cocaine exposure
DIAGNOSTIC IMAGING
MRI
▪ Optic nerve hypoplasia, septum pellucidum,
corpus callosum agenesis
OSMOSIS.ORG 521
LAB RESULTS
Genetic testing
▪ HESX1, OTX2, SOX2, PAX6 mutations
OTHER DIAGNOSTICS
TREATMENT
MEDICATIONS
▪ Hormone replacement therapy
▪ Anticonvulsants → seizure treatment,
prevention
OTHER INTERVENTIONS Figure 66.4 An MRI scan of the head in the

▪ Treat complications coronal plane of an individual with septo-
optic dysplasia. The septum pellucidum,
▫ Ophthalmic, physical, and occupational
which normally separates the two lateral
therapy
ventricles, is absent.
SPINA BIFIDA
osms.it/spina-bifida
PATHOLOGY & CAUSES RISK FACTORS

▪ Multifactorial
▪ Congenital spinal column, meninges ▫ Genetic, environmental factors
malformation
▪ Pregnancy
▪ Most common neural tube defect
▫ Folate deficiency, anticonvulsant use
▪ Improper vertebrae formation allows
▪ Obesity
meninges/spinal cord to protrude dorsally
out of spinal canal ▪ Poorly-managed diabetes mellitus
▪ Occurs in fourth week of pregnancy
▪ Usually manifests in lumbar part of spinal COMPLICATIONS
column (can occur elsewhere) ▪ Meningitis; neurogenic bladder, bowel;
▪ Most individuals with spina bifida have nerve damage paralysis; tethered cord
latex allergy (complicates medical syndrome; cognitive impairment; pressure
procedures) ulcer; seizure; hydrocephalus; orthopedic
▪ Some individuals with spina bifida have problems
intellectual impairment
▪ Can present with Arnold–Chiari
malformation
SIGNS & SYMPTOMS
▪ Associated with malformed corpus ▪ Lower-back pain, hip dysplasia, dysesthesia
callosum, cerebellum, cerebral cortex (below lesion), leg weakness, nystagmus,
clubfoot, scoliosis
522 OSMOSIS.ORG
OTHER INTERVENTIONS
DIAGNOSIS ▪ Resolve complications
DIAGNOSTIC IMAGING ▫ Seizure, hydrocephalus, orthopedic
problems
Prenatal ultrasound ▪ Physical therapy
X-ray, CT scan, MRI

▪ Show improper vertebral formation
LAB RESULTS
▪ ↑ alpha-fetoprotein
▫ Spina bifida occulta does not show ↑
▪ Genetic tests
OTHER DIAGNOSTICS
▪ Visual examination
▫ Visible meningocele, myelomeningocele
at birth
TREATMENT
SURGERY Figure 66.5 An individual with spina bifida
▪ Reposition meninges, spinal cord into spinal and a an associated myelomeningocoele, also
canal known as spina bifida cystica.
OSMOSIS.ORG 523
SYRINGOMYELIA
osms.it/syringomyelia

▪ Cerebrospinal fluid-filled cyst around spinal SURGERY
cord’s central canal ▪ Cyst drainage; flow restoration
▪ Cyst in nerve tissue (syrinx); spinal cord
(myelia)
▫ E.g. brainstem syrinx (syringobulbia)
▪ As cyst forms, grows → fluid collects within
spinal cord tissue → ↑ pressure within
spinal cord → damage
▪ Symptoms progress slowly, often adult
diagnosis
RISK FACTORS
▪ Congenital: Arnold–Chiari malformation,
genetic mutation
▪ Acquired: trauma; spinal cord tumor,
bleeding; scoliosis
SIGNS & SYMPTOMS

▪ Various locations, syringomyelia severity
▪ Chronic pain, dysesthesia, paresis/paralysis Figure 66.6 An MRI scan of the head and
▪ Suspended sensory level neck in the sagittal plane demonstrating
syringomyelia extending from approximately
▫ Sensory perception defect only on body
the level of C4 to T3. There is also a Chiari I
parts innervated by syringomyelia-
malformation.
affected structures
DIAGNOSIS
DIAGNOSTIC IMAGING
MRI
▪ Syrinx visualization in spine
OTHER DIAGNOSTICS
Neurological exam
▪ For suspended sensory level
524 OSMOSIS.ORG
TETHERED SPINAL CORD

SYNDROME (TCS)
osms.it/tethered-spinal-cord-syndrome
PATHOLOGY & CAUSES

▪ Pathological spinal cord fixation to spinal
canal wall
▪ AKA occult spinal dysraphism sequence
▪ Spinal cord movement restricted
▫ Normally, spinal cord floats freely in CSF
▫ TCS: restricted movement → physical
strain → spinal cord damage
CAUSES
▪ Primary: congenital short filum terminale
▪ Secondary: surgery/trauma → scar tissue
attachment; (myelo)meningocele
Figure 66.7 An MRI scan of the spine in

SIGNS & SYMPTOMS the sagittal plane demonstrating a tethered
spinal cord associated with a lipoma of the
▪ Lower-back pain, scoliosis, clubfoot, filum terminale.
neurogenic bladder, bowel, paresis/
paralysis below lesion
TREATMENT
DIAGNOSIS
SURGERY
DIAGNOSTIC IMAGING ▪ Relieve spinal cord strain (if possible)
▪ Corrective orthopedic surgery
Spinal MRI
▪ Conus medullaris located below the normal
L2–3 level OTHER INTERVENTIONS
▪ Physical therapy
OTHER DIAGNOSTICS
OSMOSIS.ORG 525
NOTES
NOTES
CHILDHOOD PRIMARY
BRAIN TUMORS

▪ Most common solid tumor in children < 15 ▪ May be subtle (slow-onset)/progress
years old quickly
▪ 20% of all childhood cancer ▪ Headache, nausea/vomiting
▪ Most pediatric brain, spinal cord tumors ▫ Morning often worse (waking up)
are primary tumors; originate from central ▫ Cough, exercise, body-position change
nervous system (CNS) cells may exacerbate headache
▪ Most common types ▪ Mental change
▫ Astrocytomas, medulloblastomas, ▫ Personality/behaviour change,
ependymomas, brainstem gliomas concentration difficulty
▪ Better prognosis (generally) than adult ▪ Other associated symptoms
brain tumors ▫ Balance/gait disturbance; visual
disturbance/loss; hearing/speech
RISK FACTORS difficulty; weakness; numbness
▪ Biologically-male > biologically-female
individuals
▪ Varies with tumor type
DIAGNOSIS
DIAGNOSTIC IMAGING
COMPLICATIONS
▪ Dependent on tumor type, location, grade, CT scan/MRI
child’s age ▪ Head
▪ Dependent on size, location, malignant ▫ Identify lesion’s size, location
potential of tumor; lesion’s mass effect →
complications LAB RESULTS
▫ Increased intracranial pressure (ICP) →
headache, nausea, vomiting Biopsy
▫ Vision, balance, gait disturbance ▪ Open surgery/stereotactic biopsy (definitive
(common) diagnostic tool)
▫ May be mental changes, normal growth/ ▪ Determine type, stage, grade
development disturbance ▫ Grade: degree of differentiation (tumor
cells)
▫ Stage: extent of spread (tumors cells)
526 OSMOSIS.ORG
Chapter 67 Childhood Primary Brain Tumors
Lumbar puncture MEDICATIONS

▪ Cerebrospinal fluid (CSF) analysis → ▪ Chemotherapy
malignant cell detection ▫ Residual tumor/metastasis
▪ Corticosteroids, diuretics
OTHER DIAGNOSTICS ▫ Reduce swelling, alleviate associated ↑
▪ Visual field examination ICP symptoms
▫ ↑ ICP → mass effect/swelling → detect ▪ Pain management
central/peripheral vision defects
▪ Childhood primary brain tumor grades SURGERY
▫ Based on World Health Organization ▪ Resection
(WHO) grading system (see table)
OTHER INTERVENTIONS
TREATMENT ▪ Radiation
▫ Residual tumor/metastasis
▪ Depends on tumor size/location, child’s age
▪ Goals
▫ Eliminate tumor, relieve symptoms,
restore brain function
OSMOSIS.ORG 527
CRANIOPHARYNGIOMA
osms.it/craniopharyngioma

▪ Rare benign non-glial epithelial CNS tumor DIAGNOSTIC IMAGING
▫ Often within sellar/suprasellar space
CT scan/MRI
▪ Hypothesis
▪ Mass visualization
▫ Derived from Rathke’s cleft/squamous
▪ Other common findings
cell crests along craniopharyngeal duct
▫ Suprasellar region calcification, one/
▪ Gross pathology
more supra/parasellar region cysts
▫ Cholesterol crystals in “motor oil”-like
fluid within tumor, homogeneous Histopathology
▪ Cysts with stratified squamous epithelium,
TYPES cholesterol crystals, keratin pearls
▪ Adamantinomatous
▫ Primarily children, often single/multiple
cysts
▪ Papillary
▫ Adults (almost exclusively), solid lesions
RISK FACTORS
▪ Bimodal age distribution
▫ 5–14 years old (children), 50–70 years
old (adults)
COMPLICATIONS
▪ Hypopituitarism, hydrocephalus, ↑ ICP
SIGNS & SYMPTOMS

▪ Headache, nausea, vomiting Figure 67.1 An MRI scan of the head
▪ Visual disturbance/loss (i.e. bitemporal in the sagittal plane demonstrating a
hemianopia) craniopharyngioma, adamantinomatous
▪ Endocrine abnormality subtype. The tumor has clear solid and cystic
components with abundant calcification.
▫ Affects growth, thyroid/adrenal function,
diabetes insipidus
▪ Behavioral change (ie. hypersomnia)
528 OSMOSIS.ORG
TREATMENT
MEDICATIONS
▪ Endocrine replacement therapy: specific
endocrine deficiency-dependent
SURGERY
▪ Resection
OTHER INTERVENTIONS
▪ Radiotherapy
Figure 67.2 A histological section of a

craniopharyngioma, adamantinomatous type.
The tumor is composed of cystic spaces,
calcifications and keratin.
EPENDYMOMA
osms.it/ependymoma
RISK FACTORS
PATHOLOGY & CAUSES ▪ Neurofibromatosis type II (NF2)-diagnosed
individuals (more common)
▪ Uncommon glial tumor
▫ Arises from ependymal cells lining
ventricular system, spinal cord’s center COMPLICATIONS
▪ Located intracranially (children), within ▪ Fourth ventricle blockage → hydrocephalus
spinal canal (adults) → headache, nausea, vomiting
▪ Often form ependymal pseudorosettes ▪ Tumor mass effect
▫ Tumor cells arranged around vessels,
fibrils pointing towards vessel
SIGNS & SYMPTOMS
TYPES ▪ Headache, visual disturbance/loss, nausea,
▪ Five subtypes: WHO grade classification vomiting, ataxia (gait, balance disturbance),
▫ Subependymoma: grade I vertigo, papilledema, cranial-nerve palsy,
▫ Myxopapillary ependymoma: grade I seizure/focal neurologic deficit, back pain,
limb numbness/weakness
▫ Ependymoma: grade II
▫ RELA fusion–positive ependymoma:
grade II/grade III (with RELA gene
change)
▫ Anaplastic ependymoma: grade III
OSMOSIS.ORG 529
DIAGNOSIS TREATMENT
▪ Chemotherapy
CT scan
▪ Hyperdense with enhancement, commonly
see cysts, calcifications SURGERY
▪ Resection
MRI
▪ Hypointense lesion, extension into Luschka
foramen may be seen
OTHER INTERVENTIONS
▪ Adjuvant radiotherapy
LAB RESULTS
Histological examination
▪ Cells with round/oval nuclei, dense fibrils
forming canal structure
▪ Perivascular pseudorosettes
▫ Cells arranged around vessels with thin
ependymal processes directed inwards
▪ Immunohistochemical markers include glial
fibrillary acid protein, epithelial membrane
antigen
CSF cytology
▪ Guides tumor staging
an ependymoma. The tumor is composes of
monomorphic cells which form ependymal
rosettes, with a central clearing.
Figure 67.4 An MRI scan of the head of a

child demonstrating an ependymoma in the
posterior fossa, compressing the cerebellum.
530 OSMOSIS.ORG
MEDULLOBLASTOMA
osms.it/medulloblastoma
Group 4
PATHOLOGY & CAUSES ▪ Poor prognosis
▪ Most common pediatric malignant primary ▪ 2:1 biologically male/biologically female
brain tumor ratio
▫ Arises from cerebellum’s primitive ▪ 4–16 years old
neuroepithelial cells ▪ Classic histology, well-defined lesions
▪ Usually forms midline mass along roof (limited contrast enhancement)
of fourth ventricle (between brainstem/
cerebellum) RISK FACTORS
▪ WHO grade IV classification ▪ 2:1 biologically male/biologically female
ratio
TYPES ▪ 3–8 years old
▪ Categorized as desmoplastic, classic, large- ▪ Certain inherited familial syndromes
cell, anaplastic, variants ▫ Ataxia-telangiectasia, Rubinstein–Taybi
▪ Gene expression profiling recognizes four syndrome, Gorlin syndrome, Turcot’s
molecular subgroups syndrome, Li–Fraumeni syndrome
Wingless (WNT)
COMPLICATIONS
▪ Excellent prognosis
▪ Frequent metastasis → other brain, spinal
▪ 1:1 biologically male/biologically female cord parts
ratio
▪ Fourth ventricle blockage → hydrocephalus
▪ 10–12 years old (peak incidence) → headache, nausea, vomiting
▪ Classic histology (majority) ▪ Tumor’s mass effect
▪ Often CTNNB1 gene (encodes beta-
catenin) mutation
SIGNS & SYMPTOMS
Sonic Hedgehog (SHH)
▪ Intermediate prognosis ▪ Headache; nausea; vomiting; ataxia (gait/
▪ 1:1 biologically male/biologically female balance disturbance), falls; diplopia;
ratio papilledema; positional dizziness,
▪ Infants < four years old, adults > 16 years nystagmus; bulging anterior fontanelle;
old visual disturbance/loss
▪ Classic, large-cell, anaplastic, desmoplastic,
with extensive nodularity
DIAGNOSIS
Group 3
▪ Poor prognosis DIAGNOSTIC IMAGING
▪ 2:1 biologically male/biologically female
CT scan
ratio
▪ Often appear as vermis mass → fourth
▪ 4–16 years old
ventricle effacement → obstructive
▪ Classic/large-cell anaplastic histology, hydrocephalus
associated with Myc amplification,
▪ Hyperdense, +/- cysts, +/- calcifications
poorly-defined lesions (better contrast
enhancement than group 4 lesions)
OSMOSIS.ORG 531
MRI
▪ Heterogeneous mass; calcification,
necrosis, cyst formation
▪ May see surrounding edema
LAB RESULTS
Histological examination
▪ Variable cellular atypia
▪ Homer Wright rosette; dark tumor
cells spherically arranged around pale
eosinophilic neurofibrils
▪ INI1-positive (tumor suppressor gene
marker)
Lumbar puncture
▪ CSF analysis
Figure 67.5 An MRI scan of a child
▫ Malignant cell detection
in the sagittal plane demonstrating a
medulloblastoma. In childhood, they
TREATMENT commonly arise in the posterior fossa at the
roof of the fourth ventricle.
MEDICATIONS
▪ Chemotherapy
SURGERY
▪ Tumor resection
OTHER INTERVENTIONS
▪ Radiotherapy
Figure 67.6 A medulloblastoma forming

Homer–Wright rosettes, with no central
clearing.
532 OSMOSIS.ORG
PILOCYTIC ASTROCYTOMA
osms.it/pilocytic-astrocytoma
▪ Spectroscopy/perfusion MRI head
PATHOLOGY & CAUSES ▫ Determines tumor grade
▪ Primary tumor
▫ Arises from astrocytes LAB RESULTS
▫ AKA juvenile pilocytic astrocytoma/ Biopsy
cystic cerebellar astrocytoma
▪ Mass
▪ Mainly occurs in children (majority 0–30
▫ Heterogeneous/homogeneous/mixed;
years old)
cystic; solid; with/without hemorrhage,
▪ Often arises in cerebellum, hypothalamic necrosis
region, along optic pathway
▪ Tumors slow growing, benign (WHO
grade I) OTHER DIAGNOSTICS
▪ Associated with cyst formation, often well- ▪ Ophthalmological evaluation/visual field
circumscribed testing
▪ Strong neurofibromatosis type I (NF-1) ▫ May detect visual field deficit
association
▪ Microscopic appearance
▫ Elongated hair-like projections,
Rosenthal fibers (characteristic feature)
SIGNS & SYMPTOMS

▪ Altered mental status; headache, nausea,
vomiting; gait disturbance, ataxia;
weakness; seizure; visual disturbance,
nystagmus, papilloedema; aphasia/
dysphasia
Figure 67.7 A brain biopsy smear from

DIAGNOSIS a pilocytic astrocytoma demonstrating
malignant astrocytes with pleomorphic,
DIAGNOSTIC IMAGING hyperchromatic nuclei. In addition there is an
eosinophilic granular body, commonly seen in
CT scan such tumors.
▪ Lesion (hypodense), calcification/
hemorrhage area (hyperdense)
MRI (head) TREATMENT

▪ Range of appearances
▫ Cystic component(s) with mural MEDICATIONS
nodule (enhancing, nonenhancing ▪ Chemotherapy
cyst wall); heterogeneous, mixed solid;
homogeneous solid
OSMOSIS.ORG 533
SURGERY
▪ Resection (location often prohibits total
resection)
OTHER INTERVENTIONS
▪ Radiotherapy
▪ Observation (when asymptomatic)

a pilocytic astrocytoma. There are bipolar
neoplastic cells arranged in fascicles with
elongated hair-like processes.
PINEALOMA
osms.it/pinealoma
COMPLICATIONS
PATHOLOGY & CAUSES ▪ Precocious puberty
▫ Homeostatic hypothalamic-pituitary
▪ Rare tumor that arises from cells in the
axis disruption → puberty onset
pineal region
in biologically-male individuals (<
▪ May result in endocrine disruption, nine years old), biologically-female
obstructive hydrocephalus, and individuals (< eight years old)
compression of adjacent structures
▫ ↓ melatonin production (may result) →
(cerebellum, brainstem)
impaired circadian rhythm regulation
▪ Occurs any age; malignancy more common
▪ Physical ventricular system obstruction → ↑
in children (< eight years old)
ICP → hydrocephalus
TYPES
▪ Four pinealoma types SIGNS & SYMPTOMS
▫ Germ cell tumors
▫ Papillary tumors ▪ Parinaud’s syndrome (upward gaze
paralysis, pupillary areflexia), pseudo-Argyll
▫ Pineal parenchymal cell tumors
Robertson pupils, convergence-retraction
▫ Glial cell tumors nystagmus, eyelid reaction (Collier’s sign)
▪ Other miscellaneous tumors and cysts in ▪ Headache; nausea; vomiting; visual,
the pineal region balance, gait disturbance; fatigue/
irritability; insomnia
RISK FACTORS
▪ RB1 gene inheritance
▪ Previous radiation exposure
534 OSMOSIS.ORG
DIAGNOSIS TREATMENT
▪ Resection +/- shunt (drain excess CSF)
Head CT scan/MRI
▪ May appear cystic/partially cystic
▪ Often lobulated, seen as heterogeneous OTHER INTERVENTIONS
mass ▪ Adjuvant radiotherapy (malignant tumors)
▪ Usually 2.5–4 cm/1–1.6in wide, well
circumscribed in pineal region; contrast-
enhanced rim in cystic forms
LAB RESULTS
▪ Hormonal evaluation
▫ Melatonin (indicates pineal gland
pathology)
▪ Lumbar puncture
▫ CSF analysis for detection of malignant
cells
▫ α-fetoprotein/β-HCG tumor markers
indicate germinal origin
▪ Biopsy
▫ Determines type, stage; open surgery/
stereotactic biopsy
OTHER DIAGNOSTICS
▪ Visual field examination
▫ Defect detection: central, peripheral
vision; swelling around optic nerve (↑
ICP sign)
OSMOSIS.ORG 535
NOTES
NOTES
CNS DEMYELINATING
DISORDERS

▪ Disorders affecting brain, spinal cord; DIAGNOSTIC IMAGING
damage to oligodendrocytes → loss of
myelin, axons CT scan, MRI
▪ Damage mostly caused by autoimmune ▪ Abnormal signals in white matter regions
reaction
▫ Inflammatory cells release cytotoxic LAB RESULTS
molecules/engulf cells ▪ Cerebrospinal fluid (CSF)
▪ Trigger unknown ▫ ↑ cell count, ↑ protein level
RISK FACTORS OTHER DIAGNOSTICS

▪ Genetic predisposition ▪ Neurologic symptoms
▪ Environmental factors (e.g. infections)
TREATMENT
SIGNS & SYMPTOMS
MEDICATIONS
▪ Motor: weakness, tremors, paraparesis/ ▪ Reduce inflammation (e.g. corticosteroids)
quadriparesis
▪ Sensory: abnormal sensations, numbness,
OTHER INTERVENTIONS
visual problems
▪ Plasma exchange
▪ Autonomic: sphincter, sexual dysfunction
▪ Manage symptoms
536 OSMOSIS.ORG
Chapter 68 CNS Demyelinating Disorders
ACUTE DISSEMINATED
ENCEPHALOMYELITIS
osms.it/acute-diss-encephalomyelitis

▪ Autoimmune disease characterized by ▪ Sudden onset of symptoms 1–3 weeks
sudden inflammation of brain, spine; after interaction with pathogen
destruction of myelin sheath at multiple ▪ Systemic inflammation (fever, headache,
locations nausea, vomiting)
▪ Sensory, visual deficits
Type IV hypersensitivity reaction
▪ Seizures, confusion, drowsiness
▪ Cell-mediated
▪ Motor deficits, weakness, ataxia
▪ T-cells penetrate blood brain barrier,
activated by myelin antigens (myelin ▪ Oculomotor deficits, nystagmus, dysarthria
basic protein, proteolipid protein, myelin ▪ Coma
oligodendrocyte protein) → release of
cytokines (IL-1, IL-6, TNF-alpha, interferon-
gamma) DIAGNOSIS
▫ Direct damage to oligodendrocytes,
myelin DIAGNOSTIC IMAGING
▫ Blood brain barrier expresses more MRI
receptors → attracts more immune cells
▪ Multiple lesions in white matter regions of
(B-cells, macrophages) → blood vessel
central nervous system (CNS)
dilatation
▪ Open ring sign with contrast enhancement
▪ B-cell activation → production of
autoantibodies against myelin proteins ▪ Edema
▪ Macrophages look for antibody marked CT scan
oligodendrocytes, destroy them
▪ Emergency cases
▪ Low density lesions in white matter region
CAUSES
▪ Antigen mimicry
LAB RESULTS
▫ Antibodies aimed against pathogen
▪ Lumbar puncture
antigens bind to myelin proteins
▫ ↑ protein, ↑ cell count (lymphocytes),
high level of antibodies, CSF culture
RISK FACTORS
▪ Genetic predisposition
OTHER DIAGNOSTICS
▪ Infections
▪ Clinical
▫ Viral (measles, mumps, rubella);
▫ Polyfocal neurologic symptoms,
bacterial (Mycoplasma pneumoniae,
encephalopathy
beta-hemolytic Streptococci)
▪ Microscopically
▪ Vaccination
▫ All lesions similar, preserved axons with
▫ Measles-mumps-rubella (MMR)
myelin loss, mononuclear infiltration,
vaccination
foamy macrophages
▪ Usually affects children
OSMOSIS.ORG 537
TREATMENT
MEDICATIONS
▪ Corticosteroids
▫ Reduce inflammation
▫ E.g. glucocorticoids
▪ Cyclophosphamide
▫ Cell cycle inhibition
OTHER INTERVENTIONS
▪ Intravenous immune globulins
▫ Neutralize antibodies
▪ Plasma exchange
Figure 68.1 An MRI scan of the head of

an individual with acute disseminated
encaphalomyelitis. There are bilateral,
asymmetrical, tumefactive lesions of the
cerebral white matter.
CENTRAL PONTINE MYELINOLYSIS

osms.it/central-pontine-myelinolysis
▫ Potassium, sodium surge back into
PATHOLOGY & CAUSES astrocytes → ↑ cation concentracion
▫ Shrinkage of endothelial cells →
▪ Destruction of myelin sheath around nerve
distortion of blood brain barrier →
cells in pons due to rapid osmotic changes
complements, cytotoxic elements form
(osmotic demyelination syndrome)
blood leak into brain
▪ ↓ sodium level in serum → water leakage
▪ Damage astrocytes, induce apoptosis
through blood brain barrier → ↑ brain
volume ▫ Interruption of myelin-making process in
oligodendrocytes
▪ Activation of defense mechanisms
▫ Release of cytokines
▫ After few minutes: ↑ intracranial
pressure pushes excess water, sodium ▫ Activation of microglia
into CSF → ↓ brain volume
▫ After few hours: astrocytes release RISK FACTORS
organic solutes → release of excess ▪ Sodium level < 120meq/L
intracellular water → evening osmolarity ▪ Hyponatremia lasts > two days
with serum
▪ Syndrome of inappropriate diuretic
▫ After two days: fully adapted to altered hormone (SIADH)
osmolarity
▫ Kidneys retain too much water
▪ Sudden correction of hyponatremia in
▪ Alcoholism, malnutrition
already adapted brain
538 OSMOSIS.ORG
COMPLICATIONS
▪ Respiratory failure, aspiration pneumonia,
TREATMENT
coma, death
OTHER INTERVENTIONS
▪ Correcting serum sodium slowly
SIGNS & SYMPTOMS ▪ 6–8 weeks; endotracheal intubation,
ventilator support
▪ Movement disorders
▪ Paraparesis/quadriparesis
▪ Severe cases
▫ “Locked-in” syndrome (conscious,
paralyzed; can only move eyes, blink)
▪ Dysarthria, dysphagia, diplopia
▪ Seizures, confusion, lethargy, coma
DIAGNOSIS
DIAGNOSTIC IMAGING
MRI
▪ Earliest changes seen in diffusion weighted
imaging (DWI)
▫ Restriction in pons region
▪ Later changes
▫ High T2, low T1 signal
▫ “Trident sign” (trident spear-shaped Figure 68.2 An MRI scan of the head and
lesion in pons) neck in the sagittal plane demonstrating
a hypointense lesion in the pons of an
CT scan individual with central pontine myelinolysis.
▪ Low sensitivity; low attenuation signal in
pons
PET
▪ Initial high uptake
OSMOSIS.ORG 539
MULTIPLE SCLEROSIS (MS)
osms.it/multiple-sclerosis
years apart
PATHOLOGY & CAUSES ▫ Improvement after attack
▪ Autoimmune demyelinating disease ▫ Residual permanent damage
of nerve cells in brain, spinal cord accumulates
characterized by various neurological ▫ Disabilities do not increase between
disorders bouts
▪ Cell-mediated (Type IV) hypersensitivity ▪ Secondary progressive multiple sclerosis
reaction (SPMS)
▫ T cells, B cells, macrophages ▫ Starts as RRMS
▫ Over time attacks become constant →
T cells progression of disabilities
▪ Break through blood brain barrier → ▪ Primary progressive multiple sclerosis
activated by myelin proteins (myelin basic (PPMS)
protein) ▫ One constant attack → progression of
▪ Th17 cells produce cytokines → attract disabilities over lifetime
other leukocytes ▪ Progressive-relapsing multiple sclerosis
▪ Th1 cells produce interferon gamma → (PRMS)
activation of macrophages ▫ One constant attack
▪ Produce cytokines (IL-1, IL-6, TNF-alpha) ▫ Superimposed bouts → faster
▫ Oligodendrocytes damaged progression of disabilities
▫ Blood brain barrier expresses more
receptors for other leukocytes
RISK FACTORS
▫ Blood vessels dilate; easier passage for
▪ Genetic
other leukocytes
▫ Individuals who are biologically female
B cells twice as susceptible
▪ Produce antibodies that bind to myelin ▫ Polymorphisms of certain alleles of
proteins, mark them major histocompatibility complex (e.g.
HLA-DR2; identifying, binding of foreign
Macrophages molecules)
▪ Recognize marked oligodendrocytes, engulf ▪ Environmental
them ▫ Infections (e.g. Epstein–Barr virus
▪ Attacks infection)
▫ Early: regulatory T cells reduce ▫ Vitamin D deficiency
inflammation → oligodendrocytes heal, ▪ Usually affects young adults
renew myelin (remyelination)
▫ Later: repetitive extensive damage →
death of oligodendrocytes → loss of MNEMONIC: MS MS
myelin → damage, loss of axons Pathology of multiple
sclerosis
TYPES Multiple Sclerosis affects
▪ Relapsing-remitting multiple sclerosis Myelin Sheath
(RRMS)
▫ Bouts of autoimmune attacks, months/
540 OSMOSIS.ORG
OTHER DIAGNOSTICS
SIGNS & SYMPTOMS ▪ Clinical
▫ Neurologic symptoms with relapsing-
▪ Charcot’s neurologic triad
remitting course
▫ Dysarthria, nystagmus, intention tremor
▪ Visual evoked potential
▪ Lhermitte’s sign
▫ Measure response to visual stimuli
▫ Bending neck forward → electric shock
runs down back, radiates to limbs
▪ Higher order activities
▫ Poor concentration, critical thinking;
depression, anxiety
Plaque location
▪ Brainstem
▫ Conscious movements (e.g. difficulty
talking/eating)
▫ Unconscious movements (e.g. difficulty
swallowing)
▪ Eye nerves
▫ Optic neuritis (e.g. loss of vision)
▫ Eye movement nerves (e.g. double
vision)
▪ Motor pathways
▫ Muscle weakness, spasms, tremors,
ataxia, paralysis Figure 68.3 An MRI scan of the head in
the sagittal plane demonstrating multiple
▪ Sensory pathways
demyelinating plaques adjacent to the corpus
▫ Numbness; pins, needles; paresthesias callosum. This radiological sign is known as
(tingling, itching, burning) Dawson’s fingers and is specific for multiple
▪ Autonomic nervous system sclerosis.
▫ Constipation, urinary incontinence,
sexual dysfunction
DIAGNOSIS
DIAGNOSTIC IMAGING
MRI
▪ Hypointense T1, hyperintense T2 lesions
▪ ≥ one lesions in periventricular,
juxtacortical, infratentorial, spinal cord
▪ Gadolinium-enhanced, nonenhanced
lesions simultaneously
▪ Dawson’s fingers
▫ Plaques radiating outwards from corpus
callosum in sagittal images
LAB RESULTS Figure 68.4 An MRI scan of the head in

▪ CSF the axial plane demonstrating the multiple
▫ High levels of antibodies demyelinating plaques present in the brain of
an individual with multiple sclerosis.
OSMOSIS.ORG 541
▪ Progressive MS
TREATMENT ▫ Manage symptoms (e.g. urinary
incontinence), physical therapy,
MEDICATIONS cognitive rehabilitation therapy,
▪ RRMS vitamin D
▫ Corticosteroids, cyclophosphamide,
intravenous immunoglobulin
OTHER INTERVENTIONS
▪ RRMS
▫ Plasmapheresis: removing antibodies
▫ Immunosuppressants
TRANSVERSE MYELITIS
osms.it/transverse-myelitis

▪ Rare immune disorder affecting spinal cord; ▪ Motor: extremity weakness → paraparesis
causes acute motor, sensory, autonomic ▪ Sensory: abnormal sensations, numbness,
defects pain
▪ Perivascular inflammation (monocytes, ▪ Autonomic: sphincter, sexual dysfunction
lymphocytes) → damage to
oligodendrocytes → loss of myelin sheath
around axons → loss of axons, neurons DIAGNOSIS
TYPES DIAGNOSTIC IMAGING
▪ Acute partial
MRI
▫ Asymmetric dysfunctions
▪ Hypointense/isointense T1, hyperintense
▫ 1–2 segments involved T2 signal
▪ Acute complete ▪ Abnormal contrast enhanced signal on ≥
▫ Symmetric dysfunctions one segment
▫ 1–2 segments involved ▪ Spinal cord swelling
▪ Longitudinally extensive
▫ Symmetric/asymmetric dysfunctions LAB RESULTS
▫ > two segments involved ▪ CSF
▫ ↑ cell count (lymphocytes), ↑ protein
RISK FACTORS level
▪ CNS, systemic infections
▪ CNS disease (e.g. multiple sclerosis) OTHER DIAGNOSTICS
▪ Clinical
▫ Motor, sensory, autonomic defects
542 OSMOSIS.ORG
TREATMENT
OTHER INTERVENTIONS
▪ Intravenous glucocorticoids
▪ Plasma exchange
Figure 68.5 An MRI scan of the spine in

the sagittal plane demonstrating increased
T2 signal uptake in the spinal cord, typical
of transverse myelitis, extending from C7
downwards and ending at T12 (not shown).
OSMOSIS.ORG 543
NOTES
NOTES
CONGENITAL MYOPATHIES

▪ Inherited, progressive myopathic disorders ▪ Motor development milestone delays (e.g.
caused by genetic dystrophin gene walking)
mutation (dystrophinopathies) ▪ Progressive limb, girdle weakness
▪ Duchenne and Becker’s muscular ▪ Gowers’ sign
dystrophy (most common types) ▫ Weak hips, upper legs → using arms to
▫ X-linked recessive inheritance pattern help stand
▪ Dystrophin protein ▪ Waddling gait
▫ Normally links intracellular actin, ▪ Musculoskeletal abnormalities (e.g. calf
dystrophin-associated protein complex pseudohypertrophy, scoliosis, contracture)
to extracellular matrix to stabilize ▪ Progressive mobility impairment
sarcolemma
▪ Genetic defect → misshapen/absent
dystrophin protein → weak sarcolemma, DIAGNOSIS
cell damage → creatine kinase escapes
from/calcium enters damaged cell → ▪ See individual myopathies
cell death → muscle degeneration →
progressive weakness
TREATMENT
▪ See individual myopathies
BECKER'S MUSCULAR DYSTROPHY

osms.it/beckers-dystrophy
MNEMONIC: BMD
PATHOLOGY & CAUSES Cause of Becker’s Muscular
Dystrophy
▪ Caused by misshapen dystrophin gene due
Badly
to missense mutation
Made
▫ See mnemonic: BMD
Dystrophin (truncated protein)
COMPLICATIONS
▪ Rapidly progressive heart failure,
arrhythmia
544 OSMOSIS.ORG
Chapter 69 Congenital Myopathies

▪ Milder form, later onset than Duchenne ▪ No cure
muscular dystrophy
▪ Symptoms appear 10–20 years old MEDICATIONS
▪ Intellectual disability, contractures not as ▪ Glucocorticoids to slow muscle
common/severe as Duchenne muscular degeneration
dystrophy
▪ Cardiac fibrosis may be predominant
presentation feature OTHER INTERVENTIONS
▫ Starting with right ventricular ▪ Vitamin D, calcium supplements support
involvement, left ventricular dysfunction bone health
later ▪ Physical therapy, conditioning
▪ Complication management
DIAGNOSIS
LAB RESULTS
▪ ↑ serum creatine kinase
▪ Mutations in dystrophin by DNA test/
Western blot
▪ Muscle biopsy
▫ Stain for dystrophin
DUCHENNE MUSCULAR
DYSTROPHY
osms.it/duchenne_muscular_dystrophy
COMPLICATIONS
PATHOLOGY & CAUSES ▪ Wheelchair needed for mobility → scoliosis
▫ Scoliosis → poor pulmonary function
▪ Caused by absent dystrophin gene due to
nonsense/frameshift mutation ▪ Weak diaphragm → respiratory failure (may
develop)
▫ See mnemonic: DMD
▪ Fibrosis progression in dilated
cardiomyopathy → mitral regurgitation
MNEMONIC: DMD (may develop)
Cause of Duchenne Muscular ▪ Dilated cardiomyopathy (late stages) →
Dystrophy heart failure, arrhythmias (may develop)
Doesn’t ▪ Falling → arm, leg fractures
Make ▫ Vertebral compression fractures with
glucocorticoid therapy
Dystrophin
▪ Respiratory insufficiency/cardiomyopathy
→ death (late teens, early twenties)
OSMOSIS.ORG 545
SIGNS & SYMPTOMS
▪ More severe dystrophinopathy form
▪ Symptoms appear by five years old;
weakness usually occurs 2–3 years old
▪ Walking begins later in childhood; may
have slow, ungainly run; difficulty jumping,
walking up steps
▪ Proximal-limb muscle weakness before
distal, lower extremities before upper
▪ Gowers’ sign
▪ Waddling gait, calf pseudohypertrophy Figure 69.1 A muscle biopsy from an
▪ Decreased mobility individual in the later stages of Duchenne
muscular dystrophy. The myocyte
▫ May lead to independent ambulation
hypertrophy is even more pronounced and
impairment, wheelchair-use by 12 years
there is marked fatty replacement of the
old (usually)
muscle.
▪ Primary dilated cardiomyopathy,
conduction abnormalities
TREATMENT
▪ No cure
MEDICATIONS
▪ Glucocorticoids to slow muscle
degeneration
OTHER INTERVENTIONS
▪ Vitamin D, calcium supplements support
bone health
▪ Physical therapy, conditioning
▪ Complication management
Figure 69.2 A muscle biopsy from an

individual in the early stages of Duchenne
muscular dystrophy. There is variation in
myocyte size with small atrophic myocytes
juxtaposed with large, rounded hypertrophic
myocytes. There is intervening fibrosis.
DIAGNOSIS
LAB RESULTS
▪ ↑ serum creatine kinase
▪ Mutations in dystrophin by DNA test/
Western blot
Figure 69.3 A histological section of muscle
▪ Muscle biopsy
showing complete fibrofatty replacement in
▫ Stain for dystrophin end stage Duchenne muscular dystrophy.
546 OSMOSIS.ORG
NOTES
NOTES
CORTICAL DISORDERS

▪ Cortical structure damage in brain → DIAGNOSTIC IMAGING
functional regional-specific impairment ▪ CT scan, MRI, single-photon emission
computerized tomography (SPECT),
CAUSES positron emission tomography (PET)
▪ Stroke (common), hemorrhage, infection,
tumor, trauma, surgery, degenerative LAB RESULTS
disease (e.g. Broca’s aphasia, Wernicke’s ▪ Cerebrospinal fluid (CSF) analysis
aphasia, Klüver–Bucy syndrome)
OTHER DIAGNOSTICS
SIGNS & SYMPTOMS ▪ Functional assessment
▪ Affected brain region dependent
▪ Broca’s aphasia
▫ Expressive nonfluent aphasia
TREATMENT
▪ Wernicke’s aphasia
OTHER INTERVENTIONS
▫ Receptive fluent aphasia
▪ Address underlying cause
▪ Klüver–Bucy syndrome
▫ Amnesia, compulsive eating,
hypersexuality MNEMONIC: MD vs. DPM
Cortical brain
Memory Discrimination
Subcortical brain
Devoid of seizure
Primary sensation through
thalamus
Movement disorders (most)
OSMOSIS.ORG 547
BROCA'S APHASIA
osms.it/brocas-aphasia
▪ Broca’s area: anterior to primary motor
PATHOLOGY & CAUSES cortex, damage to adjacent areas
→ individual may have associated
▪ Aphasia contralateral hemiparesis, hemisensory loss
▫ Language loss/defect (speaking, fluency,
reading, writing, comprehension)
▫ Injury to brain’s language centers → DIAGNOSIS
different aphasia types
▫ Most lesions involve dominant DIAGNOSTIC IMAGING
hemisphere (left in 95% of right-handed ▪ Findings vary by underlying aphasia cause
individuals, right in 50% of left-handed ▫ May include evidence of bleeding/
individuals) hypodensities (stroke); mass effect,
▪ Broca’s aphasia overt tumors (cancer)
▫ Broca’s area: responsible for language ▫ Functional imaging will reveal regional
comprehension perfusion deficits
▫ Damage to Broca’s area → expressive
Brain CT scan
nonfluent aphasia (trouble expressing
language → “individuals know what ▪ With/without contrast
they want to say, but cannot get it out”)
MRI
▪ Standard MRI
CAUSES ▪ Diffusion tensor imaging (images white
▪ Stroke (superior division of left-middle matter tracts)
cerebral artery), traumatic brain injury, brain ▪ Functional MRI (images neurological
tumor, cerebral hemorrhage activity)
SPECT/PET
SIGNS & SYMPTOMS ▪ Images neurological activity
▪ Slowed, effortful speech

OTHER DIAGNOSTICS
▪ Short sentences without grammatical
construction (content appropriate, ▪ Language assessment, screening tools
meaningful)
▪ Individual with Broca’s aphasia may
describe trip to barber for haircut as follows
TREATMENT
▫ “Yes... errr... Tuesday... er... Dad and ▪ Treat underlying cause
Kevin T... (his own name), and Dad.... er...
▪ Most individuals improve/recover
the mall... and ah... Tuesday... Tuesday,
spontaneously within one month
ten o’clock... and.. oh barber... one... um’
barber... and er... hair...”
▪ Written, spoken language comprehension OTHER INTERVENTIONS
intact (or mildly impaired) ▪ Speech therapy (early initiation)
▪ Self-monitoring speech (generally still
capable) → awareness of speech deficit
548 OSMOSIS.ORG
Chapter 70 Cortical Disorders
KLÜVER–BUCY SYNDROME
osms.it/kluver-Bucy_syndrome

▪ AKA bilateral temporal lobe disorder ▪ Three/more symptoms present (most
▪ Caused by bilateral lesions to medial commonly placidity, hyperorality, dietary
temporal lobe changes)
▫ Hippocampus, surrounding structures
including amygdala; vital for declarative, DIAGNOSTIC IMAGING
long-term memory
CT scan/MRI
▪ Temporal lobe lesions
CAUSES
▪ Trauma/lobectomy, herpes simplex
encephalitis, stroke, Pick's disease, LAB RESULTS
Alzheimer’s disease ▪ If viral encephalitis underlying cause → CSF
analysis, serology
▪ CSF fluid analysis
SIGNS & SYMPTOMS ▫ Normal/mild protein ↑, normal/low
glucose content, normal/raised red cell
▪ Amnesia (profound antero-, retrograde count, lymphocytosis
amnesia), inappropriate things/compulsive
▪ CSF serology
eating, inappropriate object insertion into
mouth, hypersexuality, visual agnosia ▫ CSF antibodies compared to serum-
(inability to recognize familiar objects/ specific antibodies
people), docility (diminished fear/aggression ▫ 4x rise in virus specific IgG/positive IgM
response) ▪ CSF polymerase chain reaction (PCR) →
specific virus identification
TREATMENT
MEDICATIONS
▪ Herpes simplex encephalopathy →
antivirals
OSMOSIS.ORG 549
WERNICKE'S APHASIA
osms.it/wernickes-aphasia

▪ Wernicke’s aphasia DIAGNOSTIC IMAGING
▫ Wernicke’s area: assigns speech sounds ▪ Findings vary by aphasia cause
meaning ▫ May include evidence of bleeding/
▫ Damage to Wernicke’s area → receptive, hypodensities (stroke); mass effect,
fluent aphasia (trouble interpreting tumor (cancer)
language) ▫ Functional imaging reveals regional
perfusion deficits
CAUSES Brain CT scan
▪ Typically stroke (left middle cerebral artery), ▪ Vary by aphasia cause
traumatic brain injury, brain tumor, cerebral
▪ With/without contrast
hemorrhage
MRI
SIGNS & SYMPTOMS ▪ Vary by aphasia cause
▪ Standard MRI
▪ Impaired written, spoken language ▪ Diffusion tensor imaging
comprehension ▪ Functional MRI
▪ Unaware of speech error, meaninglessness
SPECT/PET
▪ Speech-specific symptoms
▪ Vary by aphasia cause
▪ Jargon: neologisms, real words used
meaninglessly; structurally intact speech,
typical intonation but lacks content OTHER DIAGNOSTICS
▫ Literal (phonemic) paraphasia: ▪ Language assessment, screening tools
substitution, addition, rearrangement
of sounds → errors sound like intended
word( e.g. “nog” instead of “dog”) TREATMENT
▫ Verbal (semantic) paraphasia: related
word instead of intended word (e.g OTHER INTERVENTIONS
“spoon” instead of “fork”) ▪ Most individuals improve/recover
▫ Neologism: made-up non-word instead spontaneously within one month
of intended word (e.g. “fluparp” for ▪ Speech, comprehension therapy (early
“kettle”) initiation)
▫ Circumlocution: describe intended word
(e.g. “it’s pointed, thin, you write with it”,
in reference to a pen)
▫ Run-on speech: verbalized idea stream
related to topic (e.g. asked what do you
do at the pet store: “The pet store is a
place, it is a place with many pets, and
pet food, my favourite animals are dogs,
at the pet store I buy food for my dog,
there are also fish at the pet store…”)
550 OSMOSIS.ORG
Chapter 70 Cortical Disorders
OSMOSIS.ORG 551
NOTES
NOTES
CRANIAL NERVE INJURY

▪ Brain/cranial nerves injury → neurological DIAGNOSTIC IMAGING
dysfunction
CT scan/MRI
▪ Specific, focused neurological functioning
CAUSES tests
▪ Trauma (accidental, inflicted), autoimmune,
infectious, idiopathic

▪ Varies widely ▪ Symptomatic complications, treat
▫ Area-dependent underlying causes
BELL'S PALSY
osms.it/bells-palsy
RISK FACTORS
PATHOLOGY & CAUSES ▪ Age (peak incidence > 50), diabetes
mellitus, pregnancy (third trimester), early
▪ Lower motor neuron weakness of cranial postpartum
nerve VII (facial nerve) → acute, peripheral
facial palsy
▪ Adversely affects facial motor activity; COMPLICATIONS
lacrimal, salivary glands (parasympathetic ▪ Corneal exposure → keratitis, motor
fibers); taste (afferent fibers on anterior regeneration → oral incompetence,
two-thirds of tongue); external auditory reinnervation “miswiring” → synkinesis
canal, pinna (somatic afferents) (involuntary muscle movement)
▪ Etiology unknown ▪ Incomplete sensory regeneration
▫ Potentially viral-associated ischemia, ▫ Dysesthesia (unpleasant/abnormal
demyelination (e.g. herpes zoster, touch), dysgeusia (distorted taste),
herpes simplex (HSV), Epstein–Barr ageusia (decreased taste)
virus, Lyme disease)
552 OSMOSIS.ORG
Chapter 71 Cranial Nerve Injury

▪ Unilateral facial weakness evolves rapidly LAB RESULTS
over 48 hours ▪ Serologic testing if viral infection suspected
▫ Eyebrow sags, eye won’t close, mouth
corner droops (drooling, difficulty eating/
OTHER DIAGNOSTICS
drinking), decreased tear production →
ocular dryness, hyperacusis (↓ everyday ▪ House–Brackmann facial nerve dysfunction
sound tolerance), ageusia (decreased classification
taste sensation) ▫ Grades facial muscle impairment degree
▪ Prodromal symptoms (pre-onset) ▫ Normal, mild, moderate, moderately-
▫ Ear pain, dysacusis (sound distortion) severe, severe, total paralysis
▪ See mnemonic: BELL’S Palsy ▪ Palpebral-oculogyric reflex (Bell
phenomenon)
▫ Attempted eyelid closure → upward eye
MNEMONIC: BELL'S Palsy deviation
Symptoms of Bell’s palsy ▪ Stethoscope loudness test
Blink reflex abnormal ▫ Individual listens to tuning fork through
Ear sensitivity stethoscope
Lacrimation: deficient, excess ▫ Hyperacusis indicates paralyzed
stapedius muscle on affected side
Loss of taste
▪ ↓ pinprick sensation in posterior auricular
Sudden onset
area
Palsy: CN VII nerve muscles
▪ ↓ taste
(All symptoms are unilateral)
▫ Sweetness, saltiness, acidity
▪ Motor nerve conduction studies (NCS)
▫ Estimates axonal loss degree
TREATMENT
MEDICATIONS
▪ Corticosteroids
▫ Symptom onset → begin within 3–4
days
OTHER INTERVENTIONS
▪ Artificial tears, eye patching
▫ Reduce corneal damage risk
▪ Physical therapy (e.g. facial exercise,
neuromuscular retraining)
▪ May resolve spontaneously within three
weeks
Figure 71.1 An individual with Bell’s palsy

affecting the right side of the face.
OSMOSIS.ORG 553
TRIGEMINAL NEURALGIA
osms.it/trigeminal-neuralgia

▪ AKA tic douloureux; stimulating facial DIAGNOSTIC IMAGING
trigger zone → intense, stabbing,
paroxysmal pain in trigeminal nerve (cranial CT scan/MRI
nerve V—usually V2/V3 subdivisions) ▪ May identify lesion/vascular compression
▫ Triggers: touching/moving tongue, lips, ▪ Electromyographyrigeminal reflex testing
face; chewing; shaving; brushing teeth; ▫ Measures muscles’, controlling nerves’
blowing nose; hot/cold drinks electrical activity
TYPES OTHER DIAGNOSTICS

▪ Classic ▪ Classic trigeminal neuralgia
▫ Most common; unknown etiology, ▫ No clinically evident neurologic deficit,
artery/vein compressing cranial nerve no better explanation via another
(CN) V root may → pain diagnosis, ≥ three attacks of unilateral
▪ Secondary facial pain fulfilling criteria A and B
▫ Nonvascular lesion compressing nerve ▫ A: Occurs in ≥ one trigeminal nerve
→ pain divisions, no radiation beyond trigeminal
distribution
▫ B: Pain has three or more of the
RISK FACTORS
following four characteristics: recurring
▪ Biological sex (female > male) paroxysmal attacks (< two minutes);
▪ Age (peak incidence 50–60) severe intensity; shock-like, shooting,
▪ Demyelinating disorders (e.g. multiple stabbing, sharp pain; stimulating
sclerosis) affected facial side → > two attacks
▪ Postherpetic trigeminal neuropathy (other attacked may be spontaneous)
▪ Acoustic neuroma
▪ Saccular aneurysm
TREATMENT
▪ Vestibular schwannoma
MEDICATIONS
SIGNS & SYMPTOMS ▪ Pain management
▪ Pain paroxysms SURGERY

▫ Last one–several seconds; may repeat; ▪ Microvascular decompression
usually unilateral ▪ Neuroablation
▪ Dull pain between paroxysms ▫ Rhizotomy with radiofrequency
▪ Facial muscle spasms/autonomic symptoms thermocoagulation/mechanical balloon
(e.g. lacrimation, diffuse conjunctival compression/chemical (glycerol) injection
injection, rhinorrhea) ▫ Radiosurgery
▫ Peripheral neurectomy, nerve block
554 OSMOSIS.ORG
NOTES
NOTES
DEMENTIA

▪ Acquired, progressive cognitive impairment ▪ Memory loss, difficulty retaining new
▪ Involving one/more cognitive functions information
▫ Memory, concentration, language, ▪ Language impairment
learning, praxis, judgment, executive ▪ Executive dysfunction
functions, social cognition ▫ Difficulty in handling complex tasks,
▪ Previous functional-level deterioration; concentration loss, poor judgement
consciousness remains intact ▪ Visuospatial ability impairment
▪ Apraxia (inability to perform an action)
CAUSES ▪ Behavioral disturbance
▪ Increasing age; most important risk factor ▪ Personality change
▪ Alzheimer disease
▪ Vascular dementia including multi-infarct
dementia, Binswanger’s disease DIAGNOSIS
▪ Lewy body dementia (DLB)
DIAGNOSTIC IMAGING
▪ Frontotemporal dementia (e.g. Pick disease)
CT scan
COMPLICATIONS ▪ Reveals microinfarcts indicative of vascular
▪ Inability to function independently in dementia
everyday life
▪ Debilitated state infections (death OTHER DIAGNOSTICS
secondary) ▪ Mental status examination
▪ See mnemonic for summary ▫ Identify cognitive impairment with
standardized mental status scales
▪ Montreal cognitive assessment (MoCA),
MNEMONIC: DEMENTIA mini-mental state examination (MMSE)
Common causes of Dementia ▪ Neuropsychological testing
Diabetes ▫ Quantitate cognitive impairment degree/
Ethanol domains involved (e.g. animal-naming
Medication test)
Environmental (eg CO ▪ Post-autopsy brain biopsy
poisoning)
Nutritional
Trauma
Infection
Alzheimer’s
OSMOSIS.ORG 555
neurotransmitter) levels; used for
TREATMENT Alzheimer disease, DLB
▪ Memantine
▪ Treatment/control of reversible causes
▫ N-methyl-D-aspartate (NMDA) receptor
antagonist (neuroprotective, disease-
MEDICATIONS modifying drug) for advanced dementia
▪ Acetylcholinesterase inhibitors
▫ ↑ acetylcholine (brain’s primary
ALZHEIMER'S DISEASE (AD)

osms.it/alzheimers-disease
RISK FACTORS
PATHOLOGY & CAUSES ▪ ↑ age (> 60 years old → risk doubling every
five years)
▪ Neurodegenerative disease; beta amyloid
▪ Family history
plaque, neurofibrillary tangle formation
→ impaired neuronal signaling, neuron ▪ Trisomy 21 (Down syndrome)
apoptosis ▪ Gene mutations affecting APP, presenilin 1
▪ Most common form of dementia and 2 (gamma secretase subunits)
▪ Sporadic (95% of cases), typically > 60 ▪ Apolipoprotein E-e4 alleles (ApoEe4)
years old ▫ ApoE normally breaks down beta
▫ Early AD onset unusual, mostly familial amyloid, e4 alleles encode less effective
ApoE
▪ Amyloid precursor protein (APP)
▪ History of hypertension, dyslipidemia,
▫ Normally located in neuronal membrane
cerebrovascular disease, altered glucose
▫ Growth, neuron-repair contributor metabolism, brain trauma
▫ Abnormal APP degradation via beta
secretase (normally degraded by
gamma, alpha secretase) → APP cut COMPLICATIONS
into insoluble fragments → create beta ▪ Complete debilitation, dependence on
amyloid plaque → AD results others
▫ Beta amyloid plaque pathology: ▪ Debilitation → dehydration, malnutrition,
signalling obstruction → deposits infection
around vessels (amyloid angiopathy), ▪ Death occurs 5–10 years after symptoms
↑ hemorrhage risk → initiates onset
inflammatory response
▪ Tau proteins
▫ Intracellular microtubule-associated MNEMONIC: RONALD
proteins Features of AD
▫ In AD, Tau proteins become Reduction of Ach
pathologically hyperphosphorylated Old age
→ aggregate, stop supporting Neurofibrillary tangles
microtubules → form neurofibrillary Atrophy of cerebral cortex
tangles → obstruct neuronal signaling (diffuse)
→ neuron apoptosis
Language impairment
Dementia (MC in elderly)/
Down’s syndrome
556 OSMOSIS.ORG
Chapter 72 Dementia
MNEMONIC: ALZHEIMER'S
SIGNS & SYMPTOMS Characteristics of AD
Anterograde amnesia
▪ Insidious onset, symptom progression
Life expectancy increase in
Early stages population shows increased
▪ Initial symptom prevalence
▫ (Commonly) recent memory impairment; Zapped (loss of)
inability to acquire, remember new acetylcholinergic neurons
information Hereditary disease
▪ Executive dysfunction Entire hippocampus affected
▫ Impaired reasoning, handling complex Identified by neurofibrillary
tasks, concentration/motivation loss, tangles
difficulty making/executing plans, poor Mutation in amyloid genes
judgement Entorhinal areas degenerate
▫ Impaired visuospatial skills first
▫ Reduced insight into cognitive deficit Retrograde amnesia
(anosognosia) Senile plaques at synapse
▫ Sleep disturbance
Intermediate/later stages OTHER DIAGNOSTICS

▪ Behavioral, psychological symptoms ▪ Mental status scale clinical assessment
(e.g., MoCA, MMSE)
▫ Apathy, social disengagement,
irritability, agitation, aggression, ▪ Neuropsychological testing
wandering, psychosis (hallucination, ▫ Confirm cognitive impairment diagnosis
delusion) ▪ Post-autopsy brain biopsy
▪ Motor task completion ▫ Shows characteristic beta-amyloid
▫ Difficulty (dyspraxia)/inability (apraxia) plaque, neurofibrillary tangle
▫ Impaired language function (e.g. word-
finding deficit)
▫ Remote memory loss
▫ Seizure
▫ Motor signs (e.g. pyramidal signs)
Advanced
▫ Complete debilitation, dependence on
others, urinary/fecal incontinence
DIAGNOSIS
▪ Diagnosis of exclusion
DIAGNOSTIC IMAGING
CT scan/MRI Figure 72.1 An MRI scan in the axial plane
demonstrating prominent sulci and gyri in an
▪ Exclude other dementia causes
individual with Alzheimer’s disease.
▪ Brain scans show diffuse cortical (especially
hippocampus) atrophy, gyri narrowing, sulci
widening, ventricle enlargement
OSMOSIS.ORG 557
TREATMENT
▪ No cure
MEDICATIONS
▪ Vitamin E supplementation may provide
benefit
▪ Memantine (advanced stages)
Figure 72.2 A histological section of the

hippocampus from an individual with
Alzheimer’s disease demonstrating a
neurofibrillary tangle.
Figure 72.3 A histological section of brain

from an individual with Alzheimer’s disease
demonstrating multiple amyloid plaques.
LEWY BODY DEMENTIA

osms.it/lewy-body-dementia
COMPLICATIONS
PATHOLOGY & CAUSES ▪ Persistent psychotic symptoms, especially
visual hallucinations
▪ Degenerative disease
▪ Depression
▫ Early dementia, visual hallucinations
▪ Complete debilitation, dependence on
onset; later parkinsonian clinical feature
others
onset, presence of Lewy bodies
▪ Debilitation infection often → death; life
▪ Occurs at 50–85 years old (typically)
expectancy ↓
▪ More rapid cognitive decline than AD
▪ Neuroleptic-agent sensitivity
▫ Adverse effects (parkinsonism) ↑
CAUSES severity, symptom exacerbation
▪ Alpha-synuclein protein aggregation in
neurons (particularly cortex, substantia
nigra) forming Lewy bodies, → apoptosis
558 OSMOSIS.ORG
Chapter 72 Dementia

Early stages ▪ No cure
▪ Progressive, fluctuating cognitive function
impairment MEDICATIONS
▫ Attention, executive, visuospatial
functions; memory affected later Alleviate symptoms
▪ Visual hallucination, disorganized speech, ▪ Acetylcholinesterase inhibitors
depression ▫ Cognitive symptoms
▪ Dopamine analogue
Later stages
▫ Motor symptoms
▪ Motor symptoms mimic Parkinson’s disease
▪ Atypical neuroleptic agents
▫ Resting tremor, stiffness, slow
movement, reduced facial expressions ▫ Persistent disabling hallucinations,
psychotic features (used very cautiously)
Other clinical features
▪ Rapid eye movement (REM) sleep behavior
disorder
▫ Sleep disturbance (sleep walking,
talking)
▪ Autonomic nervous system dysfunction
▫ Orthostatic hypotension, syncope,
urinary incontinence/retention,
constipation, impotence
▪ Repeated falls (parkinsonism), cognitive
fluctuation/orthostatic hypotension
▪ Neuroleptic sensitivity
Figure 72.4 A histological section of the brain

DIAGNOSIS demonstrating a Lewy body. They are caused
by the abnormal deposition of the protein
▪ Exclude other dementia causes alpha synuclein.
DIAGNOSTIC IMAGING
Single-photon emission computerized
tomography (SPECT) scanning
▪ Dopamine transporter ligand ioflupane
I-123 (DaTSCAN) shows ↓ transporter
perfusion
OTHER DIAGNOSTICS
▪ Neuropsychological testing
▫ Confirms cognitive-impairment
diagnosis
▪ Mental status scale assessment (e.g.
MoCA, MMSE) Figure 72.5 Immunohistochemical tain for the
▪ Post-autopsy brain biopsy protein alpha synuclein highlights the Lewy
bodies in the brain tissue of an individual with
▫ Shows Lewy bodies as eosinophilic
Lewy body dementia.
intracytoplasmic inclusions in cortical
neurons
OSMOSIS.ORG 559
FRONTOTEMPORAL DEMENTIA
(FTD)
osms.it/frontotemporal-dementia

▪ Heterogeneous degenerative frontal/ ▪ Frontal lobe involvement → behavior/
temporal lobe disease emotional changes
▫ Presents with personality/behavioral ▪ Disinhibition, emotional blunting, apathy/
disturbances/aphasia empathy-loss, hyperorality, compulsive
▪ Occurs < 65 years old (typically) behavior, family/friend dissociation
▫ Memory loss develops later (argumentative/hostile behavior)
▪ Inherited/sporadic ▪ Temporal lobe involvement → language
impairment, emotional disturbance
▪ Associated with specific-protein cellular
inclusions ▪ Difficulty finding correct word, progressive
aphasia, impaired word comprehension,
▫ Tau proteins (Pick disease)
emotional impairment (anxiety/irrational
▫ TAR DNA-binding protein 43 (TDP43) fear), sarcasm-recognition difficulty
▪ Protein buildup → stop neuronal signaling, ▪ Later stages → cognitive decline
lead neurons to apoptosis
▪ Worsening memory, inability to learn new
▪ Concomitant motor disease: 15–20% (e.g. things, concentration loss
parkinsonism, motor neuron disease)
TYPES
Pick disease
▪ Specific pathological FTD subtype
characterized by presence of Pick bodies
(tangles of abnormal Tau proteins—3R tau
isoforms)
▫ 3R tau isoforms (particular amino-acid
sequence repeated three times) are
hyperphosphorylated, stop supporting
microtubules, tangle into round silver-
staining inclusion bodies (Pick bodies)

axial plane demonstrating frontotemporal
volume loss.
560 OSMOSIS.ORG
Chapter 72 Dementia
DIAGNOSIS TREATMENT
▪ Exclude other dementia causes ▪ No cure
▫ Laboratory, imaging tests
MEDICATIONS
DIAGNOSTIC IMAGING
Symptom alleviation
MRI ▪ Antidepressants
▪ Structural imaging ▫ Severe behavioral symptoms
▪ Unilateral frontal/temporal atrophy, may → ▪ Atypical antipsychotic drugs have
both hemispheres, ventricle enlargement significant side effects
▪ Cholinesterase inhibitors
SPECT/perfusion-MRI/PET
▫ No convincing evidence of benefit
▪ Functional imaging
▪ Affected-lobe hypometabolism,
hypoperfusion OTHER INTERVENTIONS
▪ Physical exercise; physical, occupational,
speech therapy; ↑ supervision
LAB RESULTS
Genetic testing
MNEMONIC: PICK
▪ Familial FTDs
Features of Pick disease
Pick disease-specific biopsy findings Progressive degeneration of
▪ Pick bodies neurons
▫ Round/oval, Tau-positive, neuronal Intracytoplasmic Pick bodies
cytoplasmic inclusions Cortical atrophy
▪ Pick cells Knife edge gyri
▫ Swollen (ballooned) neurons
OTHER DIAGNOSTICS
▪ Neuropsychological tests
▫ Normal in early stages
▪ Mental status scale assessment (e.g.
MoCA, MMSE)
▪ Post-autopsy brain biopsy shows
characteristic microscopic findings
▫ Microvacuolation, neuronal loss, swollen
neurons, myelin loss, astrocytic gliosis,
abnormal protein inclusions
Figure 72.7 A brain at post mortem with

frontotemporal degeneration.
OSMOSIS.ORG 561
VASCULAR DEMENTIA
osms.it/vascular-dementia
▪ Deficits due to subcortical infarcts
PATHOLOGY & CAUSES
▫ Focal motor signs
▪ Heterogenous dementia ▫ Gait disturbance
▫ Results from multiple cerebrovascular ▫ Urinary frequency/urgency
events/chronic ischemia ▫ Personality, mood change
▪ Second most common dementia cause in ▫ Relatively mild memory deficit
elderly ▫ Improvements may occur between
▪ High Alzheimer disease comorbidity cerebrovascular events
▪ Multiple, bilateral, cortical, subcortical
infarcts/chronic ischemia → ↓ brain blood
supply → stepwise cognitive function DIAGNOSIS
decline, gait abnormality, focal neurological
deficits DIAGNOSTIC IMAGING
▫ Prominent executive function deficit MRI/CT scan
▫ Late-onset memory impairment ▪ Show multiple cortical, subcortical infarcts
▪ Binswanger’s disease ▪ Microinfarcts identified
▫ Large subcortical white matter areas ▫ Initiate evaluation to define etiology
involved
▫ Carotid Doppler ultrasound: reveal
carotid plaques
CAUSES ▫ Echocardiogram: reveal cardiogenic
▪ Cerebral artery atherosclerosis emboli
▪ Carotid artery/heart embolization
▪ Chronic hypertension → cerebral arterioles OTHER DIAGNOSTICS
sclerosis ▪ Neuropsychological testing
▪ Vasculitis ▫ Detects cognitive impairment, domains
involved
RISK FACTORS ▫ Similar language, construction, memory
▪ Smoking, hypertension, diabetes, registration deficits with AD, but more
insulin resistance, hyperlipidemia, impaired executive functioning
hyperhomocysteinemia ▪ Microinfarcts identified
▫ Initiate evaluation to define etiology
▫ Holter monitor (detect arrhythmias)
SIGNS & SYMPTOMS ▫ Risk factor screening
▪ Progressive, stepwise cognitive function
impairment (affected cortical area-
dependent)
▫ Frontal: executive dysfunction (frontal)
▫ Left parietal: aphasia, apraxia, agnosia
▫ Right parietal: hemineglect, confusion,
agitation, visuospatial, constructional
difficulty
▫ Temporal: anterograde amnesia
562 OSMOSIS.ORG
Chapter 72 Dementia
TREATMENT
▪ No cure
MEDICATIONS
▪ Vascular risk factor control
▫ Antihypertensive drugs, antidiabetic
agents, statins, antiplatelet agents
▪ Acetylcholinesterase inhibitors/memantine
OTHER INTERVENTIONS
▪ Vascular risk factor control
▫ Lifestyle changes
Figure 72.8 An MRI scan in the axial plane

of the head of an individual with cognitive
impairment. There are multiple small white
matter infarcts and an absence of cortical
atrophy.
OSMOSIS.ORG 563
NOTES
NOTES
EAR PATHOLOGY

▪ Structural, functional pathology affecting DIAGNOSTIC IMAGING
different ear components ▪ Otoscopy
▪ Outer ear: auricle, pinna, ear canal ▫ Tympanic membrane visualization
▫ Inflammation/infection → otitis externa
▪ Outer ear, middle ear: separated by OTHER DIAGNOSTICS
tympanic membrane (eardrum); normally
▪ Outer ear inspection
no air passage/fluids between two
compartments ▪ Hearing screening tests (Weber, Rinne
tests)
▫ Perforated eardrum → communication
through tympanic membrane ▫ Distinguishes between conductive,
sensorineural hearing loss
▪ Middle ear: tiny chamber; contains
functional ear bones (malleus, incus,
stapes)
TREATMENT
▫ Inflammatory middle ear disease →
otitis media MEDICATIONS
▪ Eustachian tube: connects middle ear to ▪ Topical otic drops/systemic agents
nasopharynx
▪ Antihistamines/corticosteroids/
▫ Failure to open/close, remove secretions decongestants (guided by specific
→ Eustachian tube dysfunction diagnosis)

▪ Drain fluid accumulation/debride
▪ Hearing loss granulation tissue/repair defect
▪ Ear pain
▪ Ear discharge
564 OSMOSIS.ORG
Chapter 73 Ear Pathology
EUSTACHIAN TUBE DYSFUNCTION

osms.it/eustachian-tube-dysfunction
PATHOLOGY & CAUSES Ciliary dyskinesia

▪ Acquired: toxins → ciliary damage,
▪ Any primary Eustachian tube function paralysis → mucociliary elevator failure
failure ▫ Cilia can’t flick back and forth (e.g.
▪ Failure to equalize/dilatory dysfunction cigarette smoke)
▫ Eustachian tube may not open → ▪ Congenital: cystic fibrosis → very thick
tympanic membrane stretches → pain secretions not adequately cleared
Patulous dysfunction (chronic patency)
▪ Normal Eustachian tube is two-way valve COMPLICATIONS
(opens to equalize pressure, closed at rest) ▪ Conductive hearing loss, otitis media,
▪ Persistent opening → irritant/bacteria tympanic membrane perforation,
entering middle ear cholesteatoma
Ciliary dyskinesia
▪ Tiny cilia line Eustachian tube, clear out SIGNS & SYMPTOMS
middle ear mucus secretion
▪ Ciliary dysfunction/dyskinesia: cilia fail ▪ Affected ear is clogged, muffled
to clear section → stagnant secretion → ▪ Ear pain
complications (e.g. otitis media) ▪ Autophony (hearing one’s own voice,
breathing)
CAUSES ▫ Encountered primarily in patulous
dysfunction
Failure to equalize/dilatory dysfunction ▪ If inner ear affected → balance problems
▪ Functional: inflammation (viral infection—
e.g. common cold, allergy) → Eustachian
tube swelling, secretion accumulation → DIAGNOSIS
Eustachian tube mechanical blockage →
equalization failure DIAGNOSTIC IMAGING
▪ Anatomical: regional mass pressure (e.g.
tumour) or previous trauma scar/medical CT scan / MRI
procedure ▪ Contrast in persistent effusion cases
▫ Neoplasm may cause Eustachian tube
Patulous dysfunction (chronic patency) obstruction
▪ Weight-loss (> 6 lbs/2.7 kg) → tissue
atrophy (e.g. chronic illness) Nasal endoscopy
▪ Chronic allergy/gastric-content reflux → ▪ Inflammation, secretion, allergic
mucosal atrophy manifestation signs
▪ Chronic gum-chewing → repeated muscle- ▫ Eustachian tube opening quality
facilitated Eustachian tube opening (assessed through yawn, swallowing
▪ Short, floppy Eustachian tubes (in children) maneuvers)
→ provide little resistance against middle- Otoscopic ear examination
ear reflux during ↑ positive pressure on
▪ Normal tympanic membrane appears shiny,
nasopharyngeal end of tube (e.g. crying/
translucent
nose blowing)
OSMOSIS.ORG 565
▪ Examine for abnormality (e.g. retraction,
effusion, perforation) TREATMENT
▫ Dull bluish-gray/yellowish coloration
denotes effusion behind membrane;
MEDICATIONS
reddish coloration, engorged vessels ▪ Dilatory dysfunction
signal inflammation ▫ Upper respiratory tract inflammation
▪ Pneumatic examination (viral infection, allergy) → short
intranasal/systemic decongestant,
▫ Fluid-filled ear minimizes tympanic
corticosteroid course
membrane excursion with insufflation
▪ Patulous dysfunction
▫ Avoid decongestants/corticosteroids
OTHER DIAGNOSTICS
▪ Hearing tests for conductive hearing loss
▫ Weber test: sound lateralized to
SURGERY
affected ear ▪ Dilatory dysfunction
▫ Rinne test: BC > AC ▫ Tympanostomy tubes: hollow tubes
inserted into eardrum → create direct
opening between middle, outer ear
→ allow easy pressure equilibration,
accumulated debris drainage
OTHER INTERVENTIONS
▪ Patulous dysfunction
▫ Hydration, nasal saline drops/irrigation
OTITIS EXTERNA
osms.it/otitis-externa
RISK FACTORS
PATHOLOGY & CAUSES ▪ Frequent swimming
▪ Mechanical cleaning/irritation (cotton
▪ AKA “swimmer’s ear”
swabs/scratching)
▪ Outer ear canal irritation
▪ Ear canal occlusion (hearing aid,
headphone)
CAUSES ▪ Diabetes
▪ Outer ear canal microbial infection (primary
cause)
▫ Bacterial (90%): Pseudomonas SIGNS & SYMPTOMS
aeruginosa, Pseudomonas vulgaris, E.
coli, S. aureus ▪ Acute (< six weeks)
▫ Fungal: Candida albicans, Aspergillus ▫ Pinna traction → aggravated pain
niger ▫ Otorrea: sticky yellow discharge)
▪ Dermatological conditions ▫ Swelling, purulent debris → external
▫ Allergic contact dermatitis, psoriasis, canal obstruction → conductive hearing
atopic dermatitis loss, +/- aural fullness
▫ Posterior auricular lymphadenopathy
566 OSMOSIS.ORG
▫ Complicated otitis externa: periauricular

soft tissue erythema, swelling TREATMENT
▪ Chronic (> three months)
MEDICATIONS
▫ External ear canal pruritus; epidermis
▪ General
atrophy, scaling; otorrhea; normal
tympanic membrane ▫ Burow’s solution: topical drops
application (buffered aluminum sulfate,
acetic acid mixture)
DIAGNOSIS ▪ Bacterial
▫ Antipseudomonal otic drops/topical
LAB RESULTS steroid drops/combination
▪ Discharge ▫ 3% acetic acid solution → acidify ear
▫ Gram stain, culture canal (bacteriostatic acidic pH)
▫ Systemic antibiotics (lymphadenopathy/
cellulitis)
OTHER DIAGNOSTICS
▪ Fungal
▪ Note physical outer ear change (discharge,
erythema, scaling) ▫ Topical antifungal preparation (e.g.
gentian violet, boric acid)
▪ Hearing tests for conductive hearing loss
▪ Chronic otitis externa (pruritus without
▫ Weber test: sound lateralized to
obvious infection)
affected ear
▫ Corticosteroid otic drops alone
▫ Rinne test: BC > AC
OTHER INTERVENTIONS
▪ General
▫ Clean ear under magnification →
irrigation, suction, dry-swabbing
▪ Fungal
▫ Debridement
Figure 73.1 An individual with otitis externa

of the left ear.
OSMOSIS.ORG 567
OTITIS MEDIA
osms.it/otitis-media
CAUSES
PATHOLOGY & CAUSES ▪ Bacteria
▪ Inflammatory middle ear diseases ▫ S. pneumoniae, H. influenzae, M.
catarrhalis, group A streptococcus, S.
aureus)
TYPES ▪ Virus
Acute otitis media ▫ Respiratory syncytial virus, influenza,
parainfluenza, adenovirus)
▪ Acute middle ear compartment infection
(< three weeks) ▫ Often viral/bacterial coinfection
▪ Acute infection/allergies → nasopharyngeal
mucous membrane inflammation → RISK FACTORS
Eustachian tube dysfunction → secretion ▪ Smoke, air-pollution exposure
reflux/aspiration from nasopharynx to ▪ Immunosuppression
middle ear (normally sterile) → infection
▪ Pacifier use; daycare
Otitis media with effusion ▪ Down syndrome
▪ Fluid presence in middle ear, with/without ▪ Recent upper-respiratory tract viral
infection signs infection
▪ Eustachian tube dysfunction → trapped ▪ Craniofacial malformation (cleft lip/palate,
fixed gas volume in middle ear → microcephaly)
surrounding tissue slowly absorbs gas → ↓ ▪ Cystic fibrosis
middle-ear pressure
▫ Sufficient ↓ middle-ear pressure →
surrounding tissue fluid drawn into
middle ear cavity → middle-ear effusion
(transudate)
▪ Most common pediatric hearing loss cause
Chronic suppurative otitis media

▪ Acute otitis media complication → chronic
suppurative otitis media
▪ Perforated tympanic membrane with
persistent drainage (> 6–12 weeks)
▪ Acute otitis media → prolonged
inflammatory response → middle ear
mucosal oedema; tympanic membrane
ulceration, perforation → chronic middle
ear, mastoid cavity inflammation →
persistent discharge from middle ear
through perforated tympanic membrane
▪ Persistent infection/inflammation → Figure 73.2 A tympanic mebrane bulging as
granulation tissue → polyps within middle- due to the accumulation of pus in the middle
ear space → inflammation, ulceration, ear of an individual with otitis media.
infection, granulation tissue formation cycle
→ eventual surrounding bony structure
destruction
568 OSMOSIS.ORG
COMPLICATIONS ▪ Chronic suppurative otitis media

▪ Tympanic membrane perforation, ▫ Perforated tympanic membrane;
mastoiditis, cholesteatoma, bacterial otorrhea; visible granulation tissue
meningitis, dural sinus thrombosis, (medial canal/middle-ear space); middle
conductive/sensorineural hearing loss ear mucosa (through perforation)
may be edematous, polypoid, pale,
erythematous
SIGNS & SYMPTOMS
OTHER DIAGNOSTICS
▪ Acute otitis media
▫ Otalgia, fever, conductive hearing loss Otitis media with effusion
(triad) ▪ Hearing tests for conductive hearing loss
▫ Children: ear pulling, crying, poor sleep, ▫ Weber test: sound lateralized to
irritability affected ear
▫ Crying → small blood vessel distension ▫ Rinne test: BC > AC
on tympanic membrane → mimics otitis ▪ Audiological investigation
media redness (confounds diagnosis)
▫ Flat audiogram, tympanogram
▪ Otitis media with effusion
▫ Ear fullness, conductive hearing loss +/-
tinnitus, no pain/fever TREATMENT
▪ Chronic suppurative otitis media
▫ Perforated tympanic membrane; MEDICATIONS
otorrhea; hearing loss; no pain/ ▪ Acute otitis media
discomfort; fever, vertigo, pain → ▫ Analgesics
danger signs (possible complications)
▫ Systemic antibiotics if severe/persistent
(> three days)
DIAGNOSIS ▪ Otitis media with effusion
▫ Avoid antihistamines, decongestants →
DIAGNOSTIC IMAGING secretions thicken
▪ Chronic suppurative otitis media
CT scan/MRI ▫ Corticosteroid drops → ↓ granulation
▪ Acute otitis media tissue
▫ Severe cases with hearing loss/high ▫ Antibiotics (topical/drops)
fever) ▫ Granulation tissue control: granulation
▫ Excludes more serious complications tissue prevents affected-site topical
(e.g. bony destruction/meningitis) medication penetration
Otoscopy
▪ Acute otitis media SURGERY
▫ Tympanic membrane ↓ mobility, ▪ Acute otitis media
hyperemia, bulging membrane (pus ▫ Frequent recurrence: tympanostomy
behind tympanic membrane), landmark tubes
loss (malleus handle, long process not ▪ Otitis media with effusion
visible) ▫ Severe cases: tympanostomy tubes,
▪ Otitis media with effusion myringotomy (tiny eardrum incision) +/-
▫ Amber/dull grey tympanic membrane ventilating-tube insertion
discoloration; meniscus fluid level ↑ ↓,
air bubbles behind tympanic membrane;
air insufflation → immobile tympanic
membrane
OSMOSIS.ORG 569
OTHER INTERVENTIONS ▪ Chronic suppurative otitis media
▪ Otitis media with effusion ▫ Mechanical/irrigative debris clearing:
▫ Watchful waiting: 90% of children aural toilet (mechanical removal of
clear fluid in three months without mucoid exudates, desquamated
intervention epithelium, associated debris prior
▫ Minor cases: may resolve to medication administration); aural
spontaneously; manual autoinflation irrigation (50% acetic acid/sterile water
(manually pinch nasal passage, close ear-rinse solution)
back of pharynx → forceful diaphragm
contraction)
PERFORATED EARDRUM
osms.it/perforated-eardrum

▪ Tympanic membrane communication DIAGNOSTIC IMAGING
between middle ear, external environment
Otoscopy
▪ Perforation visualization
CAUSES
▪ Otitis media
▪ Trauma
OTHER DIAGNOSTICS
▪ Hearing tests: conductive hearing loss
▪ Explosive/percussive force, exceptionally
loud noise ▫ Weber test: sound lateralized to
affected ear
▪ Iatrogenic, sudden pressure ↑ ↓ (with
blocked Eustachian tubes) ▫ Rinne test: BC > AC
▪ Audiometry: conductive hearing loss
COMPLICATIONS
▪ Chronic infection → permanent hearing loss TREATMENT
MEDICATIONS
SIGNS & SYMPTOMS ▪ Avoid otic drops containing gentamicin,
neomycin sulfate, tobramycin
▫ Hearing loss
▫ Ototoxicity → permanent hearing loss
▫ Tinnitus
▪ Otorrhea control
▫ Ear-ache (infection association)
▫ Topical: fluoroquinolone otic drops
▫ Otorrhea
▫ Systemic: antibiotics covering
▫ Nausea/vomiting respiratory flora
570 OSMOSIS.ORG
SURGERY
▪ Tympanoplasty: surgical repair
OTHER INTERVENTIONS
▪ Watchful waiting
▫ Perforations may heal in weeks/months
Figure 73.3 A partial perforation of the ear

drum.
OSMOSIS.ORG 571
NOTES
NOTES
ENCEPHALOPATHY

comprehensive metabolic panel (CMP)
PATHOLOGY & CAUSES ▫ ↑ ammonia, ↑ transaminases, ↑
prothrombin time, hyper/hypoglycemia
▪ Abnormal brain structure/function
▪ Permanent/reversible brain injury due to Cerebrospinal fluid (CSF)
direct injury/other illness ▪ Determine underlying cause, rule out other
causes
SIGNS & SYMPTOMS

OTHER DIAGNOSTICS
▪ Altered mental status Electroencephalogram (EEG)
▫ Irritability, agitation, confusion, ▪ High-amplitude low-frequency, triphasic
somnolence, stupor, coma, psychosis, waves
delirium
▪ Seizure, myoclonus, asterixis, ataxia, tremor
TREATMENT
▪ Anticonvulsants
DIAGNOSTIC IMAGING
▫ Individuals with seizures due to
Brain imaging (CT scan, MRI, etc.) encephalopathy
▪ Changes indicative of Wernicke–Korsakoff
syndrome (e.g. shrunken mammillary OTHER INTERVENTIONS
bodies) ▪ Careful monitoring, supportive measures
(e.g. IV fluids, nutritional support)
LAB RESULTS
Blood studies
▪ Complete blood count (CBC),
572 OSMOSIS.ORG
Chapter 74 Encephalopathy
BERIBERI
osms.it/beriberi

▪ Thiamine (vitamin B1) deficiency DIAGNOSTIC IMAGING
▫ Decreased intake/inability to absorb
CT scan/MRI
thiamine
▪ Changes indicative of Wernicke–Korsakoff
syndrome (e.g. shrunken mammillary
RISK FACTORS bodies)
▪ Common in individuals who are alcoholic,
malnourished, elderly
OTHER DIAGNOSTICS
▪ History
COMPLICATIONS ▫ Alcoholism/low nutritional state
▪ “Wet beriberi”
▫ Cardiomegaly, cardiomyopathy, heart
failure TREATMENT
MEDICATIONS
SIGNS & SYMPTOMS ▪ IV thiamine supplementation
▫ Avoid glucose before thiamine
▪ Nystagmus, ataxia, ophthalmoplegia if alcoholic; can precipitate
(triad of Wernicke–Korsakoff syndrome), encephalopathy
confusion
▪ Wet beriberi: tachycardia, dyspnea, edema
▪ Dry beriberi: peripheral neuropathy,
confusion, pain; AKA Wernicke–Korsakoff
syndrome
HEPATIC ENCEPHALOPATHY
osms.it/hepatic-encephalopathy
▪ Other injuries (e.g. alkalosis, metabolic
PATHOLOGY & CAUSES abnormalities, medications, bleeding,
infection) → hepatic encephalopathy
▪ Brain injury due to toxic metabolites; not
removed by liver due to liver dysfunction
▪ Accumulation of toxic metabolites
(e.g. ammonia), byproduct of nitrogen
metabolism
▪ Ammonia detoxification in astrocytes →
glutamine accumulation → osmotic stress
→ swelling
OSMOSIS.ORG 573
OTHER DIAGNOSTICS
SIGNS & SYMPTOMS ▪ Psychometric tests
▫ Inhibitory control test (ICT); mental
▪ Mental status: confusion, poor
status changes
concentration, stupor, coma
▪ History
▪ Neuromuscular: asterixis, rigidity,
hyperreflexia ▫ Liver disease, altered mental status
▪ Graded by severity EEG
▫ Grade I: mild; short attention span; ▪ High-amplitude low-frequency, triphasic
mood, sleep problems waves
▫ Grade II: moderate; decreased energy,
slurred speech, tremors
▫ Grade III: severe; confusion, stupor, TREATMENT
anxiety
▫ Grade IV: coma MEDICATIONS
▪ Lactulose
▫ Decrease absorption of ammonia
DIAGNOSIS ▪ Rifaximin
▫ Kill bowel flora that produce ammonia
DIAGNOSTIC IMAGING
T1-weighted MRI OTHER INTERVENTIONS
▪ Hyperintensity of globus pallidus ▪ Nutritional support
▫ Limit protein intake
LAB RESULTS
▪ Blood tests
▫ ↑ ammonia
REYE SYNDROME
osms.it/reye-syndrome
brain barrier → swelling, oxidative damage
PATHOLOGY & CAUSES to astrocytes → brain inflammation, edema
→ encephalopathy
▪ Encephalopathy, liver failure associated
with salicylate use in children with viral
illness SIGNS & SYMPTOMS
▪ Rare syndrome in children ages 4–12;
associated with aspirin use during viral ▪ Five stages
infection (e.g. varicella, influenza A/B) 1. Quiet, sleepy, vomiting
▪ Uncoupling of oxidative phosphorylation 2. Stupor, seizures, decorticate response,
reactions intact pupillary reflex
▪ Oxidative phosphorylation in mitochondria 3. Possible coma, decerebrate response,
fails → liver damage → nitrogen-containing absence of pupillary reflex
toxins not removed from blood → ammonia
4. Coma, absence of deep tendon reflex
accumulates in blood → crosses blood-
5. Death
574 OSMOSIS.ORG
Chapter 74 Encephalopathy
OTHER INTERVENTIONS
DIAGNOSIS ▪ Hyperventilation
LAB RESULTS ▫ Manage cerebral edema
▪ Blood studies ▪ Careful monitoring, supportive measures
(e.g. IV fluids)
▪ ↑ ammonia, ↑ transaminases, ↑ prothrombin
time, hyper/hypoglycemia
OTHER DIAGNOSTICS
▪ History
▫ Viral illness, aspirin use
TREATMENT
MEDICATIONS
▪ Mannitol, glycerol
▫ Manage cerebral edema
of the liver of a child who died from
Reye syndrome. The hepatocytes have
accumulated fat droplets which causes a pale
appearance.
OSMOSIS.ORG 575
NOTES
NOTES
EPILEPSY & SEIZURES

▪ Idiopathic seizures/epilepsy disorder
PATHOLOGY & CAUSES ▫ Most common
▪ Seizure: brain neurons → abnormal, ▪ Disorders
excessive, synchronized electrical activity ▫ Brain injury, brain abscess, brain tumors,
period eclampsia, encephalitis, Angelman
▫ Clusters of brain neurons temporarily syndrome
impaired (seconds-minutes) → ▪ Cerebrovascular disease
paroxysmal electrical discharges → ▫ Intracranial bleeding; perinatal hypoxia,
disordered awareness, behavior, ischemia; ischemic stroke
movement ▪ Systemic disorders
▫ → too much excitatory, too little ▫ Uremic encephalopathy, hepatic
inhibitory activity encephalopathy, electrolyte imbalances,
hypoglycemia, thiamine deficiency,
CAUSES vitamin B12 deficiency
▪ Many unknown causes; some known Nonepileptic seizures
causes (e.g. brain infection): ▪ → fainting spell, psychological conditions,
▫ ↑ excitation: long-lasting/fast activation stress, not epileptic brain activity
of NMDA receptor via glutamate
▫ ↓ inhibition: genetic mutations →
dysfunctional GABA receptors SIGNS & SYMPTOMS
▪ Causation → classification
▪ Subtle signs
Provoked seizures ▫ Spacing out, unusual sensations, brief
▪ Triggers → abnormal brain activity; subside muscle jerks
once trigger removed ▪ Life-threatening
▪ Medication ▫ Generalized muscle contractions > five
▫ Aminophylline, bupivacaine, bupropion, minutes
butyrophenones
▪ Recreational drugs
▫ Amphetamines, cocaine, DIAGNOSIS
methylphenidate, psilocybin, psilocin
▪ Alcohol consumption/ withdrawal DIAGNOSTIC IMAGING
▪ Flashing lights MRI/CT scan
▫ Photosensitive epilepsy ▪ Detects structural brain abnormalities (brain
▪ Fever tumors or vascular disorders)
▫ Febrile seizures
Epileptic seizures LAB RESULTS

▪ Recurring, unpredictable seizures; brain ▪ Electrolytes; blood glucose; complete
dysfunction → abnormal brain activity; blood cell count; liver, renal function; serum
seizures triggered calcium; urinalysis
576 OSMOSIS.ORG
Chapter 75 Epilepsy & Seizures
▫ Assess possible underlying infection, MNEMONIC: SICK DRIFT3R

genetic condition, metabolic disorder, Differential diagnosis for
other causes seizures
Substrates: sugar, oxygen
OTHER DIAGNOSTICS Isoniazid
Cations: Na, Ca, Mg
Electroencephalogram (EEG)
Kids: pregnancy/eclampsia
▪ Detects abnormal, epileptiform brain
Drugs
electrical activity
Rum: alcohol withdrawal
Clinical history Illnesses: chronic
▪ Assess type of seizure; differentiate Fever
between primary, secondary seizures Trauma
Neurological exams 3 “antis”: antihistamine,
antidepressant,
▪ Assess behavior, motor abilities, mental
anticonvulsants
functions → underlying seizure cause, type
Rat poison
TREATMENT
MEDICATIONS
Epilepsy
▪ Antiepileptic medication
▫ Depends on type of seizures, age,
lifestyle, and comorbidities
OTHER INTERVENTIONS
Provoked seizures
▪ Address trigger
ABSENCE SEIZURE
osms.it/absence-seizure
CAUSES
PATHOLOGY & CAUSES ▪ Cause → abnormal neuronal activity
unknown
▪ Formerly called petit mal seizures
▪ Generalized seizure; brief loss of
awareness/responsiveness; sudden onset, COMPLICATIONS
termination; usually no postictal state ▪ May progress into generalized tonic-clonic
▪ Most common in children; can occur seizures
50–100 times/day; often misdiagnosed as ▪ Learning difficulties
inattentiveness, daydreaming ▪ Behavior problems
OSMOSIS.ORG 577
(e.g. lip smacking, chewing motions, eyelid
flutters)
▪ Possible sign of coexisting seizure types
▪ No recollection of seizure
DIAGNOSIS
DIAGNOSTIC IMAGING
MRI/CT scan
▪ To rule out brain abnormalities
OTHER DIAGNOSTICS
EEG
▪ Shows generalized spike-and-slow wave
discharges
Figure 75.1 An EEG taken from an individual
having an absence seizure. ▪ Easily induced by hyperventilation (most
reliable test)

▪ Sudden loss of awareness, responsiveness ▪ Usually resolves as child ages
→ from few seconds-half a minute
▪ Blank stare MEDICATIONS
▪ Preceding activity ceases
▪ Ends abruptly or followed by automatisms Anticonvulsant medication
▪ Valproic acid (drug of choice in case
of other coexisting types of seizures),
ethosuximide (only for absence seizures)
EPILEPTIC SEIZURE
osms.it/epileptic-seizure
Generalized seizures
PATHOLOGY & CAUSES ▪ Affect both brain hemispheres
▪ Recurrent, unprovoked seizures → epilepsy ▫ Subcategories: tonic seizures, atonic
symptoms seizures, clonic seizures, tonic-clonic
seizures, myoclonic seizures, absence
seizures
TYPES
Focal (partial) seizures CAUSES
▪ Affect one brain hemisphere ▪ Seizures genetic/idiopathic
▫ Subcategories: Focal aware seizure; ▪ Cerebrovascular disease
focal impaired awareness seizure ▫ Intracranial bleeding; perinatal hypoxia,
578 OSMOSIS.ORG
ischemia; cerebrovascular insult ▪ Tonic-clonic seizures

▪ Neurological disorder/illness ▫ Tonic phase → muscles suddenly stiffen;
▫ Brain tumors, metastases; brain injury; clonic phase → muscles rapidly contract,
brain abscess; encephalitis; eclampsia; relax
Angelman syndrome; multiple sclerosis; ▪ Myoclonic seizures
systemic lupus erythematosus ▫ Short, one/multiple muscle twitches over
▪ Systemic disorders short time
▫ Uremic encephalopathy; hepatic ▪ Absence seizures
encephalopathy; electrolyte imbalances ▫ Loss of awareness/responsiveness;
(hypercalcemia, hyponatremia); staring spell
hypoglycemia, hyperglycemia; thiamine,
pyridoxine, vitamin B12 deficiency Generalized seizures often → postictal
state
▪ Confusion, drowsiness, sleepiness, total
COMPLICATIONS
amnesia for hours
▪ Injury → falling, drowning, car crash during
attack Todd’s paralysis or paresis
▪ Pregnancy complications → seizures during ▪ May follow; affects arms/legs, usually
pregnancy; → antiepileptic medication → limited to one side
teratogenic effects ▫ Lasts about 15 hours; temporary, but
▪ Status epilepticus severe suppression of brain activity in
▫ Continuous seizure activity > five seizure-affected area
minutes → permanent brain damage,
death
▪ Sudden unexpected death in epilepsy DIAGNOSIS
(SUDEP) → frequent tonic-clonic seizures,
inadequate antiepileptic treatment DIAGNOSTIC IMAGING
MRI/CT scan
SIGNS & SYMPTOMS ▪ Detect structural brain abnormalities (brain
tumors, vascular disorders)
Focal seizures
▪ Focal aware seizure LAB RESULTS
▫ No awareness impairment; motor, ▪ Electrolytes, blood glucose and calcium
sensory, autonomic, psychological levels
sensations ▫ Assess possible underlying infection,
▪ Focal impaired awareness seizure genetic condition, metabolic disorder,
▫ May include automatisms (e.g. lip other causes
smacking, chewing, swallowing,
unpurposeful walking, etc.) OTHER DIAGNOSTICS
Generalized seizures ▪ ≥ two unprovoked seizures required for
▪ Tonic seizures epilepsy diagnosis
▫ Sudden, continuous muscle EEG
contractions; causes falling, often ▪ Detect abnormal, epileptiform electrical
backwards brain activity
▪ Atonic seizures
▫ Sudden muscle relaxation; causes Neurological exam
falling, often forwards ▪ Assess behavior, motor abilities, mental
▪ Clonic seizures functions → underlying cause, type of
▫ Rhythmic muscle contractions seizure
(convulsions)
OSMOSIS.ORG 579
▫ If unsure: broad spectrum
TREATMENT anticonvulsants (effective for all types):
valproate, lamotrigine, topiramate
MEDICATIONS
Anticonvulsant medications SURGERY
▪ Depends on type of seizures, age, lifestyle, ▪ Surgical resection in certain cases (e.g.
comorbidities brain tumors or vascular disorders)
▫ Focal epilepsy: lamotrigine,
oxcarbazepine, carbamazepine
▫ Generalized epilepsy: valproate,
lamotrigine, ethosuximide (only for
absence seizures)
FEBRILE SEIZURE
osms.it/febrile-seizure
RISK FACTORS
PATHOLOGY & CAUSES
▪ Genetic susceptibility
▪ Triggered by fever ▪ Age 6 months–5 years
▪ Exact mechanism unknown; proposed ▪ Infections
explanations ▫ Usually common infections, e.g. otitis
▫ ↑ body temperature during fever → ↑ media
excitability of neurons
▫ Hyperventilation during fever → ↓
CO2 levels → respiratory alkalosis → ↑
SIGNS & SYMPTOMS
neuronal excitability
▪ High body temperature: >38° C/100.4° F
▫ ↑ cytokine levels during fever →
enhancement of NMDA receptors → ↑ ▪ Simple febrile seizure
neuronal excitability ▫ Presents as tonic-clonic seizures
▫ Tonic phase (muscles stiffen, go rigid) →
clonic phase (muscles rapidly contract,
TYPES relax) → convulsions
Simple febrile seizure (most common) ▫ Followed by postictal state, residual
▪ Affects whole body (tonic-clonic seizures) arm/leg weakness
▪ Lasts < 15 minutes
▪ Does not repeat within 24 hours DIAGNOSIS
Complex febrile seizure
LAB RESULTS
▪ If 1/3 criteria met
▪ Laboratory studies
▫ Affects specific body part corresponding
to specific brain part ▪ Lumbar puncture to distinguish from other
underlying causes of fevers, seizures (e.g.
▫ Lasts > 15 minutes
encephalitis, meningitis)
▫ Repeats within 24 hours
580 OSMOSIS.ORG
MEDICATIONS
TREATMENT ▪ Anticonvulsant
▫ Complex febrile seizures
▪ Simple febrile seizures usually resolve by
themselves ▪ Antipyretic medications (ibuprofen,
acetaminophen)
▫ Fever management
FOCAL SEIZURE
osms.it/focal-seizure
▪ Psychological symptoms
PATHOLOGY & CAUSES ▫ Sudden unusual feeling of sadness,
happiness, fear, anger; feelings of
▪ Seizure that initially stems from localized
derealization (environment is not real) or
brain region; limited to one hemisphere
depersonalization (dissociation from the
environment or self); feeling of déjà vu
TYPES ▪ Speech difficult/impossible
Focal aware seizure Focal impaired awareness seizure
▪ Affects small brain area ▪ Impaired consciousness
▪ Individual awake, alert; remembers seizure ▪ Often preceded by aura (symptoms of focal
aware seizure)
Focal impaired awareness seizure
▪ May involve automatisms (e.g. lip smacking,
▪ Unilaterally affects larger area of one chewing, swallowing, unpurposeful
cerebral hemisphere walking, etc.)
▪ Individual loses awareness, responsiveness; ▪ Amnesia (no recollection of seizure)
does not remember seizure
▪ May develop into a secondary generalized
seizure (focal onset bilateral tonic-clonic
seizure) DIAGNOSIS
DIAGNOSTIC IMAGING
SIGNS & SYMPTOMS MRI/CT scan
▪ Identify structural brain abnormalities (brain
Focal aware seizures
▪ Symptoms may be subtle, last ≥ two
minutes, vary by affected lobe
▫ Preserved consciousness LAB RESULTS
▪ Motor symptoms ▪ Blood tests
▫ Twitching, muscle jerking ▫ Detect possible underlying infection,
genetic condition, metabolic disorder,
▪ Sensory symptoms
other causes
▫ Unusual auditory, gustatory, tactile,
olfactory sensations
▪ Autonomic symptoms
▫ Sweating, piloerection, dilation of pupils,
incontinence, unusual feelings of nausea
OSMOSIS.ORG 581
OTHER DIAGNOSTICS
TREATMENT
EEG
▪ Detect epileptiform, abnormal electrical MEDICATIONS
brain activity ▪ Anticonvulsant medications
▫ E.g. lamotrigine, oxcarbazepine,
Neurological exam carbamazepine
SURGERY
▫ E.g. brain tumors, vascular disorders →
surgical resection
MYOCLONIC SEIZURE
osms.it/myoclonic-seizure

▪ Type of generalized seizure; presents with ▪ Brief body jerks; most commonly facial
myoclonus muscles, limbs
▫ Sudden, brief, involuntary muscle jerks ▪ Preserved consciousness, recollection of
lasting 1–2 seconds seizure
▪ Epileptic; non-epileptic, e.g. physiologic
while falling asleep, waking up; myoclonic
jerks → nervous system disorders, DIAGNOSIS
metabolic abnormalities, etc.
▪ Associated with epileptic syndromes: OTHER DIAGNOSTICS
▫ Juvenile myoclonic epilepsy EEG
▫ Progressive myoclonus epilepsy ▪ Detect abnormal, epileptiform electrical
▫ Myoclonic epilepsy with ragged-red brain activity
fibers (MERRF)
▫ Lafora disease
▫ Unverricht–Lundborg disease TREATMENT
▫ Neuronal ceroid lipofuscinosis
MEDICATIONS
▪ Anticonvulsant medication
COMPLICATIONS ▫ Clonazepam, valproate, levetiracetam;
▪ May become generalized tonic-clonic carbamazepine, oxcarbazepine,
seizures pregabalin, others contraindicated
582 OSMOSIS.ORG
STATUS EPILEPTICUS
osms.it/status-epilepticus
rigid), followed by clonic phase (muscles
PATHOLOGY & CAUSES rapidly contract, relax) → convulsions
▪ NCSE
▪ Medical emergency involving one acute
prolonged seizure ≥ five minutes or multiple ▫ Prolonged/repeated absence or focal
seizures occurring close together without impaired awareness seizure
recovery between ▫ Long-lasting stupor, staring;
unresponsiveness
TYPES
▪ Convulsive status epilepticus (CSE) DIAGNOSIS
▪ Nonconvulsive status epilepticus (NCSE)
▪ Continuous seizure lasting > five minutes
or recurrent seizures without regaining
CAUSES
consciousness in between them for > five
▪ Epilepsy minutes
▫ Usually triggered by medication change/
inadequate treatment
▪ Alcohol consumption/fasting while on
DIAGNOSTIC IMAGING
anticonvulsant MRI/CT scan
▪ Acute cerebral injury ▪ Detect structural brain abnormalities
▪ Brain disorders
▫ Brain tumors, brain injury, brain abscess,
LAB RESULTS
encephalitis
▪ Identify underlying cause
▪ Systemic process/illness
▫ Uremic encephalopathy, hepatic
encephalopathy OTHER DIAGNOSTICS
▪ Cerebrovascular disease EEG
▫ Intracranial bleeding, cerebrovascular ▪ Detect abnormal, epileptiform electrical
insult brain activity
▪ Eclampsia
▪ Delayed treatment → irreversible
neurological damage
MEDICATIONS
▪ Immediate application of benzodiazepines
▪ Prolonged muscle activity → hyperpyrexia,
followed by antiseizure drug phenytoin
acidosis
▪ If uneffective
▫ Valproic acid, phenobarbital, propofol, or
SIGNS & SYMPTOMS ketamine
▪ CSE OTHER INTERVENTIONS

▫ Prolonged/repeated tonic-clonic ▪ Oxygen, intravenous fluids
seizures
▫ Tonic phase (muscles stiffen and go
OSMOSIS.ORG 583
TONIC-CLONIC SEIZURE
osms.it/tonic-clonic-seizure

▪ Formerly called grand mal seizure DIAGNOSTIC IMAGING
▪ Characterized by tonic (rigid) stage and
MRI/CT scan
clonic (convulsion) stage
▪ Detect structural brain abnormalities (brain
▪ Most common seizure type
▪ May occur as one or multiple episodes as
part of epilepsy disorder
▪ Can initiate in both brain hemispheres LAB RESULTS
(generalized tonic-clonic seizure) or initiate ▪ Electrolytes; blood glucose, calcium levels
in one and spread to both (focal to bilateral ▫ Identify possible underlying infection,
tonic-clonic seizure) genetic condition, metabolic disorder,
▪ Episode > five minutes → status epilepticus other causes
OTHER DIAGNOSTICS
SIGNS & SYMPTOMS
EEG
▪ May be preceded by unusual sensations, ▪ Detect abnormal epileptiform electrical
e.g. visual, auditory, olfactory hallucinations; brain activity
dizziness (called an aura)
▪ Characterized by two phases
▫ Tonic phase: rigid, stiffening muscles; TREATMENT
contracting chest muscles → cry/groan;
biting of tongue, cheeks MEDICATIONS
▫ Clonic phase: muscles rapidly, ▪ Antiepileptic medication
rhythmically contract, relax; elbows, ▫ Valproate, lamotrigine, topiramate,
hips, knees bend, relax; urinary/fecal phenytoin
incontinence
▪ Tonic-clonic seizure → postictal state SURGERY
▫ Confusion, drowsiness, sleepiness, total ▪ Surgical resection for brain tumors, vascular
amnesia for hours after seizure disorders
▪ May be followed by Todd paralysis/paresis
for minutes–hours following seizure
584 OSMOSIS.ORG
NOTES
NOTES
EYE INFECTIONS

▪ Ocular disorders with infectious, DIAGNOSTIC IMAGING
noninfectious etiologies → inflammation, ▪ Fundoscopy
damage to eye structures
CT scan/MRI
▪ Orbits, sinuses
RISK FACTORS
▪ Immunocompromised state, contact with
infectious agent, ocular trauma, certain LAB RESULTS
systemic diseases ▪ Giemsa/Gram stains; cultures
COMPLICATIONS OTHER DIAGNOSTICS

▪ Range from benign, self-limiting to vision- ▪ Snellen chart
threatening infections
TREATMENT
SIGNS & SYMPTOMS
MEDICATIONS
▪ Structural damage, functional impairment ▪ Antimicrobials
OTHER INTERVENTIONS
▪ Address comorbidities
OSMOSIS.ORG 585
CHALAZION
osms.it/chalazion
may demonstrate diffuse inspissation of
PATHOLOGY & CAUSES yellowish contents from eyelid margin
orifices
▪ Firm, painless lipogranulomatous
inflammatory lump in eyelid; caused by
blockage of ocular sebaceous glands
▫ Deep chalazion: inflammation of
meibomian sebaceous glands
▫ Superficial chalazion: inflammation of
Zeis sebaceous glands
▪ Gland obstruction → impissation
(decreased flow of secretions) →
granulomatous inflammatory response →
lipogranuloma inflammation → lesion forms
on upper (most common)/lower eyelid
▪ Slow growing; may persist for weeks/
months; deeper within eyelid than
hordeolum (stye)
RISK FACTORS Figure 76.1 A chalazion of the left upper

▪ Rosacea, seborrhea, blepharitis, inflamed eyelid.
hordeolum
COMPLICATIONS
▪ If large chalazion presses on cornea →
visual changes
▪ Recurring chalazion: may signal carcinoma
(rare)
SIGNS & SYMPTOMS

▪ Eyelid erythema; swelling; firm, nodular,
rubbery consistency
DIAGNOSIS of a chalazion. There is granulomatous
inflammation with giant cells, numerous
macrophages as well as neutrophils and
OTHER DIAGNOSTICS eosinophils surrounding a nidus of lipid.
▪ Clinical history, physical examination
▪ Histological examination: chalazia may
indicate eyelid carcinoma
Slit-lamp
▪ Determine status of meibomian glands;
586 OSMOSIS.ORG
Chapter 76 Eye Infections
OTHER INTERVENTIONS
TREATMENT ▪ Warm, wet compresses encourage
drainage
MEDICATIONS
▪ Ocular cleansing pads applied to eyelid
▪ Recalcitrant chalazia: intralesional steroid
margin
injection
▪ Treat comorbidities (e.g. blepharitis,
rosacea)
SURGERY ▪ Small chalazion may resolve on own
▪ Recalcitrant chalazia: incision, curettage
CHORIORETINITIS
osms.it/chorioretinitis

▪ Inflammation of choroid, retina; AKA ▪ Floaters (vitritis), blurred vision, impaired
posterior uveitis color/night vision, ocular pain, photophobia,
excessive lacrimation
CAUSES
Infectious DIAGNOSIS
▪ Bacterial: tuberculosis, syphilis
DIAGNOSTIC IMAGING
▪ Viral: cytomegalovirus, West Nile virus,
herpes simplex virus (HSV) 1 Fluorescein angiography
▪ Parasitic: toxoplasmosis, onchocerciasis ▪ Irregularities
▪ Fungal: Candida albicans
Fundoscopy
Noninfectious ▪ Creamy white/yellow/gray lesions; keratic
▪ Sarcoidosis, Behçet’s disease, traumatic precipitates; retinal edema, necrosis;
chorioretinitis chorioretinal atrophy, neovascularization;
cotton-wool infiltrates (Candida-associated
chorioretinitis); polymorphic retinochoroidal
RISK FACTORS
scars (toxoplasmosis-associated
▪ Immunodeficiency, contact with infectious chorioretinitis)
agent, traumatic eye injury, systemic
disease associated with chorioretinitis
OTHER DIAGNOSTICS
COMPLICATIONS
▪ Retinal hemorrhage/detachment, visual
impairment with macular involvement TREATMENT
MEDICATIONS
▪ Corticosteroids/antimicrobials
OSMOSIS.ORG 587
Figure 76.3 A retinal photograph displaying
the features of chorioretinitis. There are
numerous, patchy, cream-colored lesions and
retinal edema.
CONJUNCTIVITIS
osms.it/conjunctivitis
▪ Common causes: Staphylococcus aureus,
PATHOLOGY & CAUSES Streptococcus pneumoniae, Haemophilus
influenzae
▪ Inflammation of conjunctiva, transparent
▪ Hyperacute bacterial conjunctivitis
mucous membrane covering inside of
eyelids (tarsal conjunctiva), globe (bulbar ▫ Causes: Neisseria gonorrhoeae (most
conjunctiva) common)/Neisseria meningitidis
▫ Non-keratinized epithelium containing ▫ Oculogenital disease: usually
goblet cells, highly vascularized transmitted from genitals to eyes via
substantia propria hands
▫ Turns pink/red when inflamed: diffuse ▫ Vision-threatening
conjunctival injection ▪ Chlamydial
▪ Infection, inflammation → dilatation ▫ Caused by Chlamydia trachomatis
of conjunctival vessels → conjunctival ▫ Adult inclusion conjunctivitis: chronic,
hyperemia, edema → inflammatory indolent
discharge ▫ Trachoma: infectious blindness cause
worldwide; active trachoma caused
TYPES by serotypes A, B, Ba, C (low-income
country-endemic, mostly in children);
Infectious (bacterial) initial follicular inflammation progresses
▪ Highly contagious; spread by direct contact in severity → cicatricial disease, vision
loss
588 OSMOSIS.ORG
Infectious (viral) ▪ Infected eye “stuck” shut from morning

▪ Highly contagious; spread by direct contact crusting; gritty, burning sensation (viral);
▪ Causes: adenovirus (most common), HSV itching (allergic); photophobia (corneal
(in children), varicella zoster virus (VZV) involvement); transient visual impairment
▫ Ocular manifestation of systemic ▪ Preauricular lymphadenopathy
infection
▫ Epidemic keratoconjunctivitis (EKC):
caused by adenovirus 8, 19, 37;
fulminant conjunctivitis, keratitis
(epithelium of conjunctiva, cornea);
corneal inclusions degrade visual acuity
Noninfectious (allergic)
▪ Caused by airborne allergens (seasonal,
perennial)
▪ Immunoglobulin E (IgE)-mediated → local
mast cell degranulation
Noninfectious (nonallergic) conjunctivitis.
▪ Caused by mechanical/chemical insult

▪ Exposure to causative agent,
immunocompromised state, atopy (allergic LAB RESULTS
conjunctivitis) ▪ Adenoviral conjunctivitis: rapid point-of-
▪ Contact lens wear: common source of care adenovirus antigen test
mechanical injury, nonallergic, infectious ▪ Recalcitrant conjunctivitis: conjunctival
conjunctivitis biopsy (rule out neoplasm)
Giemsa/gram stains
COMPLICATIONS ▪ Confirm identity of organism in suspected
▪ Cornea: keratitis (inflammation), ulcer, infectious cause
perforation, scarring
▪ Dacryocystitis (bacterial infection of lacrimal
sac) OTHER DIAGNOSTICS
▪ Vision loss ▪ Clinical history, physical examination
▪ Appearance: unilateral/bilateral
MEDICATIONS
inflammation; pinkish-red eye; eyelid ▪ Ocular lubricant drops/ophthalmic ointment
edema; chemosis (conjunctival edema); ▪ Allergic conjunctivitis: antihistamine drops
excessive lacrimation ▪ Adult inclusion conjunctivitis: systemic
▪ Discharge therapy to eradicate Chlamydia infection
▫ Bacterial: purulent/mucopurulent; white/ (antibiotics)
yellow/green ▪ Bacterial conjunctivitis: Topical antibiotic
▫ Gonococcal: hyper-purulent, profuse drops/ointment
▫ Viral: watery; stringy ▪ Epidemic keratoconjunctivitis (EKC): topical
glucocorticoids
▫ Allergic: watery, mucoid
▫ Nonallergic: mucoid
OSMOSIS.ORG 589
OTHER INTERVENTIONS
▪ Warm, wet compresses encourages
drainage
▪ Hyperacute conjunctivitis, EKC: immediate
specialized ophthalmologist referral
▪ Viral conjunctivitis: self-limiting; usually
resolves in 2–3 weeks
KERATITIS
osms.it/keratitis
▪ Immunocompromised state
PATHOLOGY & CAUSES ▪ Topical (ocular) corticosteroid use
▪ Cornea inflammation → corneal tissue ▪ Contributing disorders: rosacea;
destruction keratoconjunctivitis sicca (dry eye
syndrome); neurotrophic keratitis (lesion on
▪ Inflammatory response → stromal damage
cranial nerve V); autoimmune diseases (e.g.
from infection, host response → edema,
rheumatoid arthritis, cicatricial pemphigoid)
infiltrates, necrotic ulceration, focal thinning,
perforation
COMPLICATIONS
CAUSES ▪ Endophthalmitis (interior eye inflammation),
intraocular damage, vision loss, keratolysis
Infectious (corneal melting)
▪ Bacteria: Staphylococcus aureus,
Pseudomonas aeruginosa, coagulase-
negative Staphylococcus, diphtheroids, SIGNS & SYMPTOMS
Streptococcus pneumoniae
▪ Viruses: HSV, herpes zoster ▪ Erythema
▪ Fungi: Candida supp., Aspergillus supp., ▪ Preauricular lymphadenopathy
Fusarium supp. ▪ Discharge: mucopurulent (bacterial), watery
▪ Parasites: Acanthamoeba (viral)
▪ Corneal opacity, stromal infiltrate (immune
Noninfectious complex deposits), ulcer
▪ Corneal inflammation with no known ▫ Bacterial keratitis: yellow infiltrates
infectious etiology ▫ Fungal keratitis: white infiltrates,
feathery borders
RISK FACTORS ▫ Acanthamoeba: Wessely ring infiltrate
▪ Corneal epithelium disruption ▪ Hypopyon (layer of white cells in anterior
▫ Contact lenses (contact lens-related chamber): fulminant bacteria
keratitis); esp. improper use (e.g. ▪ Foreign body sensation; difficulty keeping
overnight wear, poor hygiene) eye open; photophobia; pain; decreased
▫ Recent keratoplasty, trauma, corneal visual acuity, blurred vision; blepharospasm
exposure (e.g. Graves’ ophthalmopathy,
Bell’s palsy)
590 OSMOSIS.ORG
Penlight
▪ Visualizes infiltrate/ulcer (> 0.5mm); round,
white spot (bacterial keratitis)
Fluorescein dye
▪ Corneal uptake of dye
▫ Visualize loss of epithelial cells,
ulceration
▫ Green glow under cobalt blue light
Figure 76.5 An individual with sterile keratitis
▫ Diffuse white opacity/dull corneal light
of the left eye.
reflex
▫ Seidel sign (leaking aqueous humor
→ fluorescein streaming): penetrating
DIAGNOSIS trauma
DIAGNOSTIC IMAGING Snellen chart

▪ ↓ visual acuity
Fundoscopy
▪ Slit beam; examine contour abnormalities of
cornea, lens, retina; small corneal infiltrates; TREATMENT
faint branching grey opacity (viral keratitis)
MEDICATIONS
LAB RESULTS ▪ Topical antimicrobials for infectious etiology
▪ Corneal scrapings, cultures: suspected
infectious etiology OTHER INTERVENTIONS
▪ Control of associated comorbidities
OTHER DIAGNOSTICS ▪ Temporary discontinuation of wearing
▪ Clinical history, physical examination contact lenses
ORBITAL CELLULITIS
osms.it/orbital-cellulitis
RISK FACTORS
PATHOLOGY & CAUSES ▪ More common in children
▪ Migration from other infections
▪ Serious infection involving contents of orbit
(ocular muscles, surrounding fat; not globe) ▫ Bacterial rhinosinusitis: Staphylococcus
aureus, streptococci (common); fungal
rhinosinusitis (rare)
CAUSES ▫ Dacryocystitis: lacrimal sac infection
▪ Entry of microorganisms into orbital space ▫ Infected mucocele: mucus-containing
▫ Via anatomical perforations of nerves, cystic lesion of salivary gland
blood vessels in paranasal sinuses (e.g. ▫ Infections involving teeth, middle ear,
ethmoid) face
▫ Migration from surrounding tissues (e.g. ▪ Direct inoculation: ophthalmic surgical
face, eyelids) after local trauma/surgery procedures; orbital trauma with fracture/
▫ Inflammatory response → tissue foreign body
destruction
OSMOSIS.ORG 591
▪ Extraorbital extension: epidural/subdural
Complete blood count (CBC)
empyema; brain abscess; meningitis;
cavernous sinus thrombosis; dural sinus ▪ Leukocytosis; ↑ absolute neutrophil count
thrombosis; involvement of cranial nerves (ANC)
III, IV, V, VI; optic neuritis
Blood/orbital/subperiosteal aspirates cul-
▪ Endophthalmitis: interior eye inflammation tures
▪ Vision loss ▪ Identify causative organism
▪ Potentially fatal if sepsis develops
OTHER DIAGNOSTICS
SIGNS & SYMPTOMS ▪ Clinical history, physical examination
▪ Ocular motility: pain with movement
Systemic ▪ Pupillary light reflex: sluggish/absent reflex
▪ Fever; severe headache, vomiting, mental → optic nerve involvement
status changes (intracranial complications) ▪ Exophthalmometry: measures degree of
proptosis
Ocular
▪ Asses color vision acuity: determines optic
▪ Red, swollen eyelids; chemosis nerve involvement
(conjunctival edema); pain (esp. with eye
▪ Intraocular pressure measurement (↑)
movement); ophthalmoplegia (paralysis
of eye muscles); proptosis (abnormal
displacement of eye); impaired visual acuity,
color vision; abnormal pupillary light reflex
TREATMENT
MEDICATIONS
DIAGNOSIS ▪ Antimicrobials

CT scan/MRI ▪ External (through orbit)/endoscopic
transcaruncular approach
▪ Orbits, sinuses; detects abscess,
intracranial changes
Dilated fundoscopy
▪ Determines optic neuropathy/retinal
vascular occlusion
592 OSMOSIS.ORG
OSMOSIS.ORG 593
PERIORBITAL (PRESEPTAL)
CELLULITIS
osms.it/periorbital-cellulitis

▪ Mild infection of superficial tissues of ▪ Ocular pain, eyelid swelling, erythema,
anterior eyelid (tissues anterior to orbital fever, lymphadenopathy
septum); more common than orbital
cellulitis
DIAGNOSIS
CAUSES
DIAGNOSTIC IMAGING
▪ Introduction/migration of microorganisms
into preseptal space: Staphylococcus Contrast-enhanced CT scan (orbits, sinus-
aureus, Streptococcus pneumoniae, other es)
streptococci, anaerobes ▪ Distinguishes between preseptal, orbital
cellulitis; associated sinusitis
RISK FACTORS
▪ More common in children LAB RESULTS
▪ Migration from other infections: sinusitis;
upper respiratory tract infection; CBC
dacryocystitis; bacteremia (rare) ▪ Leukocytosis
▪ Direct inoculation: trauma (e.g. insect bites,
Cultures (abscess contents, paranasal sinus
animal bites, introduction of foreign bodies);
secretions)
ophthalmic surgical procedures
▪ Identify causative agent
COMPLICATIONS
OTHER DIAGNOSTICS
▪ Orbital cellulitis
TREATMENT
MEDICATIONS
▪ Oral antibiotics
Figure 76.6 An individual with left-sided

periorbital cellulitis.
594 OSMOSIS.ORG
STYE (HORDEOLUM)
osms.it/stye

▪ Blockage, purulent inflammation of upper/ ▪ Tenderness; fluctuant pustule; localized
lower eyelid swelling, erythema; excessive lacrimation;
photophobia
CAUSES
▪ Sterile/bacterial (e.g. Staphylococcus DIAGNOSIS
aureus, Staphylococcus epidermidis)
Internal DIAGNOSTIC IMAGING

▪ Meibomian sebaceous gland; points toward Slit lamp, fundoscopy
conjunctival side of lid → conjunctival ▪ Determine infection extension to other
inflammation tissues
External
▪ Zeiss/Moll sebaceous glands; points toward OTHER DIAGNOSTICS
skin surface of eyelid ▪ Clinical history, physical examination
▪ Visual acuity assessment
RISK FACTORS
▪ Touching eyes with contaminated hands,
chronic blepharitis, seborrhea, improper TREATMENT
contact lens hygiene, sleeping with eye
makeup, immunocompromised state MEDICATIONS
▪ Topical antibiotic ointment
COMPLICATIONS
▪ Hardens → chalazion SURGERY
▪ Incision, curettage: if progresses to
chalazion
OTHER INTERVENTIONS
▪ Warm compresses encourage drainage
▪ Usually self-limiting with spontaneous
resolution
Figure 76.7 A stye on the right lower eye

lid.
OSMOSIS.ORG 595
UVEITIS
osms.it/uveitis
TYPES
PATHOLOGY & CAUSES
Anterior (most common)
▪ Inflammation of uveal tract (choroid, ciliary ▪ Anterior uveal tract; iritis, iridocyclitis
body, iris); unilateral/bilateral (inflammation of ciliary body)
▪ Onset: rapid/insidious
Panuveitis
▪ Course: acute/recurrent/chronic
▪ Anterior chamber, vitreous body, retina/
▪ Duration: persistent (> three months)/
choroid
limited (≤ three months)
Posterior uveitis
▪ Retina/choroid
596 OSMOSIS.ORG
Intermediate uveitis LAB RESULTS

▪ Vitreous body; chorioretinal inflammation
Microscopy, cytology, culture, polymerase
chain reaction (PCR)
CAUSES ▪ Fluid sampling/biopsy; identify presence of
▪ Bacterial: tuberculosis, syphilis infectious agent
▪ Viral: cytomegalovirus, HSV
▪ Fungal: candidiasis, Pneumocystis jirovecii OTHER DIAGNOSTICS
▪ Parasitic: Acanthamoeba, toxoplasmosis ▪ Clinical history, physical examination
▪ Noninfectious systemic: Crohn’s disease,
ankylosing spondylitis Snellen chart
▪ Conditions confined to eye: trauma, acute ▪ ↓ visual acuity
retinal necrosis
Pupillary light reflex
▪ Sluggish pupillary reaction to light →
RISK FACTORS synechiae
▪ Systemic infectious, inflammatory
conditions Intraocular pressure
▪ No change if uncomplicated uveitis; ↑ in
acute uveitis-induced glaucoma
COMPLICATIONS
▪ Intraocular hypertension, glaucoma;
increased intraocular pressure; posterior TREATMENT
synechiae (iris adheres to lens); band
keratopathy (corneal calcium deposits); MEDICATIONS
cataract; vision loss
▪ Corticosteroids: topical, local injection,
implantable, systemic
SIGNS & SYMPTOMS ▪ Recalcitrant uveitis: immunomodulatory
agents (if corticosteroid response
inadequate)
▪ Ocular erythema
▪ Recalcitrant uveitis: tumor necrosis factor
▪ Impaired vision
(TNF) inhibitor (if resistant to treatment)
▪ Pain, photophobia, vision distortion, floaters
▪ Posterior synechiae prevention: mydriatic/
(vitritis), photopsia (flashing lights)
cycloplegic medications
▪ Viral-associated uveitis: antivirals
DIAGNOSIS
DIAGNOSTIC IMAGING
Fluorescein/indocyanine green angiography
(posterior uveitis)
▪ Evaluate status of retinal vascular
circulation; identify choroidal disease
Fundoscopy
▪ Ciliary flush: perilimbal redness
▪ Keratic precipitates: inflammatory deposits
on cornea
▪ Hypopyon: white blood cells settle on
bottom of anterior chamber
Figure 76.8 An individual with a hypopyon
▪ Haziness of aqueous humor: protein
of the left eye as a result of severe anterior
accumulation
uveitis.
OSMOSIS.ORG 597
NOTES
NOTES
GLOBE PATHOLOGY

▪ Disorders affecting eye structures; if MEDICATIONS
untreated → severe visual impairment ▪ Corneal ulcer
▪ Due to damage to cornea, retina, lens, optic ▫ Antimicrobial, steroid eye drops;
nerve analgesics
▪ Inherited/acquired ▪ Age-related macular degeneration (ARMD)/
diabetic retinopathy (DR)
COMPLICATIONS ▫ Intravitreal injections of vascular
▪ Impaired vision, blindness endothelial growth factor (VEGF)
antagonists
▪ Glaucoma
SIGNS & SYMPTOMS ▫ Beta blockers, alpha agonists
▪ Early stages often asymptomatic SURGERY

▪ Visual changes ▪ Cataract
▫ Small incision; removal of opacified lens
DIAGNOSIS ▫ Alternative: leaving lens capsule intact
(extracapsular cataract extraction), eye
DIAGNOSTIC IMAGING without lens (aphakic eye)
▪ DR
Direct/indirect fundoscopy ▫ Laser photocoagulation of peripheral
▪ Visualize retina retina, vitrectomy
▪ Glaucoma
OTHER DIAGNOSTICS ▫ Laser surgery, trabeculectomy,
▪ Clinical presentation: history; visual acuity, peripheral iridotomy
field loss
Slit lamp
OTHER INTERVENTIONS
▪ ARMD
▪ Visualize sclera, conjunctiva, iris, lens,
cornea ▫ Vitamin, antioxidant supplements;
smoking cessation
▪ DR
▫ Glucose, blood pressure control
598 OSMOSIS.ORG
Chapter 77 Globe Pathlogy
AGE-RELATED MACULAR
DEGENERATION (ARMD)
osms.it/macular-degeneration
hyperlipidemia
PATHOLOGY & CAUSES
▪ Acquired degenerative disease of macula COMPLICATIONS
→ loss of central vision; peripheral vision ▪ Severe visual impairment: impacts
preserved; most common cause of severe functional status, quality of life; complete
visual impairment in older adults in high- loss of vision rare
income countries
▪ Results from damage to photoreceptors of
macula SIGNS & SYMPTOMS
▪ Unilateral/bilateral; contralateral eye at high
risk ▪ Early stages: often asymptomatic; blurred
vision; metamorphopsia (straight lines seen
curved)
TYPES ▪ Loss of central vision; gradual progression
Nonexudative ARMD in nonexudative, rapid over weeks/months
in exudative
▪ AKA dry/atrophic; most common
▪ Drusen: extracellular deposits between
Bruch membrane, retinal pigment DIAGNOSIS
epithelium (RPE)
▫ ↑ size, number of soft drusen → ↑ risk of DIAGNOSTIC IMAGING
progression to advanced ARMD
▪ RPE changes: geographic atrophy, Fluorescein dye retinal angiography
detachments, subretinal clumping ▪ Fluorescein leaks from abnormal vessels
Exudative ARMD Optical coherence tomography

▪ AKA wet/neovascular; less common ▪ Retinal edema/subretinal fluid
▪ Neovascularization: abnormal vessel
Amsler grid
formation under retina originating from
choroidal circulation, penetrating through ▪ Individual holds grid at 36–41cm/14–16in,
Bruch membrane beneath RPE → leakage looks at center dot
of serous fluid, blood → collections, fibrosis ▫ Curvy lines, blurry spots, scotomas
Direct/indirect fundoscopy
RISK FACTORS ▪ Nonexudative ARMD
▪ ↑ age; > 65 most common ▫ Drusen: white-yellowish, round/oval
▪ Family history: associated with deposits
polymorphisms in complement regulatory ▫ Retinal atrophy: round patches of
genes, esp. complement factor H (CFH) depigmentation
▪ More common in individuals who are ▫ RPE clumping: increased pigmentation
biologically female, white people of ▪ Exudative ARMD
Ashkenazi Jewish descent
▫ Neovascularization: gray discoloration
▪ Smoking, intense light exposure, heavy
▫ Subretinal fluid/hemorrhage
alcohol use, obesity, hypertension,
OSMOSIS.ORG 599
OTHER DIAGNOSTICS
▪ Clinical presentation: history; ↓ visual
acuity, visual fields (central vision loss)
TREATMENT
MEDICATIONS
▪ Exudative ARMD
▫ Intravitreal injections of
VEGF antagonists to reduce
neovascularization
▫ Alternative: photodynamic therapy;
injection of photosensitive dye
verteporfin → damages neovascular
endothelium; application of photo- Figure 77.1 Drusen in the macula of individual
activating laser with age-related macular degeneration.
OTHER INTERVENTIONS
▪ No curative method; therapy aimed at
slowing progression
▪ Vitamin, antioxidant supplements
▪ Nonexudative ARMD
▫ Smoking cessation
CATARACT
osms.it/cataract
nucleus (cortex)
PATHOLOGY & CAUSES ▪ Mild degradation of vision
▪ Painless, gradual decline in vision due to Posterior subcapsular
opacification of lens ▪ Opacification in posterior cortical layer
▪ Proteins deposit on lens → reduce under lens capsule
transmission of light to retina → decrease ▪ Rapid progression
in vision
▪ Often bilateral but asymmetrical; congenital/
acquired RISK FACTORS
▪ Age-related cataract; usually > 60
▪ Smoking, excessive alcohol use, prolonged
TYPES
drug use (esp. glucocorticoids), exposure to
Nuclear UV light, eye trauma/infections, radiation of
▪ Opacification of lens nucleus intraocular tumor, trisomies (13, 18, 21)
▪ Slow progression of vision loss ▪ Metabolic diseases: diabetes mellitus,
Wilson disease, galactosemia, myotonic
Cortical dystrophy
▪ Opacification of lens fibers surrounding
600 OSMOSIS.ORG
COMPLICATIONS
▪ Blindness (if untreated)
SIGNS & SYMPTOMS
▪ Secondary posterior subcapsular cataract
▪ Painless visual impairment; progresses
due to migration of lens epithelium
slowly over many years
posterior cortical layer
▪ Myopic shift: improvement in
Secondary glaucoma nearsightedness before decline in vision;
▪ Phacolytic lens sclerosis → increase in refractive
power
▫ Lysed lens proteins clog trabecular
meshwork → ↑ pressure ▪ Blurry vision, poor vision at night, dullness
of colors
▪ Phacoanaphylactic
▪ Glare, halos around bright lights;
▫ Autoimmune reaction to proteins → ↑
predominant in cortical cataract
pressure
▪ Phacomorphic
▫ Swollen lens → closed angle glaucoma DIAGNOSIS
Surgery
DIAGNOSTIC IMAGING
▪ Residual lens epithelial cells migrate over
capsule → opacification, reduction in vision Slit lamp
▪ Endophthalmitis, bullous keratopathy, ▪ Loss of lens transparency
intraocular lens dislocation, cystoid macular
edema, retinal detachment Indirect/direct fundoscopy
▪ Toxic anterior segment syndrome ▪ Degree of lens opacity
▫ Inflammation of anterior segment due to ▪ Obscuration of fundus details
noninfectious contaminants of surgical ▪ Darkening of normal red reflex from fundus
equipment
OTHER DIAGNOSTICS
▪ Clinical presentation: history; ↓ visual acuity
TREATMENT
SURGERY
▪ Small incision
▫ Phacoemulsification of lens,
implantation of synthetic intraocular lens
▪ Removal of opacified lens (alternative)
▫ Leaving lens capsule intact
(extracapsular cataract extraction), eye
without lens (aphakic eye)
Figure 77.2 The eye of a 50-year-old male
with a cataract.
OSMOSIS.ORG 601
CORNEAL ULCER
osms.it/corneal-ulcer

▪ Inflammatory condition of cornea; usually MEDICATIONS
infectious → dissolution of corneal stroma ▪ Antimicrobial eye drops
▪ Presents as open corneal sore ▪ Analgesics for pain control
▪ AKA ulcerative keratitis ▪ Steroid eye drops after treatment of
▪ Exudate, cells leak into anterior chamber → infection to reduce swelling, prevent
form hypopyon if sufficient quantity scarring
CAUSES SURGERY
▪ Bacteria, fungi, viruses (esp. herpes ▪ Corneal transplantation to replace damaged
simplex, zoster), protozoa (e.g. cornea if scarring decreases vision
Acanthamoeba)
RISK FACTORS
▪ Improper usage of contact lens, corneal
abrasions, eye burns, xerophthalmia (i.e.
dry eye), eyelid disorders, steroid eye drops,
vitamin A deficiency
SIGNS & SYMPTOMS

▪ Red eye, severe pain, soreness, discharge
(tearing, pus), eyelid swelling, blurred
vision, vision loss, photophobia
DIAGNOSIS
Figure 77.3 A corneal ulcer caused by herpes
DIAGNOSTIC IMAGING simplex keratitis viewed with fluorescein
▪ Slit lamp under a UV lamp. The ulcer has a classical
▪ Reveals corneal ulcer/hypopyon dendritic pattern.
▪ Fluorescein dye
▫ Ulcer margins (absorbed by exposed
corneal stroma, appears green)
▪ Herpes simplex ulcers
▫ Typical dendritic/geographic pattern
OTHER DIAGNOSTICS
▪ Clinical presentation: history; ↓ visual acuity
602 OSMOSIS.ORG
DIABETIC RETINOPATHY (DR)

osms.it/diabetic-retinopathy
microaneurysms, microocclusions,
PATHOLOGY & CAUSES exudates, nerve-fiber layer infarcts (cotton
wool spots), intraretinal hemorrhage,
▪ Type of retinopathy affecting individuals macular edema
with diabetes mellitus → vision loss
▪ Long-standing diabetes mellitus/poor
glycemic control → chronic hyperglycemia OTHER DIAGNOSTICS
→ retinal vascular changes (e.g. abnormal ▪ Ophthalmologic screening: annual
vascular permeability, vascular occlusions) screening suggested for individuals with
→ ischemia → production of VEGF → diabetes
formation of abnormal blood vessels ▪ Clinical presentation: ↓ visual acuity
(neovascularization)
TYPES
Proliferative DR
▪ Presence of neovascularization
Nonproliferative DR
▪ Absence of neovascularization; majority
of cases; can progress to proliferative;
hypertension, fluid retention exacerbate
condition
COMPLICATIONS
▪ Visual loss due to
▫ Macular edema (most common); vitreal Figure 77.4 A retinal photograph
hemorrhage from neovascularization; demonstrating proliferative diabetic
retinal detachment; neovascular retinopathy. There are cotton wool spots and
glaucoma as well as neovascularisation of the retina.
SIGNS & SYMPTOMS

TREATMENT
▪ Usually asymptomatic until late stages
▪ Decreased/fluctuating vision; presence MEDICATIONS
of floaters, flashes of lights (photopsias); ▪ Intravitreal VEGF inhibitors for proliferative
scotomas DR, significant macular edema
SURGERY
DIAGNOSIS ▪ Laser photocoagulation of peripheral retina
DIAGNOSTIC IMAGING ▪ Vitrectomy for vitreous hemorrhage/
severe proliferative DR nonresponsive to
Direct/indirect fundoscopy photocoagulation
▪ Thickening of basement membrane,
OSMOSIS.ORG 603
OTHER INTERVENTIONS
▪ Glucose, blood pressure control to reduce
progression of nonproliferative DR
GLAUCOMA
osms.it/glaucoma
family history
PATHOLOGY & CAUSES
Closed angle
▪ Group of eye disorders; intraocular ▪ ↑ age, family history, biologically-female
hypertension damages optic nerve → individuals of Asian descent, hyperopia,
progressive peripheral visual field loss medications (e.g. mydriatic eye drops),
▪ Aqueous humour drainage pathway pseudoexfoliation
becomes partially/completely blocked →
fluid cannot easily drain out → pressure of
anterior chamber builds up → intraocular
COMPLICATIONS
hypertension (pressure > 21mmHg/2.8kPa) ▪ If untreated, blindness
→ affects eye structures → atrophy of outer
rim of optic nerve → peripheral vision loss
▪ Intraocular pressure increases → continued
SIGNS & SYMPTOMS
damage to optic nerve → ganglion cell loss
→ loss of central vision Open angle
▪ Asymptomatic
TYPES Closed angle

▪ Chronic: often asymptomatic, peripheral
Open Angle Glaucoma
vision loss
▪ Angle between cornea, iris; most common
▪ Acute (ophthalmic emergency): abrupt
▪ Increased aqueous production/decreased onset of severe eye pain, redness, blurry
outflow vision/vision loss, headache, nausea, halos
▪ Secondary to uveitis, vitreous hemorrhage, around lights, fixed mid-dilated pupil,
retinal detachment conjunctival redness, corneal edema
Closed Angle Glaucoma
▪ Narrowing/closure of anterior chamber DIAGNOSIS
angle → inadequate drainage of aqueous
humor → increased intraocular pressure → DIAGNOSTIC IMAGING
optic nerve damage
▪ Acute: rapid buildup of pressure Tonometry
▪ ↑ intraocular pressure
Normal Tension Glaucoma
▪ Genetic hypersensitivity to intraocular Direct/indirect fundoscopy
pressures in normal range ▪ Cupping: hollowed-out appearance of optic
nerve (thinning of outer rim)
RISK FACTORS ▪ Increased cup-to-disc ratio; > 0.5
suggestive of glaucoma
Open angle
Slit lamp
▪ ↑ age, black people of African descent,
▪ Special lens to visualize angle (gonioscopy)
604 OSMOSIS.ORG
OTHER DIAGNOSTICS ▫ Open trabecular meshwork, increase

▪ Clinical presentation: history, ↓ visual aqueous outflow (trabeculoplasty);
acuity, visual field (peripheral vision loss; destroy humor producing cells; create
central loss at late stages) new channel for aqueous humour
drainage
▪ Surgical trabeculectomy
TREATMENT ▫ Create alternate drainage pathway
MEDICATIONS Acute closed angle

▪ Peripheral iridotomy with laser
Open angle
▫ Small hole through iris for aqueous
▪ Beta-adrenergic receptor antagonists, humor drainage
carbonic anhydrase inhibitors, alpha
adrenergic agonists
▫ ↓ production of aqueous humor
▪ Prostaglandin analogs, alpha adrenergic
agonists
▫ ↑ outflow of aqueous humor
Acute closed angle

▪ Eye drops (e.g. beta-blockers, alpha
agonists); systemic (e.g. acetazolamide,
urea, mannitol, glycerol)
SURGERY
Open angle
▪ Laser surgery Figure 77.5 A photograph of the eye of an
individual with acute angle closure glaucoma.
There is ciliary flush and a hazy cornea.
RETINAL DETACHMENT (RD)

osms.it/retinal-detachment
TYPES
PATHOLOGY & CAUSES
Rhegmatogenous
▪ Separation of retinal photoreceptors from ▪ Most common
underlying retinal pigment epithelium ▪ Full thickness retinal break → vitreous fluid
(RPE), choroid; if untreated leads → vision passes into subretinal space → retinal
loss detachment
▪ Detachment of neurosensory retinal ▪ Causes
layer from underlying layers → ischemia,
▫ Posterior vitreous detachment: most
progressive degeneration of photoreceptors
common, age 50–75, separation of
→ vision loss
OSMOSIS.ORG 605
posterior vitreous membrane from retina ▪ Tractional: smooth concave retinal surface;
due to natural age-related liquefaction minimal shifting with eye movements
of vitreous → retinal breaks can occur in ▪ Exudative: smooth retinal surface, shifting
areas of strong vitreoretinal attachment fluid
▫ Ocular trauma
Nonrhegmatogenous LAB RESULTS

▪ Vitreous traction ▪ Diabetes: traction, exudative RD; find
▫ Abnormally strong vitreoretinal underlying cause
adhesion → contraction → detachment;
proliferative diabetic retinopathy, OTHER DIAGNOSTICS
retinopathy of prematurity ▪ Clinical history, physical examination
▪ Exudative
▫ Fluid accumulation between layers;
inflammatory conditions, choroidal TREATMENT
neoplasms
SURGERY
RISK FACTORS ▪ Laser photocoagulation/cryoretinopexy:
seal retinal breaks, prevent retinal
Rhegmatogenous detachment
▪ High myopia; lattice degeneration (thinning ▪ Rhegmatogenous RD
of retinal periphery); family history; history ▫ Pneumatic retinopexy: intraocular
of retinal detachment; ocular trauma; injection of gas to tamponade
previous intraocular surgery (e.g. cataract retinal break (along with laser or
surgery) cryoretinopexy)
▫ Scleral buckles: silicone bands
COMPLICATIONS placed are sewed to sclera under
rectus muscles (along with laser or
▪ Vision loss, proliferative retinopathy
cryoretinopexy)
▫ Vitrectomy: removal of vitreous body to
SIGNS & SYMPTOMS reduce the effect of vitreous traction to
retina
▪ Sudden onset: floaters/flashes of light; if ▪ Tractional RD
preceded by posterior vitreous detachment ▫ Vitrectomy with scleral buckling
▪ Monocular vision loss: curtain drawn over
vision field
DIAGNOSIS
DIAGNOSTIC IMAGING
▪ ↓ visual acuity
Ocular ultrasound
▪ E.g. choroidal masses
▪ Traction, exudative RD; find underlying
cause
Direct/indirect fundoscopy axial plane demonstrating detachment of the
right retina.
▪ Rhegmatogenous: wavy appearance,
changes with eye movements, changes in
vessel direction
606 OSMOSIS.ORG
RETINOBLASTOMA
osms.it/retinoblastoma
▫ Blood → lungs, bones, liver
PATHOLOGY & CAUSES ▫ Lymphatic vessels → conjunctiva,
eyelids, extraocular tissue
▪ Intraocular malignant tumor; affects
children; presents as leukocoria ▪ Heritable retinoblastoma
▪ Most common primary intraocular ▫ Secondary malignancy (e.g. bone, soft
malignancy of childhood; usually < two tissue sarcomas)
years
▪ Associated with intracranial tumor
▫ Pinealoblastoma (trilateral
retinoblastoma)
▪ Mutational inactivation of both alleles of
retinoblastoma (RB1) gene located in
chromosome 13
TYPES
Heritable (40%)
▪ Germline mutations: inherited/de novo
▪ Presents at early age; bilateral/multifocal;
50% risk of passing to offspring
Nonheritable (60%)
▪ Somatic mutations in both alleles; negative
family history
▪ Presents later in life; unilateral Figure 77.7 The gross pathological
appearance of a retinoblastoma.
RISK FACTORS
▪ Family history
▪ 13q14 deletion syndrome
▫ Microdeletions in region 1 band 4
located in large arm (q) of chromosome
13
COMPLICATIONS
▪ Fatal if untreated; with prompt treatment,
survival > 95%
▪ Spreads via
▫ Choroid → sclera, orbit → destruction of
globe → vision loss
Figure 77.8 A child with retinblastoma
▫ Optic nerve → brain causing whitening of the right pupil known as
▫ Subarachnoid space → contralateral leukocoria.
optic nerve, brain
OSMOSIS.ORG 607
SIGNS & SYMPTOMS
▪ Leukocoria (abnormal white reflexion from
retina)
▪ Strabismus, nystagmus, red eye
DIAGNOSIS
DIAGNOSTIC IMAGING
MRI (brain, orbits)
▪ T1-weighted: bright
▪ T2-weighted: dark compared to vitreous
▪ Detect optic nerve involvement, associated
intracranial tumor
Direct/indirect fundoscopy
▪ Well-circumscribed, translucent, white
intraretinal mass
Ocular ultrasound Figure 77.9 An MRI scan of the head in the

▪ Normal globe size, calcification axial plane demonstrating a retinoblastoma of
the left globe.
LAB RESULTS
▪ Genetic testing
▫ Estimate risk in family members, future
offspring
OTHER DIAGNOSTICS
▪ Metastasis evaluation (e.g. bone marrow
aspiration, lumbar puncture)
TREATMENT
MEDICATIONS
▪ Local/systemic chemotherapy
▫ Preserve vision, optimize survival Figure 77.10 A retinoblastoma as seen on
fundoscopy.
SURGERY
▪ Cryopexy, laser photoablation, enucleation
▫ Preserve vision, optimize survival
608 OSMOSIS.ORG
RETINOPATHY OF PREMATURITY
osms.it/retinopathy-of-prematurity
▪ Classification
PATHOLOGY & CAUSES ▫ Location: three concentric zones from
optic disc to periphery
▪ AKA retrolental fibroplasia
▫ Extent: retina divided in 12 parts (hours
▪ Proliferative retinopathy, occurs in preterm
of a clock)
infants; if untreated → vision loss
▫ Stage I: thin white demarcation line
▪ Common cause of childhood blindness
separating vascularized from avascular
▪ Premature birth interrupts development → retina
↑ risk of vascular insult
▫ Stage II: ridge of fibrous tissue into
▪ Supplemental oxygen administration → vitreous between vascularized,
disruption of normal angiogenesis → avascular retina
abnormal growth of blood vessels, fibrous
▫ Stage III: abnormal growth of
tissue affecting temporal part of retinal
fibrovascular tissue on ridge; extension
periphery
into vitreous
▪ Regress spontaneously in most cases
▫ Stage IV: partial retinal detachment
▫ Stage V: total retinal detachment
RISK FACTORS ▫ Plus disease: increased venous dilation,
▪ Gestational age < 30 weeks; birth weight tortuosity of posterior retinal vessels,
≤ 1.5kg/3.3lbs; excessive oxygen therapy; vitreous haze
supplemental oxygen
OTHER DIAGNOSTICS
COMPLICATIONS ▪ Screening of preterm infants
▪ Retinal bleeding, scarring
▪ Contraction of fibrovascular tissue → retinal
detachment → blindness TREATMENT
▪ Refractive errors: myopia, anisometropia
▪ Squint/strabismus MEDICATIONS
▪ Glaucoma ▪ Intravitreal injection of VEGF antagonists
SURGERY
SIGNS & SYMPTOMS ▪ Ablation of retina with laser
photocoagulation
▪ Blindness due to retinal detachment, if
untreated
DIAGNOSIS
DIAGNOSTIC IMAGING
Fundoscopy
▪ Direct/indirect following pupil dilation
▫ Disorganized growth of vessels, fibrous
tissue
OSMOSIS.ORG 609
Figure 77.11 A CT scan of the head in the axial
plane demonstrating increased density and
asymmetry of the globes in a one year old
biologically-female individual. The increase
in density is caused by retinal detachment
and subsequent fibrous reorganisation of the
vitreous.
610 OSMOSIS.ORG
NOTES
NOTES
HEAD INJURY

▪ Shaken baby syndrome
PATHOLOGY & CAUSES ▫ Fundoscopy (retinal hemorrhage),
neuro-imaging reveals characteristic
▪ External force to head → brain injury
intracranial injury (intracranial
(stretching, compression, impact, rotational)
hemorrhage, edema)
→ cellular dysfunction
OTHER DIAGNOSTICS
SIGNS & SYMPTOMS ▪ Concussion
▫ Functional assessment
▪ Mental-status change
▪ Consciousness loss
▪ Headache TREATMENT
▪ Irritability
▪ Lethargy SURGERY
▪ Vomiting ▪ Significant injury
▪ Seizure ▫ Drain ventricle if needed
▫ Drain intracranial hemorrhage if required

▪ Mild injury
DIAGNOSTIC IMAGING
▫ Rest
▪ Concussion
▪ Significant injury
▫ Neuro-imaging rules out more extensive
▫ Monitor intracranial pressure (ICP)
injury
OSMOSIS.ORG 611
CONCUSSION
osms.it/concussion
impact point → brain injury at contact
PATHOLOGY & CAUSES point
▫ Contrecoup injury: brain may collide
▪ AKA mild traumatic brain injury
with skull opposite initial impact sight
▪ Direct blow to head, face, neck, other body during rebound
part transmitting to head → acute, mildly
▪ Torque injury
traumatic brain injury → mental status
alteration, potential consciousness loss ▫ Rotational force → different rotational
velocity dependent on variable distance
▪ Concussion alters cellular functioning
from rotation’s center, differing grey/
▫ Physical trauma → nerve cell membrane white matter density → neuron
disruption → intracellular ion migration stretching (more severe injury →
(potassium, calcium) to extracellular shearing)
space → unregulated glutamate release
▫ Brain regions most affected: midbrain,
→ depolarization
diencephalon
▫ Ion shifts at axon level/axonal rupture →
▫ Injury disrupts normal cellular activity
disrupted cellular oxidative metabolism
in reticular activating system →
→ cell death → functional disturbance
consciousness loss
→ temporary (normal function) brain
impairment
▫ Ion regulation loss → ↑ membrane pump RISK FACTORS
activity (e.g. sodium-potassium ion ▪ Biologically-male
channels) → ↑ ATP, glucose utilization ▪ Contact sport, cycling injury, combat-
▫ Paradoxical ↓ cerebral blood flow → related traumatic brain injury (TBI)
cellular energy crisis → susceptible ↑ ▪ Hospital-admission history (intoxication-
further injury related)
▫ Excitatory neurotransmitters released ▪ Low socioeconomic status
(e.g. acetylcholine, glutamate, aspartate) ▪ Lower cognitive function
+ free-radical generation generation →
secondary injury
▫ Initial ↑ glucose utilisation → ↓ COMPLICATIONS
energy-use metabolic state; neuronal ▪ Seizure, intracranial hemorrhage, skull
suppression may persist weeks post- fracture, dementia pugilistica, ↑ further
injury concussion risk
▪ Second-impact syndrome (SIS)
CAUSES ▫ Further head injury (post-concussion
period) during ↓ blood supply → rapid
▪ Traumatic head injury (e.g. motor vehicle
cerebral edema
crash, combat, contact sport)
▪ Postconcussive syndrome (PCS)
▪ Force transmission (head/body injury)
→ diffuse neuronal-level brain injury → ▫ Persistent post-concussive
temporary (reversible) brain-function neurocognitive symptoms
loss → mental status alteration, +/- ▪ Repeated concussion → ↑ later-life risk
consciousness loss with little/no resultant of chronic traumatic encephalopathy
imaging change (tau protein accumulation in neurons
▪ Coup-contrecoup injury → neuronal death → brain atrophy),
Parkinson’s disease, depression
▫ Coup injury: compressive force at
612 OSMOSIS.ORG
Chapter 78 Head Injury
Neuropsychological testing
SIGNS & SYMPTOMS ▪ Assess functional impairment (also
assesses recovery)
▪ Develop after initial injury, may continue
developing days afterwards ▫ Standardized Assessment of
Concussion (SAC)
▪ Physical
▫ Post-Concussion Symptom Scale and
▫ Headache; dizziness; vomiting; nausea;
Graded Symptom Checklist
concussive convulsion (immediately
post-injury); light/sound sensitivity; ▫ Sport Concussion Assessment Tool
tinnitus; cranial nerve impairment (SCAT5)
(extraocular muscle weakness, vertigo, ▫ Westmead post-traumatic amnesia
nystagmus); incoordination scale
▪ Cognitive
▫ Blunted affect, confusion, difficulty TREATMENT
focusing attention, consciousness loss,
pre-/post-traumatic amnesia, sleeping-
MEDICATIONS
pattern change, slow answering
questions, memory deficit ▪ Analgesia
▪ Emotional ▫ Paracetamol, NSAIDS
▫ Irritability, anhedonia, tearfulness, ▫ Avoid narcotics (prevent further
restlessness consciousness-clouding)
OTHER INTERVENTIONS
DIAGNOSIS ▪ Physical, cognitive rest (1–2 days) →
gradual full-function return
DIAGNOSTIC IMAGING ▫ Delay return to contact sport until
Contrast-CT scan/MRI complete symptom resolution
▪ Concussion → normal findings without ▪ 24 hour observation period for neurological
other injury deterioration (diagnostic findings →
outpatient/in-hospital)
▪ Contusion, hemorrhage → abnormality
▪ Functional single concussion recovery
(usually 48–72 hours), headaches (over 2–4
OTHER DIAGNOSTICS weeks)
Diagnostic criteria
▪ Consciousness loss: < 30 minutes
▪ Memory loss: < 24 hours
▪ Glasgow Coma Scale: score 13–15 (eye
opening, verbal/motor/orientation response)
▪ More severe symptoms → moderate/severe
traumatic brain injury
OSMOSIS.ORG 613
SHAKEN BABY SYNDROME
osms.it/shaken-baby-syndrome
COMPLICATIONS
PATHOLOGY & CAUSES ▪ Retinal hemorrhage (diffuse, multilayered);
subdural hemorrhage; diffuse brain injury;
▪ AKA abusive head trauma/shaking-impact global hypoxia, ischemia; increased
syndrome intracranial pressure, herniation; skull
▪ Child head injury caused by another person fracture; spinal cord/paraspinal injury;
▪ Traumatic shaking → child’s head flung hemorrhagic shock open fontanelle, (cranial
violently back/forth (may strike surrounding sutures allow large blood accumulation)
surfaces/objects) → acceleration–
deceleration, rotational force → bridging
vessels tear (subdural hematoma), diffuse SIGNS & SYMPTOMS
axonal injury, oxygen deprivation, brain
swelling, ↑ ICP ▪ Trauma signs may be invisible
▪ Infant anatomy → ↑ neurological-injury risk ▪ Retinal hemorrhage; long bone, rib fracture;
from shaking soft-tissue scalp swelling; bruising;
▫ Large head:body ratio, weak cervical irritability; poor feeding; lethargy, coma;
paraspinal muscles → acceleration- vomiting; seizure; bulging fontanel (↑ ICP)
deceleration force movement ▪ Late, severe neurologic deterioration signs
▫ Thin, pliable infant skull → ↑ force ▫ Bradycardia, pupillary change
transfer across subarachnoid space
▫ Relatively flat skull base → ↑ brain
movement with deceleration force DIAGNOSIS
▫ Soft infant brain (↑ water content
compared to adult), incompletely- DIAGNOSTIC IMAGING
myelinated infant neurons → ↓ blood
flow autoregulation Brain CT scan/MRI
▪ Intracranial hemorrhage
▫ Hematoma; subarachnoid, subdural
RISK FACTORS (most common), epidural hemorrhage;
▪ Age (often first year of life), abusive intraparenchymal bleeding
caregiver; caregivers hold unrealistic
▪ Cerebral contusion/edema
expectations of child; emotional stress;
aggression; biological sex (male > female); ▪ Uncal, subfalcine, transtentorial herniation
perinatal illness (e.g. premature birth, ▪ Hypoxia/ischemia
difficult labor, hospitalization, congenital ▫ Loss of grey-white distinctions
conditions); incessant crying ▪ Skull fracture
▪ Family/individual factors ▪ Appendicular, axial skeleton survey
▫ Family dysfunction history (abuse, ▫ Detects additional injuries
neglect; domestic violence; drug/alcohol
abuse) Fundoscopy
▫ Young/single parent, parental ▪ Retinal hemorrhage (before intracranial
depression, low socioeconomic status pathology evident)
(financial stress), limited education,
biologically-male > -female (stepfather/ X-ray
maternal boyfriend) ▪ Limb X-ray → metaphyseal fractures
▪ Chest X-ray → rib fractures
614 OSMOSIS.ORG
Chapter 78 Head Injury
OTHER DIAGNOSTICS
▪ Diagnostic triad
▫ Subdural, subarachnoid hemorrhage
▫ Metaphyseal fractures (extremities flail
uncontrollably during shaking)
▫ Retinal hemorrhage
TREATMENT
SURGERY
▪ Monitor ICP → cerebral ventricle drainage
may be required
▪ Intracranial hematoma → drain blood
collection (when indicated)
Figure 78.1 An MRI scan in the coronal
OTHER INTERVENTIONS plane of an three month old female with
head injury secondary to abuse. There is
▪ Many countries have mandatory suspected
intraparenchymal hemorrhage as well as
child abuse reporting laws → report
sub-falcine and transtentorial herniation of
incident
the brain.
OSMOSIS.ORG 615
NOTES
NOTES
HEADACHES

▪ Cranial pain, disturbs everyday life DIAGNOSTIC IMAGING
CT scan/MRI
TYPES ▪ Used to exclude other diseases
Primary ▫ Unusual neurological symptomatology;
▪ Migraine, tension headache, cluster headache accompanied by ↑ body
headache temperature, stiff neck; new headache in
individual with HIV/cancer
Secondary
▪ Headaches caused by other disorders
TREATMENT
CAUSES MEDICATIONS
▪ Genetic, environmental factors; stress ▪ Prophylactic management
▫ Prevention of further attacks
SIGNS & SYMPTOMS ▪ Symptomatic treatment
▫ Pain, symptom-management
▪ Unilateral/bilateral, localized/diffuse head medications
pain
▪ Nausea, vomiting, aura/autonomic
symptoms
CLUSTER HEADACHE
osms.it/cluster-headache
afferents travel to nucleus caudalis
PATHOLOGY & CAUSES ▫ Projection to thalamus, sensory cortex
→ perception of pain
▪ One-sided headache in ophthalmic
nerve distribution region with autonomic ▫ Hyperactivation of parasympathetic
symptomatology pterygopalatine ganglion → autonomic
symptoms
▪ Hypothalamus involvement
▪ Cavernous sinus walls inflammation → ↓
▫ Episodic occurrence of cluster attacks
venous flow → injury of internal carotid
▪ Posterior hypothalamic activation → artery sympathetic fibers
secondary trigeminal stimulation →
616 OSMOSIS.ORG
Chapter 79 Headaches
TYPES
DIAGNOSIS
Episodic
▪ Daily episodes over 6–12 weeks; “clusters” DIAGNOSTIC IMAGING
followed by remission period up to 12
CT scan/MRI
months
▪ Exclude possible cranial lesions
Chronic
▪ Episodes without substantial remission OTHER DIAGNOSTICS
period
▪ Requires each of following
▫ Five unilateral/orbital/supraorbital/
CAUSES temporal attacks; 1–8 episodes daily, ≤
▪ Unknown; possibly genetic three hours
▫ Agitation/restlessness
RISK FACTORS ▫ ≥ one autonomic symptom on same side
▪ More common in individuals who are as headache
biologically male
▪ Stressful periods, allergic rhinitis, sexual
intercourse, tobacco, excessive alcohol use
TREATMENT
MEDICATIONS
COMPLICATIONS
▪ Progresses episodic → chronic Acute management
▪ Supplemental oxygen/intranasal
sumatriptan/zolmitriptan
SIGNS & SYMPTOMS ▫ Initial treatment
▪ Intranasal lidocaine/oral ergotamine/IV
▪ Headache dihydroergotamine
▫ One-sided sharp, stabbing, burning ▫ If initial treatment not effective
orbital/supraorbital/temporal head pain
▪ Autonomic Prophylaxis
▫ Ipsilateral conjunctival hyperemia with ▪ Verapamil
lacrimation, nasal discharge, miosis, ▫ Episodic attacks > two months/chronic
edema, drooping eyelid cluster headaches
▪ Episodes ▪ Glucocorticoids (e.g. prednisone); can be
▫ 1–8 per day; lasts five minutes to three used together with verapamil
hours ▪ Lithium
▪ Restlessness, agitation, suicidal ideation ▫ If other medications contraindicated
SURGERY
▪ Block greater occipital nerve
▪ Percutaneous radiofrequency ablation of
pterygopalatine ganglion
▪ Gamma knife radiosurgery
▪ Stimulation of pterygopalatine ganglion
▪ Posterior hypothalamus deep brain
stimulation
OSMOSIS.ORG 617
MIGRAINE
osms.it/migraine
TYPES
PATHOLOGY & CAUSES
Migraine with aura
▪ Disease characterized by one-sided head ▪ Typical aura migraine with/without
pain headache
▪ Probable mechanism ▪ Brainstem aura migraine
▫ ↑ neuronal hyperexcitability → cortical ▪ Hemiplegic migraine
spreading depression wave across ▫ Familial; types I, II, III
cortex → release of proinflammatory
▫ Sporadic
cytokines, matrix metalloproteinases
(MMP), nitric oxide (NO), glutamate, ▪ Ocular migraine
adenosine triphosphate (ATP),
Migraine without aura
potassium ions from neurons/glial/
vascular cells → alters blood-brain ▪ Menstrual migraine
barrier → activates perivascular ▫ Develops ≤ two days before, continues
trigeminal nociceptors ≤ three days after menstrual period
▫ Release of substance P, calcitonin ▪ Chronic migraine
gene-related peptide, neurokinin A ▫ ≥ 15 headaches per month for ≥ three
→ neurogenic inflammation with months
meningeal blood vessels dilatation, ▫ Analgesics, nonsteroidal anti-
protein exudation → further nociceptor inflammatory drugs (NSAIDs) overuse
stimulation biggest risk factor
▫ Projection of afferents to trigeminal
nucleus-pars caudalis → fibers relay to Probable migraine
thalamus, sensory cortex → perception ▪ Attacks similar to migraine without one
of pain feature needed for migraine diagnosis
▪ Trigeminal nociceptors innervate anterior
head region, upper cervical dorsal roots CAUSES
innervate posterior head region → ▪ Inheritance
converge in trigeminal nucleus caudalis →
▫ ↑ neuronal excitability
characteristic pain distribution affecting
anterior, posterior head region ▪ Familial hemiplegic migraine (FHM)
▪ Aura likely caused by depression spreading ▫ Type I: CACNA1A gene mutation
to areas where perceived consciously ▫ Type II: ATP1A2 gene mutation
▪ Serotonin receptors possibly involved in ▫ Type III: SCN1A gene mutation
migraine pathogenesis
▫ Directly acting on blood vessels/ RISK FACTORS
affecting pain pathways ▪ Individuals who are biologically female, age
▪ If nociceptors stimulated too frequently → 30–39
neuronal sensitization, cutaneous allodynia ▪ Stress, hormone oscillations, irregular
phenomenon (nociceptive response to non- eating/sleeping, weather, light, alcohol,
nociceptive stimuli) tobacco, odors
▪ Syndromes associated with migraine
▫ Recurrent gastrointestinal (GI)
disturbance; benign paroxysmal vertigo,
torticollis
618 OSMOSIS.ORG
COMPLICATIONS impairment to aphasia

▪ Status migrainosus ▪ Subtypes
▫ Migraine lasting ≥ 72 hours without ▫ Brainstem aura: dizziness, double vision,
spontaneous resolution tinnitus, speech difficulties, altered
▪ Persistent aura without infarction consciousness
▫ ≥ one week ▫ Hemiplegic: aura usually includes one-
▪ Migrainous infarction sided motor weakness; vision, sensory
defects, ↑ body temperature, seizures,
▫ Preceded by migraine attack with aura
coma
symptoms ≥ one hour; retinal migraine
→ permanent blindness ▫ Ocular: loss of vision/scotomas in one
eye; headache
▪ Migraine aura-triggered seizure
▪ Rebound headache due to medication
overuse DIAGNOSIS
LAB RESULTS
SIGNS & SYMPTOMS
▪ ↓ serum N-acetyl-aspartate levels
▪ One-sided, pulsatile headache worsened
by physical activity, with maximum pain at OTHER DIAGNOSTICS
supraorbital location; followed by nausea,
vomiting, hypersensitivity to light and Non-aura migraine
sounds ▪ Requires each of following
▫ May be accompanied by cutaneous ▫ ≥ five attacks: lasting 4–72 hours
allodynia phenomenon ▫ ≥ two of the following: one-sided,
▪ Prodromal symptoms (appear hours/days throbbing quality, moderately severe
before attack) pain, worsening with physical activity
▫ ↑ irritability to light, sound, smells; ▫ ≥ one of following with headache:
yawning, food cravings, mood changes, nausea/vomiting; light, sound sensitivity
constipation/diarrhea
Migraine with aura
▪ Postdrome symptoms
▪ Requires each of following
▫ Lasting approx. one day after headache;
sudden movements → short-lasting ▫ Aura symptoms: visual, sensory, motor,
pain in previously affected regions; speech
exhaustion/tiredness/euphoria ▫ ≥ two of following: ≥ one aura symptom
lasting ≥ five minutes, followed by other
Aura aura symptomatology; auras lasting five
▪ Negative features (areas of vision loss) minutes–one hour; one aura, one-sided;
▫ Hemianopia/quadrantanopia, peripheral aura precedes headache that occurs
vision loss, spot-like scotomas, within 60 minutes
blurriness/blindness ▫ ≥ two attacks: with listed characteristics
▪ Positive features
▫ Scintillating scotoma: glimmering
geometric shapes (e.g. zigzag line)
appearing centrally with expansion to
periphery; visual hallucinations
▫ Visual: most common
▫ Sensory: tingling sensations beginning
from one hand → arm, face → short-
lasting numbness
▫ Motor: facial/extremities weakness
▫ Language: progresses from mild speech
OSMOSIS.ORG 619
▪ Dexamethasone
TREATMENT ▫ Combined with symptomatic therapy →
↓ early headache recurrence rate
MEDICATIONS
▪ Antihypertensives
Mild/moderate ▫ Beta blockers (propranolol/metoprolol/
▪ NSAIDs (e.g. aspirin, naproxen, diclofenac, timolol)
ibuprofen) ▫ Calcium channel blockers (verapamil/
▪ Paracetamol nifedipine)
▫ Angiotensin-converting enzyme
Moderate/severe inhibitors (ACEI)/angiotensin II
▪ Triptans receptor blockers (ARBs); e.g. lisinopril/
▫ Serotonin agonists; constrict blood candesartan respectively
vessels, alter pain pathways ▪ Antidepressants
▫ Sumatriptan, zolmitriptan, naratriptan, ▫ Tricyclic antidepressants (amitriptyline,
eletriptan nortriptyline, doxepin)
▫ Oral/nasal/subcutaneous administration ▫ Serotonin-norepinephrine reuptake
▫ Triptan, NSAID combination; more inhibitors (SNRIs) (e.g. venlafaxine)
effective than individual medications ▪ Anticonvulsants
(e.g. sumatriptan, naproxen) ▫ Topiramate/valproate
▫ Ergots (ergotamine)
▪ IV triptans
OTHER INTERVENTIONS
▪ Dopamine antagonists
▪ Complementary, alternative medicine
▫ IV metoclopramide; IV/IM
▫ Herbs: butterbur (Petasites hybridus),
chlorpromazine
feverfew (Tanacetum parthenium)
▪ Ergots (e.g. dihydroergotamine)
▫ Supplementation: riboflavin, coenzyme
Q10, magnesium
TENSION HEADACHE
osms.it/tension-headache
▪ Common (≤ 14 headaches monthly)
PATHOLOGY & CAUSES
Chronic
▪ Bilateral, “tightening” headache (most ▪ ≥ 15 headaches monthly
common headache type)
▫ ↑ tenderness of pericranial myofascial
structures → activation of vasculature-
CAUSES
surrounding nociceptors → episodic ▪ ↑ muscle tenderness
TH → prolonged nociceptor stimulation ▪ Combination of genetic, environmental
→ pain pathway sensitization with factors
hyperalgesia → chronic TH ▫ Episodic TH
▪ Multifactorial inheritance
TYPES ▫ Chronic TH
Episodic
RISK FACTORS
▪ Rare (≤ one headache monthly)
▪ White individuals who are biologically
620 OSMOSIS.ORG
female of Ashkenazi Jewish descent

▪ Age ≥ 40
TREATMENT
▪ Stress, anxiety, depression, poor posture MEDICATIONS
COMPLICATIONS Immediate symptoms

▪ Rebound headache ▪ Analgesics
▪ Progresses episodic → chronic ▫ NSAIDs
▫ Paracetamol
▪ Caffeine
SIGNS & SYMPTOMS ▪ Butalbital
▫ If contraindication for NSAIDs/caffeine-
▪ Moderate, bilateral, non-pulsating head combined analgesics
pain
▫ Band-like distribution, without Prophylactic management
worsening during physical activity, few ▪ Antidepressants
minutes to one week ▫ Tricyclic antidepressants (amitriptyline,
▪ Photophobia/phonophobia nortriptyline/protriptyline)
▪ Stiffness/tenderness of head, neck, ▫ Mirtazapine/venlafaxine
shoulder muscles ▪ Anticonvulsants
▫ Topiramate/gabapentin
DIAGNOSIS
PSYCHOTHERAPY
OTHER DIAGNOSTICS ▪ Behavioral, cognitive-behavioral,
biofeedback therapy
Requires each of following
▪ Absence of nausea, vomiting
OTHER INTERVENTIONS
▪ Light/sound hypersensitivity without other
▪ Acupuncture, heating/icing, resting for
aura symptoms
immediate symptoms
▪ ≥ two of following
▫ Both sides of head affected
▫ Non-throbbing quality
▫ Moderate intensity
▫ No worsening during physical activity
OSMOSIS.ORG 621
NOTES
NOTES
HEARING LOSS

Weber
PATHOLOGY & CAUSES ▪ Distinguishes between conductive,
sensorineural hearing loss
▪ Decrease in ability to perceive sound
▪ Examiner places vibrating tuning fork
▪ Variable etiology
(128Hz) at apex of head → individual
▫ External, middle, inner ear, associated indicates loudest side
neurological input/processing structures
▫ One ear preferred/louder indicative of
possible hearing loss
SIGNS & SYMPTOMS Rinne
▪ Compares air, bone conduction of sound
▪ Hearing loss
▪ Examiner places vibrating tuning fork
▪ Balance issues, headache, tinnitus (512Hz) at mastoid process → individual
indicates when vibration heard → examiner
moves vibrating tuning fork outside of
DIAGNOSIS pinna → individual indicates if vibration
heart
OTHER DIAGNOSTICS ▫ Bone conduction (mastoid placement
▪ Bedside (otoscopy to Rinne) and formalized of tuning fork) > air conduction (i.e.
(audiogram) testing individual cannot hear vibration after
first step complete) indicative of possible
Otoscopy
hearing loss
Whisper test
Audiogram
▪ Examiner speaks in whispered voice
▪ Pure tones of varying frequencies (Hz) at
0.61m/2ft away → individual covers far
varying volume of sound
ear with hand → examiner whispers word/
phrase → individual repeats word/phrase ▪ Plot individual’s 50% correct response rate
(dependent on volume) for each frequency
Finger rub
▪ Examiner speaks closer to pinna →
individual indicates if sound heard TREATMENT
▪ Specific to underlying etiology; some
etiologies irreversible
622 OSMOSIS.ORG
Chapter 80 Hearing Loss
CONDUCTIVE HEARING LOSS

osms.it/conductive-hearing-loss
Eustachian tube dysfunction
PATHOLOGY & CAUSES ▪ Results in abnormal pressure/reflux/
clearance of middle ear contents
▪ Disability of sound waves
▪ Shorter eustachian tubes in children → ↑
▫ Unable to be amplified, transmitted by
reflux of nasopharynx contents → otitis
external/middle ear
media
▫ Higher incidence in children with
CAUSES abnormal craniofacial anatomy (e.g.
Down syndrome, Treacher Collins
Bony outgrowth syndrome)
▪ Exostoses: form at suture lines of external
auditory canal bony suture lines; associated Otitis externa
with repeated cold water exposure (e.g. ▪ AKA swimmer’s ear
swimmers) ▪ Commonly bacterial
▪ Osteomas: form at tympanosquamous ▫ Pseudomonas aeruginosa (most
suture line common pathogen)
Cerumen impaction ▪ Chronic/repeated infections → polyps (can
occlude external auditory canal)
▪ ↑ Incidence in elderly
Otitis media
Congenital
▪ Infection → effusion → poor transmittance
▪ Microtia: malformation/absence of auricle;
of sound wave in middle ear → hearing loss
1st, 2nd branchial arch derivative; mild-
moderate conductive hearing loss ▪ Highest incidence
▪ External auditory canal atresia: associated ▫ 6–18 months of age
with craniofacial diseases (e.g. Treacher ▪ Microbiology: Staphylococcus pneumoniae,
Collins syndrome, Robin sequence, Haemophilus influenzae, Moraxella
Crouzon syndrome) catarrhalis
▪ Commonly of ossicular chain (most ▪ Risk factors: daycare, bottle feeding
commonly malformation of stapes) → ▪ Complications: mastoiditis, cholesteatoma,
inability to reverberate → ↓ sound wave permanent hearing loss → deafness
transmittance to oval window
OSMOSIS.ORG 623
Otosclerosis
▪ Bony overgrowth of stapes to oval window
TREATMENT
→ inability to vibrate → inability to conduct
▪ Specific to underlying etiology
sound waves; can be autosomal dominant
with variable penetrance
MEDICATIONS
Trauma
▪ External ear
▪ Complete external auditory canal occlusion
▫ Mild: topical acidifying agent,
Tumors of middle ear glucocorticoid
▪ Cholesteatomas (most common overall) ▫ Moderate/severe: topical/oral antibiotics
▫ Desquamated, stratified, squamous ▪ Middle ear
epithelium in middle ear space ▫ Pain control (e.g. ibuprofen,
▫ Accumulation → erosion of middle acetaminophen), antibiotics
ear contents (ossicular chain) →
surrounding structures: external SURGERY
auditory canal (EAC), mastoid bone ▪ External ear
▪ Squamous cell carcinoma (most common ▫ If repeat infections/↑ size
malignant tumor)
▪ Middle ear
Tympanic membrane perforation ▫ Tissue graft
▪ Common; due to trauma/barotrauma to ear/ ▫ Surgical removal
face
OTHER INTERVENTIONS
SIGNS & SYMPTOMS ▪ External ear
▫ Cerumenolytics/irrigation/manual
▪ Decreased perception of sound removal
▫ Especially poor perception of low- ▫ Repeat infections/↑ size: EAC occlusion
frequency sound ▪ Middle ear
▫ Overcome by volume of stimulus ▫ Hearing aids
DIAGNOSIS
OTHER DIAGNOSTICS
▪ History, associated symptoms
▪ Otoscopy
▪ Special testing
▫ Weber (localization of vibration to
affected ear)
▫ Rinne (abnormal; bone conduction > air
conduction)
▪ Audiogram
▫ Universal/low-frequency deficit in pure
tone discrimination
624 OSMOSIS.ORG
OSMOSIS.ORG 625
SENSORINEURAL HEARING LOSS
osms.it/sensorineural-hearing-loss
▪ Unilateral, episodic loss concurrent with

PATHOLOGY & CAUSES tinnitus, vertigo
▫ Pathogenesis: unknown; possible
▪ Disability of inner ear (cochlea/CN VIII)
infection, autoimmune, vascular
to transduce sound waves → viable
constriction, congenital malformation
neurologic input → brain
→ endolymphatic hydrops (e.g.
overproduction of endolymph,
CAUSES distension of endolymphatic space)
Central nervous system (CNS) Noise-induced

▪ Acoustic neuroma (CN VIII; AKA vestibular ▪ Cause: chronic exposure to loud (> 85dB)
neuroma) auditory stimuli
▫ ↑ size → compress cerebellum → ataxia ▪ Pathogenesis: overstimulation of hair cells
▪ Meningitis in organ of Corti → nitric oxide, free radical
▫ Infection (via cerebrospinal fluid) → release → damage, death of hair cells
cochlea → cochleitis → direct damage ▪ ↓ Mg2+ → ↓ Ca2+ intracellular concentration
to inner hair cells → ↑ cell damage, death
▪ Meningioma Presbycusis
▪ Acoustic nerve neuritis ▪ Most common
▫ Multiple sclerosis, syphilis ▪ Gradual, symmetric hearing loss in elderly
Congenital ▪ More significant loss with higher
▪ Spontaneous/genetic frequencies
▪ Acquired ▪ Pathogenesis: degeneration of hair cells at
base of cochlea
▫ Toxoplasmosis, other (syphilis,
varicella-zoster, parvovirus B19), Trauma
rubella, cytomegalovirus (CMV), herpes ▪ Skull fracture → injury to CN VIII/cochlea
(TORCH) infections
Drug-induced
SIGNS & SYMPTOMS
▪ Aminoglycoside antibiotics (most common);
cisplatin
▪ Decreased perception of sound (esp. high-
▪ Aspirin (high-dose 6–8g/day), quinidine, pitched sounds, speech discrimination)
loop diuretics (e.g. furosemide, ethacrynic
acid) → reversible hearing loss, tinnitus
Inner ear infection

DIAGNOSIS
▪ Labyrinthitis (inflammation, spinning,
DIAGNOSTIC IMAGING
ringing)
MRI
Menière’s disease
▪ Identifies causes such as acoustic neuroma,
▪ Rare
perilymphatic fistula
626 OSMOSIS.ORG
OTHER DIAGNOSTICS ▪ Antibiotics

▪ History, associated symptoms ▫ Meninges
▪ Otoscopy
▫ Rules out causes of conductive hearing SURGERY
loss ▪ Surgical resection
▪ Special testing ▫ Acoustic nerve
▫ Weber: lateralization of sound to
unaffected ear
▫ Rinne: air, bone conduction (AC > BC)
OTHER INTERVENTIONS
▪ Hearing aids
▪ Audiogram
▫ Hair cells of organ of Corti
▫ Identifies deficit in high-pitched pure
tone discrimination ▪ Dietary changes (↓ Na+)
▫ Endolymph of labyrinthine systems
▪ Radiotherapy
TREATMENT ▫ Acoustic nerve
▪ Specific to underlying etiology
MEDICATIONS
▪ Antiemetics, vestibular suppressants (e.g.
benzodiazepines), diuretics
▫ Endolymph of labyrinthine systems
OSMOSIS.ORG 627
NOTES
NOTES
INCREASED INTRACRANIAL
PRESSURE

CAUSES
PATHOLOGY & CAUSES ▪ Cerebral edema (e.g. acute hypoxic
ischemic encephalopathy, trauma)
▪ Abnormal ↑ intracranial pressure
▪ Intracranial space occupying lesion (e.g.
▫ Normal: 10–15mmHg (adults); tumor, aneurysm, hemorrhage, etc.)
5–20mmHg (infants)
▪ ↑ CSF production
Monro-Kellie hypothesis ▪ Obstructive hydrocephalus
▪ Fixed cranial volume in skull ▪ ↓ CSF absorption
▪ Three main components ▪ Venous outflow obstruction
▫ Cerebrospinal fluid (CSF), blood, brain ▪ Idiopathic intracranial hypertension
tissue
Intracranial compliance (ICC) SIGNS & SYMPTOMS

▪ Changes in intracranial content volume and
changes in intracranial pressure (ICP) ▪ Deteriorating level of consciousness (early
▪ Slight ↑ volume → compensatory sign)
mechanisms → slight ↑ ICP ▪ Headache
▫ CSF displacement into thecal sac ▪ Nausea
▫ Venoconstriction/extracranial drainage ▪ Vomiting
→ ↓ cerebral venous blood volume ▪ Ocular palsies
▪ Drastic volume increase → ↓ ICC → ↑ ICP ▪ Mydriasis (dilated pupils)
↑ ICP ▪ Papilledema
▪ → compression of blood vessels → ↓ brain ▪ Dyspnea
perfusion → brain ischemia → edema → ▪ Back pain
↑↑ ICP ▪ Decorticate/decerebrate posturing
▫ Cerebral perfusion pressure (CPP) =
mean arterial pressure (MAP)−ICP
▫ ↓ CPP → ↑ systemic blood pressure/ DIAGNOSIS
vasodilation → ↑ cerebral blood volume
→ ↑ ICP → ↓ ↓ CPP DIAGNOSTIC IMAGING
Nerve compression CT scan
▪ → impaired brain function ▪ Mass lesions, midline shift, basilar cisterns
effacement
628 OSMOSIS.ORG
Chapter 81 Increased Intracranial Pressure
OTHER DIAGNOSTICS OTHER INTERVENTIONS

▪ ICP monitoring ▪ Target → ICP < 20mmHg, MAP >
▫ Intraventricular catheter (gold standard) 90mmHg, CPP > 65mmHg
▫ Intraparenchymal fiberoptic catheter ▪ Elevate head (30°) → maximize venous
outflow
▪ Airway, breathing, and circulation (ABCs),
TREATMENT maintain adequate oxygenation
▪ Treat shock (if applicable): hypertonic
MEDICATIONS saline (HTS) (e.g 7.5%) to treat edema; HTS
▪ Sedation (propofol), osmotic diuretics, maintains high serum osmolality → reduces
prophylactic anticonvulsants cerebral edema (> 280 mOsm/L); ↑ serum
osmolarity prevents intravascular fluid
leakage to brain tissue; ↑ serum osmolarity
SURGERY
draws excess water from brain tissue → ↓
▪ Surgical removal of space-occupying lesion ICP
▪ Decompressive craniectomy ▪ Hyperventilation
▪ Extraventricular drain (EVD)
BRAIN HERNIATION
osms.it/brain-herniation
site (craniectomy) → decortication of
PATHOLOGY & CAUSES herniated gyrus
▪ Brain tissue displacement: through skull Infratentorial herniation

opening or dural fold ▪ Tonsillar
▪ Damages associated with herniated section ▫ Cerebellar tonsils herniate in foramen
magnum → brainstem, spinal cord
TYPES compression
Supratentorial herniation
CAUSES
▪ Cingulate/subfalcine
▪ ↑ ICP
▫ Gyrus forced under falx cerebri →
cerebral artery compression → cerebral
ischemia then edema → ↑ ICP SIGNS & SYMPTOMS
▪ Uncal/transtentorial
▫ Cranial nerve (CN) compression in ▪ Decorticate/decerebrate posturing
nerves III, IV, posterior cerebral artery ▪ Seizures
→ ipsilateral visual cortex ischemia → ▪ ↓ level of consciousness, coma
homonymous hemianopsia
▪ Glasgow Coma Scale (GCS) 3–5
▪ Central
▪ Mydriasis (dilated pupils)
▫ Temporal lobes squeezed through notch
▪ Irregular/slow pulse
in tentorium cerebelli → basilar artery
stretched → tearing, bleeding (Duret ▪ Respiratory/cardiac arrest
hemorrhage) ▪ Loss of brainstem reflexes (blinking,
▪ Transcalvarial gagging, pupillary reflex)
▫ Brain herniates through fracture/surgical
OSMOSIS.ORG 629
DIAGNOSIS
DIAGNOSTIC IMAGING
Head CT scan/MRI
▪ Depending on the cause, results show
mass lesions (e.g. tumor, aneurysm,
infarction, hemorrhage etc.) and
subsequent displacement of the brain away
from the mass, depending on localization
TREATMENT
MEDICATIONS
▪ Osmotic diuretics
▪ Paracetamol (manage fever)
▪ Sedation/paralytic agents Figure 81.1 An MRI scan of the head in the
▪ ↓ metabolism → ↓ O2 consumption + ↓ CO2 coronal plane demonstrating herniation of the
production → no systemic vasodilation → ↓ cerebellar tonsils secondary to hypoxic brain
cerebral blood volume → ↓ ICP injury.
▪ Prophylactic anticonvulsants
SURGERY
▪ Decompressive craniectomy
OTHER INTERVENTIONS
▪ HTS boluses → support circulation
▫ HTS → ↑ serum osmolarity → draw
excess water from brain tissue → ↓ ICP
▪ Hyperventilation
▫ Helps avoid ↑ PaCO2 or hypoxemia →
systemic vasodilation → ↑ ↑ cerebral
blood volume → ↑ ICP

axial plane demonstrating a right sided acute
subdural hemorrhage. The pressure effect
has pushed the medial aspect of the right
cerebral hemisphere underneath the falx
cerebri, known as sub-falcine herniation.
630 OSMOSIS.ORG
Chapter 81 Increased Intracranial Pressure
IDIOPATHIC INTRACRANIAL
HYPERTENSION (IIH)
osms.it/idiopathic-intracranial-hypertension

▪ AKA pseudotumor cerebri ▪ Goal: treat symptoms/preserve vision
▪ Chronic ↑ ICP, no obvious cause
MEDICATIONS
CAUSES ▪ Carbonic anhydrase inhibitor
▪ ↑ ICP → CN II compression → visual (acetazolamide) → ↓ CSF production
impairment ▫ Contraindication: pregnancy
▪ Loop diuretics (furosemide) → ↓
RISK FACTORS papilledema and ↓ mean CSF pressure
▪ Overweight, biologically female, fertile ▫ Contraindication: pregnancy
individuals
SURGERY
▪ Optic nerve sheath fenestration (ONSF)
SIGNS & SYMPTOMS
▪ Papilledema OTHER INTERVENTIONS
▪ Visual field loss ▪ Weight loss
▪ CN palsies, typically CN VI (long intracranial
course)
▪ Headache
▪ Pulsatile tinnitus
▪ Photopsia (seeing flashes of light)
▪ Diplopia (double vision)
▪ Temporary visual disturbance
▪ Retrobulbar pain
▪ Back pain
DIAGNOSIS
OTHER DIAGNOSTICS
▪ Headache & papilledema with
▫ No secondary cause of ↑ ICP: normal
neuroimaging (MRI, contrast CT scan),
normal CSF composition Figure 81.3 A retinal photograph
▫ No malignant hypertension: mimics IIH demonstrating an expanded optic disc
caused by intracranial hypertension.
▫ Lumbar puncture: ↑ opening pressure
OSMOSIS.ORG 631
NOTES
NOTES
MOTOR NEURON DISEASES

▪ Group of degenerative motor neuron OTHER DIAGNOSTICS
diseases ▪ History, physical examination (upper, lower
▫ Progressive muscle weakness, disability motor neuron signs)
▪ Muscle biopsy
CAUSES ▪ Electromyography (EMG)
▪ Mainly genetic
TREATMENT
SIGNS & SYMPTOMS
MEDICATIONS
▪ Muscle weakness, fatigue → disability ▪ Emerging disease-modifying agents
(limited efficacy)
OTHER INTERVENTIONS
▪ Primarily supportive care
AMYOTROPHIC LATERAL
SCLEROSIS (ALS)
osms.it/amyotrophic-lateral-sclerosis
chromosome 9; 20% of familial ALS
PATHOLOGY & CAUSES ▫ Gain-of-function mutation → misfolding
→ protein aggregation → direct
▪ Progressive, degenerative motor neuron
neuronal injury, unfolded protein
disease; upper, lower motor neuron signs
response → death
▫ AKA Lou Gehrig’s disease
▫ Interference with organelle autophagy,
▪ Genetic associations in familial ALS provide proteasome function
insight to pathogenesis
▫ Interference with axonal transport,
▪ Protein aggregation → neuronal injury, mitochondrial function
death → retrograde neuronal degeneration
▫ Further protein sequestration within
→ gliosis
protein aggregate
▪ Superoxide dismutase 1 (SOD1):
▪ C9orf72: protein of unknown significance;
antioxidant protein encoded on
40% of familial ALS
632 OSMOSIS.ORG
Chapter 82 Motor Neuron Disease
▫ Hexanucleotide repeat expansion COMPLICATIONS

→ long 5’ end of RNA transcript → ▪ Frontotemporal lobar dementia (FTLD)
abnormal transcription, novel protein ▫ Disinhibition, compulsivity, loss of
production → aggregation empathy
▫ Unknown specific pathogenesis ▫ Pseudobulbar affect (PBA): common;
▫ Accumulated, novel proteins; dead inappropriate, labile, expressive
neurons emotions (e.g. crying, yawning)
▪ TDP-43, FUS: RNA-binding genes ▪ Neuromuscular respiratory failure
▫ Abnormal RNA processing → abnormal ▪ Dysphagia → pneumonia
protein accumulation → neuronal injury
▫ Pathway not completely known
▪ Inflammatory response SIGNS & SYMPTOMS
▫ Cerebral inflammatory response
primarily mediated by microglia, ▪ Early symptoms
astrocytes ▫ Asymmetric hand weakness →
▫ Natural killer, peripheral T-cells, dropping of objects (e.g. glasses of
monocytes infiltrate, contribute to water)
inflammation ▫ Cramping of upper extremities
▫ Microglial response → nitric oxide, (common)
oxygen radical, cytokine, glutamate ▫ Dysarthria, dysphagia, dysphonia
release → motor neuron cell death develop later
▫ SOD1 mutations especially susceptible ▪ Atrophy → ↓ strength → ↓ muscle bulk,
to pathologic inflammatory response abnormal tone → fasciculations
▫ Weakness → inability to ambulate →
wheelchair use
TYPES
▪ Late symptoms
Progressive motor atrophy ▫ Respiratory weakness → dyspnea →
▪ Predominant lower motor neuron respiratory infection
degeneration ▫ Recurrent bouts of cough, fever, chill →
pneumonia
Primary lateral sclerosis
▪ Predominant upper motor neuron
degeneration DIAGNOSIS
Progressive bulbar palsy (AKA bulbar ALS)
LAB RESULTS
▪ Affected cranial nerves → abnormal
▪ ↑ creatinine kinase (due to muscle atrophy)
deglutition, phonation → ventilator support
required ▪ Heavy-metal levels, lyme disease
▪ Poor prognosis ▫ Negative
▫ Mortality rate > 50% at two years
OTHER DIAGNOSTICS
CAUSES ▪ El Escorial criteria (all three required)
▪ May be sporadic ▫ Evidence of lower motor neuron (LMN)
disease by clinical/electrophysiologic/
▪ Familial (5–10%)
neuropathic examination
▫ Multiple genes (e.g. SOD1)
▫ Evidence of upper motor neuron (UMN)
disease by clinical examination
RISK FACTORS ▫ Progressive spread of signs/symptoms
▪ Family history, age, cigarette smoking within/outside of body region, as
determined by history/examination
▪ Family history
OSMOSIS.ORG 633
▪ Neurological OTHER INTERVENTIONS
▫ Upper, lower motor neuron signs ▪ Nothing curative, management of symptom
▪ Psychiatric progression, severity
▫ Mental status examination → apathy, ▪ Symptom management
disinhibition, PBA in FTLD individuals ▫ Multidisciplinary approach: neurologists,
physical therapists, speech therapists,
EMG dietitians
▪ Helps differentiate from other ▫ Respiratory management: ↓ aspiration
neuromuscular junction diseases event → ↓ rate of progression to
▪ Acute denervation tracheostomy, ventilator-dependence
▫ Fibrillations of muscle fibers → active ▫ Respiratory evaluation every three
denervation → improper neuronal months after diagnosis
discharge → small-amplitude baseline
variance
▪ Chronic denervation
▫ Large amplitude, long duration, complex
motor potentials
▫ Denervation injury → ↑ muscle fiber
recruitment, ↓ neuronal innervation
TREATMENT
MEDICATIONS
Disease-modifying agents
▪ New to market, mild/modest benefit
▪ Riluzole
▫ Indicated for mild-moderate disease of <
five year duration
▫ Mechanism of action: ↓ any Figure 82.1 Amyotrophic lateral sclerosis is
excitotoxic interplay by glutamate in also known as Lou Gehrig’s disease. Gehrig
neuronal toxicity → ↓ rate of neuron played for the Yankee’s and died of ALS at
degeneration, symptom progression the age of 37.
▪ Edaravone
▫ Mechanism of action: free-radical
scavenger → ↓ oxidative stress → ↓ rate
of neuronal death, symptom progression
▪ Symptom management
▫ Muscle spasms: quinine
▫ Muscle spasticity: muscle relaxants
634 OSMOSIS.ORG
SPINAL MUSCULAR ATROPHY

osms.it/spinal-muscular-atrophy
SMN2 pseudogene point mutation
PATHOLOGY & CAUSES ▪ Encodes similar protein as SMN1
▪ Genetically-mediated degenerative ▫ Difference: exon 7 (c.840C>T)
neurologic disease of childhood ▫ ↑ susceptibility for protein degradation
▫ Lower motor neuron weakness, → ↓ functional protein at baseline
muscular atrophy ▪ SMN1 deficient → SMN2 responsible for
▪ Survival of motor neuron-1 (SMN1) loss- SMN protein production → poor production
of-function mutation → ↓ motor neuron of viable protein → motor neuron cell death
survival → loss of alpha motor neurons ▫ Copy number variation correlates with
(even in utero) → degeneration of anterior clinical presentation
horn cells → denervated skeletal muscle →
hypotonia, muscle atrophy RISK FACTORS
▪ Family history
CAUSES
SMN1 loss-of-function mutation COMPLICATIONS
▪ Autosomal recessive ▪ Sleep disturbance
▪ Encoded on chromosome 5q ▪ Cardiac arrhythmias (esp. SMA 1, 2, 3)
▪ Multiple physiologic roles ▪ Restrictive respiratory disease (esp. SMA
0,1)
▫ Spliceosome assembly: ↓ nuclear
expression of SMN1 in spinal muscular ▫ Diaphragmatic involvement →
atrophy (SMA) respiratory collapse
▫ Inhibition of caspase system: ↓ SMN1 ▪ Dysphagia → aspiration → pneumonia
expression → disinhibition of caspase ▪ Poor ambulation → delayed gastric
→ ↑ caspase expression → cellular emptying → gastrointestinal (GI) reflux,
apoptosis constipation
▫ Unclear role in alpha motor neuron
(patho)physiology
OSMOSIS.ORG 635
▪ Lower motor neuron signs MEDICATIONS
▫ Proximal limb severity (more common
Experimental disease-modifying therapy
than distal), ↓ muscle strength, tone;
↓/absent DTRs, muscle atrophy, ▪ Nusinersen
fasciculations ▫ Antisense oligonucleotide → binds
SMN2 mRNA → ↓ exon 7 splicing → ↑
levels of functional SMN protein
DIAGNOSIS ▫ Limited effectiveness
OTHER DIAGNOSTICS
OTHER INTERVENTIONS
▪ Neurological
▪ Pulmonary
▫ Fasciculations; ↓ muscle strength, tone;
▫ Secretion management → ↓ aspiration
DTRs
events → ↓ pneumonia
▪ Muscle testing
▫ Ventilator support (SMA 0,1)
▫ EMG
▪ Nutrition, GI
▫ Abnormal spontaneous activity,
▫ Manage food consistency → ↓
fibrillations, positive sharp waves
aspiration
▪ Muscle biopsy
▫ Gastrostomy tube placement in SMA 1
▫ Large zones of severely atrophic
▫ Encourage ambulation → ↓ gastric
myofibers
emptying time → ↓ constipation, GI
▫ Remaining innervated fibers → reflux
unchanged/hypertrophied size
▪ Orthopedic, musculoskeletal
▫ Physical therapy
▫ Spinal bracing → ↓ scoliosis → ↓
incidence of restrictive lung disease
Figure 82.2 A muscle biopsy demonstrating

neurogenic atrophy as would be seen in
motor neurone diseases like spinal muscular
atrophy. Denervated muscle fiber bundles are
small and atrophied whilst those that remain
innervated retain their normal size.
636 OSMOSIS.ORG
OSMOSIS.ORG 637
NOTES
NOTES
MOVEMENT DISORDERS

▪ Motor abnormality
PATHOLOGY & CAUSES ▫ Hypokinesia: ↓ amplitude
▪ Disorders causing abnormal movement ▫ Bradykinesia: ↓ speed
▫ Increased voluntary/involuntary ▫ Dyskinesia: unwanted, characterized
movement (hyperkinetic disorders); motor movement
reduced movement (hypokinetic ▫ Tremor: rhythmic motor movement;
disorders) resting, action, postural
▫ Rigidity: abnormal, uncoordinated
muscle tone across joint
TYPES
Acute fulminant episodes
▪ Reaction to trigger, medication (neuroleptic
DIAGNOSIS
malignant syndrome)
OTHER DIAGNOSTICS
Benign chronic conditions ▪ Neurologic examination
▪ Restless legs syndrome (RLS), essential ▫ Observation of spontaneous movement,
tremor strength testing, tone evaluation, reflex
exam
Progressive chronic syndromes
▪ Parkinson’s disease (PD), Friedreich’s ataxia
TREATMENT
CAUSES
MEDICATIONS
▪ Often idiopathic; genetic mutations,
medication ▪ Beta blockers, anti-epileptics,
benzodiazepines; dopamine replacement,
agonists
SIGNS & SYMPTOMS
OTHER INTERVENTIONS
▪ Mild, unpleasant sensations, intention/ ▪ Avoid caffeine, nicotine, etc.
action tremors; rigidity, catatonia ▪ Educational, supportive therapy
638 OSMOSIS.ORG
Chapter 83 Movement Disorders
ESSENTIAL TREMOR
osms.it/essential-tremor

▪ Most common movement disorder; OTHER DIAGNOSTICS
involuntary, rhythmic shaking ▪ Postural/action tremor of hands/head;
▪ Usually affects hands, fingers; sometimes duration ≥ three year
head, vocal cords ▪ Alleviation with alcohol intake
▪ Action tremor (occurs during muscle effort)
▫ Postural/intention tremor
▪ Fine postural, action tremor in hands, head/
voice
CAUSES ▪ Asymmetric/symmetric: cogwheel rigidity,
▪ Unknown; may be familial with autosomal resting tremor, dystonia (esp. head)
dominant inheritance pattern

▪ Meat consumption
MEDICATIONS
▫ Exposure to heterocyclic amines (e.g.
▪ If disabling, symptomatic treatment
harmane, harmaline)
▫ Beta blockers
▪ Associated with dystonia (cervical,
spasmodic, cranial dystonia, writer's ▫ Anti-epileptics
cramp), parkinsonism ▫ Benzodiazepines
▫ Botulinum toxin (head tremors not
responsive to medication)
SIGNS & SYMPTOMS
OTHER INTERVENTONS
▪ Rhythmic, symmetrical tremor
▪ Avoid caffeine, nicotine, etc.
▫ Hands, head, vocal cords, neck, face,
leg, tongue, trunk ▪ Get enough sleep
▪ High frequency tremor (4–12Hz)
exacerbated by muscle contraction
▪ Inability to perform precise tasks
▪ Intention tremor
▫ Intensifies upon touching nose with
finger
▪ Postural tremor
▫ During outstretched arms
▪ Walking difficulties
▪ ↓ tremor with alcohol intake
OSMOSIS.ORG 639
FRIEDREICH'S ATAXIA
osms.it/friedreichs-ataxia
▫ 600–1200 trinucleotide repeats →
PATHOLOGY & CAUSES Friedreich’s ataxia
▪ Genetic disorder; causes progressive

central nervous system (CNS) damage, COMPLICATIONS
movement problems
Progressive loss of cells
▪ Predominantly affects CNS; also affects
▪ In CNS, heart, pancreas
heart, pancreas
▪ Limb, gait ataxia → wheelchair bound →
▪ ↓ frataxin → ↓ mitochondrial oxidative
bedridden
phosphorylation → cell damage, death
▪ Dysphagia, dysarthria → aspiration →
▪ ↓ frataxin → ↑ free iron → ↑ oxidative stress
gastric bacteria insult to respiratory
→ cell damage, death
parenchyma
▪ Neuronal cell death affects posterior
▪ Hypertrophic cardiomyopathy (secondary
columns of spinal cord, distal corticospinal
to myocardial cell death)
tracts, spinocerebellar tracts, brain stem,
cerebellum ▫ Fibrosis → arrhythmia, hypertrophic
cardiomyopathy → heart failure
▪ Gene silencing → no frataxin synthesized
→ iron accumulates in cell, reacts with ▫ Most common cause of death in
oxygen → unstable oxygen radicals → cell affected individuals (age 40–50)
death ▪ Diabetes mellitus
▫ Loss of beta cells of pancreas
CAUSES ▪ 25% of affected individuals
▪ Trinucleotide repeat GAA expansion ▪ Musculoskeletal abnormalities
(chromosome 9q13) → ↓ production of ▫ Muscle denervation → abnormal forces
mitochondrial inner membrane protein, about joints → abnormalities
frataxin ▪ Kyphoscoliosis
▫ Autosomal recessive inheritance pattern ▫ Severe → ↓ total lung capacity →
▫ ↑ repeats → ↑ severity, ↓ age of onset restrictive lung disease
640 OSMOSIS.ORG
▪ Pes cavus OTHER DIAGNOSTICS

▫ Similar restrictive lung disease in severe ▪ Symptom progression, family history
cases ▪ Neurological exam
▪ Hammer toes ▫ Ataxia (gait, hand); ↓ vibratory
sensation, proprioception; ↓ deep
tendon reflexes, nystagmus
SIGNS & SYMPTOMS
Electromyogram
▪ Ataxia ▪ Absent/reduced sensory nerve action
▫ Falling/staggering while walking, wide- potentials
based gait ▪ Normal/only slightly decreased motor nerve
▫ Gait ataxia most common (age 0–10); conduction velocities
most individuals progress to wheelchair ▪ Abnormal auditory, visual, somatosensory-
dependence within 11–25 years evoked responses
▪ Loss of vibratory sense, proprioception
▪ Muscle weakness, chest pain,
dyspnea, heart palpitations, absence TREATMENT
of tendon reflexes in legs, involuntary
eye movements, action tremor, hand OTHER INTERVENTIONS
clumsiness, dysarthria, fatigue ▪ Occupational, physical therapy
▫ Balance, ataxic progression
▪ Cardiology
DIAGNOSIS ▫ Annual electrocardiogram,
echocardiogram
LAB RESULTS ▪ Severe scoliosis
Genetic testing ▫ Orthopedic referral
▪ Confirms diagnosis ▪ Annual diabetes screening
▪ GAA repeats; examine first intron in frataxin ▪ Genetic, psychological counseling services
gene
OSMOSIS.ORG 641
NEUROLEPTIC MALIGNANT
SYNDROME
osms.it/neuroleptic-malignant-syndrome
▪ Lithium/alcohol/psychoactive substance use
PATHOLOGY & CAUSES ▪ Previous episode of neuroleptic malignant
syndrome
▪ Life-threatening idiosyncratic reaction
to antipsychotic drugs; muscle rigidity, ▪ Acute injury (e.g. trauma, surgery, infection)
fever, altered mental status, autonomic ▪ Psychiatric conditions (e.g. acute catatonia,
dysfunction severe agitation)
▪ Dopamine blockade theory ▪ Lewy body dementia
▫ Central dopamine blockade →
hypothalamus → hyperthermia, COMPLICATIONS
dysautonomia ▪ Rhabdomyolysis, renal failure
▫ Nigrostriatal dopamine blockade → ▪ Seizures
tremor, rigidity
▫ Due to hyperthermia, metabolic
▪ Peripheral muscle theory imbalances
▫ Direct toxic effect of neuroleptics → ▪ Encephalopathy, stupor, coma
mitochondria of skeletal muscle →
▪ Cardiac arrhythmias (e.g. torsades de
rigidity, fever
pointes, cardiac arrest)
▪ Sympathetic nervous system theory
▪ Disseminated intravascular coagulation
▫ ↓ dopamine inhibitors → ↑ sympathetic
output
▫ ↑ sudomotor, vasomotor activity → fever SIGNS & SYMPTOMS
CAUSES Altered mental status

▪ Agitated delirium with confusion (initial
Reaction to medications symptom); coma
▪ First-generation neuroleptic (most
common) Muscular abnormalities
▫ Haloperidol, fluphenazine, ▪ Generalized muscular rigidity (“lead-pipe
chlorpromazine rigidity”)
▪ Second-generation neuroleptic medication ▫ Associated dysphonia, dysarthria
▫ Clozapine, risperidone, olanzapine ▪ Catatonic signs
▪ Antiemetic ▪ Extrapyramidal symptoms
▫ Metoclopramide, promethazine, ▫ Tremor, chorea, akinesia
droperidol ▪ Less common
▪ Withdrawal of L-Dopa/dopamine agonist ▫ Dystonic movements (e.g. opisthotonos,
therapy (Parkinson disease) trismus, blepharospasm), mutism,
dysarthria, dysphagia
RISK FACTORS Hyperthermia
▪ Increase in dose/change of neuroleptic ▪ Temperatures > 38–40°C/100.4–104°F
medication
▪ Abrupt cessation/reduction of dopaminergic
medication
642 OSMOSIS.ORG
Autonomic dysfunction
▪ Tachycardia, labile/elevated blood pressure,
TREATMENT
tachypnea, sialorrhea, profuse diaphoresis
(sweating), flushing, incontinence
MEDICATIONS
▪ Discontinue offending neuroleptic agent
▪ Dantrolene (skeletal muscle relaxant),
DIAGNOSIS bromocriptine (dopamine agonist); both
(if severe) to reduce muscle rigidity,
LAB RESULTS hyperthermia
▪ Severe ↑ creatine kinase (CK)
▫ Correlates with rigidity severity → OTHER INTERVENTIONS
1–100k international units/L ▪ Maintain cardiorespiratory stability
▪ Mild ↑ lactate dehydrogenase, alkaline ▫ Intubation, mechanical ventilation
phosphatase, liver transaminases ▪ Temperature reduction
▪ Electrolyte imbalances ▫ Cooling blankets, ice water
▫ ↓ Ca2+, ↓ Mg2+, ↓ Na+/↑ Na+, ↑ K+, gastric lavage, ice packs in axilla;
metabolic acidosis acetaminophen/aspirin
▪ ↑ white blood cell count (leukocytosis) ▪ Correct fluid, electrolyte imbalance
10–40k ▫ ↓ CK damage/accumulation; replete
▪ Myoglobinuria insensible losses from diaphoresis
▪ ↓ serum iron concentration ▫ Benzodiazepines: ↓ uncontrollable
agitations
OTHER DIAGNOSTICS ▪ Electroconvulsive therapy
▪ Clinical presentation ▫ If not responsive to medical therapy in
▫ Altered mental status → hyperthermia, first week; if severe/lethal catatonia
rigidity → autonomic dysfunction
OSMOSIS.ORG 643
PARKINSON'S DISEASE
osms.it/parkinsons-disease
COMPLICATIONS
PATHOLOGY & CAUSES
▪ Freezing phenomenon
▪ Degeneration of dopaminergic neurons in ▫ Progressive hypokinesia, bradykinesia
substantia nigra → tremor, rigidity, akinesia, → (akinetic) pauses in movement;
postural instability common when walking; tend to occur at
thresholds (e.g. door frames)
▪ Most common neurological disorder; onset
after age 50 ▪ Falls
▪ Degeneration of neurons in substantia nigra ▫ Secondary to postural instability, poor
→ dopamine depletion from basal ganglia movement amplitude
→ disruption of connection to thalamus, ▪ Dystonia
motor cortex → Parkinsonism ▫ Abnormal tone across joints →
▪ Exact mechanism unknown; build-up disfiguring, painful posturing; universal
of abnormal proteins into Lewy bodies flexion of joints → severely kyphotic
in neurons; accompanied by death of posturing → poor ability to ambulate,
astrocytes, significant increase in microglia ventilate
of substantia nigra ▪ Dementia
▪ Protein (e.g. alpha-synuclein) accumulation ▫ Common after prolonged, primarily
in neuron → abnormal intracellular transit motor disease (in contrast to Lewy body
→ neuronal damage, death → motor dementia); psychosis, hallucinations
symptoms (severe)
▫ Asymptomatic neuronal degeneration:
brainstem (locus coeruleus)
▫ Symptomatic neuronal degeneration: SIGNS & SYMPTOMS
basal ganglia; dopaminergic substantia
nigra pars compacta neurons diseased, ▪ Psychiatric
die → dennervate striatum → ▫ Depression, anxiety, mood disturbances;
dysfunctional basal ganglia → hypo/ impairment of cognitive function,
bradykinetic motor output dementia (advanced stages)
▫ Late degeneration: cerebral cortex; ▪ Sleep disturbances
leads to cognitive impairment ▫ Wild dreams
▪ Autonomic dysfunction
CAUSES ▫ Orthostatic hypotension, constipation,
▪ Usually idiopathic increased sweating
▪ Mutation of PINK1, parkin, alpha synuclein ▪ ↓ olfactory sense
genes ▫ Common first symptom; history of ↓ /
▪ Toxicity in recreational drug MPPP changed sense of taste, smell prior to
(synthetic opioid); rare motor symptoms
▪ Micrographia
RISK FACTORS
▪ Family history, previous head injuries,
pesticides exposure
▫ Caffeine, nicotine
644 OSMOSIS.ORG
MNEMONIC: TRAPS MNEMONIC: SALAD

Parkinson’s disease Common Parkinsonism
symptoms treatments
Tremor (resting tremor) Selegiline
Rigidity Anticholinergics:
Akinesia trihexyphenidyl, benzhexol,
Postural changes (stooped) orphenadrine
Stare (serpentine stare) L-Dopa + peripheral
decarboxylase inhibitor:
carbidopa, benserazide
Amantadine
Dopamine postsynaptic
receptor agonists:
bromocriptine, lisuride,
pergolide
Dopamine replacement
▪ Precursor to dopamine → ↑ dopamine
synthesis → ↑ synaptic dopamine → ↓
motor symptoms
▪ Commonly formulated with carbidopa
(peripheral decarboxylase inhibitor)
▫ Carbidopa-mediated inhibition of liver,
DIAGNOSIS systemic carboxylation → levodopa
cross blood brain barrier (BBB) → ↑
dopamine formation
OTHER DIAGNOSTICS
▪ Adverse effects
▫ On/off phenomena: return of symptoms
▫ Resting tremor, rigidity, bradykinesia
prior to next dose; due to half life of
▫ Dopaminergic medication response levodopa (approx. 90 minutes)
▪ Postmortem autopsy ▫ Dyskinesia, dystonia: abnormal,
▫ Loss of pigmented dopaminergic repetitive movement (dyskinesia),
neurons of substantia nigra pars abnormal sustained muscle contraction
compacta (dystonia); head, neck (e.g. tardive
▫ Lewy bodies (intracytoplasmic dyskinesia of tongue, cervical torticollis);
eosinophilic inclusions), neurites ↑ incidence with ↑ dosing, duration of
disease
▫ Neuroleptic malignant syndrome: when
TREATMENT discontinued abruptly/high, multiple
doses missed
MEDICATIONS
▪ Symptomatic treatment; see mnemonic Dopamine agonists
▪ ↑ dopaminergic stimulation of postsynaptic
receptors → ↓ motor symptoms
▪ Adverse effects
▫ Dyskinesia
▫ Impulse control disorder: ↑ risk-taking
behavior (e.g. pathologic gambling;
compulsive sexual behavior, shopping)
OSMOSIS.ORG 645
Monoamine oxidase B (MAO-B) inhibitors SURGERY
▪ ↓ MAO-B-related dopamine metabolism → ▪ Deep brain stimulation (DBS)
↑ synaptic dopamine → ↓ motor symptoms ▫ Direct neural stimulation of basal
▪ Most effective for mild-moderate symptoms ganglia (either subthalamic nucleus
of globus pallidus interna) → ↑ motor
Anticholinergic output of basal ganglia → ↓ motor
▪ Improves neurochemical imbalance in basal symptoms
ganglia ▫ Severe/medication nonresponsive
▪ Most useful in young (< 70) individuals with disease
tremor as primary symptom; less useful for
rigidity, bradykinesia
OTHER INTERVENTIONS
▪ Anticholinergic side effects common
▪ Education, support
Amantadine ▫ Physical, emotional aspect of
▪ Antiviral drug degenerative, debilitating disease
▫ Known NMDA receptor agonist; ↓ ▪ Physical therapy
neurotransmitter imbalance i ▫ Exercise → ↓ incidence of falls
▪ Most useful in mild disease
Catechol-O-methyltransferase (COMT)
inhibitors
▪ ↓ dopamine, levodopa metabolism → ↑
synaptic dopamine → ↓ motor symptoms
▪ Rarely used as monotherapy
RESTLESS LEG SYNDROME

osms.it/restless-legs-syndrome
TYPES
PATHOLOGY & CAUSES
Primary RLS
▪ Uncontrollable urge to move legs, relieved ▪ Idiopathic; runs in families; onset < 45 years
by movement old; progressive, worsens over time
▪ Affects legs, feet bilaterally; less commonly
affects arms Secondary RLS
▪ Associated with underlying medical
conditions, medications; onset > 45 years
CAUSES
▪ Unknown
▪ CNS
RISK FACTORS
▪ Pregnancy, iron deficiency/anemia,
▫ ↓ iron, dopamine
smoking, caffeine, Parkinson’s disease,
▪ Peripheral nervous system family history, renal failure, obesity
▫ Abnormal A fibers, peripheral nerve ▪ Peripheral neuropathy (due to diabetes,
microvasculature alcoholism, rheumatoid arthritis, etc.)
646 OSMOSIS.ORG
▪ Medications
▫ Antidepressants, antiemetics,
TREATMENT
antipsychotics, antihistamines, calcium
channel blockers
MEDICATIONS
▪ If other interventions not effective
biologically female ▪ Dopamine agonists (e.g. pramipexole,
ropinirole)
▪ Alpha-2-delta calcium channel ligands (e.g.
COMPLICATIONS pregabalin, gabapentin)
▪ Insomnia → daytime drowsiness ▪ Benzodiazepine
▫ Individuals with intermittent symptoms
SIGNS & SYMPTOMS ▪ Iron replacement
▫ ↓ symptom severity when low (< 75ng/
▪ Strong urge to move legs while resting; ml) serum iron levels repleted
unpleasant sensations (e.g. tingling,
burning, crawling, itching, aching) OTHER INTERVENTIONS
▪ Relief by movement; worsening of ▪ Lifestyle changes
symptoms in evening/night → insomnia
▫ Avoid aggravating factors/situations, ↓
▪ Nighttime leg twitching while asleep caffeine intake
Aggravating factors ▪ Mental alert activities
▪ Antihistamines ▫ Distract individual in times of symptoms
▫ Commonly used for sleep assistance
▪ Dopamine antagonists
▪ Psychiatric medications
▫ Selective serotonin reuptake inhibitors
(SSRIs), serotonin norepinephrine
reuptake inhibitors (SNRIs), tricyclic
antidepressants (TCAs)
DIAGNOSIS
OTHER DIAGNOSTICS
Clinical Presentation
▪ Urge to move limbs with/without
unpleasant sensations
▪ Improvement with activity
▪ Worsening at rest/in evening
OSMOSIS.ORG 647
NOTES
NOTES
NEUROCUTANEOUS DISORDERS

▪ Various disorders, primarily affecting skin, DIAGNOSTIC IMAGING
nervous system
MRI, CT scan
▫ Characterized by inherited/de novo
tumor suppressor gene mutations → ↑ ▪ See individual disorders
tumor formation incidence
▪ Tumor suppressor gene mutation → LAB RESULTS
abnormal/absent protein → loss of control ▪ Genome testing
over important cell cycle regulators;
cell growth, proliferation; intercellular
communication → tumor formation OTHER DIAGNOSTICS
▪ Eye examination
RISK FACTORS
▪ Parents with germline mutation TREATMENT
SURGERY
▪ Various neurologic signs (lesion site-
dependent) OTHER INTERVENTIONS
▪ Eye, visual problems ▪ No current underlying mutation treatment
▪ Mental, cognitive problems ▪ Surveillance
▪ Skin lesions ▪ Symptom management
▪ Benign, malignant nervous/other organ-
system tumors
648 OSMOSIS.ORG
Chapter 84 Neurocutaneous Disorders
ATAXIA-TELANGIECTASIA
osms.it/ataxia-telangiectasia
▪ Thymus hypoplastic
PATHOLOGY & CAUSES ▫ Fewer lymphocytes, Hassall’s corpuscle
absence
▪ Rare autosomal recessive disorder
▫ Involves defective DNA repair
▫ Characterized by progressive COMPLICATIONS
neurological abnormalities, most ▪ Dysphagia → aspiration
noticeably ataxia, oculocutaneous ▪ Pulmonary disease (chronic infection,
telangiectasias (superficial, dilated blood restrictive interstitial lung disease)
vessels of skin), immune deficiency, ▪ Malignancies
malignancy ▪ Infection (due to T cell deficiency, inability
▪ Mutation in ataxia-telangiectasia mutated to produce some antibodies, etc.)
(ATM) gene on chromosome 11; believed
to be DNA surveillance (looks for damage
→ stops cell cycle to repair it/activates SIGNS & SYMPTOMS
apoptosis)
▪ Telangiectasias (blood vessel dilation in skin
Abnormal ATM protein
of face, neck, bulbar conjunctiva)
▪ Unable to phosphorylate
▪ Skin lesions (e.g. café au lait spots—flat,
▫ Tumor suppressor protein p53 → lightly-brown pigmented birthmarks)
cell-cycle slowing/apoptosis absence
▪ Immune deficiency in cellular, humoral
→ DNA repairing absence →
immunity
mutation accumulation → malignant
transformation → ↑ cell susceptibility to Neurologic
ionizing radiation ▪ Abnormal gait, stance
▫ Tumor suppressor BRCA1 → ↑ breast ▪ Ataxia (tremors, lack of voluntary
cancer susceptibility coordinated movement)
▫ eIF-4E binding protein 1 controls ▪ Dystonia (muscle contractions → repetitive
protein synthesis when insulin present movement/abnormal posture)
→ probable cause of insulin resistance,
▪ Oculomotor apraxia (inability to coordinate
disturbed growth
head, eye movements)
▪ Loses ribonucleotide reductase control
▪ Nystagmus, acquired strabismus, reading
→ abnormal mitochondrial DNA
problems
synthesis, repair → probable cause of
neurodegeneration, premature aging ▪ Problems with speaking, chewing,
swallowing can → aspiration
▪ → chromosomal translocation, lymphocyte
inversion → ↑ tendency of leukemias, ▪ Cognitive impairment
lymphomas
Pulmonary disease
Histology ▪ Respiratory muscles weakness
▪ Central nervous system (CNS) ▪ Aspiration
▫ Brain atrophy, Purkinje cell loss in ▪ Interstitial lung disease
cerebellum (contributes to ataxia)
▪ Peripheral nervous system (PNS)
▫ Malformed nuclei in Schwann cells
OSMOSIS.ORG 649
DIAGNOSIS
▪ Neurological symptom presence (e.g.
progressive cerebellar ataxia)
LAB RESULTS
▪ Genetic testing
▫ Mutation identification in both ATM
gene copies
▪ Laboratory studies
▫ ↑ alpha-fetoprotein in serum
▫ ↓ ATM protein
▫ ↓ immunoglobulins in serum (usually Figure 84.1 An ocular telangiectasia in an
IgA, IgG) individual with ataxia telangiectasia.
▫ Cell culture exposed to radiation (e.g.
X-ray) → ↑ cell, chromosomal breakage
TREATMENT
OTHER INTERVENTIONS
▪ Occupational, physical therapy (functional
deficits)
▪ Monitor, treat main mortality causes
▫ Infections, dysphagia, pulmonary
disease, malignancy
NEUROFIBROMATOSIS TYPE I (NF1)

osms.it/neurofibromatosis-type-i
▪ Deletion of one NF1 gene → more severe
PATHOLOGY & CAUSES phenotypes
▪ New mutation appearing in postzygotic
▪ Rare autosomal dominant disorder
stage → some cells have normal NF1
▫ Characterized by ↑ tumor incidence genes, some have mutations → segmental
▫ AKA von Recklinghausen disease, NFI neurofibromatosis
▪ Mutation in neurofibromin 1 gene (NF1) ▪ Both NF1 genes mutated → complete NF1
on chromosome 17 → abnormal/absent protein production loss
neurofibromin 1 protein (usually acts as
tumor suppressor) → unable to control RAS
pathway (stays trapped in active form) → COMPLICATIONS
loss of cell growth, division control ▪ Cognitive/learning disability, seizure,
hypertension
TYPES
▪ Small mutations in one NF1 gene copy →
mild phenotypes
650 OSMOSIS.ORG
SIGNS & SYMPTOMS

▪ ≥ six café au lait macules
Freckling
▪ Similar to cafe au lait macules but smaller,
appearing later in groups with tendency for
inguinal, axillary region
Lisch nodules (NF1-specific)

▪ Lifted tan-colored iris hamartomas
Neurofibromas Figure 84.2 Lisch nodules in the iris of

an individual with neurofibromatosis.
▪ Peripheral
Hamartomata of the iris constitute part of the
▫ Benign peripheral nerve sheath tumors; diagnostic criteria for neurofibromatosis.
consist of many cells (primarily Schwann
cells)
▫ Location: skin, along nerve, nerve root
next to spine DIAGNOSIS
▪ Plexiform (leading morbidity cause)
▫ Superficial, deep/mixed nerve
DIAGNOSTIC IMAGING
overgrowth MRI
▫ Can compress adjacent structures (e.g. ▪ Bright spots (areas of ↑ signals in T2
airways), invade surrounding tissue, imaging)
become malignant
▪ Nodular Neuroimaging
▫ Superficial/deep hard lesions ▪ Megalencephaly (↑ brain volume)
▫ Usually not invading tissue but can
become malignant LAB RESULTS
Optic pathway glioma (OPG) ▪ Genetic testing (diagnosis confirmation)
▪ Proptosis, visual problems
OTHER DIAGNOSTICS
Malignant peripheral nerve sheath tumor ▪ Clinically
(MPNST)
▫ Neurology, genetics, ophthalmology
▪ Swelling in extremity; pain; numbness, evaluation
burning sensation; extremity movement
▫ Parent, sibling history, examination
difficulty
helpful
Neurologic manifestations ▪ At least two following features needed for
▪ Speech, language delays; attention deficit diagnosis
hyperactivity disorder (ADHD) ▫ ≥ six café au lait macules
▫ ≥ two neurofibromas
Bone abnormalities
▫ Freckling
▪ Long bone dysplasia (anterolateral bowing)
▫ Optic glioma
▫ Narrowed medullary canal, cortical
▫ ≥ two Lisch nodules
thickening, pathologic fractures
▫ Characteristic bony lesion
▪ Pseudoarthrosis
▫ First-degree relative diagnosed with
▫ Fake joint forming at previous fracture
NF1
site
▪ Scoliosis; osteoporosis
▪ Short stature
OSMOSIS.ORG 651
treatment → volume shrinkage
MPNSTs / OPGs
▪ Chemotherapy
Neurologic abnormalities
▪ Stimulants
SURGERY
Mass effect tumors
▪ Surgical removal
Figure 84.3 Numerous cutaneous MPNSTs

neurofibromata on the skin of an individual ▪ Surgical excision with radiation therapy
with type I neurofibromatosis.
PSYCHOTHERAPY
TREATMENT Neurologic abnormalities

▪ Speech, occupational therapy
MEDICATIONS
OTHER INTERVENTIONS
Mass effect tumors
▪ Orthopedic interventions
▪ Selumetinib
▫ MEK 1/2 inhibitor; orphan drug for NF1 Neurologic abnormalities
NEUROFIBROMATOSIS TYPE II (NF2)

osms.it/neurofibromatosis-type-ii
TYPES
PATHOLOGY & CAUSES ▪ Phenotype is mutation type-dependent
▫ Nonsense, frameshift → severe
▪ Uncommon autosomal dominant disorder
phenotypes
▫ Characterized by ↑ neural tumor
▫ Missense, inframe deletions → mild
incidence (schwannomas, meningiomas)
phenotypes
▪ Mutations in neurofibromin 2 (NF2) gene on
chromosome 22 → abnormal NF2 protein
(i.e. merlin) COMPLICATIONS
▫ Cell membrane protein acts as tumor ▪ Vestibular schwannoma
suppressor → loss of contact inhibition ▪ Meningiomas (intracranial, spinal)
(likely) → ↑ tumor development risk ▪ Neuropathies (facial, polyneuropathy)
▪ Usually appears in young adulthood ▪ Gliomas
▪ Eye lesions (e.g. cataracts, retinal
hamartomas)
652 OSMOSIS.ORG
▪ Other non-neoplastic lesions (e.g.

meningioangiomatosis—benign
leptomeninges lesions with good
vascularization)
▪ Visual impairment
DIAGNOSIS
DIAGNOSTIC IMAGING
MRI
▪ Nervous system
▫ For individuals with first-grade relatives
diagnosed with NF2
LAB RESULTS
▪ Molecular testing for mutation
diagnosed with NF2
OTHER DIAGNOSTICS
▪ At least one of following needed
▫ Bilateral vestibular schwannomas < 70
years old
▫ Unilateral vestibular schwannoma < 70
years of age + first degree relative with
Figure 84.4 An MRI scan of the head in the NF2
axial plane demonstrating bilateral acoustic ▫ Neurofibroma, meningioma, glioma,
Schwannomas in an individual with type II non-vestibular schwannoma, cataract
neurofibromatosis. or cerebral calcifications + first degree
relative with NF2/unilateral vestibular
schwannoma without schwannomatosis
gene mutations
SIGNS & SYMPTOMS ▫ Multiple meningiomas + unilateral
vestibular schwannoma/two of
▪ Skin lesions (cutaneous, subcutaneous neurofibroma, glioma, cerebral
tumors) calcification, cataract, non-vestibular
schwannoma
Neurologic disorders
▫ NF2 gene mutation from blood/detecting
▪ Vestibular schwannomas (may be bilateral)
same mutation in two different tumors
▫ Progressive hearing loss, balance
▪ Skin, eye examination
problems, tinnitus
▪ Meningiomas
diagnosed with NF2
▫ Extremity weakness, double vision,
incontinence, seizure
▪ Gliomas
▫ Headache, vomiting, visual loss
▪ Spinal tumors
▫ Muscle pain, weakness; paresthesias
OSMOSIS.ORG 653
TREATMENT
MEDICATIONS
▪ Monoclonal antibodies against vascular
endothelial growth factor (VEGF) →
hearing improvement, tumor shrinkage
SURGERY
▪ Removal
▫ Vestibular schwannomas; meningioma
(surveillance until symptomatic)
OTHER INTERVENTIONS
▪ Stereotactic radiosurgery, radiotherapy
▫ Vestibular schwannomas; meningioma
(surveillance until symptomatic) Figure 84.5 An MRI scan of the head in the
axial plane demonstrating bilateral acoustic
Schwannomas in an individual with type II
neurofibromatosis.
654 OSMOSIS.ORG
STURGE–WEBER SYNDROME
osms.it/sturge-Weber-syndrome
Seizures (epilepsy)
PATHOLOGY & CAUSES ▪ Affect young children
▪ Uncommon congenital disorder affecting ▪ Usually start as focal → become
blood vessels on face, brain, eyes generalized
▪ GNAQ gene mutation → abnormal guanine Hemiparesis
nucleotide binding protein → loss of ▪ Affects extremities contralateral to brain
some intracellular signal pathway control lesion
→ capillary angiomatosis development
▪ ↓ motor function
→ hypoxia, venous stasis, thrombosis
(probable tissue damage cause) Ophthalmologic problems
▪ Mutation occurrence ▪ Visual defects when brain’s occipital region
▫ Early embryogenesis stages → probably affected
affect more vascular cell precursors → ▪ Choroid hemangiomas → ↑ intraocular
Sturge–Weber syndrome (SWS) pressure
▫ Later embryogenesis stages → believed ▪ Episcleral, conjunctival hemangiomas
to affect endothelial cell precursors
→ nonsyndromic port wine stains Endocrine problems
(malformed facial capillaries) ▪ Growth hormone deficiency
▪ Central hypothyroidism
COMPLICATIONS
▪ Intellectual disability
▪ Hydrocephalus (probably due to venous
DIAGNOSIS
stasis, thrombosis)
DIAGNOSTIC IMAGING
▪ Glaucoma (↑ intraocular pressure)
MRI
▪ Contrast enhancement
SIGNS & SYMPTOMS ▪ Presence, position, range of malformed
capillaries, veins
Port wine stain
▪ Newborns CT scan
▫ Flat pink lesions ▪ Calcifications
▪ Grows bulging out, turns to red wine color
as individual ages OTHER DIAGNOSTICS
▪ Dilated blood vessels injury-prone → ▪ Characteristic neurologic, ophthalmic, skin
superficial bleeding → hypertrophy, manifestations
nodularity
▪ Usually appears on forehead, upper eyelids
Leptomeningeal vascular malformation

▪ Big malformed intracerebral veins, usually
drain in deep venous system
▪ Venous stasis → chronic ischemia →
atrophied brain parenchyma, calcific
deposits
OSMOSIS.ORG 655
TREATMENT
MEDICATIONS
▪ Antithrombotic therapy
▪ Topical medications
▫ Managing intraocular pressure
▪ Anticonvulsants
▫ Manage seizure
SURGERY
▪ Epileptogenic tissue removal
▫ Manage seizure
▪ Hemispherectomy (disabling half of brain)
▫ Manage seizure
OTHER INTERVENTIONS Figure 84.6 A CT scan of the head in the

▪ Photothermolysis (laser produced heat) axial plane of an individual with Sturge-
▫ Skin lesions Weber syndrome. There is calcification and
volume loss of the cerebral cortex on the
right side.
TUBEROUS SCLEROSIS
osms.it/tuberous-sclerosis
▪ Mutation range-dependent
PATHOLOGY & CAUSES ▫ One copy mutated → cortical,
subependymal tubers
▪ Autosomal dominant disorder
▫ Both copies mutated → subependymal
▫ Characterized by hamartoma, benign
giant-cell astrocytomas
neoplasm development involving many
organ systems ▪ ↑ malignancy risk
▪ Mutation in one/both genes
▫ TSC1 on chromosome 9 → abnormal/ COMPLICATIONS
absent hamartin ▪ Seizure (leading morbidity cause)
▫ TSC2 on chromosome 16 (more ▪ Autism spectrum disorders
commonly mutated) → abnormal/absent ▪ Intellectual disability
tuberin ▪ Pneumonia
▪ Abnormal hamartin, tuberin can not form/ ▪ Heart, renal failure
form inactive complex → control loss over
kinase mechanistic target of rapamycin
(mTOR)
▫ Anabolic metabolism, cell size regulator
→ giant-cell tumors
656 OSMOSIS.ORG
LAB RESULTS
SIGNS & SYMPTOMS
Genetic testing
Skin lesions ▪ Mutation identification in TSC1/TSC2 genes
▪ Ash-leaf spots (hypomelanotic macules) of healthy tissue cells
▪ Angiofibromas on cheeks ▫ Can establish diagnosis without clinical
▪ Ungual fibromas (small tumors growing manifestation
under nails) ▪ Clinically uncertain diagnosis confirmation
▪ Shagreen patches (thick, pigmented, ▪ Prenatal diagnosis
dimpled skin lesion usually on lower back)
▪ Characteristic brown plaques on infant OTHER DIAGNOSTICS
forehead
▪ Presents with at least two major symptoms
Brain lesions ▪ Presents with one major, two/more minor
▪ Glioneuronal hamartomas, subependymal symptoms
nodules ▫ “Confetti” skin lesions (small
▫ Seizure, intellectual disability hypomelanotic macules)
▪ Subependymal giant-cell tumors ▫ ≥ three dental enamel pits
▫ Hydrocephalus → headaches, vomiting, ▫ ≥ two intraoral fibromas
visual problems, depression, appetite ▫ Retinal achromic patch
loss ▫ Multiple renal cysts
▪ White matter lesions ▫ Nonrenal hamartomas
▪ Full parental evaluation once child
Cardiovascular lesions
diagnosed
▪ Cardiac rhabdomyoma (benign heart
▪ Skin, neurologic, ophthalmic examination
tumor)
▪ Vogt triad
▫ Blood flow obstruction, cardiac murmurs
▫ Seizure, facial angiofibroma, intellectual
Renal lesions (angiomyolipomas) disability
▪ Pain, irregular renal function
Pulmonary lesions
▪ Diffuse interstitial fibrosis/
lymphangioleiomyomatosis (systemic
disease → cystic lung destruction)
▫ Dyspnea, pneumothorax
Ophthalmic lesions
▪ Retinal hamartomas (flat, translucent
lesions); eyelid angiofibromas
DIAGNOSIS Figure 84.7 Numerous facial angiofibromas

in an individual with tuberous sclerosis.
DIAGNOSTIC IMAGING
MRI
▪ With, without contrast enhancement
▫ Cortical glial hamartomas
▫ Subependymal nodules/giant-cell tumor
▫ White matter lesions
▫ Renal angiomyolipomas/cysts
OSMOSIS.ORG 657
Lungs
TREATMENT ▪ Lung transplantation
MEDICATIONS
PSYCHOTHERAPY
Seizure management, monitoring
▪ Infantile seizures: corticotropin (ACTH)/ Cognitive, behavioral problems
vigabatrin ▪ Special needs educational programs
▪ Partial seizures: many drugs (such as ▪ Occupational therapy
oxcarbazepine) ▪ Social support
▪ Refractory epilepsy ▪ Psychiatric therapy
▫ Everolimus (mTOR inhibitor)
Tumor management OTHER INTERVENTIONS

▪ Medical therapy (e.g. everolimus) Seizure management, monitoring
▪ Refractory epilepsy
SURGERY ▫ Ketogenic diet
▫ Vagus nerve stimulation
Seizure management, monitoring
▪ Refractory epilepsy Skin lesions
▫ Epilepsy surgery ▪ Sun protection
▪ Laser therapy
Tumor management
▪ Dermabrasion (wearing away of skin)
▪ Surgical removal if possible
▪ Angiomyolipoma embolization Lungs
▪ Pleurodesis
▫ Adhesion of two pleurae →
pneumothorax prevention
VON HIPPEL–LINDAU DISEASE

osms.it/von-hippel-lindau
growth dysregulation → highly vascular
PATHOLOGY & CAUSES tumor formation
▫ Cilia centrosome, microtubules
▪ Autosomal dominant disorder
dysregulation → cyst formation in
▫ Characterized by formation of many pancreas, liver, kidneys
different benign, malignant tumors
▫ Dysregulation of extracellular matrix →
(hemangioblastomas, renal cell
malignant behavior
carcinoma, pheochromocytoma)
▪ Affected people usually have one inherited
▪ Mutation affects von Hippel–Lindau (VHL)
mutated allele but development requires
tumor suppressor gene on chromosome 3
other allele mutation/deletion/inactivation
→ abnormal VHL protein
▫ Lost ability to deactivate hypoxia
induced factor 1 alpha (HIF1A), 2 alpha TYPES
(HIF2A) → HIF1A starts continuously ▪ Two types of VHL disease (based on
producing erythropoietin while HIF2A pheochromocytoma development risk)
produces VEGF → cellular metabolism,
658 OSMOSIS.ORG
Type 1
▪ ↓ risk
DIAGNOSIS
▪ Usually associated with large deletions, DIAGNOSTIC IMAGING
frameshift, nonsense mutations
CT scan
Type 2
▪ ↑ risk
▪ ELSTs
▪ Usually associated with missense
▫ Retrolabyrinthine calcifications
mutations
MRI
SIGNS & SYMPTOMS
▪ ELSTs
Hemangioblastomas ▫ Hyperintense T1, heterogeneous T2
focal signals
▪ Usually affect cerebellum, spinal cord, retina
▫ Benign, well defined tumors
▫ Highly vascular LAB RESULTS
▫ Can pressure adjacent structures/bleed ▪ Pheochromocytomas
▫ Serum testing: ↑ normetanephrine to
Retinal capillary hemangioblastomas metanephrine ratio
▪ Visual loss ▪ Genome testing
▪ Retinal detachment ▫ Southern blotting
▪ Glaucoma ▫ Genome sequencing
▪ Prenatal diagnosis
Renal cell carcinomas (RCC)
▫ Amniocentesis
▪ Haematuria
▫ Chorionic villus sampling
▪ Flank pain (between ribs, hips)
▪ Abdominal mass
OTHER DIAGNOSTICS
Pheochromocytomas ▪ Retinal examination
▪ Headaches ▪ ELSTs
▪ High blood pressure, ↑ heart rate ▫ Auditory tests
▪ Skin sensations ▪ Genetic counseling
Pancreatic tumors
▫ Epigastric pain TREATMENT
▫ Diarrhea
MEDICATIONS
Endolymphatic sac tumors of middle ear
▪ Pheochromocytomas
(ELSTs)
▫ Alpha-adrenergic blockade
▪ Hearing loss
▪ Tinnitus
▪ Vertigo SURGERY
▪ CNS hemangioblastomas, pancreatic
tumors, ELSTs
▫ Removal (when symptomatic)
▫ Cochlear implants: individuals with
hearing loss
OSMOSIS.ORG 659
▪ RCC ▪ Retinal capillary hemangioblastomas
▫ Partial nephrectomy ▫ Laser photocoagulation
▪ Pheochromocytomas ▫ Cryotherapy
▫ Removal ▪ RCC
▫ Cryotherapy
OTHER INTERVENTIONS ▫ Radiofrequency ablation
▪ CNS hemangioblastomas, pancreatic ▪ Pheochromocytomas
tumors, ELSTs ▫ Catecholamines production surveillance
▫ Stereotactic radiosurgery, radiation
therapy
660 OSMOSIS.ORG
NOTES
NOTES
NEUROMUSCULAR JUNCTION
DISEASES

LAB RESULTS
PATHOLOGY & CAUSES ▪ Serologic test for specific antibodies
▪ Disorders impairing neuromuscular
transmission lead to muscle fatigability, OTHER DIAGNOSTICS
weakness
Electrophysiologic study
▪ Repetitive nerve stimulation
CAUSES ▫ Decremental response/improvement
▪ Autoantibody production
▪ Electromyogram
▫ Targeted against neuromuscular
▫ ↓ muscle action potential
transmission pathway proteins
▪ Myasthenia gravis (MG) Pulmonary function test (PFT)
▪ Lambert–Eaton myasthenic syndrome ▪ Periodically
(LEMS) ▫ Detect respiratory muscle involvement
▪ Transient acquired neonatal myasthenia in forced vital capacity (FVC) ↓
▪ Genetic mutation
▫ Affecting pathway components (e.g.,
congenital myasthenia) TREATMENT
▪ Treat underlying cause (e.g. LEMS
COMPLICATIONS malignancy)
▪ Respiratory muscles involved → potentially
fatal respiratory failure
MEDICATIONS
SIGNS & SYMPTOMS ▫ Inhibit acetylcholine degradation
→ ↑ acetylcholine concentration in
▪ Primary clinical manifestation neuromuscular junction (symptomatic
▫ Painless muscle weakness without therapy)
significant muscle atrophy ▪ Immunomodulating agents
▫ Ocular, extraocular, oropharyngeal, ▫ ↓ autoantibody production
bulbar, neck, limb, respiratory muscles ▫ Individuals with poor
acetylcholinesterase inhibitor response
▫ Corticosteroids/other
DIAGNOSIS immunosuppressive agents
▪ If above fails/emergency (e.g., myasthenic
DIAGNOSTIC IMAGING crisis)
CT scan ▫ Plasmapheresis/intravenous
▪ Thymoma (MG) immunoglobulin (IVIG)
▪ Small-cell lung carcinoma (LEMS)
OSMOSIS.ORG 661
LAMBERT–EATON MYASTHENIC
SYNDROME (LEMS)
osms.it/lambert-eaton-myasthenic
lymphoproliferative disorders (e.g.,

PATHOLOGY & CAUSES Hodgkin’s lymphoma)
▪ Autoimmune diseases
▪ Rare autoimmune disorder
▫ Hashimoto’s thyroiditis, diabetes
▫ Autoantibodies inhibit presynaptic
mellitus type 1, vitiligo
calcium channels on motor neurons
→ reduced acetylcholine release in
neuromuscular junction COMPLICATIONS
▪ Muscle weakness ▪ Respiratory muscle involvement →
▫ Improves temporarily after repeated respiratory failure
muscle use (no significant muscle ▪ Underlying malignancy → can lead to death
atrophy)
▪ Mostly affects somatic nervous system,
can also affect autonomic nervous system’s SIGNS & SYMPTOMS
parasympathetic part
▪ Middle-aged adults (most cases) ▪ Progressive, symmetrical proximal muscle
weakness (e.g., shoulders, hips, thighs) →
difficulty climbing stairs/standing when
CAUSES seated
Type II hypersensitivity reaction ▫ Paraneoplastic LEMS: more rapidly
progressive course
▪ B cells produce antibodies that target, block
voltage-gated calcium channels located ▪ Warming-up phenomenon
presynaptically on motor neurons → only ▫ Repeated muscle use → weakness
few unbound channels available to open, temporarily relieved
allow calcium in → ↓ calcium within neuron ▪ Reflex strength ↓
(insufficient to trigger acetylcholine release) ▫ Muscle activation → reflex recovery/
→ ↓ acetylcholine release in neuromuscular improvement
junction → attached muscle fiber does not ▪ Small minority
contract
▫ Ocular, oropharyngeal muscle
▪ Repeated stimulation by brain’s electrical involvement
impulses → enough calcium might get
▪ Advanced stages
through remaining unbound calcium
channels → acetylcholine release → muscle ▫ Possible respiratory muscles
contraction involvement → respiratory failure
(myasthenic crisis)
▪ Autonomic symptoms
RISK FACTORS ▫ Dry mouth (most common),
▪ Malignancy constipation, blurry vision, erectile
▫ Strong small-cell lung cancer dysfunction, urinary problems, syncope
association; stimulus for antibody
production is same calcium channel
expression in neoplastic cells
▫ Other associated malignancies include
662 OSMOSIS.ORG
Chapter 85 Neuromuscular Junction Disorders
DIAGNOSIS TREATMENT
▪ Symptomatic therapy
CT scan
▫ Acetylcholinesterase inhibitors: minimal
▪ Chest
effect
▫ Detect underlying small-cell lung cancer
▫ Aminopyridines: block potassium
▪ Abdomen, pelvis also recommended channels → prolonged nerve membrane
▪ Negative initial malignancy evaluation depolarization → ↑ calcium entry → ↑
▫ Periodical screening recommended acetylcholine release in neuromuscular
junction
▪ If above methods fail
LAB RESULTS
▫ Immunomodulating agents can
▪ Serological tests
be used (corticosteroids, other
▫ Detect antibodies against the voltage- immunosuppressive agents)
gated calcium channels
OTHER INTERVENTIONS
OTHER DIAGNOSTICS
▪ Occasionally treated with IVIG/
▪ Electrophysiologic studies plasmapheresis
▫ Repetitive nerve stimulation: ↑ muscle ▫ More severe cases
action potential amplitude
▫ Electromyogram: ↑ muscle action
potential amplitude after exercise
▪ PFT
▫ ↓ FVC → respiratory muscle
involvement
MYASTHENIA GRAVIS
osms.it/myasthenia-gravis
(MuSK) → ↓ in acetylcholine receptor
PATHOLOGY & CAUSES function
▪ Acetylcholine cannot bind → normal action
▪ Autoimmune disorder; significant skeletal
potentials cannot be generated (adjacent
muscle weakness
muscle
▫ Decreased acetylcholine receptor
▪ Complement activated → inflammatory
function → worsens with muscle use
response initiation → postsynaptic
▫ Most common neuromuscular junction membrane damage → acetylcholine
disorder receptor destruction
▪ Type II hypersensitivity reaction ▪ Bimodal onset age
▫ B cells produce antibodies against ▫ 20–30 years old (biologically-female
postsynaptic nicotinic acetylcholine predominance)
receptors of neuromuscular junction/
▫ 60–70 years old (biologically-male
receptor-associated proteins
predominance)
▫ Autoantibodies targeted against
▪ Associated with thymic abnormality;
muscle-specific receptor tyrosine kinase
thymus considered antigen source
OSMOSIS.ORG 663
promoting autoantibody production (most dysphagia), palatal (nasal tone,
cases) prolonged speech → hypophonia)
▪ Neonatal myasthenia gravis ▪ Facial muscle
▫ Transient myasthenia form (newborn ▫ Facial weakness, facial expression loss
from individual with myasthenia gravis) ▪ Neck muscle
▫ Maternal antibodies → transplacental ▫ Cannot keep head up (“drooped head
passage → neuromuscular junction syndrome”)
function interference ▪ Limb muscle
▪ Rare non-immune mediated forms ▫ Proximal, asymmetric muscle weakness
▫ E.g. congenital myasthenia gravis ▪ Respiratory muscle
▫ Mutations affecting neuromuscular ▫ Respiratory failure (myasthenic crisis)
transmission
▪ Myasthenic crisis
▫ Decreased respiratory muscle function
DIAGNOSTIC IMAGING
→ life-threatening respiratory failure CT scan
(requires mechanical ventilation)
▪ Chest scan to detect associated thymic
▫ Occurs spontaneously/precipitated abnormalities
(e.g. surgery, infection, medication,
▫ Abnormal thymus (most cases)
immunosuppressive-agent withdrawal)
▫ Thymoma

▪ Serologic test
▪ Fluctuating muscle weakness ▫ Acetylcholine receptor antibodies
▫ Exacerbated by repetitive muscle use (AChR-Abs)/muscle-specific receptor
throughout day/after exertion/repetitive tyrosine kinase antibodies (MuSK-Abs)
movement ▫ Most specific tests
▪ Improves with rest ▫ Seronegative for AChR-Abs, MuSK-Abs
▪ Progression
▫ Symptoms continuously present,
fluctuate from mild–severe
OTHER DIAGNOSTICS
▪ Electrophysiologic studies
▪ Sensation, reflexes preserved
▫ Repetitive nerve stimulation studies:
Clinical MG forms progressive decline in muscle action
▪ Ocular myasthenia potential amplitude (decremental
▫ Limited (eyelid, extraocular muscle); response)
individuals (50%) with ocular ▫ Single-fiber electromyography:
myasthenia will → generalized increased jitter
myasthenia (< two years) ▪ Tensilon test
▪ Generalized myasthenia ▫ Edrophonium: acetylcholinesterase
▫ Ocular, bulbar, facial, limb, respiratory inhibitor with rapid onset, short acting
muscle duration
▪ Ocular muscles ▫ Prolongs acetylcholine presence in
▫ Eyelid (ptosis), extraocular (binocular neuromuscular junction → marked
diplopia) improvement
▪ Bulbar muscle ▫ Easy to perform/limited utility;
high false-positive rate, possible
▫ Jaw closure (prolonged chewing →
complications from muscarinic effects
weakness), oropharyngeal (dysarthria,
664 OSMOSIS.ORG
Chapter 85 Neuromuscular Junction Disorders
(especially older adults, e.g. bradycardia, SURGERY

bronchospasm) ▪ Thymectomy, especially for thymoma;
▪ PFTs myasthenia often improves/disappears
▫ Periodical FVC monitoring; FVC ↓ ▪ Rapidly worsening myasthenia/myasthenic
reveals respiratory muscle involvement crisis
▪ Ice pack test ▫ Intubation
▫ Ice pack application (2–5 minutes) → ▫ Plasmapheresis/intravenous
MG-affected muscles immunoglobulin (IVIG)
▫ Neuromuscular transmission ▫ Long-acting immunotherapy (e.g.,
improvement in low temperature corticosteroids, azathioprine)
MNEMONIC
Edrophonium vs.
pyridostigmine
eDrophonium for Diagnosis
pyRIDostigmine is to get RID
of symptoms
Figure 85.1 A biologically-female individual

with myasthenia gravis demonstrating ptosis
of the right eye before treatment (above) and
after treatment (below) with edrophonium.
TREATMENT
▪ No curative method
MEDICATIONS
▪ Avoid MG-exacerbating drugs (e.g.
aminoglycosides, tetracyclines, beta-
blockers, quinidine)
▫ Symptomatic therapy
▪ Immunomodulating agents ↓ autoantibody
production
▫ Individuals with poor
acetylcholinesterase inhibitor response
▪ Corticosteroids, other immunosuppressive
agents
OSMOSIS.ORG 665
NOTES
NOTES
NEUROPATHIES

OTHER INTERVENTIONS
PATHOLOGY & CAUSES ▪ Physiotherapy
▪ Peripheral nervous system (PNS) disorders ▫ Helps restore muscle function (if nerves
caused by neuronal damage are not severed → may help motor
function with partial lesions)
▪ Splinting (e.g. wrist, ankle)
SIGNS & SYMPTOMS
▪ Impairment/loss of motor/somatosensory MNEMONIC: DANG
function; “pins and needles” sensation THERAPIST
(paresthesia) Peripheral neuropathies
common differential
diagnosis
DIAGNOSIS Diabetes
Amyloid
▪ History: characteristic symptoms, Nutritional (e.g. B12 deficiency)
sometimes preceding injury
Guillain-Barre
DIAGNOSTIC IMAGING Toxic (e.g. amiodarone)

▪ Imaging for some conditions Hereditary (Charcot-Marie-
Tooth)
OTHER DIAGNOSTICS Endocrine
▪ Electromyography (EMG), nerve conduction Recurring (10% of Guillain–
studies (NCS) Barre)
Alcohol
Pb (lead)
TREATMENT Idiopathic
MEDICATIONS Sarcoid
▪ For neuropathic pain Thyroid
SURGERY
▪ Surgery to relieve nerve compression
666 OSMOSIS.ORG
Chapter 86 Neuropathies
CARPAL TUNNEL SYNDROME

osms.it/carpal-tunnel-syndrome

▪ Nerve entrapment disorder → compression ▪ Usually unilateral symptoms
of wrist’s median nerve ▪ Individual may awake with numbness,
▫ Median nerve passes through carpal tingling (after day of use → worsens at
tunnel night)
▪ Carpal tunnel ▪ Initially dull ache, discomfort; paresthesia,
▫ Floor: carpal arch sharp pain extending to forearm
▫ Roof: flexor retinaculum (transverse ▪ Pain, numbness, tingling in thumb, index
carpal ligament) finger, middle finger, thumb side of ring
▫ Contains nine flexors, median nerve finger on palmar side of hand
▪ Repetitive stress injury in susceptible ▪ Clumsiness, dropping small objects
people → inflammation → edema → fluid ▪ No sensation loss in palm’s central region
in narrow space compresses structures → ▫ Palmar branch of median nerve
nerve injury, impaired neuronal transport/ innervates it, branches off before going
vessel compression, nerve ischemia through carpal tunnel
CAUSES DIAGNOSIS
▪ Tendonitis, edema, repetitive stress injury
(typing) OTHER DIAGNOSTICS
RISK FACTORS EMG

▪ Obesity, pregnancy, other underlying ▪ Identifies neuropathic changes (sharp
conditions (rheumatoid arthritis), trauma, waves, ↑ insertional activity)
genetic predisposition, occupation NCS
▪ ↓ response amplitude
COMPLICATIONS
▪ Thenar muscle atrophy Physical exam
▪ Findings that support diagnosis
▫ Phalen maneuver: pressing of upper
MNEMONIC: TRAMP hands together while flexing wrists
Carpal tunnel syndrome induces pain
common causes ▫ Tinel’s sign: tapping on wrist over
Trauma (occupational) median nerve elicits pain
Rheumatoid arthritis ▫ Durkan’s test: pressing of median nerve
Acromegaly for 30 seconds worsens symptoms
Myxoedema ▫ Thenar eminence atrophy
Pregnancy
OSMOSIS.ORG 667
MNEMONIC: WRIST
TREATMENT Carpal tunnel syndrome
treatment
MEDICATIONS
Wear splints at night
▪ Corticosteroid injections → ↓ inflammation
Rest
Inject steroid
SURGERY Surgical decompression
▪ If symptoms persist, cut transverse Take diuretics
ligament to relieve pressure
OTHER INTERVENTIONS
▪ Behavior modification (e.g. adjusting typing
position, weight loss)
▪ Wrist supports, splints
▫ Helps relieve wrist strain, ↓ symptom
severity
Figure 86.1 Relative wasting of the right

thenar eminence in a case of carpal tunnel
syndrome.
ERB–DUCHENNE PALSY
osms.it/erb-duchenne-palsy
▪ Upper brachial plexus stretching → nerve

PATHOLOGY & CAUSES damage
▪ Type of neonatal brachial plexus palsy

▫ Caused by upper part of brachial plexus TYPES
injury ▪ Brachial plexus injuries
▫ AKA Erb’s palsy ▫ Neuropraxia (most common, nerve
▫ Brachial plexus: group of nerves provide stretched but not torn)
movement, feeling to shoulder, arm, ▫ Avulsion (most severe, roots torn from
hand, fingers; roots included in plexus spinal cord)
are C5–T1 forming superior, middle, ▫ Rupture (nerve torn)
inferior trunks which form lateral, ▫ Neuroma (nerve torn → healed, scar
posterior, medial cords puts pressure on injured nerve)
▪ Nerves affected
▫ Axillary RISK FACTORS
▫ Musculocutaneous (biceps brachii, ▪ Shoulder dystocia, macrosomia,
brachioradialis) malpresentation, maternal obesity,
▫ Suprascapular cephalopelvic disproportion, prolonged/
668 OSMOSIS.ORG
difficult labor, precipitous delivery

DIAGNOSIS
COMPLICATIONS DIAGNOSTIC IMAGING
▪ Affected arm grows shorter than other
▪ Limited range of motion X-ray
▪ Muscle weakness ▪ Rule-out fracture
Ultrasound
SIGNS & SYMPTOMS ▪ May show shoulder dislocation
▪ “Waiter’s tip” OTHER DIAGNOSTICS

▫ Hanging arm rotated medially, extended ▪ Neurological exam
forearm, fixed wrist ▫ Difficult due to limited child movement
▪ Affected arm may be held against body; ▫ Involves evaluation of arm range of
flaccid, flexed at elbow movement, motility
▪ Lateral part of forearm sensation loss,
circulatory disturbances, paralysis Electromyoneurography (EMNG)
▪ Asymmetric Moro reflex ▪ Shows damage extent
▫ Infant spreads only one arm (instead of
two) when it feels like it’s falling
TREATMENT
SURGERY
▪ Nerve repair/reconstruction
OTHER INTERVENTIONS
▫ Promotes muscle strengthening, normal
function
Figure 86.2 An illustration of the “waiter’s

tip” position.
OSMOSIS.ORG 669
KLUMPKE PARALYSIS
osms.it/klumpke-paralysis
PATHOLOGY & CAUSES

▪ Type of brachial plexus palsy affecting
lower brachial plexus nerve roots C8–T1
▪ Abducted arm during childbirth → arm
traction, pulling → nerve stretching in
inferior brachial plexus area → brachial
plexus damage
CAUSES
▪ Obstetric injury in adulthood
▫ Caused by grabbing things when falling
from height Figure 86.3 An illustration of the claw hand
position.
RISK FACTORS
▪ Birth injury
▫ Macrosomia, cephalopelvic DIAGNOSIS
disproportion, shoulder dystocia,
prolonged/difficult labor, precipitous OTHER DIAGNOSTICS
delivery, abnormal presentations ▪ Clinical diagnosis through neurological
▪ Adult trauma exam
▫ Car crashes, falls, contact sports ▫ Testing mobility, sensation, Horner’s
syndrome symptoms
COMPLICATIONS EMG/NCS
▪ Severe pain, arm immobility ▪ Confirms lesion location, assesses severity

▪ Claw hand OTHER INTERVENTIONS
▫ Intrinsic hand muscle atrophy → ▪ Physiotherapy, electrical nerve stimulation,
flexion of interphalangeal, extension of occupational therapy
metacarpophalangeal joints
▪ Repositioning, splinting (extreme damage
▪ Sensation loss in appropriate dermatome cases)
(medial side of arm), upper-arm weakness
Horner’s syndrome
▪ Ptosis (drooping eyelid)
▪ Enophthalmos (deep-set eye)
▪ Miosis (constricted pupil)
▪ ↓ sweating on one side of face
670 OSMOSIS.ORG
SCIATICA
osms.it/sciatica

▪ Type of neuralgia following sciatic nerve ▪ Sudden shooting pain onset radiating
along its distribution path from lumbar spine → down leg → areas
▪ Lumbosacral radiculopathy (spinal nerve innervated by sciatic nerve (side, back)
root disorder) → radicular (radiating, ▫ Mostly unilateral
shooting) pain ▪ Pain may involve lower back, hip, foot
▪ Most commonly caused by spinal disc ▪ Numbness, muscle weakness, burning
disease → narrowing of neural foramen/ sensation
intraspinal space → disc profusion outside
spinal column border → lumbar/sacral
nerve root compression → nerve irritation DIAGNOSIS

▪ Spinal disc herniation (most common) X-ray, MRI
▪ Spinal stenosis (spinal canal narrowing) ▪ Confirms disc herniation, stenosis, tumors
▪ Piriformis syndrome as etiology; determines management
▫ Rare variation of sciatic nerve passing
through piriformis muscle → symptoms
OTHER DIAGNOSTICS
▪ Pregnancy
▪ Clinically diagnosed
▫ Due to ligament loosening, shifting of
▫ Straight leg raise test: passive straight
center of gravity pressure on nerve
leg raising between 30–70° while lying
▪ Nerve tumors (schwannoma), trauma down, produces Lasègue’s sign (positive
▪ Younger individuals if pain present); not very specific
▫ Infection ▫ Crossed straight leg raising test: has
higher specificity, not very sensitive
RISK FACTORS
▪ Preexisting spinal disorders
TREATMENT
▪ Age: ↑ risk
▪ Biologically-male individuals MEDICATIONS
▪ Pain management (nonsteroidal anti-
COMPLICATIONS inflammatory drugs (NSAIDs), opioids)
▪ Nerve damage, muscle atrophy, immobility,
permanent sensation loss SURGERY
▪ Spinal disc repair (severe symptoms)
OTHER INTERVENTIONS
▪ Recommend normal activity
OSMOSIS.ORG 671
THORACIC OUTLET SYNDROME
osms.it/thoracic-outlet-syndrome
RISK FACTORS
PATHOLOGY & CAUSES ▪ Coagulation disorders, pregnancy, tumors,
trauma
▪ Compression of neurovascular bundle in
▪ Repetitive movement sports (swimming,
space between clavicle, first rib; traverses
handball)
thoracic outlet
▫ Can result from combination of
developmental abnormalities, injuries, COMPLICATIONS
physical activities that predispose ▪ Stroke (arising from retrograde thrombi);
neurovascular compression deep venous thrombosis; arterial
thromboembolism; atrophy; neural damage,
paralysis; limb ischemia
TYPES
Structures involved
▪ Neurogenic SIGNS & SYMPTOMS
▫ Brachial plexus compressed
▪ Differ according to structure involved,
▫ Most common unilateral presentation more common
▪ Venous ▪ Neurogenic
▫ Subclavian vein ▫ Pain, numbness, paresthesia (tingling),
▪ Arterial weakness when raising arm, muscle
▫ Subclavian artery atrophy (thumb muscles)
▪ Venous
Obstruction areas
▫ Swollen, painful, cyanotic (blue) arm;
▪ Anterior scalene
spontaneous edema, may cause
▫ Inflammation/structural anomaly paresthesia
(multiple attachments) → scalene
▪ Arterial
muscle presses down onto structures,
brachial plexus compressed ▫ Cold, painful, pale arm; ↓ systolic
blood pressure in affected arm,
▫ Most common
diminished distal pulses, aneurysmal
▪ Cervical rib change in artery after compression
▫ Congenital abnormality of additional rib, may → thrill over subclavian artery;
subclavian vein compressed thromboembolism → worsening
▫ More common in biologically-female symptoms, ischemia
individuals
▪ Costoclavicular
▫ All structures may be involved DIAGNOSIS
▫ Second most common
DIAGNOSTIC IMAGING
CAUSES Upper-extremity ultrasound, angiography
▪ Repetitive motion → chronic inflammation ▪ Shows blood clot formation in vessels;
▪ Congenital distinguishes between arterial, venous
etiology
▫ Cervical rib, supernumerary muscle
insertions
▪ Neck hyperextensions
672 OSMOSIS.ORG
Chest X-ray
▪ Identifies bone abnormalities
TREATMENT
CT scan MEDICATIONS
▪ Identifies compression areas in greater ▪ Local corticosteroid, anesthetic injections
detail (symptom relief)
▪ Thrombolysis (in vascular clot cases)
MRI
▪ Identifies brachial plexus compression,
contrast displays vessel occlusion level
SURGERY
▪ Decompression techniques
OTHER DIAGNOSTICS
OTHER INTERVENTIONS
Physical exam ▪ Physical therapy
▪ Examine limbs for signs of neural, venous/ ▫ Stretching, exercise
arterial insufficiency
▪ Blood pressure difference between arms
indicates arterial involvement
▪ Adson test: raising arms above head
induces further compression → distal pulse
diminishment
EMNG
▪ Confirms neurological dysfunction
ULNAR CLAW
osms.it/ullnar-claw
▫ Cause: usually trauma/repetitive
PATHOLOGY & CAUSES movement
▪ High
▪ Two medial fingers (fourth, fifth) become
flexed at interphalangeal level, extended at ▫ Cause: regularly leaning against elbows
metacarpophalangeal level
▫ Due to ulnar nerve damage, hand CAUSES
resembles “claw” ▪ Prolonged pressure on Guyon’s canal
▪ Prolonged ulnar nerve pathway pressure (where ulnar nerve passes)
→ nerve injury → hand muscle wasting ▪ Trauma
(except thenar, two lateral lumbricals);
flexor carpi ulnaris, flexor digitorum
profundus → fourth, fifth finger flexion RISK FACTORS
at interphalangeal joint, extension at ▪ Biologically-male individuals: ↑ BMI
metacarpophalangeal joint ▪ Biologically-female individuals: ↓ BMI
▪ Cubitus valgus (forearm at pathological
Injury level angle)
▪ Low ▪ Cycling
▫ Wrist, damage usually more severe ▪ Leaning against desk
▫ Lesion site of nerve within wrist area
doesn’t influence symptoms
OSMOSIS.ORG 673
▪ Tool use requiring downward pressure
(musical instruments) DIAGNOSIS
DIAGNOSTIC IMAGING
COMPLICATIONS
▪ Nerve palsy Ultrasound
▪ Identifies local inflammation in Guyon’s
canal (where ulnar nerve passes)
SIGNS & SYMPTOMS
MRI
▪ Range in severity from mild intermittent ▪ Identifies nerve thickening
paresthesia to complete sensation loss,
atrophy OTHER DIAGNOSTICS
▪ Flexion at interphalangeal joints, extension
at metacarpophalangeal Clinical exam
▪ Weakness, dexterity loss ▪ Identify injury level
▫ Elbow has different muscles involved
(flexor carpi ulnaris, flexor digitorum
profundus)
▫ Froment’s sign: card gripped using
interphalangeal joints (abductor pollicis
weak)
▫ Finger abduction, pressing hands
together causes one side to collapse
EMNG
▪ Identifies neural damage level in fingers
TREATMENT
SURGERY
▪ Severe injury
▫ Nerve decompression at level of
Guyon’s canal
OTHER INTERVENTIONS
▪ Lighter injury
▫ Physical therapy, occupational therapy
▪ Splints, avoiding exacerbation
Figure 86.4 A left hand demonstrating an

ulnar claw.
674 OSMOSIS.ORG
WINGED SCAPULA
osms.it/winged-scapula

▪ Abnormal scapula protrusion from back of DIAGNOSTIC IMAGING
chest wall, usually unilateral
X-ray
▫ AKA scapula alata
▪ Confirms absence of fractures, structural
▪ Caused by muscle weakness
irregularities
▫ Serratus anterior: damage either to
brachial plexus, long thoracic nerve
(most common) OTHER DIAGNOSTICS
▫ Trapezius: damage to accessory nerve ▪ Scapular asymmetry, winging
▫ Rhomboid: damage to dorsal scapular
nerve
▪ Nerve damage, irritation/muscular
TREATMENT
dystrophy → muscle weakness → scapula
elevation from thoracic wall → scapula
SURGERY
winging ▪ Nerve transfer, scapular fixation
RISK FACTORS OTHER INTERVENTIONS

▪ Neck lymphadenectomy ▪ May resolve spontaneously
▪ Neuromuscular disorder ▪ Massage therapy
▪ Idiopathic ▫ Muscle relaxation
▪ Traumatic ▪ Physical therapy
▫ Neck injury, repetitive movement, ▫ Improves shoulder weakness
backpack straps, sleeping in bad
position, surgery
▪ Non-traumatic
▫ Viral neuritis (influenza), allergy,
toxic; neuromuscular disorders
(facioscapulohumeral muscular
dystrophy)
COMPLICATIONS
▪ Compensatory back muscle imbalance
SIGNS & SYMPTOMS

▪ Fatigue
▪ Neck, shoulder pain
▪ Scapular winging, shoulder asymmetry
▪ Muscle weakness, difficulty lifting objects,
Figure 86.5 Winged scapula in an individual
difficulty raising arm above head
with a long thoracic nerve palsy.
OSMOSIS.ORG 675
NOTES
NOTES
PNS DEMYELINATING DISORDERS

LAB RESULTS
PATHOLOGY & CAUSES ▪ Guillain–Barré
▫ Albuminocytologic dissociation in
▪ Progressive peripheral nervous system
(PNS) disorders; destruction of myelin,
disruption of motor, sensory function
OTHER DIAGNOSTICS
TYPES ▪ Electromyography (EMG), nerve conduction
studies (NCS)
Charcot–Marie–Tooth disease ▫ ↓/blocked nerve conduction velocity
▪ Genetic mutations → defective myelin ▪ History, physical examination
sheath, impaired neuronal mitochondrial
function
TREATMENT
Guillain–Barré syndrome
▪ Acute triggering event (e.g. infection) → MEDICATIONS
aberrant autoimmune response → myelin
▪ Guillain–Barré
sheath destruction
▫ Intravenous immunoglobulin (IVIG)
COMPLICATIONS
SURGERY
Charcot–Marie–Tooth disease ▪ Charcot–Marie–Tooth
▪ Muscle atrophy, impaired ambulation, foot ▫ Correction of severe skeletal
irregularities irregularities
Guillain–Barré syndrome
▪ Respiratory failure, cardiac arrhythmias, OTHER INTERVENTIONS
quadriplegia ▪ Charcot–Marie–Tooth
▫ Genetic testing, orthotics, physical/
occupational therapy
SIGNS & SYMPTOMS ▪ Guillain–Barré
▫ Plasmapheresis; supportive care (e.g.
▪ ↓/absent deep tendon reflexes, paresthesia, respiratory/hemodynamic support)
muscle weakness, ↓ touch sensation ▪ Pain management
▫ Acetaminophen, nonsteroidal anti-
DIAGNOSIS inflammatory drugs (NSAIDs),
gabapentin, carbamazepine
DIAGNOSTIC IMAGING
Gadolinium-enhanced MRI
▪ Guillain–Barré
▫ Intrathecal spinal nerve root thickening
676 OSMOSIS.ORG
Chapter 87 PNS Demyelinating Disorders
CHARCOT–MARIE–TOOTH
DISEASE
osms.it/Charcot-Marie-Tooth

▪ Group of hereditary, progressive ▪ Onset in first to third decade of life,
neurological disorders; disruption of PNS depending on type
processes, impaired sensory/motor function ▪ Progressive distal muscle weakness;
▪ Genetic mutations → defective structure, atrophy of hands, feet
function of proteins in myelin sheath/ ▪ Distal sensory loss, paresthesias, loss of
neuron’s axon proprioception
▪ Classification: Types I-VII; Type X (X-linked) ▪ ↓ deep tendon reflexes, areflexia
▫ Subtypes based on associated genes ▪ Foot irregularities
and phenotypes ▫ Foot drop, high arches (pes cavus),
hammer toes, flail foot, cavovarus foot
TYPES ▪ Unsteady gait, toe-walking
Charcot–Marie–Tooth I (CMT1)
▪ Demyelinating form
▫ Caused by mutations in PMP22, MPZ
genes (encode for myelin sheath
proteins) → ↓ nerve conduction velocity
▫ Autosomal dominant/sporadic
inheritance
CMT2
▪ Axonal form
▫ Caused by mutations in MFN2 gene
(encodes for mitofusin-2 protein in
neuronal mitochondria) → neuronal
death
▫ Autosomal dominant/recessive
inheritance
RISK FACTORS Figure 87.1 An MRI scan of the foot of an

▪ Inheritance of defective gene(s) individual with Charcot-Marie-Tooth disease.
There is wasting of the plantar muscles and
COMPLICATIONS prominent pes cavus as well as a hammer
irregularity of the great toe.
▪ Muscle atrophy, loss of ambulation;
deafness, intellectual disability, optic
neuropathy, feeding difficulties, hip
dysplasia
OSMOSIS.ORG 677
OTHER INTERVENTIONS
DIAGNOSIS ▪ Physical/occupational therapy
OTHER DIAGNOSTICS ▫ Strengthening, range of motion, balance,
maintenance of mobility, activities of
▪ NCS, EMG
daily living
▫ ↓ nerve conduction velocity
▪ Orthotics
▪ History, physical examination (e.g. age of
onset)
▪ Genetic testing
TREATMENT
MEDICATIONS
▪ Pain management
▫ Acetaminophen, NSAIDs, gabapentin,
carbamazepine
SURGERY
▪ Correction of severe skeletal irregularities
Figure 87.2 A section of a peripheral nerve
from an individual with Charcot–Marie–Tooth
disease.
GUILLAIN–BARRÉ SYNDROME
osms.it/guillain-barre-syndrome
Variants
PATHOLOGY & CAUSES ▪ Acute inflammatory demyelinating
polyradiculoneuropathy (AIDP)
▪ Acute, progressive demyelinating PNS
disease; sensory, motor, cognitive deficits ▪ Miller–Fisher syndrome
▪ AKA acute inflammatory demyelinating ▫ Affects cranial nerves (CN) III, IV, VI
polyneuropathy ▪ Acute motor axonal neuropathy (AMAN)
▪ Abnormal autoimmune response ▪ Acute sensorimotor axonal neuropathy
▫ Myelin autoantigen picked up by (AMSAN)
antigen-presenting cells (e.g. dendritic)
→ antigen presented to helper T-cells CAUSES
→ production of cytokines → activation ▪ Molecular mimicry between microbe, nerve
of B-cells and macrophages → B-cells antigens
make antibodies, mark autoantigens;
▫ Most commonly associated with
macrophages use antibody markers
Campylobacter jejuni, Mycoplasma
to attack myelin sheath on peripheral
pneumoniae, cytomegalovirus, Epstein–
neurons → ↓/blocked nerve conduction
Barr, influenza A, Zika, HIV
velocity; axonal degeneration
678 OSMOSIS.ORG
Chapter 87 PNS Demyelinating Disorders
RISK FACTORS
▪ Acute infection
DIAGNOSIS
▪ ↑ age DIAGNOSTIC IMAGING
biologically male Gadolinium-enhanced MRI (spine)
▪ T1-weighted images
COMPLICATIONS ▫ Thickening of intrathecal spinal nerve
▪ Acute roots
▫ Ileus, urinary retention, cardiac
arrhythmias, pneumonia, respiratory LAB RESULTS
failure, quadriplegia ▪ CSF
▪ Long-term ▫ Albuminocytologic dissociation (high
▫ Chronic fatigue, chronic pain, relapses levels of protein without increase in cell
counts)
▪ Serum immunoglobulin G (IgG) antibodies
SIGNS & SYMPTOMS to ganglioside Q1b (GQ1b)
▫ Miller–Fisher
▪ Variable presentation, depending on
affected nerve
▪ Bilateral, flaccid, ascending weakness of
OTHER DIAGNOSTICS
limbs, peaking ≤ four weeks ▪ EMG, NCS
▪ ↓ deep tendon reflexes, areflexia, touch ▫ ↓/blocked nerve conduction velocity
sensation ▪ History, physical examination
▪ Paresthesia
▪ Diaphragmatic weakness → breathing
difficulties (e.g. hypoventilation, requires
TREATMENT
mechanical ventilation)
MEDICATIONS
▪ Autonomic involvement
▪ IVIG
▫ Hypertension/hypotension/postural
hypotension, bradycardia ▪ Gabapentin/carbamazepine
▪ CN involvement ▫ Pain management
▫ Blurred vision, dysarthria, abnormal
pupillary response to light OTHER INTERVENTIONS
▪ Plasmapheresis
▪ Respiratory/hemodynamic support
OSMOSIS.ORG 679
NOTES
NOTES
SPINAL CORD INJURY

▪ Damage/inflammation of spinal cord → loss DIAGNOSTIC IMAGING
of function, sensation
MRI
▪ Secondary compression of spinal cord
RISK FACTORS
▪ Traumatic spine injury, tumours,
inflammatory disease TREATMENT
SURGERY
SIGNS & SYMPTOMS ▪ Decompression surgery
▪ Brown–Sequard syndrome (BSS)
▫ Contralateral loss of pain, temperature; OTHER INTERVENTIONS
ipsilateral hemiparesis ▪ Stabilize vitals, immobilize acute injuries
▪ Cauda equina syndrome (CES)
▫ Severe back pain, sciatica, saddle
anesthesia, incontinence, sexual
dysfunction
680 OSMOSIS.ORG
Chapter 88 Spinal Cord Injury
BROWN–SÉQUARD SYNDROME
(BSS)
osms.it/brown-sequard-syndrome
COMPLICATIONS
PATHOLOGY & CAUSES ▪ Progression to complete paralysis
▪ AKA spinal hemiparaplegia
▪ Spinal cord hemisection (damage limited to SIGNS & SYMPTOMS
one half) → paralysis on side of lesion; loss
of sensation on opposite side ▪ Contralateral pain, temperature loss;
▪ Neurological fallout from damage to spinal ipsilateral hemiparesis, proprioception/
tracts vibration sense loss
▫ Corticospinal tract: loss of upper motor
neuron innervation → ipsilateral spastic
paralysis, below level of lesion; damage DIAGNOSIS
to lower motor neuron at level of spinal
injury → ipsilateral flaccid paralysis of DIAGNOSTIC IMAGING
muscles supplied at spinal level
▫ Dorsal column (medial lemniscus): MRI
ipsilateral loss of vibration, ▪ Unilateral spinal cord pathology/
proprioception, fine touch hemisection of spinal cord
▫ Spinothalamic tract: contralateral loss of
pain, temperature sensation; 1–2 levels
below lesion
TREATMENT
OTHER INTERVENTIONS
CAUSES ▪ Traumatic injuries
▪ Spinal fractures, gunshot wounds, ▫ Cervical spine/lower dorsal vertebra
stab wounds, crush injury, tumours, immobilization
inflammatory diseases
CAUDA EQUINA SYNDROME (CES)

osms.it/cauda-equina-syndrome
CAUSES
PATHOLOGY & CAUSES ▪ Lower back disc herniation, spinal
stenosis, cancer, trauma, epidural abscess/
▪ Simultaneous compression of multiple hematoma
lumbosacral nerve roots below level (L2)
of conus medullaris (distal bulbous part of
spinal cord) → neuromuscular, urogenital
symptoms
OSMOSIS.ORG 681
COMPLICATIONS
▪ Paraplegia, persistent bowel/bladder
TREATMENT
problems, sexual dysfunction, loss of
sensation
SURGERY
▪ Surgical decompression (e.g. laminectomy)

▪ Red flags (urgent investigation/treatment Sudden onset CES
required) ▪ Medical emergency
▫ Severe back pain; saddle anesthesia; ▫ Early treatment (< 48hrs) of
incontinence/sexual dysfunction compressive lesions → significantly
▪ Muscle weakness in lower leg with absent/ better outcomes, prevents progression
reduced deep tendon achilles/patellar reflex to paraplegia
▪ Gait disturbance
▪ Sciatica-like pain in one/both legs: low back
pain, radiates down leg
▪ Numbness in saddle distribution
▫ Anesthesia/paresthesia of S3–S5
dermatomes → anesthesia/paresthesia
perineum, external genitalia, anus,
perianal region
▪ Loss of bowel/bladder control
▪ Absent anal reflex, bulbocavernosus reflex
▪ Decreased tone of urinary, anal sphincters
▪ Detrusor weakness → urinary retention/
post-voiding residual incontinence
▪ Sexual dysfunction
DIAGNOSIS
DIAGNOSTIC IMAGING Figure 88.1 An MRI scan of the spine in
the sagittal plane demonstrating a L4/L5
Spine MRI (with gadolinium contrast) intervertebral disc prolapse compressing the
▪ Compression of S2–S4 nerve roots by cauda equina. The individual presented with
mass/herniation symptoms of cauda equina syndrome.
Bladder ultrasound
▪ Post-void residual > 250ml
OTHER DIAGNOSTICS
Clinical examination
▪ Regional anesthesia, muscle weakness,
abnormal reflexes, abnormal gait
682 OSMOSIS.ORG
NOTES
NOTES
VISION DISORDERS

▪ Vision deficit disorders OTHER DIAGNOSTICS
▪ Correlate with anatomical lesions along ▪ History
visual pathway ▪ Physical/neurologic examination
▫ Light → cornea → lens → media → ▪ Cranial nerve (CN) testing
retina → optic nerve → chiasmal ▫ CN II: visual fields and acuity
decussation → optic radiations (parietal,
▫ CN II/III: pupillary reflex
temporal paths) → primary visual cortex
in occipital lobe ▫ CN III/IV/VI: ocular movement
CAUSES TREATMENT
▪ Mass effect → impingement of structures
▪ Vascular → brain parenchyma infarction MEDICATIONS
along visual pathway ▪ Vascular: thrombolytics
SURGERY
SIGNS & SYMPTOMS ▪ Masses: resection
▪ Impaired vision
OSMOSIS.ORG 683
BITEMPORAL HEMIANOPSIA
osms.it/bitemporal_hemianopsia
▪ Ophthalmoplegia (especially large mass
PATHOLOGY & CAUSES lesions, pinealomas)
▪ Hormonal deficiency/excess (if pituitary
▪ Visional deficit: lateral vision loss
growth is functional)
▫ Optic chiasm lesions (commonly)
▪ Pathogenesis: ↑ sellar mass size → presses
optic chiasm → impinges decussating DIAGNOSIS
visual fibers (most medial) → bitemporal
hemianopsia DIAGNOSTIC IMAGING
MRI
CAUSES
▪ Visualize mass at area of optic chiasm;
▪ Pituitary enlargement gadolinium-enhanced images aid
▫ Hyperplasia (i.e. pregnancy or lactation); elucidating pituitary tissue (↑ gadolinium
adenoma (specific, hormone-secreting uptake in pituitary)
pituitary hyperplasia); cyst; abscess
▪ Craniopharyngioma CT scan
▪ Meningioma (in sella turcica) ▪ Less diagnostic; may reveal sellar
▪ Saccular aneurysm (anterior calcification, mass
communicating artery)
▪ Primary malignancy
TREATMENT
▫ Germ cell tumor (AKA ectopic
pinealoma); chordoma; central nervous MEDICATIONS
system (CNS) lymphoma
▪ Smaller, hormone-responsive adenomas
(prolactinomas → dopamine agonists first-
COMPLICATIONS line therapy)
▪ ↑ size → further impinges surrounding
structures SURGERY
▫ Cavernous sinus impingement → CN III, ▪ Neurosurgery: nasal aperture, posterior
IV, VI → diplopia → ophthalmoplegia nasopharynx, sublabial (upper lip) incision
▪ Dorsal extension of mass → dorsal accesses inferior aspect of cerebrum
midbrain impingement → Parinaud’s ▫ Fluoroscopic visualization: navigation,
syndrome pituitary visualization
▫ Upgaze paralysis ▪ First-line therapy for all other pituitary
▫ Pinealomas (posterior, common) adenomas, sellar masses with meaningful
visual field impingement/other symptom
severity
SIGNS & SYMPTOMS
▪ Vision loss
▫ Lateral fields, both eyes (may go
unnoticed; chronic, progressive)
▪ Headache
▪ Diplopia
684 OSMOSIS.ORG
Chapter 89 Vision Disorders
COLOR BLINDNESS
osms.it/color-blindness

▪ Altered color perception ▪ Limited color discrimination
▪ Pathogenesis
▫ Atypical cone type(s) function → altered
color hue → limited color discrimination DIAGNOSIS
(commonly)
▫ Optic nerve/other retinal lesions ▪ Family, medication history
(uncommon)
OTHER DIAGNOSTICS
CAUSES ▪ Ishihara plates: visual stimuli, colors offer
wavelength-specific stimulation for three
Congenital cone types
▪ Three cone types (opsins) ▫ Inability to perceive numbers/letters on
▫ Red, green opsins (X-chromosome): plate → reveal cone type deficit(s)
most inherited color blindness X-linked
recessive → predominantly biologically-
male individuals TREATMENT
▫ Blue opsin (VII-chromosome): blue
wavelength deficiency, very rare OTHER INTERVENTIONS
▪ Associated with Turner syndrome ▪ No curative therapy
▪ Acquired disease
Acquired ▫ Glaucoma: regular eye examinations
▪ Optic neuropathies ▫ Diabetes: glycemic control → ↓
▫ Optic neuritis: persistent color blindness microvascular disease; regular eye
after visual deficit restoration; early examinations
multiple sclerosis symptom ▪ Individual education → lifestyle adaptation
▫ Diabetic retinopathy: neoproliferation, → proper visual cue interpretation
microvascular disease → retinal ▫ Unable to perceive red vs. green light
dysfunction (glaucoma) difference on traffic signals → location
▪ Bilateral, ventral occipital stroke → cerebral discrimination education → top vs.
achromatopsia (rare) bottom light interpretation
Iatrogenic
▪ Ethambutol → poor red-green
discrimination
▪ Digoxin → yellowish hue disturbance
▪ Other
▫ Ibuprofen, quinine, acetaminophen,
sildenafil citrate, tobacco
COMPLICATIONS
▪ Nyctalopia: limited night vision
OSMOSIS.ORG 685
CORTICAL BLINDNESS
osms.it/cortical-blindness

▪ Acquired blindness: bilateral lesions to DIAGNOSTIC IMAGING
visual cortex in occipital lobe
MRI
Pathogenesis ▪ Some cases, detects cause (e.g. vascular
▪ Vascular occlusion occlusion, infarction)
▫ Bilateral, distal posterior cerebral artery
(PCA) occlusion; commonly embolic OTHER INTERVENTIONS
▫ Basilar artery occlusion → ↓ blood flow
in bilateral distal PCAs History, physical examination
▪ Vascular flow dysregulation → posterior ▪ Assess non-cortical functions: normal
reversible encephalopathy syndrome pupillary light reflex
(PRES) ▫ Limited/no visual response with intact
pupillary light reflex → blindness
neurological not ocular
CAUSES
▪ Primary visual cortex lesions (calcarine Fundoscopy
fissure in occipital lobe) ▪ Normal
▫ Neighboring lesions → similar anopsia
▪ Anton–Babinski syndrome (visual
MEDICATIONS
anosognosia)
▪ Vascular occlusion: thrombolysis
▫ Individual unable to perceive vision →
blindness denial ▪ PRES: emergent antihypertensives
▫ Image confabulation common
OTHER INTERVENTIONS
▪ Spontaneous recovery
SIGNS & SYMPTOMS ▫ Visual defects may persist (e.g.
prosopagnosia—inability to recognize
▪ Inability to perceive visual input faces)
▪ CN testing: II/III preserved pupillary light
reflex
686 OSMOSIS.ORG
Chapter 89 Vision Disorders
HEMIANOPSIA
osms.it/hemianopsia
▫ Lesion to non-dominant lobe
PATHOLOGY & CAUSES → Gerstmann syndrome (finger
agnosia, acalculia, agraphia, right-left
▪ Individual loses half of visual field, visualization)
commonly due to retrochiasmatic lesion of
▪ Temporal lobe involvement → seizure
visual tract
Pathogenesis
▪ Vascular
SIGNS & SYMPTOMS
▫ Middle cerebral artery (MCA): complete
▪ Visual field loss
contralateral hemianopia
▫ Unilateral hemianopia: contralateral
▫ Unilateral posterior cerebral artery
optic tract lesion (homonymous
(PCA): contralateral hemianopia with
hemianopia); large, contralateral optic
macular sparing
radiation lesion
▪ Mass
▫ Superior quadrantanopia: contralateral
▫ Visual pathway compression temporal lobe lesion of optic radiation
loop
CAUSES ▫ Inferior quadrantanopia: contralateral
▪ Unilateral optic tract lesion parietal lobe lesion of optic radiation
▪ Large (complete) unilateral optic radiation loop
lesion ▪ Neurologic examination
▪ Quadrantanopia: sub-complete lesion, ▫ CN II testing: visual field
corresponds to lesioned optic radiation ▫ Motor/sensory testing for concomitant
▫ Upper outer-quadrant deficit (“pie-in- symptoms
the-sky” defect) → temporal lobe loop
lesion
▫ Lower inferior quadrant deficit →
DIAGNOSIS
parietal lobe lesion
▪ Large, unilateral primary visual cortex lesion
▫ Macular visual field spared
▪ Bilateral upper/lower visual cortex lesion → DIAGNOSTIC IMAGING
altitudinal hemianopia
MRI
▫ Upper/lower field visual defect
▪ Mass lesions/old stroke (preferred method)
COMPLICATIONS CT scan
▪ Vascular/mass effect territory-dependent ▪ Mass lesion and acute, hemorrhagic stroke
▪ PCA distribution
▫ Diplopia, dizziness, balance issues TREATMENT
▪ Anterior cerebral artery (ACA)/MCA
distribution SURGERY
▫ Ipsilateral motor and sensory symptoms ▪ Resection: mass compressing the visual
▪ Parietal lobe involvement → contralateral pathway
neglect
OSMOSIS.ORG 687
OTHER INTERVENTIONS
▪ Peripheral prism spectacles
▫ High-power prism segments in regular
spectacle lens → expands visual field up
to 30°
▪ Saccadic eye movement training (scanning
therapy)
▫ Individual makes compensatory
saccadic eye movements to side with
lost visibility without moving head → ↑
function, injury prevention
HOMONYMOUS HEMIANOPSIA
osms.it/homonymous-hemianopsia

▪ Lesion in optic tract → vision loss in each ▪ History, physical examination
eye (corresponding halves of visual field)
▪ Pathogenesis DIAGNOSTIC IMAGING
▫ Vascular: large MCA/smaller anterior
choroidal artery stroke MRI
▫ Mass effect: tumor, cyst, arteriovenous ▪ Mass lesions/old stroke (preferred method)
malformation (AVM)
CT scan
▪ Mass lesion/acute, hemorrhagic stroke
CAUSES
▪ Unilateral optic tract lesion
TREATMENT
▪ Resection: mass compressing the visual
▪ Half of visual field lost pathway
▫ Not relieved by monocular vision (vision
deficit persists despite closing one eye)
OTHER INTERVENTIONS
▪ Peripheral prism spectacles
▪ Saccadic eye movement training (scanning
therapy)
688 OSMOSIS.ORG
NOTES
NOTES
ANXIETY DISORDERS

▪ Mental disorders characterized by ▪ Excessive, unreasonable fear/distress
excessive, unreasonable fear, distress ▪ Struggle to control symptoms
▪ May be omnipresent/in response to ▪ Lasts > six months
particular stimulus ▪ Affects day-to-day functioning
▪ Awareness of condition often causes more ▪ Not explained by other condition/substance
distress
CAUSES TREATMENT
▪ May be genetic, environmental
▪ Often associated with other mental MEDICATIONS
disorders (mood, substance-related) ▪ Selective serotonin reuptake inhibitors
(SSRIs), other antidepressants,
benzodiazepines
SIGNS & SYMPTOMS
PSYCHOTHERAPY
▪ Persistent fear/distress
▪ E.g. cognitive behavioral therapy
▪ Nausea, difficulty sleeping, headache
▫ Identify, explain thoughts/feelings,
change flawed ones
▫ Better long-term prognosis; no side
effects, no dependency
OSMOSIS.ORG 689
AGORAPHOBIA
osms.it/agoraphobia

▪ Fear, avoidance of public places ▪ Unreasonable fear/anxiety associated with
▪ Individuals refuse to leave “safety” of home public places
▪ Caused by underlying fear of feeling
trapped, unable to receive help
CAUSES
▪ Resulting avoidance of public places
▪ Lasts > six months
▪ Associated with other anxiety disorders,
e.g. panic disorder ▪ Distress affects day-to-day functioning
▪ Not explained by other condition/substance
SIGNS & SYMPTOMS

TREATMENT
▪ Fast heartbeat, dizziness, trembling
▪ Thinking about/avoidance of public places
MEDICATIONS
causes distress ▪ SSRIs, benzodiazepines
PSYCHOTHERAPY
▪ E.g. cognitive behavioral therapy,
systematic desensitization
Figure 90.1 Illustration showing how other disorders can lead to agoraphobia. If someone with
panic disorder has panic attacks outside frequently, they may develop agoraphobia and avoid
going outdoors altogether.
690 OSMOSIS.ORG
Chapter 90 Anxiety Disorders
GENERALIZED ANXIETY
DISORDER
osms.it/generalized-anxiety-disorder

▪ Excessive, unreasonable, persistent fear, ▪ Excessive, unreasonable anxiety
distress ▪ Struggle to control anxiety
▪ Persistent fear/distress, nausea, difficulty
CAUSES sleeping, headache
▪ May be genetic, environmental; higher in ▪ > three symptoms listed above (children >
some groups one year old)
▪ Associated with depressive disorders ▪ Lasts > six months
▪ Distress affects day-to-day functioning
SIGNS & SYMPTOMS
▪ Restlessness, difficulty concentrating, TREATMENT
irritability
▪ Muscle tension (→ aching and soreness), MEDICATIONS
fatigue, insomnia (→ chronic fatigue) ▪ SSRIs, antidepressants, benzodiazepines
PSYCHOTHERAPY
Figure 90.2 Illustration of the different levels of anxiety.
OSMOSIS.ORG 691
PANIC DISORDER
osms.it/panic-disorder

▪ Recurrent panic attacks → sudden periods ▪ Recurrent, unpredictable panic attacks (>
of intense fear/discomfort two)
▪ Attacks unpredictable ▪ Distress affects day-to-day functioning
▪ Behavioral changes to avoid further attacks
CAUSES ▪ Presence of > four symptoms
▪ May be genetic, environmental; higher in ▪ Not explained by other condition/substance
some groups
▪ Associated with major depressive disorder,
social and generalized anxiety disorders,
TREATMENT
obsessive-compulsive disorder
MEDICATIONS
▪ SSRIs and other antidepressants,
SIGNS & SYMPTOMS benzodiazepines
▪ Antiseizure medications
▪ Feelings of choking, derealization, fear of
losing control/dying PSYCHOTHERAPY
▪ Elevated heart rate, chest pain/discomfort, ▪ E.g. cognitive behavioral therapy
sweating, trembling, shortness of breath,
nausea, dizziness, chills, numbness
Figure 90.3 Illustration showing possible causes for panic disorder, and avenues to treatment.
692 OSMOSIS.ORG
PHOBIAS
osms.it/phobia

▪ Excessive, unreasonable, persistent fear ▪ Unreasonable fear/anxiety associated with
resulting in avoidance of particular object/ phobic stimulus
situations (phobic stimulus) ▪ Resulting avoidance (which may itself
cause distress) of phobic stimulus
TYPES ▪ Lasts > six months
▪ As listed in the DSM-5 ▪ Distress affects day-to-day functioning
▫ Fear of animals ▪ Not explained by other condition/substance
▫ Fear of natural environment
▫ Fear of blood, needles TREATMENT
▫ Situational fears
▫ “Other” fears (AKA none of the above) MEDICATIONS
▪ SSRIs, benzodiazepines
CAUSES
▪ May be genetic, environmental PSYCHOTHERAPY
▪ Associated with anxiety, mood, substance ▪ E.g. cognitive behavioral therapy,
use disorders systematic desensitization
SIGNS & SYMPTOMS

▪ Response to phobic stimulus: elevated
heartbeat, dizziness, trembling
▪ Excessive thinking about/avoidance of
phobic stimulus causes distress
Figure 90.4 Illustration of different specific phobias making someone feel powerless.
OSMOSIS.ORG 693
SEPARATION ANXIETY DISORDER
osms.it/separation-anxiety-disorder

▪ Excessive, unreasonable, persistent fear of ▪ Excessive, unreasonable, persistent fear of
being separated from individual/location being separated from individual/location
▪ Adults: lasts > six months
CAUSES ▪ Children: lasts > four weeks
▪ May be genetic, environmental ▪ Not explained by other condition/substance
▪ Associated with all other anxiety disorders
TREATMENT
SIGNS & SYMPTOMS
MEDICATIONS
▪ Distress caused by thought of experiencing ▪ SSRIs, benzodiazepines
separation
▪ Nightmares, headaches, nausea PSYCHOTHERAPY
SOCIAL ANXIETY DISORDER

osms.it/social-anxiety-disorder
PATHOLOGY & CAUSES

SIGNS & SYMPTOMS
▪ Excessive, unreasonable, persistent fear of
being judged ▪ Trembling, blushing, derealization
▪ Avoidance of social situations ▪ Excessive thinking about/avoidance of
social situations/circumstances, associated
distress
CAUSES
▪ May be genetic, environmental; higher in
some groups DIAGNOSIS
▪ Associated with mood disorders,
substance-related disorders, eating ▪ Excessive, unreasonable, persistent fear of
disorders, obsessive-compulsive disorders being judged
▪ Avoidance of social situations/
circumstances, associated distress
▪ Fear of others judging anxious feelings
▪ Lasts > six months
694 OSMOSIS.ORG
TREATMENT
MEDICATIONS
▪ SSRIs, antidepressants, benzodiazepines
PSYCHOTHERAPY
Figure 90.5 Illustration of the possible causes of social anxiety disorder, which are still unclear,
as well as the DSM-5’s criteria for a diagnosis of the condition.
OSMOSIS.ORG 695
NOTES
NOTES
COGNITIVE & DISSOCIATIVE
DISORDERS

SIGNS & SYMPTOMS
PATHOLOGY & CAUSES
▪ Cognitive disorders: involve cognitive
decline
▪ Dissociative disorders: involve detachment DIAGNOSIS
from past/present versions of oneself/the
world ▪ See individual disorders
CAUSES
TREATMENT
▪ Past trauma/stress may cause/worsen
condition
COMPLICATIONS
▪ Personality changes, depression
AMNESIA
osms.it/amnesia
▪ Associated with storage and retrieval
PATHOLOGY & CAUSES phases of memory
▪ Usually involves damage to cortex
▪ Acute loss of memory
CAUSES
TYPES
▪ Head trauma, infection, neurodegenerative
Anterograde amnesia diseases (e.g. dementia/Alzheimer’s),
▪ Inability to form new memories brain tumours, thiamine deficiency
(causing Wernicke–Korsakoff syndrome),
▪ Associated with encoding and
benzodiazepines, electroconvulsive therapy
consolidation phases of memory
▪ Usually involves damage to prefrontal
cortex/hippocampus COMPLICATIONS
▪ Range of potential complications (e.g.
Retrograde amnesia confusion, loss of identity)
▪ Inability to recall old memories (may result
in creation of false memories)
696 OSMOSIS.ORG
Chapter 91 Cognitive & Dissociative Disorders

▪ Acute memory loss, affects memories PSYCHOTHERAPY
created before/after an event (or onset of ▪ Occupational and cognitive therapies to
illness) enhance memory

▪ Often temporary (address cause)
DIAGNOSTIC IMAGING ▪ Mobile phones and digital devices as
workarounds to memory loss
MRI/CT scan
▪ Brain damage/abnormalities
LAB RESULTS
▪ Nutritional deficiencies/infections
DELIRIUM
osms.it/delirium

▪ Fast decline in attention/consciousness, ▪ Difficulties with attention span,
thinking concentration, remaining conscious
▪ Sometimes accompanied by symptoms of ▪ Disorganized/delayed thinking
hyper/hypoactivity ▪ Hyperactive symptoms
▫ Agitated/aggressive
RISK FACTORS ▫ Delusions/hallucinations
▪ Disease (e.g. dementia, constipation, ▪ Hypoactive symptoms
pneumonia, UTIs) ▫ Sluggish, drowsy
▪ Post-surgical complications ▫ Less reactive, withdrawn
▫ Medications (e.g. narcotic pain
medications, benzodiazepines,
hypnotics, anticholinergics) DIAGNOSIS
▫ Altered metabolic homeostasis (e.g.
electrolyte or imbalance), chronic fatigue ▪ Issues with attention/consciousness and
▪ Increases risk of falling over → broken cognition, developing over short time
bones, head injuries, bruises, bleeds → (several days or fewer)
longer hospitalizations, more complications, ▫ Difficulties with attention span,
higher mortality rates concentration, remaining conscious
▫ Disorganized/delayed thinking
▪ Not explained by pre-existing
neurocognitive condition
▪ Explained by other medical condition and/or
exposure to/withdrawal from a substance
OSMOSIS.ORG 697
OTHER INTERVENTIONS
TREATMENT
Preventative
MEDICATIONS ▪ Make high-risk targets feel oriented,
comfortable (reducing excess noise/
Severe symptoms
stimulation; make sure glasses, hearing aids
▪ Haloperidol/second generation are used if needed; encourage daily routine)
antipsychotics
▪ Avoid opiates, other causative medications;
avoid restraints
DISSOCIATIVE DISORDERS
osms.it/dissociative-disorders
▪ Worsens under stress
PATHOLOGY & CAUSES
High severity: dissociative identity disorder
▪ Characterized by disruptions or ▪ Feeling of having multiple identities which
breakdowns of memory, awareness, act/think/perceive differently, thus impairing
identity, or perception. ability to recall everyday/important
information about oneself
TYPES ▪ Two categories of dissociative identity
▪ Three types on scale of severity disorder
▫ Covert: individual aware of identity
Low severity: depersonalization/derealiza- shifts, struggles to manage them
tion disorder ▫ Overt: individual completely assumes
▪ Depersonalization: feeling detached from different identities while unaware
own body/mind (e.g. feeling one’s body is a ▪ Can involve dissociative fugue (individual
robot/ feeling of watching self) becomes confused about identity, starts
▪ Derealization: feeling of world not being sudden travel/ wandering)
fully real (e.g. feeling outside world not real/
lacks lucidity)
CAUSES
Middle severity: dissociative amnesia ▪ Thought to be primarily caused by
▪ Inability to recall significant information psychological trauma; associated with
about oneself (e.g. location of childhood sexual abuse, post-traumatic stress
home, what mother looked like) disorder, depression, substance abuse,
▪ Four categories of amnesia borderline personality, somatoform
conditions
▫ Localized: trouble recalling traumatic
event (and surrounding period) ▪ More common in biologically-female
indiviudals
▫ Generalized: trouble recalling significant
portion of one’s past
▫ Systematized: trouble recalling specific SIGNS & SYMPTOMS
category of information
▫ Continuous: trouble recalling events Depersonalization/derealization disorder
after they occur ▪ Explicit thoughts/behaviors related to
▪ Can involve dissociative fugue (individual depersonalization/derealization
becomes confused about identity, starts ▪ Emotional/physical numbness; weak sense
sudden travel/ wandering) of self
698 OSMOSIS.ORG
Chapter 91 Cognitive & Dissociative Disorders
▪ Deadpan speech
▪ Altered sense of time
TREATMENT
▪ Brain fog/lightheadedness MEDICATIONS
▪ Prone to rumination, anxiety ▪ Antidepressants (like selective serotonin
▪ Severe symptoms: difficulty recognizing reuptake inhibitors)
familiar places, people, objects ▪ Mood stabilizers
Dissociative amnesia & Dissociative identi- ▪ Neuroleptics
ty disorder
▪ Inability to recall significant information PSYCHOTHERAPY
about oneself ▪ E.g., psychodynamic, cognitive, cognitive
▪ Altered consciousness (e.g. behavioral, supportive
depersonalization, derealization)
▪ Depression, suicidal ideation
OTHER INTERVENTIONS
▪ Memory aids: alarms, reminders, media
DIAGNOSIS (e.g. photos/videos/recordings)
▪ Occupational therapy
Depersonalization/derealization disorder
▪ Presence of depersonalization/derealization
▪ Symptoms affect day-to-day functioning
▪ Not caused by other condition/substance
Dissociative amnesia
▪ Inability to recall significant information
about oneself, beyond everyday forgetting
Dissociative identity disorder

▪ Feeling of having multiple identities which
act/think/ perceive differently
▪ Inability to recall significant information
about oneself, beyond everyday forgetting
▪ Not described by cultural/religious practices,
nor by play (e.g. imaginary friends)
OSMOSIS.ORG 699
NOTES
NOTES
DEPRESSIVE & BIPOLAR
DISORDERS

Mental disorders involving mood changes ▪ Excessive, unreasonable fear/distress
▪ Often involve depression, sometimes ▪ Struggle to control symptoms
mania/hypomania (see below) ▪ Lasts > six months
▪ Affects day-to-day functioning
CAUSES ▪ Not explained by other condition/substance
▪ Genetic (especially between close relatives)
▪ Linked to neurotransmitter regulation
(norepinephrine, serotonin, dopamine)
TREATMENT
▪ High comorbidity with other mental
MEDICATIONS
disorders
▪ Antidepressants, lithium
COMPLICATIONS
PSYCHOTHERAPY
▪ Self-harm/suicide
▪ Social consequences (e.g. losing friends)
OTHER INTERVENTIONS
SIGNS & SYMPTOMS ▪ Lifestyle changes
▫ Improved diet, more exercise, more
▪ Manic episodes featuring a mood sunlight
disturbance, increased energy/activity,
and ≥ three of following for ≥ one week,
affecting day-to-day functioning
▪ Hypomanic (“less than manic”) episodes
featuring a mood disturbance, increased
energy/activity, and ≥ three of the above
during a period > four days, not affecting
day-to-day functioning
▪ Major depressive episodes featuring ≥ five
of following in a two week period
▪ Other mood changes, including more mild
depression; see individual disorders
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Chapter 92 Depressive & Bipolar Disorders
BIPOLAR I DISORDER
osms.it/bipolar-I

Bipolar disorder characterized by extreme ▪ Mood swings
mood swings with combination of manic, ▪ Manic episodes
hypomanic, depressive episodes ▪ Usually, hypomanic and depressive
episodes
CAUSES
Genetic (especially between close relatives)
▪
DIAGNOSIS
▪ Medications (e.g. SSRIs)
▪ Often no particular trigger ▪ ≥ one manic episode
▪ High comorbidity with other mental ▪ Symptoms affect day-to-day functioning
disorders
MNEMONIC: DIG FAST

Characteristics of manic TREATMENT
episode
Distractibility MEDICATIONS
Indiscretion: excessive ▪ Atypical antipsychotics (e.g. olanzapine),
involvement in pleasurable in combination with mood stabilizers (esp.
activities lithium)
Grandiosity
Flight of ideas PSYCHOTHERAPY
Activity increase ▪ E.g. cognitive behavioral therapy,
Sleep deficit/decreased need interpersonal
for sleep
Talkativeness/pressured OTHER INTERVENTIONS
speech
▪ Electroconvulsive therapy (ECT)
OSMOSIS.ORG 701
BIPOLAR II DISORDER
osms.it/bipolar-II

Bipolar disorder characterized by mood ▪ ≥ one hypomanic episode
swings with hypomanic, depressive episodes. ▪ ≥ one major depressive episode
CAUSES ▪ Not caused by other condition/substance
▪ Genetic (especially between close relatives)
Medications (e.g. SSRIs)
▪
TREATMENT
▪ Often no particular trigger
▪ High comorbidity with other mental MEDICATIONS
disorders
▪ Atypical antipsychotics (e.g. olanzapine),
in combination with mood stabilizers (esp.
lithium)
SIGNS & SYMPTOMS
▪ Mood swings PSYCHOTHERAPY
▪ Hypomanic, depressive episodes ▪ E.g. cognitive behavioral therapy,
interpersonal
MAJOR DEPRESSIVE DISORDER

osms.it/major-depressive-disorder

Depressive disorder characterized by one or ▪ Major depressive episodes
more episodes of a strongly depressed mood
▪ Episodes interfere with day-to-day life
in activities such as eating, working, and DIAGNOSIS
sleeping
▪ One or more major depressive episodes
▪ The symptoms cause distress in other
CAUSES areas of life
▪ Exact cause unknown; runs in families,
▪ The disturbance is not better explained
especially between close relatives;
by or accounted for by another medical
linked to neurotransmitter regulation
condition or substance
(norepinephrine, serotonin, dopamine); high
comorbidity with other mental disorders ▫ There has not been a manic or
hypomanic episode
702 OSMOSIS.ORG
Chapter 92 Depressive & Bipolar Disorders
MNEMONIC: SIG ED CAPS

Diagnostic criteria for Major
TREATMENT
depressive disorder
MEDICATIONS
Sleep: increased or decreased
▪ Antidepressants (SSRIs, SNRIs, NDRIs)
Interest: decreased
Guilt/worthlessness
Energy: decreased or fatigued PSYCHOTHERAPY
Depressed mood most of the ▪ E.g., cognitive behavioral therapy,
day interpersonal
Concentration/difficulty making
decisions OTHER INTERVENTIONS
Appetite and/or weight ▪ Improved diet, more exercise, more sunlight
increase or decrease
Psychomotor activity:
increased or decreased
Suicidal ideation/ thoughts of
death
PREMENSTRUAL DYSPHORIC
DISORDER
osms.it/premenstrual-dysphoric-disorder
▫ Inability to sleep/oversleeping
PATHOLOGY & CAUSES
▫ Feelings of being overwhelmed
▪ Depressive disorder characterized by mood ▫ Mild physical symptoms (e.g.
changes during menstrual cycle tenderness/swelling)
CAUSES DIAGNOSIS
▪ Unknown; possible sensitivity to hormonal
changes ▪ Mood changes ≤ one week before menses,
as evidenced by presence of ≥ five of
symptoms (≥ one from each category),
SIGNS & SYMPTOMS resolving within one week post-menses
▪ Must occur during majority of menstrual
▪ Emotional cycles over past year
▫ Affective lability ▪ Symptoms affect day-to-day life
▫ Irritability/anger ▪ Not caused by other condition/substance
▫ Anxiety/angst
▪ Other symptoms
▫ Diminished interest/pleasure
▫ Decreased concentration
▫ Fatigue
▫ Weight loss/gain
OSMOSIS.ORG 703
PSYCHOTHERAPY
TREATMENT ▪ E.g. cognitive behavioral therapy,
interpersonal
MEDICATIONS
▪ SSRIs, oral contraceptives
OTHER INTERVENTIONS
▪ Lifestyle changes: improved diet, more
exercise, more sunlight
SEASONAL AFFECTIVE DISORDER

osms.it/seasonal-affective-disorder

▪ Depressive disorder characterized by one ▪ One or more major depressive episodes
or more episodes of a strongly depressed ▪ The symptoms cause distress in other
mood areas of life
▪ Episodes interfere with day-to-day life ▪ The disturbance is not better explained
in activities such as eating, working, and by or accounted for by another medical
sleeping condition or substance
▪ Occurs most commonly in seasons of lower ▫ There has not been a manic or
light, like winter hypomanic episode
CAUSES
TREATMENT
▪ Exact cause unknown; runs in families,
especially between close relatives;
MEDICATIONS
linked to neurotransmitter regulation
(norepinephrine, serotonin, dopamine); high ▪ Antidepressants (SSRIs, SNRIs, NDRIs)
comorbidity with other mental disorders
PSYCHOTHERAPY
▪ E.g. cognitive behavioral therapy,
SIGNS & SYMPTOMS interpersonal
▪ Major depressive episodes

OTHER INTERVENTIONS
▪ Improved diet, more exercise, more sunlight
704 OSMOSIS.ORG
NOTES
NOTES
ELIMINATION DISORDERS

▪ Repeated voluntary/involuntary passage of ▪ Repeated voluntary/involuntary passage of
feces/urine into inappropriate places feces/urine into inappropriate places
▫ Encopresis: feces ▪ > five years old
▫ Enuresis: urine ▪ Not caused by other condition/substance
▪ Disorders can be functional; often explained
by/causing distress
TREATMENT
CAUSES MEDICATIONS
▪ Genetic, environmental ▪ Laxatives, desmopressin, to manage
elimination
SIGNS & SYMPTOMS
PSYCHOTHERAPY
▪ Repeated voluntary/involuntary passage of ▪ E.g. cognitive behavioral therapy
feces/urine into inappropriate places
ENCOPRESIS
osms.it/encopresis

▪ Repeated voluntary/involuntary passage of ▪ Repeated passage, voluntary or
feces into inappropriate places uncontrolled, of feces into inappropriate
▪ Often functional, caused by overflow due to places
withholding feces (e.g. fear of defecation);
constipation-related
▪ When feces deposited in abnormal places,
DIAGNOSIS
may be neurodevelopmental/induced by
fear of toilets ▪ Repeated passage, voluntary or
uncontrolled, of feces into inappropriate
places
CAUSES ▪ Occurs at least once a month for three
▪ Genetic, environmental months in a row
▪ Often associated with psychiatric
comorbidities
OSMOSIS.ORG 705
▪ Age: > four years old OTHER INTERVENTIONS
Dietary
(except constipation)
▪ Avoid constipating foods
▪ Adequate hydration
TREATMENT ▪ Increase fiber intake; fiber tablets
MEDICATIONS Remove fecal impaction

▪ Daily laxatives (stool softeners: 1g/kg ▪ Polyethylene glycol/mineral oil
polyethylene glycol per day) ▪ Rectal enema
PSYCHOTHERAPY
▪ Behavioral therapy
▫ Encourage toilet usage, normalize bowel
movements
ENURESIS
osms.it/enuresis

▪ Repeated voluntary/involuntary passage of ▪ Repeated voluntary/involuntary passage of
urine into inappropriate places urine into inappropriate places
▪ Can be nocturnal, diurnal, both ▪ “Clinically significant”: occurs > two times
▪ Can involve poor bladder control per week for > three consecutive months or
(physiological developmental reasons)/ affects day-to-day life
exceeding bladder capacity ▪ Age: > five years old
▪ Not caused by other substance
CAUSES
▪ Genetic, environmental; stress-related TREATMENT
▫ Often associated with psychiatric
comorbidities MEDICATIONS
▫ More common in biological males ▪ Desmopressin (reduce urine production)
SIGNS & SYMPTOMS PSYCHOTHERAPY

▪ Behavioral therapy (e.g. bedtime alarm
▪ Repeated voluntary/involuntary passage of therapy), bladder program
urine into inappropriate places
706 OSMOSIS.ORG
NOTES
NOTES
FACTITIOUS DISORDERS
MUNCHAUSEN SYNDROME
osms.it/munchausen-syndrome

▪ Fabricating/exaggerating physical/ Munchausen syndrome
psychological symptoms in oneself/another ▪ Fabricating/exaggerating physical/
▪ Both types motivated by desire for psychological symptoms
sympathy/attention ▪ Seeks self to be treated as ill/impaired/
injured
TYPES Munchausen syndrome by proxy
Munchausen syndrome ▪ Purposefully inducing symptoms in another
▪ Faking/exaggerating symptoms in oneself ▪ Seeks victim to be treated as ill/impaired/
▫ AKA factitious disorder injured
▪ Diagnosis for perpetrator, not victim
Munchausen syndrome by proxy
▪ Purposefully inducing symptoms in another Both
(e.g. a child, elder, family member, pet) ▪ Behavior occurs even without obvious
▫ AKA factitious disorder by proxy/ rewards (e.g. insurance claim)
factitious disorder imposed on another ▪ Not caused by other condition
▪ Can occur once, multiple times
CAUSES
▪ High comorbidity with mood/personality TREATMENT
disorders
PSYCHOTHERAPY
▪ Various psychotherapy methods
SIGNS & SYMPTOMS
Munchausen syndrome by proxy
Munchausen syndrome ▪ Family therapy helpful
▪ Feigned symptoms ▪ Separate perpetrator, victim
Munchausen syndrome by proxy ▪ Treat victim for induced illness/injury/
emotional trauma
▪ Purposefully inducing symptoms in another
▪ High level of perceived interest in victim/
victim’s condition (if applicable)
Both types
▪ Limited but highly-relevant medical
knowledge
OSMOSIS.ORG 707
NOTES
NOTES
FEEDING & EATNG DISORDERS

▪ Psychological disorders causing unhealthy ▪ Unhealthy relationship with food
relationship with food, body image (physically, mentally)
▪ Often begin in teens/early adulthood ▪ Distorted view of body, belief that body
weight/appearance crucial for self-worth
CAUSES ▪ Restrictive food intake/compensatory
behaviors (purging/excessive exercise)
▪ Genetic, environmental
▪ High comorbidity with obsessive-
compulsive disorder, depression, anxiety DIAGNOSIS
COMPLICATIONS ▪ See individual disorders
▪ Refeeding syndrome (refeeding →
secretion of insulin → cells take in
electrolytes from already low serum levels TREATMENT
→ even lower serum electrolyte levels →
cardiac arrhythmia/death) PSYCHOTHERAPY
OTHER INTERVENTIONS
▪ Careful weight gain
708 OSMOSIS.ORG
Chapter 95 Feeding & Eating Disorders
ANOREXIA NERVOSA
osms.it/anorexia-nervosa
hair falls out, menstruation stops, difficulty
PATHOLOGY & CAUSES breathing, slow heartbeat, hypotension,
congestive heart failure, edema (especially
▪ Eating disorder characterized by restrictive in feet), bone marrow shuts down (→
food intake (leading to significantly low dampened immune response, low energy
body weight), fear of weight gain, distorted levels, easier bleeding/bruising)
view of body ▪ If purging by vomiting: enamel erosion,
▪ Often begins in teens/early adulthood parotid gland swelling, bad breath, bruised/
calloused knuckles (Russell’s sign), stomach
TYPES tearing, fast heartbeat, depletion of
electrolytes
Atypical anorexia nervosa
▪ Label for individuals with anorexia
symptoms without significantly low body DIAGNOSIS
weight
▪ Restrictive food intake (leading to
Restricting anorexia nervosa significantly low body weight)
▪ Individual loses weight only by via highly ▫ If body weight cannot be described as
restricted food intake/excessive exercise significantly low, diagnosis = atypical
anorexia nervosa
Binge-eating/purging anorexia nervosa
▪ Fear of weight gain
▪ Individual loses weight by purging (e.g.
▪ Distorted view of body
vomiting, use of laxatives/diuretics/enemas)
▪ Restricting type: individual has not
repeatedly binge-eaten or purged over ≤
CAUSES three months (instead, attempts to lose
▪ Genetic (e.g. abnormalities in hunger weight by restricting food intake/exercising
signals), environmental (e.g. peer pressure/ excessively)
forces of popular culture) ▪ Binge-eating/purging anorexia nervosa:
▪ High comorbidity with obsessive- repeated binge-eating/purging over ≤ three
compulsive disorder, depression, anxiety months
Specify severity
COMPLICATIONS ▪ Mild: BMI > 17
▪ Refeeding syndrome, difficulty breathing,
▪ Moderate: BMI 16–17
heart failure, brain damage, suicidal
ideation, death ▪ Severe: BMI 15–16
▪ Extreme: BMI < 15
SIGNS & SYMPTOMS

TREATMENT
▪ Fear of weight gain → restrictive food
behaviors, purging, excessive exercise, PSYCHOTHERAPY
weight checks, food rituals ▪ E.g. cognitive behavioral therapy
▪ Restrictive food intake → electrolyte
abnormalities, vitamin deficiencies, muscle OTHER INTERVENTIONS
loss, low creatinine levels, fatigue → brain ▪ Careful weight gain
damage, weakened bones, dry/scaly skin,
OSMOSIS.ORG 709
BULIMIA NERVOSA
osms.it/bulimia-nervosa
▪ Compensatory behaviors to prevent weight
PATHOLOGY & CAUSES gain, concurrent with binge-eating
▪ Distorted view of body, belief that body
▪ Eating disorder characterized by repeated weight/appearance crucial for self-worth
binge-eating, compensatory behaviors
to prevent weight gain, belief that body Specify severity
weight/appearance crucial for self-worth ▪ Mild: 1–3 compensatory behaviors/week
▪ Compensatory behaviors/”purges”: ▪ Moderate: 4–7 compensatory behaviors/
vomiting, use of laxatives/diuretics/enemas week
▪ Attempts to conceal behaviors ▪ Severe: 8–13 compensatory behaviors/
▪ Often begins in teens/early adulthood week
▪ Extreme: > 14 compensatory behaviors/
CAUSES week
▪ Genetic (e.g. abnormalities in hunger
signals), environmental (e.g. peer pressure/
forces of popular culture)
TREATMENT
▪ High comorbidity with obsessive-
MEDICATIONS
compulsive disorder, depression, anxiety
▪ Antidepressants (e.g. selective serotonin
reuptake inhibitors)
COMPLICATIONS
▪ Refeeding syndrome, diabetes mellitus, fast
PSYCHOTHERAPY
heartbeat, suicidal ideation, death

▪ Careful weight gain
▪ Binge-eating, compensatory behaviors
(usually purposeful vomiting)
▪ Endocrine changes → menstruation stops/
never starts, increased risk of diabetes
mellitus
▪ If purging by vomiting: enamel erosion,
parotid gland swelling, bad breath, bruised/
calloused knuckles (Russell’s sign), stomach
tearing, fast heartbeat, depletion of
electrolytes
DIAGNOSIS
▪ Must occur exclusive of anorexia nervosa
▪ Repeated binge-eating over ≤ three Figure 95.1 Erosion of the enamel of the
months mandibular teeth of an individual with bulimia
▪ Binge-eating classification requires sense nervosa.
of loss of control
710 OSMOSIS.ORG
NOTES
NOTES
NEURODEVELOPMENTAL
DISORDERS

▪ Mental disorders causing difficulties ▪ See individual disorders
in everyday activities/skills (e.g.
communication, learning), occurring over
an extended period, beginning during DIAGNOSIS
development
▪ Often causes social isolation/anxiety → ▪ See individual disorders
depression
TREATMENT
CAUSES
▪ Genetic, environmental ▪ Not curative
COMPLICATIONS
▪ Reduced success in various areas of life
(esp. social, academic)
ATTENTION DEFICIT
HYPERACTIVITY DISORDER (ADHD)
osms.it/ADHD
CAUSES
PATHOLOGY & CAUSES ▪ Genetic, environmental
▪ Associated with neurotransmitter activity
▪ Developmental disorder characterized by
(low amounts of dopamine/norepinephrine)
inattentiveness/hyperactivity/impulsiveness,
lasting for > six months
COMPLICATIONS
TYPES ▪ Reduced success in various areas of life
(esp. social, academic)
▪ Inattentive, hyperactive/impulsive, or both
OSMOSIS.ORG 711
▫ Struggles to stay seated
SIGNS & SYMPTOMS ▫ Restless
▪ Inattentiveness (careless mistakes, not ▫ Struggles to keep quiet
listening, easily distracted) ▫ Likes to keep moving
▪ Hyperactivity/impulsiveness (restlessness) ▫ Talks before others have finished
▪ Developmental delay (e.g. in linguistic/ ▫ Doesn’t like waiting
social/ motor skills) ▫ Interrupts/bothers others
▪ Symptoms for either category must
▫ Persist > six months
DIAGNOSIS ▫ Present < 12 years old
▫ Present in multiple settings
▪ For inattentive diagnosis, ≥ six of following
(≥ five if age > 16) ▫ Affect day-to-day functioning
▫ Makes careless mistakes/overlooks ▫ Not caused by other condition
details
▫ Struggles to stay focused
TREATMENT
▫ Doesn’t appear to listen
▫ Doesn’t follow instructions MEDICATIONS
▫ Has poor organizational skills ▪ Stimulants to slowly release
▫ Avoids mentally-engaging tasks neurotransmitter (e.g. amphetamines =
▫ Often loses things Adderall/ methylphenidate = Ritalin)
▫ Is easily distracted
▫ Is forgetful PSYCHOTHERAPY
▪ For a hyperactive/impulsive diagnosis, ≥ six ▪ Behavioral therapy focused on decreasing
of following (≥ five if age > 16) distractions/improving time management,
▫ Often fidgets organizational skills
AUTISM SPECTRUM
DISORDER (ASD)
osms.it/autism
CAUSES
PATHOLOGY & CAUSES ▪ Genetic, environmental
▪ Developmental disorder characterized

by difficulties with social interaction/ COMPLICATIONS
communication as well as restricted/ ▪ Reduced success in various areas of life
repetitive behaviors, interests, activities (esp. social, academic)
▪ Encompasses autism, Asperger syndrome,
childhood disintegrative disorder, and PDD-
NOS (pervasive developmental disorder not
otherwise specified)
712 OSMOSIS.ORG
Chapter 96 Neurodevelopmental Disorders
▪ Restricted/repetitive behaviors, interests, or

SIGNS & SYMPTOMS activities, with ≥ two of following
▫ Repetition of particular movements/
▪ Difficulties with social interaction,
phrases
communication (doesn’t understand others’
emotions/respond to them, struggles to ▫ Specific routines/rituals, resistant to
make friends) change
▪ Restricted/repetitive nature regarding ▫ Restricted interests (e.g. highly specific
particular behaviors/interests/activities knowledge in a subject)
▫ Highly sensitive to/interested in
surroundings
DIAGNOSIS ▪ Symptoms must have been present in
development, and affect day-to-day
▪ Struggles with social interaction/ functioning
communication ▪ Not caused by other condition
▫ Poor emotional reciprocity (doesn’t
respond to/communicate emotions,
thoughts) TREATMENT
▫ Poor non-verbal communication
(especially poor understanding thereof) PSYCHOTHERAPY
▫ Impaired joint attention (doesn’t share ▪ Educational programs, behavioral therapy
interests with others) tailored to individual
▫ Difficulty in developing/maintaining
relationships
DISRUPTIVE, IMPULSE CONTROL,

AND CONDUCT DISORDERS
osms.it/conduct-disorder
CAUSES
PATHOLOGY & CAUSES ▪ Generally unknown (genetic +
environmental); tend to run in families
▪ Mental disorders characterized by impulsive
behaviors or a general lack of self-control
▪ No underlying motives for resulting MNEMONIC
behaviors Conduct disorders are seen in
▪ Tend to start in childhood and persist into Children
adulthood Antisocial personality disorder
▪ Includes is seen in Adults
▫ Conduct disorders
▫ Intermittent explosive disorder
▫ Oppositional defiant disorder
▫ Pyromania
▫ Kleptomania
OSMOSIS.ORG 713
▪ Persistent, aggressive or harmful behaviors PSYCHOTHERAPHY
▫ May involve aggression or harm towards ▪ Focused on therapy, not medications
other individuals or animals ▪ Cognitive behavioral therapy, social skills
▫ May involve damage to or stealing training, anger management, parent
physical property management training
DIAGNOSIS
▪ Multiple impulsive behaviors observed over
an extended period of time
714 OSMOSIS.ORG
Chapter 96 Neurodevelopmental Disorders
LEARNING DISABILITY
osms.it/learning-disability

▪ Difficulty with learning/developing certain ▪ ≥ one of following for at ≥ six months
skills ▫ Poor reading skills
▫ Poor reading comprehension
TYPES ▫ Difficulties with spelling
▪ Dyslexia: difficulty reading ▫ Other difficulties with written language
▪ Dysgraphia: difficulty writing ▫ Trouble with mathematics
▪ Dyscalculia: difficulty with mathematics ▫ Trouble with mathematical reasoning
▪ Academic skills significantly lower than
CAUSES what would otherwise be expected, as
confirmed by testing
▫ Learning difficulties must begin during
▪ Not due to lack of intelligence/desire to
school years but may not be problematic
learn/education
until later
▪ Not caused by other condition/
COMPLICATIONS environmental factor
▪ Reduced success in various areas of life
(esp. academic)
TREATMENT
▪ Modified approaches to education (e.g. one
▪ Difficulty with learning/developing certain on one tutoring)
skills ▪ Specific techniques/workarounds
▫ Dyslexia: slow, effortful reading/poor dependent on symptoms (e.g. using specific
understanding fonts to alleviate dyslexia)
▫ Dysgraphia: poor spelling, grammar,
handwriting
▫ Dyscalculia: poor arithmetic
▪ Often comorbid with anxiety, depression
OSMOSIS.ORG 715
TOURETTE SYNDROME
osms.it/tourette-syndrome

▪ Developmental disorder characterized by ▪ ≥ two motor tics, ≥ one vocal tic
tics (rapid, repeated, involuntary, often ▪ Must last ≥ one year from first tic
inappropriate movements/vocalizations) ▪ Must start < 18 years old
▫ Simple: short, involving particular body ▪ Not caused by other condition/substance
part
▫ Complex: comprised of multiple
simultaneous tics TREATMENT
TYPES MEDICATIONS
▪ Motor tics: repeating movements of others ▪ Antipsychotics/epilepsy medications (only
(echopraxia), making obscene gestures in severe cases)
(copropraxia) ▪ Botox injections may decrease appearance
▪ Vocal tics: repeating same words/ of facial tics
phrases (echolalia, palilalia), blurting out
inappropriate language (coprolalia) PSYCHOTHERAPY
▪ Cognitive behavioral therapy
CAUSES ▪ Habit reversal training
COMPLICATIONS
▪ Often comorbid with anxiety, depression
SIGNS & SYMPTOMS

▪ Simple/complex tics of either/both types
716 OSMOSIS.ORG
NOTES
NOTES
OBSESSIVE-COMPULSIVE
DISORDERS

▪ Mental disorders characterized by ▪ Presence of obsessions, compulsions
obsessions and/or compulsions ▪ Not caused by other condition/substance
▪ Obsessions: recurrent, intrusive thoughts
(often causing anxiety)
▪ Compulsions: repeated, purposeful, TREATMENT
ritualistic behaviors (often attempts to
alleviate anxiety from obsessions) MEDICATIONS
▪ Obsessions/compulsions give feelings of ▪ Selective serotonin reuptake inhibitors
gratification but affect day-to-day life (SSRIs), other antidepressants
CAUSES PSYCHOTHERAPY
▪ Genetic, often associated with psychiatric ▪ E.g. cognitive behavioral therapy
comorbidities
▪ Can lead to depressive/substance use
disorders
SIGNS & SYMPTOMS

▪ Obsessions, compulsions causing distress
OSMOSIS.ORG 717
BODY DYSMORPHIC DISORDER
osms.it/BDD

▪ Characterized by an obsessive belief that ▪ Not caused by other condition/substance
one’s appearance is flawed
▪ Can cause compulsive behaviors (e.g.
excessive grooming) TREATMENT
▪ No consensus on optimal treatment
CAUSES
▪ Genetic, environmental; linked to issues
with serotonin neurotransmitters MEDICATIONS
▪ SSRIs and other antidepressants
SIGNS & SYMPTOMS PSYCHOTHERAPY

▪ Obsessive belief that one’s appearance is
flawed
▪ Compulsive behaviors in response
BODY FOCUSED REPETITIVE

DISORDERS
osms.it/repetitive-disorders

TYPES ▪ Purposeful skin-picking (excoriation)
or hair-pulling (trichotillomania) with
Excoriation disorder associated damage
▪ Characterized by compulsive skin-picking ▪ Causes distress in other areas of life
▪ Can lead to infection/tissue damage
Trichotillomania
▪ Characterized by compulsive hair-pulling
DIAGNOSIS
▪ Not explained by any other condition/
CAUSES substance
▪ High comorbidity with other mood
disorders; stress-related
▪ Trichotillomania: genetic
718 OSMOSIS.ORG
Chapter 97 Obsessive-Compulsive Disorders
TREATMENT
▪ No consensus on optimal treatment
MEDICATIONS
▪ SSRIs and other antidepressants
PSYCHOTHERAPY
OTHER INTERVENTIONS
▪ Physical prevention (e.g. covering exposed Figure 97.1 An individual with excoriation
skin or hair) syndrome and numerous, small skin sores
caused by constant skin scratching and
picking.
OBSESSIVE–COMPULSIVE
DISORDER
osms.it/OCD

▪ Characterized by obsessions and/or ▪ Obsessions and/or compulsions
compulsions ▫ Must be time consuming (affecting day-
▪ Obsessions, compulsions vary in scope, to-day life)
type ▫ Must not be caused by effects of a
substance or other medical condition
CAUSES ▪ Not explained by other condition/substance
▪ Genetic, environmental; linked to issues
with serotonin neurotransmitters
TREATMENT

▪ SSRIs, other antidepressants
▪ Obsessions (e.g. with germs, unsafeness)
and/or compulsions (e.g. repeated hand- PSYCHOTHERAPY
washing, checking stove burner) ▪ E.g. cognitive behavioral therapy (exposure
▪ Distress affects day-to-day functioning and response therapy)
OSMOSIS.ORG 719
NOTES
NOTES
PERSONALITY DISORDERS:
CLUSTER A

▪ Deviations from cultural expectations → PSYCHOTHERAPY
worsens day-to-day life, relationships. ▪ Focused on supporting individual, not
▪ Paranoid, schizoid, schizotypal personality challenging beliefs
disorders ▫ Challenging beliefs often elicits negative
responses, affects treatment
CAUSES
▪ Linked to schizophrenia (esp. schizotypal)
SIGNS & SYMPTOMS

▪ Unusual behavior
▪ Poor relationships
DIAGNOSIS
▪ Unusual behaviors/traits
Figure 98.1 Illustration depicting different types of cluster A personality disorders.
720 OSMOSIS.ORG
Chapter 98 Personality Disorders: Cluster A
PARANOID PERSONALITY
DISORDER
osms.it/paranoid-personality-disorder

▪ Overlaps with schizotypal personality ▪ ≥ four of following
disorder ▫ Irrational belief that others are harmful/
▪ Generally distrustful of others; demands deceptive
loyalty of family, friends ▫ Doubts trustworthiness of close
▪ Individual harbors grudges if feeling lied to/ individuals
slighted ▫ Reluctance to confide in others, fearing
▪ Suspiciousness damages relationships it may be used against oneself
▫ Sees hidden threats in everyday
CAUSES scenarios
▪ May be genetic, environmental ▫ Holds prolonged grudges
▫ Constantly feels attacked
▫ Suspicion of partner’s fidelity
SIGNS & SYMPTOMS ▫ Not explained by other condition/
substance
▪ Excessive distrust of others
▪ Prolonged grudges, superficial
relationships, isolation TREATMENT
PSYCHOTHERAPY
▪ Aimed at improving social understanding;
can be challenging due to trust issues
Figure 98.2 Illustration depicting thoughts and symptoms of paranoid personality disorder.
OSMOSIS.ORG 721
SCHIZOID PERSONALITY
DISORDER
osms.it/schizoid-personality-disorder

▪ Overlaps with negative symptoms of ▪ ≥ four of following
schizophrenia (blunted emotions/flat affect) ▫ Does not want/enjoy close relationships
▪ Disinterested in, avoids social interaction ▫ Prefers solitude
▫ Not caused by paranoia/social anxiety ▫ Lack of interest in sexual activities
▪ Dislikes physical contact ▫ Hard to please
▫ Lacks close friends
CAUSES ▫ Unbothered by others’ comments
▪ May be genetic, environmental ▫ Flat affect/emotional blunting
▫ Not explained by other condition/
substance
SIGNS & SYMPTOMS
▪ Flat affect/blunted emotions TREATMENT
▪ Lack of desire for intimacy
▪ Chooses solitary activities PSYCHOTHERAPY
▪ Takes pleasure in few activities ▪ Aimed at improving social understanding;
can be challenging due to trust issues
Figure 98.3 Illustration depicting thoughts and symptoms of schizoid personality disorder.
722 OSMOSIS.ORG
Chapter 98 Personality Disorders: Cluster A
SCHIZOTYPAL PERSONALITY
DISORDER
osms.it/schizotypal-personality-disorder

▪ Overlaps with paranoid personality disorder ▪ ≥ five of following
▪ Excessive magical thinking (linking ▫ Ideas of reference
unrelated events) ▫ Magical thinking that changes behavior
▪ Ideas of reference (believes everything ▫ Altered perception
relates to personal destiny) ▫ Unusual thinking/talking
▪ Beliefs cause overconfidence, self-centered ▫ Suspiciousness/paranoia
thinking
▫ Inappropriate/flat affect
▪ Poor at gauging how others perceive them
▫ Eccentric/unusual behavior
▪ Maintain desire for relationships (unlike
▫ Lack of close friends
schizoid)
▫ Social anxiety (related to paranoia, not
▫ schizoiD = “Distant”
fear of judgment)
▫ schizoTypal = “magical Thinking”
CAUSES
▪ May be genetic, environmental TREATMENT
▪ Linked to schizophrenia
PSYCHOTHERAPY
▪ Aimed at improving social understanding;
SIGNS & SYMPTOMS can be challenging due to trust issues
▪ Ideas of reference
▪ Altered perception
▪ Unusual thinking/talking (vague, not
incoherent)
▪ Paranoia/anxiety
Figure 98.4 Illustration depicting thoughts and symptoms of schizotypal personality disorder.
OSMOSIS.ORG 723
NOTES
NOTES
CLUSTER B

▪ Antisocial, borderline, histrionic, narcissistic ▪ Unusual behaviors/traits
personality disorders ▪ Not explained by other condition/substance
▪ Deviations from cultural expectations →
affects day-to-day life, relationships
▪ Linked to depressive, substance use TREATMENT
disorders
MEDICATIONS
▪ Antidepressants
CAUSES
PSYCHOTHERAPY
SIGNS & SYMPTOMS
Figure 99.1 Illustration depicting the four cluster B personality disorders: antisocial personality
disorder, borderline personality disorder, histrionic personality disorder, and narcissistic
personality disorder.
724 OSMOSIS.ORG
Chapter 99 Personality Disorders: Cluster B
ANTISOCIAL PERSONALITY
DISORDER
osms.it/antisocial-personality-disorder

▪ Uses charisma to manipulate others. ▪ ≥ three of following
▪ Disregard for moral values, societal norms, ▫ Does not conform to societal norms
rights of others ▫ Deceitful
▪ Poor impulse control, lacks empathy ▫ Impulsive
▪ Willing to hurt others for own benefit → ▫ Irritable/aggressive
aggressive, unlawful behavior → often ▫ Reckless
given “sociopath”/“psychopath” label
▫ Irresponsible
▪ Associated with substance use disorders,
▫ Unremorseful
overrepresented in prisons
▪ Age > 18, conduct disorder since age < 15
▪ Not explained by other condition
CAUSES
▪ May be genetic, environmental; more
common in biological males MNEMONIC: CC/AA
Conduct disorder/antisocial
personality disorder
SIGNS & SYMPTOMS Conduct disorder is seen in
children
▪ Outwardly normal behavior
Antisocial personality disorder
▪ Hidden hostility, callousness, disregard for is seen in adults
others
TREATMENT
PSYCHOTHERAPY
▪ E.g. self help groups
Figure 99.2 Illustration depicting thoughts and symptoms of antisocial personality disorder.
OSMOSIS.ORG 725
BORDERLINE PERSONALITY
DISORDER
osms.it/borderline-personality-disorder

▪ Unstable moods (intense joy ← → rage) ▪ ≥ five of following
▪ Intense relationships that sour over time ▫ Frantic avoidance of abandonment
▪ “Stable instability” (consistent pattern of ▫ Unstable, intense relationships
instability) ▫ Unstable self-image
▪ Splitting (extreme perspectives: things seen ▫ Self-destructive impulsivity
as completely good/completely bad) ▫ Suicidal/self-harming behavior
▪ Fear of abandonment ▫ Emotional instability
▫ Feeling empty
CAUSES ▫ Anger management issues
▪ May be genetic, environmental ▫ Transient paranoid thinking
▫ Not explained by other condition
SIGNS & SYMPTOMS

TREATMENT
▪ Unstable mood
▪ Fear of abandonment (real/imagined) MEDICATIONS
▪ Splitting ▪ Antipsychotics, antidepressants
▪ Suicidal/self-harming behavior
PSYCHOTHERAPY
▪ E.g. dialectical behavior therapy,
mentalization-based therapy, transference-
focused therapy
Figure 99.3 Illustration depicting thoughts and symptoms of borderline personality disorder.
726 OSMOSIS.ORG
Chapter 99 Personality Disorders: Cluster B
HISTRIONIC PERSONALITY
DISORDER
osms.it/histrionic-personality-disorder

▪ Attention-seeking, excessive emotionality. ▪ ≥ five of following
▪ Manipulative tendencies ▫ Must be center of attention
▪ Superficial relationships ▫ Inappropriate (e.g. provocative)
▪ Shallow, flighty, egocentric interactions
▫ Fast changing, shallow emotions
CAUSES ▫ Uses appearance to draw attention
▪ May be genetic, environmental ▫ Vague speech
▫ Exaggerated manner
▫ Easily affected by others/situations
SIGNS & SYMPTOMS ▫ Mistakes relationships as more intimate
▪ Not explained by other condition
▪ Exaggerated thoughts, feelings (e.g.
tantrums)
▪ Superficial relationships TREATMENT
▪ Excessively seductive behavior
▪ Attention-seeking behavior PSYCHOTHERAPY
▪ Psychoanalytic therapy
Figure 99.4 Illustration depicting thoughts and symptoms of histrionic personality disorder.
OSMOSIS.ORG 727
NARCISSISTIC PERSONALITY
DISORDER
osms.it/narcissistic-personality-disorder

▪ Grandiose self-image ▪ ≥ five of following
▪ Demands special treatment ▫ Grandiose self-image
▪ Thinks ideas are best, should be supported ▫ Fantasies of grandiosity
▪ Fragile self-esteem, lashes out if slighted ▫ Believes they are “special”
▪ Lacks empathy ▫ Seeks admiration
▪ Exploitative of others ▫ Entitled
▪ Only involved in what advances personal ▫ Exploitative
agenda ▫ Thoughtless
▫ Envious/jealous
CAUSES ▫ Arrogant
▪ May be genetic, environmental ▪ Not explained by other condition

▪ Sense of entitlement MEDICATIONS
▪ Arrogant behavior ▪ Lithium, SSRIs, other antidepressants
▪ Vulnerable to criticism
▪ Exploitative of others PSYCHOTHERAPY
▪ Psychoanalytic therapy, group therapy
Figure 99.5 Illustration depicting thoughts and symptoms of narcissistic personality disorder.
728 OSMOSIS.ORG
NOTES
NOTES
CLUSTER C

▪ Avoidant, obsessive-compulsive and ▪ Unusual behaviors/traits
dependent personality disorder ▪ Not explained by other condition/substance
▪ Deviations from cultural expectations →
worsens day-to-day life and relationships
TREATMENT
CAUSES MEDICATIONS
▪ Antidepressants
▪ Linked to anxiety disorders
PSYCHOTHERAPY
SIGNS & SYMPTOMS ▪ E.g. behavioral therapy, group therapy,
assertiveness training
Figure 100.1 Illustration depicting the three cluster C personality disorders: avoidant personality
disorder, obsessive-compulsive personality disorder, and dependent personality disorder.
OSMOSIS.ORG 729
AVOIDANT PERSONALITY
DISORDER
osms.it/avoidant-personality-disorder

▪ Shyness, social inhibition, low self-esteem ▪ ≥ four of following
▪ Wants close relationships, but doesn’t take ▫ Avoids social situations
social risks ▫ Unwillingness to interact
▪ Hypersensitive to rejection, criticism ▫ Limits intimate relationships
▪ Overlap with dependent personality ▫ Preoccupation with rejection, criticism
disorder, others from clusters A, B ▫ Low self-esteem
▫ Fears embarrassment associated with
social risk-taking
SIGNS & SYMPTOMS ▪ Not explained by other condition/substance
▪ Hypersensitivity to rejection, criticism
▪ Resulting timidness TREATMENT
▪ Desire for relationships
MEDICATIONS
▪ Beta blockers, selective serotonin reuptake
inhibitors (SSRIs)
PSYCHOTHERAPY
▪ E.g. group therapy, assertiveness training
Figure 100.2 Illustration depicting thoughts/symptoms typical of avoidant personality disorder.
730 OSMOSIS.ORG
Chapter 100 Personality Disorders: Cluster C
OBSESSIVE-COMPULSIVE
PERSONALITY DISORDER
osms.it/obessive-complusive

▪ Obsessed with orderliness, perfection, ▪ ≥ four of following
need to be in control ▫ Preoccupation with details
▪ Inflexible, easily stressed, inefficient ▫ Disruptive perfectionism
(because of excessive planning) ▫ Work eclipses personal life
▪ Rigid beliefs → “stubborn” label ▫ Rigid, loud beliefs (religious, ethical)
▪ OCD ego-dystonic; OCPD ego-syntonic ▫ Tendency to hoard possessions
▫ Refuses to delegate
▫ Excessively frugal
SIGNS & SYMPTOMS ▫ Stubbornness
▪ Preoccupation with rules, details, perfection ▪ Not explained by other condition/substance
▪ Rigid, inflexible behavior
▪ Lacking sense of humor TREATMENT
▪ Indecisive (for fear of making wrong
decision) MEDICATIONS
PSYCHOTHERAPY
▪ Cognitive behavioral therapy, group therapy
Figure 100.3 Illustration depicting differences between obsessive compulsive disorder and
obsessive compulsive personality disorder.
OSMOSIS.ORG 731
DEPENDENT PERSONALITY
DISORDER
osms.it/dependent-personality-disorder

▪ Excessive fear of separation/rejection ▪ ≥ five of following
▪ Overly dependent on others ▫ Can’t make everyday decisions
▪ Lack self-confidence ▫ Overly dependent on others
▪ Overly indecisive ▫ Scared to disagree with others
▪ Possessive of individuals they depend on ▫ Lack of self-motivation
▪ Overlap with avoidant personality disorder, ▫ Craves approval
others from clusters A, B ▫ Uncomfortable/afraid of being alone
▫ Quick to replace lost relationships
SIGNS & SYMPTOMS
▪ Dependent, submissive TREATMENT
▪ Overly indecisive
▪ Clings onto others MEDICATIONS
PSYCHOTHERAPY
▪ E.g. insight oriented, behavioral, family,
group, assertiveness training
Figure 100.4 Illustration depicting thoughts/symptoms typical of dependent personality disorder.
732 OSMOSIS.ORG
NOTES
NOTES
SCHIZOPHRENIA & PSYCHOTIC
DISORDERS

Negative symptoms
PATHOLOGY & CAUSES ▪ Impairment of normal functioning in
emotional expression, communication,
▪ Mental disorders characterized by purposeful activities
fragmented patterns of thinking
▫ Flat affect (less emotional response)
▪ Feature positive, negative symptoms
▫ Alogia (lack of content in speech)
▫ Avolition (decrease in motivation)
CAUSES
▪ Multiple factors: genetic vulnerability, Cognitive symptoms
physiological/biochemical dysfunction, ▪ Difficulties with memory, learning,
psychosocial stressors understanding
Mood-related symptoms
SIGNS & SYMPTOMS ▪ Sometimes
Positive (psychotic) symptoms

▪ Delusions
DIAGNOSIS
▫ False beliefs remaining even when
▪ Based on symptoms’ presence over certain
opposing evidence presented (e.g.
time period (varies by disorder)
delusions of control/reference)
▪ Affects day-to-day functioning (e.g. social,
▪ Hallucinations
occupational, academic)
▫ Perceptual experiences occurring
without sensory stimuli (e.g. visual,
auditory, tactile hallucinations)
▪ Disorganized speech (e.g. word salad) TREATMENT
▪ Disorganized behavior (e.g. wearing warm
clothes on a hot day; may include catatonic MEDICATIONS
behavior; e.g. resistant movement/
▪ Antipsychotics
unresponsiveness)
PSYCHOTHERAPY
▪ E.g. individual/group therapy, rehabilitation
OSMOSIS.ORG 733
Figure 101.1 Illustration depicting positive, negative, and cognitive syjmptoms.
DELUSIONAL DISORDER
osms.it/delusional-disorder
Non-bizarre delusions
PATHOLOGY & CAUSES ▪ Persecutory
▫ Others conspiring against/following
▪ Mental disorder characterized by persistent
oneself
delusions
▪ Jealous
▪ Delusions may be bizarre (impossible)/non-
bizarre (possible, but still wrong) ▫ One’s partner unfaithful
▪ Delusions remain even when opposing ▪ Of guilt/sin
evidence presented ▫ One wrongly feels guilty
▪ Of reference
▫ One believes messages directed at
SIGNS & SYMPTOMS them/are especially significant
▪ Somatic
Delusions
▫ One’s body is diseased/changed
▪ Of control
▪ Erotomanic
▫ Others control one’s actions/thoughts
▫ Another is in love with oneself
▪ Of thought broadcasting
▪ Grandiose
▫ Others can hear one’s thoughts
▫ One believes they have special talents/
▪ Of thought withdrawal abilities
▫ One’s thoughts are being stolen ▪ Religious
▪ Nihilistic ▫ Involving spiritual aspect
▫ World/self doesn’t exist
734 OSMOSIS.ORG
Chapter 101 Schizophrenia & Psychotic Disorders
DIAGNOSIS TREATMENT
▪ ≥ one delusion, over ≥ one month MEDICATIONS
period, without meeting other criteria for ▪ Antipsychotics, antidepressants
schizophrenia
▫ Hallucinations may occur in some cases
PSYCHOTHERAPY
of delusional disorder
SCHIZOAFFECTIVE DISORDER
osms.it/schizoaffective-disorder

▪ Mental disorder characterized by symptoms ▪ Treat depressive, schizophrenic symptoms
of schizophrenia + a mood disorder separately
MEDICATIONS
SIGNS & SYMPTOMS
▪ Antipsychotics, antidepressants
▪ Positive symptoms
▫ Delusions, hallucinations, disorganized PSYCHOTHERAPY
speech, disorganized behavior ▪ Dialectical behavior therapy, mentalization-
▪ Negative symptoms based therapy, transference-focused
▫ Flat affect, alogia, avolition therapy
▪ Mood-related symptoms
▫ Depression, suicidal ideation
▫ Manic episodes (e.g. euphoria,
grandiosity, hyperactivity)
DIAGNOSIS
▪ ≥ two of following (+ at least one of first
three) + a mood disorder
▫ Delusions
▫ Hallucinations
▫ Disorganized speech
▫ Disorganized or catatonic behavior
▫ Negative symptoms
▪ Delusions/hallucinations last ≥ two weeks
beyond mood episode
OSMOSIS.ORG 735
SCHIZOPHRENIA
osms.it/schizophrenia

▪ Mental disorder characterized by ▪ ≥ two of following (+ at least one of first
fragmented patterns of thinking for > six three), over one month
months ▫ Delusions
▪ Individuals cycle through three phases, ▫ Hallucinations
normally in order ▫ Disorganized speech
▫ Prodromal phase: socially withdrawn; ▫ Disorganized or catatonic behavior
blunted affect
▫ Active phase: severe positive, negative
▪ Other signs of disturbance (with prodromal,
symptoms
residual symptoms) persist ≥ six months
▫ Residual phase: cognitive symptoms;
periods of remission
CAUSES
▪ Success of treatment with dopamine TREATMENT
antagonists suggests link to increased
dopamine levels MEDICATIONS
▪ Genetic; more common in biological males ▪ Antipsychotics
RISK FACTORS PSYCHOTHERAPY

▪ Suicidal ideation → death ▪ E.g. individual/group therapy, rehabilitation
SIGNS & SYMPTOMS

▪ Positive symptoms
▫ Delusions, hallucinations, disorganized
speech, disorganized behavior
▪ Negative symptoms
▫ Flat affect, alogia, avolition
▪ Cognitive symptoms
▫ Difficulties with memory, learning,
understanding
736 OSMOSIS.ORG
Chapter 101 Schizophrenia & Psychotic Disorders
Figure 101.1 Illustration depicting positive, negative, and cognitive syjmptoms.
SCHIZOPHRENIFORM DISORDER
osms.it/schizophreniform-disorder

▪ Mental disorder characterized by ▪ ≥ two of following (+ at least one of first
fragmented patterns of thinking over three), over one month
reduced period (1–6 months) ▫ Delusions
▪ Similar to active phase of schizophrenia ▫ Hallucinations
(severe positive, negative symptoms), ▫ Disorganized speech
minus prodromal phase
▫ Disorganized or catatonic behavior
SIGNS & SYMPTOMS ▪ Other signs of disturbance (with prodromal,
residual symptoms) do not persist ≥ six
▪ Positive symptoms months (if ≥ six months, diagnosis =
schizophrenia)
▫ Delusions, hallucinations, disorganized
speech, disorganized behavior ▪ Affects day-to-day functioning
▪ Negative symptoms ▪ Not caused by other condition/substance
▫ Flat affect, alogia, avolition
▪ Cognitive symptoms TREATMENT
▫ Difficulties with memory, learning,
understanding MEDICATIONS
▪ Antipsychotics
PSYCHOTHERAPY
OSMOSIS.ORG 737
738 OSMOSIS.ORG
NOTES
NOTES
SEXUAL DYSFUNCTION

▪ Sexual function disturbances, often causing ▪ Sexual dysfunction
distress ▫ E.g. ↓/absent orgasmic function, altered
▪ May be lifelong/acquired, mild/moderate/ libido
severe, generalized/situational ▪ Anxiety, distress
Associated factors
▪ Medical diagnoses DIAGNOSIS
▫ E.g. diabetes mellitus, thyroid
dysfunction OTHER DIAGNOSTICS
▪ Relationship issues ▪ Based on specific sexual-disturbance
▫ E.g. impaired interpersonal presence
communication, intimate partner ▫ Causing individual distress
violence ▫ Not better explained/accounted for by
▪ Cultural/religious factors another medical condition, non-sexual
▫ E.g. negative attitudes/prohibitions psychological disorder, interpersonal
regarding sexual activity stress, substance
▪ Individual vulnerabilities
▫ E.g. history of abuse, psychiatric
comorbidity—anxiety, depression,
TREATMENT
intrapsychic conflict, psychosocial
stressors MEDICATIONS
▪ Partner issues ▪ See individual disorders
▫ E.g. mental, physical, sexual health
issues PSYCHOTHERAPY
OSMOSIS.ORG 739
FEMALE SEXUAL INTEREST/
AROUSAL DISORDER
osms.it/female-arousal-disorder
▫ Sexual/erotic thoughts
PATHOLOGY & CAUSES ▫ Sexual activity initiation; partner
initiation receptivity
▪ Disorder characterized by either absence
▫ Pleasure/excitement during ≥ 75% of
or ↓ frequency/intensity of sexual/erotic
sexual encounters
activity or thoughts in biological females
▫ Interest/arousal in sexual/erotic-cue
settings
SIGNS & SYMPTOMS ▫ Genital/non-genital sensation during ≥
75% of sexual encounters
▪ Self-reported ↓/absent sexual pleasure,
genital/nongenital sensations, ↓ vaginal
lubrication → anxiety/distress TREATMENT
MEDICATIONS
DIAGNOSIS ▪ Flibanserin, bupropion
OTHER DIAGNOSTICS PSYCHOTHERAPY

▪ Absence of/↓ frequency/intensity of at
▪ Cognitive-behavioral and/or psychosexual
least three of following; persisting for ≥ six
therapy
months → distress; not better explained by
non-sexual factors
▫ Interest in sexual activity
GENITO-PELVIC PAIN AND/OR

PENETRATION DISORDER
osms.it/genito-pelvic-pain
(gynecological exams, tampon insertion)
PATHOLOGY & CAUSES
Associated factors
▪ Disorder characterized by difficulty with ▪ Medical conditions
intercourse due to vulvovaginal/pelvic pain, ▫ E.g. anatomic anomalies, atrophic
anticipatory fear of pain during penetration, vaginitis, obstetric perineal injury (e.g.
pelvic floor muscle tension during episiotomy)
penetration
▪ Sexually-transmitted disease history
▪ Penetration concerns may be related
▪ Vulvodynia (persistent idiopathic vulvar
to vaginal intercourse/other situations
pain)
740 OSMOSIS.ORG
Chapter 102 Sexual Dysfunction
▪ Low estrogen levels intercourse/penetration attempts

▫ Fear/anxiety in anticipation of, during,
after penetration
SIGNS & SYMPTOMS ▫ Pelvic floor muscle tensing during
penetration attempts
▪ Dyspareunia
▫ Pain described as superficial/deep;
throbbing, shooting, burning TREATMENT
▪ Pelvic floor muscle guarding, reflexive
spasms PSYCHOTHERAPY
▪ Avoidance of intimate sexual activity/ ▪ Cognitive-behavioral and/or psychosexual
recommended gynecological exams therapy
▪ Resulting anxiety/distress
OTHER INTERVENTIONS
▪ Pelvic physical therapy
DIAGNOSIS
▪ Address underlying cause
OTHER DIAGNOSTICS ▫ E.g. ospemifene for dyspareunia
▪ Recurring one/more difficulties persisting (vulvovaginal atrophy)
for ≥ six months → distress, not better
explained by non-sexual factors
▫ Vaginal penetration during intercourse
▫ Vulvovaginal/pelvic pain during
MALE HYPOACTIVE SEXUAL

DESIRE DISORDER
osms.it/male-hypoactive-desire

▪ ↓/non-existent sexual desire, interest, ▪ Persistent, ↓/non-existent sexual desire,
arousal in biological males, persisting for ≥ interest, arousal → anxiety/distress
six months → distress, not better explained
by non-sexual factors
DIAGNOSIS
Associated factors
▪ Medical conditions OTHER DIAGNOSTICS
▫ E.g. impaired erectile/ejaculatory ▪ Absence of/↓ frequency/intensity of sexual
function; diabetes mellitus; desire or sexual/erotic thoughts; persisting
hyperprolactinemia; low testosterone for ≥ six months → distress; not better
levels explained by non-sexual factor
▪ Psychological/social conditions
▫ E.g. depression, stress, substance abuse
OSMOSIS.ORG 741
TREATMENT
MEDICATIONS
▪ Bupropion
PSYCHOTHERAPY
▪ Cognitive-behavioral/psychosexual therapy
ORGASMIC DYSFUNCTION
osms.it/orgasmic-dysfunction
Male
PATHOLOGY & CAUSES
▪ ED: presence of one of following symptoms
experienced during ≥ 75% of sexual
▪ Orgasmic sensation absence, infrequency, activity; persisting for ≥ six months →
↓ intensity, delay distress; not better explained by nonsexual
Female cause
▪ Female orgasmic disorder: difficulty ▫ Difficulty obtaining erection
experiencing normal orgasmic function ▫ Difficulty maintaining erection
▫ ↓ erectile rigidity
Male ▪ Abnormal ejaculation
▪ Erectile dysfunction (ED): persistent ▫ Delayed ejaculation
inability to obtain/maintain erection
▫ Ejaculation infrequency/absence
▪ Abnormal ejaculation (premature, delayed)
▫ Premature ejaculation

▪ Reported impaired orgasmic function
during sexual activity
MEDICATIONS
▪ Sildenafil
▪ Low self-esteem, ↓ sense of sexual self →
depressed affect
PSYCHOTHERAPY
▪ Cognitive-behavioral/psychosexual therapy
DIAGNOSIS
OTHER DIAGNOSTICS
Female
▪ Presence of one of following symptoms
experienced during ≥ 75% of sexual
activity; persisting for ≥ six months →
distress; not better explained by nonsexual
cause
▫ Orgasm delay, infrequency, absence
(specify if orgasm never experienced)
▫ ↓ orgasmic intensity
742 OSMOSIS.ORG
NOTES
NOTES
SLEEP & SLEEP-WAKE
DISORDERS

▪ Mental disorders impacting normal sleep ▪ See individual disorders
CAUSES DIAGNOSIS
▪ Stress, substance use, medical conditions
COMPLICATIONS
▪ Affects quantity/quality of sleep, causing
lack of restorative sleep → irritability, TREATMENT
anxiety, depression
BRUXISM
osms.it/bruxism

▪ Repeated teeth grinding/clenching ▪ Dental abfraction/attrition →
▪ Nocturnal (sleep bruxism) or diurnal (awake hypersensitivity
bruxism) ▪ Tooth fractures/loosening/loss
▪ Awake variant more associated with stress ▪ Tongue biting → crenated/scalloped tongue
▪ Cheek biting → canker sores
CAUSES ▪ Sleep bruxism: jaw pain in morning
▪ Obstructive sleep apnea, misaligned teeth, ▪ Awake bruxism: jaw pain increases
stress, dehydration, medication side effects, throughout day
illicit drugs
DIAGNOSIS
COMPLICATIONS
▪ Can cause temporomandibular joint OTHER DIAGNOSTICS
disorder ▪ Persistent grinding/clenching of teeth
▪ Not caused by other condition
OSMOSIS.ORG 743
TREATMENT
MEDICATIONS
▪ Avoid stimulants, depressants
OTHER INTERVENTIONS
▪ Sleep bruxism: mouth guards, occlusal
splints, dental plates, muscle relaxants, oral
surgery
▪ Awake bruxism: behavior modification
Figure 103.1 Bruxism causes flattening of the ▪ Minimize chewing
occlusal surfaces as seen here.
INSOMNIA
osms.it/insomnia

▪ Repeated difficulty falling asleep, waking OTHER DIAGNOSTICS
up throughout night, waking up too early ▪ Poor sleep quantity/quality, associated with
▪ Affects quantity/quality of sleep, causing ▫ Difficulty falling asleep
lack of restorative sleep ▫ Difficulty maintaining sleep (waking up/
▪ Individuals often self-medicate with being unable to fall back to sleep)
alcohol/benzodiazepines ▫ Waking up too early, being unable to fall
back to sleep
CAUSES ▪ Affects day-to-day functioning
▪ Stress, stimulants, depressants, psychiatric/ ▪ Difficulty with sleep ≥ three nights a week
physical conditions (e.g. pulmonary disease) for ≥ three months
▪ Must have sufficient opportunity to sleep
RISK FACTORS
▪ Heightened cortisol levels/ sensitivity TREATMENT
▪ Reduced levels of estrogen/progesterone
▪ Increases with age MEDICATIONS
▪ Melatonin agonists, non-benzodiazepine
sedatives, occasionally benzodiazepines
SIGNS & SYMPTOMS
▪ Excessive time spent falling asleep OTHER INTERVENTIONS
▪ Repeated waking up during night ▪ Improve sleep hygiene
▪ Daytime sleepiness, fatigue → irritability, ▫ Regular sleep schedule, exercise; reduce
anxiety, depression alcohol, caffeine, smoking (esp. in
evening); avoid daytime naps and going
to sleep hungry
▪ Stimulus control
▫ Use bed only to sleep; remove bright
744 OSMOSIS.ORG
Chapter 103 Sleep & Sleep-Wake Disorders
lights, minimize noise

▪ Don’t force sleep (try for 20 min, then stop)
▪ Behavior therapy
NARCOLEPSY
osms.it/narcolepsy

▪ Recurrent sleep phenomena (e.g. OTHER DIAGNOSTICS
sleepiness/dreaming) during wakefulness ▪ Recurrent feelings of sleepiness during
▪ Associated with a lack of orexin daytime > three times/week ≥ three
(neuropeptide) months
▪ Orexin (A and B) increases state ▪ ≥ one of following
of wakefulness when binding with ▫ Cataplexy
postsynaptic neurons ▫ Hypocretin deficiency
▪ Individuals fall asleep faster and enter REM ▫ Short rapid eye movement (REM) sleep
faster
CAUSES
▪ Damage to orexin-transporting neurons TREATMENT
▫ By autoimmune process/injury)
MEDICATIONS
▪ Selective serotonin reuptake inhibitors
RISK FACTORS (SSRIs), stimulants (e.g. modafinil)
▪ Genetic factors, low levels of histamine,
infections, autoimmune diseases
SIGNS & SYMPTOMS

▪ Daytime sleepiness
▪ Cataplexy (strong emotions cause muscle
weakness)
▪ Hallucinations
▫ Hypnagogic: happen when falling
asleep
▫ Hypnopompic: happen when waking up
▪ Sleep paralysis
▫ Regaining consciousness while body’s
muscles are paralyzed during sleep
OSMOSIS.ORG 745
NIGHT TERROR
osms.it/night-terror

▪ Repeated night/sleep terrors OTHER DIAGNOSTICS
▫ Periods of intense fear occurring at night ▪ Presence of night terrors
▪ Usually occur during deep non-REM sleep ▪ No recollection of imagery during episode
▪ Incomplete/absent memory of episode
CAUSES ▪ Affects day-to-day life
▪ Linked to past traumatic events, sleep ▪ Not caused by other condition/substance
deprivation
TREATMENT
RISK FACTORS
▪ Most common in children (3–8 years old) OTHER INTERVENTIONS
▪ Reduce stress, follow nighttime routine
▪ Often resolves spontaneously (esp. in
SIGNS & SYMPTOMS children)
▪ Night terrors
▫ Begins with sharp scream → individual
sits up → unresponsive → when
awoken, individual confused, has no
memory of episode
NOCTURNAL ENURESIS
osms.it/nocturnal-enuresis

▪ Repeated, uncontrolled passage of urine ▪ Repeated, uncontrolled passage of urine
into bed/clothes, during nighttime into bed/clothes during the nighttime
▪ Often occurs during REM sleep
DIAGNOSIS
CAUSES
▪ Poor bladder control (for physiological OTHER DIAGNOSTICS
developmental reasons)/simply exceeding ▪ Repeated, uncontrolled passage of urine
bladder capacity into bed/clothes during the nighttime
▪ Genetic, environmental ▪ “Clinically significant”
▫ Comorbid with other mental disorders ▫ Occurs ≥ two times/week for ≥ three
▫ More common in biological males consecutive months or affects day-to-
746 OSMOSIS.ORG
Chapter 103 Sleep & Sleep-Wake Disorders
day functioning
▪ ≥ five years old
TREATMENT
▪ Often resolves spontaneously
MEDICATIONS
▪ Desmopressin → reduces urine production
PSYCHOTHERAPY
▪ Behavioral therapy
▫ Esp. bedwetting alarm therapy
▫ Moisture-detecting alarm wakes
individual up during enuresis
OTHER INTERVENTIONS
▪ Bladder program
▫ To build good habits
OSMOSIS.ORG 747
NOTES
NOTES
SUBSTANCE USE &
RELATED DISORDERS

▪ Maladaptive pattern of substance use OTHER DIAGNOSTICS
▪ Dependence: inability to feel “normal” ▪ ≥ two of following
without using substance ▫ Consuming more of a substance than
▪ Addiction: compulsive substance use to intended
achieve reward stimuli, despite negative ▫ Inability to cut down
effects ▫ Use takes up a lot of time
▪ Continued consumption causes tolerance ▫ Cravings
▫ Receptors become less sensitive, ▫ Use affects responsibilities
or neurons have fewer receptors ▫ Using in spite of social problems caused
(downregulation)
▫ Use replaces important activities
▫ Must consume more of substance to feel
▫ Using in physically dangerous situations
desired effect (positive reinforcement)
▫ Using even if it worsens a problem
▪ Stopping use causes withdrawal
▫ Developing tolerance
▫ Body predictively counters consumption
symptoms; no consumption = nothing to ▫ Feeling withdrawal symptoms
counter ▪ Mild = 2–3 symptoms, moderate = 4–5
▫ Must consume more to avoid discomfort symptoms, severe = ≥ 6 symptoms
(negative reinforcement)
▪ Possibly fatal complications (e.g. cancer,
heart attack, overdose)
TREATMENT
MEDICATIONS
SIGNS & SYMPTOMS ▪ To reduce cravings, mimic substance, or
change its effects
▪ Increased tolerance
▪ Upon withdrawal PSYCHOTHERAPY
▫ Anxiety, depression, irritability, fatigue, ▪ E.g. motivational interviewing, cognitive
tremors, palpitations, clammy skin, behavioral therapy, peer-support programs
dilated pupils, sweating, headaches,
difficulty sleeping, vomiting, seizures,
changes in vital signs
748 OSMOSIS.ORG
Chapter 104 Substance Use & Related Disorders
ALCOHOL USE DISORDER

osms.it/alcohol-use-disorder

▪ Inability to feel “normal” without alcohol OTHER DIAGNOSTICS
▪ Alcohol use disorder: maladaptive pattern ▪ ≥ two of following
of alcohol consumption ▫ Consuming more alcohol than intended
▪ Alcohol = depressant ▫ Inability to cut down
▪ Develop alcohol tolerance ▫ Alcohol use takes up a lot of time
▫ GABA, glutamate, dopamine, serotonin ▫ Cravings to use alcohol
receptors become less sensitive/neurons ▫ Alcohol use affects responsibilities
have fewer receptors (downregulation)
▫ Using alcohol despite social problems
▫ Must drink more to feel euphoric
▫ Giving up important activities for alcohol
(positive reinforcement)
▫ Using alcohol in dangerous situations
▪ Withdrawal
▫ Using alcohol even if worsens a problem
▫ Becoming tolerant to alcohol
COMPLICATIONS ▫ Withdrawal symptoms
▪ Heart damage (dilated cardiomyopathy,
▪ Mild = 2–3 symptoms, moderate = 4–5
arrhythmias, stroke), liver damage
symptoms, severe = ≥ six symptoms
(steatosis, steatohepatosis, fibrosis,
cirrhosis), pancreatitis, cancers (mouth,
esophagus, throat, liver, breast), death by TREATMENT
overdose (cardiac, respiratory depression)
MEDICATIONS
SIGNS & SYMPTOMS ▪ Naltrexone (reduces cravings), acamprosate
(stabilizes withdrawal), disulfiram
(increases ethanol sensitivity)
▪ Increased alcohol tolerance
▪ Upon withdrawal
▫ Anxiety, depression, irritability, fatigue, PSYCHOTHERAPY
tremors, palpitations, clammy skin, ▪ Motivational interviewing, cognitive
dilated pupils, sweating, headaches, behavioral therapy, peer-support programs
difficulty sleeping, vomiting, seizures
▫ Delirium tremens (high fever,
hallucinations, intense agitation) MNEMONIC: COAT RACK
Wernicke’s encephalopathy
Confusion
MNEMONIC: CANs of beer Ophthalmoplegia
Wernicke-Korsakoff triad Ataxia
Confusion Thiamine tx.
Ataxia
Nystagmus Korsakoff’s psychosis
Retrograde amnesia
Anterograde amnesia
Confabulation
Korsakoff’s psychosis
OSMOSIS.ORG 749
Figure 104.1 Illustration showing alcohol’s effects on the hypothalamus, pituitary glands, and
medulla.
Figure 104.2 Illustration showing the effects of alcohol withdrawal.
CANNABIS DEPENDENCE
osms.it/cannabis_dependence
▪ Continued cannabis use causes tolerance
PATHOLOGY & CAUSES ▫ Cannabinoid receptors become less
sensitive/neurons have fewer receptors
▪ Inability to feel “normal” without cannabis (downregulation)
▪ Cannabis use disorder: maladaptive pattern ▫ Must consume more to feel euphoric
of cannabis use (positive reinforcement)
▪ Cannabis = depressant/stimulant ▪ Withdrawal
750 OSMOSIS.ORG
COMPLICATIONS ▫ Giving up important activities for

▪ Anxiety, depression, psychotic disorders cannabis
(e.g. schizophrenia), hyper-inflated ▫ Using cannabis in dangerous situations
lungs (when smoking cannabis), chronic ▫ Using cannabis even if it worsens a
bronchitis, respiratory infections, heart problem
attacks, strokes ▫ Becoming tolerant to cannabis
▪ Teenagers at higher risk (developing brain ▫ Withdrawal symptoms
more sensitive)
SIGNS & SYMPTOMS
▪ Increased cannabis tolerance
TREATMENT
▪ Upon withdrawal PSYCHOTHERAPY
▫ Cravings, irritability, anxiety, difficulty ▪ Motivational interviewing
sleeping
DIAGNOSIS
OTHER DIAGNOSTICS
▫ Consuming more cannabis than
intended
▫ Inability to cut down
▫ Cannabis use takes up a lot of time
▫ Cravings to use cannabis
▫ Cannabis use affects responsibilities
▫ Using cannabis despite social problems
Figure 104.3 Illustration showing the stimulant effects of tetrahydrocannabinol (THC) versus the
depressant effects of cannabidiol (CBD). CBD’s properties mean it can be used medicinally in
some cases.
OSMOSIS.ORG 751
Figure 104.4 Illustration showing the potential physical and mental effects of severe cannabis
dependence.
COCAINE DEPENDENCE
osms.it/cocaine-dependence

▪ Inability to feel “normal” without cocaine ▪ Increased cocaine tolerance
▪ Stimulant use disorder: maladaptive ▪ Upon withdrawal
pattern of stimulant use ▫ Depression, anxiety, fatigue, reduced
▪ Cocaine = stimulant concentration, cravings, tiredness,
▪ Continued cocaine use causes tolerance increased appetite, excessive sleeping,
▫ Dopaminergic receptors become less vivid dreaming, suicidal ideation,
sensitive/neurons have fewer receptors nausea, vomiting, hallucinations
(downregulation)
▫ Must consume more to feel euphoric DIAGNOSIS
(positive reinforcement)
▪ Withdrawal OTHER DIAGNOSTICS
COMPLICATIONS ▫ Consuming more stimulants than
▪ Hyperthermia, seizures, stroke, brain intended
hemorrhage, heart attack, death by ▫ Inability to cut down
overdose ▫ Stimulant use takes up a lot of time
▫ Cravings to use stimulants
▫ Stimulant use affects responsibilities
752 OSMOSIS.ORG
▫ Using stimulants despite social

problems
▫ Giving up important activities for
stimulants
▫ Using stimulants in dangerous situations
▫ Using stimulants even if they worsen a
problem
▫ Becoming tolerant to stimulants
▫ Withdrawal symptoms
symptoms, severe ≥ six symptoms
TREATMENT
MEDICATIONS
▪ Modafinil (stimulates, reduces cravings) Figure 104.6 An individual with a perforated
nasal septum secondary to cocaine abuse.
Cocaine causes vasoconstriction and
PSYCHOTHERAPY ischemic necrosis. The hole has been closed
▪ Motivational interviewing, peer-support with a translucent silicone button to provie
programs structural support.
Figure 104.5 Illustration showing the symptoms of cocaine withdrawal.
OSMOSIS.ORG 753
Figure 104.7 Illustration showing some of the recommended approaches to immediate treatment
of someone experiencing a cocaine overdose.
OPIOID DEPENDENCE
osms.it/opioid-dependence

▪ Inability to feel “normal” without opioid use ▪ Increased opioid tolerance
▪ Opioid use disorder: maladaptive pattern of ▪ Upon withdrawal
opioid use ▫ Anxiety, shivering, tremors, yawning,
▪ Opioids = depressants body aches, sweating, runny nose,
▪ Continued opioid use causes tolerance abdominal cramps, diarrhea, vomiting,
▫ Opioid receptors become less sensitive, increased heart rate, blood pressure
/neurons have fewer receptors
(downregulation)
DIAGNOSIS
▫ Must use more to feel euphoric (positive
reinforcement)
OTHER DIAGNOSTICS
▪ Withdrawal
▫ Consuming more opioids than intended
COMPLICATIONS ▫ Inability to cut down
▪ Disease transmission from shared needles, ▫ Opioid use takes up a lot of time
death by overdose (cardiac, respiratory
▫ Cravings to use opioids
depression)
▫ Opioid use affects responsibilities
754 OSMOSIS.ORG
▫ Using opioids despite social problems

▫ Giving up important activities for opioids
TREATMENT
▫ Using opioids in dangerous situations MEDICATIONS
▫ Using opioids even if they worsen a ▪ Naloxone (blocks opioids), naltrexone,
problem methadone (opioid for maintenance/
▫ Becoming tolerant to opioids tapering consumption), buprenorphine
▪ Mild = 2–3 symptoms, moderate = 4–5 PSYCHOTHERAPY
▪ Motivational interviewing, peer-support
programs, cognitive behavioral therapy
Figure 104.8 Illustration with examples of endogenous and exogenous opioids.
Figure 104.9 Illustration showing the ways opioids are most commonly self-administered by
people with opioid use disorder.
OSMOSIS.ORG 755
TOBACCO DEPENDENCE
osms.it/tobacco-dependence
▫ Using tobacco in dangerous situations
PATHOLOGY & CAUSES ▫ Using tobacco even if it worsens a
problem
▪ Inability to feel “normal” without tobacco
▫ Becoming tolerant to tobacco
use (nicotine)
▪ Tobacco use disorder: maladaptive pattern
of tobacco use ▪ Mild = 2–3 symptoms, moderate = 4–5
▪ Tobacco = depressant, stimulant
▪ Continued tobacco use causes tolerance
▫ Nicotinic receptors become less
sensitive/neurons have fewer receptors
(downregulation)
▫ Must use more to feel euphoric (positive
reinforcement)
▪ Withdrawal
COMPLICATIONS
▪ Heart attack, stroke, peripheral vascular
disease, pulmonary disease, cancer (mouth,
throat, lungs, bladder, pancreas, uterus)
SIGNS & SYMPTOMS

▪ Increased tobacco tolerance
▪ Upon withdrawal
▫ Cravings, irritability, anxiety, anger, poor
concentration, restlessness, impatience,
increased appetite, weight gain,
insomnia
DIAGNOSIS Figure 104.10 An individual with tar stained

fingers caused by tobacco smoking.
OTHER DIAGNOSTICS
▫ Consuming more tobacco than intended TREATMENT
▫ Inability to cut down
▫ Tobacco use takes up a lot of time
MEDICATIONS
▪ Nicotine replacement therapies (gum,
▫ Cravings to use tobacco
sprays, patches) to taper dose
▫ Tobacco use affects responsibilities
▪ Bupropion (antidepressant; reduces
▫ Using tobacco despite social problems cravings, withdrawal symptoms),
▫ Giving up important activities for varenicline (reduces cravings, enjoyment of
tobacco tobacco)
756 OSMOSIS.ORG
PSYCHOTHERAPY
▪ Motivational interviewing, peer-support
programs
OTHER INTERVENTIONS
▪ Switch to electronic cigarettes
Figure 104.11 Illustration showing the effects of nicotine on the brain after binding to nicotinic
receptors.
Figure 104.12 Illustration showing the half-life of nicotine, which can lead to chain smoking.
OSMOSIS.ORG 757
758 OSMOSIS.ORG
NOTES
NOTES
TRAUMA– & ABUSE–RELATED
DISORDERS

▪ Mental disorders caused by/associated with ▪ See individual disorders
past traumatic/stressful event
▪ Abuse: intentional mistreatment of others;
may be directed at anyone; often features TREATMENT
children or the elderly
▫ Increases risk of the target developing MEDICATIONS
a mental disorder; generally results in ▪ See individual disorders
depression or aggressiveness; may
incite posttraumatic stress disorder PSYCHOTHERAPY
▪ Psychological symptoms → behavioral ▪ Abuse-related: cognitive behavioral
changes therapy
▪ Individuals might self-medicate with
substance use
OTHER INTERVENTIONS
▪ Manage substance use
SIGNS & SYMPTOMS
▪ Anxiety/fear associated with traumatic/
stressful stimuli
▪ Reduced pleasure, self-acceptance;
depression; anger, aggressiveness;
dissociation (detachment from present in
cognitive/sensory capacity); etc.
PHYSICAL & SEXUAL ABUSE

osms.it/physical_and_sexual_abuse
COMPLICATIONS
PATHOLOGY & CAUSES ▪ Increases risk of the target developing
a mental disorder; generally results in
▪ Intentional injuring of others, which may depression or aggressiveness; may incite
include hitting, burning, or even poisoning posttraumatic stress disorder
▪ Sexual abuse: forced or otherwise ▪ Severe abuse may cause prolonged or
inappropriate (e.g. in age difference) sexual irreversible damage to the body
behavior with others
OSMOSIS.ORG 759
▪ Bruising, cuts, sores, burns or rashes; MEDICATIONS
fractured or broken bones; damage to ▪ Sexual abuse: may require emergency
internal organs; failure to thrive contraceptives or STD prophylactics
▪ Anxiety related to the abuse
▪ Dissociative reactions PSYCHOTHERAPY
▪ Depression ▪ Focus on screening and prevention;
▪ Aggressiveness may include symptomatic treatment or
▪ PTSD psychotherapy (esp. cognitive behavioral
▪ Sexual abuse therapy)
▫ Fear of or anxiety towards sexual
activity OTHER INTERVENTIONS
▫ Increased risk of suicide ▪ Medical intervention, as needed
▫ If appropriate, physical symptoms (e.g. ▪ Referral to protective services for legal/
physical trauma, STIs, UTIs) social support
DIAGNOSIS
OTHER DIAGNOSTICS
▪ Based on individual history and presence of
above symptoms
POSTTRAUMATIC STRESS
DISORDER (PTSD)
osms.it/PTSD

▪ Memory of past traumatic event → ▪ Psychological
recurrent mental, physical stress ▫ Nightmares, flashbacks, intrusive
▫ E.g. car crashes; sexual abuse; military thoughts
service; natural disasters ▪ Behavioral
▪ Psychological symptoms → behavioral ▫ Avoidance of situations/environments,
changes hypervigilance, hyperarousal → trouble
▪ Individuals might self-medicate with sleeping, general irritability, emotional
substance use outbursts
▪ Neurological factors ▪ Children less likely to show distress; often
▫ Dysfunctions in hypothalamic-pituitary- use play to express memories
adrenal axis/endogenous opioid system;
deficits in arousal, sleep regulation;
family history
760 OSMOSIS.ORG
Chapter 105 Trauma- and Abuse-Related Disorders
▪ Disturbance cannot be better explained by

DIAGNOSIS another condition/substance
OTHER DIAGNOSTICS
▪ Exposure to traumatic event TREATMENT
▪ Intrusive symptoms
▫ Recurrent, distressful memories, dreams MEDICATIONS
▫ Dissociative reactions ▪ Antidepressants, esp. selective serotonin
▫ Distress/physiological reactions in reuptake inhibitors (SSRIs); anti-anxiety;
response to stimuli sleep aids
▪ Avoidance of associated stimuli,
psychological (e.g. memories)/tangible (e.g. PSYCHOTHERAPY
places) ▪ Exposure, group therapy
▪ Negative changes in thoughts, feelings
▪ Increased sensitivity to event, associated OTHER INTERVENTIONS
stimuli
▪ Manage substance use
▪ Disturbance lasts > one month → distress
in other areas of life
SOMATIC SYMPTOM DISORDER

osms.it/somatic-symptom-disorder

▪ Extended periods of unexplainable physical OTHER DIAGNOSTICS
symptoms ▪ ≥ one somatic symptoms → distress in
▪ Individuals not faking symptoms (unlike other areas of life, last > six months
factitious disorder) ▪ Changes in behavior/thinking, related to
▪ Thinking about physical symptoms → somatic symptoms
cognitive symptoms (e.g. stress/anxiety) ▫ Excessive thought about severity of
▪ Cause unknown; affected individuals symptoms
sensitive to physical changes → everyday ▫ Anxiety about symptoms/health
experiences misinterpreted ▫ Devotion of time/energy to symptoms/
▪ High comorbidity with depressive, anxiety health
disorders ▪ Severity determined by changes in
behavior/thinking
▫ Mild = one change
SIGNS & SYMPTOMS
▫ Moderate = ≥ two changes
▪ Somatic symptoms (e.g. pain, sexual, ▫ Severe = ≥ two changes + multiple
gastrointestinal problems); change over physical symptoms/one severe symptom
time
▪ Cognitive symptoms (e.g. worry, anxiety)
TREATMENT
PSYCHOTHERAPY
▪ Improve cognitive symptoms (e.g.
cognitive-behavioral/group therapy)
OSMOSIS.ORG 761
NOTES
NOTES
ACUTE & CHRONIC
KIDNEY DISEASE

▪ Decline of kidney function DIAGNOSTIC IMAGING
Ultrasound, CT scan
TYPES ▪ Obstructive renal failure
Acute kidney injury (AKI)
▪ Decline over < three months LAB RESULTS
▪ Divided by cause ▪ Urine electrolytes, osmolality, cellular casts,
▫ Prerenal azotemia: kidney proteinuria, hematuria
hypoperfusion ▪ Acid-base status, electrolytes, protein
▫ Intrarenal azotemia: injury within kidney levels
▫ Postrenal azotemia: obstructed urine ▪ Blood urea nitrogen (BUN)-to-creatinine
outflow distally ratio (BUN:Cr)
▫ Prerenal azotemia: > 20:1
Chronic kidney disease (CKD) ▫ Renal azotemia: < 15:1
▪ Decline over > three months ▫ Postrenal azotemia: > 15:1; over time,
▪ Any etiology causing decreased kidney < 15:1
function
TREATMENT
SIGNS & SYMPTOMS
MEDICATIONS
▪ Electrolyte imbalance (e.g. ↑ K+, ↓ Na+, ▪ Correct acid-base status, electrolytes,
↓ Ca2+) volemia
▪ Decreased waste elimination (azotemia/
uremia)
OTHER INTERVENTIONS
▪ Fluid retention
▪ Hemodialysis (not used for prerenal
azotemia)
762 OSMOSIS.ORG
Chapter 106 Acute & Chronic Kidney Disease
CHRONIC KIDNEY DISEASE

osms.it/chronic-kidney-disease
▪ Less common
PATHOLOGY & CAUSES ▫ Glomerulonephritis (e.g. lupus nephritis);
rheumatoid arthritis; HIV nephropathy;
▪ Gradual decline of kidney function over ≥ long term medication use (e.g. NSAIDs);
three months polycystic kidney disease
▪ Affects all physiologic roles of kidney
▪ ↓ Glomerular filtration rate (GFR) → ↓
waste products excretion → build-up of
RISK FACTORS
nitrogenous compounds → ↑ BUN, Cr, urea ▪ Family history
(azotemia/uremia) ▪ Reflux nephropathy
▫ Inflammation (e.g uremic pericarditis) ▪ Other congenital kidney disorders
▫ Interferes with neurotransmitter
metabolism → encephalopathy COMPLICATIONS
▫ Platelet dysfunction → bleeding (platelet ▪ Uremic fibrinous pericarditis, uremic
adhesion, aggregation) gastroenteritis
▫ Excess urea through eccrine glands → ▪ Renal osteodystrophy → increased risk of
crystallizes on skin → uremic frost skeletal fractures; caused by secondary
▪ ↓ reabsorption, secretion → impaired hyperparathyroidism (compensatory
electrolyte homeostasis parathyroid hormone release due to lack of
▫ ↑ K+, ↓ Na+, ↓ HCO3-, ↓ Ca2+ vitamin D)
▪ Impaired hormone secretion ▪ Renovascular hypertension
▫ ↓ erythropoietin → anemia ▫ Development/exacerbation of
▫ ↓ GFR → ↑ renin → hypertension hypertension due to increased RAAS
▫ ↓ vitamin D activation → ↓ intestinal ▪ Congestive heart failure
absorption of Ca2+ → hypocalcemia ▪ Coma, death by severe encephalopathy
CAUSES
▪ Hypertension (most common)
SIGNS & SYMPTOMS
▫ ↑ blood pressure → hypertrophy/
sclerosis of renal arteries →
▪ Less advanced stages usually
hypoperfusion, ischemic injury →
asymptomatic
growth factor secretion by macrophages
→ mesangial cells regress to ▪ Oliguria
mesoangioblasts, secrete extracellular ▫ Urine output < 400mL in 24 hour
matrix → glomerulosclerosis, loss of ▪ ↑ fluid volume
function ▫ Peripheral edema
▪ Diabetic nephropathy ▪ Azotemia/uremia
▫ ↑ blood glucose → non-enzymatic ▪ Skin
glycosylation of efferent arterioles → ▫ Uremic pruritus, excoriations
initial hyperinflation → mesangial cells
▪ GI tract
secrete structural matrix → nodular
glomerulosclerosis, loss of function ▫ Ulcerations, bleeding, diarrhea, vomiting
▪ Encephalopathy
▫ Fatigue, somnolence, appetite loss,
asterixis, confusion
OSMOSIS.ORG 763
▪ ↑ K+ (> 5.5mEq/L) increased GFR (> 90mL/min/1.73m2)
▫ Cardiac arrhythmias ▫ Stage II: mild reduction in GFR (60–
▪ Anemia 89mL/min/1.73m2)
▫ Low erythropoietin production by ▫ Stage IIIa: moderate reduction in GFR
kidneys (45–59mL/min/1.73m2)
▫ Stage IIIb: moderate reduction in GFR
(30–44mL/min/1.73m2)
DIAGNOSIS ▫ Stage IV: severe reduction in GFR
(15–29mL/min/1.73m2)
DIAGNOSTIC IMAGING ▫ Stage V: end stage kidney failure (GFR <
15mL/min/1.73m2 or dialysis)
Ultrasound
▪ Etiological investigation; polycystic kidney
disease (PCKD), renal artery stenosis, TREATMENT
hydronephrosis, etc.; decreased kidney
volume MEDICATIONS
▪ ACE inhibitors, angiotensin II receptor
LAB RESULTS antagonists (ARBs)
▪ Iron deficiency anemia
▪ Metabolic acidosis, ↑ PO3-, ↑ K+, ↓ Na+, ↓ SURGERY
HCO3-, ↓ Ca2+ ▪ Kidney transplantation
▪ Biopsy ▫ Severe (e.g. Stage V CKI)
▫ Glomerulosclerosis/interstitial fibrosis
OTHER INTERVENTIONS
OTHER DIAGNOSTICS ▪ Dialysis
▪ Rise of serum Cr over months/years ▫ Severe (e.g. Stage V CKI)
▪ Increased blood urea nitrogen:creatinine ▪ Hemodialysis
(BUN:Cr)
▫ Remove excess waste products, fluids
▪ Cr clearance to assess glomerular filtration via artificial kidney (dialyzer)
rate (GFR)
▫ Stage I: kidney damage with normal/
▫ Remove excess waste products, fluids
via peritoneal membrane
POSTRENAL AZOTEMIA
osms.it/postrenal-azotemia
↓ GFR
PATHOLOGY & CAUSES
▪ Acute kidney injury due to obstructed CAUSES
urine outflow distally → ↑ nitrogenous ▪ Compression
compounds in blood ▫ Ureters (e.g. intra abdominal tumors);
▪ Obstruction of urine outflow → reversal urethra, benign prostatic hyperplasia
of Starling forces → pressure backs up (BPH)
to kidneys, tubules → reduced pressure ▪ Obstruction
gradient between arterioles, tubules → ▫ Ureters; urethra, kidney stones
764 OSMOSIS.ORG
▪ Congenital abnormalities CT scan

▫ Vesicoureteral reflux ▪ Confirmation
▪ Hyperdense foci; dilation of ureter
COMPLICATIONS
▪ Hydronephrosis; urinary tract infection LAB RESULTS
(UTI), obstruction, urosepsis ▪ Urinalysis
▫ UNa+ < 20 mEq/L; over time > 40mEq/L
SIGNS & SYMPTOMS ▫ FENa > 1%; severe: FENa > 2%
▫ Uoms > 500mOsm/kg; over time
▪ Normotensive/hypertensive 350mOsm/kg
▪ Renal colic
▫ Acute complete obstruction, dysuria, OTHER DIAGNOSTICS
urgency, overflow incontinence, ▪ Physical exam
frequent urination ▫ Palpable bladder
▪ Abdominal distention ▪ Digital rectal examination
▫ Urinary retention ▫ Enlarged prostate
▪ Costovertebral angle tenderness
▪ Pain
▫ Bladder distention, secondary infection,
TREATMENT
stones, masses
SURGERY
▪ Decreased urine output, hematuria
▪ Percutaneous nephrostomy, lithotripsy
▫ Stones
▫ Obstruction by stones

▪ Short term hemodialysis (severe)
DIAGNOSTIC IMAGING ▪ Placement of Foley catheter, ureteral stent/
Renal ultrasound nephrostomy
▪ Detect obstruction; hydronephrosis, stones
> 3mm
▫ Echogenic foci, acoustic shadowing
OSMOSIS.ORG 765
PRERENAL AZOTEMIA
osms.it/prerenal-azotemia
▪ Dehydration: dry mucous membranes, skin
PATHOLOGY & CAUSES turgor loss, thirst, xerostomia (dry mouth),
tachycardia, orthostatic hypotension
▪ Acute renal injury ▪ Congestive heart failure: jugular vein
▫ Kidney hypoperfusion → increased distention, edema
nitrogenous compounds in blood (BUN, ▪ Underlying liver failure: ascites
Cr)
▪ Decreased blood flow to kidney →
↓ glomerular filtration rate (GFR), DIAGNOSIS
accumulation of waste products (BUN, Cr)
in blood → azotemia DIAGNOSTIC IMAGING
▪ ↓ GFR → renin–angiotensin–aldosterone
system (RAAS) activation → aldosterone Doppler renal ultrasound
secretion → Na+, water retention → urea ▪ Renal artery stenosis/embolus
follows Na+ → ↑ BUN:Cr (> 20:1)
LAB RESULTS
CAUSES ▪ Absolute fluid loss
▪ Absolute fluid loss ▫ ↑ Na+, ↑ Ca2+, ↑ hematocrit, ↑ HCO3, ↑
▫ Burns, dehydration, long term vomiting, protein/albumin
diarrhea, hemorrhage ▪ Relative fluid loss
▪ Relative fluid loss ▫ ↓ Na+, ↓ protein/albumin
▫ Congestive heart failure, distributive ▪ Urine sodium (UNa+) < 20mEq/L
shock ▪ Fraction of sodium excreted to sodium
▪ Renal artery stenosis/embolus filtered (FENa) < 1%
▪ Liver failure ▪ Urine osmolality (Uoms) > 500mOsm/kg
▫ Portal hypertension → systemic,
splanchnic vasodilation → ↓ effective
OTHER DIAGNOSTICS
blood volume, ↑ sequestration in
peritoneal cavity (ascites) → relative ▪ BUN:Cr > 20:1
hypovolemia → ↓ renal perfusion
TREATMENT
RISK FACTORS
▪ Gastrointestinal (GI) tract disorders (e.g. MEDICATIONS
diarrhea, vomiting) ▪ Diuretics, angiotensin-converting enzyme
▪ Liver disease (ACE) inhibitors, beta blockers, nitrates,
▪ Congestive heart failure positive inotropic agents
▫ Congestive heart failure

▪ Oliguria: urine output < 400mL in 24 hours ▪ Correct fluid, electrolyte imbalances with IV
fluids
▪ Azotemia: confusion, lethargy, asterixis,
appetite loss, nausea, bleeding (platelet ▫ Crystalloid solutions: isotonic solutions
dysfunction), uremic frost containing electrolytes, small organic
molecules (e.g. isotonic saline, Ringer’s
766 OSMOSIS.ORG
lactate); most common

▫ Colloid solutions: hypertonic solutions
containing larger molecules; albumin,
hyperoncotic starch (e.g. glucose,
dextrose)
▫ Blood transfusion: in case of
hemorrhage

uremic frost in an individual with azotemia.
RENAL AZOTEMIA
osms.it/renal-azotemia
granular casts in urine
PATHOLOGY & CAUSES
▫ Ischemic tubular necrosis: caused by
▪ Acute renal injury caused by problem prerenal issues (hypoperfusion due to
within kidney → increased nitrogenous absolute, relative fluid loss)
compounds in blood ▫ Nephrotoxic tubular necrosis: caused
▪ Kidney injury → ↓ GFR → accumulation of by nephrotoxins, like organic solvents
waste products in blood → azotemia (carbon tetrachloride), heavy metal
poisoning (lead, mercury), ethylene
glycol, radiocontrast agents, certain
CAUSES medications (aminoglycosides)
Glomerular injury ▪ Shedded tubular cells, granular casts
obstruct tubule → ↑ tubular pressure
▪ Glomerulonephritis
→ reduces pressure gradient between
▫ Inflammation of glomeruli (e.g. arterioles, tubules → ↓ GFR → oliguria
poststreptococcal glomerulonephritis,
Goodpasture’s syndrome, Wegener’s Interstitial injury
granulomatosis, IgA nephropathy) ▪ Acute interstitial nephritis
▫ Deposition of immune complexes on ▫ Caused by Type I, IV hypersensitivity
glomerular basement membrane → due to nonsteroidal anti-inflammatory
activation of complement system → drugs (NSAIDs)/penicillin/diuretics
chemoattraction of macrophages, ▫ Inflammation of interstitium → renal
neutrophils → mediator release → papillary necrosis → hematuria
inflammation, podocyte damage →
▪ Bilateral pyelonephritis
protein, blood cell leakage → reduces
pressure gradient between arterioles, Glomerular endotheliopathy
tubules → ↓ GFR, oliguria
▪ Thrombotic microangiopathy, hyaline
Tubular injury arteriolosclerosis, scleroderma
▪ Acute tubular necrosis: damage to tubular
epithelial cells; shedding of tubular cells,
OSMOSIS.ORG 767
RISK FACTORS OTHER DIAGNOSTICS
▪ Family history of congenital/systemic ▪ BUN:Cr < 15:1
diseases (e.g. diabetes, hypertension, ▪ Interstitial nephritis
systemic lupus erythematosus, hepatitis ▫ Hypersensitivity, acute interstitial
B, C) nephritis
▫ ↑ IgE: Type I
SIGNS & SYMPTOMS ▫ Skin test: T-cell mediated Type IV
▫ Eosinophilia
▪ Oliguria, hematuria, flank pain, livedo
reticularis (lace-like purplish skin
discoloration)
TREATMENT
▪ Fluid build-up
MEDICATIONS
▫ Hypertension, hypertensive retinopathy,
▪ Glomerulonephritis; treat according to
edema
etiology (e.g. corticosteroids)
▪ Azotemia
▪ Pyelonephritis
▫ Confusion, lethargy, asterixis, loss of
▫ Antibiotics
appetite, nausea, bleeding (platelet
dysfunction)
▪ Hypersensitivity OTHER INTERVENTIONS
▫ Rash, fever, joint swelling/tenderness ▪ Avoid nephrotoxins/allergens
▪ Glomerulonephritis; treat according to
etiology (e.g. plasmapheresis)
DIAGNOSIS ▪ Hemodialysis
LAB RESULTS
▪ UNa+ > 40mEq/L
▪ FENa < 2%
▪ Uoms > 350mOsm/kg
▪ Erythrocyte, leukocyte, epithelial casts:
glomerulonephritis
▪ Pigmented muddy brown granular/tubular
epithelial cells cylinders: acute tubular
necrosis
768 OSMOSIS.ORG
NOTES
NOTES
BLADDER & URETHRAL CONGENITAL
DISORDERS

▪ Congenital abnormalities in bladder, urethra DIAGNOSTIC IMAGING
▪ Benign/kidney failure/systemic involvement
Prenatal ultrasound
▪ Diagnosis difficult
CAUSES
▪ Interferences in fetal development OTHER DIAGNOSTICS
▪ Bladder exstrophy, hypospadias,
epispadias: visible at birth
SIGNS & SYMPTOMS
▪ May be asymptomatic until complications TREATMENT
develop
SURGERY
BLADDER EXSTROPHY
osms.it/bladder-exstrophy
the mesenchymal tissue towards midline →
PATHOLOGY & CAUSES rupture of cloacal membrane → herniation
of lower abdominal components through
▪ Congenital disorder, inside-out bladder the lower abdominal wall surface
protruding out of abdomen
▪ Part of the exstrophy-epispadias complex
(EEC) that includes epispadias and cloacal
RISK FACTORS
exstrophy ▪ Genetic predisposition
▪ Bladder fails to fully form anteriorly, pushed ▪ Biological males > biological females
through front anterior abdomen wall ▪ Firstborn > subsequent births
▪ Infants born to white parents
CAUSES
▪ Occurs during embryological development: COMPLICATIONS
overdevelopment of cloacal membrane ▪ Urinary and/or fecal incontinence, UTIs,
disrupts development of the lower abnormal gait, hip dysplasia, rectal
abdominal wall → prevents migration of prolapse; inguinal hernia, uterine prolapse
OSMOSIS.ORG 769
SIGNS & SYMPTOMS
▪ Observable changes in pelvis, pelvic floor,
genitalia
▫ Exposed bladder and urethra
▫ Low-set umbilicus
▫ Abnormalities of the pelvic bone,
vertebral column, and spinal cord
▫ Flattened puborectal sling, anus
anteriorly displaced
▫ Biological males: epispadias, absent Figure 107.1 A newborn baby with a severe
dorsal foreskin, open prostate, case of bladder exstrophy. The genitals are
shortened penis also grossly irregular.
▫ Biological females: vagina wider,
shorter, more vertically oriented;
displaced, narrowed vaginal orifice; bifid
clitoris; divergent labia TREATMENT
▫ Epispadias
SURGERY
▪ Performed within first weeks of life
DIAGNOSIS ▪ Staged surgeries required over months/
years
DIAGNOSTIC IMAGING
CT scan
▪ CT scan detects skeletal abnormalities
Ultrasound and MRI

▪ Often made by prenatal ultrasound, can be
confirmed by MRI
OTHER DIAGNOSTICS
▪ Clinically recognizable at time of delivery
Figure 107.2 Illustration of the bladder pushing through the symphysis pubis and abdominal wall
during bladder exstrophy.
770 OSMOSIS.ORG
Chapter 107 Bladder & Urethral Congenital Disorders
Figure 107.3 A plain pelvic radiograph demonstrating a wide symphysis pubis in a case of
bladder exstrophy.
HYDRONEPHROSIS
osms.it/hydronephrosis
CAUSES
PATHOLOGY & CAUSES ▪ Fetus: antenatal hydronephrosis
▫ Often unknown, may disappear on own
▪ Dilation of renal pelvis, calyces associated
with kidney atrophy ▫ Congenital malformation: ureteropelvic
junction obstruction, vesicoureteral reflux
▪ Severe, long-standing hydronephrosis →
kidney failure ▪ Children:
▪ Urinary tract obstruction/compression → ▫ Congenital malformation: ureterocele,
build up of urinary pressure → progressive posterior urethral valves
dilation ▪ Adults:
▪ Dilation starts at blockage, continues up ▫ Acquired disease: kidney stones
towards kidneys (most common cause), benign
▫ Hydroureter: dilation of ureter prostatic hyperplasia, blood clot,
contiguous malignant diseases
▫ Hydronephrosis/hydroureteronephrosis:
(prostate/bladder/cervix cancer,
dilation of ureter, renal pelvis, calyces
retroperitoneal lymphoma), contiguous
▪ Grading inflammation (prostatitis, ureteritis,
▫ 0: no dilation urethritis, retroperitoneal fibrosis), tissue
▫ I: dilation of renal pelvis scarring from injury/surgery, uterus
▫ II: dilation of renal pelvis, calyces enlargement during pregnancy
▫ III: moderate dilation of renal pelvis,
calyces; mild cortical thinning, flattening
of papillae
▫ IV: severe renal dilation; cortical thinning
OSMOSIS.ORG 771
MNEMONIC: SIP BaN
Causes of acquired
TREATMENT
hydronephrosis
SURGERY
Stones
▪ Restore urine flow: upper blockage
Inflammation
▫ Acute: nephrostomy tube
Prostate hypertrophy
▫ Chronic: ureteric stent/pyeloplasty
Baby (pregnancy) / Blood clot
Neoplasm
OTHER INTERVENTIONS
▪ Restore urine flow: lower blockage
▫ Urinary or suprapubic catheter
SIGNS & SYMPTOMS
▪ Acute with sudden onset: intense pain in
flank, called Dietl’s crisis
▪ Nausea, vomiting
DIAGNOSIS
DIAGNOSTIC IMAGING
▪ Dilation of renal calyces
▪ Increased anteroposterior diameter
▪ Dilated ureter, if obstruction is distal
Prenatal ultrasound
▪ Oligohydramnios if bilateral obstruction
Intravenous (IV) urography/pyelography Figure 107.4 An abdominal CT scan in

▪ Demonstrates distal obstruction the coronal plane demonstrating severe
hydronephrosis of the left kidney.
772 OSMOSIS.ORG
POSTERIOR URETHRAL VALVE

osms.it/posterior-urethral-valve
Antenatal ultrasound
PATHOLOGY & CAUSES ▪ Hydronephrosis (10% may be normal)
▪ Trabeculated and thick-walled bladder with
▪ Congenital disorder, posterior urethra
elongation and dilation of posterior urethra
obstructed by membranous folds/tissue flap
▪ Valve may be seen as echogenic line
▪ Most common cause of bladder outlet
obstruction in infants who are biologically Voiding cystourethrogram (VCUG)
male
▪ Dilation and elongation of posterior urethra
▪ Obstruction increases bladder pressure
▪ Vesicoureteral reflux (in half of instances)
→ bladder wall hypertrophy → decreases
bladder compliance → repeats ▪ Bladder trabeculation or diverticula
▪ Obstruction increases bladder pressure ▪ Radiolucent linear band (representing
→ ureterovesical junction dysfunction → valve)
vesicoureteral reflux
▪ Urine retention by obstruction → urine TREATMENT
backs up → bilateral hydronephrosis
▪ Severe obstructions in utero → SURGERY
oligohydramnios → Potter syndrome
▪ Surgical ablation of membrane
▫ Limb irregularities, facial anomalies,
▪ Prenatal surgery
kidney failure, pulmonary hypoplasia
CAUSES
▪ Unknown; theory: abnormal integration of
Wolffian duct → large plicae colliculi fuse
anteriorly
SIGNS & SYMPTOMS

▪ Posterior urethra obstructed by
membranous folds/tissue flap
DIAGNOSIS
DIAGNOSTIC IMAGING
Prenatal ultrasound
▪ Generally seen > 26 weeks gestation
▪ Noticeable distension and hypertrophy of
bladder
▪ Possitlbe hydronephrosis and hydroureter Figure 107.5 A lateral view of a micturating
▪ Keyhole sign: distended proximal urethra cystourethrogram demonstrating a proximally
and thick-walled bladder, resembles dilated urethra in case of posterior urethral
keyhole valve.
OSMOSIS.ORG 773
VESICOURETERAL REFLUX
osms.it/vesicoureteral-reflux
▪ Children: discomfort with urination; bowel
PATHOLOGY & CAUSES and bladder dysfunction
▪ Retrograde flow of urine from the bladder

into the ureters and kidneys SIGNS & SYMPTOMS
▪ Grading
▫ Grade I: urine goes into ureters ▪ Infants: asymptomatic, fever, lethargy, poor
▫ Grade II: urine fills entire ureter, renal apetite
pelvis ▪ Children: discomfort with urination
▫ Grade III: urine fills, stretches ureter,
renal pelvis
▫ Grade IV: ureter swollen, curvy; renal
DIAGNOSIS
pelvis, calyces swollen, distorted
DIAGNOSTIC IMAGING
▫ Grade V: urine fills ureter, pelvis, calyces;
swell completely Abdominal ultrasound
▪ Primary vesicoureteral reflux (most ▪ Assesses renal parenchyma for scarring or
common type): due to congenital defect at anatomical abnormalities
ureterovesical junction (congenital absence/ ▪ Presence of hydronephrosis
shortening of intravesical portion of ureter)
▫ Inadequate closure of the ureterovesical VCUG
junction → urine builds up in bladder ▪ Should be performed on first UTI in child <
→ ureter fails to act as valve → urine six years old
returns to ureters ▪ Used for grading
▪ Secondary vesicoureteral reflux: due to ▪ Presence of other anatomical abnormalities
failure of the ureterovesical junction to close
during bladder contraction; often due to a
blockage in urinary tract
TREATMENT
▫ Pressure increases in urinary tract →
urine follows path of least resistance,
SURGERY
back into ureters
▪ Primary vesicoureteral reflux
▫ Surgery to repair valve at ureterovesical
RISK FACTORS junction
▪ Genetic predisposition ▫ Infants, children: no intervention; child
▪ Neonates: prenatal hydronephrosis grows → ureters lengthens → valve
▪ Children: febrile UTIs function improves
▪ Individuals of white, Northern European ▪ Secondary vesicoureteral reflux
descent ▫ Surgery to remove blockage
COMPLICATIONS
▪ Recurrent UTIs, pyelonephritis, renal
scarring/fibrosis, hypertension, kidney
failure
▪ Infants: asymptomatic, fever, lethargy, poor
appetite
774 OSMOSIS.ORG
Figure 107.6 A voiding cystourethrogram

demonstrating bilateral vesicoureteric reflux.
OSMOSIS.ORG 775
NOTES
NOTES
BLADDER CANCER

▪ Cellular cancers in bladder lining/wall LAB RESULTS
▪ Cystoscopy-guided biopsy (definitive
TYPES diagnosis)
▪ Non-urothelial
▪ Transitional cell carcinoma (AKA urothelial) TREATMENT
RISK FACTORS ▪ See individual disorders; depends on tumor
▪ Irritants, carcinogens (e.g. smoking) stage, grade, location; kidney condition;
localized/regional/metastatic
SIGNS & SYMPTOMS

▪ Hematuria, pain
NON-UROTHELIAL BLADDER
CANCERS
osms.it/non-urothelial-bladder
standing kidney stones, infection with
PATHOLOGY & CAUSES Schistosoma haematobium, a type of
flatworm)
▪ Bladder cancers that do not arise from the
▪ Primary adenocarcinomas
urothelium
▫ Frequently metastasize
▪ More invasive, poorer prognosis; may arise
from urothelial layer but cells differentiate ▫ Derive from glandular tissue → produce
a lot of mucin
▪ Squamous cell metaplasia: cells of
urothelium → pancake-like appearance ▫ Primary form of bladder tumor
of squamous cells → differentiate into associated with bladder exstrophy
squamous cell carcinoma ▫ Can develop as complication of
▫ Grow in multiple locations Schistosoma haematobium infection
▫ Cause extensive keratinization ▪ Adenocarcinomas of urachus
▫ Caused by chronic irritation (e.g. ▫ Similar to bladder adenocarcinomas
recurrent urinary tract infections, long- ▫ Arises from urachus (fibrous tissue
776 OSMOSIS.ORG
Chapter 108 Bladder Cancer
sitting at dome of bladder)

DIAGNOSIS
RISK FACTORS LAB RESULTS
▪ Chronic urinary tract infections (UTIs) ▪ Cystoscopic biopsy
▫ Definitive diagnosis based on cellular
COMPLICATIONS morphology
▪ Metastasis
TREATMENT
SIGNS & SYMPTOMS
SURGERY
▪ Bladder irritation ▪ Transurethral resection, small tumors
▪ Pain (location determined by tumor size/ resected with cystoscope
extent—flank, suprapubic, perineal, ▪ Radical cystectomy, complete bladder
abdominal, etc.) removal, dissection of surrounding lymph
▪ Hematuria nodes
▪ Adenocarcinomas secrete mucin → ▪ Urachal adenocarcinomas → remove dome
mucusuria of bladder, urachal ligament, umbilicus
▪ Urachal adenocarcinomas → abdominal
mass
Figure 108.1 Histological appearance of Schistosoma haematobia eggs in a bladder biopsy.
OSMOSIS.ORG 777
Figure 108.2 Illustration of a cytoscopy being performed. A tissue sample will be collected
and tested to determine if the tumor is the result of a squamous cell carcinoma or an
adenocarcinoma.
TRANSITIONAL CELL CARCINOMA

osms.it/transitional-cell-carcinoma
RISK FACTORS
PATHOLOGY & CAUSES ▪ Advanced age, heavy alcohol use, human
papillomavirus (HPV) infection, more
▪ Most common form of lower urinary tract common in individuals who are biologically
cancer (bladder, urethra) male, chronic extended dwell times (not
▪ AKA urothelial cell carcinoma voiding bladder for long periods)
▪ Can also affect upper urinary tract (e.g.
renal pelvis, ureter)
COMPLICATIONS
▪ Usually due to bladder urothelium
▪ Metastasis
▪ Mutations in tumour suppressor protein
p53 → horizontally growing, flat tumours
(invasive) MNEMONIC: P-SAC
▫ p53 independent mutations → outward Risk factors: exposure to
facing finger-like projections (non- carcinogens
invasive, less aggressive) Phenacetin: banned analgesic,
▪ Tumours often multifocal once common
▫ Field effect: entire urothelial field Smoking: primary risk factor
exposed to carcinogens, all cells bathed Aniline: compound used in
in urine rubber/dye manufacturing
▫ Implantation theory: tumour cells detach Cyclophosphamide: cytotoxic
from one site, implant at another medicine, cancer/autoimmune
conditions
778 OSMOSIS.ORG
Chapter 108 Bladder Cancer

▪ Hematuria (typically intermittent, painless, ▪ Depends on tumor stage, grade, location;
present throughout urination) kidney condition; localized/regional/
▪ Pain (location determined by size/extent metastatic
of tumor: flank, suprapubic, perineal,
abdominal, etc.) MEDICATIONS
▪ Constitutional symptoms (severe disease)
▪ Dysuria; frequent/urgent urination Chemotherapy
▪ Non-aggressive: localised via catheter
▪ Aggressive: systemic
DIAGNOSIS
▪ Non-aggressive: transurethral resection via
Cystoscopy cystoscopy (localized, non-invasive tumors)
▪ Aggressive: complete removal of prostate,
LAB RESULTS bladder (cystoprostatectomy)
▪ Identify presence of blood in urine
▪ Cystoscopy-guided biopsy of tumour
(definitive diagnosis)
Figure 108.3 Histological appearance of muscle-invasive transitional cell carcinoma of the

bladder.
OSMOSIS.ORG 779
Figure 108.4 An MRI scan in the axial plane Figure 108.5 Transitional cell carcinoma
demonstrating a transitional cell carcinoma of can occur anywhere from the renal pelvis
the bladder. to the distal urethra. This coronal CT scan
demonstrated a transitional cell carcinoma of
the mid ureter.
Figure 108.6 Immunohistochemical staining with compound CK20 demonstrating urothelial

carcinoma in situ. The urothelium has undergone malignant transformation but has not yet
begun to invade surrounding tissue.
780 OSMOSIS.ORG
NOTES
NOTES
BLADDER PATHOLOGY
NEUROGENIC BLADDER
osms.it/neurogenic-bladder
Urge incontinence
PATHOLOGY & CAUSES ▪ Multiple sclerosis (MS) → autoimmune
damage to nerve myelin sheath in S2-S3
▪ Impaired control of bladder emptying due level in spinal cord
to nerve damage
▪ Spinal shock
▪ Bladder fills → damaged S2-S3 nerves
▪ Stroke
→ impaired signal transmission, lack of
voluntary control → incontinence ▪ Chronic processes affecting central
nervous system (CNS): Parkinson’s disease,
Overflow incontinence brain tumor
▪ Bladder reaches maximum capacity,
releases urine involuntarily all at once RISK FACTORS
▪ Results from impaired capacity to detect ▪ Any disease affecting central, peripheral
bladder filling nervous system
Urge incontinence ▫ Diabetes, syphilis, herpes, spinal birth
defects, spinal cord injuries, stroke,
▪ Small amount of urine initiates micturition
traumas
reflex involuntarily
▪ Results from impaired capacity to inhibit
micturition reflex COMPLICATIONS
▪ Rashes/skin infections
CAUSES ▪ Recurrent urinary tract infections (UTIs)
Overflow incontinence
▪ Diabetes mellitus (most common); ischemic, SIGNS & SYMPTOMS
metabolic, endothelial damage
▪ Syphilis → tabes dorsalis; inflammation, ▪ Depends on nerves damaged, extension
scarring of dorsal root nerves ▪ Urge, overflow incontinence
▪ Herpesvirus → latent in dorsal nerve roots
▪ Spinal injury → micturition center (S2-S3
level) affected
▫ Once shock resolves → normal
micturition reflex
▫ May also lead to urge incontinence;
impaired transmission of inhibitory
signal for micturition reflex
OSMOSIS.ORG 781
DIAGNOSIS TREATMENT
▪ Post-voiding residual measuring: amount ▪ Urge incontinence: anticholinergic drugs to
of urine in bladder after urination relax detrusor muscle
▪ Pressure, flow of urine measurements
OTHER INTERVENTIONS
▪ Overflow incontinence: catheter to drain
urine
Figure 109.1 Illustration of syphilis and herpes viruses attacking the nerves of the bladder, which
ultimately leads to overflow incontinence.
Figure 109.2 Illustration of causes of overflow incontinence. Spinal injuries can temporarily impair
bladder functioning, while chronic conditions affecting the nervous system, like Parkinson’s
disease, have more permanent effects.
782 OSMOSIS.ORG
NOTES
NOTES
CONGENITAL KIDNEY CONDITIONS

▪ Kidney abnormalities present at birth DIAGNOSTIC IMAGING
▪ Polycystic kidney disease, multicystic
Ultrasound, CT scan, intravenous urethro-
dysplastic kidney, horseshoe kidney, renal
gram, MRI
agenesis
Developmental phases LAB RESULTS

▪ Pronephros → mesonephros → migrate ▪ Evaluate renal function; blood urea nitrogen
upwards into abdomen → separate into (BUN), creatinine, estimated glomerular
two kidneys filtration rate (eGFR), serum electrolytes
COMPLICATIONS OTHER DIAGNOSTICS

▪ Progressive renal damage, renal failure ▪ Visible at birth: bladder exstrophy,
hypospadias, epispadias
RISK FACTORS
▪ More common in individuals who are TREATMENT
biologically male
▪ Pregnancy: high BMI, alcohol abuse, MEDICATIONS
smoking, teratogenic medication
▪ Support renal function
▪ Genetics
▫ Diuretics, erythropoietin (EPO),
medication for electrolyte imbalances,
SIGNS & SYMPTOMS angiotensin converting enzyme (ACE)
inhibitors, angiotensin receptor blockers
▪ Potter sequence (epicanthal folds, low-set
ears, flat nose, recessed chin) SURGERY
▪ Kidney transplant
OTHER INTERVENTIONS
Dialysis
▪ If kidney(s) no longer functional, machine
performs kidney function; filtering, purifying
blood by removing waste, excess fluid
OSMOSIS.ORG 783
HORSESHOE KIDNEY
osms.it/horseshoe-kidney

▪ AKA renal fusion, congenital disorder; two ▪ Mostly asymptomatic, sweating, nausea,
kidneys fuse during fetal development → vomiting; hematuria; fever, chills; cloudy
one large, horseshoe-shaped kidney urine
▪ Week 7–8
▫ Horseshoe-shaped kidney tries to
migrate from pelvis up into abdomen →
DIAGNOSIS
gets hooked around inferior mesenteric
artery → remains low in abdomen ▪ Usually incidental
Mechanical fusion Ultrasound

▪ Metanephros stage (gestation week 5) ▪ Periodic monitoring for early Wilms’ tumor
detection
▪ Flexion/growth of developing spine, pelvic
organs → pushes kidneys together → CT scan
lower poles of kidneys fuse → fibrous
▪ 3D scanning: evaluate anatomy, collecting
isthmus forms
system
▫ Isthmus made of connective tissue
MRI
Teratogenic event
▪ Provide anatomical information
▪ Posterior nephrogenic cells (help form
▪ Evaluate arterial anatomy before surgery
part of kidney) migrate to wrong spot →
parenchymal isthmus forms → connects ▪ Check renal artery stenosis in hypertensive
kidneys people
▫ Isthmus made of kidney cells
LAB RESULTS
RISK FACTORS ▪ BUN, creatinine, glomerular filtration rate
(GFR), serum studies, 24-hour kidney stone
risk assessment
biologically male
▪ Chromosomal disorders (e.g. Turner
syndrome, trisomy 13, 18, 21) TREATMENT
▪ Neural tube defects
MEDICATIONS
COMPLICATIONS ▪ For renal disease (e.g. erythropoietin, ACE
▪ Hydronephrosis, kidney stones, infection, inhibitors)
kidney cancer (especially Wilms’ tumor,
carcinoid tumor), obstruction, vesicoureteral SURGERY
reflux, infection, polycystic kidney disease ▪ Possibly corrective surgery
784 OSMOSIS.ORG
Chapter 110 Congenital Kidney Conditions
Figure 110.1 An abdominal CT scan in the Figure 110.2 A 3D-reconstruction MRI

axial plane demonstrating a horseshoe in an anterior view in an individual with a
kidney. There is renal tissue connecting the horseshoe kidney.
right and left kidneys.
MEDULLARY CYSTIC KIDNEY

DISEASE (MCKD)
osms.it/mdullary-cystic-kidney-disease
ADTKD due to REN mutations: REN (ADT-
PATHOLOGY & CAUSES KD-REN)
▪ Caused by REN gene mutations
▪ A group of autosomal dominant kidney
▪ Encodes renin, a key hormone in the RAAS
diseases that cause progressive renal
pathway
failure
▪ Intracellular pre-prorenin accumulation
▪ AKA autosomal dominant tubulointerstitial
→ structural damage, apoptosis of renin-
kidney disease (ADTKD)
producing cells → progressive renal failure
+ ↓ renin production → ↓ blood pressure,
TYPES anemia
Uromodulin kidney disease (UKD) Mucin-1 kidney disease (MKD)

▪ Caused by UMOD gene mutations ▪ Caused by MUC1 gene mutations
▪ Encodes uromodulin (Tamm–Horsfall ▪ Encodes mucin-1
protein), a non-ciliary protein ▪ Pathophysiology not completely
▫ Maintains integrity of the thick understood; results in progressive renal
ascending limb of the loop of Henle failure
▪ Intracellular abnormal uromodulin
accumulation → tubular cell atrophy →
progressive renal failure + ↓ urate excretion
→ hyperuricemia, gout
OSMOSIS.ORG 785
COMPLICATIONS UKD (presumptive diagnosis factors)
▪ Gout, chronic kidney disease, end-stage ▪ All three of the following
renal disease (ESRD), low blood pressure, ▫ Strong family history of kidney disease
anemia ▫ Family history of gout
▫ Urinalysis: bland urinary sediment;
SIGNS & SYMPTOMS absence of proteinuria or hematuria
ADKTD-REN (presumptive diagnosis fac-

▪ Clinical manifestations of chronic kidney tors)
disease ▪ Family history of chronic kidney disease,
UKD plus one of the following
▪ Gout occurs at early age ▪ Unexplained anemia out of proportion to ↓
glomerular filtration rate
ADTKD-REN ▪ Evidence of acute kidney injury; bland
▪ Low/low-normal blood pressures, urinary sediment
anemia (occurs in childhood; resolves in ▪ Chronic kidney disease + hyperkalemia,
adolescence from the influence of sex low or low-normal blood pressure, and
hormones), mild hyperkalemia hyperuricemia
MKD MKD (presumptive diagnosis factors)

▪ ↑ serum creatinine, hyperuricemia and gout ▪ Presentation chronic kidney disease plus
occurring later in life each of the following findings
▫ Urinalysis: bland urinary sediment; little
or no proteinuria
DIAGNOSIS ▫ Absence of symptoms associated with
UKD (precocious gout) or ADKTD-REN
DIAGNOSTIC IMAGING (childhood anemia, hyperkalemia, and
hyperuricemia)
Ultrasound
▪ Small to normal kidneys with occasional
cysts TREATMENT
Urinalysis UKD
▪ See presumptive diagnosis factors for each ▪ Gout: allopurinol
subtype
ADTKD-REN
Biopsy ▪ Symptomatic anemia: erythropoietin
▪ Interstitial fibrosis ▪ Low blood pressure, hyperkalemia:
fludrocortisone
OTHER DIAGNOSTICS ▪ Avoid NSAIDs
▪ Confirmed through genetic testing
SURGERY
▪ Treat progressive renal failure; kidney
transplantation
786 OSMOSIS.ORG
MEDULLARY SPONGE KIDNEY

(MSK)
osms.it/medullary-sponge-kidney

▪ Rare congenital disorder characterized ▪ Often discovered incidentally during
by ectasia (dilation) of the renal collecting investigations for another indication
ducts
▪ Genetic basis for developmental DIAGNOSTIC IMAGING
abnormality is incompletely understood;
may involve embryonic disruption of the Intravenous pyelography
ureteral-bud and the metanephric blastema ▪ Cystic dilatations have brushlike
▪ Renal collecting duct dilation, distension appearance; enlarged pyramids; clusters of
→ urinary stasis → medullary cyst stones
formation → impaired acidification in the
terminal collecting duct → ↑ urine pH → CT scan
nephrocalcinosis ▪ Medullary nephrocalcinosis

▪ Associated conditions include ▪ Hypercalciuria, hyperuricosuria,
hemihypertrophy, Beckwith–Wiedemann hypocitraturia, and hyperoxaluria
syndrome
TREATMENT
COMPLICATIONS
▪ Urinary tract infections MEDICATIONS
▪ Nephrocalcinosis
▪ Renal calculi (calcium phosphate, calcium Treat complications
oxalate) ▪ Urinary tract infection: antibiotics
▪ Chronic kidney disease ▪ Recurrent stone formation: potassium
citrate, thiazide diuretics, ↑ fluid intake, ↓
sodium in diet
SIGNS & SYMPTOMS
▪ Often asymptomatic, flank pain, renal colic,
hematuria, dysuria, nocturia
OSMOSIS.ORG 787
Figure 110.3 An X-ray image of the kidney,
ureters and bladder. The dilated collecting
ducts of the nephron give a paintbrush effect
to each renal calyx.
MULTICYSTIC DYSPLASTIC
KIDNEY (MCDK)
osms.it/dysplastic-kidney
CAUSES
PATHOLOGY & CAUSES ▪ Mostly sporadic
▪ Potential link to medication during
▪ Congenital disease, one/both kidneys
pregnancy
do not form correctly → urine does not
drain properly, builds up in kidneys, forms ▫ ACE inhibitors, illicit drugs (e.g. cocaine)
multiple fluid-filled sacs (cysts) ▪ Without treatment → kidney involutes
▪ Result of abnormal induction of (shrinks due to inactivity)
metanephric blastema by ureteric bud
▫ Possibly due to malformation of RISK FACTORS
mesonephric duct/ureteric bud/both ▪ More common in individuals who are
▪ Ureteric bud fails to produce ureters, renal biologically male, genetic syndromes
calyces, collecting ducts, collecting tubules (papillorenal syndrome; error in genes
▫ Urine cannot exit kidney, builds up → EYA1, SIX1, PAX2)
forms fluid-filled cysts
▫ Fluid-filled cysts composed of abnormal COMPLICATIONS
connective tissue replace normal kidney
tissue → kidney function decreases Bilateral MCDK
▪ Potter sequence
Unilateral MCDK
▪ Uncommon, risk of chronic kidney disease
788 OSMOSIS.ORG

Unilateral MCDK SURGERY
▪ Asymptomatic/palpable flank mass
Mild bilateral MCDK
Bilateral MCDK ▪ Dialysis, kidney transplant
▪ Potter sequence ▪ Newborn requires dialysis/kidney transplant
OTHER INTERVENTIONS
DIAGNOSIS
Unilateral MCDK
▪ May go undiagnosed if unilateral, no ▪ Observation
palpable flank mass, remaining kidney
▫ Affected kidney involutes
compensating fully
▪ Follow-up
▫ Serial ultrasound evaluation at birth, four
DIAGNOSTIC IMAGING weeks, two years, five years, 10 years
of age; blood pressure, urinalysis (for
Antenatal ultrasound
proteinuria), renal function studies
▪ Most common
▪ Visualize kidney containing multiple large, Severe bilateral MCDK
peripheral cysts ▪ Provide support for Potter sequence
▪ Newborns generally don’t survive
Ultrasound
▪ Performed on neonate if health
professionals detect palpable flank mass
Figure 110.4 Pathological features of

multicystic dysplastic kidney.
OSMOSIS.ORG 789
POLYCYSTIC KIDNEY DISEASE
(PKD)
osms.it/polycystic-kidney
fluid (oligohydramnios)
PATHOLOGY & CAUSES ▪ Inherited mutation on both copies of
polycystic kidney hepatic disease 1
▪ Genetic disease, kidneys fill with hundreds (PKHD1) gene, fibrocystin protein
of cysts → become larger, unable to
▫ Fibrocystin co-localizes with PKD2
function
regulation pathway, calcium signaling
▪ Cysts in outer layer (cortex), inner layer similar to autosomal dominant
(medulla) of kidneys
▪ Cysts lined with renal tubular epithelium,
become larger RISK FACTORS
▪ Cysts make kidneys larger over time → Autosomal dominant
compress blood vessels of neighboring
▪ One parent passes along PKD1/PKD2
healthy nephrons → starve neighboring
mutation
nephrons of oxygen → poor perfusion
of kidneys activates renin-angiotensin- Autosomal recessive
aldosterone system → retain fluid → ▪ Both parents pass along PKHD1 mutation
hypertension
▪ Large cysts → compress collecting system
→ urinary stasis → kidney stones COMPLICATIONS
▪ Renal insufficiency → renal failure
▪ Kidney stones
TYPES
Autosomal dominant
Autosomal dominant
▪ Cerebral artery berry aneurysms
▪ AKA adult PKD; usually manifests in
adulthood ▪ Mitral valve prolapse
▪ Polycystin 1 (PKD1), polycystin 2 (PKD2) ▪ Benign hepatic cysts
▫ Necessary for inhibition of cell ▪ Heart failure (due to aortic root dilation)
proliferation; if absent, cells proliferate
Autosomal recessive
abnormally, water moves to cyst lumen
▪ Congenital hepatic fibrosis → portal
▪ PKD1 gene mutation → more severe,
hypertension
earlier onset
▪ Ascending cholangitis (due to obstructed
▪ PKD2 gene mutation → less severe, later
biliary tree)
onset
Autosomal recessive
▪ AKA infantile PKD; usually manifests in
SIGNS & SYMPTOMS
infancy
▪ Flank pain, high blood pressure, hematuria
▫ Possible renal failure before birth →
(blood in urine), renal insufficiency, renal
trouble producing urine → low amniotic
failure, fetal oligohydramnios in autosomal
recessive PKD
790 OSMOSIS.ORG
DIAGNOSIS TREATMENT
▪ Hypertension: ACE inhibitors, angiotensin
Prenatal ultrasound
receptor blockers
▪ For autosomal recessive polycystic kidney
▪ Cholestasis: ursodiol (slows down rate of
disease
cholesterol absorption by intestines)
▪ Bilaterally large kidneys with cysts,
oligohydramnios
SURGERY
LAB RESULTS
▪ Complete blood count (CBC), urinalysis, Portal hypertension
urine culture ▪ Portocaval shunt → bypasses liver,
connects portal vein to inferior vena cava;
liver transplant
OTHER INTERVENTIONS
▪ Dialysis
Figure 110.5 Histological appearance of renal

parenchyma in a case of polycystic kidney
disease.

demonstrating innumerable cysts in the
kidneys and liver in autosomal dominant
polycystic kidney disease.

appearance of polycystic kidneys.
OSMOSIS.ORG 791
RENAL AGENESIS
osms.it/renal-agenesis

▪ Ureteric bud fails to induce metanephric ▪ Oligohydramnios/anhydramnios (no
blastema to develop → one/both kidneys amniotic fluid)
don’t form ▪ Symptoms at birth include high blood
pressure, protein/blood in urine, swelling of
TYPES face/extremities
Unilateral renal agenesis (URA) URA

▪ One kidney does not develop ▪ Bsually asymptomatic if other kidney
healthy
▫ Usually asymptomatic if other kidney
healthy, able to compensate BRA
▫ Predisposes individuals to more serious ▪ Babies ill at birth, usually do not live
renal problems ▫ Widely separated eyes with epicanthal
Bilateral renal agenesis (BRA) folds
▪ Neither kidney develops ▫ Low set ears
▫ Incompatible with life outside womb ▫ Flat, broad nose
▫ Usually fatal within first few days after ▫ Small chin
birth; no treatment ▫ Underdeveloped lungs
CAUSES DIAGNOSIS
▪ Combination of genetic/in utero
environmental factors (toxins, infections) DIAGNOSTIC IMAGING
Prenatal ultrasound/MRI
RISK FACTORS
▪ Confirm diagnosis
biologically male
OTHER DIAGNOSTICS
▪ Oligohydramnios/anhydramnios
COMPLICATIONS
URA
▪ Hypertrophy of remaining kidney, TREATMENT
infections, kidney stones, hypertension,
renal failure SURGERY
BRA
▪ Oligohydramnios, pulmonary hypoplasia,
OTHER INTERVENTIONS
Potter sequence
▪ Routine monitoring
▪ Dialysis
792 OSMOSIS.ORG
Figure 110.8 A 3D reconstruction of a CT

scan demonstrating left-sided renal agenesis.
Figure 110.9 An MRI scan in the coronal

plane demonstrating right-sided renal
agenesis.
OSMOSIS.ORG 793
NOTES
NOTES
HYPERCALCEMIA &
HYPOCALCEMIA

▪ Calcium concentrations in the blood falling LAB RESULTS
outside of the normal reference range ▪ Blood calcium levels
▪ Hypocalcemia: < 8.5mg/dL ▪ Determination of underlying cause (blood
▪ Hypercalcemia: > 10.5mg/dL tests for levels of)
▫ Parathyroid hormone, vitamin D,
albumin, phosphorus, magnesium
SIGNS & SYMPTOMS
OTHER DIAGNOSTICS
▪ Variations that are mild, or slow in onset,
usually asymptomatic ECG
▪ Hypercalcemia → less excitable neurons ▪ Identify associated organ dysfunction
and associated symptoms across multiple
systems
▪ Hypocalcemia → more excitable neurons TREATMENT
and associated symptoms across multiple
systems MEDICATIONS
Hypercalcemia
▪ Lower blood calcium levels
▫ Rehydrate, loop diuretics,
glucocorticoids, bisphosphonates or
calcitonin, dialysis
Hypocalcemia
▪ Raise calcium levels
▫ Calcium gluconate
▫ Vitamin D supplementation
794 OSMOSIS.ORG
Chapter 111 Hypercalcemia & Hypocalcemia
HYPERCALCEMIA
osms.it/hypercalcemia
▫ Thiazide diuretics (increase calcium
PATHOLOGY & CAUSES reabsorption in distal tubule of kidney)
▫ Lithium (increase calcium reabsorption
▪ High blood calcium (> 10.5mg/dL) from the loop of Henle, also interferes
▪ True hypercalcemia due to elevation of free with normal hypercalcemic feedback on
ionized calcium (not protein-bound, which the parathyroid gland)
is 40–45% of total calcium) ▫ Calcium carbonate supplementation
▪ Milk-alkali syndrome
CAUSES ▫ Extra calcium from diet, alkali found in
antacids)
Excessive bone resorption
▫ Hypercalcemia, metabolic alkalosis,
▪ Hyperparathyroidism
renal insufficiency
▫ Increased osteoclastic bone resorption Insufficient excretion
▫ Overactive parathyroid → releases more ▪ Adrenal insufficiency (e.g. Addisonian crisis)
parathyroid hormone → stimulates ▪ Adrenal failure (e.g. rhabdomyolysis)
osteoclasts → osteoclasts break down
bone → release calcium into blood False hypercalcemia / pseudohypercalcemia
▪ Thyrotoxicosis ▪ Hyperalbuminemia → ↑ albumin → ↑
▫ Thyroid hormone mediated increase in protein-bound calcium → ↑ total calcium
bone reabsorption ▫ Free ionized calcium concentrations
▪ Malignant tumors remain the same (hormonal regulation)
▫ Can secrete parathyroid hormone- ▫ Total calcium high, free ionized calcium
related protein (PTHrP) normal
▫ Can cause osteoblast cells to die ▫ Rare cause: dehydration
▫ Can also cause overstimulation of
osteoclasts → lytic bone lesions COMPLICATIONS
▫ Can directly invade bone ▪ Calcium oxalate kidney stones
▪ Uncommon causes (hypercalciuria, fluid loss)
▫ Immobilisation, Paget disease of ▪ Osteoporosis (depletion of calcium stores in
bone, anti-oestrogen treatment, bone)
hypervitaminosis A (retinoic acid → ▪ Renal failure
dose dependent increase in bone ▪ Cardiac arrhythmias
resorption) ▪ Confusion, dementia, coma
Excessive calcium absorption
▪ Excess vitamin D
▫ Stimulates active intestinal absorption,
resorption from bone and increased
renal reabsorption
▪ Diet or excessive supplementation
▫ When intake exceeds 2 grams daily,
passive transport may also lead to
hypercalcemia
▪ Medications
OSMOSIS.ORG 795
▪ Vitamin D: may be ↑ in intoxication
SIGNS & SYMPTOMS ▪ Phosphate: ↑ or ↓ depending if PTH-
dependent (high in renal insufficiency,
▪ Many individuals asymptomatic
hypoparathyroidism, low in vitamin D
▪ Slow chronic onset, better tolerated deficiency)
▪ Neurological ▪ Magnesium: hypercalcemia may ↓ Mg
▫ Neurons less excitable levels
▫ Blurred vision, slow or absent reflexes
▫ Central nervous system: fatigue, OTHER DIAGNOSTICS
anxiety, confusion, hallucinations, stupor
▪ Cardiovascular ECG
▫ Arrhythmias, shortened QT interval, ▪ Bradycardia
bradycardia, hypertension ▪ Atrioventricular block
▪ Musculoskeletal ▪ Shortening of QT interval
▫ Generalized muscle weakness, bone ▪ Osborn wave (positive deflection at junction
pain, weak bones between QRS complex and ST segment)
▪ Gastrointestinal
▫ Anorexia, nausea and vomiting,
constipation TREATMENT
▪ Renal
MEDICATIONS
▫ Hypercalciuria, polyuria, polydipsia,
▪ Main goal: lower calcium levels in blood
kidney stones, distal renal tubular
acidosis, nephrogenic diabetes insipidus, ▪ Rehydrate: increases urinary excretion of
renal insufficiency calcium
▪ Loop diuretics: inhibit calcium reabsorption,
so more is excreted
DIAGNOSIS ▪ Glucocorticoids: decrease gastrointestinal
calcium absorption
LAB RESULTS ▪ Bisphosphonates or calcitonin: inhibit
▪ High calcium levels in blood > 10.5mg/dL osteoclasts, prevent bone resorption
▪ Calcium levels must be corrected for ▪ Dialysis: if renal failure is present, consider
albumin levels or measure free ionized hemodialysis or peritoneal dialysis
calcium
▫ Albumin: may be ↑ in
pseudohypercalcemia MNEMONIC
▪ Parathyroid hormone: ↑ or ↓ The effects of hypercalcemia
▪ PTH-related hypercalcemia: primary Stones: renal or biliary calculi
hyperparathyroidism and familial Bones: bone pain
hyperparathyroidism Groans: abdominal pain/
▪ Non-PTH-related hypercalcemia: primary nausea
malignancy, intoxication of vitamin D, Thrones: polyuria
granulomatosis Psychiatric overtones:
▪ PTH-related peptide: may ↑ in certain depression, anxiety, coma,
malignancies insomnia
796 OSMOSIS.ORG
Figure 111.1 Illustration of the potential sequelae of hypercalcemia.
HYPOCALCEMIA
osms.it/hypocalcemia
▫ Often occurs in setting of vitamin D
PATHOLOGY & CAUSES deficiency, hypoparathyroidism and
parathyroid hormone resistance
▪ Low blood calcium (< 8.5mg/dL)
Too much calcium leaving blood
CAUSES ▪ Kidney failure: nephron doesn’t effectively
reabsorb calcium
Less calcium entering blood ▪ Tissue injury: burns, rhabdomyolysis, tumor
▪ Most common cause lysis syndrome
▪ Low vitamin D: deficient diet, ▪ Acute pancreatitis: free fatty acids bind to
malabsorption, cirrhosis, lack of sunlight, ionized calcium
chronic renal failure ▪ Inflammatory processes (eg. sepsis and
▪ Hypoparathyroidism: low levels or low severe illness)
activity of parathyroid hormone ▫ Up to 90% of critically-ill individuals,
▫ Hypomagnesemia (Mg serum or those that have had major surgery
concentration < 1mg/dL) can facilitate develop hypocalcemia
parathyroid hormone resistance via ▪ Too many blood transfusions → additives
suppressing secretion bind to ionised calcium → additives in
▪ Pseudohypoparathyroidism type 1A: blood (citrate, ethylenediaminetetraacetic
kidney unresponsive to parathyroid acid (EDTA) chelate (bind) to calcium →
hormone complexed calcium, an inactive molecule
▫ Pseudohypoparathyroidism: end-organ ▪ Hyperphosphatemia: results in calcium
parathyroid hormone resistance being deposited in bone and extraskeletal
▪ Inhibition of bone resorption (uncommon) tissue
▫ Medications such as bisphosphonates, ▪ Calcium complex formation: formation of
calcitonin and denosumab complexes → reduced availability of ionized
OSMOSIS.ORG 797
calcium for cellular processes joints flex)
▫ Foscarnet, drug for treatment of ▫ Muscle cramps
refractory herpes and cytomegalovirus ▫ Abdominal pain
▫ Fluoride poisoning, causes ▫ Perioral tingling (tingling around mouth)
hypocalcemia partially due to formation ▫ Paresthesias (abnormal sensation felt
of fluorapatite on skin, eg. tingling, tickling, prickling,
numbness, burning)
False hypocalcemia / pseudohypocalcemia
▫ Carpopedal spasm (spasmodic
▪ Hypoalbuminemia (low albumin): loss of
contraction of muscles in hands, feet,
bound calcium
ankles, wrists)
▫ Hormonal regulation means free ionized
▫ Hyperactive deep tendon reflexes
calcium concentrations stay essentially
the same ▫ Seizures (extreme cases)
▫ Less overall calcium due to less bound ▪ Cardiovascular: decrease in rate, strength
calcium, but free ionized calcium levels of contractions
remain the same ▫ Hypotension
▫ Heart failure
COMPLICATIONS ▫ Arrhythmias
▪ Osteopenia, osteoporosis, cardiovascular
collapse, vasogenic shock (calcium required
in vascular smooth muscle contraction), DIAGNOSIS
cardiac arrhythmias, seizures, tetany,
basal ganglia calcification, parkinsonism, LAB RESULTS
hemiballismus, choreoathetosis ▪ Low level of calcium in blood (< 8.5mg/dL)
▪ Calcium levels must be corrected for
albumin levels or measure free ionized
calcium
▫ Albumin may be low in
pseudohypocalcemia
▪ PTH-related hypocalcemia
▫ ↓ : hypoparathyroidism
▫ ↑ : kidney disease, vitamin D deficiency,
pseudohypoparathyroidism
▪ Non-PTH-related hypocalcemia:
hypomagnesemia
▪ Autosomal dominant hypocalcemia:
mutation in calcium-sensing receptor gene
Figure 111.2 Trousseau’s sign of latent tetany. ▪ PTH
▫ ↑ in kidney disease, vitamin D deficiency,
pseudohypoparathyroidism
SIGNS & SYMPTOMS ▫ ↓ in hypoparathyroidism
▪ Vitamin D
▪ Neurological → neurons hyperexcitable ▫ Hypocalcemia may be caused by ↓
▫ Involuntary contraction of muscles vitamin D (which ↑ PTH secretion)
▫ Chvostek’s sign (facial muscles twitch ▪ Phosphate
after facial nerve lightly finger tapped ▫ ↑ in hypoparathyroidism (in
1cm/0.39in below zygomatic process) absence of kidney disease) or
▫ Trousseau’s sign (blood pressure cuff pseudohypoparathyoidism (PTH
occludes brachial artery → pressure resistance)
makes nerve fire → muscle spasm ▫ ↓ in secondary hyperparathyroidism
makes wrist and metacarpophalangeal
798 OSMOSIS.ORG
▫ Normal in setting of hypocalcemia:

hypomagnesemia/mild vitamin D
deficiency
▪ Magnesium: ↓ levels can cause
hypocalcemia
OTHER DIAGNOSTICS
ECG
▪ Prolonged QT segment
▪ Prolonged ST segment
▪ Arrhythmias (torsades de pointes, atrial
fibrillation)
TREATMENT
MEDICATIONS Figure 111.3 Hypocalcemia can can cause
tetany, seen here in the face of this individual.
▪ Main goal: normalize calcium levels
▫ Calcium gluconate
▫ Vitamin D supplementation
OSMOSIS.ORG 799
NOTES
NOTES
HYPERKALEMIA & HYPOKALEMIA

▪ Imbalances of potassium levels in blood MEDICATIONS
▪ Etiologies influence potassium intake, ▪ Discontinue medication that aggravates
excretion, transcellular shift potassium homeostasis
▪ Low serum K+
▫ Oral K+ can be supplemented
SIGNS & SYMPTOMS ▪ High serum K+
▫ Agents/procedures that remove
▪ Mild variations usually asymptomatic,
extracellular K+, into cells/↑ secretion
severe imbalances may be fatal
from body
DIAGNOSIS
LAB RESULTS
▪ Blood potassium levels; further tests useful
to establish underlying cause
HYPERKALEMIA
osms.it/hyperkalemia
▫ Renin inhibitors, angiotensin converting
PATHOLOGY & CAUSES enzyme (ACE) inhibitors, angiotensin II
receptor antagonists, potassium-sparing
▪ High potassium levels in blood > 5.5 diuretics, nonsteroidal anti-inflammatory
milliequivalents/liter (mEq/L) drugs (NSAIDs), cyclosporine,
trimethoprim-sulfamethoxazole
CAUSES
Transcellular shift
Decreased kidney excretion ▪ Uncontrolled Type I diabetes
▪ Decreased glomerular filtration rate in ▫ Lack of insulin → decreases sodium/
acute/chronic kidney disease potassium pump action
▪ Adrenal insufficiency → primary ▪ Acidosis
hypoaldosteronism ▫ Excess hydrogen ions move into cells
▫ Principal cells secrete less potassium via ion transporters that exchange
▪ Drugs hydrogen ions for potassium ions
▫ Respiratory acidosis; metabolic acidosis
800 OSMOSIS.ORG
Chapter 112 Hyperkalemia & Hypokalemia
from organic acids are two exceptions MNEMONIC: MURDER

▪ Hyperosmolarity Signs & symptoms of
▫ Gradient pulls water out of cells → Hyperkalemia
intracellular concentration potassium Muscle weakness
goes up → potassium pushed out Urine: oliguria, anuria
▪ Massive cell lysis Respiratory distress
▫ E.g. tumor lysis syndrome, Decreased cardiac contractility
rhabdomyolysis, massive hemolysis EKG changes: peaked T waves;
▫ Intracellular potassium released into QRS widening
bloodstream (98% of K+ found within Reflexes: hyperreflexia or
cells) areflexia (flaccid)
▪ Drugs
▫ Beta2-adrenergic antagonists, digoxin
toxicity DIAGNOSIS
▪ Exercise
▫ Cellular ATP consumed → potassium LAB RESULTS
channels open ▪ Potassium levels in blood > 5.5mEq/L
▫ Shift usually small, can exacerbate
condition in individuals with OTHER DIAGNOSTICS
hyperkalemia
ECG
Increased intake ▪ Prolonged PR interval, tall, peaked T-waves
▪ Excessive potassium oral intake with narrow base, shortened QT interval,
▫ Unusual, can exacerbate condition in depressed ST segment
individuals with hyperkalemia ▪ Severe
▪ Rapid, excessive potassium infusion (rare) ▫ Small/indiscernible P wave, widened
QRS complex → strip mimics sine wave
SIGNS & SYMPTOMS

▪ Mostly asymptomatic
▪ Severe/rapid-onset hyperkalemia
▫ Muscle weakness, flaccid paralysis
(starts in lower extremities, moves
upward) → respiratory failure
▫ Decreased deep tendon reflexes
▫ Arrhythmias, cardiac arrest
▫ Nausea, vomiting, intestinal colic,
diarrhea
Figure 112.1 An ECG demonstrating the
changes of hyperkalemia, including elevated
T waves, bizarre, broad QRS complexes and
a prolonged QT interval.
OSMOSIS.ORG 801
▪ Insulin with dextrose + beta2-adrenergic
TREATMENT agonists
▫ Increase potassium shift into cells
MEDICATIONS
▪ Kayexalate
▪ Initial treatment (individuals with ECG
changes) ▫ Bind potassium → decrease potassium
absorbed from gastrointestinal (GI) tract
▫ Calcium to stabilize myocardial cell
membranes ▪ Loop diuretics
▫ Increase potassium excretion in kidneys
MNEMONIC: C BIG K DROP OTHER INTERVENTIONS

Treatment of Hyperkalemia ▪ Severe hyperkalemia/renal failure
Calcium gluconate ▫ Hemodialysis (most rapid, effective way
Beta 2 agonist to lower serum K+)
Insulin + Glucose
Kayexalate
Diuretics/Dialysis
Figure 112.2 The ECG features found in hyperkalemia.
802 OSMOSIS.ORG
Chapter 112 Hyperkalemia & Hypokalemia
HYPOKALEMIA
osms.it/hypokalemia

▪ Low potassium levels in the blood < ▪ Mostly asymptomatic
3.5mEq/L ▪ Severe/rapid-onset hypokalemia
▫ Constipation, paralytic ileus
CAUSES ▫ Muscle weakness, cramps, flaccid
paralysis
▪ Increased kidney excretion
▫ Decreased deep tendon reflexes
▫ Hyperaldosteronism; drugs (e.g. loop,
thiazide diuretics, amphotericin B, ▫ Arrhythmias (prolong cardiac
cisplatin); renal tubular defects (e.g. conduction), cardiac arrest
Bartter syndrome); hypomagnesemia ▫ Polyuria, polydipsia, nausea, vomiting
▪ Increased gastrointestinal excretion ▫ Exacerbates digitalis toxicity
▫ Vomiting (direct loses minimal, causes
metabolic alkalosis); diarrhea
▪ Increased sweat production
DIAGNOSIS
▫ Relevant for individuals who exercise in
LAB RESULTS
hot climate
▪ Blood potassium level < 3.5mEq/L
▪ Shift from extracellular to intracellular space
▫ Insulin overdose in Type I diabetes;
excess insulin → increases sodium/ OTHER DIAGNOSTICS
potassium pump action
ECG
▪ Alkalosis
▪ Flattened/inverted T waves, U waves, ST
▫ Hydrogens move out of cells using depression, prolonged PR interval
ion transporter that exchanges with
▫ Prominent U waves fused to T waves,
potassium ions
mimic prolonged QT
▫ Respiratory alkalosis an exception
▪ Atrial, ventricular tachyarrhythmias
▪ Drugs
▫ Beta2-adrenergic agonists
TREATMENT
Other causes
▪ Low dietary intake (e.g. prolonged fasting, MEDICATIONS
anorexia, ketogenic diet)
▪ Replenish potassium with supplementation
▪ Insulin administration
▫ In acute coronary ischemia, active
▪ Antibiotics (TMP-SMX/amphotericin B) arrhythmias
▪ Epinephrine (beta 2-agonists) ▪ Oral KCl administration (safest)
▫ Slightly more than half of trauma cases ▪ IV administration for individuals taking nil
present with hypokalemia (increased per os
epinephrine levels)
▫ 10mEq KCl increases K+ by 0.1MEq/L
▪ Magnesium replacement
▪ If diuretic therapy needed
▫ Potassium-sparing diuretic
OSMOSIS.ORG 803
NOTES
NOTES
HYPERMAGNESEMIA &
HYPOMAGNESEMIA

▪ Abnormal levels of magnesium in the blood LAB RESULTS
▪ Hypomagnesemia: < 1.7mg/dL ▪ Assessment of blood magnesium levels
▪ Hypermagnesemia: > 2.4mg/dL ▪ Further tests are useful to establish
underlying cause
SIGNS & SYMPTOMS

TREATMENT
▪ Mild variations are usually asymptomatic,
severe imbalances may result in potentially MEDICATIONS
fatal arrhythmias and neurological ▪ Identify and treat any underlying causes
complications ▪ Hypermagnesemia
▫ Administer calcium gluconate →
competes for magnesium binding sites
▪ Hypomagnesemia
▫ Supplemental magnesium
HYPERMAGNESEMIA
osms.it/hypermagnesemia
▫ Excessive IV administration (e.g.
PATHOLOGY & CAUSES treatment of preeclampsia)
▪ Cellular breakdown (excessive release)
▪ Blood magnesium levels above 2.4mg/dL
▫ Tumour lysis syndrome, rhabdomyolysis
CAUSES
COMPLICATIONS
▪ Renal failure
▪ Impaired signal transmission across
▫ Kidneys unable to efficiently excrete neuromuscular junction → muscle
magnesium (most common cause) weakness (magnesium inhibits calcium
▪ Excessive intake influx at neuromuscular junction),
▫ Ingesting larger amounts of magnesium inhibition of parathyroid hormone release,
than the kidneys are able to excrete hypocalcemia, cardiac bradyarrhythmias
(supplements or medication e.g.
magnesium hydroxide, often used for
heartburn or constipation)
804 OSMOSIS.ORG
Chapter 113 Hypermagnesemia & Hypomagnesemia

▪ Nausea MEDICATIONS
▪ Drowsiness ▪ Calcium gluconate injection
▪ Tingling sensation in the face (facial ▫ Calcium and magnesium compete for
paresthesia) binding sites
▪ Progressive loss of deep tendon reflexes ▫ Reserved for severe, symptomatic
(earliest sign) hypermagnesemia
▪ Coma ▪ Loop diuretics increases the urinary
▪ Muscular paralysis excretion of magnesium
▪ Respiratory failure
▪ Cardiac arrest OTHER INTERVENTIONS
▪ Identify and stop the source of excessive
intake
DIAGNOSIS ▫ If normal renal function, with relevant
history or possible iatrogenic cause,
▪ ECG changes similar to those of cessation of excessive intake sufficient
hyperkalemia, increased PR interval, treatment
widened QRS complex, bradyarrhythmias ▪ Hemodialysis
▫ In severe cases magnesium can be
LAB RESULTS externally filtered from the blood
▪ Blood free magnesium level > 2.4mg/dL
▪ Renal function testing
▫ Urea, creatinine clearance test (levels
increase with renal failure)
OTHER DIAGNOSTICS
▪ Thorough examination of individual’s
history often reveals cause
Figure 113.1 Illustration depicting calcium channel inhibition due to hypermagnesemia, causing
delayed muscle contraction.
OSMOSIS.ORG 805
HYPOMAGNESEMIA
osms.it/hypomagnesemia

▪ Low levels of magnesium in the blood, ▪ Neuromuscular
<1.7mg/dL ▫ Without magnesium, calcium more
readily enters neuron, exits sarcoplasmic
CAUSES reticulum → more excitable nerves,
muscles
▪ Insufficient renal reabsorption
▪ Cardiac arrhythmias
▫ Loop and thiazide diuretics
▫ Premature atrial contractions
▫ Nephrotoxic drugs (amphotericin B,
calcineurin inhibitors, cisplatin) ▫ Premature ventricular contractions
▫ Hypercalcemia ▫ Increased risk of torsades de pointes
(particularly with concurrent class III
▫ Channelopathies (genetic mutations
antiarrhythmics)
that affect the ion channels through
which electrolytes like magnesium are ▫ Increased risk of arrhythmias associated
reabsorbed) with digoxin toxicity
▫ Diabetes (osmotic diuresis carries ▪ ECG changes
electrolytes along with water) ▫ PR prolongation
▪ Insufficient gastrointestinal absorption ▫ QT prolongation
▫ Malnutrition: dietary insufficiency ▫ T wave flattening
▫ Malabsorption: sufficient quantities are ▪ Hypocalcemia often occurs alongside
consumed, but insufficient amounts hypomagnesemia. Either/both conditions
are absorbed because of rapid may cause
gastrointestinal transit time (e.g., chronic ▫ Tetany (intermittent muscle spasms
diarrhea) or medications (e.g., proton throughout the body)
pump inhibitors) ▫ Hyperreflexia
▪ Hungry bone syndrome ▫ Chvostek’s sign (facial muscles twitch
▫ Surgical removal of the thyroid or after facial nerve lightly finger tapped
parathyroid 1cm/0.39in below zygomatic process)
▫ Trousseau’s sign (blood pressure cuff
RISK FACTORS occludes brachial artery → pressure
makes nerve fire → muscle spasm
▪ Alcohol use disorder (causes a mixed
makes wrist and metacarpophalangeal
hypomagnesemia, poor diet and alcohol
joints flex)
increases excretion)
▫ Seizures
COMPLICATIONS
▪ Hypokalemia: magnesium interferes with DIAGNOSIS
excretion of potassium
▪ Hypocalcemia: parathyroid gland is LAB RESULTS
dependent on magnesium to function ▪ Measure free unbound magnesium in the
serum, <1.7mg/dl
806 OSMOSIS.ORG
Chapter 113 Hypermagnesemia & Hypomagnesemia
TREATMENT
MEDICATIONS
▪ Mild asymptomatic: oral supplementation
usually sufficient
▪ Severe and/or symptomatic: magnesium
sulphate may be administered
intravenously
OSMOSIS.ORG 807
NOTES
NOTES
HYPERNATREMIA &
HYPONATREMIA

▪ Sustained blood/sodium imbalance LAB RESULTS
▪ Sodium does not easily cross cell ▪ Serum sodium levels
membrane → water drawn to ↑ ▪ Urine sodium, osmolality
concentration areas
TREATMENT
SIGNS & SYMPTOMS
OTHER INTERVENTIONS
▪ Hypernatremia ▪ Cause-dependent
▫ Intracellular dehydration/systemic fluid ▫ Fluids/electrolyte administration
depletion ▫ Fluid restriction to restore balance
▪ Hyponatremia
▫ Fluid shift into cells/systemic fluid
overload
HYPERNATREMIA
osms.it/hypernatremia
CAUSES
PATHOLOGY & CAUSES
Water loss > sodium loss
▪ High sodium concentration in extracellular ▪ Extrarenal water loss
fluid ▫ Skin losses (sweating when hot,
▫ Sodium > 145 milliequivalents/liter exercising, fever), gastrointestinal (GI)
(mEq/L) losses (vomiting, drainage, diarrhea)
▪ Draws water out of cells ▪ Hypothalamic lesions
▪ Acute onset: no cellular adaptation → cells ▫ Antidiuretic hormone (ADH) ↓ → dilute
shrivel, die water loss
▪ Slow onset: osmotically active particles ▫ Thirst center loss (insufficient intake), ↑
generate → prevent water loss serum sodium
▫ Both
▪ Renal water loss (e.g. nephrogenic diabetes
insipidus)
808 OSMOSIS.ORG
Chapter 114 Hypernatremia & Hyponatremia
Sodium ↑
▪ ↑ sodium intake, kidney dysfunction
DIAGNOSIS
▪ Iatrogenic LAB RESULTS
▫ Intravenous (IV) sodium-containing ▪ Measure blood sodium
solutions administered too quickly/too
▫ Hypernatremia: > 145mEq/L
high concentration
Intravascular volume hypovolemic
RISK FACTORS ▪ Drinking too little/losing too much water
▪ Uncontrolled diabetes, underlying polyuria ▫ Urine osmolality: > 600 milliosmoles per
disorder, diuretic therapy, inability to act kilogram (mOsm/kg)
on thirst impulse, age extremes (elderly/ ▫ Urine sodium: < 20mEq/L
neonate), mental/physical impairment, ▪ Kidneys losing sodium
nursing home residency, hospitalization
▫ Urine sodium: > 20mEq/L
▫ Kidney disease, medications (e.g.
COMPLICATIONS osmotic,loop diuretics)
▪ Acute hypernatremia ▪ Euvolemic
▫ Demyelinating brain lesions, rapid brain ▫ Urine osmolality: < 300mOsm/kg
volume ↓ → blood vessel rupture → ▫ Urine sodium: < 20mEq/L
cerebral haemorrhage
▫ Kidneys losing water (diabetes
insipidus)
SIGNS & SYMPTOMS
TREATMENT
▪ Dehydration
▫ Thirst, sunken orbits, dry mucous OTHER INTERVENTIONS
membranes, reduced skin turgor, ▪ ↓ sodium concentration
postural hypotension, tachycardia
▪ ↑ water intake
▪ Acute hypernatremia
▫ Extrarenal water loss
▫ Lethargy, weakness, irritability,
▫ Diabetes insipidus, normal thirst
twitching, seizure, coma
mechanism
▪ Long-standing hypernatremia
▪ Monitor serum sodium, glucose
▫ Fewer symptoms, cells adjust
▫ Dextrose water hydration, isotonic to
plasma, electrolyte free
MNEMONIC: FRIED SALT ▫ Overly dextrose water infusion →
Hypernatremia Signs & hyperglycemia → osmotic diuresis,
Symptoms counteracting rehydration efforts
Fever (low), Flushed skin ▪ Chronic cases
Restless (irritable) ▫ Slower correction
Increased fluid retention, ▪ IV 5% dextrose water → lowers sodium
Increased blood pressure ▫ Hypernatremia correction with IV fluids
Edema (peripheral, pitting) → practice care to avoid cerebral edema
Decreased urinary output, Dry ▪ Rapid overcorrection
mouth ▫ Administer sodium-containing IV fluids
Skin flushed (e.g. saline, Ringer’s lactate)
Agitated ▪ Concomitant extracellular fluid depletion
presenting with severe hypernatremia,
Low-grade fever
hypovolemia signs
Thirst
▫ Isotonic sodium containing fluids
OSMOSIS.ORG 809
HYPONATREMIA
osms.it/hyponatremia
CAUSES
PATHOLOGY & CAUSES ▪ Sodium loss > water loss
▪ Water gain > sodium gain
▪ Low sodium concentration in extracellular
fluid
▫ < 135mEq/L COMPLICATIONS
▪ Sudden/severe hyponatremia → water
shifts into brain cells → swelling →
TYPES ↑ intracranial pressure → ischaemia/
Hypervolemic hyponatremia herniation → respiratory center damage →
death
▪ Significant total body water ↑, small
sodium ↑ ▪ Excessively rapid sodium-level correction
→ cerebral pontine myelinolysis (rapid
▪ Congestive heart failure, hepatic cirrhosis,
sodium, water shifts → myelin-loss in pons)
nephrotic syndrome, water lost to
extracellular space → circulating volume
↓ → ADH, aldosterone released → pure
water retention ↑, sodium retention ↑
(further pure water retention ↑) SIGNS & SYMPTOMS
Hypovolemic hyponatremia ▪ Nausea, vomiting, muscle cramps,
▪ Small total body water, large sodium ↓ confusion, seizure, coma
▪ Diarrhea, vomiting, medications (e.g.
diuretics) → sodium actively pumped into
GI tract DIAGNOSIS
▪ Cerebral salt wasting, intracranial injury/
infection disrupts kidney sympathetic LAB RESULTS
stimulation → ↑ sodium loss ▪ Measure serum sodium concentration
▫ <135mEq/L
Euvolemic hyponatremia ▪ Measure serum osmolality (hyponatremia,
▪ ↑ body water, no body sodium change pseudohyponatremia)
▪ Dilute urine ▪ Edema: hypervolemic hyponatremia
▫ Adrenal insufficiency, hypothyroidism, ▪ Dehydration: hypovolemic hyponatremia
polydipsia (excessive water drinking), ▪ Urine osmolality: dilute, concentrated
potomania (excessive beer drinking) euvolemic hyponatremia
▪ Concentrated urine ▪ Urine concentration
▫ Syndrome of inappropriate antidiuretic ▫ > 100mOsm/kg → SIADH
hormone secretion (SIADH)
▪ Dilute urine
False hyponatremia/pseudohyponatremia ▫ < 100mOsm/kg → excessive fluid
▪ No water, sodium level changes intake
▪ Hypertriglyceridemia (excessive lipid ▪ Urine sodium
concentration), multiple myeloma ▫ > 20–40mEq/L → SIADH, cerebral salt
(excessive protein concentration) → affect wasting
lab equipment → false sodium reading ▪ Urine sodium
▫ < 20mEq/L → hypovolemia
810 OSMOSIS.ORG
Chapter 114 Hypernatremia & Hyponatremia
TREATMENT
OTHER INTERVENTIONS
▪ SIADH
▫ Fluid restriction
▪ Hypovolemia
▫ Fluids
▪ Hyponatremia
▫ Hypertonic saline (slowly—prevents
cerebral pontine myelinolysis)
Figure 114.1 An MRI scan in the sagittal plane

demonstrating central pontine myelinolysis.
There is faint, but well demarcated,
hypoattenuation in the centre of the pons.
OSMOSIS.ORG 811
NOTES
NOTES
HYPERPHOSPHATEMIA &
HYPOPHOSPHATEMIA

▪ Phosphate imbalances in blood LAB RESULTS
▫ Hyperphosphatemia: > 4.5mg/dL ▪ Assess blood phosphate levels
▫ Hypophosphatemia: < 2.5mg/dL
▪ Phosphate intake; absorption through
gastrointestinal (GI) tract; kidney excretion;
TREATMENT
transcellular shift; balance between uptake,
release by bone tissue ▪ See individual disorders
SIGNS & SYMPTOMS

▪ Mild: usually asymptomatic
▪ Severe: may be fatal
Figure 115.1 Illustration depicting parathyroid hormone preventing reabsorption of phosphate

and promoting reabsorption of calcium.
812 OSMOSIS.ORG
Chapter 115 Hyperphosphatemia & Hypophosphatemia
HYPERPHOSPHATEMIA
osms.it/hyperphosphatemia
1cm/0.39in below zygomatic process)
PATHOLOGY & CAUSES ▫ Trousseau’s sign (blood pressure cuff
occludes brachial artery, pressure on
▪ High phosphate levels in blood > 4.5mg/dL nerve leads to muscle spasm, flexing
▪ 70% of individuals with advanced chronic wrist, metacarpophalangeal joints)
kidney disease ▫ Hyperreflexia
▫ Individuals with chronic kidney ▫ Tingling around mouth
disease, hyperphosphatemia →
▫ Seizures
secondary hyperparathyroidism, renal
osteodystrophy → bones thin, weak ▫ Bone pain
▪ Risk of metastatic calcification (e.g. kidney
stones, nephrocalcinosis)
DIAGNOSIS
CAUSES LAB RESULTS
▪ Decreased kidney excretion ▪ ↑ phosphate
▫ Decreased glomerular filtration rate in ▪ ↓ calcium
acute/chronic kidney disease ▪ ↑ vitamin D
▫ Hypoparathyroidism ▪ ↓ parathyroid hormone
▫ Pseudohypoparathyroidism ▪ ↑ urinary phosphate excretion
▫ Vitamin D intoxication: increased
phosphate absorption through Gl tract
OTHER DIAGNOSTICS
▪ Increased phosphate intake
▫ Only acute phosphate load (e.g. too
much phosphate-based laxative)
▪ Transcellular shift TREATMENT
▫ Massive cell death (e.g. tumor lysis
syndrome, rhabdomyolysis, crush MEDICATIONS
injuries, massive hemolysis— ▪ Decrease phosphate absorbed from GI tract
intracellular phosphate released into
▫ Phosphate binders (e.g. aluminium salts,
bloodstream)
calcium carbonate)
▫ Acidosis
▪ Increase phosphate excretion
▫ Healthy kidneys: forced diuresis,
COMPLICATIONS intravenous (IV) saline, loop diuretic
▪ Metastatic calcification (furosemide) → overwhelm proximal
▪ Renal calcinosis convoluted tubule of nephron → unable
to effectively reabsorb solutes (e.g.
phosphates)
SIGNS & SYMPTOMS ▫ Life-threatening hyperphosphatemia:
dialysis
▪ Mild: asymptomatic
▪ Severe: hypocalcemia OTHER INTERVENTIONS
▫ Tetany ▪ Decrease phosphate intake; avoid high-
▫ Chvostek’s sign (facial muscles twitch phosphate foods (e.g. dairy, meat, soda)
after facial nerve lightly finger tapped
OSMOSIS.ORG 813
HYPOPHOSPHATEMIA
osms.it/hypophosphatemia

▪ Low phosphate levels in blood < 2.5mg/dL ▪ Mild: asymptomatic
▪ Severe:
CAUSES ▫ Muscle weakness, respiratory/cardiac
▪ Increased kidney excretion insufficiency
▫ Primary hyperparathyroidism ▫ Altered mental status
▫ Fanconi syndrome: proximal convoluted ▫ Seizures
tubule loses capacity to reabsorb
solutes (e.g. phosphates)
DIAGNOSIS
▪ Decreased intake, absorption through GI
tract
LAB RESULTS
▫ Low intake dietary phosphate (unusual)
▪ ↓ phosphate
▫ Medications impair absorption (e.g.
▪ ↑ calcium
antacids with aluminum/calcium/
magnesium) ▪ ↓ vitamin D
▫ Alcohol use disorder → low dietary ▪ ↑ parathyroid hormone
phosphate intake, vitamin D deficiency
▪ Transcellular shift OTHER DIAGNOSTICS
▫ Refeeding syndrome in severely ▪ History, physical examination
malnourished individuals →
hypokalemia, cardiac arrhythmias,
neurologic problems TREATMENT
▫ Insulin treatment in diabetic
ketoacidosis; insulin makes phosphate MEDICATIONS
move from the bloodstream inside the ▪ Replenish phosphates
cells ▫ Oral administration, diet alone may
▫ Respiratory alkalosis suffice
▫ IV for life-threatening
RISK FACTORS hypophosphatemia
▪ Alcoholism, diabetes, sepsis
OTHER INTERVENTIONS
COMPLICATIONS ▪ Avoid refeeding syndrome by gradually
increasing caloric intake, supplements over
▪ Rhabdomyolysis, kidney damage
several days
▪ Chronic hypophosphatemia
▫ Osteomalacia (adults), rickets (children)
814 OSMOSIS.ORG
NOTES
NOTES
KIDNEY DISORDERS

▪ Urinalysis
PATHOLOGY & CAUSES ▫ Physical, chemical, microscopic data;
compare to serum concentration
▪ Group of diseases involving renal system,
commonly due to systemic disease/ Urine microscopy
iatrogenic factors (medications, fluid ▪ Cell/substance accumulation in tubules →
management) casts → molds to tubular form → excreted
▪ Common complication of hospitalized as tubular-shaped mass
individuals, esp. elderly with chronic ▪ Eosinophils, epithelial cells, erythrocytes
disease
▪ Kidneys sensitive to any systemic change
due to high metabolic demand OTHER DIAGNOSTICS
▪ Classification: pre-, intra-, post-renal ▪ Medical history
causes; based on location of pathology in ▫ Medication, exposure
urinary system ▪ Physical examination
▫ Systemic signs of disease
▫ Limited for renal-specific disease;
SIGNS & SYMPTOMS identify gross abnormalities of lower
urinary tract
▪ Widely variable, universally includes urine
abnormalities (amount, composition, color)
▪ May be easily evident (hematuria)/indolent TREATMENT
(oliguria)
▪ Goal: achieve adequate volume,
composition
DIAGNOSIS
▪ Blood urea nitrogen (BUN)-to-creatinine ▪ Treat underlying systemic disease
(BUN:Cr) ratio ▫ Withdrawal of offending agent (e.g.
▫ Filtration/reabsorptive function medication)
▪ Glomerular filtration rate (GFR)
▫ Estimated value, correlates to filtration
function
OSMOSIS.ORG 815
ACUTE TUBULAR NECROSIS
osms.it/acute-tubular-necrosis
▫ ↓ blood flow → endothelial cell, ↑
PATHOLOGY & CAUSES vasoconstrictor release; endothelin
+ ↓ vasodilators release; nitric oxide
▪ Disease of tubular epithelial cell death; (NO), prostacyclin (PGI2) → net effect
most common cause of acute kidney injury of afferent arteriole constriction → ↓
(AKI) in hospitalized individuals; potential glomerular filtration rate (GFR)
for permanent kidney failure ▪ Ischemic conditions/diseases
▪ AKA acute tubular injury (ATI) ▫ Shock; heart failure; renal artery
▪ Death of tubular epithelial cells → stenosis; excessive gastrointestinal
disruption of basolateral cell surface → (GI) fluid loss; malignant hypertension;
sloughing, obstruction of tubules → ↑ microangiopathies
tubular hydrostatic pressure → ↓ GFR → ▫ Systemic disease associated with
filtration/reabsorption → ↓ urine output → thrombosis: hemolytic-uremic syndrome
oliguria → azotemia (HUS), thrombotic thrombocytopenic
purpura (TTP), disseminated
intravascular coagulation (DIC)
MNEMONIC: LIFELESS ▫ Microscopic polyangiitis
Differences between ▫ Surgical procedures, esp. cardiac,
apoptosis and necrosis abdominal aortic aneurysm (AAA) repair
Leaky membranes
Inflammatory response Nephrotoxins
Fate ▪ Direct tubular epithelial cell injury due to
toxins encountered by kidney
Extent
▪ Most common in proximal convoluted
Laddering
tubule; first tubular site in nephron for
Energy dependent filtered toxin
Swell or shrink ▪ Pathophysiology
Stimulus ▫ Direct toxic renal epithelial tubular cell
injury; death
▪ Endogenous toxins
CAUSES
▫ Myoglobin, hemoglobinuria; uric acid
Ischemia (tumor lysis syndrome); monoclonal light
▪ Death of tubular epithelial cells due to chains (multiple myeloma)
insufficient oxygen to meet metabolic ▪ Exogenous toxins
demand ▫ Medications: aminoglycosides (most
▫ Most common in proximal, thick common), cisplatin, amphotericin B,
ascending tubules; most metabolically nonsteroidal anti-inflammatory drugs
active sites across nephron due to high (NSAIDs)
amounts of active sodium reabsorption ▫ Heavy metals (lead); ethylene glycol;
▫ ↓ blood delivery to tubular epithelial cells radiocontrast agents; organic solvents
→ hypoxia → ischemia
816 OSMOSIS.ORG
Chapter 116 Kidney Disorders
TREATMENT
OTHER INTERVENTIONS
Hydration
▪ Return to euvolemic fluid status/eliminate
offending nephrotoxin
▪ 1–2 weeks for epithelial cells to regenerate
Prevention
Figure 116.1 Histological appearance of acute ▪ Identification of nephrotoxins, elimination/
tubular necrosis. The tubular epithelial cells limitation of use
are poorly demarcated and there is loss of ▪ Identification of high-risk individuals,
nuclei, consistent with necrosis. situations for acute ↓ renal blood flow,
ensure adequate intravascular volume
status
▪ Add allopurinol in tumor lysis syndrome
SIGNS & SYMPTOMS (TLS) cases
▫ Prophylactic/therapeutic
▪ Onset: triggering event
▪ Oliguric phase (10–14 days): may advance
to anuria if unrecognized, untreated
▪ Diuretic phase (> 500ml urine per day):
due to regeneration of functional tubular
epithelial cell growth, outflow of fluid
overload during oliguric phase, osmotic
diuresis from retained solutes
▪ Recovery phase (normal urine output,
concentration): parallels full recovery of
tubular epithelial cell function
DIAGNOSIS
LAB RESULTS
▪ Intrarenal AKI
▪ ↓ BUN:Cr ratio: < 15
▪ ↑ FeNa: > 2%
▪ Dilute urine: ↓ Uosm; < 500mOsm/kg
▪ ↑ K+
▪ Urinalysis: brown granular casts
▫ Sloughed-off epithelial cells in tubules,
excreted as mass)
OSMOSIS.ORG 817
KIDNEY STONES
osms.it/kidney-stone
▪ Uric acid: breakdown product of purines
PATHOLOGY & CAUSES ▪ Pathology: excessive dietary purine → ↑
uric acid as metabolite → hyperuricosuria
▪ AKA nephrolithiasis
▪ Stones form in kidney when solutes Struvite stones (infection/triple stones)
precipitate out as crystals in urine ▪ Dirty white
▪ Solute supersaturated with crystalline ▪ Composite of magnesium, ammonium,
constituents → precipitate out of solution phosphate
→ form crystals → further precipitation → ▪ Urea-splitting bacteria (e.g. Proteus
more solutes deposit, build up → stones vulgaris, Staphylococci) convert urea to
▪ Occurs when ↑ solute, ↓ solvent, ammonia → urine more alkaline → favors
combination of both (e.g. dehydration) precipitation of magnesium, ammonium,
▪ Some stones < 5mm can be passed phosphate
through urinary stream within hours ▪ Often form largest stones; can form
without intervention staghorn calculi, branch into renal calyces
▪ Pathology: ammonium ions from urease-
TYPES producing bacteria + alkaline urine →
precipitation
Calcium stones
▪ Calcium oxalate (most common) Cystine stones (less common)
▫ Black/dark brown ▪ Yellow/light pink
▫ Positively-charged calcium ion binds ▪ Composed of amino acid cystine
to negatively-charged oxalate ion in ▪ Pathology: autosomal recessive/dominant
medullary interstitium disorder → defective renal transport of
▫ More likely in acidic urine cystine → ↓ renal reabsorption + increased
urinary cystine excretion → cystinuria
▫ Pathology: primary hyperoxaluria
(autosomal recessive disorder → Xanthine stones (rare)
excessive hepatic oxalate production); ▪ Brick red
acquired hyperoxaluria (e.g. enteric
▪ Composed of xanthine, usually found in
oxaluria; → excessive absorption of
xanthinuria
oxalate in gut)
▪ Pathology
▪ Calcium phosphate
▫ Hereditary xanthinuria: autosomal
▫ Dirty white
recessive disorder → ↓ xanthine oxidase
▫ Calcium binds to negatively charged → ↓ conversion of xanthine to uric acid
phosphate group → ↑ urinary excretion of xanthine
▫ More likely in alkaline urine ▫ Acquired: xanthine oxidase inhibitors
▫ Pathology: alteration in calcium (e.g. allopurinol) or liver disease → ↓
absorption in gut/renal reabsorption → xanthine oxidase
hypercalciuria
Uric acid stones RISK FACTORS

▪ Red brown ▪ Genetic predisposition
▪ Physiologic pH uric acid, proton loss ▫ Positive family history; genetic
→ urate ion → binds sodium → forms mutations (e.g. primary hyperoxaluria)
monosodium urate → crystallizes → stones
818 OSMOSIS.ORG
▪ Renal/urinary tract disorders

▫ Vesicoureteral reflux; urinary tract
SIGNS & SYMPTOMS
infections (UTIs); congenital urinary tract
▪ Dull, localized flank pain in mid, lower back;
malformations (e.g. horseshoe kidney);
one/both sides
cystic kidney diseases; neurogenic
bladder ▫ Pain caused by dilation, stretching,
spasm due to obstruction of ureter
▪ Factors associated with hyperuricemia; diet
high in purines (e.g. red meat, organ meat, ▫ Subsides once stone reaches bladder
shellfish, anchovies); cellular depletion (e.g. ▪ Renal colic
leukemia, cytotoxic medications); gout ▫ Intense bouts of pain caused by smooth
▪ Factors associated with increased serum muscle peristalsis against obstruction
calcium ▫ Caused by sharp stone moving through
▫ Primary hyperparathyroidism; ureter
inflammatory bowel disease; diets ▪ Pain on urination (dysuria); cloudy, red/
high in calcium oxalate (beer, brown urine
chocolate, nuts); excessive calcium ▪ Fever, chills (infection); nausea, vomiting
supplementation
▪ Excessively salty foods; low fluid intake,
dehydration; ↑ BMI/obesity; more common DIAGNOSIS
in individuals who are biologically male
DIAGNOSTIC IMAGING
COMPLICATIONS X-ray
▪ Gout ▪ Radiopaque
▫ May exacerbate existing gout/cause ▫ Calcium oxalate, phosphate
new onset gout
▪ Radiolucent
▪ Infections
▫ Uric acid stones, struvite stones, cystine
▫ UTIs; pyelonephritis; urosepsis; abscess stones, xanthine stones
▪ Scarring, stenosis; urinary fistula;
obstruction of ureter → hydronephrosis; CT scan
renal failure ▪ Abdomen, pelvis (preferred)
▪ Performed without contrast (contrast ↓
sensitivity for stones < 3mm)
▪ Accurately detects size, location
▪ Density, location, appearance determines
category; cannot identify type of calcium
stones (e.g. oxalate/phosphate)
Ultrasound
▪ Preferred initial modality for pregnant
individuals
Figure 116.2 A single calcium oxalate kidney ▪ Reliably detects hydronephrosis (if stone
stone. obstructive)
▪ Stones detected as echodensities (with
shadow effect); less sensitive than CT scan
OSMOSIS.ORG 819
Figure 116.4 Scanning electron micrograph
Figure 116.3 An abdominal CT scan in the of the surface of a calcium oxalate stone.
axial plane demonstrating a stone in the renal
pelvis. There is prominent hydronephrosis.
OTHER DIAGNOSTICS
History
▪ Prior stones, colicky episodes of flank pain,
passage of stone/gravel in urine
Physical exam
▪ Ancillary findings support etiologies/risk
factors (e.g. hypovolemia, podagra of gouty
arthritis)
TREATMENT
MEDICATIONS
▪ Analgesics
▫ Treat pain
▪ Potassium citrate treatment
Figure 116.5 A plain abdominal radiograph ▫ Makes urine alkaline, ↓ salt
demonstrating a staghorn calculus of the left crystallization, ↓ stone formation
kidney. ▪ Alpha-adrenergic blockers, calcium channel
blockers
▫ ↓ spasms, help stones pass through
Intravenous pyelography (IVP) relaxed ureters, ↓ pain
▪ Less common ▪ Magnesium, citrate
▪ Radiographic imaging ▫ Inhibit crystal growth, aggregation;
▫ IV iodinated contrast administration prevent kidney stones forming
▪ Reliable for hydronephrosis; less sensitive, ▪ Shockwave lithotripsy
specific than CT scan for stone detection ▫ Noninvasive treatment; acoustic pulses
travel through body to break up kidney
LAB RESULTS stones into smaller fragments
▪ Microscopic/gross hematuria
▪ Crystals may be present
820 OSMOSIS.ORG
SURGERY
▪ Surgery, endoscopic stent placement
▫ For larger stones
OTHER INTERVENTIONS
▪ Hydration
▫ Reverse precipitation, facilitate passage
OSMOSIS.ORG 821
RENAL PAPILLARY NECROSIS
osms.it/renal-papillary-necrosis

▪ Damage to renal papillary tissue, severe ▪ Recent infection/immune challenge may
enough to result in cell death; multiple trigger symptoms
etiologies ▪ Colicky flank pain
▪ Located within renal medulla near end of
vasa recta → ↑ susceptibility to ischemic
damage when vascular blood supply DIAGNOSIS
impaired
▪ Both kidneys usually involved DIAGNOSTIC IMAGING
CT scan/X-ray
CAUSES ▪ Calcifications
▪ Acute interstitial nephritis, phosphate ▫ Variable, due to underlying etiology
nephropathy; severe, acute pyelonephritis;
renal tuberculosis (rare) Kidney ultrasound
▪ Calcifications appear echodense
COMPLICATIONS
▪ Obstruction due to sloughed-off papillary LAB RESULTS
necrotic tissue ▪ Hematuria; proteinuria (foamy urine); flecks
▪ Further complicated by UTI; worsens AKI of tissue in urine; sterile pyuria
822 OSMOSIS.ORG
TREATMENT
SURGERY
▪ Remove obstruction
OTHER INTERVENTIONS
▪ Specific to underlying etiology: withdraw
offending analgesic; control RBC sickling
RENAL TUBULAR ACIDOSIS (RTA)

osms.it/renal-tubular-acidosis-
▪ Fanconi syndrome
PATHOLOGY & CAUSES ▫ Reabsorptive disease of proximal
tubular cells
▪ Group of disorders; renal tubular cell
▫ Results in prophosphaturia, glycosuria,
defects unable to acidify urine → metabolic
aminoaciduria, uricosuria, proteinuria
acidosis
▫ Due to genetic disease, medication (e.g.
tetracyclines)
CAUSES ▪ May be no change in urinary pH
RTA I (AKA distal RTA) ▫ Intact distal tubular cell function, ability
▪ Unable to secrete H+ to acidify urine
▪ Cells involved RTA III (rare)
▫ Alpha-intercalated cells in distal tubule, ▪ Cells involved: proximal, distal tubule
collecting duct ▪ Etiology mostly unknown
▪ Genetic mutations ▪ Congenital carbonic anhydrase deficiency;
▫ H+ ATPase, H/K ATPase on apical defect of carbonic anhydrase needed to
surface: unable to actively secrete H+ convert HCO3 + H+ → H2CO3; associated
into tubular lumen with osteopetrosis (carbonic anhydrase for
▫ HCO3/Cl antiporter on basolateral cell bone remodeling)
surface: unable to transport HCO3 to
bloodstream RTA IV (AKA hyperkalemic acidosis)
▪ Medications ▪ Cells involved: distal tubular cells (alpha-
▫ Lithium/amphotericin B intercalated, principal cells)
▫ Makes cells permeable for H+ to leak ▪ Aldosterone deficiency (e.g. Addison
across into cell disease)
▫ ↓ aldosterone-induced secretion of
RTA II H+ via apical transporters in alpha-
▪ Unable to resorb HCO3; lost in urine intercalated cells → ↑ cellular H+ → H+
▪ Cells involved: brush border cells in moves down gradient to peritubular
proximal tubule capillaries → acidemia
▪ Genetic mutations ▪ Aldosterone resistance
▫ Na/HCO3 cotransporter on basolateral ▫ Genetic mutation of ENac (apical cell
surface: ↓ HCO3 transport → imbalance surface of principal cells)
in H+ → acidemia
OSMOSIS.ORG 823
▪ Severe hypovolemia
▫ ↓ intracellular Na → altered Na/K
exchange → ↑ intracellular K+ →
peritubular capillaries → ↑ serum K+ and
↓ serum Na+ → acidemia
▪ Systemic lupus erythematosus (SLE)
▫ Rare complication
▪ Medications (e.g. lithium, amphotericin B)
▫ H+ diffuses across cell into blood →
acidemia
COMPLICATIONS
▪ Shock
▫ Metabolic acidosis → dilation of
peripheral arterioles → ↓ afterload,
preload → ↓ effective circulating volume
→ distributive shock → inadequate
perfusion to vital organs Figure 116.6 A plain kidney-ureter-bladder
▪ Nephrolithiasis (KUB) X-ray demonstrating medullary
calcinosis, a complication of renal tubular
▫ Alkalotic urine environment (pH >
acidosis.
6; esp. in RTA I) → hypercalciuria →
precipitation of calcium stones
TREATMENT
SIGNS & SYMPTOMS
MEDICATIONS
▪ GI ▪ RTA I, II: eplenish HCO3, correct
▫ ↓ appetite, vomiting, abdominal pain hypokalemia with potassium citrate
▪ Shock ▫ RTA II: thiazide diuretics → water loss, ↑
▫ Tachycardia; flushing; Kussmaul HCO3 reabsorption
breathing → ↓ CO2 serum levels ▪ RTA IV: treat hypoaldosteronism
▪ Nephrolithiasis (potential complication) ▫ Fludrocortisone, loop diuretics → ↑
▫ Colicky pain; hematuria; urinary Na+ delivery to collecting duct → ↑ K/H
frequency/hesitancy exchange
DIAGNOSIS
LAB RESULTS
▪ Blood studies
▫ Metabolic acidosis: pH < 7.35, < HCO3
▫ ↑ Cl-
▫ ↑ K+ (in RTA IV)
▪ Urinalysis
▫ Urinary anion gap (above 20mEq/L)
▫ Acidity
▫ RTA I, II (acutely): alkalotic (pH > 6)
▫ RTA III: not characteristically defined
▫ RTA IV: acidic (pH < 6)
824 OSMOSIS.ORG
NOTES
NOTES
NEPHRITIC SYNDROME

▪ Diseases caused by inflammation, damage LAB RESULTS
to glomeruli of kidney; become more ▪ Protein/blood, RBC casts in urine
permeable, allow red blood cells (RBCs) ▪ Decreased glomerular filtration
into urine → hematuria
Kidney biopsy
CAUSES ▪ Changes under light/electron microscope,
immunofluorescence
▪ Children/adolescents: IgA nephropathy,
post-streptococcal glomerulonephritis,
hemolytic uremic syndrome
TREATMENT
▪ Adults: systemic lupus erythematosus,
Goodpasture’s syndrome, rapidly MEDICATIONS
progressive glomerulonephritis
▪ Edema
▫ Diuretics (furosemide), medical nutrition
COMPLICATIONS therapy
▪ Acute kidney failure ▪ Blood pressure control
▫ Angiotensin converting enzyme
inhibitors (ACE) inhibitors
SIGNS & SYMPTOMS
▪ Damaged, permeable glomeruli → OTHER INTERVENTIONS
hematuria, proteinuria ▪ Reduce salt, potassium intake
▪ Decreased glomerular filtration rate →
edema, hypertension
▪ Less waste product excreted → uremia
OSMOSIS.ORG 825
ACUTE PROLIFERATIVE
GLOMERULONEPHRITIS
osms.it/proliferative-glomerulonephritis

▪ Inflammation of glomeruli, complication of ▪ Nephritic syndrome: hematuria, oliguria,
bacterial infection edema, hypertension
▪ AKA poststreptococcal glomerulonephritis ▪ Fever, headache, malaise, anorexia, nausea
▫ Commonly arises several weeks after
group A beta-hemolytic streptococcus
infection DIAGNOSIS
▪ Type III hypersensitivity reaction
LAB RESULTS
▫ IgG/IgM antibodies bind to bacterial
antigens, form immune complexes → ▪ Protein/blood in urine
complexes travel through bloodstream ▪ Antibodies against group A streptococcus
to glomerulus, deposit in glomerular (e.g. anti-DNase B antibodies, anti-
basement membrane Streptolysin O antibody)
▪ Immune complex/complement deposits ▪ Decreased complement levels
trigger immune reactions
Renal biopsy
▫ Activate complement system →
▪ Light microscopy
enzyme cascade → formation of
membrane attack complex → damage ▫ Mesangial proliferation → hypercellular
to podocytes, mesangial cells glomerulus
▫ Recruit inflammatory cells → proteases, ▪ Electron microscopy
oxidants release → basement ▫ Subepithelial deposits of immune
membrane damage → hematuria, complexes, “humps”
proteinuria → nephritic syndrome ▪ Immunofluorescence
▫ “Starry sky,” granular deposition of IgG,
CAUSES complement in basement membrane,
mesangium
▪ Group A beta-hemolytic streptococcus
infection
TREATMENT
RISK FACTORS
▪ Most commonly in children (who are ▪ Usually supportive
biologically male)
▫ Six weeks after impetigo, 1–2 weeks
after throat infection
COMPLICATIONS
▪ Rapidly progressive glomerulonephritis,
renal failure
826 OSMOSIS.ORG
Chapter 117 Nephritic Syndrome
Figure 117.1 The effect of crescentic glomerulonephritis on the nephron.
Figure 117.2 The constituent parts of the crescent seen in crescentic glomerulonephritis.
Figure 117.3 Histological appearance

of the glomerulus in post-infective
glomerulonephritis. The glomerulus is
expanded and compressed due to infiltration
of neutrophils and other inflammatory cells.
OSMOSIS.ORG 827
GOODPASTURE'S SYNDROME
osms.it/goodpasture-syndrome

▪ AKA anti-GBM antibody disease; damage LAB RESULTS
of basement membrane in lungs, kidneys;
mostly composed of Type IV collagen Renal biopsy
▪ Damaged by Type II hypersensitivity ▪ Light microscopy
reaction ▫ Crescentic glomerulonephritis
▫ IgG antibodies (rarely IgM/IgA) bind ▪ Electron microscopy
to alpha 3 folded chain → activate ▫ Diffuse thickening of glomerular
complement system → damage basement membrane
collagen fibers of basement membrane ▪ Immunofluorescence
▫ Linear deposition along basement
RISK FACTORS membrane
▪ Bimodal distribution with peak incidence
age 20–30 (biologically male), 60–70
(biologically female) TREATMENT
▪ Genetic: predisposition for genes that
code for HLA-DR15 (immune molecule;
MEDICATIONS
identifies, binds to foreign molecules) ▪ Corticosteroids, cyclophosphamide,
plasmapheresis to filter plasma/fluid of
▪ Environmental: infection, smoking,
blood (reduces risk of chronic renal failure)
oxidative stress, hydrocarbon-based
solvents
COMPLICATIONS
▪ Chronic renal failure; require dialysis/kidney
transplant; hemoptysis
SIGNS & SYMPTOMS

▪ Pulmonary manifestations usually occur
before renal ones; minority (20–40%) with
only renal manifestations
▫ Damaged lung alveoli → cough, Figure 117.4 Histological appearance
hemoptysis, dyspnea of the kidney in a case of crescentic
glomerulonephritis caused by Goodpasture’s
▫ Kidney filtration problems (e.g.
syndrome.glomerulonephritis on the nephron.
hematuria, proteinuria) → nephritic
syndrome
828 OSMOSIS.ORG
Figure 117.5 Immunofluorescence with

positive signal for antibodies to IgG. In
addition the IgG deposition is linear. These
features are consistent with Goodpasture’s
syndrome.
HEMOLYTIC-UREMIC SYNDROME
osms.it/hemolytic-uremic-syndrome
CAUSES
PATHOLOGY & CAUSES ▪ Escherichia coli (E. coli) from contaminated
food/drink
▪ Small blood clots in tiny blood vessels,
▫ Enterohemorrhagic E. coli (EHEC,
mostly in kidneys → RBCs break down,
serotype O157:H7); may be caused by
kidney function decreases → urea levels in
other strains
blood increase
▫ E. coli attaches to intestinal wall →
▪ Triggered by bloody diarrhea
secretes Shiga-like toxin → absorbed by
▫ Diarrhea-positive/D+ hemolytic uremic intestinal blood vessels → attaches to
syndrome (HUS/typical HUS) immune cells → toxins from white blood
cells (WBCs) bind to endothelial cells
Atypical hemolytic uremic syndrome
of glomerular capillaries → inhibition of
▪ D-hemolytic uremic syndrome protein synthesis → apoptosis → many
▫ No preceding diarrhea tiny blood clots form in kidneys
▪ Damage to endothelial cell lining of
glomerular capillaries from infections
not related to diarrhea, medication,
RISK FACTORS
autoimmune causes ▪ Children < five years old, people 75+ years
old, genetic predisposition to endothelial
▪ Infants, children
cell damage
▫ Streptococcus pneumoniae presents as
pneumonia/meningitis
▪ Familial forms
▫ Genetically increased tendency for
endothelial cell damage
OSMOSIS.ORG 829
▪ Bloody diarrhea MEDICATIONS
▪ Weakness, fatigue, lethargy, jaundice due
Typical, D+ hemolytic uremic syndrome
to red blood cell destruction
▪ Shiga-like toxin clears in days to weeks,
▪ Fever, blood clots: affect brain blood supply
antibiotics not recommended as dead
→ visual disturbances, altered mental
bacteria potentially release more toxins
status, seizures, stroke → death
Atypical hemolytic uremic syndrome
DIAGNOSIS ▪ Identify underlying cause
LAB RESULTS
▪ Requires thrombocytopenia,
microangiopathic hemolytic anemia
(MAHA), acute renal failure
▪ Proteinuria, hematuria
▪ Schistocytes/helmet cells
▪ D+ hemolytic uremic syndrome
▫ Shiga toxin (ELISA), gene encoding
Shiga toxin (PCR)
▪ Differential diagnosis
▫ Thrombotic thrombocytopenic purpura
(TTP) hemolytic uremic syndrome:
measure ADAMTS13 activity in plasma
▫ Disseminated intravascular coagulation
(DIC): DIC panel (e.g. pTT, INR, d-dimer,
fibrinogen)

acute thrombotic microangiopathy which is
the pathological mechanism of renal failure
in hemolytic uremic syndrome. Endothelial
damage caused thrombus formation in small
Figure 117.6 90% of hemolytic-uremic
capillaries.
syndrome cases are a result of a prior
infection with Shiga toxin producing E. coli.
830 OSMOSIS.ORG
IgA NEPHROPATHY
osms.it/IgA-nephropathy

▪ AKA Berger’s disease; abnormal IgA forms, LAB RESULTS
deposits in kidneys → kidney damage ▪ RBCs, RBC casts
▪ Abnormal post-translational modification
of IgA → development of IgA immune Renal biopsy
complexes preferentially deposited in ▪ Light microscopy
mesangium → alternative complement ▫ Mesangial proliferation, immune
pathway activated → cytokines released complexes deposited in mesangium
→ macrophages migrate to kidney → ▪ Electron microscopy
glomerular injury → RBCs leak into urine ▫ Immune complexes deposited in
▪ Associated with gastrointestinal (GI)/ mesangium
respiratory tract infections ▪ Immunofluorescence
▫ Mesangial IgA deposits, +/- IgA, +/- IgM
RISK FACTORS
▪ Most common nephropathy worldwide;
usually presents in childhood TREATMENT
▪ Highest prevalence in people of East Asian/
European ancestry MEDICATIONS
▪ Family history of chronic nephritis, alcohol ▪ Corticosteroids
consumption, recurrent infections ▫ Prevent immune system making
defective IgA1, anti-glycan IgG
COMPLICATIONS
▪ Nephrotic syndrome, chronic kidney
disease
SIGNS & SYMPTOMS

▪ Episodic hematuria
▫ Sometimes accompanying upper
respiratory tract infections
▪ Asymptomatic microscopic hematuria
▫ With subnephrotic proteinuria
▪ Classic nephrotic syndrome/kidney injury
(minority)
Figure 117.8 Immunofluorescence with
positive signal for antibodies to IgA
immunoglobulin. The pattern of deposition in
the glomerulus is granular.
OSMOSIS.ORG 831
RAPIDLY PROGRESSIVE
GLOMERULONEPHRITIS
osms.it/progressive-glomerulo

▪ Inflammation of kidney’s glomeruli → ▪ Nephritic syndrome
crescent-shaped proliferation of cells in ▫ Hematuria, oliguria, edema,
Bowman’s capsule → renal failure within hypertension
weeks/months
▪ Inflammation damages glomerular
basement membrane → inflammatory DIAGNOSIS
mediators, complement proteins, fibrin,
monocytes macrophages pass into LAB RESULTS
Bowman’s space → expansion of parietal
layer of cells into thick, crescent-moon Kidney biopsy
shape → may undergo sclerosis/scarring ▪ Light microscopy: crescent-shaped
glomeruli
TYPES Immunofluorescence
▪ Type I: linear, antibodies bind to collagen of
Primary
glomerular basement membrane
▪ Idiopathic
▪ Type II: granular, immune complex
Secondary deposition in subendothelium
▪ Type I: anti-GBM antibodies ▪ Type III: negative (pauci-immune)
▫ Goodpasture syndrome ▫ Type III associated with ANCAs in blood
▪ Type II: immune complexes
▫ Poststreptococcal glomerulonephritis,
systemic lupus erythematosus, IgA
TREATMENT
nephropathy, Henoch-Schonlein
purpura
MEDICATIONS
▪ Pulse methylprednisolone, then
▪ Type III: anti-neutrophilic cytoplasmic
prednisone/cyclophosphamide/rituximab/
antibodies (ANCA)
plasmapheresis
▫ Cytoplasmic ANCA (C-ANCA):
Wegener’s granulomatosis
▫ Perinuclear ANCA (P-ANCA): OTHER INTERVENTIONS
microscopic polyangiitis, Churg-Strauss ▪ If renal failure irreversible
syndrome ▫ Dialysis/kidney transplant
COMPLICATIONS
▪ If untreated: rapid progression to acute
renal failure
832 OSMOSIS.ORG
OSMOSIS.ORG 833
834 OSMOSIS.ORG
NOTES
NOTES
NEPHROTIC SYNDROME

▪ Collection of diseases caused by LAB RESULTS
inflammation, damage to glomeruli of ▪ Protein/blood in urine
kidney; glomeruli become more permeable, ▪ Decreased glomerular filtration rate:
allow proteins from blood into urine → estimated from serum creatinine clearance
proteinuria
Kidney biopsy
Proteinuria
▪ Changes under light/electron microscope,
▪ Hallmark of nephrotic syndromes immunofluorescence
▫ Loss of protein (mostly albumin) → ▪ Blood test: albumin, cholesterol levels
hypoalbuminemia; lowers oncotic
pressure in blood → water moves out of
vessels into interstitium → edema TREATMENT
▫ ↓ proteins → ↑ lipids → hyperlipidemia;
↑ lipids filtered in glomeruli → lipiduria; MEDICATIONS
fatty casts, foamy urine ▪ Edema
▫ Diuretics (furosemide), medical nutrition
CAUSES therapy
▪ Immune-mediated, metabolic, ▪ Blood pressure control
hemodynamic disturbances ▫ Angiotensin converting enzyme (ACE)
▪ Primary: kidney lesion inhibitors
▫ Minimal change disease, focal ▪ Hyperlipidemia
segmental glomerulosclerosis, ▫ Reduce cholesterol, saturated fat intake
membranous glomerulonephritis, ▪ Hypercoagulability
membranoproliferative
▫ Heparin
glomerulonephritis
▪ Infections
▪ Secondary: systemic disease
▫ Antibacterial drugs
▫ Diabetic nephropathy, lupus nephritis
▫ Cyclophosphamide, prednisone
COMPLICATIONS
▪ Loss of proteins (e.g. anticoagulants, iron-
carrying proteins): thromboembolism, renal MNEMONIC: Protein LEAC
vein thrombosis, microcytic hypochromic Nephrotic syndrome findings
anemia, infections, hypocalcaemia
Proteinuria
Lipid up
SIGNS & SYMPTOMS Edema
Albumin down
▪ Proteinuria, hypoalbuminemia, edema, Cholesterol up
hyperlipidemia, lipiduria, hypercoagulability
OSMOSIS.ORG 835
DIABETIC NEPHROPATHY
osms.it/diabetic-nephropathy
RISK FACTORS
PATHOLOGY & CAUSES ▪ Family history; poor control of diabetes,
duration of diabetes (more common if
▪ Kidney damage caused by Type I, Type II developed at younger age); poor control of
diabetes hypertension; obesity
CAUSES
SIGNS & SYMPTOMS
Excess glucose in blood
▪ Overrides renal threshold for glucose ▪ Mostly asymptomatic
(160–180mg/dl) → glycosuria
▪ Non-enzymatic glycation of proteins →
basement membranes thicken → hyaline DIAGNOSIS
arteriosclerosis
▪ Hyaline arteriosclerosis, arteriole dilatation LAB RESULTS
increases pressure in glomerulus → ▪ Microalbuminuria (30–300mg/day),
increased glomerular filtration rate (first macroalbuminuria (> 300mg/day)
stage)
▪ Thickening of basement membrane →
glomerulus expands, filtration slits widen → TREATMENT
increased permeability
▪ High-pressure state → supportive
MEDICATIONS
mesangial cells secrete more structural ▪ Control hyperglycemia
matrix → Kimmelstiel–Wilson nodules ▪ ACE inhibitors/angiotensin receptor
▪ Damage glomeruli → decreased glomerular blockers: reduce constriction of efferent
filtration rate (second stage) arteriole → lower pressure in glomerulus

glomeruli in a case of diabetic nephropathy.
There is diffuse sclerosis of the glomerulus.
836 OSMOSIS.ORG
Chapter 118 Nephrotic Syndrome
FOCAL SEGMENTAL
GLOMERULOSCLEROSIS
osms.it/focal-segmental

▪ Histologic finding of glomerular damage, LAB RESULTS
not distinct disease. ▪ Protein in urine > 3.5g/L
▪ Affects parts (segmental) of some (focal)
glomeruli of nephron; damage, scarring → Kidney biopsy: most definitive
proteinuria ▪ Light microscopy: segmental sclerosis,
▪ Foot processes of podocytes damaged → hyalinosis of glomeruli
plasma proteins, lipids permeate glomerular ▪ Electron microscope: effacement of foot
filter processes of podocytes
▪ Proteins, lipids trapped → build up ▪ Immunofluorescence: nonspecific focal
inside glomeruli → hyalinosis (hyaline/ deposits of IgM, complement proteins
glassy view on histology) → scar tissue not always seen (sometimes trapped in
(glomerulosclerosis) hyalinosis)
CAUSE TREATMENT
▪ Primary: unknown
▪ Secondary: result of underlying cause MEDICATIONS
▫ Sickle cell disease, HIV, renal ▪ Blood pressure reduction
hyperfiltration (e.g. unilateral renal ▫ ACE inhibitors
agenesis), heroin abuse ▪ Edema
▪ Genetic forms: FSGS 1–6 ▫ Diuretics
▪ Prednisone/calcineurin inhibitors
RISK FACTORS ▫ Depend on nephrotic-range proteinuria,
▪ More common in black people of African likelihood of reversibility
descent/people of Latin American descent
▪ Morbid obesity
▪ Chronic kidney disease (congenital
malformation)
COMPLICATIONS
▪ End-stage renal failure: inconsistent
response with treatment; adults—more
involved segments of kidney’s glomeruli →
kidney failure

SIGNS & SYMPTOMS focal segmental glomerulosclerosis. There is
sclerosis and hyalinosis of only one part of
▪ Proteinuria, hypoalbuminemia, edema, the glomerulus, in this case the hilar part. The
hyperlipidemia, lipiduria, hypercoagulability more distal part is normal.
OSMOSIS.ORG 837
LUPUS NEPHRITIS
osms.it/lupus-nephritis

▪ Inflammation of kidney due to systemic LAB RESULTS
lupus erythematosus.
Kidney biopsy
▪ Focal (nephrons in one area)/diffuse (all
nephrons in both kidneys) ▪ Microscopic presentation depends on class
of lupus nephritis
▪ Caused by antinuclear antibodies (anti-
dsDNA): bind to nuclear antigens, form
antigen-antibody complexes
▪ Antigen-antibody complexes deposit in
capillary walls, basement membrane,
Bowman’s space → initiate inflammatory
response → Type III hypersensitivity
reaction
TYPES
Class I
▪ Minimal mesangial glomerulonephritis
Class II
▪ Mesangial proliferative glomerulonephritis
Class III
▪ Focal glomerulonephritis
Class IV
▪ Diffuse proliferative nephritis
Class V
▪ Membranous glomerulonephritis
Class VI
▪ Advanced sclerosing lupus nephritis
COMPLICATIONS
▪ Renal vein thrombosis, pulmonary Figure 118.3 Gross pathological appearance
embolism, rapidly progressive of a kidney in case of lupus nephritis. The
glomerulonephritis renal capsule has a characteritic flea-bitten
appearance.
SIGNS & SYMPTOMS

▪ Nephrotic, nephritic syndrome
▪ Nephritic syndrome: hematuria,
hypertension, edema, proteinuria, oliguria
838 OSMOSIS.ORG
TREATMENT
MEDICATIONS
▫ Corticosteroids; mycophenolate,
cyclophosphamide

glomerulus in a case of lupus nephritis. There
is global mesangial cell proliferation and
abundant mesangial matrix.
OSMOSIS.ORG 839
MEMBRANOPROLIFERATIVE
GLOMERULONEPHRITIS
osms.it/membrano-golmerulonephritis
▫ Presence of autoantibodies against

PATHOLOGY & CAUSES proteins that regulate pathway
▪ Nephritic factor (C3NeF)
▪ Type of nephrotic syndrome; inflammation
▫ IgG antibody, binds to C3 convertase
of glomerular basement membrane,
→ C3 convertase more stable, active
mesangium → decreased kidney function,
longer
proteinuria
▫ Only complement deposits, no immune
▪ Immune complex/complement deposits
complex deposits
trigger immune reactions
▫ Autoimmune diseases: systemic lupus
▫ Activates complement system →
erythematosus, scleroderma, Sjögren
enzyme cascade → membrane attack
syndrome, sarcoidosis
complex → damage to podocytes,
mesangial cells ▫ Cancer: leukemia, lymphoma
▫ Recruits inflammatory cells → Type II
proteases, oxidants release → basement
▪ Nephritic factor (C3NeF)
membrane damage → proteins leak into
urine → nephrotic syndrome ▫ IgG antibody binds to C3 convertase
→ C3 convertase more stable, active
longer
TYPES
▪ Appearance under light microscopy Type III
▫ Type I, II, II ▪ Idiopathic
▫ All three can present as nephrotic,
nephritic syndrome RISK FACTORS
▪ Immunofluorescence: immune complex- ▪ Dysregulation of complement system
mediated MPGN, complement-mediated
MPGN
COMPLICATIONS
▪ Chronic renal failure, hypertension
CAUSES
Type I SIGNS & SYMPTOMS
▪ Chronic infection (e.g. hepatitis B, hepatitis
C) ▪ Nephrotic syndrome
▫ Antigens released → bind antibodies ▫ Proteinuria, peripheral edema, foamy
in blood → immune complexes deposit urine, hyperlipidemia, lipiduria
in glomerular basement membrane →
▪ Nephritic syndrome (more common)
activate classical complement pathway
→ complement protein + immune ▫ Hematuria, oliguria (low production of
complex deposits urine), hypertension
▪ Inappropriate activation of alternative
pathway of complement
▫ Mutation in proteins that regulate
pathway
840 OSMOSIS.ORG
▪ Type II
DIAGNOSIS ▫ Complement deposits along basement
membrane of glomeruli, tubules,
LAB RESULTS Bowman’s capsule
Kidney biopsy ▪ Type III
▫ Subepithelial deposits in mesangium,
Electron microscopy subendothelial space
▪ Type I
▫ Subendothelial deposits
▫ Thickening of basement membrane TREATMENT
▫ Mesangial interposition: mesangial cells
reach cytoplasmic arms through thick MEDICATIONS
basement membrane, split lengthwise ▪ Treatment of underlying cause (e.g. antiviral
→ duplicate basement membrane → therapy for hepatitis B virus)
“tram-track” appearance ▪ If underlying cause ruled out/nephrotic
range proteinuria
▫ Immunosuppressive therapy (steroids)
MEMBRANOUS
GLOMERULONEPHRITIS
osms.it/membranous-glomerulonephritis
enzyme cascade → membrane attack

PATHOLOGY & CAUSES complex → damage to podocytes,
mesangial cells
▪ Inflammation of glomerular basement ▫ Recruits inflammatory cells →
membrane triggered by immune complex proteases, oxidants release → basement
deposits → increased permeability, membrane damage → proteins leak into
proteinuria → nephrotic syndrome urine → nephrotic syndrome
▪ Glomerular basement membrane damaged ▪ Often benign
by immune complex deposits; sandwiched
▫ Spontaneous complete remission:
between epithelial cells of podocytes,
5–30% at five years
glomerular basement membrane
(subendothelial deposits) ▫ Spontaneous partial remission:
25–40% at five years
▪ Autoantibodies target glomerular basement
membrane
▫ Two major antigen targets on CAUSES
podocytes: M-type phospholipase A2
receptor, neural endopeptidase Primary
▪ Complexes outside kidney, carried through ▪ Mostly idiopathic
blood, deposit in basement membrane ▪ Associated with human leukocyte antigen
▫ Possible antigens: cationic bovine (HLA) alleles (e.g. HLA-DQA1)
serum albumin (cow’s milk, beef protein)
▪ Immune complex deposits → immune
reactions
▫ Activates complement system →
OSMOSIS.ORG 841
Secondary
▪ Auto-antibodies generated in response to
DIAGNOSIS
underlying conditions
LAB RESULTS
▪ Infections
▪ Proteinuria
▫ Hepatitis B virus, hepatitis C virus,
syphilis Renal biopsy
▪ Medications ▪ Light microscopy
▫ NSAIDs, penicillamine, gold ▫ Diffuse thickening of glomerular
▪ Autoimmune basement membrane
▫ Systemic lupus erythematosus ▪ Electron microscopy
▪ Malignancy ▫ “Spike and dome” appearance due to
glomerular basement matrix on top of
subepithelial deposits; effacement of
RISK FACTORS podocytes
▪ White people of European descent
▪ Immunofluorescence
▪ Increase risk of end-stage renal disease
▫ Deposits appear granular throughout
▫ Older age at onset (> 50 years), glomerular basement membrane
individuals who are biologically male,
▪ If kidney biopsy not an option
nephrotic-range proteinuria (> 8–10g/
day), increased serum creatinine ▫ Serum: assayed for antibodies
associated with membranous
glomerulonephritis (anti-PLA2R
COMPLICATIONS antibody)
▪ Chronic kidney failure, if untreated +
nephrotic range proteinuria
TREATMENT
▪ Often asymptomatic, discovered Primary cause

incidentally ▪ Diuretics (furosemide), ACE inhibitors,
▪ Proteinuria, hypoalbuminemia, edema, heparin, antibacterial drugs
hyperlipidemia, lipiduria, hypercoagulability; ▫ Symptomatic therapy
develop gradually over months ▪ Close observation, no immunosuppression
▫ If at low risk of end-stage renal disorder
(i.e. proteinuria < 3.5g/day)
▪ Prednisone + calcineurin inhibitor (e.g.
tacrolimus, cyclosporine)/cytotoxic agent
(e.g. cyclophosphamide)
▫ If at moderate/high risk of end-stage
renal disorder
▪ Rituximab
Secondary cause
▪ Treat underlying condition
OTHER INTERVENTIONS
Figure 118.5 Histological appearance ▪ Lifestyle changes
of membranous glomerulonephritis. The
▫ Medical nutrition therapy, reduce
basement membrane of the glomerulus is
cholesterol, saturated fat intake
markedly thickened.
842 OSMOSIS.ORG
MINIMAL CHANGE DISEASE

osms.it/minimal-change-disease

▪ Type of glomerulonephritis; podocytes in LAB RESULTS
glomeruli damaged by T cells cytokines ▪ Protein in urine > 3.5g/day
▪ Foot processes of podocytes damaged,
flattened (AKA effacement) → lose function Kidney biopsy
as barrier → albumin permeates, bigger ▪ Corticosteroid resistant patients
proteins cannot get through (selective ▪ Light microscopy
proteinuria) ▫ Glomeruli appear normal, hence
“minimal change disease”
CAUSES ▪ Electron microscopy
▪ Unknown; T cells release cytokines, may ▫ Effacement of foot processes.
cause effacement of podocytes ▪ Immunofluorescence
▫ Negative (no immune complex
RISK FACTORS deposition)
▪ Recent infection; immunization; immune
stimulus; medications: nonsteroidal anti-
inflammatory drugs (NSAIDs)
TREATMENT
▪ Hematologic malignancies (e.g. Hodgkin’s MEDICATIONS
lymphoma)
▪ Prednisone therapy
▪ Most common nephrotic syndrome in
▫ Excellent response, more quickly in
children
children than adults; potential relapse
COMPLICATIONS
▪ Relatively benign, does not affect kidney
function
SIGNS & SYMPTOMS

▪ Proteinuria, hypoalbuminemia, edema,
hyperlipidemia, lipiduria, hypercoagulability
▪ Onset more rapid (days to weeks) than
other nephrotic syndromes
Figure 118.6 An illustration demonstrating
the pathophysiology of minimal change
disease.
OSMOSIS.ORG 843
NOTES
NOTES
RENAL CANCER

▪ Abnormal cell growth → kidney mass DIAGNOSTIC IMAGING
(malignant/benign), caused by genetic
mutation of tumor suppressor gene CT scan/MRI/ultrasound
▪ Angiomyolipoma: most common benign ▪ See individual disorders
renal tumor
▪ Renal cell carcinoma: most common LAB RESULTS
malignant renal tumor in adults ▪ Tissue biopsy
▪ Wilms tumor: most common malignant
renal tumor in children
TREATMENT
COMPLICATIONS
MEDICATIONS
▪ Spontaneous hemorrhage, kidney highly
▪ Malignant: chemotherapy
vascular
▪ Malignant
▫ Distant metastasis SURGERY
▪ Malignant: surgical resection

▪ Angiomyolipoma: embolization, surgery not
▪ Often asymptomatic initially suitable
▪ Unilateral abdominal mass ▪ Malignant: radiotherapy
▪ Flank pain, hematuria, systemic symptoms
(e.g. fever, appetite loss)
▪ Ectopic hormone production: renin,
erythropoietin (EPO), adrenocorticotropic
hormone (ACTH), parathyroid hormone-
related peptide (PTHrP) → paraneoplastic
syndromes
844 OSMOSIS.ORG
Chapter 119 Renal Cancer
ANGIOMYOLIPOMA
osms.it/angiomyolipoma
RISK FACTORS
PATHOLOGY & CAUSES ▪ Individuals who are biologically female
▪ Tuberous sclerosis
▪ Most common benign kidney tumor
▪ Also found in liver (common), reproductive
organs (rare) COMPLICATIONS
▪ Made of blood vessels (angio), smooth ▪ Spontaneous hemorrhage risk
muscle (myo), fat (lipo) ▫ Dysregulated angiogenesis → weak
▪ Type of hamartoma: cellular tumor, blood vessels → aneurysms
disorganized architecture
▪ Genetic mutation in tumor suppressor gene
tuberous sclerosis 1 (TSC1) for hamartin/ SIGNS & SYMPTOMS
tuberous sclerosis 2 (TSC2) for tuberin
▪ Small: often asymptomatic
▫ Usually sporadic
▪ Large: mass effect on healthy kidney tissue
▫ Associated with tuberous sclerosis
→ chronic kidney disease
(multiple, bilateral angiomyolipomas)
▪ Extreme cases: end-stage renal disease
▪ Perivascular epithelioid cell tumor family
(dialysis needed)
(PEComa): epithelial-like cells around blood
vessels on microscopy
▪ More common in right kidney DIAGNOSIS
DIAGNOSTIC IMAGING
Ultrasound
▪ Fat appears hyperechogenic
MRI
▪ Small lesions with wedge-shaped pattern
which grow outward as tumor enlarges;
fat appears bright on T1-weighted images,
intermediate-dark on T2-weighted images
LAB RESULTS
Figure 119.1 Histological appearance of an
▪ Image-guided percutaneous needle biopsy
angiomyolipoma. The tumor is composed
and histological analysis
primarily of myoid cells with areas of mature
adipose tissue and numerous vessels.
OSMOSIS.ORG 845
TREATMENT
▪ Surgery unlikely to be useful, highly
vascular tumors with high bleeding risk
OTHER INTERVENTIONS
Embolization
▪ Synthetic emboli released into tumor
vessels → vessel occlusion → tumor
necrosis → tumor shrinkage, haemorrhage
less likely Figure 119.2 An abdominal CT scan
▪ Adverse effects in the axial plane demonstrating an
▫ Postembolization syndrome, fever, flank angiomyolipoma of the left kidney.
pain, malaise
RENAL CELL CARCINOMA (RCC)

osms.it/renal-cell-carcinoma
RISK FACTORS
PATHOLOGY & CAUSES ▪ Individuals who are biologically male
▪ Advanced age
▪ Most common malignant kidney tumor in
adults ▪ Lifestyle factors (e.g. smoking, obesity)
▪ “Silent cancer,” may be asymptomatic until ▪ Hypertension
late stage, poor prognosis ▪ Environmental exposures (e.g. asbestos,
▪ Spontaneous: solitary upper pole tumors heavy metals)
▪ Inherited: young adults; multiple, bilateral ▪ Existing kidney disease
tumors ▫ Acquired renal cystic disease, long-term
▫ Von Hippel–Lindau (VHL) disease: dialysis, renal transplant
inherited RCC ▪ Genetic mutations in chromosome 3p
common in spontaneous, inherited
TYPES
STAGING
Clear cell carcinoma ▪ Tumor, nodes, metastasis (TNM), scored
▪ Epithelial cells in proximal convoluted 0–4
tubule in renal cortex ▫ T: size, sites invaded (e.g. renal vein)
▫ Polygonal epithelial cells: clear ▫ N: degree of spread to retroperitoneal
cytoplasm, full of carbohydrate, fat lymph nodes
▫ Fat in tumor cells → yellow tumor ▫ M: presence of distant metastasis
Papillary carcinoma
Chromophobe carcinoma
846 OSMOSIS.ORG
SURGERY
SIGNS & SYMPTOMS
Resection
▪ Flank pain ▪ If localized
▪ Hematuria
▪ Palpable mass in abdomen/lower back
▪ Systemic symptoms (e.g. fever, weight loss,
night sweats, weakness, malaise)
▪ Ectopic hormone secretion →
paraneoplastic syndromes
▫ Erythropoietin: polycythemia →
hyperviscosity symptoms
▫ Renin: hypertension
▫ PTHrP → hypercalcemia
▫ ACTH → cortisol release → Cushing
syndrome
▪ Left varicocele (testicular swelling)
renal cell carcinoma. The tumor is of the clear
▫ RCC in left kidney → obstructs left renal cell subtype.
vein → drains left testicular vein
▪ Lung/bone presentations
▫ RCC invades renal vein/inferior vena
cava (IVC) → quick metastasis
DIAGNOSIS
DIAGNOSTIC IMAGING
▪ Some of newly diagnosed individuals
▫ Metastases on radiology, esp. lungs/
bones
CT scan of chest/abdomen with contrast

▪ CT scan chest to evaluate metastasis
Ultrasound
TREATMENT demonstrating a renal cell carcinoma (RCC) of
the left kidney.
▪ Chemotherapy/radiotherapy resistant
MEDICATIONS
▪ Immunomodulatory drugs
▫ Activate immune system to attack
tumor; interferon, interleukin-2 (IL-2),
monoclonal antibodies (nivolumab)
▪ Molecular targeted drugs
▫ Inhibit growth receptors; everolimus,
temsirolimus
OSMOSIS.ORG 847
Figure 119.5 Histological appearance of a papillary renal cell carcinoma. The tumor is composed
of numerous clusters of malignant cells arranged around fibrovascular cores.
WAGR SYNDROME
osms.it/WAGR-syndrome
CAUSES
PATHOLOGY & CAUSES
Contiguous gene deletion syndrome
▪ Genetic disorder affecting children ▪ Heterozygous deletion of several genes
predisposed to Wilms tumor beside each other on p arm of chromosome
▫ Wilms’ tumor 11
▫ Aniridia (total/partial absence of iris) ▫ Deletion of WT1 → Wilms’ tumor,
▫ Genitourinary anomalies genitourinary malformations
▫ Intellectual disability (previously mental ▫ Deletion of PAX6 protein → aniridia
Retardation) ▫ Genetic basis for intellectual disability
▪ Sporadic mutation → autosomal dominant unclear
inheritance
COMPLICATIONS
TYPES ▪ Streak ovaries in individuals who are
biologically female; gonadoblastoma
WAGRO (O for obesity) subtype
▪ Additional deletion of brain-derived
neurotrophic factor (BDNF) gene → obesity
848 OSMOSIS.ORG

▪ Few patients with WAGR exhibit all ▪ Each symptom addressed independently
symptoms
▪ Wilms’ tumor (nephroblastoma) MEDICATIONS
▫ Only ⅓ of individuals with WAGR
▪ Aniridia (since birth) Chemotherapy
▫ Most common feature ▪ Wilms’ tumor
▫ Blurry vision, photophobia
▪ Genitourinary anomalies SURGERY
▫ In individuals who are biologically male:
Nephrectomy
cryptorchidism (undescended testes),
hypospadias (urethra opens onto ▪ Wilms’ tumor
underside of penis, not tip)
▫ In individuals who are biologically OTHER INTERVENTIONS
female: streak ovaries (undeveloped
ovaries; increased risk of Radiotherapy
gonadoblastoma) ▪ Wilms’ tumor
▫ Ambiguous genitalia
Tinted lenses
▪ Intellectual disability
▪ Photophobia from aniridia
▫ Not always present, often associated
with autism/attention deficit Medical surveillance
hyperactivity disorder (ADHD) ▪ Wilms’ tumor
▪ Other features ▫ Renal ultrasound, blood pressure
▫ Progressive kidney failure ▪ Genitourinary
▫ Growth retardation, small head size, ▫ Pelvic US for gonadoblastoma in
obesity individuals who are biologically female
▫ Cataracts, glaucoma, nystagmus
DIAGNOSIS
LAB RESULTS
Fluorescence in situ hybridization (FISH)
▪ DNA mixed with fluorescently-labeled DNA
probe
▪ Genetic deletion on one chromosome →
only one bright spot
OSMOSIS.ORG 849
WILMS' TUMOR
osms.it/wilms-tumor
COMPLICATIONS
PATHOLOGY & CAUSES ▪ Distant metastasis to brain, lungs, liver,
bones
▪ Most common malignant kidney tumor in
▪ Paraneoplastic syndrome
children, typically ages 2–5
▫ Renin secretion → high blood pressure
▪ AKA nephroblastoma (metaphrenic
→ decreased kidney function
blastemal cells)
▪ Wilms’ tumor typically appears in otherwise
healthy children SIGNS & SYMPTOMS
▫ Beta-catenin mutations in 10% of
sporadic Wilms’ tumors ▪ Large, palpable, unilateral flank mass
▪ Tumors composed of metanephric (bilateral tumors)
blastemal cells ▪ Abdominal pain
▫ Abortive/partly-developed structures of ▪ Constipation (due to kidney
nephron hemihypertrophy)
▫ Triphasic blastoma: tumor composed of ▪ Hematuria
blastemal, stromal, epithelial cells ▪ Systemic symptoms (e.g. loss of appetite,
fever, nausea, weakness)
CAUSES ▪ Renin secretion → hypertension
Genetic mutations
▪ Chromosome 11, short arm p, region 1,
band 3
▪ Loss-of-function mutation in Wilms’
Tumor 1 (WT1); may be part of wider
developmental syndrome with additional
abnormalities
▫ WAGR syndrome: genetic disorder
affecting children predisposed to Wilms’
tumor
▫ Denys–Drash syndrome: WT1
mutation → Wilms’ tumor, early-
onset nephrotic syndrome, male
pseudohermaphroditism
▪ Wilms’ Tumor 2 (WT2) mutation →
developmental syndromes (e.g. Beckwith–
Wiedemann syndrome)
▪ Majority of cases not associated with WT1/ Figure 119.6 A CT scan in the axial plane
WT2 mutations, developmental syndromes demonstrating a Wilms’ tumor of the right
kidney.
RISK FACTORS
▪ Ages 2–5
▪ Developmental syndromes: WAGR,
Beckwith–Wiedemann, Denys–Drash
▪ Family history of Wilms’ tumor
850 OSMOSIS.ORG
▪ Developmental syndromes LAB RESULTS

▫ Denys–Drash syndrome: Wilms’ tumor, ▪ Image-guided percutaneous needle biopsy
early-onset nephrotic syndrome, male and histologic analysis
pseudohermaphroditism
▫ Beckwith–Wiedemann syndrome:
Wilms’ tumor, macroglossia, TREATMENT
organomegaly, hemihypertrophy
▪ Depends on genetic mutations, tumor
aggressiveness, unilateral/bilateral
DIAGNOSIS
MEDICATIONS
▪ Never palpation
▪ Chemotherapy
▫ Risk of tumor rupture, metastasis
Abdominal ultrasound SURGERY

▪ Presence of mass, renal vein infiltration ▪ Nephrectomy
Abdominal contrast-enhanced CT scan/MRI

▪ Tumor staging; lymph node metastasis OTHER INTERVENTIONS
penetration of capsule ▪ Radiation
▫ Used with care, risk of secondary
Chest CT scan cancers
▪ Detects metastasis
Figure 119.7 Histological appearance of Wilms’ tumor. The tumor is triphasic, composed of
blastema, stroma and immature epithelial elements (glomeruli and tubules).
OSMOSIS.ORG 851
Figure 119.9 Illustration of the signs and symptoms of Wilms’ tumor, which most commonly
affects children who were otherwise healthy.
Figure 119.8 Gross pathological appearance of a nephrectomy specimen in a patient with

Wilms’ tumor.
852 OSMOSIS.ORG
NOTES
NOTES
URINARY & KIDNEY INFECTIONS

▪ Infections involving kidneys, ureters, Lower UTIs
bladder, urethra (UTI) ▪ Dysuria (painful urination), frequent
urination/urgency
TYPES Upper UTIs
Upper UTIs (kidneys) ▪ Flank pain, fever, chills, nausea, vomiting,
▪ Pyelonephritis malaise, lower UTI symptoms
Lower UTIs (bladder, urethra)

▪ Cystitis, urethritis DIAGNOSIS
DIAGNOSTIC IMAGING
CAUSES
Renal scintigraphy, dimercaptosuccinic acid
Bacterial infection (most common) (DMSA), radionuclide/DMSA scan
▪ Gram negative bacteria: Escherichia coli ▪ Kidney scarring
(E. coli), 80% of cases; Klebsiella; Proteus;
Enterobacter; Citrobacter
▪ Gram positive bacteria: Enterococcus; LAB RESULTS
Staphylococcus saprophyticus (S. ▪ Pyuria (white blood cells in urine)
saprophyticus), second most common, esp. ▪ > 105 colony-forming units/mL
in young individuals who are biologically ▪ Leukocyte esterase (enzyme created by
female, sexually active white blood cells)
Ascending infection
▪ Bacteria move from rectal area → urethra TREATMENT
→ bladder → kidney
MEDICATIONS
Descending infection
▪ Antibiotic treatment (e.g. trimethoprim-
▪ Bacteria starts in blood/lymph → kidney →
sulfamethoxazole, nitrofurantoin, penicillin)
bladder, urethra
to dialysis
▪ Pain medications
COMPLICATIONS
▪ Urosepsis, septic shock
SURGERY
▪ Kidney transplantation
OSMOSIS.ORG 853
PYELONEPHRITIS
osms.it/pyelonephritis

▪ Inflamed kidney; result of bacterial infection; ▪ May be asymptomatic
affects tubules, interstitium, renal pelvis ▪ Hematuria, polyuria/nocturia
▪ Interstitial abscesses filled with pus ▪ Flank pain
▪ Tubules damaged, contain neutrophil casts ▪ Inflammatory response
▫ Leukocytosis; fever; chills; nausea,
Chronic pyelonephritis
vomiting; gerontologic (e.g. altered
▪ Repeated episodes of acute pyelonephritis. mental status)
▪ Leads to fibrosis, renal interstitium scarring,
renal tubules atrophy Chronic pyelonephritis
▪ Localized in upper, lower poles of kidney ▪ Same as acute pyelonephritis
▪ Xanthogranulomatous pyelonephritis (XGP) ▪ Hypertension
▫ Rare type of chronic pyelonephritis
▫ Infected kidney stone forms
granulomatous tissue
DIAGNOSIS
▫ Can be mistaken for kidney tumors on
LAB RESULTS
imaging
▪ Urine culture, bacteria
▪ Pyuria, hematuria, bacteriuria, leukocyte
RISK FACTORS casts
▪ Urinary tract abnormalities, ▪ Leukocyte esterase, nitrites, hematuria
indwelling urinary catheter, diabetes,
immunocompromised status, enlarged
prostate
CAUSES
▪ Vesicoureteral reflux (VUR)
▫ VUR → predisposed to recurrent
infections
▫ Failure of vesicourethral orifice → urine
moves backward up urinary tract from
bladder
▫ Increases risk of ascending upper UTI
▫ May result from primary congenital
defect, bladder outlet obstruction

demonstrating perinephric fat stranding and
cortical rim loss seen in acute pyelonephritis.
854 OSMOSIS.ORG
Chapter 120 Urinary & Kidney Infections
TREATMENT
MEDICATIONS
▪ Antibiotics targeted to bacterial infection
SURGERY
▪ Correct kidney obstruction/VUR
▪ Nephrectomy: removal of part/all of
Figure 120.2 The histological appearance of damaged kidneys
the kidney in a case of acute pyelonephritis. ▪ Kidney transplant
There are neutrophils present in the
interstitium and within the tubular lumina. OTHER INTERVENTIONS
▪ Ensure individual well hydrated
▪ Dialysis: machine works for kidneys too
damaged to function
Figure 120.3 A CT scan of the abdomen in

the axial plane demonstrating a subcapsular
abscess secondary to pyelonephritis of the
right kidney.
OSMOSIS.ORG 855
URINARY TRACT INFECTIONS
osms.it/UTI

▪ UTI; bladder inflammation due to bacterial/ DIAGNOSTIC IMAGING
fungal infection, chemical irritants, foreign
bodies, trauma Renal ultrasound
▪ Children with kidney malformation
▪ AKA cystitis
Voiding cystourethrogram (VCUG)
CAUSES ▪ Individual given radiocontrast liquid,
▪ Most common: bacterial infections (e.g. E. fluoroscopy (real-time X-rays); healthcare
coli, S. saprophyticus) provider monitors urination
▫ Ascending infection → bacteria move ▪ Children with severe/recurrent UTIs, to
from rectal area → urethra → bladder detect vesicoureteral reflux (retrograde
movement of urine from bladder back up
▫ Descending infection → bacteria starts
into ureters, kidneys)
in blood/lymph → kidney → bladder,
urethra
LAB RESULTS
RISK FACTORS ▪ Positive for nitrites
▪ Young individuals who are biologically ▫ Gram negative organisms (e.g. E. coli)
female (shorter urethra → shorter distance convert nitrates to nitrites
for ascending bacteria) ▪ > 105 colony-forming units/mL from clean
▪ Sexual intercourse; penile foreskin catch urine sample
▪ Postmenopause (decreased estrogen levels ▪ < 105 colony-forming units/mL, infection
→ decreased vaginal flora) still possible
▪ Indwelling catheter ▪ Sterile pyuria (pyuria, urine culture without
bacteria) → urethritis (urethra inflammation)
▪ Diabetes mellitus (hyperglycemia inhibits
neutrophil diapedesis) ▫ Neisseria gonorrhoeae, Chlamydia
trachomatis: most common causes,
▪ Impaired bladder emptying/urinary stasis
sexually transmitted infections (STIs)
COMPLICATIONS Pyuria
▪ Pyelonephritis ▫ Cloudy urine
▪ Urosepsis ▫ > five white blood cells, high-powered
▪ Septic shock field on microscopy, > 10 white blood
cells/mL on hemocytometer
▫ Hematuria
SIGNS & SYMPTOMS Dipstick test
▪ Suprapubic pain, dysuria, frequent ▪ Leukocyte esterase
urination/urgency, urine voids small in
volume
▪ Infants: fussy, fever, difficulties feeding
▪ Elderly individuals: fatigue, incontinence,
altered mental status
856 OSMOSIS.ORG
Chapter 120 Urinary & Kidney Infections
TREATMENT
MEDICATIONS
▪ Antibiotics: trimethoprim-sulfamethoxazole,
ciprofloxacin, ceftriaxone, azithromycin,
penicillin
▪ Pain medications
OTHER INTERVENTIONS
▪ Increase fluid intake
OSMOSIS.ORG 857
NOTES
NOTES
URINARY INCONTINENCE

OTHER DIAGNOSTICS
PATHOLOGY & CAUSES
▪ History (e.g. voiding diary)
▪ Physical examination; urine leakage easily
▪ Inability to maintain micturition control →
established
involuntary urine leakage
▪ Urodynamic studies
▪ Chronic urinary incontinence: important
geriatric issue, affecting personal hygiene,
social life
TREATMENT
TYPES MEDICATIONS
▪ Urge, stress, mixed (combination of stress, ▪ See individual disorders
urge), overflow, functional
SURGERY
▪ Involuntary urine leakage

OTHER INTERVENTIONS
▪ Behavioral therapy, lifestyle changes,
catheterization, incontinence
DIAGNOSIS undergarments
DIAGNOSTIC IMAGING
LAB RESULTS
▪ Urinalysis
▪ Renal function
Figure 121.1 Illustration of somebody with urinary incontinence. This condition can negatively
affects one’s personal hygiene and social life.
858 OSMOSIS.ORG
Chapter 121 Urinary Incontinence
OVERFLOW INCONTINENCE
osms.it/overflow-incontinence

▪ Urinary retention → bladder pressure DIAGNOSTIC IMAGING
increases, exceeds urethral resistance
CAUSES
LAB RESULTS
Urinary flow blockage ▪ Urinalysis
▪ Benign prostatic hypertrophy, prostate ▪ Renal function
cancer, urethral strictures, severe
constipation with fecal impaction, cystocele,
prolapsed uterus
OTHER DIAGNOSTICS
▪ History (e.g. voiding diary)
Ineffective detrusor muscle ▪ Urine leakage easily established
▪ Disorders affecting autonomic innervation ▪ Urodynamic studies
of bladder (e.g. diabetes mellitus, spinal
cord injury, cauda equina syndrome, spinal
cord anomalies), anticholinergics TREATMENT
MEDICATIONS
SIGNS & SYMPTOMS ▪ Cholinergic agents (e.g. bethanechol,
increases bladder muscle tone), alpha
▪ Frequent loss of small amount of urine; blockers (e.g. prazosin, tamsulosin, relaxes
hesitancy; weak/intermittent urinary stream smooth muscle in bladder neck)
SURGERY
▪ Anterior colporrhaphy/colposuspension
OTHER INTERVENTIONS
▪ Intermittent self-catheterization
OSMOSIS.ORG 859
Figure 121.2 Illustration of overflow incontinence’s causes and possible avenues to treatment.
STRESS INCONTINENCE
osms.it/stress-incontinence

▪ Pelvic floor laxity → urethra loses support DIAGNOSTIC IMAGING
→ increase in intra-abdominal pressure →
overwhelms sphincter muscles Abdominal ultrasound

▪ Most prevalent in individuals who are ▪ Urinalysis
biologically female, < 70 years old ▪ Renal function
▪ Menopause, multiparity/childbirth-related
trauma, pressure on bladder during OTHER DIAGNOSTICS
pregnancy, obesity, urologic/retropubic ▪ History (e.g. voiding diary)
surgery ▪ Urine leakage easily established
▪ Urodynamic studies
SIGNS & SYMPTOMS
TREATMENT
▪ Spurts of urine when intra-abdominal
pressure increases (e.g. sneeze, cough, MEDICATIONS
laugh, exercise)
▪ Estrogen replacement therapy (only for
stress incontinence caused by menopause)
860 OSMOSIS.ORG
Chapter 121 Urinary Incontinence
OTHER INTERVENTIONS
▪ Lifestyle changes (e.g. weight loss)
▪ Kegel exercises to strengthen external
sphincter, pessaries, electrical stimulation
▪ Sling procedures
Figure 121.3 Illustration of stress incontinence’s causes and possible avenues to treatment.
URGE INCONTINENCE
osms.it/urge-incontinence

▪ Overactive bladder: uninhibited detrusor ▪ Sudden/great urine leakage, strong/
muscle contracts randomly immediate urge to void; frequency;
nocturnal wetting
CAUSES
▪ Urinary tract infections (UTIs) DIAGNOSIS
▪ Central nervous system (CNS) disorders:
stroke, Parkinson’s disease (PD), multiple DIAGNOSTIC IMAGING
sclerosis (MS)
RISK FACTORS
▪ Most prevalent in elderly individuals LAB RESULTS
▪ Urinalysis
▪ Renal function
OSMOSIS.ORG 861
▪ History (e.g. voiding diary) ▪ Injections with botulinum toxin → prevent
▪ Urine leakage easily established acetylcholine release, decrease detrusor
▪ Urodynamic studies muscle activity
OTHER INTERVENTIONS
TREATMENT ▪ Lifestyle changes (e.g. avoid alcohol,
diuretics)
MEDICATIONS ▪ Kegel exercises
▪ Anticholinergic agents → inhibit detrusor
▪ Bladder/toilet training
overactivity by blocking muscarinic
receptors ▫ Relaxation techniques
▪ Tricyclic antidepressants (TCAs) → ▪ Sling procedures
anticholinergic properties
862 OSMOSIS.ORG
NOTES
NOTES
VASCULAR RENAL DISEASE

▪ Variety of diseases affecting renal arteries, DIAGNOSTIC IMAGING
veins → abnormal renal circulation
Doppler ultrasound
RISK FACTORS CT scan/MRI

▪ Age, atherosclerosis, smoking, diabetes,
Renal arteriogram
high cholesterol
LAB RESULTS
COMPLICATIONS
▪ Excess nitrogen waste products
▪ Renal atrophy, kidney failure
▫ Blood urea nitrogen (BUN), creatinine
▪ Proteinuria, hematuria, cell casts
SIGNS & SYMPTOMS ▪ Biopsy
▫ Rare
▪ Impaired renal function → urine output
disorders
▪ Blood pressure disorders TREATMENT
▪ Conservative, angioplasty, bypass surgery,
hemodialysis
RENAL ARTERY STENOSIS

osms.it/renal-artery-stenosis
CAUSES
PATHOLOGY & CAUSES ▪ Atherosclerosis (most cases)
▪ Fibromuscular dysplasia (in individuals who
▪ Progressive narrowing of renal artery →
are biologically female)
decrease in renal blood flow
▪ Stimulates renin release by juxtaglomerular
cells → production of angiotensin II, COMPLICATIONS
aldosterone → vasoconstriction, increased ▪ Secondary hypertension, AKA renovascular
reabsorption of sodium, water hypertension
▪ Contraction of blood vessels, increase ▪ If severe, persistent: renal blood flow
in blood volume → blood pressure (BP) decreases → prerenal azotemia
elevation ▪ Renal atrophy, fibrosis
OSMOSIS.ORG 863
SIGNS & SYMPTOMS
▪ Sudden onset of hypertension
▫ Severe, refractory to medical therapy;
headaches, blurry vision
▪ Impaired renal function
▪ Upper abdominal bruit on auscultation,
caused by turbulence of blood flow through
stenosis
DIAGNOSIS
DIAGNOSTIC IMAGING
Renal arteriogram
Figure 122.1 A 3D-reconstructed CT scan
▪ Localize stenotic lesion
demonstrating the renal vasculature. The
Megnetic resonance angiogram (MRA) left renal artery (on the right of this image)
is completely stenosed and the left kidney is
▪ Individuals with impaired renal function, at
poorly perfused as compared to the right.
risk for contrast-induced renal failure
Doppler ultrasound of renal arteries

▪ Initial screening test

▪ Alternative
LAB RESULTS
▪ High BUN to creatinine ratio
TREATMENT
MEDICATIONS
Antihypertensive medication
▪ Angiotensin converting enzyme (ACE)
inhibitors, calcium channel blockers
Figure 122.2 A contrast CT scan
SURGERY demonstrating stenosis of the right renal
▪ Percutaneous transluminal renal artery. The right kidney is small and shows
angioplasty (PTRA) minimal contrast uptake when compared to
▪ If PTRA not successful the left.
▫ Bypass surgery
864 OSMOSIS.ORG
Chapter 122 Vascular Renal Disease
RENAL CORTICAL NECROSIS

osms.it/renal-cortical-necrosis

▪ Rare, irreversible prerenal kidney injury; DIAGNOSTIC IMAGING
sudden decrease in blood perfusion to renal
cortex CT scan with contrast
▪ AKA diffuse cortical necrosis ▪ Non-enhancing renal cortex, thin rim of
enhancement may occur (cortical rim sign)
▪ Reduced blood supply to renal tubules →
acute tubular necrosis Ultrasound
▪ Lack of anastomoses among cortical radial ▪ Hypoechoic areas in renal cortex
arteries (end arteries)
▪ High demand for blood of nephron (e.g.
proximal tubule, thick ascending loop of
LAB RESULTS
Henle) ▪ BUN, creatinine
▪ If ischemia persists → irreversible necrotic ▪ Hyperkalemia, metabolic acidosis
injury of renal cortex → renal cortical ▪ Hematuria, proteinuria, tubular cell casts
necrosis
Biopsy
▪ Patchy necrosis, atrophy of renal cortex
CAUSES
▪ Obstruction of blood flow
▫ Blood clots/vasospasms
▪ Pregnancy complications → disseminated
intravascular coagulation → widespread
blood clots → renal cortical necrosis
▫ Placental abruption, prolonged
intrauterine fetal death, infected
abortion, severe eclampsia, septic shock
COMPLICATIONS
▪ Acute kidney failure
SIGNS & SYMPTOMS Figure 122.3 The histological appearance

of renal cortical necrosis. The cells which
comprise the glomeruli and the renal tubules
▪ Sudden decrease in urine output
have a fuzzy outline and have lost their
▫ Oliguria/anuria nuclei, indicative of necrosis.
▪ Flank pain at costovertebral angle
▫ Renal edema stretching renal capsule
OSMOSIS.ORG 865
TREATMENT
OTHER INTERVENTIONS
▪ Increase blood perfusion to renal cortex
▫ Intravenous (IV) fluids
▪ If severe
▫ Hemodialysis
Figure 122.4 An abdominal CT scan in the axial plane demonstrating bilateral renal cortical
necrosis. The low-signal renal cortex surrounding the relatively high-signal renal medulla is
known as cortical rim sign.
866 OSMOSIS.ORG
NOTES
NOTES
ACUTE RESPIRATORY DISEASE

▪ Acute respiratory disorders induced by DIAGNOSTIC IMAGING
changes in atmospheric pressure/direct ▪ Medical imaging
communication between atmosphere,
vasculature/pulmonary conditions, diseases
(e.g. pulmonary trauma, pneumonia, sepsis,
OTHER DIAGNOSTICS
severe burns) ▪ Clinical presentation, history
▪ Impaired alveolar gas exchange → ▪ Arterial blood gases
hypoxemia
▪ Can lead to potentially fatal conditions
TREATMENT

▪ Oxygen therapy
▪ Hypoxemia: dyspnea, tachypnea, chest ▪ Mechanical ventilation
pain
ACUTE RESPIRATORY DISTRESS

SYNDROME (ARDS)
osms.it/ards
cardiovascular cause (noncardiogenic
PATHOLOGY & CAUSES pulmonary edema)
▪ Alveolar barrier cells damaged → alveolar
▪ Acute lung condition sacs flooded → impairs air exchange
▪ Widespread diffuse inflammation → ▫ Pro-inflammatory cytokines released:
increased vascular permeability, loss of tumor necrosis factor (TNF), interleukins
pulmonary tissue
▫ Interleukins (IL-1, IL-6, IL-8) →
▪ Triggered by pulmonary conditions, neutrophil activation → toxic substances
diseases (e.g. pulmonary trauma, (reactive oxygen species) released →
pneumonia, sepsis) alveolar and capillary damage → oncotic
gradient lost → no fluid resorption →
PATHOLOGY fluid in interstitium
▪ Refractory hypoxemia, reduced pulmonary ▪ Damaged Type II pneumocytes →
compliance, pulmonary edema without surfactant layer malfunction
OSMOSIS.ORG 867
▪ Acute inflammatory response → abnormal
extravascular fibrin deposition
▫ Increased activity of extrinsic
coagulation pathway
▫ Impaired fibrinolysis
CAUSES
▪ Systemic infections/septic shock
▪ Acute lung injury
▫ Compromises ability to regulate gas
exchange → lungs fill up with fluid in
interstitium, alveoli
▪ Gastric contents aspiration
▪ Severe pneumonia
▪ Serious burns
▪ Mechanical (e.g. near drowning) Figure 123.1 A chest radiograph
▪ Inflammatory (e.g. pancreatitis) demonstrating diffuse, bilateral, coalescent
opacities resembling ground glass.
SIGNS & SYMPTOMS

OTHER DIAGNOSTICS
▪ Usually begin within first few hours, 1–2
days 2012 Berlin definition
▪ Dyspnea, tachypnea, tachycardia, ▪ Acute pulmonary injury within week of
diaphoresis, low blood oxygenation clinical consultation
→ cyanosis, diffuse crackles on lung ▪ Bilateral opacities on chest X-ray/CT
auscultation scan unexplained by other pulmonary
pathologies (e.g. pleural effusion, lung
collapse)
DIAGNOSIS ▪ Respiratory failure without heart failure
(noncardiogenic)
DIAGNOSTIC IMAGING ▪ Minimum positive end expiratory pressure
Chest X-rays (PEEP) of 5cmH20
▪ Bilateral alveolar infiltrate, pulmonary ▪ Reduced oxygen in arteries, reduced partial
edema with no cardiovascular cause pressure arterial oxygen/fraction of intake
of oxygen (PaO2/FiO2) ratio
CT scan ▫ Mild: 201–300mmHg
▪ Bilateral airspace opacities ▫ Moderate: 101–200mmHg
▫ Serious: < 100mmHg
Ultrasound
▪ Subpleural consolidations, pleural line
irregularities, no lung gliding TREATMENT
▪ Respiratory alkalosis → respiratory acidosis ▪ Antibiotic therapy
▫ After microbiological culture, determines
appropriate course of antibiotics
▪ Diuretics
▫ Manage fluid output
868 OSMOSIS.ORG
Chapter 123 Acute Respiratory Disease
OTHER INTERVENTIONS
Mechanical ventilation
▪ Maintain gas exchange to meet metabolic
demands
▪ Endotracheal intubation/tracheostomy
(prolonged intubations)
▪ Monitor parameters
▫ PEEP: keep alveoli from collapsing,
improve oxygenation
▫ Mean airway pressure: recruit alveoli to
open
Figure 123.2 The histological appearance ▫ Plateau pressure: monitor alveoli for
of diffuse alveolar damage, the pathological overdistension
correlate of ARDS. There is a diffuse ▪ Extracorporeal membrane oxygenation
inflammatory cell infiltrate and pink, hyaline (ECMO)
membranes in the alveolar spaces.
▫ Removes blood from body, artificially
removes CO2, oxygenates red blood
cells

appearance of ARDS. There is a diffuse,
vaguely nodular infiltrate, most easily visible
at the apices.
OSMOSIS.ORG 869
ALTITUDE SICKNESS
osms.it/altitude-sickness
cell production
PATHOLOGY & CAUSES ▪ ↑ 2,3 BPG synthesis → ↓ hemoglobin
affinity for O2 → ↑ release of oxygen to
▪ Reaction to exposure to low oxygen tissues
concentrations when traveling to high
altitude Measures to avoid HAI
▫ AKA high altitude illness (HAI), acute ▪ Acclimatization: ascending slowly to high
mountain sickness (AMS) altitudes, to adjust to decreasing oxygen
▪ Partial pressure of oxygen of inspired air levels
calculated by PiO2 (mmHg) = FiO2 (%) x ▪ Preventative medications: acetazolamide
[Pb (mmHg) - 47mmHg] (diuretic); increases bicarbonate kidney
▫ FiO2: fraction of inspired oxygen, not excretion
affected by altitude, remains unchanged
in 21%
RISK FACTORS
▫ Pb: barometric pressure
▪ History of HAI episodes
▫ 47mmHg: vapor pressure of water at
▪ Prior exercise/alcohol consumption
37°C/98.6°F
▪ Rapid ascent to high altitude
▪ In high altitudes, ↓ Pb → ↓ PiO2
▪ Comorbidities that affect breathing (e.g.
▪ Partial pressure of alveolar oxygen (PAO2)
asthma)
▫ Pressure in alveolar space after
equilibration with blood
▪ PAO2 lower than PiO2 COMPLICATIONS
▫ Air enters lungs, humidified by upper ▪ Can lead to potentially fatal conditions
airway, partial pressure of water vapor ▫ High altitude cerebral edema (HACE),
reduces partial pressure of oxygen high altitude pulmonary edema (HAPE)
▫ Continual uptake of oxygen from alveoli
by pulmonary capillaries
SIGNS & SYMPTOMS
▫ Continual diffusion of CO2 from
capillaries into alveoli
▪ Usually appear within 6–12 hours of ascent
▪ ↓ PiO2 → ↓ PAO2, ↓ PaO2 → hypoxemia
▪ Headache, dizziness, fatigue, nausea,
▪ HAI starts at 1.5km/5,000ft, symptoms vomiting, loss of appetite, sleep disturbance
noticeable above 2.4km/8,000ft
▪ Often improves with time if person does
Adaptive mechanisms not ascend to higher altitude
▪ Hypoxemia → hyperventilation → ↑ ▪ HACE
expiration of CO2 by lungs → ↓ PCO2 → ↑ ▫ Excessive fatigue, confusion, neurologic
pH (respiratory alkalosis) deficits (e.g. ataxia, altered mental state)
▪ ↓ PCO2 , ↑ pH inhibit central, peripheral ▪ HAPE
chemoreceptors, decrease ventilation rate ▫ Dry cough, dyspnea
▪ Within several days ↑ HCO3-, ↓ H+
kidney excretion → ↓ pH → stimulation
of respiratory center to further increase
ventilation
▪ ↑ erythropoietin production → ↑ red blood
870 OSMOSIS.ORG
DIAGNOSIS
LAB RESULTS
▪ Arterial blood gases
▫ ↓ PaO2, ↑ PaCO2, respiratory alkalosis
OTHER DIAGNOSTICS
▪ Clinical presentation, history of living at low
altitude, recent ascent at high altitude
TREATMENT
MEDICATIONS
▪ Symptom relief
▫ E.g. analgesics for headache,
antiemetics for nausea
demonstrating acute pulmonary edema in an
▪ Carbonic anhydrase inhibitors (e.g. individual who ascended to 2700m.
acetazolamide)
▫ Increase HCO3- excretion; treat
respiratory alkalosis
OTHER INTERVENIONS
▪ Rest
▪ Descent
▪ Symptom relief
▫ E.g. oxygen to improve breathing
▪ HACE, HAPE
▫ Medical emergencies; require immediate
descent/oxygen administration
DECOMPRESSION SICKNESS (DCS)

osms.it/decompression_sickness
pressure of oxygen, nitrogen → ↑ oxygen,
PATHOLOGY & CAUSES nitrogen dissolved in blood, loaded in body
tissues
▪ Gas embolism, occurs when individuals ▫ Henry’s law: at constant temperature,
experience sudden decreases in amount of gas dissolved in liquid
atmospheric pressure directly proportional to partial pressure
▫ AKA diver’s disease ▪ If oxygen, nitrogen quantities high enough
▪ Air breathed at relatively high pressure → oxygen toxicity/nitrogen narcosis,
(e.g. diver descends from water surface) respectively
→ inspired gases compressed to higher
pressure of surrounding water → ↑ partial
OSMOSIS.ORG 871
▪ Pressure drops too rapidly (e.g. ascent
to water surface) → sum of gas tensions DIAGNOSIS
in tissue exceeds ambient pressure →
liberation of free gas from tissues due to OTHER DIAGNOSTICS
excess dissolved gases → gas bubbles ▪ Clinical presentation, history of exposure to
→ vessels blocked, tissues compressed, sudden decreases in atmospheric pressure
clotting cascade, inflammation ▪ Confirmed if symptoms relieved after
▪ Occurs in scuba, deep sea divers, recompression
underwater construction workers; during
rapid ascent of an unpressurized aircraft
▪ Caisson disease (chronic decompression TREATMENT
sickness)
▫ Tunnel workers, moving from caisson to
OTHER INTERVENTIONS
atmospheric pressure ▪ Hyperbaric oxygen therapy in
recompression chamber
▫ Under high pressure gas bubbles forced
RISK FACTORS back into solution; slow decompression
▪ Right-to-left shunt (e.g. patent foramen permits gradual gas elimination via
ovale/atrial/ventricular septal defect) lungs, prevents obstructive bubbles
▪ Air travel after diving reforming
biologically male
SIGNS & SYMPTOMS

▪ Usually develop within one hour of
surfacing
▪ Excessive fatigue, headache
▪ Depend upon size, location of gas bubbles
Type I DCS
▪ Skeletal muscles, joints
▫ Painful condition, AKA “the bends”;
arching of back, posture reminiscent of
Grecian bend
▪ Skin
▫ Itching, rash
Type II DCS (more severe)

▪ Nervous system
▫ Paresthesia, amnesia, weakness,
paralysis
▪ Lungs
▫ Edema, hemorrhage, atelectasis,
emphysema → respiratory distress,
AKA “the chokes”; cough, chest pain,
dyspnea
▪ Can progress to permanent injuries/fatal
damage
872 OSMOSIS.ORG
OSMOSIS.ORG 873
NOTES
NOTES
LOWER RESPIRATORY TRACT

▪ Structural anomalies of lung during Prenatal ultrasound, radiography, CT scan,
embryonic development MRI

▪ Asymptomatic/respiratory distress ▪ Surgical resection, respiratory support
CONGENITAL PULMONARY AIRWAY

MALFORMATION
osms.it/cpam
associated with other congenital
PATHOLOGY & CAUSES malformations (e.g. esophageal atresia with
esophageal fistula); poor prognosis
▪ Congenital pulmonary airway malformation ▪ CPAM Type 3: large; not true cysts;
(CPAM) communicates with surrounding
▪ AKA congenital cystic adenomatoid parenchyma; “adenomatoid” type; more
disorder → part of/entire lung lobe replaced common in individuals who are biologically
by non-functional cysts male
▪ Result of abnormalities in branching ▪ CPAM Type 4: rare
morphogenesis of lung
▪ Rare in general; most common congenital
lung malformation
CAUSES
▪ Possibly, in utero airway obstruction/atresia;
definitive cause unknown
TYPES
▪ CPAM Type 0: rare; multiple small cysts
composed of cartilage, mucus cells; lethal
RISK FACTORS
anomaly ▪ Occurs sporadically
▪ CPAM Type 1: most common; large (> ▪ Not related to maternal factors
2cm/0.78in) multiloculated cysts; good ▪ No genetic predisposition except Type 4
prognosis (associated with familial pleuropulmonary
▪ CPAM Type 2: small uniform cysts; blastoma syndrome)
874 OSMOSIS.ORG
Chapter 124 Lower Respiratory Tract Congenital Malformations
COMPLICATIONS diaphragm, absence of visible lung tissue

▪ Pulmonary hypoplasia
MRI/CT scan
▪ Mediastinal shift, putting pressure against
heart ▪ Delineate pathology
▪ Respiratory infections
▪ Rapid growth → venous outflow TREATMENT
obstruction, cardiac failure, hydrops fetalis,
death SURGERY
▪ Longstanding CPAMs → cancer
▪ Minimally invasive surgical resection
(thoracoscopy)
SIGNS & SYMPTOMS ▪ Large cysts: in utero placement of Harrison
thoracoamniotic shunt
▪ 75% of individuals: asymptomatic ▪ Rare: fetal surgery in utero; surgical delivery,
▪ 25% of individuals: cyanosis, ex utero intrapartum treatment (EXIT)
pneumothorax, respiratory distress, procedure
tachypnea, intercostal retractions, grunting
▪ Hyperresonance on percussion, diminished
vesicular murmur, asymmetrical thorax
Figure 124.2 A fetal MRI demonstrating a

Figure 124.1 Illustration depicting continuous congenital pulmonary airway malformation.
pulmonary airway malformation.
DIAGNOSIS
▪ Definitive diagnosis usually not possible
without surgical resection, histopathological
evaluation
DIAGNOSTIC IMAGING
Prenatal ultrasound
▪ Echogenic mass appearing in the chest,
displacement of heart, flat/everted
OSMOSIS.ORG 875
Figure 124.3 The histological appearance Figure 124.4 A CT scan of the chest
of a congenital cystic type II malformation. demonstrating a pulmonary congenital
There are multiple small cystic spaces lined cystic adenomatoid malformation, Type I,
by immature respiratory tissue. presenting as a single cyst of middle lobe in
an adult.
PULMONARY HYPOPLASIA
osms.it/pulmonary_hypoplasia
caudal regression syndrome, mediastinal
PATHOLOGY & CAUSES tumor, dextrocardia, sacrococcygeal
teratoma
▪ Underdevelopment of lungs → low number/ ▫ Bilateral renal agenesis →
size of bronchopulmonary segments/alveoli oligohydramnios → decreased lung
▪ Typically occurs prior to/after expansion, decreased mechanical
pseudoglandular stage (6–16 weeks stretching → decreased growth factors
gestation) lung synthesis → pulmonary hypoplasia
TYPES RISK FACTORS

▪ Primary ▪ Decreased amniotic fluid: severe
▫ Idiopathic, not associated with maternal/ oligohydramnios, mid-trimester rupture of
fetal abnormalities; rare membranes
▪ Secondary ▪ Disruption of signaling pathways involved
▫ Due to fetal abnormalities disrupting in growth: sonic hedgehog (SHH) signaling
lung development pathway
▫ Associated with bilateral renal ▪ Aberrant expression growth factors:
agenesis, congenital diaphragmatic vascular endothelial growth factor (VEGF),
hernia, congenital cystic adenomatoid epidermal growth factor (EGF), fibroblast
malformation, fetal hydronephrosis, growth factor (FGF)
▪ Early delivery
876 OSMOSIS.ORG
Chapter 124 Lower Respiratory Tract Congenital Malformations
COMPLICATIONS
▪ Respiratory distress, chronic respiratory
TREATMENT
failure, bronchopulmonary dysplasia,
pneumothorax, secondary scoliosis,
OTHER INTERVENTIONS
impaired cardiac function ▪ Amnioinfusion: instilling isotonic fluid into
amniotic cavity
▪ Survival depends on degree of hypoplasia,
cause of restricted growth ▪ Amniopatch: intra-amniotic injection of
platelets, cryoprecipitate → seal amniotic
fluid leak
SIGNS & SYMPTOMS ▪ Treatment of underlying condition;
respiratory support; in severe cases, fetal
▪ Prenatal: poor fetal movement, amniotic surgery
fluid leakage, oligohydramnios
▪ Postnatal: asymptomatic/severe respiratory
distress, apnea, cyanosis
▪ Small, bell-shaped chest; heart
displacement; decreased/absent breath
sounds
DIAGNOSIS
DIAGNOSTIC IMAGING
3D ultrasound
▪ Total lung volume measurement
Doppler ultrasound/magnetic resonance

angiography
▪ Shows lack of blood supply
CT scan/MRI Figure 124.5 A chest X-ray demonstrating

▪ Shows loss of lung volume a volume defect of the right thoracic cavity
caused by pulmonary hypoplasia.
Radiography
LAB RESULTS
▪ Renal function (serum creatinine, blood
urea, electrolyte levels)
▫ Oligohydramnios
OTHER DIAGNOSTICS
▪ Lung weight, lung weight to body weight
ratio, mean radial alveolar count (RAC), lung
DNA
OSMOSIS.ORG 877
NOTES
NOTES
LOWER RESPIRATORY TRACT
INFECTION

▪ Infections involving trachea, bronchi, LAB RESULTS
bronchioles, lungs ▪ Complete blood count (CBC)
Microbe identification
RISK FACTORS ▪ Blood culture, sputum culture; Gram stain,
▪ Smoking, compromised immunity, age polymerase chain reaction (PCR)
(children, elderly), comorbidities
▪ Respiratory compromise, infection spread,
sepsis MEDICATIONS
▪ Antimicrobials

▪ Ventilatory support
▪ Cough, dyspnea, fatigue, fever
BACTERIAL TRACHEITIS
osms.it/bacterial_tracheitis
RISK FACTORS
PATHOLOGY & CAUSES ▪ Antecedent viral infections, especially croup
▪ Commonly affects children
▪ Rare, potentially life-threatening exudative
infection
▫ Characterized by mucosal ulceration, COMPLICATIONS
pseudomembrane formation, airway ▪ Pneumonia, septicemia, pneumothorax,
obstruction risk (due to edema, pneumomediastinum, hypoxia (secondary
exudative sloughing) to airway obstruction), cardiorespiratory
▪ Common infective agents: Staphylococcus arrest
aureus, Moraxella catarrhalis, Streptococcus
pneumoniae, H. influenzae
878 OSMOSIS.ORG
Chapter 125 Lower Respiratory Tract Infections

▪ Prodromal respiratory viral infection MEDICATIONS
presentation → acute onset of fever, ▪ Broad antibiotic coverage
hoarseness, sore throat, stridor
▪ Productive, barky cough with copious
OTHER INTERVENTIONS
tracheal secretions, retrosternal pain
▪ Ventilatory support
▪ Progressive respiratory distress
▫ Humidified supplemental oxygen,
▫ Dyspnea, retractions, fatigue, ↓ level of
intubation, endoscopic tracheal
consciousness
debridement
▪ Fluid management
DIAGNOSIS
DIAGNOSTIC IMAGING
Chest X-ray
▪ Upper tracheal narrowing (“steeple sign”)
▪ Tracheal pseudomembranes (irregular
shadows)
LAB RESULTS
▪ CBC: leukocytosis, left shift
Microbe identification
▪ Positive tracheal culture, Gram stain
OTHER DIAGNOSTICS
▪ Laryngoscopy: subglottic edema; tracheal
lumen narrowing; presence grayish
exudate; slough, pus; friable tracheal Figure 125.1 The endoscopic appearance of
mucosa bacterial tracheitis in a nine-year-old boy.
BRONCHIOLITIS
osms.it/bronchiolitis
▪ Dead cells, mucus slide into airway → form
PATHOLOGY & CAUSES mucus plugs → trap air → airways collapse
(atelectasis)
▪ Viral small airway respiratory infection
▪ Viral spread through respiratory secretions,
contaminated hands → infects lower
CAUSES
respiratory tract cells → natural killer cells ▪ Respiratory syncytial virus (RSV): most
attack → cytokines released → epithelial common, especially during winter months
cells produce mucus, vessels vasodilate → ▪ Adenovirus, human bocavirus, human
fluid leaks, walls swell → airway narrows metapneumovirus
(more severe in children) ▪ Mycoplasma pneumoniae
OSMOSIS.ORG 879
RISK FACTORS
▪ Young age (children < two years old),
previous infection, daycare attendance,
decreased immunity, neuromuscular
disorders, premature birth, cardiovascular
malformations, airway malformations,
exposure to smoking
COMPLICATIONS
▪ Hypoxemia, sepsis
SIGNS & SYMPTOMS

▪ Congestion, pharyngitis, sore throat, cough
▪ Hypoxia → tachycardia, tachypnea,
exhaustion Figure 125.2 A plain chest radiograph in
▪ If severe: dyspnea, wheezing, central apnea a child with bronchiolitis demonstrating
(brief periodic breathing arrest), nasal bilateral hilar fullness.
flaring, retractions, cyanosis, fever, poor
feeding, ↓ activity
DIAGNOSIS
DIAGNOSTIC IMAGING
X-ray
▪ Patchy infiltrates, atelectasis
LAB RESULTS
▪ Positive rapid viral testing (RT-PCR):
suggests viral infection
TREATMENT
OTHER INTERVENTIONS
Figure 125.3 A CT scan of the chest in
Immunoprophylaxis the axial plane in an individual with severe
▪ Palivizumab: monoclonal antibody against bronchiolitis. Both lung fields demonstrate
RSV given monthly throughout RSV season the tree-in-bud pattern.
for prematurely-born infants, chronic lung
disease, congenital heart disease
▪ Heated, humidified supplemental oxygen
(high-flow nasal cannula/continuous
positive airway pressure (CPAP)), fluids,
nasal suctioning
▪ Intubation (if hypoxia continues despite
intervention)
880 OSMOSIS.ORG
COMMUNITY–ACQUIRED
PNEUMONIA
osms.it/community-acquired_pneumonia
Resolution
PATHOLOGY & CAUSES ▪ Approx. day 8, can continue for three
weeks
▪ Pneumonia acquired outside hospital/
▫ Exudate digested by enzymes, ingested
healthcare setting
by macrophages, coughed up
▪ Viral pneumonia may → superimposed
bacterial infection
COMPLICATIONS
Spread ▪ Meningitis, sepsis, pleural effusions
▪ Respiratory: from host to host
▪ Hematogenous: from another infection with
same pathogen (e.g. cellulitis) SIGNS & SYMPTOMS
Causative organisms ▪ High fever, cough, hemoptysis, pleuritic
▪ S. pneumoniae, S. aureus, H. influenzae, chest pain, tachypnea, tachycardia,
group A streptococci, influenza virus, dyspnea, muscle pain, fatigue
respiratory syncytial virus (RSV), ▪ Crepitation on palpation, dullness on
parainfluenza percussion
RISK FACTORS
▪ Advanced age, lowered immunity, smoking,
alcohol abuse, malnutrition, chronic lung
disease
STAGING
Congestion
▪ Between days 1–2
▫ Blood vessels, alveoli start filling with
excess fluid
Red hepatization
▪ Between days 3–4
▫ Exudate (contains red blood cells,
neutrophils, fibrin) starts filling airspaces
→ solidifies them → lungs develop liver-
like appearance
Figure 125.4 A plain chest radiograph
Gray hepatization demonstrating patchy peri-bronchial
shadowing in an individual with
▪ Approx. days 5–7
bronchopneumonia.
▫ Lungs remain firm but color changes →
red blood cells in exudate start to break
down
OSMOSIS.ORG 881
Prevention
DIAGNOSIS ▪ 23-valent vaccine (Pneumovax) available
against pneumococcus
DIAGNOSTIC IMAGING
▫ Recommended in splenectomised,
X-ray immunocompromised individuals
▪ Interstitial infiltrates; consolidation; may
show pleural effusion
LAB RESULTS
▪ ↓ oxygen saturation
▪ CBC: leukocytosis
▪ Organism identification: sputum Gram
stain, culture; C-reactive protein test (CRP),
PCR for typical viruses
▪ Positive urine for S. pneumoniae
TREATMENT
MEDICATIONS
▪ Antibiotics
OTHER INTERVENTIONS Figure 125.5 A plain chest radiograph

▪ Supplemental oxygen, fluids demonstrating consolidation of the right
middle lobe in an individal with lobar
pneumonia.
882 OSMOSIS.ORG

of acute pneumonia. In the affected part
of the lung (right) the alveoli are filled with
neutrophils.
CROUP
osms.it/croup

▪ Acute respiratory condition ▪ Progressive respiratory symptoms; sore
▫ Characterized by laryngotracheitis throat, hoarse voice (due to laryngeal
▪ Immune response to epithelial viral infection involvement)
▫ Upper bronchi: larynx, trachea narrow ▪ Respiratory symptoms
due to swelling ▫ “barking” cough
▫ Lower bronchi: terminal bronchioles, ▫ Tachypnea
viral pneumonia ▫ Grunting (attempt to increase end-
expiratory pressure)
CAUSES ▫ Prominent inhalation, inspiratory stridor,
apnea
▪ RSV, parainfluenza, adenoviruses
▪ Historically: Corynebacterium diphtheriae
(vaccine development → ↓ incidence) DIAGNOSIS
▪ Most common in children < six years old X-ray
▪ “Steeple sign,” narrowing below epiglottis
COMPLICATIONS
▪ Hypoxia, respiratory failure LAB RESULTS
▪ Secondary bacterial infections → ↑ ▪ CBC: normal ↑ with left shift, or ↓
mortality
OSMOSIS.ORG 883
OTHER DIAGNOSTICS
▪ Severity: Westley scale 0–17
▫ 3-7: moderate
▫ 8-11: severe
▫ 12 and above: indicates respiratory
failure
TREATMENT
MEDICATIONS
▪ Dexamethasone, epinephrine (nebulized)
OTHER INTERVENTIONS
▪ Humidified supplemental oxygen, fluids,
antipyretics
▪ Intubation (if impending respiratory failure) Figure 125.7 A plain X-ray image
demonstrating the steeple sign in an infant
with croup.
884 OSMOSIS.ORG
NOSOCOMIAL PNEUMONIA
osms.it/nosocomial-pneumonia

▪ Hospital-acquired pneumonia ▪ Nonspecific symptoms (malaise, lethargy),
▫ AKA healthcare-associated pneumonia fever, productive cough
▫ Includes ventilator-associated
pneumonia
DIAGNOSIS
▪ Involves microaspiration of organisms
from oropharyngeal tract/sometimes from
DIAGNOSTIC IMAGING
gastrointestinal tract
▪ Severity varies depending on offending Chest X-ray
organism, individual’s immune system ▪ Shows infiltrates
status
LAB RESULTS
CAUSES ▪ CBC: leukocytosis, ↑ CRP
▪ MRSA, Klebsiella pneumoniae, ▪ Positive sputum culture
Pseudomonas aeruginosa, Acinetobacter
▪ Often polymicrobial
TREATMENT
RISK FACTORS
▪ Intubation, poor staff hygiene, MEDICATIONS
contaminated equipment contact ▪ Antibiotics
COMPLICATIONS OTHER INTERVENTIONS

▪ Meningitis, sepsis, pleural effusions ▪ Supplemental oxygen, fluids
OSMOSIS.ORG 885
NOTES
NOTES
OBSTRUCTIVE LUNG DISEASE

OTHER DIAGNOSTICS
PATHOLOGY & CAUSES
Spirometry/pulmonary function test (PFTs)
▪ Obstruction of airflow from lungs ▪ Tidal volume (TV)
▪ Increased resistance to airflow → air- ▫ Volume of air inspired, expired during
trapping quiet breathing
▪ Classifications ▪ Residual volume (RV)
▫ Narrowing of lumen wall (e.g. asthma, ▫ Volume of air left in lung after maximal
chronic bronchitis) expiration
▫ Increasing pressure external to ▪ Forced vital capacity (FVC)
airway/loss of lung parenchyma (e.g. ▫ Maximum volume of air that can be
emphysema) expired after maximal inspiratory effort
▫ Obstruction of airway lumen (e.g. ▪ Forced expiratory volume (FEV)
bronchiectasis, chronic bronchitis) ▫ Volume of air forcibly exhaled per unit
of time
COMPLICATIONS ▪ Peak expiratory flow rate (PEFR)
▪ Cor pulmonale, right ventricular ▫ During FEV, maximum flow of expiration
hypertrophy ▪ Functional residual capacity (FRC)
▫ Volume of air left in lungs after quiet
expiration
SIGNS & SYMPTOMS
▪ Cough, thick mucus, dyspnea, wheezing TREATMENT
▪ See individual diseases
DIAGNOSIS
DIAGNOSTIC IMAGING
Chest X-ray/CT scan
LAB RESULTS
▪ Sputum culture
▪ Arterial blood gas (ABGs)
886 OSMOSIS.ORG
Chapter 126 Obstructive Lung Disease
ALPHA 1-ANTITRYPSIN (A1AT)

DEFICIENCY
osms.it/a1at-deficiency
amounts A1AT proteins
PATHOLOGY & CAUSES ▫ Heterozygous individuals have 60%
normal levels (enough to protect lungs
▪ Autosomal dominant (codominant) genetic in non-smokers)
disorder
▫ Increased risk of lung/liver disease
▫ Decreased production/absence of A1AT
▪ PiZZ
→ overaction of proteases → damaged
alveoli → damaged lungs, liver ▫ Homozygous
▪ Lungs ▫ Individuals only have 15–20% normal
levels
▫ Damaged alveoli inflammation →
neutrophils secrete elastase → absence ▫ Much higher risk of lung/liver disease
of/decreased A1AT → elastase overacts, ▫ Can live without lung/liver disease if
inflames → increased breakdown of environmental exposures minimal
elastin → alveoli lose elasticity, integrity ▫ Infants can develop liver failure during
→ chronic obstructive pulmonary first years of life
disease (COPD) ▫ Individuals with no production of A1AT
▪ Liver = no liver disease
▫ Genetic mutation → misfolded A1AT
build up in endoplasmic reticulum of COMPLICATIONS
hepatocytes → kill hepatocytes →
▪ COPD (emphysema, bronchiectasis, chronic
cirrhosis
bronchitis), hepatocellular carcinoma, liver
cirrhosis, chronic hepatitis
CAUSES
▪ Smoking
▫ Earlier onset of COPD in individuals with SIGNS & SYMPTOMS
A1AT deficiency
▪ Genetics ▪ COPD: shortness of breath, wheezing,
mucus production, chronic cough
▫ Serine protease inhibitor, clade A,
member 1 (SERPINA1) encodes ▪ Liver damage, cirrhosis, impaired liver
A1AT protein, located on long arm of function: inability to make coagulation
chromosome 14 factors, hepatic encephalopathy, portal
hypertension, esophageal varices, jaundice,
▪ Pi*M
hepatocellular carcinoma
▫ Normal allele
▪ Pi*Z (most common)
▫ Mutated/diseased allele
▫ Misfolded A1AT proteins aggregate
→ stick in endoplasmic reticulum of
hepatocytes → kill hepatocytes
▪ PiMZ
▫ Heterozygous (one normal allele, one
diseased allele)
▫ Mutated gene contributes 10% normal
OSMOSIS.ORG 887
DIAGNOSIS TREATMENT
▪ Augmentation therapy
Liver ultrasound
▫ Intravenous (IV) infusions of A1AT
Chest X-ray/CT scan protein from plasma donors
▪ Hyperinflated/damaged lungs, basilar ▫ Not curative, only slows progression
emphysema, panlobular emphysema ▪ Inhalers, supplemental oxygen
▫ Smoking: apically distributed ▫ COPD
emphysema ▪ Lactulose
▫ Prevent hepatic encephalopathy
LAB RESULTS ▫ For liver cirrhosis
▪ Serum A1AT levels
▪ Family history, genetic testing SURGERY
▪ Liver biopsy ▪ Liver transplant
▫ Esp. homozygous infants, liver failure
OTHER DIAGNOSTICS during first years
▪ PFT ▪ Lung transplant
▫ Measure rate air exits lungs
▪ Periodic acid-Schiff (PAS)
▫ Diastase-resistant pink globules in liver
biopsy
▫ Stains A1AT pink

the axial plane demonstrating panlobular
emphysema as a consequence of alpha
1-antitrypsin deficiency.

of the liver in an individual with alpha
1-antitrypsin deficiency. There are globular
inclusions within periportal hepatocytes.
888 OSMOSIS.ORG
ASTHMA
osms.it/asthma
▪ Individuals with atopic family history to
PATHOLOGY & CAUSES allergies
▪ Atopic triad
▪ Hyperresponsiveness disorder, reversible ▫ Asthma, atopic dermatitis, allergic
airflow obstruction rhinitis
▪ Chronic inflammation, narrowing of airways
▪ Acute (Type 1 hypersensitivity reaction) Intrinsic
▫ Initial sensitization to allergen → ▪ Nonimmune
production of cluster of differentiation 4 ▪ Viral infections, stress, exercise, smoking
(CD4), T helper 2 (Th2) cells → release
interleukin 4 (IL4), interleukin 5 (IL5) →
environmental trigger → eosinophils, SIGNS & SYMPTOMS
mast cells release inflammatory
mediators in bronchial walls (e.g. ▪ Coughing, chest tightness, dyspnea,
histamine, leukotrienes) → degradation difficulty breathing, wheezing, whistling
of lipids, proteins, nucleic acids → tissue during expiration
destruction → strong inflammatory ▪ Curschmann spirals in sputum
reaction in bronchiolar walls → smooth ▫ Spiral-shaped mucus plugs
muscle of bronchioles spasm, mucus in
▫ Casts from small bronchi
narrow airways increases → difficulty
breathing ▫ Blocks air exchange, inhaled
medications from reaching inflammation
▫ Vasodilation of pulmonary vasculature,
increased capillary permeability → ▪ Charcot–Leyden crystals in sputum
edema ▫ Needle-shaped, formed from
▫ Increased mucus production by goblet breakdown of eosinophils
cells → impaired mucociliary function
▪ Chronic inflammation → scarring, fibrosis
→ thickening of epithelial basement
DIAGNOSIS
membrane → permanently narrows airway
OTHER DIAGNOSTICS
▪ Th2 cells release IL5 → attract, activate
eosinophils ▪ Trigger test, spirometry, peak air flow
▪ Neutrophils release cytokines ▪ Classifications based on frequency of
symptoms (esp. night/morning), forced
▫ Interleukin 8 (IL8)
expiratory volume in one second (FEV1),
▫ More severe for individuals with PEFR, frequency of medication use
neutrophilic asthma (intermittent, mild persistent, moderate
▪ Triggers persistent, severe persistent)
▫ Air pollution, cigarette smoke, dust,
pet dander, cockroaches, mold, pollen,
medications (e.g. aspirin, beta-blockers) TREATMENT
TYPES OTHER INTERVENTIONS

▪ No cure; treatments manage symptoms,
Extrinsic prevent asthma attack
▪ Type 1 hypersensitivity reaction triggered ▪ Avoid triggers
by extrinsic allergens (e.g. dust, mold)
OSMOSIS.ORG 889
890 OSMOSIS.ORG

demonstrating hyperinflation in an
individual with chronic asthma. There is a
pneumothorax in the right lower zone.
BRONCHIECTASIS
osms.it/bronchiectasis
Airway obstruction
PATHOLOGY & CAUSES ▪ E.g. tumor inside/outside airway, lodged
foreign object
▪ Chronic inflammation → permanent dilation
▪ Blockage prevents mucociliary escalator
of bronchi, bronchioles → destruction of
from clearing mucus → recurrent
airways
pneumonias → chronic inflammation
▫ Damage to mucociliary “elevator” →
mucus, bacteria accumulates Infections
▪ E.g. aspergillosis, tuberculosis, adenovirus,
CAUSES Haemophilus influenzae, Staphylococcus
aureus; hypersensitivity response →
Chronic inflammation inflammation
▪ Primary ciliary dyskinesia ▫ Chronic inflammation → immune cells,
▫ Absence of dynein arm in cilia → cilia cytokines damage cilia, elastin fibers →
move abnormally → mucus stuck in airways dilated, clogged with mucus
airways → bacteria in mucus multiply → → fibroblasts deposit collagen → loss
pneumonia → chronic inflammation of elastin, buildup of collagen → lungs
▪ Cystic fibrosis (most common) less elastic → more difficult for air to
move smoothly → lung function declines
▫ Mucus too sticky → hard for cilia to
→ hypoxia → pulmonary arterioles
sweep → mucus accumulates →
constrict to divert blood away from
recurrent pneumonias → chronic
damaged areas of lung → increased
inflammation, infection
OSMOSIS.ORG 891
pulmonary vascular resistance →
right ventricular hypertrophy → cor
pulmonale → inflammation of pleura
SIGNS & SYMPTOMS

▪ Wheezing, productive cough, foul smelling
mucus, dyspnea, hemoptysis, recurrent/
persistent pneumonia, basilar crackles
▪ Long term hypoxia
▫ Digital clubbing
DIAGNOSIS
DIAGNOSTIC IMAGING
CT scan
▪ Dilated bronchi/bronchioles
Chest X-ray
▪ Increased bronchial markings at lung
periphery
LAB RESULTS
▪ Sputum culture
appearance of the lungs in a case of severe
▪ Genetic testing bronchiectasis.
OTHER DIAGNOSTICS
▪ Spirometry
▫ FEV1 decreased, FEV1/FVC ratio
decreased
▪ Sweat test
TREATMENT
MEDICATIONS
▪ Bronchodilators; beta-2 agonists (e.g.
albuterol)
▪ Inhaled corticosteroids (e.g. fluticasone
▪ Antibiotics of bronchiectasis complicated by fungal
▫ Recurrent pneumonias colonisation. There is a heavily dilated
bronchus containing an aggregation of
OTHER INTERVENTIONS fungus known as an aspergilloma.
▪ Percussion, postural drainage
▫ Recurrent pneumonias
▪ Pulmonary hygiene
▪ Adequate hydration
892 OSMOSIS.ORG
CHRONIC BRONCHITIS
osms.it/chronic-bronchitis

▪ Preventable, progressive pulmonary DIAGNOSTIC IMAGING
disease
Chest X-ray
▫ Chronic airway inflammation, limited
airflow ▪ Large, horizontal heart, increased bronchial
markings
▫ Bronchial tubes in lungs inflame →
productive cough
▪ Subset of COPD LAB RESULTS
▪ Exposure to irritants → hypertrophy/ ▪ ABGs
hyperplasia of bronchial mucous glands, ▫ Respiratory acidosis (arterial PCO2
goblet cells in bronchioles, cilia less mobile > 45mmHg, bicarbonate > 30mEq/L)
→ increased mucus production, less
movement → mucus plugs → obstruction
in bronchioles → air-trapping → productive
OTHER DIAGNOSTICS
cough ▪ Productive, mucinous cough
▪ Blocked airflow, air-trapping → increased ▫ At least three months over two
partial pressure of CO2 in lungs → less consecutive years
O2 reaches blood → cyanosis (if severe); ▪ PFTs
individuals referred to as “blue bloaters” ▫ Increased TLC, air-trapping; decreased
FVC1/FVC ratio
RISK FACTORS ▪ Postmortem measurement
▪ Smoking (primary cause), cystic fibrosis, ▫ Reid index (measure ratio of thickness
sulfur, nitrogen dioxide, dust, silica, family of bronchial mucinous glands, total
history, genetic predisposition thickness of airway, epithelium to
cartilage)
▫ > 40% (due to hyperplasia, hypertrophy
COMPLICATIONS of glands)
▪ Pulmonary hypertension, increased
workload of right ventricle, cor pulmonale,
infections distal to mucus blockages, TREATMENT
fibrosis of terminal bronchioles,
compensatory polycythemia MEDICATIONS
▪ Supplemental oxygen, bronchodilators,
inhaled steroids, antibiotics
SIGNS & SYMPTOMS
▫ Manage symptoms
▪ Wheezing (due to mucus, narrow airway), ▪ Prophylactic vaccination against
crackles/rales (small airways pop open influenza, Streptococcus pneumoniae (S.
during air movement due to narrow pneumoniae)
passageway)
▪ Hypoxemia, hypercapnia (due to mucus OTHER INTERVENTIONS
plugs blocking air flow) → cyanosis → ▪ Smoking cessation, pulmonary
tissue hypoxia rehabilitation
OSMOSIS.ORG 893
CYSTIC FIBROSIS (CF)
osms.it/cystic-fibrosis
(ABPA)
PATHOLOGY & CAUSES ▪ Sinusitis
▫ Related to chronic inflammation
▪ Autosomal-recessive multisystem disorder
▪ Significant hemoptysis
▫ Affects lungs, digestive system,
reproductive system, sweat glands ▫ Related to enlarged, tortuous bronchial
arteries
▪ Caused by CFTR gene defect (located on
long arm of chromosome 7) ▪ Bronchiectasis
▫ Encodes cyclic adenosine ▫ Due to mucus plugging
monophosphate–regulated chloride ▪ Pneumothorax
channel cystic fibrosis transmembrane ▫ Related to ruptured emphysematous
conductance regulator (CFTR) bullae
▫ Various mutations: including lack of ▪ Secondary pulmonary hypertension
protein production; protein trafficking ▫ Related to small pulmonary artery
defect, degradation within cellular hypertrophy
endoplasmic reticulum, Golgi body ▪ Nasal polyps
▪ Genetic defect → impaired sodium, chloride ▫ Related to chronic inflammation
transport across epithelial cell surface →
▪ Respiratory failure
thick, tenacious secretions
▪ Non-pulmonary complications
▫ Classic triad: ↑ sweat chloride levels,
chronic sinopulmonary disease, ▫ Cirrhosis; gallstones; pancreatitis; heat
pancreatic insufficiency exhaustion, dehydration; hypochloremic
alkalosis (excessive salt-loss in sweat);
▪ Bronchi effects
rectal prolapse; infertility (azoospermia);
▫ Goblet cell hyperplasia, submucosal fat-soluble vitamin deficiency; anemia;
gland hypertrophy → production nail clubbing
of viscous mucus, mucus plugging
→ airway inflammation → elastase
released from neutrophils → tissue SIGNS & SYMPTOMS
destruction → ↑ thickness of airway
walls, bronchiectatic cysts, ventilation- ▪ Highly variable presentation
perfusion mismatch → hypoxemia
▫ Related to specific mutation, gene
penetrance, environmental factors
RISK FACTORS ▪ Specific pulmonary manifestations
▪ Family CF history; especially carrier parents ▫ Chronic, productive cough; dyspnea; ↑
▪ ↑ incidence in white people of Northern, anterior-posterior chest diameter; digital
Central European descent clubbing; basilar crackle; expiratory
wheeze; generalized hyperresonance
COMPLICATIONS
▪ Chronic respiratory tract infections
▫ Common bacteria: Pseudomonas
aeruginosa, Staphylococcus aureus,
Haemophilus influenzae (especially
younger children)
▫ Invasive fungal disease may occur →
allergic bronchopulmonary aspergillosis
894 OSMOSIS.ORG
DIAGNOSIS
DIAGNOSTIC IMAGING
Prenatal ultrasound
▪ May detect hyperechogenic bowel,
meconium peritonitis
Chest X-ray
▪ Hyperinflation, air trapping, atelectasis,
flattened diaphragm, peribronchial
thickening, bronchovascular markings,
peribronchial cuffing, parallel lines (related
thickened bronchial walls—”tram tracks”)
CT scan
▪ Inspissated bronchial secretions; detects
degree of bronchiectasis Figure 126.6 A plain chest radiograph
demonstrating tram-track opacities and ring
shadows in an individual with cystic fibrosis.
LAB RESULTS They are particularly well demonstrated in
▪ Genetic testing the left upper zone.
▪ CFTR mutation identification
▪ Sweat chloride test
▫ ↑ sweat chloride concentration
OTHER DIAGNOSTICS
▪ Newborn screening
▫ Pilocarpine administered → stimulate
sweat; collected, analyzed for chloride ▫ Detects CF in neonatal period; initiate
content early intervention
▪ Pulmonary function tests
▫ ↓ FEV1 FEV1/FVC
▫ ↑ residual volume to total lung capacity
(RV/TLC) ratio
▫ ↓ total lung capacity
▫ ↓ vital capacity
TREATMENT
MEDICATIONS
▪ CFTR modulators
▪ Medications to clear respiratory secretions;
inhaled hypertonic saline
▪ Anti-inflammatory medications (e.g.
glucocorticoids)
▪ Antibiotics
▫ Infections
Figure 126.7 A CT scan of the chest in ▪ Bronchodilators
the coronal plane demonstrating bilateral ▫ ↓ airflow obstruction
widespread bronchiectasis in a twenty five
▪ Prevention
year old female with cystic fibrosis.
▫ Annual influenza vaccine; pneumococcal
vaccine
OSMOSIS.ORG 895
SURGERY OTHER INTERVENTIONS
▪ Lung transplantation ▪ Address complications
▪ Respiratory support ▪ Chest physiotherapy
▫ Respiratory failure → invasive ▫ Mobilize retained secretions
ventilation ▪ Respiratory support
▫ Supplemental oxygen
▫ Positive-pressure ventilation
EMPHYSEMA
osms.it/emphysema
Paraseptal emphysema
PATHOLOGY & CAUSES ▪ Distal alveoli most affected
▫ Lung tissue on periphery of lobules near
▪ COPD subset
interlobular septa
▫ Exposure to irritants → degrades elastin
▫ Ballooned alveoli on lung surface
in alveoli, airways → air-trapping, poor
rupture → pneumothorax
gas exchange.
▪ Irritants (e.g. cigarette smoke) →
attraction of inflammatory cells → release CAUSES
leukotrienes, chemical mediators (e.g. ▪ Smoking, A1AT deficiency
B4; IL8; TNF alpha/proteases, elastases/
collagenases) → destroy collagen, elastin
→ lose elasticity → low pressure during
COMPLICATIONS
expiration pulls walls of alveoli inward → ▪ Hypoxic vasoconstriction → cor pulmonale
collapse → air-trapping distal to collapse → ▫ Poor gas exchange → vessels
septa breaks down → neighboring alveoli vasoconstrict to shunt blood to
coalesce into larger air spaces → decreased better gas exchange → pulmonary
surface area available for gas exchange hypertension → increased workload
▫ Loss of elastin → lungs more compliant for right heart → right ventricular
(lungs expand, hold air) hypertrophy → cor pulmonale
▫ Alveolar air sacs permanently enlarge, ▪ Hypoxemia
lose elasticity → exhaling difficult ▪ Pneumothorax

Centriacinar/centrilobular emphysema
▪ Barrel chest (air-trapping, hyperinflation
▪ Most common
of lungs), apparent respiratory distress
▪ Damage to central/proximal alveoli of with use of accessory muscles, tripod
acinus sparing distal alveoli positioning, weight loss, exhaling slowly
▫ Individuals who smoke (irritants can’t through pursed lips (“pink puffers”),
reach distal alveoli); upper lobes of lungs hyperventilation
Panacinar emphysema ▪ Pursing lips increases pressure in airway
→ keeps airway from collapsing → weight
▪ Entire acinus uniformly affected
loss
▫ A1AT deficiency; lower lobes of lungs
▪ Dyspnea, cough (with less sputum)
896 OSMOSIS.ORG
DIAGNOSIS
DIAGNOSTIC IMAGING
Chest X-ray
▪ Increased anterior-posterior diameter,
flattened diameter, increased lung field
lucency (air-trapping)
OTHER DIAGNOSTICS
▪ Increased TLC
▪ FVC decreased (esp. FEV1)
TREATMENT
MEDICATIONS
▪ Bronchodilators
▪ Inhaled steroids
▪ Combination inhalers
▫ Bronchodilators + inhaled steroids
▪ Oral steroids
▫ Adverse effects: oral candidiasis, weight
gain, diabetes, osteoporosis
▪ Antibiotics (e.g. azithromycin prevents Figure 126.8 The gross pathological
exacerbations) appearance of emphysema. There are
▪ Supplemental oxygen numerous dilated airspaces in a peripheral
distribution.
SURGERY
▪ Lung volume reduction
▫ Removal of areas of damaged lung
tissue to create extra space in chest
cavity for healthy lung tissue to expand
▫ Can improve quality of life and prolong
survival
▪ Lung transplant
▪ Bullectomy
▫ Removal of bullae (large air spaces) to
improve air flow
OTHER INTERVENTIONS Figure 126.9 The histological appearance

▪ Pulmonary rehabilitation program of emphysema There are numerous
▫ Customized education plan consisting of hyperexpanded alveoli.
exercising training, nutrition advice, and
lifestyle counseling
OSMOSIS.ORG 897
MNEMONIC: P vs. B
Emphysema vs. Bronchitis
EmPhysema: Pink Puffer
Chronic Bronchitis: Blue
Bloater
898 OSMOSIS.ORG
NOTES
NOTES
PERINATAL ACUTE RESPIRATORY
DISEASE

OTHER DIAGNOSTICS
PATHOLOGY & CAUSES ▪ Pulse oximetry, arterial blood gases
ECG
▪ Respiratory problems in newborns/infants;
dyspnea to sudden death ▪ Congenital heart defects
▪ Respiratory distress
OTHER INTERVENTIONS
▪ Supplemental oxygen therapy, assisted
▫ Cyanosis, bradypnea, tachypnea, etc.
ventilation
DIAGNOSIS
DIAGNOSTIC IMAGING
Chest X-ray
MECONIUM ASPIRATION SYNDROME

(MAS)
osms.it/meconium-aspiration-syndrome
▫ Surfactant deactivation, synthesis
PATHOLOGY & CAUSES inhibition
▫ Chemical pneumonitis: irritates air
▪ Respiratory condition caused by aspiration pathways
of amniotic fluid contaminated by
▫ Persistent pulmonary hypertension
meconium (fetal stool) before/during birth
of newborn (PPHN): hypertrophy
▪ Bile pigments of pulmonary vessels due to chronic
▫ Meconium with black-green color distress
▪ MAS in approx. 10% of neonates exposed ▫ Medium for bacterial growth + reduces
to meconium antibacterial activity → increases risk of
▪ Meconium in airways infection
▫ Airway obstruction: atelectasis
OSMOSIS.ORG 899
CAUSES
▪ Initiated by fetal distress due to perinatal
complications (e.g. maternal hypertension,
preeclampsia, placental insufficiency,
oligohydramnios, infection, acidosis,
maternal drug abuse)
▫ Hypoxia → increased vagal stimulation
→ gastrointestinal (GI) tract peristalsis
+ sphincter relaxation → meconium
release
▫ Hypoxia → fetus gasping, aspiration of
meconium-stained amniotic fluid
RISK FACTORS
▪ Term/post-term gestation (> 40 weeks);
perinatal complications → fetal hypoxia, Figure 127.1 A plain chest radiograph of a
stress neonate demonstrating bilateral, diffuse,
coarse opacities secondary to meconium
aspiration.
COMPLICATIONS
▪ Pneumothorax, pulmonary hypertension,
neonatal infection, infant respiratory
distress syndrome, acidosis DIAGNOSIS
DIAGNOSTIC IMAGING
SIGNS & SYMPTOMS
Chest X-ray
▪ Meconium spotting during labor ▪ Patchy atelectasis, consolidation areas
▫ Green-yellow colour of amniotic fluid, ▪ Hyperexpansion due to airway obstruction
infant’s skin, umbilical cord ▪ Pneumomediastinum due to air leak
▪ Low APGAR score
Ultrasound
▫ Appearance, Pulse, Grimace, Activity,
Respiration ▪ ECG to assess pulmonary hypertension
▪ Respiratory distress
▫ Labored breathing, tachypnea, OTHER DIAGNOSTICS
bradycardia, intercostal/subcostal/
substernal retractions, cyanosis, nasal Meconium
flaring ▪ In amniotic fluid, on infant, in trachea (if
▪ Blood gas intubation required)
▫ Hypoxemia, hypercarbia, acidosis Respiratory distress
Pulse oximetry
▪ Low oxygen saturation
Auscultation
▪ Crackles, rhonchi sounds
900 OSMOSIS.ORG
Chapter 127 Perinatal Acute Respiratory Disease
Amnioinfusion
TREATMENT ▪ Intrauterine saline infusion
MEDICATIONS ▪ If meconium-stained amniotic fluid,
preventative measures
▪ Antibiotics
▪ Maintain circulatory volume; correct existing Maintain oxygenation, ventilation
metabolic imbalances ▪ Neutral thermal environment
▫ IV fluids; electrolytes, glucose; correct ▪ Decreased oxygen consumption
acidosis ▪ Supplemental oxygen
▪ Mechanical ventilation
OTHER INTERVENTIONS ▪ If PPHN
▪ Transfer to neonatal intensive care unit ▫ Inhalation of nitric oxide (iNO),
(NICU) phosphodiesterase inhibitors
▪ If severe
▫ ECMO
Figure 127.2 Flowchart depicting the pathophysiology of MAS.
OSMOSIS.ORG 901
Figure 127.3 A histology photomicrograph of the fetal membranes containing meconium laden
macrophages.
NEONATAL RESPIRATORY
DISTRESS SYNDROME
osms.it/neonatal-resp-distress
CAUSES
PATHOLOGY & CAUSES ▪ Surfactant production inhibition by insulin
due to maternal diabetes
Respiratory disease in neonates: loss of
▪ Genetic mutations affect production of
lung compliance (distensibility) due to lack of
surfactant proteins
surfactant.
▪ Surfactant inactivation by meconium
▪ AKA neonatal respiratory distress
syndrome/surfactant deficiency disorder ▪ Pulmonary inflammation, edema may
(SDD) complicate respiratory distress
▪ Surfactant deficiency → ↑ surface tension
→ ↓ lung compliance → alveoli collapse RISK FACTORS
upon expiration (microatelectasis) → V/Q ▪ Premature delivery, cesarean delivery,
mismatch → intrapulmonary shunting + maternal diabetes, intrauterine asphyxia,
extrapulmonary shunting (e.g. through meconium aspiration syndrome
patent ductus arteriosus) → hypoxemia
902 OSMOSIS.ORG
COMPLICATIONS
TREATMENT
Acute
▪ Acidosis, hypoglycemia, hypotension, OTHER INTERVENTIONS
infection, diffuse atelectasis, respiratory ▪ Reduce oxygen consumption
failure, death ▪ Radiant warmer, intravenous (IV) fluids
with glucose
Chronic
▪ Intracranial hemorrhage, retinopathy of Assisted ventilation
prematurity, bronchopulmonary dysplasia, ▪ If symptoms do not subside
pulmonary hemorrhage, neurologic ▪ Endotracheal intubation with synthetic/
impairment animal exogenous surfactant therapy
Prevention
SIGNS & SYMPTOMS ▪ Fetal lung maturity test (if preterm delivery
anticipated)
▪ Respiratory distress ▫ Assess surfactant levels by
▫ Tachypnea, tachycardia, intercostal/ amniocentesis; administer
subcostal/substernal retractions, corticosteroids, promote lung maturity
cyanosis, nasal flaring, expiratory
grunting Continuous positive airway pressure
▪ Ventilatory failure (↑ blood CO2), apnea (CPAP)
If severe
DIAGNOSIS ▪ Extracorporeal membrane oxygenation
(ECMO)
DIAGNOSTIC IMAGING INSURE
Chest X-ray ▪ INtubation-SURfactant-Extubation
▪ Low lung volume
▪ Bilateral, diffuse granular/”ground glass”
appearance
▪ Air bronchograms
▫ Pulmonary edema secondary to
inflammation, atelectasis
LAB RESULTS
▪ Oxygen saturation monitor
▫ ↓ SaO2, consider influence of preductal/
postductal gradients
▪ Metabolic acidosis, hypoxia
OTHER DIAGNOSTICS
▪ Lung auscultation (decreased breath
sounds); respiratory distress Figure 127.4 A plain chest radiograph of
a neonate with infant respiratory distress
Post-mortem histopathology syndrome. Both lung fields are granular in
▪ Lungs interspersed with hyper-distended appearance.
alveolar ducts, collapsed alveoli
▪ Hyaline membranes lining/filling alveoli
OSMOSIS.ORG 903
SUDDEN INFANT DEATH
SYNDROME (SIDS)
osms.it/sids

▪ Sudden unexplainable death of infants < ▪ Infant fed, put to bed without sign of
one year old despite thorough death scene distress; found unresponsive
investigation, analysis of perinatal history,
autopsy
▪ Leading cause of death in infants < one DIAGNOSIS
year old; peak incidence, 8–16 weeks
OTHER DIAGNOSTICS
▪ Diagnosis of exclusion
CAUSES
▪ Forensic autopsy, clinical history, death
Triple risk model scene investigation
▪ Triggering event
▫ Sleeping prone, infection
TREATMENT
▪ Underlying vulnerability
▫ Genetic polymorphisms involving OTHER INTERVENTIONS
autonomic nervous system function,
▪ Emergency responders
cardiac conduction channels, altered
cerebral serotonin (5-HT) signaling ▫ Attempt cardiopulmonary resuscitation;
document scene
▪ Developmental vulnerability
▪ Transport to healthcare facility
▫ Immature neuroregulation of
cardiorespiratory control, delayed ▫ Resuscitation attempt continued
immune functionality ▪ Physical examination, lab tests documented
▪ Interview of family members
RISK FACTORS ▫ When was infant last seen alive; who
found infant, when; history of illnesses;
▪ Previous loss of infant from SIDS
sleeping environment
▪ Periconceptional/postnatal smoking,
substance abuse
▫ Prone sleeping position, elimination
▪ Teenage (< 20 years) pregnancy
of environmental risk factors;
▪ Inadequate prenatal care breastfeeding, room-sharing, not bed-
▪ Premature birth sharing, immunizations
▪ Low birth weight
▪ Intrauterine growth restriction
▪ Infant of genetically male sex
▪ Sleep environment
▫ Prone position (strongest modifiable
risk factor); soft sleeping surface;
loose blankets, pillows, stuffed toys;
overheating; bed sharing
904 OSMOSIS.ORG
TRANSIENT TACHYPNEA OF THE

NEWBORN
osms.it/newborn-transient-tachypnea

▪ Respiratory condition; presents in first DIAGNOSTIC IMAGING
hours of life, periods of non-acute rapid
breathing Lung sonography
▪ AKA “quiet tachypnea” Chest X-ray
▪ Radiopaque levels of fluid in horizontal
CAUSES fissure of lungs; hyperinflated lungs;
▪ Delayed reabsorption of alveolar fluid diaphragm flattening
through epithelial aquaporin channels
→ increased alveolar fluid → decreased OTHER DIAGNOSTICS
pulmonary compliance, partial collapse of ▪ Pulse oximetry
small airways, air trapping → hypoxemia,
▪ Arterial blood gas assessment
hypercapnia
▫ Evaluate gas exchange, monitor acid-
base balance
RISK FACTORS
▪ Cesarean delivery without labor;
maternal diabetes, asthma, smoking TREATMENT
during pregnancy; pulmonary immaturity;
surfactant deficiency OTHER INTERVENTIONS
▪ Commonly resolves during first three days
of life
SIGNS & SYMPTOMS ▪ Supplemental oxygen therapy; nasal CPAP
if additional support required
▪ Symptoms present immediately after birth
▪ Neutral thermal environment: decrease
in response to excessive fluid in lungs
oxygen consumption
▪ Tachypnea (> 60 breaths/minute), nasal
▪ Orogastric feedings/IV fluids with glucose
flaring, expiratory grunting, intercostal/
if PO feedings avoided due to increased
subcostal/substernal retractions
respirations
▪ Hypoxemia → hypoxia, cyanosis
▪ Antibiotics, if infection suspected
OSMOSIS.ORG 905
NOTES
NOTES
PLEURA & PLEURAL SPACE

▪ Conditions that adversely affect the DIAGNOSTIC IMAGING
function of the chest wall, pleura, and
lungs resulting in impaired ventilation and Chest X-ray, CT scan, thoracic ultrasound
oxygenation
▫ Pleural effusion: abnormal accumulation LAB RESULTS
of fluid in the potential space between ▪ Pleural effusion
the visceral and parietal pleura (pleural ▫ Analysis of pleural fluid confirms
space) etiology
▫ Pneumothorax: presence of air or gas in
the space between the thoracic wall and
the lung (pleural cavity) TREATMENT
▪ Mediastinal shift → impaired cardiovascular ▪ Pleural effusion
function ▫ Thoracentesis
▪ Pneumothorax
▫ Needle chest decompression, chest tube
SIGNS & SYMPTOMS
906 OSMOSIS.ORG
Chapter 128 Pleura & Pleural Space
PLEURAL EFFUSION
osms.it/pleural-effusion

▪ Excess fluid accumulates in pleural space DIAGNOSTIC IMAGING
▪ Lung expansion limited → impaired
ventilation Chest X-ray
▪ Fluid occupies space between visceral,
Origin parietal pleural
▪ Hydrothorax (serous fluid), hemothorax ▪ Area of whiteness on standard
(blood), urinothorax (urine), chylothorax/ posteroanterior (PA) chest X-ray
lymphatic effusion (chyle), pyothorax (pus, ▪ Blunted costophrenic angles
AKA empyema) ▪ Greater density than rest of lung →
Pathophysiology gravitates towards dependent regions
▪ Transudative pleural effusion ▫ ↑ fluid on upright X-ray or lateral
decubitus X-ray
▫ Pressure driven filtration: ↑ hydrostatic
pressure/↓ oncotic pressure → force Lung ultrasound
imbalance, fluid extravasation → fluid ▪ Confirms presence of effusion and detects
leaks across intact capillary membranes pleural fluid septations
▫ Alteration in Starling forces
▪ Exudative pleural effusion
▫ Local inflammatory processes → leaky
capillaries
CAUSES
▪ Transudative
▫ Congestive heart failure, liver cirrhosis,
severe hypoalbuminemia, nephrotic
syndrome, acute atelectasis, myxedema,
peritoneal dialysis, Meigs syndrome,
obstructive uropathy, end-stage renal
disease
▪ Exudative
▫ Infection, malignancy, trauma,
pulmonary infarction, pulmonary
embolism, autoimmune processes,
pancreatitis, ruptured esophagus
Figure 128.1 A plan chest radiograph
demonstrating a large left sided pleural
SIGNS & SYMPTOMS effusion, in this case as a consequence
of metastatic melanoma. There is notable
▪ Asymptomatic (if small) tracheal deviation.
▪ Pleuritic chest pain
▪ Dyspnea
▫ Worse when lying down (orthopnea)
OSMOSIS.ORG 907
▫ Rheumatoid factor, antinuclear
antibody, complement: collagen
vascular disease
▫ Triglycerides: chylothorax from
thoracic duct leakage (trauma, cancer,
lymphoma)
OTHER DIAGNOSTICS
▪ Medical history
Clinical examination
▪ ↑ fluid on affected side
▫ ↓ chest expansion
▫ Stony dullness to percussion
▫ Diminished breath sounds
▫ ↓ vocal resonance, fremitus
Figure 128.2 A CT scan of the chest in the ▫ Tracheal deviation away from effusion
coronal plane demonstrating a right sided ▪ If lung compressed above effusion
pleural effusion. ▫ Bronchial breathing, egophony
Light’s criteria
LAB RESULTS ▪ Classification of transudative/exudative
effusion
Thoracentesis
▪ Transudative
▪ Needle inserted through chest wall, 5th–
▫ Difference between albumin in blood,
8th intercostal space, midaxillary line →
pleural fluid > 1.2g/dL
pleural space → withdraw fluid
▪ Exudative
▪ Trial diuresis for three days in heart failure
before thoracentesis ▫ Ratio of pleural fluid protein to serum
protein > 0.5
▪ Effusion analysis
▫ Ratio of pleural fluid LDH to serum LDH
▫ Amylase: pancreatitis, esophageal
> 0.6
perforation, malignancy
▫ Pleural fluid LDH > 0.6, ⅔ times lab
▫ Blood: traumatic, malignancy,
specific upper limit for serum
pulmonary embolism with infarction,
tuberculosis
▫ Cholesterol: chylous (lymphatic fluid) vs.
chyliform effusion (chyle-like fluid from
chronic disease)
▫ Cytology: malignancy, infection (reactive
effusion)
▫ Differential cell count: lymphocytic
effusion in tuberculosis, cancer,
lymphoma
▫ Glucose (low): rheumatoid arthritis,
tuberculosis, empyema, malignancy
▫ Microscopy, culture: microorganisms
▫ ↓ pH: empyema, tuberculosis,
mesothelioma Figure 128.3 The cytological appearance
▫ Protein, LDH: transudative/exudative of a benign pleural effusion. There are
numerous bland mesothelial cells mixed with
lymphocytes.
908 OSMOSIS.ORG
OTHER INTERVENTIONS
TREATMENT ▪ Supplemental oxygen
SURGERY ▪ Repeated effusions
▪ Therapeutic aspiration ▫ Chemical pleurodesis: obliteration
of pleural space; prevents fluid
▪ Insertion of intercostal drain
accumulation (talc, bleomycin,
▪ Repeated effusions tetracycline/doxycycline)
▫ Surgical pleurodesis: obliteration ▪ Pleural catheter
of pleural space; prevents fluid
▫ User-operated daily draining
accumulation
OSMOSIS.ORG 909
PNEUMOTHORAX
osms.it/pneumothorax

▪ Abnormal collection of air in pleural cavity ▪ Sharp chest pain (one-sided)
▪ Air enters through damage to chest wall/ ▪ Dyspnea
lung/gas-producing microorganisms ▪ Tachycardia
▫ Positive pressure in pleural space if air ▪ Cyanosis
enters → lung partial/complete collapse ▪ Hypercapnia → confusion, coma
▪ Diminished/absence of breath sounds
TYPES (affected side)
▪ Hyperresonance to percussion
Primary pneumothorax
▪ ↓ vocal, tactile fremitus
▪ No clear cause/no preexisting lung disease
▪ Trachea displaced away from affected side
▫ Secondary to ruptured blebs (small sacs
▪ Tension pneumothorax
of air on lung surface)
▫ ↓ blood pressure
Secondary pneumothorax ▫ ↓ oxygen saturation
▪ Occurs with existing lung disease ▫ Epigastric pain
▫ Displaced apex beat
Tension pneumothorax
▫ Distended neck veins
▪ One-way valve formed by damaged tissue
→ air enters, can’t escape → intrathoracic
pressure builds up → impaired cardiac,
respiratory function
DIAGNOSIS
Traumatic pneumothorax DIAGNOSTIC IMAGING
▪ Follows physical trauma to chest (e.g. blast Chest X-ray/CT scan
injury); result of medical procedure (e.g.
▪ Identifies atypical collections of gas,
iatrogenic pneumothorax)
changes in lung markings, presence of
mediastinal shift and/or tracheal deviation;
RISK FACTORS lucent/dark lung field, deep sulcus sign (a
▪ Smoking, chronic obstructive pulmonary deep costophrenic angle)
disease (COPD), asthma, tuberculosis
Ultrasound
biologically male ▪ Reverberation echoes of the pleural line,
absence of lung sliding at the pleural line
▪ Changes in atmospheric pressure
▪ Family history of pneumothoraces
OTHER DIAGNOSTICS
910 OSMOSIS.ORG
▪ Large bore intravenous catheter needle

inserted into pleural space
▫ Midclavicular line: second/third
intercostal space
▫ Anterior/mid axillary line: fifth intercostal
space
▫ Listen for air escaping
▫ Remove needle, leave catheter in place
▪ May cause injury, reserve for
▫ Mechanism of injury suggestive of
pneumothorax
▫ Clinical signs of respiratory distress,
persistently low oxygen saturation
despite supplemental oxygen
▫ Hemodynamic instability
▫ Prolonged transport time
Figure 128.4 A CT scan of the chest in the
coronal plane demonstrating a right-sided
pneumothorax.
OTHER INTERVENTIONS
▫ Improves rate of pneumothorax
reabsorption
TREATMENT ▪ Small pneumothoraces may resolve
spontaneously
SURGERY ▪ If wound present, cover with dressing
Pleurodesis/pleurectomy ▫ Dressing secured on three sides to
▪ Repeated pneumothoraces create “vent dressing”
▪ Chest tube (connected to water-seal
Tension pneumothorax: needle chest drainage system)
decompression ▫ Inserted into “safe triangle,” damage to
▪ AKA needle thoracostomy internal organs avoided
▪ Emergency procedure ▫ Horizontal line, nipple to lateral
▪ Not definitive, improves cardiopulmonary chest well; between latissimus dorsi,
function pectoralis major
OSMOSIS.ORG 911
NOTES
NOTES
PULMONARY VASCULAR
DISEASE

▪ Diseases affecting blood flow through X-ray, chest CT scan, spirometry, ultra-
pulmonary vasculature, or fluid flow from sound, echocardiogram, ECG
vasculature
▪ Can be caused by process within lungs/
elsewhere in body TREATMENT
▪ Supportive, treat underlying disease,
SIGNS & SYMPTOMS optimize organ function (heart, lungs)
▪ Dyspnea, poor effort tolerance, chest pain,

tachypnea
Figure 129.1 Chronic thromboembolic pulmonary hypertension is an example of a pulmonary

vascular disease that originates outside the lungs. In this case, an embolism blocks the
pulmonary vessels, causing pulmonary blood pressure to rise beyond normal levels.
912 OSMOSIS.ORG
Chapter 129 Pulmonary Vascular Disease
PULMONARY EDEMA
osms.it/pulmonary-edema
PATHOLOGY & CAUSES ▪ Free fluid predisposes to secondary

infection
▪ Alteration in Starling forces → build up of

fluid within interstitial space, air spaces of SIGNS & SYMPTOMS
lung
▪ Dyspnea, productive cough (pink frothy
CAUSES sputum), excessive sweating, anxiety,
tachycardia, end-inspiratory crackles,
Cardiogenic (heart disease) dullness to percussion, cyanosis (decreased
▪ Left sided heart failure → inefficient hemoglobin saturation)
pumping of blood from heart by left ▪ Pulmonary edema in heart failure may also
ventricle → blood backs up into left atrium include
→ pulmonary circulation → pulmonary ▫ Orthopnea (shortness of breath worse
hypertension (raised hydrostatic pressure) when lying flat)
→ more fluid in lung interstitium → ▫ Paroxysmal nocturnal dyspnea
pulmonary edema (episodes of severe sudden
▫ Severe systemic hypertension breathlessness at night)
(> 180/110mmHg) → left ventricle ▫ Peripheral pitting edema
cannot pump effectively against
▫ Raised jugular venous pressure
extreme afterload → blood backs up into
left atrium → pulmonary circulation → ▫ Hepatomegaly
pulmonary edema
Non-cardiogenic (damage to pulmonary DIAGNOSIS

capillaries or alveoli)
▪ Direct damage to alveoli/vasculature → DIAGNOSTIC IMAGING
inflammatory response → leaky capillaries
Chest X-ray
▫ Pulmonary infection, toxin inhalation,
▪ Kerley B lines (thickened subpleural
chest trauma, pulmonary vein occlusion,
interlobular septa, usually seen at base of
burns
lung)
▫ Sepsis → systemic inflammation →
▪ Increased vascular shadowing → batwing
global edema
perihilar pattern
▫ Insufficient circulation of osmotically
▪ Upper lobe diversion (prominent upper lobe
active proteins, e.g. albumin → low
pulmonary veins)
oncotic pressure in capillaries
▪ Pleural effusion (if edema severe)
▪ Malnutrition
▪ Liver failure Non-contrast high resolution chest CT scan
▪ Excessive protein loss (nephrotic syndrome, ▪ Airspace opacity
protein losing enteropathies) ▪ Smooth thickening of interlobular septae
Chest ultrasound
COMPLICATIONS
▪ Detection of small amounts of fluid
▪ Impaired gas exchange: oxygen/carbon
dioxide must diffuse through wide layer of ▪ Echo-free space between visceral and
fluid → blood unable to fully saturate parietal pleura
▪ Septations in pleural fluid → underlying
OSMOSIS.ORG 913
infection, chylothorax/hemothorax
TREATMENT
Echocardiograph
▪ Evaluation of cardiac function, can MEDICATIONS
demonstrate left ventricular failure ▪ If cardiogenic
▫ Preload reduction: nitroglycerin,
LAB RESULTS diuretics, morphine sulphate
▪ Serum electrolytes ▫ Afterload reduction: ACE inhibitors,
angiotensin II receptor blockers,
▪ Renal function
nitroprusside
▪ Inflammatory markers
▪ If non-cardiogenic
▪ Low oxygen saturation
▫ Manage illness (e.g. treat infection)
▪ Increased carbon dioxide
OTHER INTERVENTIONS
▪ Continuous positive airway pressure
(CPAP)
▪ Intubation: mechanical ventilation if level of
consciousness compromised
Figure 129.2 A CT scan of the chest

in the coronal plane demonstrating the
peribronchovascular distribution of acute
pulmonary edema.
Figure 129.3 A plain chest radiograph

demonstrating pulmonary edema. There
is interstitial edema, represented by fine
stranded opacities known as Kerley B lines,
as well as alveolar edema, represented by
confluent nodular opacities.
Figure 129.4 Illustration depicting pulmonary

edema.
914 OSMOSIS.ORG

pulmonary edema.
PULMONARY EMBOLISM
osms.it/pulmonary-embolism
RISK FACTORS
PATHOLOGY & CAUSES ▪ Virchow’s triad: endothelial injury, stasis of
blood flow, blood hypercoagulability
▪ Blockage of pulmonary artery by a
▪ > 60 years old, malignancy, history of deep
substance brought there via bloodstream
vein thrombosis/pulmonary embolism,
▪ Thrombus in remote site embolizes → hypercoagulable states, genetic disorders
lodges in pulmonary vascular tree → (e.g. Factor V Leiden thrombophilia),
“pulmonary embolism” dehydration, prolonged immobilization
▪ Obstruction of blood flow distal to (bed rest, travel), cardiac disease, obesity,
embolism → increased pulmonary vascular nephrotic syndrome, major surgery, trauma,
resistance → increased pulmonary artery pregnancy, estrogen-based medication (e.g.
pressure → increased right ventricular oral contraceptives)
pressure → cor pulmonale (if severe ▪ Increased risk of fat embolism with bone
obstruction) fractures (e.g. hip, femur)
▪ Regional decrease in lung perfusion →
dead space (ventilation, but no perfusion)
→ hypoxemia → tachypnea SIGNS & SYMPTOMS
Source of embolus
▪ Dyspnea, pleuritic chest pain, cough,
▪ Lower extremity deep vein thrombosis hemoptysis
▫ Most arise from deep veins above knee, ▪ Signs, symptoms of deep vein thrombosis
iliofemoral deep vein thrombosis
▫ Tender, swollen, erythematous
▫ Can arise from pelvic deep veins extremity
▫ Pelvic thrombi tend to advance to more ▪ Syncope
proximal veins before embolizing
▪ Often asymptomatic (in the case of small
▪ Upper extremity deep veins (rarely) emboli)
▪ Uncommon embolic material: air, fat,
amniotic fluid
OSMOSIS.ORG 915
MNEMONIC: TOM ▪ Low SpO2, tachypnea, rales, tachycardia,
SCHREPFER S4 heart sound, increased P2 (closure of
Risk factors for Pulmonary pulmonary valve), shock, low-grade fever,
embolism decreased breath sounds, percussion
Trauma dullness, pleural friction rub, sudden death
(pulmonary saddle embolism)
Obesity
Malignancy
Surgery DIAGNOSIS
Cardiac disease
Hospitalization Wells’ score
Rest (bed-ridden) ▪ Used to assess probability of pulmonary
Elderly embolism (multiple different probability
Past history tests available)
Fracture ▫ Score > 4: pulmonary embolism likely,
consider diagnostic imaging
Estrogen (pregnancy, post-
partum) ▫ Score ≤ 4: pulmonary embolism unlikely,
consider D-dimer test to rule out
Road trip
Figure 129.6 A CT pulmonary angiogram

demonstrating a pulmonary embolus and
subsequent right middle lobe infarct.
916 OSMOSIS.ORG
DIAGNOSTIC IMAGING ▫ Dominant R wave in V1

▫ S1Q3T3 pattern: Deep S wave in lead I,
Chest X-ray
Q wave in lead III, negative wave in lead
▪ Typically normal III
CT pulmonary angiography ▪ Nonspecific ST segment, T wave changes
▪ Definitive test ▪ Pulmonary embolism can be excluded if
▪ Visualize decreased blood supply ▫ SaO2 exceeds 95%
▫ Age < 50
Venous duplex ultrasound ▫ No unilateral leg swelling, hemoptysis,
▪ Of lower extremities history of deep vein thrombosis/
▫ May reveal origin of pulmonary pulmonary embolism, recent surgery/
embolism trauma, hormone use (or estrogen-
▫ Negative result does not exclude based medications), tachycardia
pulmonary embolism
Ventilation-perfusion scan TREATMENT

▪ Normal scan rules out pulmonary embolism
MEDICATIONS
LAB RESULTS Anticoagulation
▪ D-dimer (high negative predictive value) ▪ Acute phase (days–weeks)
▫ Positive result does not prove ▫ Prevent further thromboembolic events
pulmonary embolism ▫ Unfractionated heparin, low molecular
▫ Negative result rules out pulmonary weight heparin, fondaparinux
embolism ▪ Long-term (vitamin K antagonists)
▪ Arterial blood gas ▫ Warfarin, acenocoumarol,
▫ ↓ PaO2 → hypoxemia phenprocoumon
▫ Hyperventilation → ↑ PaCO2 → ↑ pH →
respiratory alkalosis Thrombolysis
▫ A-a gradient elevated (indicated V/Q ▪ Used for massive pulmonary embolism
mismatch) causing hemodynamic instability
▪ Tests for causes of secondary pulmonary ▪ Carries risk of secondary hemorrhage
embolism ▪ Thrombolytics used to break up clots
▫ Full blood count, clotting profile, ▫ Streptokinase, staphylokinase,
erythrocyte sedimentation rate, renal urokinase, anistreplase
function, liver function, electrolytes ▫ Recombinant tissue plasminogen
activators (alteplase, reteplase,
tenecteplase)
OTHER DIAGNOSTICS
ECG SURGERY
▪ Excludes other causes of chest pain
▪ ECG features of pulmonary embolism (or Pulmonary thromboendarterectomy
any pulmonary hypertension) include ▪ Surgical removal of a chronic
▫ Sinus tachycardia thromboembolism
▫ Right bundle branch block ▪ Rare
▫ Right ventricular strain pattern: T wave Inferior vena cava filter
inversion in right precordial (V1–V4), and
▪ Vascular filter inserted into inferior vena
inferior leads (II, III, aVF)
cava to prevent life-threatening pulmonary
▫ Right atrial enlargement (P pulmonale) emboli
▫ Right atrial dilatation → right axis ▪ Indications: anticoagulant therapy
deviation contraindicated, major embolic event
OSMOSIS.ORG 917
despite anticoagulation
OTHER INTERVENTIONS
Preventative measures
▪ Unfractionated heparin, low molecular
weight heparin
▪ Factor Xa inhibitor
▪ Long-term low-dose aspirin
▪ Anti-thrombosis compression stockings/
intermittent pneumatic compression
Figure 129.7 A plant chest radiograph of

the same individual, demonstrating the
pulmonary infarct which is visible as a wedge
shaped opacity in the lateral art of the right
lung field.

appearance of a pulmonary embolus.
Figure 129.9 The ECG changes associated with a pulmonary embolism. There is a right bundle
branch block, sinus tachycardia and T-wave inversions in leads V1-3 and III.
918 OSMOSIS.ORG
PULMONARY HYPERTENSION
osms.it/pulmonary-hypertension
▪ Idiopathic, inherited, drug/toxin associated
PATHOLOGY & CAUSES causes connective tissue disease, HIV
infection, portal hypertension congenital
▪ Increased blood pressure in pulmonary heart disease (shunting)
circulation
▪ Mean pulmonary arterial pressure > Group II
25mmHg (normal ~15mmHg) ▪ Pulmonary hypertension secondary to left
▪ Pulmonary hypertension → excess fluid in heart disease
pulmonary interstitium (pulmonary edema) ▪ Pulmonary hypertension due to left heart
→ impaired gas exchange disease (heart failure, valvular dysfunction)
▪ Pulmonary hypertension → strain on right → left heart fails to pump blood efficiently
heart → hypertrophy → right heart oxygen → backup of blood in pulmonary veins,
demand eventually exceeds supply → capillary beds → increased pressure in
right-sided heart failure pulmonary artery → pulmonary edema,
pleural effusion
▫ Right heart failure caused by lung
disease → cor pulmonale → backup ▪ Raised back pressure may trigger
of blood in venous system → signs, secondary vasoconstriction → increased
symptoms of right heart failure right heart strain
▪ Raised jugular venous pressure ▪ Common causes include
▪ Fluid build up in liver → hepatomegaly ▫ Left ventricular systolic/diastolic
dysfunction
▪ Fluid build up in legs → leg edema
▫ Valvular heart disease
▪ Left ventricle receives less blood →
compensation → pumps harder, faster ▫ Congenital/acquired in/out-flow tract
(tachycardia) obstruction
▫ Congenital cardiomyopathy
▫ Pulmonary venous stenosis
TYPES
Group III
Group I
▪ Pulmonary hypertension due to lung
▪ Pulmonary arterial hypertension,
disease/chronic hypoxia
pulmonary veno-occlusive disease,
pulmonary capillary hemangiomatosis ▪ Low oxygen levels in alveoli pulmonary
arteries constrict
▪ Abnormal increase in pulmonary arteriolar
resistance → increased strain on right heart ▪ Chronic lung disease → region of diseased
(pumping fluid through narrower pipe) lung → inefficient/total lack of gas
exchange → hypoxic vasoconstriction
▪ Damage to endothelial cells lining
(pulmonary arterioles) → shunting of blood
pulmonary arteries → release of
away from damaged areas
endothelin-1 serotonin, thromboxane,
produce less nitric oxide and prostacyclin ▪ Prolonged alveolar hypoxia across wide
→ constriction of arterioles, hypertrophy of portion of pulmonary vascular bed →
smooth muscle → pulmonary hypertension increase in pulmonary arterial pressure →
thickening of pulmonary vessel walls →
▪ Over time affected vessels become stiffer,
greater effort required from right heart →
thicker (fibrosed) due to vasoconstriction,
sustained pulmonary hypertension
thrombosis, vascular remodeling → greater
increase in blood pressure in lungs, more ▪ Causes include
strain on right heart ▫ COPD
OSMOSIS.ORG 919
▫ Interstitial lung disease
▫ Mixed restrictive/obstructive pattern
SIGNS & SYMPTOMS
disease
▪ Dyspnea, syncope, fatigue, chest pain,
▫ Sleep-disordered breathing poor effort tolerance, loss of appetite,
▫ Alveolar hypoventilation lightheadedness, orthopnea (left-sided
▫ Chronic exposure to high altitude heart failure)
▪ Tachycardia, cyanosis, parasternal heave
Group IV
▪ Signs of systemic congestion/right heart
▪ Chronic arterial obstruction/
failure:
thromboembolic disease
▫ Loud pulmonic component of second
▪ Recurrent blood clots in pulmonary
heart sound (P2)
vasculature
▫ Jugular venous distension
▪ Blockage/narrowing of pulmonary vessel
with unresolved obstruction (e.g. clot) ▫ Ascites
→ increased pressure, shear stress ▫ Hepatojugular reflux
(turbulence) in pulmonary circulation ▫ Lower limb edema
→ vessel wall remodelling → sustained
pulmonary hypertension
▪ Causes endothelium to release histamine, DIAGNOSIS
serotonin → constriction of pulmonary
arterioles → rise in pulmonary blood DIAGNOSTIC IMAGING
pressure → chronic thromboembolic
pulmonary hypertension Chest X-ray
▪ Other causes of arterial obstruction ▪ Enlarged pulmonary arteries
▫ Angiosarcoma, arteritis, congenital ▪ Lung fields may or may not be clear,
pulmonary artery stenosis, parasitic dependent on underlying cause
infection Echocardiogram
Group V ▪ Increased pressure in pulmonary arteries,
▪ Unclear/multifactor mechanisms right ventricles → dilated pulmonary artery
▪ Hematologic disease (e.g. hemolytic ▪ Dilatation/hypertrophy of right atrium, right
anemia) ventricle
▪ Systemic disease (e.g. sarcoidosis, ▪ Large right ventricle → bulging septum
vasculitis) Ventilation/perfusion scan
▪ Metabolic disorders (e.g. glycogen storage ▪ Identity / exclude ventilation-perfusion
disease, thyroid disease) mismatches
▪ Other (e.g. microangiopathy, chronic kidney
disease)
OTHER DIAGNOSTICS
RISK FACTORS Right heart catheterisation (gold standard)
▪ Family history, prior pulmonary embolic ▪ Catheter into right heart → most accurate
events, HIV/AIDS, sickle cells disease, measure of pressures
cocaine use, COPD, sleep apnea, living at
high altitude, mitral valve pathology ECG
▪ Right heart strain pattern: T wave inversion
in right precordial (V1–V4), and inferior leads
(II, III, aVF)
Spirometry
▪ Unidentified underlying cause
920 OSMOSIS.ORG
with prostanoids, phosphodiesterase

TREATMENT inhibitors, endothelin antagonists
▪ Pulmonary arterial hypertension
MEDICATIONS
▫ Endothelin receptor antagonists
▪ Pulmonary hypertension secondary to
left ventricular failure → optimize left ▫ Prostanoids
ventricular function
▫ Diuretics (cautiously—individuals may SURGERY
be preload dependent) ▪ Lung transplant
▫ Digoxin ▪ Repair/replace damaged valves to optimize
▫ Anticoagulants left ventricular function
▪ Cardiogenic pulmonary arterial
hypertension
▫ Relax smooth muscle (promote
vasodilation), reduce vascular
remodelling, improve exercise capacity
Figure 129.10 The gross pathological appearance of the pulmonary arteries in a case of
pulmonary hypertension. The underlying pathological process is similar to atherosclerosis found
elsewhere in the cardiovascular system.
OSMOSIS.ORG 921
of a pulmonary artery in a case of pulmonary
hypertension. There is marked thickening of
both the intima and the media.
Figure 129.11 A CT scan of the chest in the
axial plane demonstrating enlargement of
the pulmonary trunk as a consequence of
pulmonary hypertension.
922 OSMOSIS.ORG
NOTES
NOTES
RESPIRATORY TUMORS

RISK FACTORS
PATHOLOGY & CAUSES ▪ Age
▫ Malignancy more common in older
▪ Uncontrolled division of epithelial cells
individuals
lining respiratory tract → formation of solid
tumor ▪ Smoking
▪ Mutated cells become cancerous ▫ Direct, linear positive correlation
between pack years, risk of lung cancer
▫ Resist inhibitory signals, evade immune
surveillance ▪ Asbestos exposure, radon exposure,
ionizing radiation exposure
▪ Malignant tumors invade basement
membrane ▪ Chronic obstructive pulmonary disease
(COPD)
▫ Carcinoma in situ
▪ Tuberculosis
▪ Metastasis
▫ Malignant tumors establish secondary
tumors at distant site; lung cancer MNEMONIC: ABCDE
metastasizes quickly
Presentation of lung cancers
▫ Common sites: mediastinum, hilar
Bronchial Airway disruption →
lymph nodes, lung pleura, breasts, liver,
pneumonia
adrenal glands, brain, bones
Blood: hemoptysis
Cough
TYPES Distribution: mestastasis
Small-cell whEEzing
▪ Small, immature, neuroendocrine cells;
divide rapidly, spread quickly
Non-small-cell (most common) SIGNS & SYMPTOMS

▪ Large cells; divide, spread slowly
▪ Asymptomatic in early disease
▫ Adenocarcinoma (goblet cells)
▪ Nonspecific, wide overlap with other
▫ Squamous cell carcinoma (squamous
noncancerous lung conditions
cells)
▪ Constitutional symptoms: loss of appetite,
▫ Large cell carcinoma
weight loss, weakness
▫ Carcinoid tumors (mature
▪ If located in certain areas (e.g. upper lobe of
neuroendocrine cells)
lung) → compressive symptoms
Nonspecific classification ▫ Nerve compression: hoarseness
▪ Small-cell carcinoma with poorer prognosis (recurrent laryngeal nerve), Horner’s
syndrome (sympathetic chain),
diaphragmatic paralysis (phrenic nerve)
▪ Paraneoplastic syndromes
▫ Digital clubbing, muscle weakness,
syndrome of inappropriate antidiuretic
OSMOSIS.ORG 923
hormone secretion (SIADH), ectopic LAB RESULTS
adrenocorticotropic hormone (ACTH) ▪ Sputum sample
secretion, ectopic parathyroid hormone ▫ Diagnosis of central (near to main
(PTH)-like secretion, hypertrophic bronchus) tumors, not peripheral tumors
pulmonary osteoarthropathy, Eaton–
▪ Fine needle aspiration
Lambert syndrome
▫ Histopathologic diagnosis using
▫ Mostly small cell carcinoma
cytology
(neuroendocrine cells secrete hormones
with systemic effects) ▪ Endoscopic biopsy
DIAGNOSIS TREATMENT

▪ Simple analgesics, opioids (if severe)
Chest X-ray ▫ Pain management
▪ Coin lesion
CT scan SURGERY
▪ Asymmetrical, expanding nodule; used ▪ Intraoperative frozen section if diagnosis of
for staging; can demonstrate extent malignancy uncertain
of metastasis (e.g. hilar lymph node ▪ If malignancy confirmed, wedge resection
involvement) performed for small tumors
▪ Lobectomy performed for larger tumors/
PET after wedge resection if margins positive
▪ Areas of higher glucose turnover
▪ Bronchoscope
OTHER INTERVENTIONS
▪ Diagnosis of central (near to main
▪ Chemotherapy, immunotherapy, radiation
bronchus) tumors, not peripheral tumors
therapy
MESOTHELIOMA
osms.it/mesothelioma
▪ Asbestos fibers inhaled → phagocytic cells
PATHOLOGY & CAUSES attempt to phagocytose fibers → unable to
destroy fibers → apoptosis of phagocytic
▪ Cancer of mesothelium; most commonly cells → release of tumor promoting factors
lungs, chest wall pleural lining (composed → mesothelial cells of pleura inflamed →
of mesothelial cells); sometimes DNA damage → mesothelial cells divide
pericardium uncontrollably → tumor formation
▪ Commonly associated with asbestos ▪ Mesothelial plaques cover visceral, parietal
exposure pleura; extend around chest cavity
▪ Asbestos fibers ▪ Asbestos fibers can be found in stomach
▫ Mineral used as construction, insulation (via swallowing of saliva/mucus containing
material asbestos)
▫ Jagged in shape, very fine ▪ Mesothelioma can theoretically affect
▫ Increases risk of lung cancer, malignant any organ with mesothelial cells, most
mesothelioma commonly found in thoracic cavity
924 OSMOSIS.ORG
Chapter 130 Respiratory Tumors
TYPES
TREATMENT
Malignant
▪ Prognosis is poor, unless caught early; MEDICATIONS
extremely resistant to treatment; spread to ▪ Chemotherapy
multiple organs
Benign SURGERY
▪ Prognosis is excellent; surgery for isolated ▪ Excision
lesions usually curative
OTHER INTERVENTIONS
▪ Radiation
SIGNS & SYMPTOMS
▪ Angina, dyspnea, recurrent pleural
effusions, weight loss, cough
▪ If tumor invades blood vessel
▫ Blood-tinged sputum
DIAGNOSIS
DIAGNOSTIC IMAGING
Chest X-ray, CT scan
▪ Visualize mesothelioma lesions
LAB RESULTS
Biopsy
▪ Video assisted thoracoscopic surgery
(VATS) Figure 130.1 A CT scan of the chest in the
▪ Tissue sample immunostained with coronal plane demonstrating a mesothelioma
antibody that reacts to calretinin occupying the lower thoracic cavity.
▫ Calretinin: calcium-binding protein that
regulates calcium levels inside cells
▫ Distinguishes mesotheliomas from other
tumors
▪ Cancerous cells have “fried egg”
appearance
Figure 130.2 Immunohistochemical staining

with calretinin reveals the architecture of this
pleural mesothelioma.
OSMOSIS.ORG 925
of epithelioid mesothelioma. The malignant
cells are cuboidal, have moderate amounts of
cytoplasm and display conspicuous nucleoli.
Figure 130.4 The gross pathology of a large

mesothelioma of the thoracic cavity. The
tumor completely encases the normal lung
tissue (outlined).
NASOPHARYNGEAL CARCINOMA
osms.it/nasopharyngeal-carcinoma
MNEMONIC:
PATHOLOGY & CAUSES NASOPharyngeal
Types of Nasopharyngeal
▪ Cancer of nasopharynx (upper throat, malignant cancers
behind nose)
Nasopharyngeal
▪ Most common malignant tumor of
Adenocarcinoma
nasopharynx
Squamous cell carcinoma
▪ Can be clinically silent for long periods,
difficult to detect early Olfactory neuroblastoma
▪ Often metastasizes to cervical lymph nodes Plasmacytoma
▪ Associated with Epstein–Barr virus (EBV)
▪ Prognosis
Undifferentiated/basaloid carcinoma
▫ Five year survival rate, 60% (all types) (lymphoepithelioma)
▪ Most radiosensitive
TYPES
Keratinized squamous cell carcinoma RISK FACTORS
▪ Worst prognosis, least radiosensitive ▪ More common in individuals who are
biologically male, < 55 years
Nonkeratinized squamous cell carcinoma ▪ Family history
▪ Best prognosis ▪ Common in Asia, Africa (esp. children); in
southern China, common in adults, rare in
children
926 OSMOSIS.ORG
▪ Diets high in nitrosamines (fermented

foods), alcohol TREATMENT
▪ Smoking, certain chemical fumes,
formaldehyde
MEDICATIONS
▪ Monoclonal antibodies
▫ Synthetic antibodies, target epidermal
COMPLICATIONS growth factor receptors (EGFRs);
▪ Radiation adverse effects (Type III hypersensitivity
▫ Death of healthy tissue, brain stem infusion reaction, rash, fatigue,
injury, blindness, xerostomia headache, fever, diarrhea)

▪ Altered vision, recurrent ear infections,
headache, tinnitus, nosebleeds, sore throat, OTHER INTERVENTIONS
facial paresthesia ▪ Intensity-modulated radiation therapy
▪ Lump in neck, epistaxis, nasal obstruction (standard)
▫ High-precision radiation, minimizes
damage to surrounding tissues; better
DIAGNOSIS outcome, less adverse effects than
conventional radiation therapy
DIAGNOSTIC IMAGING
CT scan, MRI, PET, X-ray, nasopharyngos-
copy/nasal endoscopy
▪ Visualize carcinoma
LAB RESULTS
Biopsy
▪ Squamous cell carcinoma/undifferentiated
OTHER DIAGNOSTICS
▪ Physical exam
▫ Neck swelling
Figure 130.5 An MRI scan of the head in

the sagittal plane demonstrating a large
nasopharyngeal carcinoma blocking the
choanae and invading the skull base.
OSMOSIS.ORG 927
NON-SMALL-CELL LUNG
CARCINOMA
osms.it/nsclc

▪ Lung cancers not of small-cell type LAB RESULTS
▪ Grow, spread more slowly
Fine needle aspiration (lung)
▪ Cells demonstrate cardinal features of
TYPES malignancy
▫ Variation in nuclear size, shape;
Squamous-cell carcinoma
irregularly distributed nuclear chromatin;
▪ Centrally located, strongly associated with large prominent nucleoli
smoking
Adenocarcinoma
▪ Develops peripherally in bronchiole/alveolar
TREATMENT
sac, no link to smoking
SURGERY
Large-cell carcinomas ▪ Contraindicated in cases of metastasis
▪ Found throughout lungs; centrally, outside of chest
peripherally ▪ Recurrence likely even after complete
▪ Diagnosis of exclusion; if criteria for resection
adenocarcinoma/squamous-cell carcinoma
not met OTHER INTERVENTIONS
Bronchial carcinoid tumor ▪ Radiation, chemotherapy
▪ Low-grade malignancy of neuroendocrine
cells
▪ Same cell of origin as small-cell carcinoma;
malignant potential low
SIGNS & SYMPTOMS

▪ Cough
▪ Hemoptysis
▪ Hoarseness
▪ Chest pain
▪ Weight loss
Figure 130.6 A cytological preparation of
▪ Neurologic symptoms (brain metastasis is
a bronchial washing containing malignant
common)
squamous cells.
928 OSMOSIS.ORG

of squamous cell carcinoma of the lung.
The tumor cells have large amounts of
eosinophilic cytoplasm, have irregular nuclear
forms and are forming islets. The surrounding
lung demonstrates a chronic inflammatory
cell reaction.

appearance of squamous cell carcinoma of
the lung. There is a large primary tumor in the
upper lobe with intrapulmonary metastases
in the lower lobe.

of adenocarcinoma of the lung. The tumor is
forming slit like spaces called acini, which are
lined by malignant cells.
OSMOSIS.ORG 929
PANCOAST TUMOR
osms.it/pancoast-tumor
▫ Brachial plexus: ipsilateral paresthesia
PATHOLOGY & CAUSES
▫ Laryngeal nerves: voice hoarseness
▪ Pulmonary neoplasm located in lung apices ▫ SVC: SVC syndrome (facial flushing,
edema, dyspnea)
▪ Location enables them to impinge nerves,
vessels
▪ Majority DIAGNOSIS
▫ Non-small-cell lung tumors
(adenocarcinoma/squamous cell DIAGNOSTIC IMAGING
carcinoma)
▪ Structures most vulnerable to compression/ CT scan/chest X-ray
invasion ▪ Tumor in lung apex
▫ Cervical sympathetic nerves, brachial
plexus, laryngeal nerves, superior vena LAB RESULTS
cava (SVC)
Biopsy
▪ Confirm tumor type
MNEMONIC: Horner has a
MAP of the Coast
OTHER DIAGNOSTICS
PanCoast → Horner’s
syndrome, including: ▪ Physical examination
Miosis
Anhidrosis TREATMENT
Ptosis
▪ Impingement of important nerve /vessel;
shrink tumor before resection
SIGNS & SYMPTOMS
MEDICATIONS
▪ Cough, angina, dyspnea, hemoptysis, ▪ Chemotherapy
wheezing ▫ Late stages: chemotherapy alone;
▪ Recurrent pneumonia prophylactic radiation to decrease
▪ Constitutional symptoms chance of brain metastases
▫ Loss of appetite, weight loss, weakness
SURGERY
Local inflammation and compression
▪ Tumor causes local inflammation,
invasion of nearby nerves/vessels, direct
compression OTHER INTERVENTIONS
▪ Pain, upper extremity weakness due to ▪ Radiation
brachial plexus impingement ▫ Early stages: used with chemotherapy
▪ Compression
▫ Cervical sympathetic nerves: Ipsilateral
Horner syndrome (ptosis, miosis,
anhidrosis)
930 OSMOSIS.ORG
Figure 130.10 The gross pathological Figure 130.11 A CT scan of the chest in the
appearance of squamous cell carcinoma of coronal plane demonstrating a pancoast
the lung. There is a large primary tumor in the tumor at the apex of the right lung.
upper lobe with intrapulmonary metastases
in the lower lobe.
SMALL-CELL LUNG CANCER

osms.it/sclc
carcinoma stimulates production of
PATHOLOGY & CAUSES autoantibodies → destroy neurons
▪ Uncontrolled proliferation of small,

immature, neuroendocrine cells TYPES
▪ Strongly associated with smoking Limited
▪ Usually develops centrally in lung, near ▪ Contained within one lung, supraclavicular
main bronchus nodes (no extension to cervical/axillary
▪ Grows fastest, rapidly metastasizes to nodes)
other organs; intrapulmonary metastasis ▪ Prognosis
also common
▫ Five year survival, 10% (median survival
▪ Secretes hormones → paraneoplastic 15–20 months)
syndromes
▫ Cushing’s syndrome: excretion of Extensive
cortisol from adrenal glands → elevated ▪ Spreads beyond one lung, supraclavicular
blood glucose, high blood pressure nodes
▫ SIADH: release of antidiuretic hormone ▪ Prognosis
(ADH) from tumor → water retention ▫ Five year survival, 1% (median survival
→ high blood pressure, edema, 8–13 months)
concentrated urine
▫ Eaton–Lambert myasthenic syndrome
(Type II hypersensitivity): small-cell
OSMOSIS.ORG 931
SIGNS & SYMPTOMS
▪ Dyspnea
▪ Wheezing
▪ Cough
▪ Hemoptysis
DIAGNOSIS
LAB RESULTS
▪ Histology Figure 130.12 The histological appearance of
small cell carcinoma. The cells have minimal
▫ Large cells with limited cytoplasm,
cytoplasm and moulded nuclei.
nuclear moulding
TREATMENT
SURGERY
▪ Usually not curative
OTHER INTERVENTIONS
▪ Limited
▫ Combination of chemotherapy, radiation
therapy
▪ Extensive
▫ Chemotherapy, prophylactic radiation
Figure 130.13 A PET-CT scan in the coronal

plane demonstrating high-uptake in the left
upper lobe, corresponding with a small cell
carcinoma of the lung. The left ventricle also
demonstrates high uptake, but this is normal.
Figure 130.14 A cytology specimen

demonstrating the characteristic features
of small cell carcinoma; nuclear moulding,
salt and pepper chromatin and minimal
cytoplasm.
932 OSMOSIS.ORG
SUPERIOR VENA CAVA SYNDROME

osms.it/svc-syndrome

▪ Constellation of signs, symptoms when ▪ Edema of face, neck; inspiratory stridor;
blood flow through SVC obstructed voice changes; flushed appearance (backup
▪ Obstruction → increase in venous pressure of blood, venous stasis); dilated neck,
behind obstruction → blood rerouted chest veins; dyspnea (blockage of SVC
through collateral vessels → blood drains → decreased return of blood to heart →
into inferior vena cava, right atrium → less blood pumped to lungs); hoarseness
dilation of collateral veins → venous of voice (compression of laryngeal nerve/
pressure decreases with full dilation of muscles of larynx from excess fluid)
collateral veins
▪ Collateral vessels
▫ Azygos vein, internal mammary vein,
DIAGNOSIS
lateral thoracic vein, esophageal venous
systems DIAGNOSTIC IMAGING
Chest X-ray/CT scan/venous angiography
CAUSES ▪ Visualize tumors, collateral vessel dilation,
▪ Obstruction (external/internal) obstruction
▫ Tumor invasion, mass effect
(inflammation, swelling) LAB RESULTS
▫ Lung cancer most common (e.g.
Pancoast tumor), tumor of lymph nodes Biopsy
(e.g. lymphomas) ▪ Evaluate tumor; determine type, staging
▫ Blood clot (develops in individuals with
long-term device; e.g. indwelling central
venous catheter) TREATMENT
MEDICATIONS
COMPLICATIONS
▪ Steroids
▪ Edema, dysphagia, cerebral ischemia
▫ Reduce swelling around tumor
▪ Severe cerebral edema → compression of
▪ Anticoagulants
blood vessels in brain → cerebral ischemia
▫ Treat blood clot
OTHER INTERVENTIONS
▪ Combination of surgery, chemotherapy,
radiation therapy
▪ Keep head above level of heart to help
drain fluid from head, neck to heart
OSMOSIS.ORG 933
934 OSMOSIS.ORG
NOTES
NOTES
RESTRICTIVE LUNG DISEASE

▪ Inflammatory disorders of lung parenchyma DIAGNOSTIC IMAGING
▪ Restricts lung expansion → decreases
High resolution chest CT scan
lung volume, ventilation, gas exchange →
difficulty breathing
LAB RESULTS
RISK FACTORS ▪ Lung biopsy
▪ Exposure to occupational, biological dusts
OTHER INTERVENTIONS
▪ Spirometry
SIGNS & SYMPTOMS ▫ ↓ Vital capacity
▫ ↓ Total lung volume
▪ Dyspnea, cough
▫ ↓ Forced expiratory volume in one
second (FEV1)
▫ ↓ Diffusion capacity of carbon monoxide
▪ Bronchopulmonary lavage
TREATMENT
SURGERY
▪ Lung transplant (definitive)
Figure 131.1 Illustration depicting the various criteria examined during a spirometric test.
OSMOSIS.ORG 935
IDIOPATHIC PULMONARY FIBROSIS
osms.it/idiopathic-pulmonary-fibrosis

▪ Abnormal pulmonary healing process: ▪ Exclude known causes of interstitial lung
pulmonary insult heals → excess deposits disease (e.g. hypersensitivity pneumonitis,
of collagen, fibrotic tissue → progressive pulmonary Langerhans cell histiocytosis,
scarring of lung tissue → loss of lung asbestosis, collagen vascular disease)
compliance → dyspnea worsens, lung
function declines → hypoxemia
▪ Affects pulmonary interstitium: tissue DIAGNOSTIC IMAGING
between alveoli, airspaces, peripheral
airways, vessels High-resolution chest CT scan
▪ Chronic, irreversible, ultimately fatal disease ▪ Usual interstitial pneumonia (UIP) pattern
▫ Honeycombing with well-defined walls
▫ Reticular opacities with/without traction
CAUSES
bronchiectasis (ground glass opacities,
▪ Overproliferation of type 2 pneumocytes honeycombing, cystic spaces)
→ excessive myofibroblast population
▫ Subpleural, basal lung fields
→ excessive collagen production →
collagen accumulates → interstitial layer ▫ Absence of features inconsistent with
thickens between alveoli, capillary → poor UIP (mid to upper predominance;
ventilation/gas exchange, lung parenchyma peribronchovascular predominance;
stiffens → restricted lung expansion extensive ground glass appearance;
(restrictive lung disease) profuse micronodules; discrete cysts
away from areas of honeycombing;
diffuse air-trapping)
RISK FACTORS ▫ Bronchopulmonary consolidation
▪ Ages 50–70, history of smoking, more ▪ Thickening of interstitial walls
common in individuals who are biologically
▫ Fibrotic changes
male, exposure to occupational dusts (e.g.
metal, wood, coal, silica, stone), biologic ▫ Bases, periphery
dusts (e.g. hay, molds, spores, agricultural
products, livestock), gastroesophageal LAB RESULTS
reflux disease, genetic
Biopsy
▪ Taken from three different areas,
SIGNS & SYMPTOMS large enough to show underlying lung
architecture (bronchoscopic biopsies
▪ Worsens over time, coughing (dry non- insufficient; thoracotomy/thoracoscopy
productive cough, worse on exertion), prefered)
dyspnea (progressive exertional), cyanosis, ▪ Histology
digital clubbing, dry inspiratory bibasilar ▫ Interstitial fibrosis in patchwork
crackles on auscultation, significant pattern; interstitial scarring; honeycomb
respiratory failure with increasing tissue changes; fibroblastic foci (dense
loss collections of myofibroblasts, scar
tissue)
936 OSMOSIS.ORG
Chapter 131 Restrictive Lung Disease
OTHER INTERVENTIONS
TREATMENT
Broncheolar lavage
▪ Cytology MEDICATIONS
▫ Exclude alternative diagnoses (e.g. ▪ Antifibrotic medication
malignancy, infection, eosinophilic ▫ Slows progression
pneumonia, histiocytosis X, alveolar ▪ Seasonal influenza vaccine
proteinosis)
▪ Lymphocytes > 30% SURGERY
▫ Exclude idiopathic pulmonary fibrosis ▪ Lung transplant (definitive)
Spirometry
▪ Restrictive pattern decreased
▫ Total lung capacity
▫ Forced vital capacity (FVC)
▫ FEV1
▪ Decreased diffusing capacity of lungs for
carbon monoxide

the axial plane demonstrating marked
honeycombing of the lung and a collection
of subpleural cysts in an individual with
Figure 131.2 The clinical appearance of idiopathic pulmonary fibrosis.
digital clubbing as seen in a case of idiopathic
pulmonary fibrosis.
OSMOSIS.ORG 937
SARCOIDOSIS
osms.it/sarcoidosis
▪ Airway involvement → airway
PATHOLOGY & CAUSES hyperresponsiveness (increased sensitivity
to inhaled triggers)
▪ Disease involving formation of ▪ Pulmonary hypertension → cor pulmonale
noncaseating granulomata (clumps of
inflammatory cells) Ocular pathology
▪ Can affect any organ system ▪ Up to 25%
▫ Accumulation of monocytes, epithelioid ▪ Significantly more common in Asian people
macrophages, activated T-lymphocytes of Japanese descent (>70%)
▫ Macrophages may aggregate to ▪ Anterior uveitis
form multinucleated giant cells (AKA ▪ Uveoparotitis (inflammation of uvea, parotid
Langhans giant cells) gland)
▫ Increased production of inflammatory ▪ Retinitis
mediators (Th-1 mediated)
▫ Cytokines released from activated Cardiac pathology
immune cells → systemic effects ▪ 5% symptomatic, autopsy reports 25–70%
subclinical involvement
CAUSES ▪ Significantly more common in Asian people
of Japanese descent
▪ Unknown; may be triggered by immune
reaction in genetically predisposed ▪ Conduction defects
individuals ▫ Asymptomatic conduction abnormalities
▫ Fatal ventricular arrhythmias
RISK FACTORS ▫ Complete heart block
▪ Genetic, previous episode of sarcoidosis, ▫ Sudden cardiac death
biological females, 20–50 age group ▪ Cardiac fibrosis, interstitial fluid
accumulation, heart failure, valvular
dysfunction, pericardial disease
COMPLICATIONS
Nervous system pathology
Paradoxical effect on immune reactivity
▪ ~5%
▪ Increased macrophage and CD4
▪ AKA neurosarcoidosis
helper T-cell activation → accelerated
inflammation ▪ Variable presentation
▪ But antigen challenges, e.g. tuberculin skin ▫ Cranial nerves most commonly affected
test are suppressed ▫ Neuroendocrine changes
▪ This paradoxical hyper-/hypo-activity is ▫ Chronic meningitis
immunological anergy → increased risk of
infections, cancer Endocrine/exocrine pathology
▪ Sarcoidosis of anterior pituitary
Pulmonary pathology ▫ Deficiency of adrenocorticotropic
▪ > 90% of affected individuals hormone, thyroid-stimulating hormone,
▪ Bilateral hilar lymphadenopathy (up to 90% follicle-stimulating hormone, luteinizing
of affected individuals) hormone, insulin-like growth factor 1
▪ Predominantly upper lobe parenchymal ▪ Hypothalamic dysfunction
infiltration ▫ Hypersecretion of prolactin
938 OSMOSIS.ORG
▪ Increase in 1,25-dihydroxyvitamin D (active

form of vitamin D) SIGNS & SYMPTOMS
▫ Hydroxylation usually occurs in
▪ Varies by organ. May be asymptomatic.
kidney; in sarcoidosis it may occur in
sarcoid granulomata due to activated General
macrophages → hypercalcemia →
▪ Peripheral lymphadenopathy, fatigue (not
hypercalciuria
relieved by sleep), weight loss, arthralgia,
Hepatic pathology dry eyes
▪ Liver granulomata very common (70%) Lower respiratory manifestations
▪ Only 20–30% have detectable aberrant ▪ Wheezing, cough, dyspnea, chest pain,
liver function hemoptysis, crackles
▪ Liver granlomata → cholestatic pattern →
raised alkaline phosphatase, mildly elevated Upper respiratory sarcoidosis (uncommon)
bilirubin, aminotransferases ▪ Laryngeal sarcoid: involves supraglottis,
occasionally subglottis
Nephrological pathology
▫ Subglottis: dysphagia, dyspnea, cough,
▪ < 5% hoarseness
▪ Can cause nephritis, but renal injury from ▪ Nasal and sinus sarcoidosis: nasal
hypercalcemia more common obstruction, nasal crusting, anosmia,
▪ Nephrocalcinosis, nephrolithiasis epistaxis, nasal polyposis
Gynecological/Urological
▪ Uncommonly epididymis, tesicles, prostate,
ovaries, fallopian tubes, uterus or vulva may
be affected
▪ Biological males → infertility
Hematological
▪ Sequestration of lymphocytes into areas of
inflammation → lymphopenia
▪ Anemia
▪ Leukopenia
▫ May reflect bone marrow involvement or
redistribution of T-cells to disease sites
▪ Monocytosis cutaneous sarcoidosis.
▪ Polyclonal hypergammaglobulinemia
Rheumatological
Skin
▪ 10%
▪ Erythema nodosum
▪ Acute polyarthritis
▫ Inflammation of subcutaneous adipose
▪ Enthesitis tissue → painful nodules
▫ Inflammation at sites where tendons or ▫ Affects anterior surface of lower
ligaments insert into bone extremities
▪ Chronic sarcoid arthritis ▪ Plaques
▫ Diffuse organ involvement ▫ Often seen in chronic forms
▫ Periosteal bone resorption ▫ Affects shoulders arms, back and
buttocks
▪ Maculopapular eruptions
▫ Common manifestation
OSMOSIS.ORG 939
▫ Affects alae, nares, lips, eyelids, Hematological
forehead, nape of neck, sites of previous ▪ Signs and symptoms of anemia,
trauma immunodeficiency
▪ Subcutaneous nodules ▪ Splenomegaly
▫ Affects face, trunk, extensor surfaces ▪ Immunological abnormalities
▪ Lupus pernio ▫ Allergies to test antigens, e.g. candida or
▫ Violaceous or erythematous indurated purified protein derivative
papules, plaques/nodules
Rheumatological
▫ Primarily affects nose, cheeks, chin, ears
▪ Acute polyarthritis
Ocular involvement ▪ Symmetric involvement of ankle joints
▪ Photophobia, blurred vision ▪ Usually periarthritis not true arthritis
▪ Increased tearing or dry eyes ▪ May be present in isolation or as part of
▪ Loss of visual acuity → blindness Löfgren syndrome
▪ Heerfordt syndrome: anterior uveitis, ▪ Löfgren syndrome
parotitis, cranial nerve VII palsy, fever ▫ Acute form of sarcoidosis
▫ 95% specificity for sarcoidosis
Cardiac involvement
▫ Predominantly occurs in biological
▪ Palpitations, dizziness, chest pain
females of Scandinavian, Irish, and
Nervous system Puerto Rican descent
▪ Hearing abnormalities, headache, altered ▫ Bilaterally enlarged hilar lymph nodes
consciousness level, changes in peripheral ▫ Erythema nodosum (tender red nodules,
sensation typically pretibial surface)
▫ Arthritis most commonly occurring in
Endocrine & exocrine changes ankles > knees > wrists > elbows >
▪ General: changes in body temperature, metacarpophalangeal joints; usually not
mood alterations, swelling of salivary/ true arthritis, but periarthritis affecting
parotid glands soft tissue around joints
▪ Biological females: amenorrhea, ▫ Enthesitis (inflammation sites where
galactorrhea, nonpuerperal mastitis, tendons/ligaments insert into the bone)
changes in menstrual cycle ▪ Chronic sarcoid arthritis
▪ Biological males: hypogonadism ▫ Diffuse organ involvement
▪ Other clinical manifestations of ▫ Ankles, knees, wrists, elbows, hands
hypopituitarism, e.g. diabetes insipidus, may be affected (polyarticular pattern)
hypothyroidism, adrenal insufficiency
▫ Dactylitis (inflammation of entire digit)
Hepatic ▫ Pain, stiffness
▪ Hepatomegaly
Nephrological
▪ Reduced creatinine clearance
▪ Proteinuria
▪ Signs and symptoms of renal calculi
940 OSMOSIS.ORG
MNEMONIC: SARCOIDOSIS ▫ Noncaseating granulomata

Features of Sarcoidosis ▫ Tuberculin skin test (tuberculosis,
Schaumann calcifications sarcoidosis share many clinical features)
Asteroid bodies/ACE increase/ ▫ Exclusion of other granulomatous
Anergy causes
Respiratory complications/
Renal calculi/Restrictive DIAGNOSTIC IMAGING
lung disease/Restrictive
cardiomyopathy X-ray, CT scan
Calcium increase in serum and ▪ Staged according to extent of lung
urine/CD4 helper cells involvement (Siltzbach classification
Ocular lesions system)
Immune mediated ▫ Stage 0: normal lung at presentation
noncaseating granulomas/Ig ▫ Stage I: bilateral hilar lymphadenopathy
increase only (60% resolution within 1–2 years)
Diabetes insipidus/D vit. ▫ Stage II: bilateral hilar lymphadenopathy
increase/Dyspnea with pulmonary infiltrates (46%)
Osteopathy ▫ Stage III: pulmonary infiltrates without
Skin: subcutaneous nodules, bilateral hilar lymphadenopathy (12%)
erythema nodosum ▫ Stage IV: pulmonary fibrosis
Interstitial lung fibrosis/IL-1 ▪ CT scan-/ultrasound-guided biopsy/fine-
Seventh CN palsy needle aspiration of mediastinal lymph
nodes
▫ Flow cytometry
▫ Microscopy and staining
▫ Culture
PET scan
▪ Lamba sign → gallium uptake in
paratracheal, hilar lymph nodes
▪ Panda sign → lacrimal, parotid,
submandibular glands with normal
nasopharyngeal uptake
▪ Combination of two specific for sarcoidosis
LAB RESULTS
▪ High blood calcium (normal parathyroid
level)
▪ Elevated angiotensin converting enzyme
(level correlates with total granuloma load)
Figure 131.5 A giant cell containing an ▫ Can be used for monitoring treatment
asteroid body in a case of pulmonary and disease progression
sarcoidosis.
OTHER DIAGNOSTICS
DIAGNOSIS Lung function testing
▪ Determine level of function
▪ Diagnosis of exclusion ▪ Monitor course of disease
▪ Usually dependent on biopsy of organ ▪ Typically reveals restrictive pattern (reduced
involved vital/total lung capacity)
OSMOSIS.ORG 941
▪ Endobronchial sarcoid may lead to symptoms
impairment of airflow, obstructive pattern ▫ Topical/local therapy preferred for
organ-confined disease
Diffusion of carbon monoxide (DLCO)
▪ Most sensitive test for interstitial lung
disease MEDICATIONS
Bronchoscopy Anti-inflammatory drugs

▪ Biopsy ▪ NSAIDS
▪ Bronchoalveolar lavage ▫ Up to 75% of individuals may achieve
sufficient symptomatic control on these
▫ CD4/CD8 T cell ratio in bronchoalveolar
alone
lavage is raised > 3.5 (can be normal/
low) ▪ Corticosteroids
▫ If long course required, consider steroid-
Ophthalmological exam sparing agents
ECG Antimetabolites
▪ Methorexatem, chloroquine, azathioprine
Immunosuppressants
TREATMENT ▪ Cyclophosphamide, cladribine,
chlorambucil, cyclosporine
▪ May resolve spontaneously over years
▪ Anti-tumor necrosis factor treatment
▪ Dermatological involvement typically
resolves without treatment ▫ These agents have also been reported
to cause sarcoidosis-like illness
▪ Acute disease
▫ No therapy is a viable option for mild
Figure 131.6 The histological appearance of pulmonary sarcoidosis. There are large numbers of
giant cells visible.
942 OSMOSIS.ORG
NOTES
NOTES
SLEEP–RELATED RESPIRATORY
DISEASE

snoring, airflow, end tidal CO2, oxygen
PATHOLOGY & CAUSES saturation, cardiac rhythm, body positioning
▫ Electroencephalography: sleep pattern
▪ Impaired capacity to breathe
▫ Electrooculography: REM
▫ Electromyography: neck muscle tonicity
SIGNS & SYMPTOMS ▫ Electrocardiography: heart rhythm
▫ Video monitoring: body positioning
▪ Apneic episodes (variable duration); fatigue;
hypoxemia; hypercapnia
TREATMENT
▪ Supportive, lifestyle modification
OTHER DIAGNOSTICS
Polysomnography
▪ Measure sleep patterns, rapid eye
movements (REM), tonicity of neck muscles,
APNEA OF PREMATURITY
osms.it/apnea-of-prematurity
CAUSES
PATHOLOGY & CAUSES ▪ Immaturity of fetal brain areas responsible
for breathing
▪ Most common cause of apnea in preterm
▪ Incidence increases with degree of
neonates
prematurity
▪ Developmental disorder associated with
▫ Most neonates < 28 weeks GA
decreased responsiveness to carbon
dioxide ▫ > ½ neonates 28–36 weeks GA
▪ Respiratory pauses of ≥ 20 seconds/shorter
pause with bradycardia (< 100/minute),
cyanosis, pallor, oxygen desaturation in
SIGNS & SYMPTOMS
neonates < 37 weeks gestational age (GA)
▪ Apneic episodes ≥ 20 seconds in first 72
hours post-birth
▫ Frequency increases 14–21 days post-
birth
OSMOSIS.ORG 943
▪ Bradycardia
▪ Hypoxemia
TREATMENT
▪ Resolves spontaneously after 37 weeks
DIAGNOSIS postmenstrual age
▫ Postmenstrual age = postnatal age +
OTHER DIAGNOSTICS GA age
▪ Monitor premature neonates
▫ Cardiorespiratory monitors, pulse MEDICATIONS
oximetry ▪ Methylxanthines
▪ Exclude other causes for apnea ▫ Improve sensitivity to carbon dioxide,
▫ Metabolic disorders, neurological increase ventilations/minute, decrease
disorders, infections, antepartum drugs periodic breathing events
(e.g. opiates)
OTHER INTERVENTIONS
▪ Nasal CPAP
SLEEP APNEA
osms.it/sleep-apnea
second apnea → individual wakes from
PATHOLOGY & CAUSES sleep
▪ Most common form of sleep apnea;
▪ Irregular breathing patterns, shallow peripheral problem; obstruction at
breathing and snoring during sleep. oropharynx
▪ Apnea: momentary: pause in breathing
▪ Can last several seconds to several minutes
CAUSES
▪ More than five episodes an hour must occur
▪ Hypopnea: abnormally shallow breathing Obstructive sleep apnea
event ▪ Obesity (most common)
▪ Hypertrophic adenoid glands/palatine
TYPES tonsils
▪ Micrognathia (small chin, AKA underbite)
Central sleep apnea ▪ Sedatives (excessive muscle relaxation—
▪ Sudden failure of brain respiratory center’s alcohol, sleeping pills)
generation of spontaneous breathing ▪ Allergies
efforts
▪ Hypothyroidism (obesity, less muscle tone)
▪ Damage to brain respiratory centers→
↑ respiratory drive → hyperventilation
→ CO2 (hypocapnia) → apnea → ↑ ↑ RISK FACTORS
CO2(hypercapnia) → ↑ respiratory drive → ▪ More common in individuals who are
hyperventilation biologically male
▪ Associated with Cheyne–Stokes respiration ▪ Incidence increases with age
Obstructive sleep apnea

▪ Intermittent airway obstruction → 20–30
944 OSMOSIS.ORG
Chapter 132 Sleep-Related Respiratory Disease
COMPLICATIONS
DIAGNOSIS
Obstructive sleep apnea
▪ Systemic hypertension OTHER DIAGNOSTICS
▪ Diabetes ▪ Polysomnography
▪ Anginal chest pain, arrhythmias, heart
failure
▪ Pulmonary hypertension, cor pulmonale,
TREATMENT
respiratory failure
MEDICATIONS
▪ Central sleep apnea: respiratory stimulants
SIGNS & SYMPTOMS (acetazolamide, theophylline)
▪ Sleep deprivation, excessive daytime SURGERY

fatigue ▪ Obstructive sleep apnea: micrognathia,
▪ Headache, difficulty concentrating hypertrophic adenoids/tonsils
▪ Morning headaches
Central sleep apnea OTHER INTERVENTIONS

▪ Nocturia ▪ Continuous positive airway pressure
(CPAP)
▪ Stress-induced insomnia
▪ Central sleep apnea: supplemental oxygen
▪ Nocturnal anginal chest pain
during sleep
Obstructive sleep apnea ▪ Obstructive sleep apnea: custom
▪ Loud snoring mouthpieces, weight loss
▪ Hypopnea
▪ Repeated arousals from sleep
▪ Decreased libido
Figure 132.1 A CT scan of the head and

neck in the sagittal plane. The soft palate is
elongated, thickened and abutts the posterior
pharynx, leading to obstructive sleep apnea.
OSMOSIS.ORG 945
NOTES
NOTES
UPPER RESPIRATORY TRACT

▪ Upper-airway infection (e.g. nasal cavity, LAB RESULTS
pharynx, larynx) with pathogenic microbes ▪ Cultures, complete blood count (CBC)
▫ Bacterial involvement
RISK FACTORS
▪ Compromised immunity; genetic, congenital OTHER DIAGNOSTICS
malformations; concomitant infection ▪ Clinical presentation, physical exam
COMPLICATIONS
▪ Airway obstruction, infection spread, sepsis
TREATMENT
MEDICATIONS
SIGNS & SYMPTOMS ▪ Antimicrobials
▪ Stridor; fever (if bacterial infection); SURGERY

discharge; difficulty swallowing ▪ Surgical interventions
OTHER INTERVENTIONS
▪ Respiratory support, intubation (if severe
respiratory obstruction)
946 OSMOSIS.ORG
Chapter 133 Upper Respiratory Tract
BACTERIAL EPIGLOTTITIS
osms.it/bacterial-epiglottitis
anterior neck tenderness, anxiety
PATHOLOGY & CAUSES
▪ Inflammation of epiglottis, nearby DIAGNOSIS
supraglottic structures
▪ Fluid, inflammatory-cell accumulation → DIAGNOSTIC IMAGING
rapid, progressive swelling of epiglottis,
adjacent structures (supraglottic larynx) Laryngoscopy
→ airway narrows, ball-valve curling → ▪ Swollen, red epiglottis
airway obstruction
X-ray
▪ Shadow of enlarged epiglottis (“thumb”
CAUSES sign); ballooning of hypopharynx
▪ Bacteria from posterior nasopharynx,
Haemophilus influenzae (most common
in children), Streptococcus pneumoniae, LAB RESULTS
Staphylococcus aureus ▪ CBC: ↑ white blood cells (WBCs)
▪ ↑ C-reactive protein (CRP), positive throat
culture
RISK FACTORS
▪ Unimmunized status
▪ Mucosal trauma TREATMENT
▫ E.g. burns, caustic substance/foreign
body ingestion MEDICATIONS
▪ Most common in children 6–12 years old ▪ Empiric antimicrobial therapy
▪ Comorbidities (adults) ▫ E.g. third generation cephalosporin for
▫ E.g. diabetes mellitus, substance abuse, Haemophilus influenzae colonization
BMI > 25
OTHER INTERVENTIONS
COMPLICATIONS ▪ Airway management with humidified
▪ Airway obstruction supplemental oxygen
▪ Oropharyngeal secretion aspiration
Prevention
▪ Cardiopulmonary arrest
▪ Haemophilus Influenzae Type b (Hib)
▪ High mortality rate vaccine
SIGNS & SYMPTOMS

▪ Children: abrupt “3Ds” onset: dysphagia,
drooling, distress
▪ Respiratory: stridor, retractions, tachypnea,
cyanosis
▪ Behavioral: individual refuses to lie down;
assumes tripod posture
▪ Voice: aphonia, muffled
▪ Other: sore throat, fever, odynophagia,
OSMOSIS.ORG 947
LARYNGITIS
osms.it/laryngitis

▪ Inflammation of larynx DIAGNOSTIC IMAGING
▫ Acute: < three weeks
Laryngoscopy
▫ Chronic: > three weeks
▪ Swollen, red vocal folds; biopsy
CAUSES
LAB RESULTS
Acute ▪ Blood culture
▪ Viral
▫ Rhinovirus, influenza virus,
parainfluenza, adenovirus TREATMENT
▪ Bacterial
▫ Moraxella catarrhalis, H. influenzae, S. MEDICATIONS
pneumoniae ▪ Simple analgesics
▪ Fungal ▪ Non-steroidal anti-inflammatory drugs
▫ Candida in immunosuppressed (NSAIDs)
▪ Trauma, nerve damage ▪ If bacterial infection, antibiotics
Chronic
▪ Acid reflux, smoke exposure, allergies, OTHER INTERVENTIONS
rheumatoid arthritis, autoimmune disease ▪ Voice rest
SIGNS & SYMPTOMS

▪ Flu-like
▫ Fever, cough, malaise, enlarged lymph
nodes
▪ Stridor, hoarseness, pain, odynophagia,
lump in throat
948 OSMOSIS.ORG
NASAL POLYPS
osms.it/nasal-polyps

▪ Overgrowths of epithelial tissue lining nasal DIAGNOSTIC IMAGING
cavity, paranasal sinuses
Endoscopy
▪ Most commonly formed in maxillary/
ethmoid sinus ▪ Direct visualization of nasal polyp
▪ Results in airflow obstruction, mucus CT scan
drainage blockage ▪ Hyperdense outpouching in nasal cavity
CAUSES
▪ Unknown; associated with long-term TREATMENT
inflammatory sinus conditions
▫ Seasonal allergies, frequent asthma MEDICATIONS
exacerbations, chronic sinusitis, aspirin Topical steroids
sensitivity
▪ Nasal spray to shrink polyp; ↓ inflammation,
swelling
RISK FACTORS
▪ Cystic fibrosis, primary ciliary dyskinesia Nasal saline lavage
▪ Underlying allergy treatment
COMPLICATIONS
▪ Mucus drainage obstruction; sinusitis → SURGERY
recurrent infections ▪ Endoscopic sinus surgery if unresponsive
to steroids
SIGNS & SYMPTOMS

▪ Bacterial infection
▫ Blocked mucus drainage
▫ Fever, headache
▪ Obstructed air flow
▫ ↓ sense of smell, snorting, sleep apnea,
cyanosis (in infants)
OSMOSIS.ORG 949
a nasal polyp. There is loose, myxoid stroma
lined by respiratory epithelium.
Figure 133.2 A trans-nasal view of a polyp in

the posterior nasal passage.
RETROPHARYNGEAL &
PERITONSILLAR ABSCESS
osms.it/rp-and-pt-abscess
CAUSES
PATHOLOGY & CAUSES
Retropharyngeal abscess
▪ Abscesses of the upper respiratory tract ▪ Bacterial
▫ S. aureus, group A beta-hemolytic
TYPES bacteria, H. parainfluenzae
▪ Trauma, upper respiratory tract infections
▪ Abscess formation in retropharyngeal Peritonsillar abscess
space ▪ Streptococcus pyogenes (most common) →
▫ Between buccopharyngeal fascia, alar acute tonsillitis
fascia ▪ Staphylococcus, Haemophilus, anaerobes
▪ Bacteria of nasopharynx enter weakened of mouth flora (less common)
mucosa → white blood cells (WBCs)
follow, create pus → mass grows, pushes COMPLICATIONS
into airway
Peritonsillar abscess ▪ Spread beyond retropharyngeal space,
▪ Pus in potential space between pharyngeal mediastinitis, pericarditis; pharyngitis,
muscles, palatine tonsils airway obstruction; sepsis
Peritonsillar abscess
▪ Retropharyngeal abscess, cellulitis of head
and neck, sepsis
950 OSMOSIS.ORG
SIGNS & SYMPTOMS

▪ Fever, lethargy, swelling, sore throat
▪ Neck pain/stiffness, pharyngeal obstruction,
difficulty swallowing, dyspnea, cough,
stridor
Peritonsillar abscess
▪ Asymmetric tonsillar swelling with uvular
displacement; lymph node enlargement
▪ Muffled voice, trismus, sleep disturbance
(difficult breathing), snoring, halitosis
DIAGNOSIS
DIAGNOSTIC IMAGING Figure 133.3 Clinical appearance of a right
Contrast CT scan sided peritonsillar abscess which shows
swelling of the palatopharyngeal arch.
▪ Tissue swelling
Ultrasound
▪ Differentiate Peritonsillar abscess from
Cellulitis
LAB RESULTS
▪ Systemic spread in CBC, throat culture,
blood culture
OTHER DIAGNOSTICS
▪ Swollen pharyngeal space tissues
▪ Redness, asymmetry
TREATMENT
MEDICATIONS Figure 133.4 A CT scan of the head in the
axial plane demonstrating a peritonsillar
▪ IV antibiotics
abscess.
SURGERY
▪ Surgical drainage of abscess
▪ Peritonsillar abscess
▫ If airway obstruction, immediate
tonsillectomy/incision, drainage
OSMOSIS.ORG 951
SINUSITIS
osms.it/sinusitis
LAB RESULTS
PATHOLOGY & CAUSES ▪ CBC, leukocytes often normal
▪ Swabs, cannulation contraindicated due to
▪ Inflammation of sinuses, usually due to
high likelihood of sample contamination
infection
CAUSES TREATMENT
▪ Influenza, parainfluenza, rhinoviruses,
adenoviruses; bacteria of nasopharynx MEDICATIONS
Antibiotics
RISK FACTORS ▪ If bacterial
▪ Upper respiratory tract infections, allergies, ▪ First line treatment, penicillin (amoxicillin
teeth infections (spread to maxillary sinus), with clavulanic acid); second line,
tumors, adenitis, nasotracheal/nasogastric fluoroquinolones
tubes, genetic disorders (Kartagener, cystic
fibrosis), deformation of bone Corticosteroids (topical/systemic)
▪ Alleviate allergies
COMPLICATIONS
▪ Meningitis, cavernous sinus thrombosis, OTHER INTERVENTIONS
orbital/periorbital cellulitis, abscesses
Steam treatments
▪ Dislodge secretions
SIGNS & SYMPTOMS
▪ Bacterial
▫ Fever, headache, immediately previous
upper respiratory infection, feeling
of draining fluid, pain when leaning
forward, voice change, last > 10 days
▪ Viral
▫ Self-limiting, painful sinuses (esp.
leaning forward), discharge, last < 10
days
DIAGNOSIS
DIAGNOSTIC IMAGING
▪ Rare
CT scan Figure 133.5 A CT scan of the head in the

▪ Screen for complications coronal plane demonstrating left maxillary
sinusitis.
952 OSMOSIS.ORG

INFECTION
osms.it/upper-resp-tract-infection
(Staphylococcus aureus; Group C,
PATHOLOGY & CAUSES G Streptococcus; Arcanobacterium
haemolyticum; Fusobacterium
Pharyngitis necrophorum; Mycoplasma
▪ Clinical syndrome characterized by sore pneumoniae; Chlamydia pneumoniae;
throat, cervical lymphadenopathy; sore Corynebacterium diphtheriae; Neisseria
throat worsens with swallowing; typically gonorrhoeae; Treponema pallidum);
accompanied by reactive enlargement of viruses (respiratory syncytial viruses;
tonsils influenza A, B; HIV; Epstein–Barr virus;
▪ Inflammation of nasopharyngeal mucosa cytomegalovirus; herpes simplex virus;
with reactive inflammation of lymph nodes, parainfluenza; enteroviruses)
tonsils ▪ Noninfectious
▫ Allergic rhinitis
The common cold
▫ Irritative pharyngitis (due to dry air, esp.
▪ Mild self-limiting viral infection
in winter)
characterized by nasal congestion,
rhinorrhea, sore throat, nonproductive ▫ Medications (e.g. angiotensin-
cough, low grade fever converting enzyme inhibitors)
▪ Most common upper respiratory tract ▫ Kawasaki disease
infection ▫ Periodic fever, aphthous stomatitis,
▪ Hand contact/inhalation of airborne pharyngitis, adenitis (PFAPA) syndrome
droplets from infected individual → viral
The common cold
inoculation → deposition on nasal mucosa
→ viral replication → cytokines release from ▪ Viruses
infected cells → immune response initiates ▫ Most common: rhinoviruses (50% of all
→ inflammation, congestion of nasal cavity cases)
mucous membranes ▫ Coronaviruses, parainfluenza viruses,
▪ Resolves within one week, symptoms last RSV, influenza, adenoviruses, coxsackie
up to 10–14 days; esp. in young children < viruses
six
▪ No cross immunity between serotypes RISK FACTORS
▫ Possible reinfection with milder
symptoms, shorter duration The common cold
▪ Age, usually children < six; malnutrition;
underlying diseases; immunodeficiency
CAUSES disorders; smoking; stress; sleep
Pharyngitis disturbances; weather, high prevalence in
fall, winter
▪ Infectious
▫ Most common pathogens: respiratory
viruses (rhinovirus, echovirus, COMPLICATIONS
adenovirus, coronavirus), Group A
Pharyngitis
Streptococcus pyogenes (GAS)
▪ Severe pharyngeal inflammation, abscess
▫ Less common pathogens: bacteria
formation, tonsillar hypertrophy → upper
OSMOSIS.ORG 953
airway obstruction ulcer, viral exanthem
▪ Post streptococcal ▫ Bacterial pharyngitis: sudden
▫ Suppurative (spread of infection beyond onset of symptoms, high grade
pharynx): otitis media; peritonsillar fever, tonsillopharyngeal edema,
cellulitis/abscess; retropharyngeal tonsillar exudates, painful cervical
abscess; sinusitis; meningitis; lymphadenopathy
bacteremia; necrotizing fasciitis; jugular ▪ Symptoms resolve within 3–5 days in
vein septic thrombophlebitis viral pharyngitis; 5–7 days in bacterial
▫ Non suppurative (immune mediated): pharyngitis
acute rheumatic fever, which can
The common cold
progress to rheumatic heart disease;
post streptococcal glomerulonephritis; ▪ Immune response to infection
reactive arthritis; scarlet fever (delayed ▪ Nasal features
skin reactivity to erythrogenic toxin ▫ Congestion; clear, purulent, yellow/green
produced by GAS; requires prior discharge; sneezing; erythema, nasal
exposure to GAS; characteristic mucosa swelling
scarlet rash, white with red enlarged ▪ Nonproductive cough
papillae aka “strawberry tongue”); ▪ Sore throat
streptococcal toxic shock syndrome;
▪ Low grade fever
pediatric autoimmune neuropsychiatric
disorder associated with streptococcus ▫ Predominant in young children;
(PANDAS) uncommon in older children, adults
▪ Lemierre syndrome: suppurative ▪ Headache, malaise, abnormal middle ear
thrombophlebitis of jugular vein caused by pressure, conjunctivitis
Fusobacterium necrophorum
The common cold DIAGNOSIS

▪ Secondary bacterial infection
▫ Acute otitis media, sinusitis, pneumonia LAB RESULTS
▪ Asthma exacerbation Pharyngitis
▪ If suggestive of GAS pharyngitis (AKA
strep throat)
SIGNS & SYMPTOMS
▫ Rapid strep test (RST): detects GAS
antigens on swab sample of tonsils,
Pharyngitis
posterior pharynx
▪ Reddening; edema of pharyngeal mucosa;
▫ Throat culture: more accurate than RST,
sore throat, worsens when swallowing
takes 24 hours. If RST negative, but
▪ Neck pain/swelling due to reactive clinical suspicion of GAS pharyngitis;
lymphadenopathy beta hemolytic, bacitracin sensitive,
▫ Not prominent in viral pharyngitis pyrrolidonyl arylamidase (PYR) positive
▫ Prominent, tender, anterior cervical colonies
lymphadenopathy in bacterial ▫ Polymerase chain reaction (PCR)-based
pharyngitis assays: more sensitive, rarely available
▪ Constitutional symptoms ▫ Serological tests: (antistreptococcal
▫ Fever (low grade in viral pharyngitis, antibodies: anti-streptolysin (ASO), anti-
high grade in bacterial pharyngitis) hyaluronidase, anti-streptokinase, anti-
▫ Headache, fatigue, malaise nicotinamide adenine dinucleotidase,
▪ Swollen, reddened tonsils with white spots anti-DNase; ↑ titres suggestive of recent
of exudate from tonsillar crypts GAS infection; useful for detecting post
streptococcal complications
▪ Suggestive of
▫ Viral pharyngitis: cough, nasal
congestion, conjunctivitis, coryza, oral
954 OSMOSIS.ORG
OTHER DIAGNOSTICS ▫ Chronic tonsillitis unresponsive to

antibiotics
Pharyngitis
▫ Tonsil enlargement causing airway
▪ Oropharyngeal examination obstruction
▪ Centor criteria: predict possibility of GAS ▫ Complications of pharyngotonsillitis
pharyngitis
▫ PFAPA syndrome
▫ 1 point each: fever, tonsillar
exudates, tender anterior cervical
lymphadenopathy, absence of cough, OTHER INTERVENTIONS
age < 15; subtract 1 point if age > 44
Pharyngitis
▫ -1, 0, 1: no testing
▪ Viral pharyngitis often self-limited
▫ 2, 3: testing required
▪ Symptomatic
▫ 4, 5: empirical antibiotic treatment
▫ Rest
The common cold ▫ Adequate fluids to loosen secretions,
▪ Clinical presentation prevent airway obstruction
▪ Re-evaluation if symptoms worsen/exceed The common cold
expected recovery time
▪ Symptomatic
▫ Rest
TREATMENT ▫ Adequate fluids
MEDICATIONS
Pharyngitis
▪ Antipyretics/analgesics
▫ Aspirin, acetaminophen, nonsteroidal
anti-inflammatory drugs (NSAIDs); for
fever, pain control
▪ Salt water gargling
▪ GAS pharyngitis: antibiotics to prevent
complications, reduce symptoms, prevent
transmission
▫ First line treatment: penicillin (penicillin
V/amoxicillin)
▫ Alternatives: cephalosporins,
clindamycin, macrolides
▫ If recurrent/persistent: repeat 10 day
course of antibiotics
The common cold

▪ Topical saline/nasal suction/combination of
nasal decongestant with antihistamines
▪ Antipyretics/analgesics
▪ Dextromethorphan/codeine to suppress
cough
SURGERY
Pharyngitis
▪ Tonsillectomy
▫ Recurrent infections
OSMOSIS.ORG 955
NOTES
NOTES
CHOANAL ATRESIA
osms.it/choanal-atresia
▪ Re-narrowing of the area after surgery
PATHOLOGY & CAUSES
▪ Congenital narrowing or blockage of the SIGNS & SYMPTOMS
nasal passage (choana) by abnormal bony
or soft tissue ▪ Variance of presentation depends on
▪ Most common nasal abnormality in unilateral or bilateral defect
newborns; more than 50% have other ▪ Newborns are obligate nasal breathers →
congenital conditions difficulty breathing unless crying
▪ ⅔ present unilaterally, ⅓ bilaterally ▪ Unilateral choanal atresia may not be
▪ Cause unknown: can be associated detected for years → newborn uses
with conditions that cause depression healthy nostril to breathe; distress may be
of the nasal bridge or midface retraction intermittent
(craniosynostosis syndromes) ▪ Bilateral choanal atresia can be life-
threatening; causes acute breathing
problems and cyanosis
MNEMONIC ▪ Marked chest retraction
In context of CHARGE ▪ Inability to nurse and breathe at the same
association time
Coloboma ▪ Persistent one-sided mucous discharge
Heart defects ▪ Cyanosis
Atresia of choanae
Retardation (physical, mental)
Genitourinary abnormalities DIAGNOSIS
Ear defects
DIAGNOSTIC IMAGING
CT scan
RISK FACTORS
▪ Possible association with: low thyroid Endoscopy of the nose
hormone levels; smoking; coffee
consumption; high maternal zinc and B12 Sinus radiography
intake; exposure to agricultural chemicals;
anti-infective urinary tract medications OTHER DIAGNOSTICS
▪ Inability to pass a catheter through nasal
COMPLICATIONS passage
▪ Aspiration while feeding
▪ Respiratory arrest
956 OSMOSIS.ORG
Chapter 134 Upper Respiratory Tract Congenital Malformations
Figure 134.1 A CT scan of the head in the Figure 134.2 A CT scan of the head in the
axial plane demonstrating membranous axial plane demonstrating bilateral osseous
atresia of the right choana. choanal atresia.
TREATMENT
▪ Temporarily: oral airway placement; place
infant prone
SURGERY
▪ Definitive: surgical correction of the atresia
LARYNGOMALACIA
osms.it/laryngomalacia
laryngeal muscle tone
PATHOLOGY & CAUSES
▪ Congenital malformation of the larynx COMPLICATIONS
where the aryepiglottic folds are shorter ▪ Impaired growth and development caused
than normal by hypoventilation (hypoxemia)
▪ Short aryepiglottic folds cause folding of ▪ Associated with gastroesophageal reflux
epiglottis in a characteristic omega shape ▪ Swallowing dysfunction and choking
that prolapses during inspiration
▪ Arytenoid cartilages are enlarged and
softer than normal, so they flop into the SIGNS & SYMPTOMS
airway
▪ Most common cause of congenital stridor ▪ High-pitched stridor
and most common congenital lesion of the ▪ Noisy respirations
larynx ▪ Breathing difficulties
▪ Cause is unknown; associated with weak ▪ Gastroesophageal reflux
OSMOSIS.ORG 957
DIAGNOSIS
DIAGNOSTIC IMAGING
Laryngoscopy or bronchoscopy
▪ Confirms diagnosis
OTHER DIAGNOSTICS
▪ History and physical exam
TREATMENT
▪ Can resolve spontaneously as throat
muscles strengthen by age two
Figure 134.3 A laryngoscopic view of the
MEDICATIONS larynx in an individual with laryngomalacia in
which there is an omega-shaped epiglottis.
▪ If hypoxemic → supplemental oxygen
SURGERY
▪ If laryngomalacia persists, surgical
treatment is necessary (tracheotomy or
supraglottoplasty)
Figure 134.4 Illustration of unique shape of larynx seen in laryngomalacia.
958 OSMOSIS.ORG
PATHOLOGY VOLUME 2 INDEX
(extrinsic) allergic alveolitis, 206 412, 415, 473, 559 alimentary, 312, 350, 432
(pneumocystis pneumonia), 469 acute respiratory distress syndrome, 255, alkaline phosphatase, 160, 264, 571, 591,
22q11.2 deletion syndrome, 218 365, 373, 412, 415 597, 599, 604, 606, 769
5-alpha-reductase deficiency, 94 acute rhinitis, 220 alkalosis, 71–73, 236, 781
5p- syndrome, 149 acute schistosomiasis syndrome, 573 alkaptonuria, 231–232, 661
abdominal cavity, 800 acute tubular necrosis, 248, 415, 714 allergen, 10, 13, 205, 208, 219–220, 222,
abdominal hysterectomy, 750, 752 acute urticaria, 62 229
abdominal wall cellulitis, 45 acyanotic defects, 93, 107, 143, 169, 173, allergic asthma, 219
abduction, 664, 670, 683, 716 187, 195, 205, 241, 345, 349, 369, allergic bronchopulmonary aspergillosis,
abetalipoproteinemia, 257–258, 263 497, 499, 501, 511, 523 461–463
abg, 247, 254 acyclovir, 17, 49, 427, 823–824 allergic contact dermatitis, 12–13, 228
ablation, 58, 102, 120, 124, 133, 139, 613, ad-hies, 198 allergic reaction, 59, 221, 440, 446
742, 798 ada, 187–188 allergic rhinitis, 10, 219
abo blood group, 162 add, 45 allergy, 59, 63, 202, 205, 222, 227, 490,
abscess, 45–46, 49–50, 192, 198, 318, addison’s disease, 41, 76–78 547
340, 350–351, 355–356, 359, addisonian crisis, 77–78 allograft, 210
380–381, 383, 385–387, 402–403, adduction, 681–682 alopecia, 21–22, 41, 105, 143–144, 146,
405–406, 408, 440, 442, 445, 461, adenine, 214, 303, 354, 555 282, 390, 546
464, 466, 468, 523–524, 526–527, adenitis, 359, 488, 820 alopecia areata, 21–22
529, 531–533, 535–536, 549–550, adenocarcinoma, 69, 91, 320, 729, 741, alpha-fetoprotein, 183, 419
555–557, 559, 561, 571, 588, 745, 751, 769–770 alport syndrome, 152–153
753–755, 775, 784, 803, 810–811, adenoma, 68–71, 87–88, 104, 107–108, alt, 253, 365, 390, 419, 423, 541
825 110, 113–115, 123, 125, 132–134, alveolitis, 206
acalculous cholecystitis, 400 758 amblyopia, 39, 151
acanthamoeba, 332–333 adenopathy, 347, 473 ameba, 332, 334
acantholysis, 66 adenosine deaminase, 187 amebiasis, 402
acanthosis nigricans, 84, 98 adenosine deaminase deficiency, 187 amebic colitis, 403
ace, 62, 72, 154, 191, 362, 647, 785 adenosine triphosphate, 240, 292, 342 amenorrhea, 70, 89, 93, 98, 100, 579, 602,
ace inhibitor, 62, 72, 785 adenovirus, 308–309, 494, 643 757–758
acetabulum, 663, 682–683 adh, 110–111, 118–119 amenorrhea, primary, 602
acetaminophen, 253–254, 474, 493, 590, adhd, 175, 177–178 american trypanosomiasis, 580
662, 667, 669, 754 adrenal cortical carcinoma, 86 ami, 779
acetate, 571 adrenal crisis, 71, 73, 76, 79, 117 amino acid, 39, 137, 153, 162, 231, 233,
acetone breath, 85 adrenal gland, 68–69, 71, 78, 99, 108, 162 235–237, 239, 304
acetylcholine, 223, 316, 511 adrenal hyperfunction, 68–69, 71 amino acid metabolism disorders, 231, 233,
achilles tendon, 259, 666–667 adrenal hyperplasia, 73, 75 235, 237
achilles tendon rupture, 666 adrenal hypofunction, 76–77, 79 aminoglycosides, 285, 527, 529, 534, 536,
achlorhydria, 133, 302, 304, 317 adrenal medulla, 140 539
achondroplasia, 692–693, 699, 704 adrenocortical carcinoma, 160 aminotransferase, 365, 390, 419, 490, 541,
acid phosphatase, 600 adult intestinal toxemia botulism, 317 653, 828
acidosis, 77–78, 81, 83–85, 163, 247–249, aerobic rods, 310–311, 313, 315 amitriptyline, 641
253, 255, 267–268, 284–286, 363, afp, 183–185, 419, 772 amniocentesis, 167, 173, 178, 181, 183–
374, 407, 415, 500, 600, 714, 778, african eye worm, 446 185, 681–682, 762, 775, 787
782 agammaglobulinemia, 196, 204 amnion, 764, 776, 785
acl, 667–668, 676 agenesis, 97, 125, 167, 184–185, 758, 785 amphetamine, 254
acne, 44–45, 48–49, 57, 70, 98, 282, 758 aha, 196 amputation, 8, 321, 357, 374, 589, 609,
acne inversa, 49 aid, 18, 98, 154, 168, 320, 333, 336, 359, 712, 785
acne vulgaris, 44 367, 369, 377, 407, 412, 422, 425, amyloidosis, 110, 134–135, 625, 636
acral lentiginous melanoma, 26 428, 460–461, 463, 465–466, amyoplasia, 679–680
acrodermatitis enteropathica, 282 469–470, 475, 479, 495, 501–503, ana, 654, 656
acromegaly, 87, 108–109, 113, 133, 164, 632, 740–741 anaerobic, 51, 247, 316–317, 319–323,
602 aiha, 223 354, 380, 383, 402, 409, 434, 523,
actinic keratosis, 1–2, 29 airway obstruction, 61, 128, 168, 289, 424, 526–527, 548, 753
actinomyces israelii, 383 479 anaerobic rods, 316–317, 319, 321, 323
activated charcoal, 254 aki, 328 anal cancer, 476
acute abdomen, 319 alagille syndrome, 163 analgesia, 1, 8–9, 19, 227, 296, 424, 431,
acute bacterial prostatitis, 809 alanine aminotransferase, 365, 419, 541, 440, 453, 482, 489, 493, 596, 639,
acute bacterial rhinosinusitis, 370 828 647, 659, 665, 667, 669, 686, 696,
acute disseminated, 480 albinism, 1, 25, 27, 29, 39–40, 212–213 712, 715, 726, 784, 804, 808
acute granulomatous prostatitis, 809–810 albumin, 276, 329, 419 anaphylactic shock, 62, 441
acute hepatitis, 350, 417–421 albuminuria, 80, 82, 252 anaphylaxis, 205, 219, 221, 340
acute kidney injury, 389–390 alcohol, 46–47, 57–58, 248–250, 253, 260, anaplasma, 412, 515–516
acute leukemia, 194 302–303, 305, 376, 470, 554, anaplastic/undifferentiated carcinomas, 91
acute otitis media, 493 601–602, 627, 629, 633, 713, 722, androgen, 44, 50, 62, 73, 77, 95, 98,
acute pulmonary aspergillosis, 461 775, 782, 797, 801, 806 768–769, 799, 805
acute radiation syndrome, 241 alcohol abuse, 46–47, 302–303, 305, 523, androgen insensitivity syndrome, 95
acute renal failure, 413, 415, 423, 528, 536 529, 531, 554, 584 androstenedione, 87, 98, 100
acute respiratory distress, 255, 365, 373, aldosterone, 68, 71–73, 78, 86, 418 anemia, 122, 125, 136–137, 162, 182,
26 OSMOSIS.ORG
Pathology Volume 2 Index
194, 196–197, 214, 223–224, antidiuretic hormone secretion, 118 696, 698, 704–706, 755, 818, 820
242, 246, 252, 258, 276, 278–279, antidote, 241, 247, 255 arthrocentesis, 662
293–294, 296, 301–302, 304–306, antiemetics, 243, 331, 521, 781 arthrogryposis, 679–681
338–339, 350–351, 399, 413, antifungal, 15, 214, 332, 334, 366, 368, arthrogryposis multiplex congenita, 679
415–416, 423, 434, 437–438, 456, 463, 468, 558–559, 563–564 arthropathy, 82, 484, 509
454–455, 485–486, 519, 528, 531, antigen, 10, 12, 16, 18, 64, 135, 192, 206– arthroscopy, 621, 668
536, 541, 545, 559, 563, 574, 580, 207, 209, 219–220, 223–224, 226, arthus reaction, 226
600–601, 636–637, 646–647, 228–230, 309–310, 317–319, 322, ascaris, 436, 441–443, 451
650, 677–678, 738, 744, 764, 797, 332, 337, 341, 343, 355, 360–362, ascaris lumbricoides, 441, 443
808–809, 815, 817–818, 827 365, 393, 402, 404, 414–415, 417, ascites, 71, 271, 277, 311, 318, 340, 392,
anemia of chronic disease, 637 419, 421, 431, 433–434, 439, 448, 418, 574, 748–750, 752, 816
anesthesia, 712 455, 462–463, 466, 473–474, 484, ascorbic acid, 306
aneuploidy, 148, 682, 782, 785–786 502, 512, 530, 538, 554, 556, 559, aseptic necrosis, 296
aneurysm, 115, 153, 157, 163, 350, 545, 561, 563, 579, 632, 635–636, 643, aspartate aminotransferase, 541, 653, 828
581, 625 645, 647, 740, 769, 800, 810 aspergillosis, 460–463, 515
angelman syndrome, 169–170 antigen-antibody complex, 192 aspergillus, 54, 460–462
angina, 52, 259–260 antihistamine, 13, 220, 447, 493, 623 aspergillus fumigatus, 460
angioedema, 61–62, 191, 221–222, 441, antimalarials, 337 asphyxia, 61, 735, 775–776, 778, 782
573 antiphospholipid syndrome, 649, 788 aspiration, 90, 92, 135, 143–144, 179,
angiogenesis, 163, 636 antipsychotics, 83, 806 213, 249, 313, 341, 353, 355, 363,
angiogram, 717 antiseptic, 8, 19, 49, 51 383–384, 387, 406, 442, 483, 491,
angiostrongylus, 439 antitoxin, 221, 314, 318, 323 523, 531, 579–580, 587, 589–590,
angiotensin, 71–72, 77, 154, 157, 191, anxiety disorder, 11–12, 127, 135, 140, 656, 659–660, 664, 726, 775, 782,
418, 647 145, 151, 177–178, 180, 237, 255, 785, 794, 808–809
angiotensin converting enzyme, 72, 647 304, 623, 641, 680, 806–807 aspiration pneumonia, 179, 442, 483, 491,
anhidrosis, 136 anxiolytics, 243 523, 656
anisakis, 440 aorta, 71, 151, 156–157, 175, 545, 817 aspirin, 424, 427, 627, 629
anisocytosis, 302, 305 aortic aneurysm, 625 asplenia, 354, 412
ankle, 82, 470, 510, 589, 627, 632, 662, aortic dissection, 157 ast, 253, 390, 419, 423, 541, 653
666, 674–675, 686, 777, 788 aortic regurgitation, 625, 634 asthma, 10–11, 69, 131, 199, 201–202,
ankylosing, 602, 624–626, 634, 659, 698, aortic stenosis, 150–151, 259 219, 386, 434, 446, 461–462, 483,
704–705 aortic valve, 175, 545, 625 492–493
ankylosing spondylitis, 602, 624, 626, 634, ap, 716–717 asystole, 247
698, 705 apert syndrome, 684–685 at, 3, 13, 21, 25–26, 32–36, 47, 54, 57–59,
anorexia, 77, 119, 206, 302, 305, 326, 347, apgar score, 778, 826 61, 71, 74, 81, 90, 95–96, 99–100,
384, 386, 394–395, 412, 442, 449, aplasia, 151, 185, 218, 242, 485–486 104, 109, 112–113, 122, 125, 151,
451, 479–481, 488–489, 493, 512, aplastic anemia, 194 155–156, 160, 168, 176–177,
517, 519, 536, 581, 656 apnea, 172, 182, 247, 287, 290, 322, 346, 179, 182, 202–204, 207, 209, 211,
anosmia, 97 483, 684, 693, 820, 825 216–217, 220–221, 223, 229–230,
antalgic gait, 672, 708 apophysitis of tibial tubercle, 595 235, 242, 249, 251, 265, 267, 271,
anterior chamber disease, 448 apoptosis, 8, 159, 167, 208, 228, 301, 304, 289, 291, 300, 302, 305, 307, 311,
anterior cruciate ligament, 667–668 318, 346–347, 349, 360, 389, 392, 313, 315, 321–323, 330, 335, 344,
anterior cruciate ligament injury, 667 417, 499, 565, 568, 614, 649, 661 347, 349, 352, 356, 358, 360, 363,
anterior dislocation, 716 appendectomy, 444 365, 374–375, 378, 397, 408, 418,
anterior pituitary, 87, 89, 98, 109, 115–116, appendicitis, 356, 359, 383–384, 440, 443, 420, 423, 425, 437–438, 445, 454,
118, 128, 132–133 538 459–461, 465, 467–468, 470–471,
anteroposterior, 664, 700, 716, 718 appendix, 131, 444, 537 475, 479, 482, 484–485, 493, 498,
anthrax, 310–311 ar-hies, 198 508, 513, 520–521, 524, 535, 537,
antiandrogens, 15 arachnodactyly, 156 540–542, 545, 550, 559, 571,
antiarrhythmic, 582 arboviruses, 391 579–581, 585–586, 589, 594–596,
antibiotic resistance, 333, 380, 548–549, arc, 718–719 598, 608, 610, 612–614, 622,
585–586 ards, 373, 544 629, 632, 636, 666–672, 675, 679,
antibiotics, 5, 11, 18, 46, 48–50, 53, 58, arenavirus, 325 681–682, 685–686, 693, 701, 707,
79, 166, 196, 200–202, 213, 216, areola, 728 722, 732, 742, 759–760, 765, 774,
218, 221, 265, 277–279, 311, 315, arginine, 233, 236, 285, 636 785, 791, 801–802, 817, 819, 826
318, 323, 337, 343–344, 346, 348, arrhythmia, 219, 269–270, 328, 453, 582 ataxia, 97, 170, 177, 213, 217, 234–235,
359, 361, 374, 382, 385, 390, 403, arsenic poisoning, 245–246 239, 257, 274, 285, 298–299, 546,
408–409, 434, 461, 464, 467, 474, arterial blood gas, 247 579
513, 523, 528–529, 532–533, 535, arteriohepatic dysplasia, 163 ataxia-telangiectasia, 217
537, 541, 543, 545, 548, 550–551, arteriole, 644 atelectasis, 166, 483
553–554, 556–557, 587, 589–590, arthralgia, 60, 155, 227, 326, 351, 390, atherosclerosis, 56, 81, 256–257, 262, 268,
601, 635, 660, 706, 739, 776, 784, 412, 415, 418, 485–486, 538, 541, 342, 587
811, 821, 823, 827 543, 559–560, 562, 573 atherosclerotic, 259, 262
anticholinergic, 623 arthritis, 35–37, 47, 69, 122, 154–155, athetosis, 105, 179
anticoagulant, 125, 265, 437, 602, 650, 182, 190, 192, 196, 201, 226–228, atopic dermatitis, 10–11, 13, 200, 222, 497
762 231, 292–293, 343, 350, 354–357, atopic march, 219
anticonvulsant, 119, 178, 265, 566, 568, 359, 370–371, 418, 446, 481, atp, 240, 283, 292, 342, 346, 713
598, 641, 826 484–486, 526, 536, 549, 553, atresia, 167–168, 182, 499, 679, 786–787
antidepressants 254, 622, 641 589–590, 602, 604, 620–621, atrioventricular block, 267
antidiarrheals, 243 624–625, 627–629, 631–635, 637, atrophic gastritis, 361, 531
antidiuretic hormone, 110, 118 647–648, 650, 658–659, 664, 686, attenuated virus, 492
OSMOSIS.ORG 27
atypical antipsychotics, 83 basal metabolic rate, 128 bone marrow, 36, 137, 194, 197, 211, 213,
auspitz sign, 36 basaloid carcinoma, 767 229, 242–243, 245, 288–291,
autism spectrum disorder, 173, 177 basement membrane, 83, 153–154, 227 296–297, 302, 305, 349, 386, 392,
autoantibody, 64, 66, 126, 143, 302 bassen-kornzweig disease, 257 426, 433, 467, 531, 564, 580, 592,
autograft, 210 bcg, 459, 585–586, 809 595, 600–601, 604, 614, 677
autoimmune disorder, 41, 62, 143, 146, beckwith-wiedemann syndrome, 169, 171, bone marrow aspiration, 213
649, 653 677 bone marrow transplant, 137, 197, 211,
autoimmune hemolytic, 196–197, 223– bedsores, 56 213, 288, 290–291, 467
224, 434 bell’s palsy, 542 bone scan, 165, 591, 604, 662, 769
autoimmune hemolytic anemia, 196–197, benign prostatic hyperplasia, 799–800 bone tumors, 607, 609, 611, 613, 615, 701
223–224, 434 benzodiazepines, 249, 255, 292–293, 323, borborygmus, 363, 404
autoimmune hepatitis, 205, 489 621, 623 bordetella pertussis, 345
autoimmunity, 81, 205 beta blocker, 35, 120, 127–128, 141, 157, borrelia burgdorferi, 412, 515, 540
autonomic nervous system, 255 260, 644 borrelia species, 542
autosomal dominant osteopetrosis, 600 beta-lactamase, 369, 524, 529 botulinum toxin, 317, 622–623
autosomal recessive osteopetrosis, 600 biceps, 718 botulism, 316–317
av, 267, 540, 582, 604 bicornuate, 185 bouchard nodes, 661
avascular necrosis, 663 bile, 127, 141, 163–164, 256–257, 265, bow-legs, 688
avulsion, 55, 595, 667, 672 362, 380, 400, 523, 553, 556, 564, bowel, 59, 134, 138, 191, 228, 230,
axon, 334, 424 571 242–243, 263, 282, 302, 321, 344,
azotemia, 396, 521 bilharziasis, 573 402, 407, 441, 443, 449, 452, 538,
b cell, 143–144, 189, 204 biliary atresia, 499 703–704, 746, 750, 752, 754, 769,
ba, 343, 524–525 biliary colic, 442 790–791, 816
babesia, 412, 515, 519 bilirubin, 163–164, 254, 302, 305, 408, bowen’s disease, 29
bacillary angiomatosis, 524–525 419, 521, 544, 571, 779, 788, 816, bowenoid papulosis, 767
bacillus, 310–312, 385, 458–459, 809 828 bph, 799
bacillus anthracis, 310–311 bioterrorism, 311, 316, 347, 565, 568 brachial plexus, 778
bacillus cereus, 312 biotin, 14 brachycephaly, 167, 684
back pain, 510, 602, 625, 634, 682, 686, bisexual, 503, 508 brachydactyly, 693
690, 697, 700, 702, 704, 707, 735, bisphosphonate, 165, 591, 593, 598 brachytherapy, 742
739, 741, 766, 769, 810 bitemporal hemianopsia, 88 bradycardia, 126, 146, 735, 777, 826
bacteremia, 214, 354, 356, 370, 380–381, bk virus, 494 bradykinesia, 151, 179
407, 464, 529, 531, 544, 549–550, bladder, 151, 233, 245, 293, 494–495, brain abscess, 350, 402, 461, 468
553–554, 573, 775, 810, 820, 826 532, 551, 574, 703, 736, 752, brain parenchyma invasion, 439
bacteria, 11, 45, 51, 57, 190, 192, 195, 769–770, 790–791, 800–801, 805, brain stem, 490–491
197, 199, 203, 214, 246, 312–313, 808–809 brca, 100, 721, 746, 749, 752, 768
315–317, 320–321, 342, 345, 347, bladder cancer, 808 break-bone fever, 392
349, 352, 354, 357, 359–360, 362, blastomyces spp., 558 breast, 93, 95, 114, 159–160, 165,
369, 371, 373, 380, 382–383, 399, blastomycosis, 558–559, 563 173–175, 277, 282, 390, 501, 503,
405, 409, 447, 449, 455, 514–518, bleeding diathesis, 396, 413, 418 603, 720–731, 746, 748–750, 752,
520, 523, 538, 548, 550–552, 583, blepharitis, 15, 57, 138, 367 760, 784
587–588, 590, 635, 753–754, 809, blind, 95, 97, 285, 300, 343, 371, 390, breast abscess, 784
821, 825 447, 451, 545, 777, 822 breast cancer, 159–160, 165, 173–174,
bacterial infections, 192–193, 473, 649, blister, 17, 50, 56, 64–66 603, 720–722, 724–725, 727–728
659, 807 blm, 158–159 breast masses, 720–723, 725, 727, 729,
bacterial meningitis, 374 blood cell, 216, 255, 258, 282, 343, 408, 731
bacterial peritonitis, 529 414–415, 468, 485, 496, 528, 602, breast milk, 277, 282, 390, 501, 503, 784
bacterial pneumonia, 197, 354, 370, 473, 624, 664, 775, 778 breastfeeding, 116, 145, 265, 282, 510,
483, 579 blood clot, 658–659 605, 722, 784
bacterial prostatitis, 809–810 blood coagulation, 6 breech, 681–682
bacterial rhinosinusitis, 370 blood culture, 47, 58, 79, 276, 278–279, brenner tumor, 752
bacterial tracheitis, 478 349, 372, 374, 463, 538, 582, 820, breslow thickness, 24
bacterial vaginosis, 409, 738, 753–754, 825 bronchi, 206, 437, 439, 483
761, 775 blood group, 162, 208–209, 216, 330, 363, bronchiectasis, 166–167, 196, 386, 461,
bacteroides fragilis, 523 415 534
baker’s cyst, 658, 660 blood test, 47, 590, 604 bronchoscopy, 206, 355
balanitis, 634 blood transfusion, 336, 396, 412, 415, 486, bronchospasm, 219, 221, 791
baldness, 98, 113 503, 580–581 bronchus, 131
balloon tamponade, 737 blood urea nitrogen, 236, 246, 390, 500, brucella, 349, 351
barbiturates, 16, 285 714, 781, 800, 810 brucellosis, 349–350
bariatric surgery, 263, 303–304 blood-brain barrier, 245, 252, 302, 552 bruxism, 620–621
barium enema, 384 bloody show, 739 bubonic plague, 538
barium swallow, 442, 639 bloom syndrome, 158–159 buccal cellulitis, 45
barlow maneuver, 683 blount disease, 688 buccal mucosa, 480, 488
bartholinitis, 343 bmi, 738, 758, 778, 788, 791, 797 budd-chiari syndrome, 340
bartonella henselae, 524 body louse, 376, 542 bulbar poliomyelitis, 490
bartonella quintana, 376 body mass index, 758, 788, 791, 797 bulla, 64, 67
basal cell, 25, 767 bone density, 101, 114, 174, 264, 266, bullous, 17, 33, 50, 64–66, 223–224, 428,
basal cell carcinoma, 25–26, 767 588, 601, 603, 637 461, 546
basal ganglia, 179–180, 336–337, 462, bone fracture, 616 bullous pemphigoid, 64–66, 223–224
566 bone infections, 587 bun, 236, 246, 248, 254, 500, 714, 781,
28 OSMOSIS.ORG
800 cataract, 105, 149, 163, 182, 239, 567, 579, 581, 584, 743
bunyavirus, 327, 329 817–818 chest x-ray, 58, 60, 166, 189, 206,
burkitt’s lymphoma, 423 catecholamines, 4, 127, 135, 140, 782 276–277, 279, 309, 329, 343,
burn, 1–2, 5–6, 8–9, 19, 40, 467, 792 catheter, 318, 407–408, 549–551 365, 382, 384, 386, 428, 435, 442,
burn injury, 2 cauda equina syndrome, 703–705 450–451, 466, 469, 471, 483, 521,
bursa, 658–660 cavernous sinus, 88–89, 467 526, 529–530, 534–535, 538, 544,
bursitis, 618–619, 659–660 cavernous sinus thrombosis, 467 554, 562, 574, 581, 585, 656, 741,
c1 esterase inhibitor deficiency, 191 cavity, 220, 340, 402, 441, 493, 523, 542, 744, 765, 771, 819–820
c2 deficiency, 192 584, 791, 793, 796, 800 chiari malformation, 150
c3 deficiency, 192 cecum, 444, 454, 538 chickenpox, 429–431
c5-c9 deficiency, 193 celiac disease, 41, 96, 182, 200, 222, 302 child abuse, 641
c-reactive protein, 227, 329, 408, 525, 580, cell cycle, 304, 509, 614 childbirth, 52, 109, 127, 149, 156,
625, 643, 664, 754, 821 cellulitis, 45–46, 50, 54, 58, 214, 321, 168–169, 171, 185, 192–193,
ca, 92, 591, 597–603, 605–606, 713, 740, 354–357, 385, 405, 467, 526, 549, 202, 216, 235, 264–265, 267, 269,
745, 752, 794 555–556, 820 271, 315, 343, 371, 409, 412, 417,
cachexia, 180, 579 central hypothyroidism, 121, 125–126 420, 424–425 438, 459, 503, 553,
caffeine, 222, 644, 726, 801 central nervous system, 118, 149, 231, 576, 622, 679, 681–682, 688, 722,
cah, 73–74 293, 296–297, 332–333, 335, 337, 732–733, 735–736, 738–739,
calamine, 13, 431 386, 392, 430, 434, 461, 491, 499, 773–775, 778, 782, 785–786, 788,
calcaneus, 686 502, 511, 524, 552, 556, 558, 568, 801, 814–815, 817–818, 820, 822,
calcinosis, 640, 645, 653 786, 823 825–826
calcitonin, 91, 135, 137, 605 central nervous system infections, 332– childhood, 61, 73, 92, 109, 111, 113, 153,
calorie, 256, 277, 279 333, 335, 337 159–160, 169, 172, 177, 192, 202,
campylobacter jejuni, 358, 634 central/secondary hypogonadism, 93 213–214, 219, 231, 265, 271, 285,
cancer, 25–27, 29–30, 38–39, 60, 70, 86, cephalosporins, 46, 323, 356–357, 371– 425–426, 495, 682, 823, 827
90–92, 95–96, 98, 115, 136, 143, 372, 374, 528–529, 534–535, 539 chlamydia, 342–344, 372, 634, 753,
158–163, 165, 173–174, 196, 229, cerclage, 739, 773–774 755–756, 760, 803, 810, 822
475–476, 509, 603, 627, 720–722, cerebellum, 284, 511, 513 chlamydia trachomatis, 343–344, 755, 803,
724–725, 727–728, 741–742, cerebral, 84–85, 97, 185, 215, 236, 242, 810, 822
745–746, 748, 754, 766–770, 772, 248, 286, 302, 334–337, 340, choanal atresia, 167–168
791, 794, 808–809 386–387, 402, 406, 415, 451, 453, chocolate, 354, 356, 369–370, 572, 751,
cancer, bladder, 808 461–462, 503, 512, 535, 565, 572, 790
cancer, brain, 159 579, 650, 686, 738–739, 775–777, chocolate cysts, 751
candida, 33, 54, 188, 203, 461, 463, 465, 780, 787–788, 817, 825 choking, 281
503 cerebral aspergillosis, 461–462 cholangiocarcinoma, 571
candida albicans, 188, 203 cerebral edema, 84–85, 236, 242, 248, cholangitis, 340, 400, 571
candida esophagitis, 463 512, 565, 788, 825 cholecystitis, 350, 359, 400, 527, 531
candidiasis, 188, 198, 463–465, 503 cerebral palsy, 738–739, 775, 825 cholelithiasis, 138, 150, 256, 261
cane-cutter fever, 544 cerebritis, 355 cholera, 137, 362–363
caplan syndrome, 636 cerebrovascular disease, 256, 260–261 cholestasis, 163–164
carbapenems, 524, 527, 529, 534, 536 cerebrum, 284, 336 cholestatic hepatitis, 489
carbohydrate metabolism disorders, cervical cancer, 476, 741 cholesterol, 163–164, 256, 258–261,
238–239 cervical cerclage, 739, 774 298–299, 303, 434, 555
carcinoembryonic antigen, 135 cervical dystonia, 622 cholesterol, ldl, 260
carcinogenic, 241 cervical incompetence, 773 chondrocalcinosis, 630
carcinoid syndrome, 131, 303 cervical intraepithelial neoplasia, 741 chondromalacia, 687
carcinoid tumor, 131 cervical myoma, 796 chondrosarcoma, 616–617
carcinoma, 1, 9, 25–26, 29–32, 49, 69, 71, cervical vertebrae, 622 chorea, 179–180, 292–293
86, 90–92, 118, 134, 159–160, cervicitis, 343, 371, 409, 634–635 chorioamnionitis, 315, 552, 773, 775–776,
245, 361, 417, 721, 723, 725, 728, cervix, 315, 344, 425, 577, 736, 738–739, 785, 820, 826
740–742, 745–746, 751–752, 741, 754, 761, 773–774, 796 choriocarcinoma, 743–744, 763–764, 770,
767–768, 770, 813 ces, 243, 805 772
carcinoma in situ, 29, 721, 740 cesarean section, 732–733, 738, 760, 776 chorion, 776
cardiac arrest, 322, 582 cestodes, 338–339, 341 chorionic villus sampling, 74, 167, 178,
cardiac muscle, 336 chagas disease, 580–582 181, 183–185, 762
cardiogenic shock, 328 chancre, 545–546, 579 chorioretinitis, 326, 336–337, 394, 815,
cardiomyopathy, 125, 267, 269–271, 284, chancroid, 352–353, 545 818, 827–828
446, 518, 722, 778 chediak-higashi syndrome, 39, 212 choroiditis, 350
cardiopulmonary, 248, 328, 413 cheek, 167, 355, 484–485, 623 chromosome, 96, 132, 134, 148–150, 153,
carditis, 540–541 chemical burns, 3 158, 160–163, 167, 170–175, 177,
caries, 556 chemokine, 136, 394, 502 179, 181–184, 194, 204, 218, 269,
carpal tunnel syndrome, 108, 126, chemokine receptor, 394 271, 520, 608, 692, 729, 771
289–290, 636 chemoprevention, 723 chromosome disorders, 173, 175
cartilage, 231, 433, 587, 590, 605, chemotherapy, 28, 30, 86–87, 96, 100, chronic bacterial prostatitis, 809–810
616–619, 624, 626, 628, 630, 635, 130, 132, 137, 139, 142, 320, 333, chronic bronchitis, 173, 492
661–663, 689, 698, 705, 793 422, 428, 460–461, 464, 467, chronic fatigue syndrome, 426
cartilage tumors, 616–617, 619 494–495, 607, 609, 615, 722–723, chronic gastritis, 360–361
cat cry syndrome, 149 730, 740, 742, 744, 746–748, 750, chronic granulomatous disease, 214, 383,
cat-scratch disease, 524–525 752, 766, 768, 772 461, 464
catabolism, 128, 226, 259, 278–279, 661, chest pain, 224, 311, 341, 347, 365, 461, chronic granulomatous prostatitis, 810
782 466, 468, 480, 529, 538, 558, 562, chronic hepatitis, 417–421, 489, 517
OSMOSIS.ORG 29
chronic kidney disease, 102, 150, 377, 532, colorectal cancer, 160, 746 corn, 303
598, 605, 627 colposcopy, 476, 741–742 cornea, 161, 257, 260, 288–289, 385, 511,
chronic mucocutaneous candidiasis, 463 coma, 121, 125–127, 229, 235–236, 240, 534
chronic obstructive pulmonary disease, 386, 247–248, 253, 276, 298, 311, 335, corneal ulcer, 315
407, 470 341, 373, 395, 415, 446, 512, 523, coronal plane, 53, 141, 180, 230, 406, 609,
chronic osteomyelitis, 603, 607 565, 568, 776 670, 676, 701, 744, 771, 795, 800,
chronic urticaria, 62 comedones, 44–45, 49, 57 802, 811
chronic, delayed hypersensitivity, 228 comma-shaped rods, 358–359, 361, 363 coronary artery, 231, 259, 545
churg-strauss syndrome, 226 common bile duct, 141 coronary artery disease, 231, 259
chyluria, 455 common cold, 346 coronavirus, 365
ciliary dyskinesia, 166 common variable immunodeficiency, 196 corpus, 184–185, 286, 765, 767, 793, 797,
circulation, 5, 116, 131, 204, 260, 265, community-acquired pneumonia, 342, 354, 808, 815
441, 479, 515, 518, 542, 556, 407 cortex, 73, 76–77, 86, 135, 165, 453, 490,
573–574, 787 compartment syndrome, 6, 8, 711–714 611, 615, 619
circulatory system, 432 complement deficiencies, 190 cortical, 69, 86, 132, 179–180, 354,
cirrhosis, 52, 71, 163, 239, 264, 271, 333, complete androgen insensitivity, 95 588–589, 592, 597, 599, 606, 610,
417–418 complete blood count, 46, 60, 63, 65, 136, 612, 614, 777, 825, 828
classic melanoma, 27 189, 212, 227, 338, 343, 346, 381, corticosteroid, 13, 36, 52, 377, 382, 386,
classic msud, 235 423–424, 427, 528–529, 532, 534, 399, 402, 424, 461, 465, 510, 666
classic scabies, 378 536, 646, 678, 711, 744, 763, 794, cortisol, 4, 68–71, 73, 77–79, 87, 115, 117,
claudication, 617–618, 704 809 121, 133, 165, 268
clavicle, 608, 622, 694, 818 complete hydatidiform mole, 763 corynebacterium diphtheriae, 313
cleft lip, 113, 168, 185–186, 251 complication, 127, 317, 392–393, 408, coryza, 308, 478–480, 485, 491, 493
cleft palate, 97, 167, 185 466, 518, 636, 663, 672, 675, 707, cough, 19, 166, 205–207, 252, 308, 329,
cleidocranial dysostosis, 694 736, 784, 825, 827 336, 341, 343–347, 355, 365, 370,
cleidocranial dysplasia, 694–695 compression fracture, 697, 717 382, 384, 386, 402, 412, 435–436,
clitoris, 94 conception, 517, 582, 738, 761–762, 817 438, 442, 449, 461–462, 466,
clonic seizures, 776 conductive hearing loss, 166 468–469, 471–473, 478–480, 483,
clonorchis sinensis, 571 condyloma, 475–477 493, 517, 529–530, 538, 543–544,
clostridial gas gangrene, 320 condyloma acuminatum, 475 553–554, 558–560, 562, 564,
clostridium botulinum, 316 cone biopsy, 773 572–573, 584–585
clostridium difficile, 318 congenital adrenal hyperplasia, 73 counseling, 155, 174, 178, 180–181,
clostridium perfringens, 320–321 congenital cytomegalovirus infection, 815 183–184, 186
clostridium tetani, 322–323 congenital diaphragmatic, 689 coxiella burnetii, 517
clubfoot, 184, 491, 681, 785 congenital heart disease, 483 coxsackievirus, 204, 488, 713
coagulation, 3, 6, 61, 76, 79, 212–213, congenital hip dislocation, 682 crab louse, 376
221, 254, 265–266, 308, 320, 329, congenital hip dysplasia, 682 crabs, 572
350, 373, 389, 392, 395, 407–408, congenital hypothyroidism, 125 cradle cap, 14–15, 367
412–413, 534, 538, 548, 555, 580, congenital malformation, 292, 294, 679– cranial, 110, 156, 167, 237, 243, 315, 317,
714, 733, 735–736, 762, 775, 824 683, 685, 687, 689, 691, 804–805 322, 326, 333, 423, 430, 462, 467,
coarctation of aorta, 71, 175, 817 congenital rubella syndrome, 816 512, 540, 542, 565, 568, 597, 600,
cobalamin, 304–305 congenital syphilis, 545–546, 818–819 604, 621, 678, 694, 805, 825
cobb angle, 698–699, 702 congestive heart failure, 71, 122, 412, 485, cranial nerves, 322, 512
cocaine, 713, 735, 761 646 craniosynostosis, 684–685
cocci, 345, 349, 369, 380, 385, 518, conization, 742 craniotomy, 387
549–551, 556–557, 825 conjunctiva, 333, 344, 430, 447, 479, 492, creatine kinase, 269, 284, 544, 652, 712
coccidioides spp., 560 542 crepitus, 671
coccidioidomycosis, 560–561, 564 conjunctivitis, 19, 57, 252, 309, 329, crest syndrome, 640, 645
coccobacilli: aerobes, 345, 347 343–344, 354–355, 371, 397, 446, cretinism, 120, 281
coccus, 548 479–480, 536, 567, 581, 634–635, cri du chat syndrome, 149–150
codon, 162 755, 822–823 crohn’s disease, 440, 624
coeliac disease, 228 conn’s syndrome, 68–69, 71 croup, 478–479
coenzyme, 283, 285, 304 connective tissue, 35, 144, 152–157, 177, crouzon syndrome, 684
cognition, 151, 173, 177, 179–180, 183, 198, 321, 333, 639, 641–645, 647, crp, 46–47, 214, 227, 408, 525, 625, 637,
187, 242, 249–250, 293, 296, 305, 649, 651, 680, 686, 689, 718, 749, 643, 754, 821
422, 437, 439, 442, 454, 495, 579, 796 crs, 566–567
641 connective tissue disease, 642 cruciate ligament, 667–668
cognitive behavioral therapy, 641 connective tissue disorders, 152–155, 157, crusted scabies, 377–378
colchicine, 60, 436, 628, 630, 713 639, 641, 643–645, 647, 649, 651, cryosurgery, 26, 742, 770
colectomy, 319 689 crypt, 230, 242, 330, 359, 401, 404
colic, 191, 442, 627, 748 constipation, 68, 71, 82, 103, 121, 126, cryptococcus neoformans, 465
colitis, 214, 252, 318–319, 350, 384, 133, 135, 143–146, 148–151, 182, cryptorchidism, 95–96, 172, 174, 182–183,
402–403, 422–423, 624 281, 344, 372, 384, 425, 449, 491, 185, 679, 771, 801–802
collagen, 64, 131, 146, 152–154, 223, 231, 581, 646, 791, 797 cryptosporidiosis, 400
439, 596–598, 626, 636, 639, 645, constitutional delay, 96–97 csd, 524–525
661, 697, 750, 773 contact dermatitis, 12–13, 228–229 csf, 197, 302, 315, 326, 332, 334–336,
colon, 136–137, 154, 245, 318, 358–359, contact hypersensitivity, 228–229 354–356, 370, 374, 394, 396, 440,
402, 444, 450, 454, 537, 574 contraceptives, 59, 99, 726, 740–741, 758, 465–466, 471, 491, 496, 512, 519,
colonoscopy, 319, 384, 402, 537–538 792, 797 521, 544–546, 566, 568, 579–580,
colony-stimulating factor, 243 copd, 354, 370, 407, 470, 526, 529, 534 817, 819, 821, 824–826, 828
colorectal, 160, 320, 746 cor pulmonale, 71, 491, 574 ct scan, 7, 30, 52–53, 68–70, 76, 78–79,
30 OSMOSIS.ORG
86–87, 107–108, 111, 114, 117, deciduous teeth, 694 diaphragmatic hernia, 184, 689
129, 131, 133, 135–136, 138, 141, decongestant, 493 diarrhea, 61, 131, 133, 135, 137–138, 141,
157, 163, 166–167, 171, 207, 230, decubitus, 56, 669 158, 187–188, 195, 197, 200–201,
234, 243, 288–289, 333, 336, 338, deep vein thrombosis, 138 214, 222, 230, 234–235, 239, 245,
341, 380, 384, 402, 406, 435, 442, deficiency, 94, 112, 187, 191–193, 199– 252, 255, 265, 279, 302–305, 309,
451, 453, 462, 468–469, 472, 474, 201, 215, 236, 263, 265, 281–282, 312, 315, 318–319, 321, 329–330,
495, 512, 523, 526, 530, 532, 535, 285, 301, 303–304, 306 347, 359, 362–363, 365, 384, 389,
538, 558, 564, 570–572, 574, degeneration, 100, 161, 175, 257, 284– 394, 399–400, 402–404, 415, 427,
587–588, 590, 593, 604, 607–610, 285, 288, 290, 395, 429, 604, 615, 438, 441–442, 445, 449, 453–454,
612–613, 616–618, 628, 653, 654, 661, 707, 710, 718, 735 480, 485, 491, 499–500, 503, 519,
656, 662, 664, 678–679, 685, 690, degenerative disc disease, 697–698, 700, 527–528, 530–531, 536–538, 549,
692–693, 707–709, 740, 744–745, 703 571–573, 635, 646, 825
747–748, 750, 752, 765–767, 769, dehydration, 18, 61, 76–77, 82–83, 85, diarrheal syndrome, 312
771, 795, 802, 809–810, 813, 815, 104, 110, 138, 158, 277, 318, 330, diathesis, 395–396, 413, 418
825, 828 362–363, 399–400, 402–403, 483, dic, 79, 221, 328, 373–374, 389, 407–408,
cul-de-sac, 790 488, 499, 536, 627, 697, 739, 781 714, 733, 735, 762, 775, 824
curettage, 24, 26, 30, 43, 498, 593, 617, dehydroepiandrosterone, 76, 78, 87 dietary supplement, 303
732, 763, 765 dehydrogenase deficiency, 285 diethylstilbestrol, 760, 791, 797
cushing, 69–71, 88, 113, 160 delayed hypersensitivity, 228, 276 differential diagnosis, 483
cushing’s syndrome, 68–70, 86, 88, 133, delayed puberty, 96 digeorge syndrome, 105, 217–218
135, 165, 260, 602 delirium, 245, 395, 415, 503, 543 digital rectal exam, 769, 810
cushingoid, 70 deltoid, 513, 674 dilated cardiomyopathy, 125
cutaneous, 11, 24, 30, 33, 57, 62, 64, 84, delusions, 138, 179 dilation and curettage, 763
131, 133–135, 242–243, 259, 261, dementia, 131, 179–180, 182, 287, dilator, 8
311, 313–315, 352, 366–367, 373, 298–299, 304, 377, 503, 545–546 diphtheria, 211, 313–314, 323, 346
385–387, 402, 430, 432, 436, 438, demyelination, 81, 297–298, 339, 817 diphyllobothrium latum, 305, 339
445, 448–449, 451, 458–460, 464, denervation, 623 diplococci: aerobic, 369, 371, 373
467–468, 470–471, 475–476, 509, dengue hemorrhagic fever, 392 diploid, 743, 763
524, 534, 559, 646, 728, 817–818 dengue virus, 392 diplopia, 88, 117, 133, 224, 572
cutaneous fungal infections, 366–367 densovirinae, 484 dislocatable, 682
cutaneous leishmaniasis, 432 depression, 44, 49, 77, 113, 138, 179, 237, dislocated shoulder, 716
cutaneous mucormycosis, 467 245, 299, 306, 404, 503, 641, 680, dislocation, 154–156, 182, 251, 527,
cvid, 199, 201 701, 806 620–621, 680, 682–683, 715–717
cvs, 184–185 dermabrasion, 45 disorder, 41, 44, 49, 57–58, 62, 64, 69, 77,
cyanide poisoning, 246 dermatitis, 10–15, 33–34, 131, 138, 200, 83, 93, 95, 101, 110, 114, 123,
cyanosis, 79, 247, 311, 346, 407, 473, 479, 222, 228–229, 276–277, 304, 125, 132, 134, 143, 146, 153, 156,
483, 777, 826 366–368, 371, 376, 378, 438, 444, 162–164, 167, 170, 172, 175, 177,
cyclosporine, 12–13, 37, 230, 640 449, 465, 497–498, 562 182, 191–194, 196–197, 199–200,
cyst, 98–100, 165, 333–334, 336, 338, dermatographism, 62 204, 212–214, 223, 231, 233–234,
340–341, 404, 451, 576, 636, dermatome, 704 236–237, 239, 249, 254, 257, 259,
658–660, 718, 726, 751, 754, dermatomyositis, 652–654 283, 285, 287, 289–290, 298,
790–791, 793–795, 828 dermis, 9, 20, 25–27, 33–34, 43, 45, 47, 302–303, 305, 322, 503, 524, 555,
cystadenocarcinomas, 751 56, 64, 242, 353, 555 592, 594, 600, 621, 626, 631, 635,
cystectomy, 495, 794, 796 dermoid cysts, 746, 793 641, 649, 653, 673, 679–680, 689,
cystic hygroma, 184 dermopathy, 122, 124 692, 758, 790, 806, 811–812, 825
cystic mastitis, 725 desquamation, 9, 58, 242, 488 disorders of labor, 732–733, 735, 737, 739
cysticercosis, 338 developmental delay, 169–170, 172, 177, disseminated cutaneous sporotrichosis, 470
cystine, 233 182, 215, 249–250, 293–294, disseminated gonococcemia, 371–372
cystinuria, 233 297–299, 302 disseminated intravascular, 76, 79, 221,
cystitis, 214, 308, 380, 494–495, 526–527, developmental disorder, 270 308, 320, 328, 350, 373, 407,
529, 532–533, 551, 553, 576 developmental hip dysplasia, 682 412–413, 534, 538, 555, 714, 733,
cystitis, interstitial, 214, 308 dextrinoses, 267 735, 762, 775, 824
cystosarcoma phyllodes, 729 dextroposition, 185 disseminated intravascular coagulation, 76,
cystoscopy, 495, 800, 810 dextrose, 277, 285, 559 79, 221, 308, 320, 350, 373, 407,
cytomegalovirus, 188, 197, 203, 422, 463, dgs, 105, 217–218 412–413, 534, 538, 555, 714, 733,
503, 567, 782, 815 dhea, 76, 78 735, 762, 775
cytoplasm, 31, 88–89, 91, 143, 269, 301, diabetes, 6, 41, 46–47, 50, 52, 54, 56, 69– disseminated mucormycosis, 467
304, 327, 388, 391, 419, 478, 489, 70, 80–86, 93, 98, 108, 110–111, disseminated/invasive candidiasis, 463–464
497, 499, 502–503, 512, 520, 628, 122, 138, 145, 150, 162, 172, 174, dissociation, 435
677, 742, 746, 749, 752, 770, 772, 228, 260, 262, 333, 394, 407, 464, distal arthrogryposis, 679
794 526, 533–534, 551–552, 554, 584, diuresis, 81
cytosine, 169 587–589, 602, 627, 629–630, 661, diuretic, 72, 83, 102, 111, 119, 260, 262,
d-dimer, 79 738, 761, 777–778, 784–786, 788, 801
dactylitis, 36, 625, 634 799, 806, 817 diurnal, 579, 620
dander, 219 diabetes insipidus, 110, 394 diverticula, 151, 449, 800
dandruff, 14, 367 diabetes mellitus, 41, 46–47, 50, 56, diverticulum, 183
danlos syndrome, 152, 154–155, 698–699, 80–83, 85, 98, 111, 122, 138, 145, dizziness, 119, 210, 248, 445, 473, 541,
773 150, 162, 174, 228, 260, 464, 584, 543, 568, 697, 743
dcis, 721 602, 627, 629, 761, 778 dna, 8, 12, 25, 27, 148, 158–159, 161–
de novo lump, 26 diabetes mellitus type 1, 81 162, 169–170, 172, 178, 203, 211,
deafness, 153, 185, 300, 481, 545 dialysis, 154, 312, 329, 390, 549–550, 714 218, 241, 283–284, 301, 304, 308,
OSMOSIS.ORG 31
332–333, 335–336, 353, 378, 402, ecg, 105, 127, 246–247, 249, 269, 271, 391, 393, 418, 421, 430, 499, 512,
404, 409, 417–418, 422, 424, 429, 290, 396, 582, 788 524, 738, 777, 788
431–433, 459, 475, 484, 486, 494, echinococcosis, 340 enchondroma, 616
496–497, 501–502, 509, 514, 598, echinococcus granulosus, 340 end-stage renal disease, 153
614, 626, 645, 649, 693, 741, 761, echocardiography, 151, 271, 380, 518, endocrine disorders, 165, 602
763, 815, 819, 823 521, 535, 581, 690 endocrine tumors, 68, 86–87, 89, 91
dna polymerase, 378, 417, 509 eclampsia, 736, 776, 780, 787–788 endocrinopathy, 164–165
dna repair, 8, 614, 741 ecstasy, 254 endodermal sinus tumor, 746
dna replication, 148, 158–159, 161–162, ect, 281, 301 endometrial biopsy, 745
484, 494 ectoparasites, 375, 377, 379 endometrial cancer, 745
dna sequence, 162 ectopic, 69–71, 107–108, 118, 135, 157, endometrial hyperplasia, 745
dorsum, 12, 426, 428 343, 445, 743, 751, 754, 759–761, endometriosis, 746, 749, 752, 760,
douching, 409, 760 790, 792 790–792
down syndrome, 181, 183, 377, 663, 801 ectopic pregnancy, 343, 759–761 endometritis, 343, 383, 409, 555–556,
dr, 81, 122, 143, 635, 643 eczema, 10–11, 13, 15, 40, 46–47, 50, 65, 753, 775
drug resistance, 508 69, 198, 202–203, 219, 237, 282, endometrium, 733, 745, 752, 754,
dry eyes, 647 722, 728 757–759, 796
dry mouth, 317, 399, 623 edc, 783 endonuclease, 309
dry skin, 11, 143–146, 182, 274, 399 edwards syndrome, 183 endophthalmitis, 350, 386, 451, 529
duchenne muscular dystrophy, 701 eeg, 394, 566, 580 endoscopy, 133, 142, 450, 571, 646
ductal carcinoma in situ, 721 ef, 311, 313, 533 endothelium, 78, 81, 209–210, 215, 228,
ductus, 787, 817 effacement, 739 328, 342, 389, 392, 407, 415, 422,
ductus arteriosus, 787, 817 ehec, 527–528 479, 514–515, 518, 520, 527, 544,
dumb rabies, 512 ehlers-danlos syndrome, 154–155 636, 776, 787
duodenitis, 449 ehrlichia, 518–519 energy parasites, 342
duodenum, 132, 137, 141, 442, 449–450, ehrlichiosis, 518 entamoeba histolytica, 402–403
571–572 eiec, 527–528 enteric infectious botulism, 317
dysarthria, 252, 257, 299–300 ejaculation, 576, 766, 769, 805–806, 808 enteritis necroticans, 320–321
dysentery, 359, 402, 527–528, 536 elbow, 470, 653, 660, 680–681, 717, 719 enterobacter, 51, 526, 809
dysgerminoma, 746 elbow joint, 717 enterobiasis, 444
dyskinesia, 166 electric shock, 716 enterobius vermicularis, 444
dyslipidemia, 256–257, 259, 261 electrical burns, 3 enterococcus, 380–381, 825
dysmenorrhea, 791–792, 797 electrocardiogram, 690 enterocolitis, 134, 222, 441, 449, 499,
dyspareunia, 33, 101, 352, 371, 576, electrodesiccation, 24, 26 537–538, 550, 782, 818, 826
740–741, 745–746, 748, 750, 752, electroencephalogram, 580 enteropathy, 632
791, 793, 797 electrolyte, 74, 76, 85, 134–135, 138–139, enterovirus, 487
dyspepsia, 571, 714 242–243, 245–246, 276–279, enzootic, 458, 565, 568
dysphagia, 33, 142, 146, 179–180, 224, 311–312, 331, 363, 390–391, enzyme-linked immunosorbent assay, 289,
299–300, 314, 355, 464, 488, 512, 399–400, 418, 536, 544, 713–714, 317, 341, 361, 394, 396, 402, 433,
581, 640, 646, 652–656, 698 781 480, 514, 530, 568, 573, 582
dysplasia, 110, 162–165, 288, 483, 592– electrolyte imbalances, 138, 277, 279, 363, eosinophil, 210, 453, 823
593, 681–683, 687–688, 692–695, 714 eosinophilia, 65, 219, 340, 436, 440, 442,
706, 725, 741 electromyogram, 317 448, 453, 455, 462, 561, 571,
dysplastic nevus, 27 electron microscopy, 154, 166, 309, 325, 573–574
dyspnea, 124, 133, 146, 166, 182, 184, 364 epec, 527–528
206, 224, 248, 252, 259, 285, 311, electrophoresis, 258 epidemic keratoconjunctivitis, 308
336, 341, 345, 355, 357, 365, 370, elephantiasis, 455 epidemic typhus, 376
382, 386, 390, 436, 438, 442, 449, elisa, 289, 321, 329, 341, 351, 361, 365, epidermis, 9, 11, 20, 24–25, 27, 34–36, 43,
461, 466, 471, 473, 529–530, 538, 394, 396, 402, 433, 436, 450–451, 50, 64, 66–67, 242, 353, 424, 728
541, 559, 562, 564, 572, 574, 579, 453, 455, 480, 500, 506, 510, 514, epidermolysis bullosa, 65–66
581, 584, 698, 743, 771, 788 538, 544, 568, 571, 573–574, 582 epidermotropic theory, 728
dystocia, 736, 778 em, 540–541 epididymis, 95, 559, 803–804
dystonia, 151, 179, 285, 292–293, 299, embolism, 138, 581 epididymitis, 350, 371, 753, 755, 803–804,
622 embolization, 734, 737, 798, 809, 813 807
dysuria, 343–344, 352, 371, 380, 425, embryo, 249, 761, 764 epididymo-orchitis, 803
464, 495, 526, 529, 551, 574, 576, embryonal carcinoma, 770 epidural, 697, 705
584, 753–756, 766, 769, 791, 800, emesis, 279, 395, 441, 488 epiglottis, 355, 439
803, 810 emetic syndrome, 312 epiglottitis, 354–356
e. coli, 239, 333, 335, 527–528, 803, 807, emg, 284, 317, 323, 652, 654–656 epilepsy, 284
809, 825 emphysema, 52, 173, 207, 370, 461 epinephrine, 77–78, 84, 140, 205, 219,
ear, 14, 153, 167, 198–199, 201–202, 231, empyema, 350, 354, 356, 385–386, 526, 221, 479
288, 290, 322, 355, 370, 435, 462, 529, 554 epiphysis, 165, 307, 594, 597, 663–664,
493, 533, 542, 597, 678, 693–694 enanthem, 427, 488 687–688
ear infection, 693 encephalitic rabies, 512 episiotomy, 736
ear, external, 167 encephalitis, 315, 326, 332–333, 350, 394, epispadias, 166, 804–805
early-onset sepsis, 826 422, 425, 430, 434–435, 439, 446, epistaxis, 203, 462, 468, 543
eastern equine encephalitis virus, 565 453, 473, 480–482, 503, 511, 519, epithelial, 24, 64–66, 137, 161, 166, 209,
eating disorders, 757 521, 565–566, 568, 572 228–229, 252, 308, 328, 330,
ebola virus, 388–390 encephalomyelitis, 480 335, 343, 345, 352, 358, 360, 362,
ebv, 422–424 encephalomyopathy, 283–284 377–378, 380, 389, 399–400, 402,
ecchymosis, 675 encephalopathy, 110, 245, 253, 285, 346, 409, 429, 434, 448, 473, 475, 479,
32 OSMOSIS.ORG
483, 514, 555, 559, 571, 724–725, 250, 258, 285, 317, 338, 343, 347, fistula, 405
727, 743, 751–752, 754, 791, 794, 385, 392, 439, 442, 445–447, 459, fitz-hugh-curtis syndrome, 343, 754
799 533–534, 540–542, 584, 816, 823 flat feet, 685
epithelial hyperplasia, 559, 571, 725 eye infections, 533–534 flaviviruses, 391, 393, 395, 397
epithelium, 12, 39, 44, 90, 123, 166, 242, eye invasion, 439 flexible pes planus, 685
320, 330, 334–335, 342, 345, eyelid, 18, 134–135, 167, 220, 260, 344, flexion, 249
354, 359–360, 369, 371, 373, 401, 446, 498, 581, 822 flow cytometry, 197, 216, 510
434, 475, 481, 576, 724–728, 741, fabry disease, 295–296 flu, 506, 784
751–752, 768, 799 facial nerve, 323, 423, 430, 459 fluorescence in situ hybridization, 169, 172,
epstein-barr virus, 422–423 facial nerve paralysis, 459 183–185
equinus foot, 491 facies, 126, 133, 135, 151, 159, 165, fluorouracil, 2
erectile dysfunction, 87, 89, 799, 806, 808 176–177, 276 fmrp, 176–177
ergot, 254, 737 failure to thrive, 125, 149, 183, 187, 195, folate, 234, 251, 301–302, 304
erysipelas, 45–47 230, 235, 240, 257, 271, 302, 600 foley catheter, 318
erythema, 1, 3, 9, 14, 16–17, 19–20, 45– fainting, 346 folic acid, 277, 294, 301–302, 633, 637,
46, 52, 56–61, 63, 133, 159, 222, fallen arches, 685 761
227, 229, 242, 314, 347, 355, 367, fallopian tube, 754, 759–761, 795 follicle, 22, 44, 48, 96, 98, 107, 115, 123,
380, 386, 406, 435, 468, 484–486, familial hyperaldosteronism, 71 145, 165, 174, 376, 738, 749, 758
488, 521, 538, 540–541, 549–550, familial hypercholesterolemia, 256, 259 follicle-stimulating hormone, 96, 107, 115,
556, 560, 562, 576, 607–608, 627, familial mental retardation, 176 738
646, 653, 722 fas, 229, 249 follicular adenocarcinoma, 91
erythema infectiosum, 484–486 fascia, 51, 53 follicular thyroid, 91–92
erythema multiforme, 16–17, 19 fasciitis, 46–47, 51–53, 526, 549, 555 folliculitis, 48–49, 444
erythema multiforme major, 17 fasting blood glucose, 87 fontanelle, 251, 373, 427, 565, 568, 605,
erythema multiforme minor, 17 fasting hypoglycemia, 268 694–695, 820, 824–825
erythema nodosum, 59–60, 538, 560, 562 fat soluble vitamins deficiency, 263 food allergy, 202, 222
erythroblastosis, 224 fatty acids, 44, 84, 121, 583 food poisoning, 312, 320–321
erythroblastosis fetalis, 224 febrile, 315, 325, 392, 415, 426, 480, 485, foodborne botulism, 317
erythrocyte, 46, 60, 63, 214, 227, 408, 488, 497, 517–518, 520–521, 530, foramen, 150, 600, 693
411, 413–414, 434, 461, 522, 525, 542–543, 566–567 foramen magnum, 600, 693
559, 561, 563, 580, 625, 643, 664, febrile seizure, 415, 488 forbes disease, 270
754, 775 feces, 252, 317, 321, 325, 328, 335, 400, forceps, 736, 773
erythromycin, 353, 359, 435, 525, 823 437, 452, 517, 522, 524, 537, 542, forearm, 62, 104, 220, 711
erythroplakia, 767 582 foreskin, 805
erythroplasia of queyrat, 767 felty syndrome, 636 fornix, 792
erythropoietin, 243, 601 female genitourinary cancers, 740–741, fracture, 56, 103, 165, 346, 589, 591–592,
eschar, 56, 311 743, 745, 747, 749, 751 595–596, 598, 602–603, 607, 610,
escherichia coli, 51, 79, 332, 527 femoral anteversion, 691 614, 616, 618, 663, 667, 671–672,
esophageal dysmotility, 640, 645 femoral artery, 594 674–675, 687–688, 697–698, 701,
esophagitis, 142, 219, 222, 425, 463–464, femur, 160, 164–165, 175, 296, 592, 594, 704, 707–709, 711, 717
515, 646 604, 607–615, 618, 671, 676, 682, fragile x syndrome, 100, 176, 178, 758
esophagus, 464, 467, 570, 640, 653–654, 691–693 francisella tularensis, 347
656 fertility, 166, 174, 449, 750, 752, 757, 790, free radical, 520
essential fructosuria, 238 792–793, 797 frontal lobe, 406
estrogen, 62, 69, 95–97, 100–101, 109, fertilization, 101, 738 frostbite, 1, 3, 5–7, 9
116, 175, 178, 260, 262, 601–602, fetal alcohol syndrome, 249–250 fsh, 96–101, 107, 109, 115–116, 165, 174,
721, 723–724, 745, 758–759, fetal development, 136, 785–786 758, 802
791–792, 797 fetal growth restriction, 422, 782, 817 ftt, 183, 187, 195, 235, 239–240, 271
estrogen replacement therapy, 178, 759 fetal hydantoin syndrome, 251 fulminant meningococcemia, 373–374
eswl, 233 fetal movement, 785 fundus, 737
etec, 527–528 fetus, 15, 39, 73, 173, 188, 202, 224, 249, fungal infections, 213, 366–367, 460–461,
ethylene glycol poisoning, 248 252, 274, 325, 396, 485–486, 580, 463, 465, 467, 469, 471, 558, 825
euphoria, 248 679–680, 732–734, 736, 760–761, fungal meningitis, 465
eustachian tube, 693 764–765, 775, 778, 781–782, fungus, 14, 366–367, 461, 465, 470, 559
euthyroid, 121, 128 785–787, 814–816, 827 funnel chest, 689
euthyroid sick syndrome, 121 fgf, 87, 97 furious rabies, 512
evolution, 162, 194 fiber, 308 furunculosis, 48, 377
ewing’s sarcoma, 160, 608–609 fibroadenoma, 724 fusiform, 36
exanthem, 427, 479, 488 fibrocystic breast changes, 725 g6pd, 416, 521–522
excess vitamin a, 274 fibroid, 796 g protein, 164
excess vitamin d, 275 fibroma, 749 gag, 287, 289, 502, 509
exocrine, 647 fibromyalgia, 641 galactose, 238–239, 527
exogenous, 62, 69–70, 74, 93, 99, fibrous dysplasia of bone, 592 galactosemia, 239
120–121, 148, 260, 501, 526 fibula, 675 galeazzi sign, 683
exon, 179 filaments, 382–383, 385, 387 gallbladder, 265, 571, 584
exophthalmos, 122, 124 filariasis, 455 gallium, 245
external ear, 14, 167 filoviruses, 388–389 gamete, 148–150
extracorporeal shock wave lithotripsy, 233 fine needle aspiration, 92 gamma knife, 88–89, 134
extrapulmonary disease, 434, 530 fish, 148–149, 151, 169–170, 172, ganglion, 135, 430
extrapulmonary tuberculosis, 583–584 183–185, 305 gangrene, 51, 56, 245, 320–321, 357, 442,
eye, 39, 122, 149, 153, 179, 212, 220, fish tapeworm, 305 640, 644
OSMOSIS.ORG 33
gardner syndrome, 90 gestational hypertension, 779 growth factor, 87, 92, 108, 156, 259, 377,
gardnerella vaginalis, 409, 753 gestational trophoblastic neoplasia, 765 392, 448, 632, 641, 692, 721, 738
gas, 52–53, 85, 206–207, 245, 247, gi tract, 131, 191, 317, 359, 451–452, growth hormone, 87–89, 107, 112, 115,
320–321, 404, 523, 535, 555–556, 463–464, 467–468, 523, 645, 748 132, 165, 172, 175, 663, 817
636, 809 giant cell tumor of bone, 610–611 growth hormone deficiency, 112
gas gangrene, 320–321 giant-cell arteritis, 228, 643 gsd ia, 268
gastrectomy, 263, 304 giardia lamblia, 201, 403–404 gsd ib, 268
gastric, 132–133, 138, 141–142, 196, 249, giardiasis, 403–404 gsd ic, 268
302, 304, 315, 318, 359–361, 423, gigantism, 87, 111–113, 165 gsd iiia, 270
441, 452, 509, 531, 536, 748, 781 gilbert syndrome, 253 gsd iiib, 270
gastric atrophy, 304 gingiva, 428 gsd iiic, 270
gastric cancer, 196, 509 gingivitis, 214, 433 gtn, 763
gastric carcinoma, 361 glans, 33, 36, 352–353, 425, 767–768 guanine, 87, 293, 592, 627
gastrinoma, 132–134, 141–142 glaucoma, 70, 447, 817–818 guillain-barré syndrome, 223–224, 359,
gastrinoma syndrome, 141 gliosis, 239 394, 396, 423
gastritis, 360–361, 531 globoid cell leukodystrophy, 297 guinea worm, 445
gastroenteritis, 214, 222, 308, 315, 330, glomerulonephritis, 47, 50, 190, 192–193, guthrie test, 237
359, 441, 499, 531 226, 340, 377, 418, 555, 648, 650 gvhd, 188, 228–229
gastrointestinal disorders, 696 glossitis, 138, 224, 292, 294, 302, 305, gynecology, 740, 796
gastrointestinal infections, 282, 399, 401, 356 gynecomastia, 87, 89, 114, 174, 771
403, 537 glucagonoma, 132–134, 137–139 h. pylori, 360
gastrointestinal mucormycosis, 467 glucocorticoid, 17, 41, 44, 69, 74, 77–79, haemophilus ducreyi, 352
gastrointestinal tract, 61, 215, 264–265, 83, 86, 107, 117–118, 121, 127, haemophilus influenzae, 354
305, 338, 399, 490 166, 194, 208, 214, 227, 260, 262, hair follicle, 48, 376
gastroparesis, 82, 499 529, 628, 630, 635, 637, 654, 659, hair-related diseases, 21, 23
gastroschisis, 679 672 hallux, 182, 673
gastrostomy, 168 glucose, 52, 70, 78–85, 87, 99, 108, hallux valgus, 673
gaucher’s disease, 296–297 133–134, 137–139, 238, 254, hamstring, 673, 708
gbs, 552–553, 820–821, 825–826 257, 268, 270–272, 277, 317, 320, hand, foot and mouth disease, 488–489
gct, 770, 772 326, 333, 362, 369, 374, 408, 436, hantavirus, 328
gene expression, 171, 677 440, 466, 471, 521, 527, 627, 636, hard palate, 428
gene testing, 154 660, 775, 777–779, 783, 806, 821, hartnup disease, 233
gene therapy, 188, 288, 295–296, 298 825–826 hashimoto’s thyroiditis, 41, 125–126,
general paresis, 546 glucose tolerance test, 84, 99, 108 143–145, 228
genetic counseling, 181, 183–184, 186 glucose-6-phosphate, 268, 521 hav, 489–490
genetic disorders, 152, 181, 661 glucose-6-phosphate dehydrogenase, 521 hay fever, 11, 219–220
genetic mutations, 27, 29, 38, 87, 102–103, gluteal, 51, 711 hbv, 417–421
112, 162–163, 165–167, 177, 264, gluten, 281 hcg, 99, 123, 183–185, 743–744,
740 glycemic index, 99 746–747, 750, 752, 763–765, 770,
genetic screening, 190 glycogen storage disease, 268–272 772, 781
genital, 33, 73, 95, 114, 343, 352–353, glycogen storage disease type i, 268 hdl, 256, 261
372, 424–426, 433, 475, 502, 545, glycogenoses, 267 hdv, 421
552, 576–577, 736, 753, 756, 767, glycosaminoglycan, 122, 618 head louse, 376
804, 815, 820, 822–823 goiter, 122, 126, 128–129, 143–147, 281 headache, 34, 47, 68, 71, 79, 88–89, 108,
genital herpes, 425–426, 545 gonad, 97 111, 113–115, 117, 121, 126,
genital warts, 475, 767 gonadotropin, 93, 96, 99–100, 109, 165, 133, 140, 166, 206, 234, 236, 242,
genitalia, 61, 73–74, 94–96, 173–174, 801, 183, 743, 760, 770, 781, 792 247–248, 252, 275, 309, 315, 326,
805 gonococcal ophthalmia neonatorum, 329, 332–333, 335–336, 341,
genitourinary, 149, 178, 181–182, 266, 371–372 351, 359, 365, 370, 373, 389, 392,
308, 343, 350, 371, 383–384, 523, gonococcal urethritis, 756 394–395, 412, 415, 430, 435,
527, 533, 556, 558, 573, 576, 634, gonorrhea, 371–372, 376, 760 439–440, 446, 462, 466, 471, 473,
678, 740–741, 743, 745, 747, 749, goodpasture syndrome, 223–224 481, 483, 485, 488, 490–491, 493,
751, 753, 755, 766–767, 769, 771, gorlin syndrome, 25 512, 515, 517, 519, 521–522, 530,
799, 801 gout, 267–268, 293, 626–628, 630–631, 536, 541, 543–544, 546, 549, 554,
genitourinary tract infections, 527, 573, 659–660 562, 565, 568, 572–573, 579, 581,
753, 755 graft, 188, 208–211, 228–230 587–588, 621, 641, 643, 678, 684,
genome, 149, 159, 327, 362, 388, 391, graft-versus-host disease, 229–230 697, 743, 777, 788
396, 422, 473, 475, 484, 487, gram variable, 409 hearing aids, 154
501–502, 509, 518, 565, 568 granulation, 384, 433, 822 hearing loss, 151, 153–154, 166–167, 175,
genotype, 95, 177, 418, 497 granulocyte, 197, 243, 519 182, 249, 290, 296, 355, 390, 430,
genu valgum, 687 granuloma, 214, 228–229, 444, 451, 562, 522, 542, 545, 592, 596–597, 600,
genu varum, 605, 687–689 583, 586 694, 815, 817–818, 827–828
germ cell, 162, 173, 743, 746, 770 granulomatous amebic encephalitis, 332 heart failure, 71–72, 122, 127, 269, 290,
germ cell ovarian tumor, 746 granulomatous prostatitis, 809–810 407, 412, 435, 438, 485, 519, 579,
germ cell tumor, 173, 770, 743, 746 granulosa cell tumor, 771 581, 604, 646
german measles, 566 granulosa-theca cell tumor, 749 heart murmur, 549
gestation, 118, 178, 264–265, 302, graves’ disease, 122–124, 143, 223–224 heart valve, 131, 210, 289–290
680–681, 733, 735–736, 738–739, gray matter, 284–285, 777 heat-labile toxin, 527
743, 761, 763, 773–774, 778–779, group a streptococcus, 36, 52, 555 heat-stable toxin, 527
781–782, 787, 816, 819, 827 group b streptococcus, 552, 739, 820, 822 heberden’s node, 661
gestational diabetes, 83, 93, 98, 777 growth chart, 778 helicobacter pylori, 360
34 OSMOSIS.ORG
hemangioma, 185 hereditary fructose intolerance, 240 htlv-1, 509–510, 652, 654, 656
hemarthrosis, 667, 676 hereditary nephritis, 153 human chorionic gonadotropin, 743, 760,
hematemesis, 245, 390, 468 hernia, 171, 184, 251, 601, 689, 801 781
hematocrit, 329, 363, 390, 393, 413, 737, herniation, 333, 465, 697, 703 human endogenous retroviruses, 501
779, 781, 783 heroin, 311 human exogenous retroviruses, 501
hematologic infections, 411, 413, 415 herpangina, 488 human herpesvirus, 8, 34, 422–423,
hematoma, 622, 716, 735–737, 778, 788 herpes, 11, 16–17, 48, 353, 422, 424–427, 426–427
hematopoiesis, 301, 304, 433, 567, 600, 430–431, 463, 503, 515, 545, 567, human leukocyte antigen, 230
817 756, 815, 822–824 human monocytic ehrlichiosis, 518
hematuria, 153, 224, 233, 248, 266, herpes labialis, 425–426 human papillomavirus, 1, 475
292–293, 329, 341, 381, 395, 495, herpes simplex virus, 11, 48, 353, 422, human parainfluenza viruses, 478
544, 551, 572, 574, 628, 648, 678, 424–425, 567, 756, 822–823 human plague, 537
741, 766, 769, 791, 800, 803 herpes zoster, 430–431, 503 human roundworm disease, 451
hemianopsia, 88, 777 herpesvirus, 34, 422–423, 425–427, 429, human t-lymphotropic virus, 509
hemiparesis, 462, 495 431, 815 humerus, 160, 608, 692, 716, 718
hemiplegia, 701 heterosexual, 502 humor, 187–188, 195, 197, 199, 201, 203,
hemizygous, 150 heterotopic pregnancy, 759 208–209, 369, 390, 425, 555, 652
hemochromatosis, 115, 602, 630, 661 heterozygous, 259, 692, 694 hunter syndrome, 287, 289
hemodialysis, 249, 254 heterozygous fh, 259 huntington’s disease, 179–180
hemoglobin, 52, 82, 84, 302, 329, 352, hfmd, 488 hurler syndrome, 287, 289–291
413–414, 738, 778 hga, 515 hydatidiform mole, 763–764, 781
hemoglobin a1c, 778 hhs, 80, 83 hydrocele, 455–456, 803, 807
hemoglobinuria, 194 hhv, 34, 427 hydrocephalus, 149, 166, 180, 184, 287,
hemolysis, 194, 239, 245, 302, 305, 320, hib, 190, 354–356 289–290, 326, 335–336, 355, 422,
412, 522, 527, 552–553, 555, 788, hidradenitis suppurativa, 49 464, 600, 693, 825, 827–828
820 high ankle sprain, 674 hydronephrosis, 233, 464, 800
hemolytic anemia, 196–197, 223–224, high blood pressure, 68, 71, 108 hydrops fetalis, 288, 485
416, 434, 528, 531, 536, 545, 580, hirschsprung disease, 134 hyper igm syndrome, 197, 469
817–818 hirsutism, 87, 98, 165, 749, 758 hyperactivity, 124, 127, 149, 175, 177,
hemolytic disease of the newborn, 223 histamine, 8, 219–221, 223, 345, 375 249–250, 255, 287, 323, 603, 734
hemolytic-uremic syndrome, 536 histiocytosis, 110 hyperaldosteronism, 68–69, 71–72, 160
hemophagocytic lymphohistiocytosis, 213 histologic chorioamnionitis, 775 hyperbilirubinemia, 246, 418, 778
hemoptysis, 224, 311, 340–341, 386, 449, histoplasma capsulatum, 562 hypercalcemia, 102–104, 133–134,
461–463, 466, 468, 471, 559–560, histoplasmosis, 461, 562–563 150–151, 275, 363, 510, 768
562, 572, 584, 743, 771, 791 hit, 635 hypercalciuria, 104, 106, 133, 135,
hemorrhage, 26, 77–79, 88–89, 115–119, hiv, 14, 18, 46–47, 52, 54, 260, 262, 276, 150–151
215, 242, 265–266, 306, 311, 278–279, 333, 336, 343, 352, hypercholesterolemia, 256, 259–260
328–329, 335, 369, 373, 390, 392, 354, 359, 367, 386, 399–400, 402, hypercoagulable state, 649, 808
395, 418, 450, 453, 461, 514, 521, 407, 409, 412, 418, 422, 425, 428, hypercortisolism, 87
542, 544, 600, 711, 729, 732–738, 460–461, 463–466, 469–470, 475, hyperemesis gravidarum, 123, 764, 781
760, 775, 786, 788, 793–795, 825 495–496, 501–503, 506, 508–509, hyperglycemia, 80–83, 108, 111, 138, 363,
hemorrhagic shock, 732 524, 545–546, 554, 576, 584, 589, 762, 777–779
henoch-schönlein purpura, 226 634, 652, 656, 713, 740–741, 767 hypergonadotropic hypogonadism, 73, 93,
hepadnaviridae, 417, 419, 421 hiv infection, 354, 386, 464, 496, 502–503 96, 100
heparin, 8 hiv-1, 502–503, 506 hyperhidrosis, 48
hepatic, 137, 237, 240, 249, 253, 257– hiv-2, 502–503, 506 hyperimmunoglobulin e syndrome, 198
258, 260, 271, 333, 341, 383, 395, hiv/aids, 18, 333, 336, 359, 367, 407, 422, hyperkalemia, 77, 84–86, 390, 714
414, 418, 421, 424, 489, 515, 517, 425, 460–461, 465, 475, 740–741 hyperkeratosis, 13, 30, 55, 245, 295, 448,
519, 522, 531, 544, 649, 743, 780, hla, 18, 81, 122, 143, 208–210, 230, 461, 455, 477, 767
787–788, 816 536, 624, 629, 632, 634–635, 643 hyperlipidemia, 256–257, 259–262,
hepatic encephalopathy, 253, 418, 421 hm, 763 267–268, 806
hepatitis, 197, 205, 227, 253, 308, 347, hme, 518 hypermagnesemia, 363
350, 394–395, 417–421, 423, 451, hodgkin’s lymphoma, 585 hypernatremia, 110
489–490, 517, 542, 544, 584, 824 homocysteine, 234, 304 hyperosmolar hyperglycemic state, 80, 83
hepatitis a virus, 489 homocystinuria, 234 hyperparathyroidism, 102–105, 133–135,
hepatitis b virus, 417 homosexual, 502–503 264, 599, 602, 605–606, 630
hepatitis c, 418, 420 homozygous fh, 259 hyperphosphatemia, 104–105, 363
hepatitis d virus, 421 hookworm, 437 hyperpigmentation, 33, 38, 44, 77–78, 376,
hepatoblastoma, 171, 183 hormone replacement therapy, 93–94, 448, 455
hepatocellular carcinoma, 417 96–97, 101, 169, 172–173 hyperpituitarism, 107, 109, 111, 113, 115,
hepatomegaly, 239–240, 268–269, 275, hormone secretion, 118, 131, 137 117, 119
277, 340–341, 351, 418, 421, 451, hormone therapy, 98, 100, 175, 721, 723, hyperplasia, 11, 69, 73, 75, 83, 102–103,
517, 524, 543, 571, 818 746, 805 112, 122, 128, 134–135, 162, 171,
hepatorenal syndrome, 395, 418 horner syndrome, 136 498, 559, 571, 724–725, 745, 765,
hepatosplenomegaly, 164, 195, 224, 230, horseshoe kidney, 183, 249 777, 799–800
270, 290, 296, 299, 336, 422, 424, hpv, 1, 29, 475–476, 741–742, 767 hyperprolactinemia, 87, 112, 114, 125, 602
433, 464, 490, 510, 519, 546, hpv vaccine, 742 hypersensitivity, 10, 12, 16, 59, 62, 81,
563–564, 573, 579, 581, 600, 815, hs, 356 192, 205–211, 219, 221, 223,
817, 824, 827 hsv, 48, 50, 353, 422, 424–425, 463, 756, 225–229, 276, 374, 377–378, 461,
herald patch, 34 822–824 641, 649
hereditary angioedema, 61 ht, 243, 254–255 hypersensitivity pneumonitis, 205–208,
OSMOSIS.ORG 35
229 hypoxemia, 166, 206–207, 302, 305, 311, immunocompetent, 229, 315, 330, 333,
hypersensitivity vasculitis, 226 407, 778, 820 336, 400, 422, 429, 449–450, 460,
hypertension, 68, 70–71, 73, 102, 111, hypoxia, 221, 246–247, 302, 305, 346, 462–463, 466–467, 469, 498, 512,
124, 134–135, 140, 151, 153, 479, 644, 733–735, 782 583
162, 205, 247, 252, 255, 271, 340, hysterectomy, 732–734, 737, 742, 744, immunocompromised, 54, 58, 308–309,
418, 464, 574, 642, 646, 649, 735, 746, 750, 752, 765, 792, 797 313, 315, 323, 336, 354, 356, 359,
778–780, 782, 787–788, 797, 806, hysteroscopy, 758 370, 380, 400, 420, 422, 427, 430,
817, 820 iatrogenic, 68–69, 71, 102, 125, 317, 336, 434, 449, 461–466, 469, 475–476,
hyperthermia, 255, 713 382, 386, 428, 502, 622–623, 666, 479, 486, 490, 495, 512, 524, 529,
hyperthyroidism, 88, 120–125, 127–129, 698, 762, 791 532–534, 556, 563, 584–585, 589,
133, 143, 145–146, 165, 602, 758, iatrogenic botulism, 317 705, 809–810, 827
764, 781 ibd, 228 immunodeficiency, 188, 196
hyperthyroidism & hypothyroidism, ibuprofen, 427, 431 immunoglobulin a, 201
120–121, 123, 125, 127, 129 icterus, 490 immunoglobulin g, 423, 816
hypertonia, 255 id, 270–271 immunoglobulin m, 200, 816
hypertriglyceridemia, 256, 262, 268 idiopathic, 68–69, 71, 81, 99, 107, 110, immunohistochemistry, 153, 224, 476, 496,
hypertrophic cardiomyopathy, 778 112, 114, 182, 224, 618, 622, 626, 518, 723
hypertrophy, 72, 83, 122, 128, 151, 330, 629–630, 654, 661, 681, 687, 694, immunosuppression, 1, 4, 13, 18, 27, 29,
497, 663, 780, 800 701, 704, 762, 773, 786, 803, 808, 43, 52, 69–70, 205, 208, 211,
hyperuricemia, 267–268, 293, 627, 630, 813 332–333, 336, 365, 367, 382, 386,
714, 788 idiopathic hyperaldosteronism, 69 399, 403, 425, 428, 458, 460, 473,
hyperventilation, 236, 267–268 idiopathic thrombocytopenic, 224 497, 526, 530, 549–551, 559–562,
hypervitaminosis, 274–275, 603 iga, 159, 196–197, 201, 203, 206, 354, 564, 581
hypervitaminosis d, 603 369, 555, 636, 828 immunotherapy, 28, 678
hypo, 105, 219–220, 252, 758, 776 ige, 10–11, 197–198, 203, 205, 219–220, impetigo, 11, 46–47, 50–51, 198, 214, 377,
hypocalcemia, 102–103, 105–106, 138, 222, 441, 447, 451, 455, 461–462, 549, 555–556
146, 217–218, 248–249, 264, 278, 571, 573 impotence, 114, 579, 806
390, 600, 714, 782 igg, 64–65, 146, 159, 192, 196–197, 199, imprinting disorders, 169, 171
hypoglycemia, 76–77, 80, 113, 117, 126, 202–203, 206–207, 210, 223, in situ hybridization, 169, 172, 183–185,
137–138, 171, 240, 253, 267–268, 226–227, 326, 329, 332, 337, 348, 476
270, 276–279, 363, 415, 778, 782 351, 392–393, 419, 421–423, 425, in situ transformation theory, 728
hypogonadism, 73, 87, 89, 93, 96–97, 100, 427, 436, 447, 451–452, 455, 480, in vitro, 334, 738
114, 172–173, 175, 602, 806–807 486, 489–490, 506, 516–517, 519, in vitro fertilization, 738
hypogonadotropic hypogonadism, 93, 97 541, 555, 561, 625, 636, 816–817, in vivo, 317
hypokalemia, 68, 71–73, 85, 133, 138, 278, 828 in-toeing, 691
363, 522, 536, 544 igg subclass deficiency, 199 inappropriate adh secretion, 118
hypomagnesemia, 248–249, 278 igm, 159, 196–197, 200, 203, 206, 223, incisional biopsy, 30
hyponatremia, 77, 118–119, 126, 279, 390, 326, 329, 332, 337, 348, 351, inclusion body myositis, 652, 654–655
519, 521–522, 530, 536, 544, 566 393–394, 396–397, 419, 421, incontinence, 21, 56, 136, 221, 510, 608,
hypoparathyroidism, 102, 105–106, 146, 423–424, 434–435, 469, 480, 704, 769, 805
218, 600, 603 482, 486, 490, 506, 516–519, 541, increased intracranial pressure, 115, 465,
hypophosphatemia, 104, 278, 530, 598, 555, 561, 566–568, 579–580, 636, 512
605 816–817, 828 indigestion, 571
hypopigmentation, 39–40, 170, 233, 245 il, 10, 12, 35, 37, 121, 125, 188, 210–211, infant, 136, 185, 202, 271, 282, 291, 305,
hypopituitarism, 87–89, 107, 109, 111, 223, 228, 361, 365, 377, 392, 395, 317, 344, 420, 438, 485, 503,
113, 115, 117, 119, 125 455, 579, 624, 626, 628–630, 682–683, 778, 784, 820
hypoplasia, 39, 125, 167, 170, 183, 185, 632–633, 635–636, 638, 661, 775 infant botulism, 317
189, 217–218, 242, 249, 251, 264, ileum, 304–305, 320, 358–359, 442, infantile malignant type, 600
289–290, 430, 485, 597, 605, 679, 537–538 infarct, 412, 757
694, 785, 815 ileus, 317–318, 407, 818 infarction, 72, 77, 107, 117–118, 125, 127,
hypoprolactinemia, 116 iliac, 600, 693–694 259–260, 355, 412, 460, 467–468,
hypospadias, 94, 771, 801, 804–806 iliotibial band syndrome, 669–670 545, 644, 649, 724, 788, 795, 811,
hypospadias & epispadias, 804 im, 78, 221, 547, 819, 823 825
hypotension, 56, 71, 76–77, 79, 82, 110, immature teratomas, 746–747 infections, 11, 18, 33, 43, 45, 47–49, 51,
116–118, 126, 221, 245, 279, 317, immotile-cilia syndrome, 166 53, 55, 57, 59, 64, 77, 115, 136,
320, 329, 363, 373, 389, 395, 407, immune response, 12, 14, 190, 196, 207, 148, 166, 184, 187–189, 192–193,
413, 415, 538, 549–550, 760, 781, 209, 218, 220, 222, 276, 328, 336, 195–204, 212–214, 216–218, 227,
793, 818, 820, 826 358, 360, 369, 377, 390–391, 394, 233, 269, 282, 287–288, 290, 292,
hypotension, postural, 77, 781 407, 418, 455, 485, 489–490, 558, 299, 308, 312, 318, 322, 332–333,
hypothalamus, 96, 98–99, 110, 114, 116, 560, 562–563, 578, 632, 635, 643, 335, 337, 343, 354, 356–357, 359,
125, 636 649, 652 364, 366–367, 369–370, 376,
hypothermia, 6, 126, 277, 279 immune system, 12, 32, 35, 41, 57, 59, 380–385, 399, 401, 403, 405,
hypothyroidism, 92, 100, 114, 120–123, 162, 205, 208, 214, 218, 221, 228, 407–408, 411, 413, 415, 425, 434,
125–127, 129, 143–146, 150, 172, 306, 315, 320, 346, 373, 407, 432, 437, 458, 460–461, 463–465, 467,
175, 182, 262, 281, 630, 761, 793 462, 494–495, 501, 534, 583–584, 469, 471, 473, 475, 490–492, 503,
hypotonia, 149, 151, 179, 182–184, 267, 642 515, 517, 523, 526–537, 548–552,
269–271, 284–285, 296, 300, 317, immune thrombocytopenia, 509 554–556, 558–559, 567, 573–574,
546, 581, 815, 825–827 immune thrombocytopenic purpura, 201, 587, 589, 600–601, 640, 647, 649,
hypoventilation, 126, 194 223 652, 654, 659, 713, 738, 740–741,
hypovolemia, 81, 118, 363, 415, 521, 735 immunization, 196, 199, 313, 322–323, 753, 755, 761, 767, 805, 807–808,
hypovolemic shock, 363, 735 346, 374, 396, 420, 479, 490, 492 810, 814–815, 817, 819–823, 825,
36 OSMOSIS.ORG
827 invasive ductal carcinoma, 721 kidney transplant, 154

infectious mononucleosis, 423–424 invasive lobular carcinoma, 721 kissing bugs, 580
infective endocarditis, 380, 517, 529, 556 involution, 736 klebsiella, 51, 529, 809
inferior dislocation, 716 iodide, 60, 243 klebsiella pneumoniae, 529
infertility, 15, 73, 89, 93–98, 100–101, 114, iodine, 8, 92, 120, 122–123, 125, 127–128, klinefelter’s syndrome, 96, 173–174, 602,
124, 133, 158, 166, 173–175, 182, 143, 145, 224, 243, 280–282, 513 801
242, 343, 371, 573, 722, 753–754, iodine deficiency, 281 klippel-feil syndrome, 622
757–761, 763–765, 771, 791, 793, ipsilateral, 668, 803 knee, 231, 470, 589–590, 594, 596, 610,
795, 801, 803, 805–807, 810–811, iq, 177, 182 614, 618–619, 630–631, 658–659,
813 iris, 163, 182, 448 661–664, 666–674, 676, 680–681,
inflammation, 43 iritis, 161 683, 686–688, 693, 707
inflammatory arthritis, 624 iron, 125, 194, 277, 280, 313, 356, 437, knee replacement, 688
inflammatory connective tissue disorders, 454, 467, 492, 527, 529–531, 537, knock-knees, 687
639 636, 778 koebner phenomenon, 33, 36, 632
inflammatory myositis, 652 irrigate, 6 koplik spots, 480
influenza virus, 473 irritant contact dermatitis, 13 krabbe disease, 297
inguinal, 251, 290, 352, 538, 767–768, ischemia, 3, 6, 56, 81, 110, 115–116, 545, krukenberg tumor, 748
771, 801–802, 807 616, 618, 640, 644, 711–712, 740, kshv, 427
inguinal canal, 801–802 795 kwashiorkor, 276–277
inguinal hernias, 771 ischemic stroke, 545 kyphosis, 602, 604, 625, 693, 698–699,
inheritance, 39, 65, 107, 123, 132, 145, isolated myopathy, 283–284 701, 707
149–150, 162, 166–167, 176–177, isolated primary immunoglobulin, 200 labia, 51, 74, 352
179, 187–188, 203, 215, 235, 237, isotonic solution, 194 labia, vaginal, 352
283–284, 295–298, 300, 693–694 itching, 10, 13, 33, 36, 48, 57, 205, 219, labial, 648
inhibin, 183–185 227, 409, 444, 446, 512, 647, 728 labor, 732–739, 773–776, 778–779, 787,
inner ear, 597 iud, 760 789, 820, 826
inr, 254, 266, 408, 419, 509 iugr, 422 laceration, 437, 736
insemination, 805 jaundice, 113, 164, 224, 230, 239–240, lacrimal, 647
insomnia, 124, 165, 224, 390, 446, 579 253, 302, 305, 340, 395, 402, 418, lacrimation, 247, 317, 512
insulin, 70, 80–85, 98–99, 108, 111, 113, 421, 424, 442, 489–490, 544, 546, lactase, 222, 499
133, 137–139, 221, 229, 268, 738, 564, 571, 584, 743, 815, 817–818, lactation, 116, 239, 263, 302–303,
762, 777–779 824, 827 305–306, 378, 757, 784
insulin pump, 83 jaw, 108, 177, 384, 482, 620–621, 643 lactic acid, 268, 775
insulinoma, 82, 132–134, 137–139 jc virus, 495–496 lactose intolerance, 599
interferon, 125, 210, 214, 365, 420–421, jejunum, 137, 320, 449 langerhans cell histiocytosis, 110
562, 578, 585, 601 job syndrome, 198, 464 laparoscopy, 792, 794
interleukin, 121, 188, 210, 219, 223, 228, joint pathology, 591, 593, 595, 597, 599, laparotomy, 748, 794
407, 496, 560, 579, 643 601, 603, 605, 658–659, 661, 663 large intestine, 440, 467
international normalized ratio, 408, 419 jugular vein, 52 laryngeal papillomatosis, 476
interstitial lung disease, 299, 636, 656 juvenile gout, 293 laryngitis, 370
interventional radiology, 734, 737, 798 juvenile idiopathic arthritis, 182, 629 laryngoscopy, 355
intervertebral disc, 697–698, 703, 705, 707 juxta, 628 laryngotracheobronchitis, 478
intestinal atresia, 679, 786 kala-azar, 432 larynx, 61, 149, 476, 564
intestinal malrotation, 183 kallmann syndrome, 96–97 late-onset sepsis, 826
intestinal obstruction, 338, 441–443, 536, kaposi sarcoma, 429, 767 latent autoimmune diabetes, 81
573 karyotype, 95, 101, 159, 173–175, 682, lateral ankle sprain, 674
intestine, 131, 229, 257, 265, 282, 330, 758, 763 lateral x-ray, 596, 604, 699–700, 707
335, 340, 362, 403, 437, 440–441, karyotyping, 94, 148–149, 181, 183–185 latex allergy, 205
443–444, 451, 454, 467, 488, 523, kb, 121, 501–502, 509 lbrf, 542
529, 646 kearns-sayre syndrome, 283–284 lcis, 721
intracranial hemorrhage, 266 keratin, 31–32, 65, 245 ldl, 256–257, 259–261, 298–299, 303
intradermal, 60, 229, 474, 585 keratitis, 49, 57, 161, 343, 350, 425, 439, legg-calve-perthes disease, 594
intraductal papilloma, 727 448, 533, 545, 822 legionella, 16, 333, 530
intraepithelial, 729, 741–742, 745 keratoconjunctivitis, 308, 350, 498, 647 legionella pneumophila, 333, 530
intrahepatic, 163–164, 402, 571 keratoconus, 163 legionnaires’ disease, 530
intramural myoma, 796 keratosis, 1–2, 29 leigh syndrome, 285
intramuscular, 78, 322, 372, 420, 447, 474, kernicterus, 224 leiomyoma, 796, 798
513, 819 kernig sign, 488 leishmania, 432–433
intrauterine, 158, 184–185, 250, 350, 383, ketoacidosis, 80–81, 84, 127, 467 leishmaniasis, 432–433
422, 464, 485–486, 680, 689, 691, ketogenic diet, 286 lens, 153–157, 239, 333, 464
733, 737–738, 743, 758–762, ketohexokinase, 238 lentigo maligna melanoma, 26
775–776, 781–782, 786, 788, 814, ketone bodies, 84–85, 778 leopard/lizard/elephant skin, 447
823 khk, 238 leprosy, 228, 377, 433, 458–459
intrauterine device, 760 kidney, 58, 97, 102–103, 105, 108, 110, leptospira, 544
intrauterine growth restriction, 158, 185, 121, 150, 153–154, 183, 208, 223, leptospirosis, 544
738, 782, 788 226, 233, 239–240, 245, 249, 260, lesch-nyhan syndrome, 292–293, 627
intrauterine growth retardation, 185 264, 268, 275, 283, 292–293, 328, lesion, 1, 17, 24–25, 27, 29, 34, 40, 50–51,
intravenous immunoglobulin, 19, 424, 486 340–341, 377, 389–390, 418, 491, 62, 88–89, 284, 311, 314, 347,
intraventricular, 775, 825 532, 538, 544, 554, 584, 598, 600, 379, 384, 428–429, 459, 461,
introitus, 74, 352 605, 627–629, 712, 714, 785 466–468, 470–471, 498, 524,
intussusception, 318, 442–443, 499–500 kidney stone, 292–293, 491 534, 545, 579, 581, 592, 604, 614,
OSMOSIS.ORG 37
616–618, 663, 717, 722, 724, 730, louse-borne relapsing fever, 376, 542 361, 488, 495, 647
742, 788, 818, 824 lower limb injury, 665, 667, 669, 671, 673, lymphoid tissue, 209, 361, 488, 647
leukemia, 17, 159, 182, 194, 229, 245, 675 lymphoma, 17, 144, 174, 213, 377, 423,
465, 467, 509–510, 608 lower respiratory tract infection, 493 465, 470, 479, 503, 509–510, 585,
leukemia, myeloid, 17 lt, 527 647
leukocyte, 208, 212, 215–216, 230, 372, ludwig’s angina, 52 lysis, 65–66, 193–194, 210, 223, 337, 351,
392, 515–516, 518–519, 522, 528, lumbar, 194, 290, 332–333, 335, 430, 482, 402, 418, 484, 494–495, 515, 518,
626, 628, 630, 643, 756, 821 510, 535, 546, 584, 604, 625–626, 524, 553, 555, 627, 818
leukocyte adhesion deficiency, 215 693, 699–701, 703–704, 707–708, m deficiency, 200
leukocyte count, 216, 372, 522 769, 828 mac, 192–194, 223, 394, 653
leukocytes, 194, 216, 222–223, 297, 359, lumbar puncture, 332–333, 335, 482, 535, macrocephaly, 692
372, 419, 422, 491–492, 510, 528, 546, 828 macrocytic, 276, 278–279, 305
531, 537–538, 551, 555, 577, 579, lumbar vertebrae, 584, 604 macrocytic anemia, 305
660, 754, 756, 816 lumpectomy, 720, 723 macroglossia, 171
leukodystrophy, 297–298 lung, 70, 108, 118–119, 131–133, 196, macrognathia, 108
leukopenia, 136–137, 246, 350, 390, 393, 198–199, 206–208, 210, 214, macrolide antibiotic, 334
423, 506, 510, 515, 517, 519, 221, 223, 226, 243, 245, 287, 289, macrolides, 48, 356, 371, 435, 531, 535
600–601, 647, 650 299, 328, 340, 343, 346, 354–356, macroorchidism, 176–177
leukotriene, 8, 63, 221 382, 405, 434, 437, 439, 445, 449, macrophage, 223, 228–229, 298, 347,
leydig cells tumors, 770 460–462, 465, 467, 469, 483, 492, 479, 502, 517, 562, 583, 635–636
lgv, 344 520, 523, 526, 529–530, 548, 554, macrosomia, 171, 778
lh, 96–101, 107, 109, 115–116, 165, 174, 556, 563, 572, 584, 608, 636, 642, macula, 300
802, 806 656, 690, 722, 734, 736, 738–739, macular, 299, 488
li-fraumeni syndrome, 86, 159, 607, 677 741, 744, 767, 774, 778, 788, 819 macule, 366
libido, 77, 114, 124, 133, 806 lung cancer, 70 magnesium, 6, 102, 105, 249, 276–277,
libman-sacks endocarditis, 649–650 lung transplant, 208 280, 532, 630, 736, 739, 777, 779,
lichen planus, 32–34 lupus, 18, 41, 122, 190, 200–201, 226, 789
ligament, 154, 210, 667–668, 670–671, 333, 426, 602, 639, 644, 649–651, major depression, 503
674–676, 682, 716–717, 749, 796 659, 762, 788 major depressive disorder, 182
ligand, 197, 210, 215, 515, 692 lupus erythematosus, 18, 41, 122, 190, malabsorption, 141, 163, 188, 197, 257–
limited systemic sclerosis, 640 201, 226, 426, 602, 639, 644, 649, 258, 282, 301–304, 330, 338–339,
lip, 29, 48, 98, 113, 134, 168, 172, 762, 788 402–403, 442, 449, 499, 598, 601,
185–186, 250–251, 293, 568 lupus nephritis, 651 605, 646, 818
lipemia retinalis, 262 luteinizing hormone, 96, 107, 115, 758, malaise, 17, 58, 60, 79, 205–206, 210,
lipid, 14, 138, 252, 256–257, 259, 806 227, 253, 306, 309, 311, 314, 319,
261–262, 277, 299, 304, 325, 327, lyme disease, 412, 540–541 326, 329–330, 343, 347, 351, 357,
364, 366, 388, 472, 497, 501–502, lymph, 12, 27, 30, 46–47, 90, 130, 189, 359, 365, 372, 380, 389, 404, 407,
520, 552, 555 203–204, 210, 214, 276, 314, 328, 413, 415, 418, 421–422, 424, 430,
lipoma, 133 336–337, 344, 347, 349, 352, 451, 472–473, 479–481, 485,
lipoprotein, 256, 258–259, 262, 278, 298, 359, 372, 376, 389, 393, 395, 423, 488–489, 493, 512, 515, 517, 519,
303, 555 427–429, 433, 456, 488, 524–525, 521, 524, 528, 536, 538, 553–554,
listeria, 315 538, 564, 566–567, 579–580, 560, 568, 572, 579, 581, 634, 781,
listeria monocytogenes, 315 583–584, 651, 722–723, 740, 784, 810
listeriosis, 315 766–769, 771–772 malar, 14, 485, 649–650
lithium, 6, 35, 44, 110, 125, 254 lymph node, 130, 189, 337, 347, 352, 376, malar rash, 485, 649–650
lithotripsy, 233, 292–293 389, 393, 395, 428–429, 456, 525, malaria, 276, 278–279, 412–416
liver, 27, 91, 121, 131, 137, 163–165, 175, 564, 580, 583, 651, 722–723, 740, male genitourinary cancers, 766–767, 769,
208, 214, 223, 229–230, 235–236, 772 771
239–240, 245–246, 248, 253–254, lymphadenitis, 311, 446, 524, 537, 581, malformation, 82, 94, 150, 165, 167, 292,
257, 260, 263–271, 274–275, 584 294, 592–594, 596, 605, 607, 618,
277–279, 296, 301, 303, 329, 338, lymphadenopathy, 135, 196, 214, 227, 632, 636–638, 680–682, 684–685,
340–341, 350, 389, 392, 402–403, 308–309, 311, 336, 347, 351–353, 687–694, 696, 698, 707, 785, 805,
405, 413–414, 417–421, 432–434, 357, 376, 424–425, 427–428, 433, 811, 819
441–442, 449, 451–452, 463, 490, 448, 455, 466, 503, 510, 519, 524, malignant melanoma, 26–27
524, 529, 532, 542, 552, 554, 571, 538, 541, 544, 546, 562, 564, 567, malignant tumors, 24
573–574, 584, 598, 605, 636, 678, 579, 581, 614, 651, 767–768, 807, malleolus, 674
722, 741, 743–744, 753, 767, 771, 818, 827 malnutrition, 50, 56, 96, 242, 276–279,
780, 787–788, 816, 823, 828 lymphatic, 46–47, 90, 277, 322, 385, 395, 281–282, 330, 333, 363, 399, 402,
liver abscess, 340, 402–403, 405 455–456, 470–471, 479, 520, 583, 433, 437, 442, 467, 584–585, 601,
liver biopsy, 164, 236, 267–268, 275, 419 729, 791, 795 656
liver transplantation, 164, 420–421 lymphedema, 47, 175, 455–456, 722 mammogram, 720, 722, 724, 726–727,
lletz, 742 lymphocutaneous sporotrichosis, 470–471 729–730
loa loa, 446, 456 lymphocyte, 146, 187–189, 196–197, 204, mandible, 111, 129, 149, 164, 167, 383,
lobar, 58, 350, 559 377, 389, 417–418, 434, 648 481, 600, 621, 818
lobe, 90–92, 104, 406, 471, 530, 585 lymphocytic, 8, 21, 34, 144–145, 210, 222, mandibulofacial dysostosis, 167
lobectomy, 463 325, 330, 377, 394, 466, 471, 566, mania, 503
lobular carcinoma in situ, 721 568, 647–648 mantoux test, 228
lockjaw, 322 lymphocytic thyroiditis, 145 maple syrup urine disease, 235
loin, 329 lymphocytosis, 206–207, 345, 423–424 marasmus, 276, 279
loop diuretics, 119 lymphogranuloma venereum, 344 marfan syndrome, 152, 156–157, 701
lordosis, 693, 699, 701, 708 lymphoid, 189, 196, 209, 211, 328–329, maroteaux-lamy syndrome, 287–288
38 OSMOSIS.ORG
marrow, 36, 137, 194, 197, 211, 213, 229, 775, 820, 825–826 mitotic nondisjunction, 181, 184
242–243, 245, 288–291, 296–297, meningococcemia, 373–374 mitral valve, 156, 177, 182, 287
302, 305, 349, 386, 392, 426, 433, meniscus tear, 670 mitral valve prolapse, 177, 182
467, 531, 564, 580, 588, 592, 595, menopause, 100–101, 177, 596, 697, 721, mixed connective tissue disease, 642
600–601, 604, 614, 677 725–727, 757, 790–791, 796 mmr, 480, 482, 567, 817
massage, 621, 623, 664, 732, 737, 811 menorrhagia, 791 mmr vaccination, 817
masseter, 322–323 menstrual cycle, 99, 724–725 mmrv, 567
mast cell, 62, 219, 223 menstruation, 93, 114, 173, 194, 724, 745, mods, 407
mastectomy, 160, 720, 723, 729 754, 757, 791, 797 mohs surgery, 26, 30
mastitis, 481, 549, 725, 784 mental illness, 118, 302–303, 305–306 molar pregnancy, 743, 763–765, 781
mastoid, 622 mercury poisoning, 251 mole, 26, 763–765, 781
mastoiditis, 383, 555 merrf, 284 molluscum contagiosum, 203, 497
maternal conditions, 773, 775, 777, 779, metabolic acidosis, 81, 85, 248–249, 253, monoamine oxidase inhibitors, 254
781, 783, 785, 787, 789 255, 267–268, 363, 374, 407, 415, monoarticular, 627
mature cystic teratomas, 746 778, 782 monoclonal, 63, 87, 89, 113, 194, 201,
maxilla, 111, 383, 694, 818 metabolic alkalosis, 72, 781 211, 260, 384, 400, 625
mccune-albright syndrome, 164, 592 metabolic disease, 81 monoclonal antibody, 194, 384, 400
mcv, 302, 305, 339, 494, 497 metabolic syndrome, 69, 72 monocyte, 395, 479, 519
measles, 478–482, 566–567, 761 metabolism, 80, 109, 120–121, 125, 180, mononeuritis, 636
measles immunization, 479 215, 231, 233–235, 237–240, mononeuritis multiplex, 636
measles virus, 479–480 248–249, 254, 259, 264–265, 267, mononucleosis, 423–424
meatus, 367, 372, 755 272, 274, 285, 287, 289, 292–293, monosodium urate, 626, 660
meckel’s diverticulum, 183 295, 302–305, 383, 385, 826 monosomy, 175
meconium, 315, 775, 782, 785 metacarpal, 175 mood disorders, 178
meconium aspiration, 775, 782, 785 metachromatic leukodystrophy, 298 moraxella catarrhalis, 369–370
medial ankle sprain, 674 metastasis, 30, 86, 91, 130–131, 133–134, morphea, 646
mediastinum, 51 136, 138, 603, 616–617, 677–678, morquio syndrome, 287–288
medulla, 140, 165 722, 729, 740–741, 743–746, 748, mps, 287–290
medullary carcinoma, 92 750, 752, 764–769, 771 mps i, 287, 290
medullary thyroid carcinoma, 90–92, 134 metatarsal, 627, 686 mps ii, 287, 289
megacolon, 134, 318, 359, 402–403, 536, metatarsus adductus, 691 mps ii a, 289
581 methadone, 254 mps ii b, 289
megakaryocyte, 392 methemoglobin, 247 mps iii, 287
megaloblastic anemia, 294, 302, 305, methimazole, 125 mps iv, 287–288
338–339 methotrexate, 37, 230, 302, 633, 637, 654, mps ix, 287–288
meiotic, 173, 181, 183–184 761 mps vi, 287–288
meiotic nondisjunction, 181, 183–184 metrorrhagia, 390 mps vii, 287–288
melanin, 8, 38–39, 237, 264, 465 mhc, 208–210, 228–230, 624, 654–655 mrna, 162, 176–177, 476
melanocyte, 38, 40–41, 77 microangiopathic hemolytic anemia, 528 mrsa, 46, 48–49, 51, 549–550
melanoma, 9, 24, 26–27, 29, 161, 767 microangiopathy, 787 ms, 169, 171, 228
melas, 284–285 microcephaly, 149, 159, 170, 182, msu, 626, 628, 630
melena, 266, 329, 361, 390, 395 184–185, 237, 251, 275, 285, 326, msud, 235
membrane, 16–17, 39, 64, 83, 153–154, 396–397, 422, 430, 684, 815–817, mtdna, 283–284
192, 223, 227–228, 241, 268, 313, 827 mucocutaneous candidiasis, 198, 463
315, 318, 325, 327, 329, 337, 343, microcytic, 276, 278–279, 306 mucocutaneous growth, 464
355, 364, 370, 383, 427, 434–435, microcytic anemia, 306 mucocutaneous leishmaniasis, 432
472, 494, 497, 501–502, 515, 518, microdeletion, 150 mucopolysaccharidosis, 287, 289, 291, 698
520, 540, 542, 550, 554–555, 576, micropenis, 113, 805 mucormycosis, 467–468
578, 610, 653, 664, 674–675, 713, microphthalmia, 185, 817, 827 mucosa, 33, 51, 66, 197, 220, 224, 226,
738–739, 773, 775, 820, 822–824, middle ear, 167, 322, 693 304–305, 319, 361, 365, 383–384,
826 middle ear infection, 693 399, 402, 425, 432–433, 441,
membrane attack complex, 192, 223, 653 midfacial destruction, 433 449–450, 452–453, 458, 464, 468,
membranoproliferative, 193 mild androgen insensitivity, 95 479–480, 488, 492, 494, 499, 503,
memory, 12, 113, 126, 159, 177, 180, 205, miliary tuberculosis, 583 523, 527, 536–537, 563, 574, 650,
250, 252, 372, 509, 541, 777 milk stasis, 784 753
men 2a, 91, 134–135, 140 minamata disease, 252 mucositis, 65, 556
men 2b, 134–135, 140 mineral deficiencies, 280 mucous, 16–17, 19, 41, 64–66, 82, 138,
menarche, 721, 757, 791, 793, 797 mineralocorticoid, 70, 73–74, 77–78 204, 212, 342–343, 347, 360,
mendelian, 162 minor salivary gland, 648 362–363, 407, 429–430, 463,
meningeal, 117, 242, 333, 439, 470–471 minoxidil, 22 544–545, 550, 554–555, 580, 781,
meningeal sporotrichosis, 470–471 miosis, 136 824
meninges, 87, 89, 325, 373, 439, 465, 583, miscarriage, 315, 350, 485, 567, 761 mucus, 221, 319, 321, 345, 360, 363, 402,
743 mitochondrial, 162, 179, 246, 283–285, 454, 483, 530, 583, 753
meninges invasion, 439 432, 713 mud fever, 544
meningitis, 115, 200, 311, 315, 326, 350, mitochondrial disease, 283, 285, 713 multiple endocrine neoplasia 1, 132
354–356, 359, 373–374, 381, 383, mitochondrial dna, 283–284 multiple endocrine neoplasia 2, 134
386, 389, 394, 423, 425, 430, 439, mitochondrial myopathy, 283 multiple gestation, 680–681, 735–736,
464–465, 481–482, 488, 491, 503, mitochondrion, 578 738, 778, 781–782
522, 527–529, 532, 535, 538, 540, mitosis, 29, 414, 617 multiple organ dysfunction syndrome, 407
542, 544–546, 549–550, 553–554, mitotic, 37, 139, 181–184, 211, 509, 612, multiple osteochondromatosis, 618
559–560, 562, 572, 579, 584, 739, 730 multiple sclerosis, 228, 426, 680, 806
OSMOSIS.ORG 39
mumps, 478, 480–482, 567, 761, 771, necrotizing enterocolitis, 499, 782, 818, niemann-pick disease, 298–299
803, 807–808 826 night sweats, 101, 210, 351, 428, 471,
mumps virus, 481–482, 771 necrotizing fasciitis, 46, 51–53, 555 559, 562, 584–585
murine typhus, 522 necrotizing otitis externa, 461 nikolsky sign, 58, 65–66
muscle relaxants, 323, 621 needle biopsy, 138, 730 nipple, 722, 727–729
muscle tumors, 677 neisseria, 16, 79, 192–193, 203, 369, 371, nitrates, 247, 528, 821
muscular dystrophy, 701 373, 589, 753, 755, 803, 810, 822 nits, 376
musculoskeletal disorders, 620 neisseria gonorrhoeae, 79, 193, 369, 371, nk cell, 187
mutant, 132, 179 589, 753, 755, 810, 822 nocardia, 385–386
mutation, 1, 10, 25, 61, 87, 93–94, 97, neisseria meningitidis, 16, 79, 192, 203, nocardiosis, 387
110–111, 113, 115, 128, 132–136, 369, 373 nocturia, 110, 510, 800
140, 143, 148, 150, 152–154, nematode, 436–437, 439, 441, 443, 445, nodular melanoma, 26–27
156–164, 167, 176–177, 181, 188, 447, 449, 451, 453, 455, 457 nodular scabies, 378
197, 203–204, 212, 214–215, neonatal, 73, 156, 215, 236, 264, 266, non tuberculous mycobacterium, 458–459
231, 233, 235, 237–238, 240, 257, 315, 322–323, 326, 344, 354, 425, non-classic msud, 235
259, 262, 268–269, 271, 284–285, 503, 527, 543, 553, 738–739, 773, non-hodgkin lymphoma, 17
289–290, 293, 295, 302, 305, 775–779, 785, 814–817, 820–823, non-segmental vitiligo, 41
361, 473, 552, 597–598, 614, 618, 825–828 non-seminomas germ cell tumors, 770
692–694, 745, 751, 757 neonatal conjunctivitis, 344, 822 nonbullous impetigo, 50
myalgia, 155, 284, 309, 311, 326, neonatal herpes simplex, 823 nondisjunction, 173, 181–184
329–330, 343, 351, 359, 365, 373, neonatal meningitis, 315, 825 nongonococcal urethritis, 634
395, 412, 415, 424–425, 472–473, neonatal sepsis, 826 nonoxynol, 577
481, 485, 493, 512, 517, 522, 541, neonate, 372, 681, 695, 739, 805, nontyphoidal salmonella, 531
543, 546, 562, 573, 656 814–815, 823–826 noonan syndrome, 689
myasthenia gravis, 223–224 neoplasia, 103, 111, 132, 134, 741–742, normocytic anemia, 194, 258, 637
mycobacterium leprae, 458–459 745, 763, 765 norovirus, 330
mycobacterium tuberculosis, 583, 587 neoplasm, 125, 427, 687, 704, 724, norwalk virus, 330
mycoplasma, 16, 18, 434–435, 755 751–752, 796 norwegian scabies, 377
mycoplasma pneumoniae, 18, 434 neoplastic, 59, 591, 607, 707, 793 nosocomial, 407, 526, 532, 549, 552
mycoses, 558–559, 561–563 nephritis, 153, 308, 647, 651 nsaid, 8–9, 16, 18, 32, 37, 111, 155, 191,
mycosis fungoides, 509 nephrogenic di, 110–111 474, 486, 590, 596, 613, 621,
mydriasis, 255, 512 nephrolithiasis, 102, 133–135, 533, 628 624–625, 628, 630, 632–633,
myelin, 136, 304–305, 495–496 nephropathy, 81, 150, 153, 446, 628 635, 637, 650, 660, 662, 664–665,
myelitis, 350, 396, 423, 430, 451 nephrotic syndrome, 262, 573, 818 667–669, 674–676, 686, 697,
myelogram, 705 nerve cell, 512 704–707, 719, 726, 785, 792, 794,
myeloid, 17, 722 nerve compression, 164, 600, 604, 612, 797, 804
myeloid neoplasms, 722 696, 700, 703–705, 710 nsgct, 770–772
myelopathy, 509–510, 573–574, 697, 710 nerve growth factor, 641 nuchal, 181–185, 373, 466, 820, 825
myocardial infarction, 72, 127, 259–260, nervous system infections, 332–333, 335, nuclear medicine, 242, 588, 607, 610
412 337 nucleic acid, 344, 353, 372, 404, 577, 753,
myocarditis, 308, 313, 326, 343, 350, 394, nettleship-falls syndrome, 39 804, 820, 823
423, 451–453, 473, 488, 491, neural tube defect, 302 nucleotide, 87, 161, 292–293, 309, 420,
521–522, 530, 538, 542, 544, 579, neuralgia, 425, 430 592, 791
581, 650 neuritis, 350, 394, 423, 542, 544 nucleus, 334, 484, 494, 502, 520, 697, 770
myocardium, 289 neuroblastoma, 136, 171 nursemaid’s elbow, 717
myoclonus, 119, 284 neuroendocrine tumors, 130–131, 133, nymph, 412
myoglobin, 267, 713–714 135, 137, 139, 141 nystagmus, 39–40, 113, 213, 234, 248,
myoma, 796 neurogenic, 57, 110–111, 532, 704 258
myomectomy, 732, 797 neurogenic (central) di, 110 oa, 39
myometrium, 732, 736, 739, 759, 796 neurogenic bladder, 532 oa1, 39
myopathy, 271, 283–284, 390, 632, 680 neuron, 389, 394, 492 obesity, 45–47, 49, 83, 93, 96, 98,
myopathy with diseases of multiple neuropathic pain, 295, 439 111–112, 169, 172, 182, 262–263,
systems, 284 neuropathy, 81, 126, 213, 245, 257, 473, 627, 629, 632, 661, 663, 666,
myopericarditis, 540 297–298, 446, 458, 540, 545 686–687, 693, 696, 699, 701,
myopia, 149, 234 neurosyphilis, 545–546 703–704, 710, 722, 762, 768, 778,
myositis, 308, 394, 453, 473, 526, 642, neurotoxic, 252, 376 793, 799
652–655, 657 neurotoxin, 376, 378 obsessive-compulsive, 151, 172
myxedema, 120–122, 124–126, 144 neurotransmitter, 252, 322, 622 obstetrics, 740, 796
myxedema coma, 121, 125–126 neutropenia, 197, 213, 227, 284, 318, obstructive sleep apnea, 684, 693
myxoma, 165 460–461, 464, 467, 515, 522, oca, 39
naegleria fowleri, 332, 334–335 534–535, 636, 677, 826 oca1, 39
naegleriasis, 334 neutropenic, 320, 461–463, 467 oca2, 39
nares, 184 neutrophil, 192, 214, 239, 321, 460, 467, occipital bone, 622
nasal polyps, 166 589, 628, 820, 826 occiput, 182, 184
nasal septum, 459 nevus, 27 occult, 418, 428
nasogastric tube, 19, 318 newborn screening, 74, 235–237 occupational therapy, 148, 150–151, 299,
nasopharynx, 354, 369, 373, 430 nf, 121, 132, 138, 140, 502, 509 633, 655, 679–680
natowicz syndrome, 287–288 niacin, 131–132, 233, 303–304 ocular albinism, 39
natural menopause, 101 nicotine, 644, 806 ocular onchocerciasis, 447
nd, 55, 187, 189 nicotinic acid, 234, 261–262, 303 ocular syphilis, 545–546
necator americanus, 437 nidus, 613, 626, 630 ocular toxoplasmosis, 336
40 OSMOSIS.ORG
oculocutaneous albinism, 39, 212 698 433, 563, 678

of infancy, 202 osteogenesis imperfecta, 152, 591, pandas, 555
ogtt, 99, 108, 111 596–598, 602, 698 pannets, 133, 137
olecranon, 659–660 osteogenic bone metastasis, 603 panniculitis, 59
oligodendrocyte, 297, 496 osteoid osteoma, 611–613 pap test, 742
oligohydramnios, 184, 422, 680–682, 783, osteomalacia, 164, 264, 591, 598–599 papillary carcinoma, 90–91, 767
785, 788 osteomyelitis, 46–47, 318, 350, 354, papillary thyroid, 90, 92
oligomenorrhea, 87, 93, 98 356–357, 383, 517, 526, 549, 553, papilledema, 326, 350, 572, 684–685
oliguria, 252, 329, 363, 395, 544, 714, 788 559–560, 588–589, 595, 600–601, papillomatosis, 476, 767
omphalocele, 171, 184–185 603, 607, 820 papillomavirus, 1, 475, 477, 740–741, 767
onchocerca volvulus, 447 osteonecrosis, 594 papular, 33, 65, 135, 222, 428, 438, 447,
onchocercal skin disease, 447 osteopenia, 97–98, 588, 599, 606, 705 475, 485, 497, 573
onchocerciasis, 446–447, 456 osteopetrosis, 591, 600–601, 603 papule, 32, 311, 352, 445, 470–471
onchocercoma, 448 osteopoikilosis, 603 papulosquamous disorders, 32–33, 35, 37
oncogene, 92, 134, 136, 140, 418, 614 osteoporosis, 69–70, 89, 97, 100–102, paracetamol, 253, 427, 431
oncogenesis, 158, 161, 418 122, 124, 134, 172, 218, 234, 264, paracetamol toxicity, 253
onycholysis, 33, 36, 55 296, 491, 591, 596–599, 601–602, paracoccidioides brasiliensis, 563
onychomycosis, 54 604, 625, 694, 698–699, 705–706, paracoccidioidomycosis, 563–564
oocyte, 175, 400 758 paragonimiasis, 572
oophorectomy, 750, 752, 794, 796 osteosarcoma, 160, 164, 604, 612, paragonimus westermani, 572
oophoritis, 444, 481–482, 753 614–615 parainfluenza, 478
open wound, 52 osteosclerosis, 591, 600, 603 paralysis, 102, 105, 224, 258, 298, 313,
ophthalmia, 343, 371–372, 822 osteotomy, 662, 664 345, 376, 378, 393–394, 459, 488,
ophthalmia neonatorum, 343, 371–372, otc, 236 490–492, 512, 522, 565, 568, 579,
822 otitis, 148–150, 166, 182, 190, 197, 204, 712
ophthalmology, 135, 153, 157, 430, 458, 214, 342, 354–356, 370, 383, 461, paramyxovirus, 479, 761, 803
518, 635, 828 473, 480, 492–493, 533, 535, paramyxoviruses, 478–479, 481, 483
ophthalmopathy, 123 554–555 paraphimosis, 767
opioid, 19, 431 otitis externa, 461, 535 parasite, 333, 335, 337, 340, 377, 400,
opportunistic fungal infections, 460–461, otitis media, 148–150, 182, 197, 204, 342, 403, 412, 414, 441, 447, 449, 454,
463, 465, 467, 469, 471 354–356, 370, 383, 473, 480, 540, 571–572, 578, 580, 827
opportunistic infection, 203, 312, 369, 503, 492–493, 533, 554–555 parasitemia, 413, 415, 582
506, 508, 515 otosyphilis, 545 parasympathetic nervous system, 511
optic nerve, 87, 114, 249 ova, 94, 378 parathyroid gland, 102–103, 146
optic neuritis, 350, 394, 423, 544 ovarian adenocarcinoma, 751 parathyroid hormone, 102–103, 105, 218,
oral candidiasis, 188, 464 ovarian cancer, 748, 754, 791, 794 264, 599, 602, 606
oral contraceptive, 69 ovarian cyst, 164, 743, 791, 793–794 parenchyma, 392, 394–395, 439, 451, 453,
oral enanthem, 488 ovarian torsion, 793, 795 520, 532, 771, 794, 808
oral glucose tolerance test, 84, 99, 108 ovary, 83, 98–100, 570, 743, 747–748, paresis, 284, 430, 491, 546, 572
oral herpes, 425 750, 752, 758, 778, 792–796 paresthesia, 252, 512, 696–697, 703–704,
orbital cellulitis, 45 overgrowth syndrome, 171 710
orchidectomy, 770–772 ovulation, 98–101, 114, 795 parkinson’s disease, 56, 367
orchiectomy, 811–812 ovum, 759, 764 parkland formula, 5
orchiopexy, 802, 812 oximetry, 483, 778, 788 paronychia, 55, 377
orchitis, 326, 350, 394, 481–482, 567, 771, oxytocin, 737–738 parotid gland, 481, 647
803, 807–808 pa, 310 parotitis, 326, 481–482
orgasm, 806 paget’s disease, 591, 603–605, 607, 722, paroxysmal nocturnal, 194
ornithine transcarbamylase, 236 728–729 partial androgen insensitivity, 95
oropharynx, 51, 323, 464, 490, 556, 818 paget’s disease of bone, 603 partial hydatidiform mole, 764
orotic aciduria, 292, 294 paget’s disease of the breast, 728 parvovirinae, 484
orthohantavirus, 328 pain management, 66, 165, 243, 495, 662, parvovirus, 484–486, 643, 815
orthomyxoviruses, 472–473 697, 699–700, 706–707, 709–710, parvovirus b19, 484, 486, 643, 815
ortolani maneuver, 683 715, 719, 792, 794, 797 pasteurella multocida, 356
osgood, 591, 595–596 palate, 97, 154, 156, 167–168, 177, patau syndrome, 184–185
osgood-schlatter disease, 591, 595–596 185–186, 218, 251, 427–428, 433, patella, 672, 674
osler, 380 467, 567 patellar, 595, 668, 672–674
ossicle, 596 palliative care, 742 patellar tendon rupture, 672–673
osteitis, 102 palpitations, 124, 135, 138, 140, 145, 165, patellofemoral pain syndrome, 673
osteoarthritis, 111, 594, 600, 604, 630, 541, 781 patent ductus arteriosus, 817
658, 661–663, 668, 670, 672, 676, palsy, 323, 423, 512, 541–543, 565, 568, pathognomonic, 32, 176, 233, 480, 580,
682, 687–688, 696, 704, 710 686, 701, 738–739, 775, 778, 825 672
osteoarticular sporotrichosis, 470–471 pancreas, 132, 137, 141, 146, 229, 263, pectus carinatum, 288
osteoblast, 599, 612, 694 265, 434 pectus excavatum, 154, 166, 689–690
osteoblastoma, 611–613 pancreatic, 60, 81, 108, 133, 137–138, pediculosis, 375
osteochondroma, 616, 618–619 163, 442, 777 pediculus humanus capitis, 376
osteochondromatosis, 618 pancreatic cancer, 60 pediculus humanus humanus, 376
osteochondrosis, 154, 698 pancreatic cholera syndrome, 137 pedigree, 177
osteoclast, 103, 593, 600, 610 pancreatic neuroendocrine, 133, 137 pellagra, 131, 233–234, 303–304
osteoclastoma, 610 pancreatitis, 141, 256, 261–262, 340, 350, pelvic exam, 739, 792, 797
osteodystrophy, 103, 105, 663 394, 400, 423, 442, 481, 488, 571 pelvic inflammatory disease, 753
osteogenesis, 152, 591, 596–598, 602, pancytopenia, 194, 242, 245, 296, 350, pemphigus vulgaris, 65–67, 223–224
OSMOSIS.ORG 41
penetrance, 163, 167, 177, 179 phenylketonuria, 237 354–356, 363–364, 370, 383,
penicillin, 8, 16, 79, 219, 315, 321, 323, pheochromocytoma, 134–135, 140–141 385–386, 407–408, 423, 430,
361, 369, 374, 381, 385, 543, 545, philtrum, 185, 250 434–435, 442, 453, 468–469,
547–549, 553, 556–557, 811, phimosis, 18, 767 472–474, 478, 480–481, 483,
818–819, 821 phobias, 151 491–492, 517, 523, 526–531,
penile cancer, 767 phosphate, 102–104, 165, 214, 234, 236, 533–535, 549–550, 553–554,
penile disorders, 806 239–240, 268, 272, 276, 303, 416, 558–560, 562–563, 579, 656, 739,
penis, 33, 36, 51, 93–94, 174, 352–353, 521, 532, 782 775, 819–820, 826
378, 425–426, 767, 805 phosphorylation, 134 pneumonic plague, 538
peptic ulcer, 133 photodynamic therapy, 2, 26, 30, 55 pneumonitis, 205–208, 214, 229, 242, 350,
peptic ulcer disease, 133 photophobia, 326, 347, 373, 390, 395, 383, 422, 430, 441, 449–452, 521,
percentile, 109, 250, 256, 260, 778 439, 512, 543, 568, 777 815, 824, 827
percutaneous, 437, 445, 463, 517 photosensitivity, 161, 213, 234, 649–650 pneumothorax, 156, 340, 346, 584, 791
perianal, 45, 352, 444, 449 phototherapy, 13, 32–33, 37, 41 point mutation, 162
perianal cellulitis, 45 phthirus pubis, 376 poison ivy, 12–13, 228
pericardial, 340, 355, 385–386, 559, 581, phyllodes tumor, 729 poison oak, 12
636, 646 physical therapy, 155, 180, 397, 492, 596, poisoning, 114, 245–248, 251–252, 312,
pericardial effusion, 340, 385–386, 559, 598, 605, 620–621, 623, 626, 633, 320–321
581, 636 641, 654–656, 662, 668–670, 672, poliomyelitis, 490–491
pericarditis, 226, 342, 350, 355, 387, 402, 675, 686, 699–700, 702, 705–707, polyarteritis nodosa, 226
451, 473, 584, 636, 650 709–710, 712, 719 polyarticular, 627, 629–630, 632
pericardium, 355, 445 pick disease, 298–299 polycystic kidney disease, 110
perihepatitis, 343, 753–754 picornaviruses, 487, 489, 491, 493 polycystic ovarian syndrome, 44, 746, 793
perinatal, 167, 264, 271, 371, 417, 421, pid, 343, 753–754 polycystic ovary syndrome, 83, 98, 758,
567, 775, 778, 814–815, 817, 819, pigeon toe, 691 778
821, 823, 825, 827 pigmentation disorders, 38–39, 41, 237 polycythemia, 140–141, 627, 778, 782
perinatal infections, 567, 814–815, 817, pituitary adenoma, 69–70, 87–88, 107– polycythemia vera, 627
819, 821, 823, 825, 827 108, 110, 113–115, 123, 132–134 polydactyly, 185
perinatal transmission, 371, 417 pituitary gland, 70–71, 96, 100, 111, polydipsia, 81–82, 84, 110, 778
perineal, 810 117–118, 120 polyhydramnios, 184, 735–736, 738, 778,
perineum, 4, 51, 138, 425, 736, 808 pityriasis alba, 40 786–787
periodontal, 306, 383, 556, 647, 738 pityriasis rosea, 34–35 polymerase chain reaction, 178, 189, 283,
periodontal disease, 556, 738 pityriasis versicolor, 366 309, 317, 326, 329, 343, 346, 351,
periodontitis, 216, 433 placenta, 173, 202, 237, 245, 252, 416, 353, 378, 384, 390–391, 400, 413,
periorbital, 126, 151, 347, 355, 427, 453, 545, 732–736, 738, 775, 778–780, 418, 425, 433, 438, 459–460, 476,
468, 653 787–788, 814, 817–819 486, 489, 495, 510, 514, 523, 549,
periosteal, 588, 592, 604, 608, 612, 614, placenta accreta, 732–733, 736 554, 559, 567, 571, 581, 816, 823
616 placenta increta, 732 polymyalgia rheumatica, 643
periosteum, 588, 608, 614 placenta percreta, 732–733 polymyositis, 642, 652, 656
periostitis, 36, 545 placenta previa, 732–733, 736, 738 polyomavirus, 494–495
peripheral nervous system, 298 placental abruption, 735, 738, 786, 788 polyp, 167, 745
peripheral neuropathy, 126, 245, 298 plague, 537–539 pompe disease, 269
peripheral vascular disease, 52, 81, 245, plantar, 245, 475, 488, 510, 666, 674–675 pontiac fever, 530
261, 817 plaque, 25, 30, 32–34, 36–37, 259, 262, popliteal fossa, 658–659
peripheral/primary hypogonadism, 93 366, 383, 397, 427–428, 649 portal hypertension, 271, 340, 418, 574
peritoneum, 340, 383, 441, 443–444, 572, plaque psoriasis, 36 positron emission tomography, 608
760, 791, 793 plasmapheresis, 127, 224 post-polio syndrome, 490
peritonitis, 320, 340, 356, 402, 439, plasmodium, 412, 414, 416 post-streptococcal glomerulonephritis, 226
526–527, 529, 584, 753, 795 plasmodium species, 414 posterior chamber disease, 448
pernicious anemia, 122, 125, 223–224, plastic surgery, 374 posterior dislocation, 716–717
304–305 platelet count, 780, 788, 820 posterior pituitary, 110
perspiration, 140, 351, 367 pleomorphic, 135, 325, 383, 434, 458, 469, posterior reversible encephalopathy
perthes disease, 591, 594 478, 517, 524, 677, 723 syndrome, 788
pertussis, 314, 345–346 plethoric, 133 postherpetic neuralgia, 430
pes planus, 154, 685 pleura, 461 postmenopausal, 745, 750, 752, 794, 796
pestis, 537–539 pleural effusion, 311, 329, 340, 350, 392, postorgasmic illness syndrome, 228
pet scan, 609, 614 517, 559, 562, 572, 584, 636, 749, postpartum, 116–118, 125, 145, 556, 733,
petechiae, 203, 224, 306, 329, 346, 350, 820 736, 775–776, 779, 786, 789
357, 373, 390, 393, 395, 449, 519, pleural space, 340 postpartum hemorrhage, 116, 733, 736
521, 543, 581 pleurisy, 206 postpartum pituitary gland necrosis, 118
ph, 12, 85, 194, 254, 325, 360, 409, 532, pleuritis, 226, 636, 650 postpartum thyroiditis, 145
536, 576–577, 600, 626, 781, 809 plummer, 128 poststreptococcal glomerulonephritis, 50,
phagocyte, 209, 212–215, 349, 385 pml, 495–496 226
phagocyte deficiencies, 212 pmr, 643 postural hypotension, 77, 781
phalanges, 599, 606, 613, 693 pneumococcus, 16, 167 potassium, 6, 55, 60, 68, 71–72, 74, 78–79,
pharyngitis, 204, 343, 347, 356, 371–372, pneumocystis carinii, 469 85, 87, 138, 243, 245, 276–277,
424, 538, 544, 555–556 pneumocystis jirovecii, 203, 469 280, 362, 498, 781
pharynx, 437, 441, 488, 570 pneumocystis pneumonia, 469 pott’s disease, 584, 588, 705
phenotype, 176–177 pneumonia, 18, 58, 119, 131, 149, 179, poxviridae, 497
phenylalanine, 231–232, 237 190, 197, 204, 214, 300, 308, 311, prader, 112, 162, 169, 172
phenylalanine embryopathy, 237 315, 342–344, 346–347, 350, prader-willi syndrome, 169, 172
42 OSMOSIS.ORG
precancerous, 1, 29, 741, 745 pseudogout, 630–631 radiology, 232, 734, 737, 798
precocious puberty, 99, 165, 746 pseudomembranous colitis, 318 radiolucent, 264, 600, 614, 628, 817
prediabetes, 82–84 pseudomonas aeruginosa, 48, 533, 587 radiopaque, 532
preeclampsia, 735, 738, 764, 776, psoriasis, 21, 35–37, 632–633 radiotherapy, 17, 30, 100, 130, 164, 616,
778–780, 782, 785, 787–789 psoriatic arthritis, 36–37, 632–633 687, 729–730, 740, 744–747, 750,
prehn sign, 803 psychogenic, 757, 806 752, 766, 768, 770, 772
premalignant, 722, 763, 799 psychogenic amenorrhea, 757 radius, 104, 605, 610
premature birth, 169, 171, 264, 409, 412, psychosis, 70, 138, 180, 252, 579, 650 rai, 224
735, 814, 818, 825 psychotherapy, 174, 178, 180, 641, 758, range of motion, 470–471, 590, 594, 604,
prenatal care, 738, 823 807 610, 612, 617–618, 621, 625,
prenatal diagnosis, 74, 181, 183–185, pterygium, 33 627–628, 638, 643, 661, 666, 685,
288–289, 297, 692, 732, 817 ptosis, 136, 224, 284, 317, 467 697, 707, 710, 715–716, 718–719
prepuce, 352, 767 puberty, 40, 74, 94–101, 109, 113, 165, rapidly progressive, 467, 534
pres, 777, 788 171, 173–174, 746, 749–750, 752, rash, 10, 13, 16–17, 32–36, 46–47, 138,
preterm birth, 553, 733, 738, 774–775, 758 159, 188, 190, 192, 198, 206,
782, 786, 826 pubic louse, 376 226–227, 230, 303, 314, 357,
priapism, 806, 808–809 pubic symphysis, 736 373–374, 389, 392, 394, 397, 418,
primary amoebic meningoencephalitis, 332, pubis, 375–376, 694 424, 426–427, 429–430, 438, 445,
334 pulmonary artery, 163, 817 479–480, 485, 488, 497, 514–515,
primary ciliary dyskinesia, 166 pulmonary aspergilloma, 461–463 519, 521–522, 540–541, 543,
primary cutaneous infections, 385 pulmonary disorders, 289, 509 545–546, 549, 556, 566–567, 573,
primary hypothyroidism, 114, 125–126 pulmonary edema, 247–248, 328, 579, 595, 639, 646, 649–650, 653,
primary teeth, 198 412–413, 450, 521, 787 722, 767, 815, 817–818, 827
primary tuberculosis, 583–584 pulmonary embolism, 138 raynaud syndrome, 644
primary/hypergonadotropic hypogonadism, pulmonary hypertension, 574, 642, 646, raynaud’s disease, 644–645
96 782, 820 raynaud’s phenomenon, 645–646
prion, 179 pulmonary hypoplasia, 183, 597, 679, 785 reactivation tuberculosis, 583–584
probiotic, 319 pulmonary mucormycosis, 467–468 reactive arthritis, 226, 228, 343, 359, 536,
proctitis, 343, 371–372, 425 pulmonary sporotrichosis, 470 634, 755
progesterone, 74, 96, 100–101, 109, 721, pulmonary stenosis, 131 reading frame, 162
723, 758, 774 pulse, 52, 124, 319, 339, 363, 435, 483, recombinant, 113, 172, 243, 290–291,
progestin, 116, 758, 797 617–618, 712, 716, 737, 778, 788 363, 420, 508
prognathism, 108, 694 punch biopsy, 448, 512, 729 recombination, 148, 158
prognosis, 27–28, 136, 290, 369, 418, 645, pupil, 317, 467, 546 rectal prolapse, 151, 454
654, 721, 728 purine, 162, 292–293, 304, 626–627, 629 rectouterine pouch, 791
progressive multifocal leukoencephalopathy, purpura, 79, 201, 223–224, 226, 350, 357, rectum, 137, 358–359, 444, 454, 574, 770,
503 373, 390, 528, 566 810
prolactin, 87, 89, 96, 108, 113–116, 133, purulent, 19, 45–47, 343–344, 352–355, recurrent laryngeal nerve, 143–144, 146
144, 165, 758, 806 357, 370–372, 384, 435, 471, 473, red blood cell, 258, 282, 414–415, 485,
prolactinoma, 89, 113–114, 132–133, 758 493, 554, 584, 741, 754–756, 775 778
promoter, 162, 176–177, 502 purulent cellulitis, 46 refeeding syndrome, 276
proprioception, 305, 546, 699, 707 pus, 36, 49, 352, 402, 405, 589 regurgitation, 131, 545, 581, 625, 634
prostaglandin, 8, 221, 448, 613, 739, 763, pyelonephritis, 110, 233, 380, 464, rehabilitation, 40, 652, 668, 673, 675, 696,
807–808 526–527, 529, 532–533, 551, 553, 704, 715
prostate, 576, 603, 768–770, 799–801, 584, 753, 810 reinke crystals, 749, 770
803, 805, 807–811, 813 pyknodysostosis, 603 reiter syndrome, 634
prostate cancer, 768, 808 pyridoxine, 14 relapsing hepatitis, 489
prostate enlargement, 769 pyrimidine, 25, 161–162, 292–294, 304, relaxant, 620, 623
prostate gland, 768, 809, 811 626 remission, 395
prostatectomy, 770, 801, 806 pyruvate dehydrogenase deficiency, 285 renal, 4, 18, 58, 71, 80–81, 86, 102–103,
prostatitis, 371, 526–527, 529, 532, 553, pyuria, 343, 381, 528, 532, 544, 574, 584, 105, 110–111, 114, 136, 151,
559, 753, 755, 809–811 800, 804 153–154, 162–163, 165, 167,
prosthetics, 549–550 q fever, 517 171, 175, 231, 233, 240, 243, 245,
protease, 304, 322, 354, 369, 501, 506, quadriceps, 595, 672, 674 248–249, 251–255, 262–264, 267,
520, 548, 635–636, 713 quadriparesis, 439 272, 293, 296, 313, 320, 328–329,
protease inhibitor, 506 quadriplegia, 491 333, 347, 363, 380, 390, 395–396,
proteinuria, 52, 153, 226–227, 329, 381, quiescent, 414 413, 415, 418, 423, 464, 468, 515,
390, 396, 528, 544, 648, 779–780, quinidine, 416 519, 521–522, 528–530, 532–533,
787–788 quinine, 416 536, 555, 573, 600, 627, 639, 642,
proteus mirabilis, 532 quinolones, 357, 528, 533 646–647, 649–650, 678, 714, 735,
prothrombin, 254, 266, 390, 419, 521, 548 rabies, 511–513 782, 785–788, 800, 812–813,
prothrombin time, 254, 266, 419 radiation burns, 3 817–818
protozoa, 197, 411, 576, 578, 827 radiation pneumonitis, 242 renal agenesis, 785
pruritus, 10–14, 17, 27, 33–34, 59, 61, 64, radiation therapy, 24, 86–89, 96, 134, 160, renal calculus, 533
66, 164, 221–222, 340, 366–367, 607, 609, 611, 678, 722–723, 742 renal cell carcinoma, 813
371–372, 375–379, 444–446, 448, radiculitis, 350 renal disorders, 650
490, 498, 574, 576, 579, 755 radioactive iodine, 120, 145, 224 renal failure, 4, 18, 114, 153, 245, 248,
pruritus ani, 444 radiography, 658, 662–663 254–255, 262, 264, 272, 293, 296,
psa, 769–770, 800, 810 radioimmunoassay, 402 313, 347, 363, 395, 413, 415, 423,
psammoma bodies, 751 radioisotope, 123, 129 515, 519, 528–530, 536, 573, 627,
pseudoaneurysm, 616, 618–619 radiologic, 596 649, 735, 788, 800
OSMOSIS.ORG 43
renal osteodystrophy, 103 rotterdam criteria, 99 408, 461, 522, 525, 559, 561, 563,
renal tubular acidosis, 163, 600 roundworm, 436–437, 439, 441, 443, 445, 580, 590, 625, 643, 664, 754, 775
reoviruses, 499 447, 449, 451, 453, 455, 457 segmental vitiligo, 41
respiratory alkalosis, 236 rrna, 384, 519 segond fracture, 667
respiratory disorders, 283 rsv, 478, 483 seizure, 227, 229, 249, 302, 341, 386,
respiratory distress syndrome, 149, 245, rubella, 480, 482, 566–567, 782, 815–817 390–391, 393, 415, 451, 488, 495,
255, 365, 373, 412, 415, 560 rubella virus, 566–567, 816 512, 519, 565, 776–777, 789, 815,
respiratory failure, 252, 285, 365, 389–390, rufous oculocutaneous albinism, 39 824–825, 827
407, 434, 461, 478–479, 491–492, runny nose, 166 seizure disorder, 249, 825
522, 564, 568, 597 sacral, 698, 703 selective immunoglobulin a, 201
respiratory syncytial virus, 478, 483 sacrum, 56, 608 selenium, 280, 368
reticulocyte, 302, 305 sagittal, 88, 129, 157, 602, 604, 659, 673, sella turcica, 88, 108, 114, 291
reticulocyte count, 302, 305 684, 699, 703, 708–709, 741, 755, semen, 390, 813
retina, 153, 299–300 774, 797 semen analysis, 813
retinal detachment, 154, 156, 451 salicylates, 612–613, 635 seminomas, 770, 772
retinitis pigmentosa, 258 saline, 85, 119, 166, 285, 341, 409, 577, sennetsu fever, 518–519
retinoblastoma, 607, 614 754, 809 sensorineural hearing loss, 815, 817–818,
retinopathy, 81, 153, 163, 817 salivary gland, 414, 482, 647–648 827–828
retrovirus, 501–503, 505, 507, 509 salmonella, 16, 531, 634 sentinel lymph node, 389, 723
reverse transcriptase, 331, 501 salmonellosis, 531 sentinel lymph node biopsy, 723
reye’s syndrome, 424, 427 salpingitis, 343, 444, 753, 760 sepsis, 5, 18, 46, 56, 58, 76, 79, 200, 239,
rf, 36, 625, 634, 636–637, 642, 648 salpingo-oophorectomy, 750, 752, 796 315, 318, 320, 333, 347, 357, 369,
rhabdomyolysis, 255, 267, 269–270, 272, salt, 52, 73–74, 77, 91, 119, 246, 281, 385, 373, 377, 389, 402, 405, 407, 464,
308, 347, 394, 473, 544, 711–714 548 522, 528, 532–534, 538, 549–550,
rhabdomyosarcoma, 171, 677 salter-harris fracture, 663 552–556, 588, 739, 753, 775, 811,
rhabdomyosarcoma, embryonal, 677 san joaquin valley fever, 560 820, 825–826
rhabdoviruses, 511, 513 sarcoidosis, 59, 228, 350, 461, 585 septate, 560
rheumatic fever, 223–224, 555 sarcoma, 159–160, 422, 427–429, septic, 52, 192, 320, 322, 354–357, 370–
rheumatism, 560 608–609, 687, 729, 767 371, 407, 412, 449, 464, 515, 517,
rheumatoid arthritis, 36, 122, 196, 201, sarcomatoid carcinoma, 767 526–527, 535, 549, 553, 589–590,
228, 589, 602, 621, 629, 632, 635, sarcoptes scabiei, 377 659–660, 664, 762, 775, 820
637, 647–648, 658–659, 686, sars, 364–365 septic arthritis, 354–357, 370, 526, 549,
704–705 scabies, 377–378 553, 589–590, 664, 820
rheumatoid factor, 36, 625, 648 scalded skin syndrome, 58 septic bursitis, 659–660
rheumatoid nodule, 638 scapula, 618, 818 septic shock, 357, 407, 412, 449, 464, 515,
rheumatoid spondylitis, 624 scarlet fever, 555–556 526–527, 535, 775, 820
rhinitis, 10, 166–167, 219–220, 344, 483, scc, 29, 767 septicemia, 78, 354, 370, 374, 415, 535,
546, 554, 818 scheuermann’s disease, 699 538
rhinocerebral mucormycosis, 467 schistosomes, 570, 573 septo-optic dysplasia, 110
rhinophyma, 57 schizophrenia, 218, 299, 503 septum, 459, 462, 469
rhinorrhea, 219–221, 247, 308, 365, 483, schlatter disease, 591, 595–596 sequencing, 149, 158, 165, 203, 283, 678
493 schnitzler syndrome, 603 serositis, 650
rhinovirus, 483, 487, 492 sciatic nerve, 707 serotonin, 8, 131, 137, 178, 180, 254–255,
rib, 34, 290, 346, 597, 625, 689 sciatica, 703, 708 641, 806
ribonucleic acid, 577 scid, 187–189, 218, 500 serotonin syndrome, 254
ribosome, 167, 520 scintigraphy, 7, 133, 139, 142, 591–592, serotype, 395, 527–528, 624
rickets, 264, 591, 598, 605–606, 688–689 594, 604, 613, 648 serratia marcescens, 535
rickettsia, 520, 522 sclera, 231, 597 sertoli cells tumor, 770
rickettsia typhi, 522 scleritis, 636 sertoli-leydig cell tumors, 749
rickettsial diseases, 514–517, 519, 521 sclerodactyly, 640, 642, 645 serum sickness, 226–227
riedel’s thyroiditis, 146 scleroderma, 644–646, 659 severe combined, 187–188, 218, 469
right heart, 340 sclerosing adenosis, 724–725 severe combined immunodeficiency, 188
rigid pes planus, 685 sclerosing cholangitis, 400 severe dengue, 392
rind sign, 592 sclerosis, 228, 426, 589, 600, 604, 608, severe respiratory syndrome, 365
ritter disease, 549 610, 612, 625, 640, 642, 645–646, sex chromosome, 173–175
rna, 177, 304, 325, 327–328, 330, 364, 662, 680, 718, 788, 806, 817 sex chromosome disorders, 173, 175
388, 390–391, 417, 421, 472–473, scoliosis, 97, 149, 154, 156–157, 164, sex cord-gonadal stromal tumor, 749
478, 480, 482, 484, 487, 491, 499, 172, 184, 249, 592, 597, 612–613, sex cord/gonadal stromal tumors, 770
501–502, 506, 508–509, 511–512, 701–702 sexual abuse, 797
565–568, 577, 816 scrofula, 584 sexual dysfunction, 704
rna polymerase, 388 scrotum, 51, 94–95, 803–804, 811–813 sexually transmitted disease, 343, 576,
rocky mountain spotted fever, 520 scurvy, 306–307 754–755
rods, 310–311, 313, 315–317, 319, 321, sebaceous gland, 14 sheehan’s syndrome, 116–118, 125
323, 358–359, 361, 363, 523, seborrheic dermatitis, 367–368 shigella, 536–537, 634
525, 527, 529, 531, 533, 535, 537, seborrhoeic dermatitis, 14, 366–367 shigellosis, 528, 536
539–540, 591, 598 sebum, 14, 44–45, 366 shingles, 429–431
rosacea, 57 secondary, tertiary hypothyroidism, 125 shock, 52, 62, 76–77, 79, 115, 118, 219,
roseola, 422, 426–427 secondhand smoke, 306 221, 233, 245, 311, 320, 328, 352,
roseola infantum, 427 secretin, 142 357, 363, 373, 389–390, 392–393,
rotator cuff, 718 sedatives, 440 395, 407, 412, 415, 441, 449, 464,
rotavirus, 499 sedimentation rate, 46, 60, 63, 214, 227, 499, 515, 519, 522–523, 526–527,
44 OSMOSIS.ORG
533, 535, 548–549, 553, 555–556, soft tissue, 7, 30, 43, 45, 47, 49, 51, 53–55, status epilepticus, 776
697, 716, 732, 735, 737, 775, 820 57, 108, 133, 216, 288, 356–357, std, 576, 754–755
shock treatment, 519 383, 405, 523, 526, 529, 533, 549, stem cell, 187, 197, 243, 297–298, 392,
short-term memory, 177, 541 555–556, 559, 595–596, 608, 422, 461, 494, 772
shoulder, 509, 589, 609, 643, 680, 694, 611–612, 614, 637, 679, 696, 709, stem cell transplantation, 187, 197,
702, 710, 716–719, 736, 760, 778, 715, 736 297–298
793 somatic, 81, 132, 162–164, 641 stenosis, 71, 131, 150–151, 163, 167, 182,
shunt, 283 somatostatin, 88, 107–108, 112, 132–133, 259, 288, 693, 704–705, 707, 808,
siadh, 118–119 137, 139, 142 817
sibling, 249 somatostatinoma, 133–134, 137–139 stereotactic, 88–89, 134
sicca syndrome, 647 somatotropin, 112 sternum, 15, 184, 689–690
sickle cell anemia, 162, 809 south american blastomycosis, 563 steroid, 22, 69–71, 73–74, 76, 93, 101,
sickle cell disease, 485 spasm, 322–323, 355, 683, 788 378, 449, 594, 705
sickle cell trait, 415 spasticity, 257, 292–293, 297, 510, 686 stevens-johnson syndrome, 18–19
sigmd, 200 spect scan, 7 stillbirth, 315, 567, 778, 818
sigmoid, 693 speculum, 577, 754, 763 stomatitis, 138, 302, 305
sigmoidoscopy, 319, 402 speech disorder, 239 stool, 139, 312, 319, 321, 330–331,
silver, 36, 461, 469–470, 524–525, 530, speech therapy, 168–170, 174, 655 338–339, 359, 361–363, 365,
543, 563, 633 sperm, 93–94, 97, 166, 763–764, 813 399–400, 402, 404, 418, 421, 438,
sinus, 49–50, 88–89, 198–199, 202, 251, spermatic cord, 803, 811, 813 441–442, 450–451, 454, 489, 500,
352, 355, 383–384, 435, 461, spermicides, 755 531, 537–538, 571–574, 635
467–468, 588, 693, 746, 770 sphincter, 512 strabismus, 40, 149, 151, 249, 258
sinusitis, 166, 197, 200, 204, 342–343, sphingolidosis, 297, 299 straight leg raise test, 703
354–356, 462, 473, 493, 554–555, spinal column, 696, 703, 710 strain, 363, 416, 453, 473, 520–521, 555,
678 spinal cord, 136, 288, 290, 322, 340, 383, 621
sipple syndrome, 134 445, 490, 510–511, 545, 574, 602, strep, 552, 555, 820
siv, 502–503 612, 622, 636, 704–705, 769, 808 streptococcus, 36, 47, 52, 59, 79, 192–193,
sixth disease, 427 spinal disc herniation, 703 197, 199, 203, 473, 552–553,
sjögren’s syndrome, 647–648, 654 spinal disorders, 41, 696–697, 699, 701, 555–557, 739, 775, 784, 820, 822
skeletal dysplasia, 687–688, 692–695 703, 705, 707, 709 streptococcus agalactiae, 552, 820
skeletal muscle, 121, 124, 267, 452, 654, spinal nerve, 136, 701 streptococcus pneumoniae, 79, 192–193,
677, 783 spinal stenosis, 693, 704–705, 707 197, 199, 203, 473, 553
skeleton, 156, 616, 626 spine, 36, 182, 231, 592, 600, 602, 608, streptococcus pyogenes, 47, 555
skin biopsy, 2, 10, 16, 19, 25, 33, 35–36, 612–613, 624–626, 661, 696–697, streptococcus viridans, 556
38, 48, 58, 64, 66, 153, 155, 459, 699–700, 703, 705, 707–709, 769 stroke, 56, 71–72, 115, 118, 234, 260, 284,
597 spirochete, 542, 544–545, 818 430, 523, 535, 545, 649, 788
skin breach, 45 spleen, 223, 296, 299, 389, 415, 432–433, strongyloides stercoralis, 449
skin cancer, 25–26, 29, 38–39, 161 463, 524 struvite stones, 532, 535
skin disorders, 10, 17, 32, 48 splenectomy, 203, 588 stuttgart disease, 544
skin lesions, 1, 29, 33, 36, 60, 159, 282, splenomegaly, 194, 267, 351, 380, 418, subacute bacterial endocarditis, 226
315, 349, 427–428, 430, 433, 458, 422, 432, 524, 636 subacute sclerosing panencephalitis, 480
471, 497, 510, 559, 564, 823 spondylitis, 350, 602, 624–626, 634, 659, subarachnoid, 115, 119, 335, 542
skull, 108, 136, 156, 164–165, 290, 572, 698, 704–705 subarachnoid hemorrhage, 115, 335, 542
592, 597, 600, 604–605, 684, spondyloarthritis, 705 subclinical disease, 207
693–695 spondylodiscitis, 705 subcutaneous, 27, 30, 45–46, 51–53, 56,
slapped cheek disease, 484 spondylolisthesis, 699, 706–709 59, 159, 241–242, 266, 276, 279,
sle, 190, 192, 200, 226–227, 639, 642, spondylolysis, 708–709 317, 320, 322, 385, 445–448, 455,
644, 649–650 spondylosis, 625, 704, 710 470, 524, 555, 572, 579, 782–783
sleep, 14, 172, 194, 287, 290, 302, 355, spontaneous abortion, 162, 389, 543, 761, subdural hematoma, 778
492, 542, 579, 641, 684, 693, 811 764 subluxatable, 682
sleep apnea, 172, 290, 684, 693 spontaneous bacterial peritonitis, 529 subluxation, 287, 290, 595, 636, 668, 682,
sleep disturbances, 579, 641 sporothrix schenckii, 470 717
sleeping sickness, 578–579 sporotrichosis, 470–471 submucosal myoma, 796
slipped capital femoral epiphysis, 663 sprain, 674–675 subserosal myoma, 796
slipped disc, 703 sprained ankle, 674 sudden cardiac death, 259
slow virus, 603 sputum, 166, 309, 369–370, 436, 442, sudden infant death, 317
sly syndrome, 287–288 460, 462, 469, 471, 473, 529, 531, sudden infant death syndrome, 317
small cell prostate cancer, 768 538, 543, 559, 561, 563, 573, sulcus, 352
small for gestational age, 783, 815, 817 584–586, 777 sulfonamide, 16, 18, 59, 386
small intestine, 131, 265, 330, 335, 362, squamous-cell carcinoma, 9, 29–32, 49, sulfonylurea, 84, 119
403, 437, 441, 443–444, 451, 454, 245, 741–742, 767–768 sunburn, 8–9, 39–40
646 staphylococcal infection, 376 sunscreen, 2, 9, 58, 161, 264, 654
smallpox, 497 staphylococcal scalded-skin syndrome, 58, superior vena cava syndrome, 128
smooth muscle, 219, 259, 780, 796, 798, 549 supination, 717
800–801 staphylococcus, 11, 16, 52, 79, 333, suprasternal notch, 129
snail fever, 573 548–551, 587, 705, 784, 822, 825 surface epithelial-stromal tumor, 751
sodium, 6, 52, 71–72, 74, 77–79, 103, 111, staphylococcus aureus, 11, 52, 333, 548, surfactant, 12, 560, 778
118, 137, 141, 233, 236, 243, 587, 705, 784 sv, 242
246–247, 249, 277, 280, 320, 362, staphylococcus epidermidis, 550 swamp fever, 544
495, 662, 781 staphylococcus saprophyticus, 551 sweating, 48–49, 56, 108, 135–136, 140,
soft palate, 427, 567 statin, 257, 260–262, 713, 806 165, 240, 512
OSMOSIS.ORG 45
swimmer’s itch, 573 testicle, 771, 802–803, 807, 811–813 tongue, 61, 126, 134–135, 168–170, 179,
swineherd’s disease, 544 testicular cancer, 95, 770, 772 182, 288, 290, 428, 464, 488, 568
sympathetic nervous system, 120, 644 testicular disorders, 799, 801, 803, 805, tonic-clonic seizure, 776–777
symphysis pubis, 694 807, 809, 811, 813 tonsillitis, 190, 347, 383
syncope, 77, 221, 399, 760 testicular torsion, 801, 804, 807, 811–812 tophaceous gout, 628
syndactyly, 685 testosterone, 73, 87, 94–98, 109, 116, 165, tophi, 292–293, 626, 628
syndesmotic sprain, 674–675 174, 749, 758, 769–770, 799, 802, tophus, 628–629
syndrome of inappropriate, 118 806 torches, 567
syndrome of inappropriate antidiuretic, 118 testosterone replacement therapy, 174 torsades des pointes, 105
syndromes, 27, 86, 130, 134, 136, 141, tetanus, 221, 252, 314, 322–323, 346, 513 torticollis, 622, 682
148–149, 151, 154, 242, 308, tetany, 105, 146, 218, 735 torticollis, congenital, 682
327–328, 364, 423, 472, 497, 553, tetracyclines, 285, 323, 357, 435, 531– toxemia, 317
559–560, 562–563, 677, 685, 753, 532, 539 toxic epidermal necrolysis, 18–20
801 tetralogy of fallot, 162–163, 218 toxic multinodular goiter, 128
synovia, 632 thalamus, 566 toxic shock syndrome, 549, 555–556
synovial sarcoma, 687 thalassemia, 485, 808 toxocara canis, 451–452
synovitis, 634, 642, 664 therapeutic, 159, 254, 317, 518, 665, 726, toxoplasma gondii, 16, 332, 335–337, 567,
syphilis, 353, 545–546, 650, 815, 818–819 782 827
systemic lupus erythematosus, 18, 41, 122, thermal burns, 2 toxoplasmic chorioretinitis, 336–337
190, 226, 426, 602, 644, 649, 762, thiamine, 286 toxoplasmosis, 332, 335–337, 412, 503,
788 thiazide diuretics, 72, 83, 111, 260, 262 567, 761, 782, 815, 827
systemic mycoses, 558–559, 561–563 thiazides, 627, 629 tpn, 265
systemic plague, 538 thin basement membrane nephropathy, trachea, 146, 435, 439, 442
systemic sclerosis, 640, 642, 645–646 153 tracheostomy, 168
systolic, 393, 779 third-degree burns, 713 trachoma, 343
t cell, 10, 18, 189, 197, 210–211, 217–218, thrombi, 522, 582 traction, 595, 667, 689, 736
228–229, 479, 509–510, 624, 632, thrombin, 736 transfer rna, 502
647, 652 thromboangiitis obliterans, 644 transfusion, 209, 223–224, 228, 329, 336,
t cell leukemia/lymphoma, 509 thrombocytopenia, 136, 197, 203, 246, 393, 396, 412–413, 415, 422, 486,
t-cell deficiencies, 187, 217 296, 299, 329, 350–351, 365, 374, 503, 509, 580–581, 734, 736, 738,
tabes dorsalis, 546 390, 393, 413, 416, 423–424, 509, 786
tachycardia, 79, 127, 135, 140, 145, 221, 517, 519, 521, 528, 530, 536, 538, transfusion reactions, 224
224, 242, 245, 247–248, 255, 363, 541–542, 574, 580, 600, 647, 650, transient aplastic crisis, 485–486
373, 407, 430, 512, 623, 739, 760, 677, 787, 817–818, 827 transient hypogammaglobulinemia, 202
764, 775, 777, 781, 793, 826 thrombophilia, 761 transient synovitis, 664
tachypnea, 79, 124, 166, 206, 248, 255, thrombophlebitis, 52 transitional cell cancer, 768
363, 390, 407, 469, 483, 529, 690, thrombosis, 3, 78, 138, 194, 320, 373, translation, 177, 391, 484
820, 825–826 407–408, 439, 464, 467, 538, 616, translocation, 149, 181–184, 313, 414,
taenia, 338 618–619, 649, 761, 788 608, 677
talipes equinovarus, 681 thrush, 188, 463–464 transplant, 103, 137, 154, 197, 205, 208,
talus, 681, 686 thymine, 8 210–211, 213, 229, 235–236, 243,
tamoxifen, 147, 165, 793 thymus, 131, 217–218, 276 254, 288, 290–291, 308, 319, 336,
tanner scale, 93, 97, 100, 109 thyroglobulin, 125, 144–145 386, 422, 426, 428, 450, 460–461,
tapeworm, 305, 338–341 thyroid cancer, 90–91, 143 464, 467, 469, 494, 530, 554, 581
target lesions, 17 thyroid gland, 90, 92, 120, 123, 125, 128, transplant rejection, 205, 208, 229
tay-sachs disease, 300 143–144, 146, 243 transurethral resection, 801
tb, 228–229, 583–586, 633 thyroid gland dysfunction, 125 transvaginal ultrasound, 739, 760, 764,
tbrf, 542 thyroid hormone, 92, 96, 107, 120, 123, 774, 797
td, 314, 323 125, 128, 143–145, 147, 223, 281 transverse, 55, 175, 182, 245, 423, 540,
te, 320 thyroid scan, 92 599, 604, 606, 707
teeth, 97, 108, 151, 170, 198, 218, 306, thyroid storm, 120, 122–123, 127 transverse myelitis, 423
383, 437, 596–597, 620, 694, 746, thyroid-stimulating hormone, 63, 107, 115, trauma complications, 697, 703, 711, 713
770, 818 132, 165, 281, 602 travellers’ diarrhea, 527
telangiectasia, 25, 57–58, 161, 217, 640, thyroidectomy, 120, 123–124, 129, 135 treacher collins syndrome, 167–168
645 thyroiditis, 41, 125–126, 143–147, 228 trematodes, 570–571, 573, 575
telogen effluvium, 22 thyrotropin, 88, 116, 120 tremor, 124, 145, 151, 177, 224, 234, 252,
temporal arteritis, 643 thyroxine, 120, 145, 602 255, 394, 568, 579, 581, 764
temporal bone, 593 tibia, 588, 592, 607, 610, 612–614, 618, trench fever, 376
temporomandibular joint, 620–621 668–669, 671, 674–676, 818 treponema pallidum, 353, 545–546, 818
temporomandibular joint dysfunction, tibial torsion, 691 trich, 576
620–621 tick bite, 515–516, 518–521, 540 trichinella spiralis, 452
tendinopathy, 673, 719 tick-borne relapsing fever, 542 trichomona, 16, 576–577
tendonitis, 634, 686 tinea barbae, 48 trichomonas vaginalis, 576
tenesmus, 344, 359, 363, 372, 425, 454, tinea capitis, 55 trichomoniasis, 576
528, 536 tinea unguium, 54 trichuris trichiura, 454
tension, 15, 669 tinea versicolor, 366–368 tricuspid regurgitation, 131, 581
teratogen, 782 tinnitus, 545, 621 trigeminal nerve, 430, 621
teratoma, 747, 770, 793 tmj, 620–621 triglyceride, 256–257, 262
terminal ileitis, 537 tobacco, 29, 483, 626, 766–767, 775 triiodothyronine, 120, 145, 165
testes, 93, 95–96, 99, 149, 174, 177, 542, tocolytic, 739 trimester, 274, 389, 396, 567, 760, 764,
570, 801–802, 811 togaviruses, 565, 567, 569 773, 778, 782, 801
46 OSMOSIS.ORG
trinucleotide repeat expansion diseases, 478–479, 483, 530, 664 vasodilator, 221
176–177, 179 upper respiratory tract infections, 434 vasomotor, 77
triple i, 775 urate, 293, 626–629, 660 vasopressin, 77, 110–111, 787
triploid, 764 urea, 55, 119, 236, 246, 276, 278–279, vasopressors, 53, 77, 79, 205, 221, 408,
trisomies, 162, 181, 183, 185 360–361, 390, 500, 532, 714, 781, 826–827
trisomy 13, 21, 181–182, 184 800, 810 vasospasm, 644
trna, 388 urea breath test, 361 venereal disease, 546, 819
tropical spastic paraparesis, 509–510 uremia, 544 venom, 62, 713
truncus arteriosus, 218 uremic syndrome, 536 ventilation, 206, 208, 243, 318, 329, 365,
trypanosoma, 578–582 ureter, 233, 293 380, 390, 408, 483, 492, 513, 526,
trypanosoma brucei, 578–579, 581 urethra, 551, 576, 755, 768–769, 804–805 534–535, 827
trypanosoma cruzi, 580 urethral strictures, 214, 371 ventilator, 407–408, 534
tsh, 107, 115–116, 120–128, 132–133, urethritis, 343–344, 370–371, 532, 536, ventral, 437, 570, 804
144–146, 165, 281, 602 553, 576, 634–635, 755–756 ventricular dysrhythmias, 245, 255
tsi, 120, 122, 124, 531–532 uric acid, 267–268, 293, 626–629 ventricular hypertrophy, 72
tss, 549 urinalysis, 60, 80, 82, 119, 131, 153, 227, ventricular septal defect, 249
ttp, 528 233, 248, 253, 329, 381, 495, 526, verruca, 475
tubal pregnancy, 760 528, 532, 544, 551, 574, 647, 711, verrucous carcinoma, 767
tubercle, 595, 804 781, 799–800, 810, 821 vertebra, 288, 588, 607, 698–699, 702,
tuberculosis, 59, 77–78, 110, 119, urinary bladder, 769 705
228–229, 461, 503, 583–588, 698, urinary incontinence, 608, 704 vertebral artery, 697
705, 803 urinary tract, 33, 148, 150–151, 233, vertebral column, 533, 602
tubes, 95, 166, 524, 751, 753–754, 775, 292–293, 380, 491, 494, 526, vertical fetal infection, 485
790 532–533, 535, 550–551, 738, 753, vertical transmission, 422, 425, 475,
tularemia, 347 767, 785, 803, 805, 810 485–486, 501, 826
tumor debulking, 740 urinary tract infection, 494, 803, 810 vertigo, 697
tumor necrosis factor, 8, 50, 121, 210, 229, urine ph, 532 vesical, 573
449 urine test, 174 vesicle, 369, 378, 425, 622
tumor suppressor gene, 92 urogenital, 181, 343, 574 vesicular, 180, 222, 430, 438, 488–489,
turbinate, 462 urogenital infection, 343, 574 511, 546, 764, 818
turner syndrome, 96, 100, 112, 175, 758 urticaria, 59, 61–63, 191, 219, 221–222, vesiculobullous diseases, 64–65, 67
twin, 738, 786 226, 340, 441, 445–446, 449, 451, vessels, 3, 6, 25, 27, 36, 61–62, 81, 90,
tympanic membrane, 355, 370, 427, 435, 573 103, 146, 156–157, 166, 184, 208,
554 uterine fibroid, 796 262, 295, 320, 373, 456, 498, 579,
type i, 41, 51, 80–81, 84, 111, 122, 150, uterine rupture, 736 594, 603, 636, 640, 644–645, 653,
152, 205, 219, 221, 228, 234, 256, uterus, 15, 95, 185, 570, 732–733, 656, 681, 733, 735–736, 740, 746,
268, 296, 596–597, 652, 661, 663, 735–738, 740–741, 753, 760, 764, 775, 795
677, 680, 685 790, 792, 795, 797 vibrio, 52, 362, 527
type i hypersensitivity, 219, 221 uti, 359, 380–381, 551 vibrio cholerae, 362, 527
type ia: immune-mediated diabetes, 81 uv, 3, 8–9, 25, 27, 29, 38, 57, 161, 325, vipoma, 132–134, 137–139
type ib: idiopathic diabetes, 81 649 viral hepatitis, 395
type ii, 52, 80, 82–84, 108, 142, 172, 180, uvb, 1, 13, 598, 605 viral infection, 354, 392, 394, 473, 478,
205–206, 223, 225, 234, 269, 296, uveitis, 350, 390, 394, 425, 447, 451, 459, 647, 656
597, 636, 649, 661, 663, 685 509, 544–545, 625, 818 viremia, 392–394, 481, 484–485, 488,
type ii hypersensitivity, 223, 225, 649 uvula, 427, 433 490–491, 566, 816
type iii, 52, 192, 205–206, 226–227, 234, vaccination, 79, 167, 190, 193, 199, 318, virion, 391, 494, 501–502, 509, 566
256, 270, 296, 531, 597, 649, 663, 322–323, 356, 419, 459, 481, 490, visceral leishmaniasis, 432
685 513, 545, 817 visual acuity, 39, 153, 336, 546
type iii hypersensitivity, 192, 226–227 vaccine, 189–190, 199, 204, 214, 227, vitamin a, 258, 274–275, 277, 480, 764
type iv, 12, 16, 52, 59, 81, 152–153, 205, 309, 311, 314, 318, 346, 351, 356, vitamin b12 deficiency, 304
223, 228–229, 256, 271, 349, 360, 363, 369, 372, 386, 391, 396–397, vitamin c, 302, 306
369, 377 420–421, 431, 474, 476, 479–482, vitamin c deficiency, 306
type iv hypersensitivity, 16, 81, 228–229, 490, 492, 500, 512, 518, 554, 567, vitamin d, 37, 98, 102, 104, 106, 169, 172,
377 585–586, 742 218, 263–264, 275, 591, 598–599,
type v, 256, 272 vagina, 33, 95, 425, 464, 549, 551, 601–603, 605–606, 687–689, 759,
ulcer, 30, 56–57, 82, 133, 142, 315, 344, 735–736, 741, 743, 753 797
347, 352–353, 407, 433, 445, 466, vaginal introitus, 352 vitamin d deficiency, 263
646, 767 vagus nerve, 312 vitamin e, 257–258
ulceration, 19, 25–26, 56, 242, 311, 314, valgus, 605, 667, 673, 676, 693 vitamin k, 265–266
343, 384, 386, 399, 425, 445, 449, valley fever, 560 vitamin k deficiency, 265
459, 462, 470, 502, 538, 644, 822 varicella, 46–47, 188, 203, 422, 429–431, vitiligo, 21, 41–42, 77
ulna, 605 815 vitiligo universalis, 41
ulnar, 156, 636–637 varicella zoster virus, 429 vkdb, 265
ultraviolet a, 33, 37 varicocele, 812–813 vl, 432–433
umbilical cord, 184, 216, 736, 775, 783, varus, 592, 681, 693 volar, 11, 220, 378
785–786, 818–819 vas deferens, 95, 803 volvulus, 441, 443, 447–449
umbilicus, 15 vasculitis, 59, 62, 199, 226, 350, 429–430, vomitus, 317, 330, 360
undescended testes, 174, 801–802 451, 520, 522, 579, 647, 650, 803 von gierke disease, 268
unhappy triad, 676 vasoconstriction, 6, 8, 418, 788 von willebrand disease, 736
upper limb injury, 715, 717, 719 vasodilation, 3, 6, 9, 59, 61, 138, 191, 219, vulgar psoriasis, 36
upper respiratory tract, 34, 345, 434, 458, 389, 407, 418 vulva, 33, 425, 430
OSMOSIS.ORG 47
vulvovaginal candidiasis, 463, 465
vulvovaginitis, 444
vvc, 463
wallace rule of nines, 5
warfarin, 265
wart, 497–498, 560, 818
warty tumors, 767
water soluble vitamins deficiency, 301
waterborne fever, 544
waterhouse-friderichsen syndrome, 76, 78
wbc, 46, 408, 469, 528, 590, 624, 775,
821, 825
weil’s disease, 544
west nile virus, 393
western blot, 329, 436, 453, 510, 514, 541
western equine encephalitis virus, 568
wf, 76–77, 83
wheals, 13, 62
wheezing, 131, 133, 182, 184, 207, 343,
357, 435–436, 442, 449, 462
whipworm, 454
white blood cell, 216, 255, 408, 468, 496,
528, 624, 664, 775
white blood cell count, 216, 255, 496, 624,
664
white matter, 453, 495–496, 510, 579,
775, 777, 815, 825
whooping cough, 345
wickham striae, 32
willi syndrome, 169, 172
williams syndrome, 150
wilms’ tumor, 171, 183, 616
wiskott-aldrich syndrome, 199, 203
wound botulism, 317
ws, 524–525
wuchereria bancrofti, 455
x chromosome, 96, 162, 173, 175, 194
x-linked agammaglobulinemia, 204
x-linked recessive, 39, 95, 188, 203–204,
231, 293, 295
xanthoma, 259, 261
xeroderma, 1, 25, 27, 29, 161
xeroderma pigmentosum, 1, 25, 161
xerosis, 161
y chromosome, 162, 173
y-linked, 162
yeast, 55, 348, 366–367, 420, 463,
469–470, 530, 558–560, 562–563
yellow fever, 395
yellow fever virus, 395
yersinia, 59, 537–539, 634
yersinia enterocolitica, 537–539, 634
yersinia marcescens, 537
yersinia pestis, 537–539
yersiniosis, 537
yolk sac, 746, 770
yolk sac tumor, 746, 770
zika virus, 396–397
zinc, 13, 82, 277, 280, 282, 352, 363, 368,
403, 493, 622
zinc oxide, 13
zollinger-ellison syndrome, 141
zoonosis, 347, 503
zygomatic bone, 167
zygote, 335
48 OSMOSIS.ORG

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NOTES

GENERALLY, WHAT ARE THEY?

SIGNS & SYMPTOMS TREATMENT

Figure 1.4 Histological appearance of the

PATHOLOGY & CAUSES TREATMENT

SIGNS & SYMPTOMS

PATHOLOGY & CAUSES DIAGNOSIS

SIGNS & SYMPTOMS TREATMENT

GENERALLY, WHAT ARE THEY?

Figure 2.1 Illustration of blood ﬂow through a ventricular septal defect.

ATRIAL SEPTAL DEFECT (ASD)

PATHOLOGY & CAUSES

SIGNS & SYMPTOMS

COARCTATION OF THE AORTA

Figure 2.7 A chest radiograph demonstrating

PATENT DUCTUS ARTERIOSUS

PATHOLOGY & CAUSES DIAGNOSIS

Figure 2.9 Volume-rendered CT scan of the

VENTRICULAR SEPTAL DEFECT

PATHOLOGY & CAUSES DIAGNOSIS

Size of defect ECG

species, Aspergillus, Candida, aorta, inferior vena cava/duodenum,

CTA scan OTHER INTERVENTIONS

GENERALLY, WHAT ARE THEY?

PATHOLOGY & CAUSES SIGNS & SYMPTOMS

BUNDLE BRANCH BLOCK

Rate-related bundle branch block

RISK FACTORS ▪ LBBB only

Figure 4.5 Illustration depicting mnemonic “WiLLiaM MaRRoW.”

Figure 4.7 ECG demonstrating right bundle branch block.

Figure 4.8 Illustration depicting wide QRS in bundle branch block.

PATHOLOGY & CAUSES SIGNS & SYMPTOMS

RISK FACTORS Pacemaker implantation

GENERALLY, WHAT ARE THEY?

PATHOLOGY & CAUSES SIGNS & SYMPTOMS

Figure 5.1 Surgically excised atrial myxoma. A

Figure 5.2 Histological appearance of a

Figure 5.3 A sagittal CT scan demonstrating

GENERALLY, WHAT IS IT?

RISK FACTORS TREATMENT

SIGNS & SYMPTOMS TREATMENT

DIAGNOSIS OTHER INTERVENTIONS

Figure 6.2 A chest radiograph demonstrating

Chest X-ray SURGERY

Calcium channel blockers

Figure 6.4 The histological appearance of

Figure 6.3 Gross pathology of hypertrophic

STABLE ANGINA PECTORIS

CAUSES Protective factors

GENERALLY, WHAT ARE THEY?

SIGNS & SYMPTOMS MEDICATIONS

PATHOLOGY & CAUSES SIGNS & SYMPTOMS

▪ Truncus arteriosus fails to divide into aorta/

Figure 8.4 Gross pathology of a persistent

PATHOLOGY & CAUSES SIGNS & SYMPTOMS

PATHOLOGY & CAUSES SIGNS & SYMPTOMS

Cardiac variant Chest X-ray

▫ If present, pulmonary venous

GENERALLY, WHAT IS IT?

Right heart (pulmonary artery) catheter-

▪ Right ventricular hypertrophy, dilation,

Cardiac catheterization OTHER INTERVENTIONS

DIASTOLIC HEART FAILURE

PATHOLOGY & CAUSES SIGNS & SYMPTOMS