Resistance is {{c3::inversely}} proportional to the {{c1::fourth}} power of the

{{c2::radius}} of the blood vessel via R = 8ηl/πr4 (Poiseuille's equation) R =

resistance η = viscosity of blood l = length of blood vessel r4 = radius of blood
vessel -By this equation, if radius falls by 50%, resistance will increase by a
factor of 16. Conversely, if radius doubles, resistance will decrease by a factor
of 16.
Scurvy is associated with {{c1::perifollicular}} hemorrhages and
{{c2::subperiosteal}} hemorrhages These patients will have fragile blood vessels
resulting in bleeding / bruising -Perifollicular hemorrhages: fancy way of saying
red-blue spots surrounding hairs of lower leg
Where is the 1st synapse in the lateral corticospinal tract? (aka where does UMN
meet LMN) {{c1::cell body of anterior horn in spinal cord}}Decussates in caudal
medulla.
Name the acid/base disturbance: pH: High PCO2: Low HCO3: Low {{c1::Respiratory
Alkalosis}}
Name the acid/base disturbance: pH: High PCO2: High HCO3: High {{c1::Metabolic
Alkalosis}}
Name the acid/base disturbance: pH: Low PCO2: Low HCO3: Low {{c1::Metabolic
Acidosis}}
Name the acid/base disturbance: pH: Low PCO2: High HCO3: High {{c1::Respiratory
Acidosis}}
What is the formula for cardiac output? {{c1::CO = SV x HR}} Or use Fick's
equation: (Rate of O2 consumption)/(arterial O2 - venous O2)
The aortic arch sends afferent signals in response to high blood pressure only via
the {{c1::vagus}} nerve baroreceptor
Most of coronary blood flow occurs during {{c1::diastole}} in tachycardia, less
time in diastole = less flow = possible hypoxia
What layer of the heart is most succeptible to ischemia? {{c1::subendocardium}}
coronary arteries are in epicardium
What is the formula for net pressure across capillary walls? {{c1::NP = (Pc - Pi) -
(πc - πi)}} P = hydrostatic, π = oncotic (solutes) Flow = (NP)*Kf
What is the mechanism of edema in heart failure? {{c1::↑ capillary pressure, ↑ Pc}}
What is the mechanism of edema in nephrotic syndrome and liver failure? {{c1::↓
plasma protein = ↓ πc}}
What is the mechanism of edema with burns, infections, and toxins? {{c1::↑
capillary permeability = ↑ Kf}}
What is the formula for Ejection Fraction? {{c1::EF = (EDV - ESV)/ EDV}}
List what the venous pressure values mean: a wave:{{c1::Atrial contraction}} v
wave: {{c1::Venous filling}} c wave: {{c1::RV Contraction}} x descent: {{c1::atrial
relaXation}} y descent: {{c1::emptYing of RA}}
In JVP tracings, an absent a wave indicates {{c1::Atrial Fibrillation}}
In JVP tracings, a giant V wave indicates {{c1::tricuspid regurgitation}}
What does this ECG indicate? {{c1::Subendocardial ischemia}} many other causes
of ST depression tho
What conditions can cause inverted T waves on ECG? {{c1:: Subendocardial ischemia
Raised ICP Resolving pericarditis Bundle branch blocks Ventricular hypertrophy}}
What ECG abnormality indicates either a current or past Myocardial infarction?
{{c1:: Q waves - T wave inversion happens within the first week and returns to
normal}}
What is the earliest sign of transmural ischemia on ECG? {{c1:: Hyperacute T
waves }}
What gross and micro pathological changes are found in the myocardium 0-4 hours
after ischemia? {{c1::NONE. NADA. ZILCH.}} Like the Browns win column in 2017
What gross and micro pathological changes are found in the myocardium 4-12 hours
after ischemia? {{c1:: Gross: Mottled Micro: Necrosis, edema, hemorrhage}}
What gross and micro pathological changes are found in the myocardium 5-10 days
after ischemia? {{c1:: Gross: central yellowing Micro: granulation tissue}}
What gross and micro pathological changes are found in the myocardium 7+ weeks
after ischemia? {{c1::SCAR}}
What is the major cause of death 0-4 days after an MI? {{c1::arrythmia}}
What is the common cause of death weeks after an MI? {{c1::ventricular aneurysm}}
more common in anterior infarct - risk of thrombus → stroke
Ventricular Pseudoaneurysms commonly occur sooner after an MI (<2 weeks) and are
seen in the {{c1::inferior}} wall
What are the differences between fibrinous and Dressler's pericarditis after an MI?
{{c1:: Timing: Fibrinous occurs w/in days, Dressler's occurs weeks after MI
Dressler's IS autoimmune, Fibrinous is not}}
What is the most common cause of stent thrombosis? {{c1::missed medication doses}}
Anterior leads (V1-V4) correspond to which artery? {{c1::LAD}}
Lateral leads (I, VL, V5, V6) correspond to which artery? {{c1::left circumflex}}
Inferior leads (II, III, avF) correspond to which artery? {{c1::Posterior
descending}} 90% branch from RCA, 10% LCX
A STEMI in lead avR indicates what? {{c1::Left main occlusion}} aVR can be
elevated from a proximal LAD, but aVR > V1 = LMCA occlusion
In treatment of STEMIs, emergency angioplasty should be done within {{c1::90
minutes}}
In treatment of STEMIs, option 2 in thrombolysis (tPa) which should be done within
{{c1::30 minutes}} if angioplasty is unavailable
When are Beta Blockers contraindicated in emergent STEMI treatment? {{c1::inferior
MI}} inferior MI stimulates Vagus nerve → bradycardia and AV block can develop
When are Nitrates contraindicated in emergent STEMI treatment? {{c1::RV infarct}}
RV infarct → poor RV contractility ↓ preload → hypotension
"What is Monday Disease? {{c1::workers in nitroglycerin manufacturing facilities
develop tolerance → lose tolerance over weekend → ""monday morning headache""
phenomenon}}" re-exposure on Monday results in prominent vasodilation,
tachycardia, dizziness, headache
What two Beta Blockers are cardioselective (B1) drugs used for angina? {{c1::
Metoprolol Atenolol}}
What are the main two calcium channel blockers that primarily act as vasodilators
lowering BP, reducing afterload, and dilating coronary arteries? {{c1::Nifedipine
Amlodipine}} "All ""-apines"" - dihydropyridines: block L-type calcium
channels in smooth muscle plasma membrane. Good for HTN."
What calcium channel blockers are primarily negative ionotropes which act by
reducing HR and contractility? {{c1:: Verapamil Diltiazem}}-Both block L-type
calcium channels, thus inhibiting passive transport of calcium ions in
cardiomyocytes. can cause acute HF if LVEF is very low
What is the cause of variant (Prinzmetal) angina? {{c1::ischemia from VASOSPASM}}
spontaneous episodes of angina at rest late at night early morning, smoking,
transient ischemia, ST-elevation
What drug can you inject into the coronary artery that acts on endothelial
muscarinic receptors to induce vasospasm to diagnose Variant (Prinzmetal) Angina?
{{c1::acetylcholine}}
What drug do you want to AVOID in the treatment of Variant (Prinzmetal) Angina?
{{c1::Propanolol}} tx is quit smoking + Ca-channel blockers, nitrates
What four short-acting vasodilators would you give before a chemical stress test to
diagnose coronary steal? {{c1:: dipyridamole adenosine persantine regadenoson}}
What are the three most common causes of Torsade de Pointes? {{c1:: Antiarrhythmic
drugs Hypokalemia Hypomagnesemia}} sometimes hypocalcemia
What is the cause of Congenital Long Qt Syndrome? {{c1::abnormal K channels}}
Defective K channels → hyperpolarization (same effect as Ia & III anti-
arrhythmics) → long QT Romano-Ward → AD, no HL Jervell & Lange-Nielsen → AR,
sensorineural HL
What three drugs most commonly cause Acquired Long Qt Syndrome? {{c1::
Antiarrhythmics Levofloxacin (antibiotic) Haloperidol}} 3 most important
according to Dr Ryan
U-waves on ECG are always seen with what metabolic abnormality? {{c1::Hypokalemia}}
What are two possible ECG findings with AV Blocks? {{c1:: prolonged PR interval
(normal <200ms) non-conductive P-wave (severe)}}
What is the main symptom of AV blocks? {{c1::Bradycardia}} fatigue, dizziness,
syncope
Type {{c1::1}} AV Blocks caused prolonged PR interval only (all p waves are
conducted)
Type {{c1::2}} AV Blocks cause some p waves to be NOT conducted (some are conducted
tho)
Type {{c1::3}} AV Blocks cause NO impulse conduction from atria to ventricles
What are the common causes of type 1 AV block? {{c1:: Beta blockers Calcium channel
blockers Well-trained athletes}} AV NODE - so its not that bad
What type of AV block results in progressive PR prolongation and grouped beating?
{{c1::2nd degree AVB - Mobitz I (Wenckebach)}} RR intervals are not regular -
usually in AV node (similar symptoms, causes as 1st degree AV block)
What type of AV block involves normal PR intervals followed by a third dropped
beat? {{c1::2nd degree AVB - Mobitz Type II}} in contrast to Mobitz I, block in
II is usually in His-Purkinje system often seen together with bundle branch block
What infection can lead to AV block? {{c1::Borrelia burgdorferi (Lyme Disease)}}
Stage 2: Lyme Carditis
What is the common cause of high-degree heart block in the elderly? {{c1::fibrosis
and sclerosis of conduction system}}
What ECG abnormality will be seen in a one sided bundle branch block? {{c1::long
QRS (normal <120 ms)}}
Untreated, rapid A-Fib can lead to what 3 complications? {{c1:: cardiomyopathy ↓
LVEF systolic HF}}
How does A-fib alter the preload? {{c1::decrease}} "loss of ""atrial kick"" -
elimate ventricular prefilling"
What valvular heart disease is associated with A-fib? {{c1::Mitral stenosis}}
associated w rheumatic fever - VERY high risk of thrombus
What are the biggest risk factors for A-fib? {{c1:: AGE women HTN CAD Heart failure
valvular disease}} HF and valve disease dilate the atria
What do you do for rhythm control in A-fib patients? {{c1::Cardioversion}}
synchronize shock at time of QRS to restore sinus rhythm
What drug is used in chemical rhythm control in A-fib patients? {{c1::Ibutilide}}
Class III anti-arrhythmic
What antiarrhythmic medications are given before/after cardioversion to restore
normal sinus rhythm in A-fib patients? {{c1:: Class I: Flecainide, Propafenone
Class III: Amiodarone, Sotalol, Dofetilide}}
{{c1::Paroxysmal Supraventricular Tachycardia::type of arrhythmia}} are
intermittent sudden onset/offset tachycardia (HR > 100 bpm)origin of ventricular
activity is above ventricle → narrow QRS complex <120 ms
What is the cause of AVNRT? {{c1::dual pathways → slow & fast conduction pathways
in AV node}} occurs usually in young women
What is the hallmark of AVNRT on ECG? {{c1::Retrograde P waves - after QRS
complex}}
What causes Wolf-Parkinson White Syndrome? {{c1::Accessory atrioventricular pathway
→ bypasses AV node through bundle of kent}}
What are the ECG abnormalities seen in WPW syndrome? {{c1:: Delta wave & short PR
interval }}
How do you treat WPW with A-fib? {{c1:: cardioversion antiarrhythmics - ibutilide,
procainamide}} usual A-fib therapies are contraindicated
Class {{c1::Ic}} antiarrhythmics are pure sodium channel blockers flecainide,
propafenone
Class {{c1::Ia}} antiarrhythmic drugs block sodium channels and have some K-
blocking effects quinidine, procainamide, disopyramide
What are the three main class Ia antiarrhythmics? {{c1:: quinidine procainamide
disopyramide}}
What are the two main effects of class Ia antiarrhythmics? {{c1:: prolong QRS
prolong QT (↓K outflow)}}
{{c1::Procainamide}} is a class Ia antiarrhythmic that is given intravenously and
used to slow conduction in accessory pathways (i.e. WPW)
{{c1::Quinidine}} is a class Ia antiarrhythmic drug given orally used to decrease
the recurrence of atrial fibrillation associated w/ increased mortality dont
give with Digoxin!
What is the unusual side effect of Procainamide? {{c1::drug-induced lupus}} often
develop rash, arthritis, anemia
What is the key diagnostic feature in drug-induced lupus? {{c1::anti-histone
antibodies}} -One of the component of histones targeted by the reaction is H1
histone linker protein, which binds to the nucleosome and stabilizes chromatin
fibers. -Anti-nuclear antibody is found in normal lupus
What dugs are classically associated with drug-induced lupus? {{c1:: Sulfonamides
Hydralazine Isoniazid Procainamide Phenytoin Etanercept}} -SHIPPE
What are the two class Ib antiarrhythmics? {{c1:: lidocaine mexiletine}}
Class {{c1::Ib}} antiarrhythmics block voltage-gated Sodium channels in the
depolarized state and are effective in treating ischemic arrhythmias -Inhibits
passive transport of sodium ions. lidocaine, mexiletine
What is a common side effect of class Ib antiarrhythmics? {{c1:: CNS stimulation
(tremor) bradycardia}}
What is the main side effect of class Ic antiarrhythmics? {{c1::serious QRS
prolongation}} Propafenone, flecainide. Demonstrate Use-Dependence: at ↑ HR, Na-
blocking effect intensifies (↑↑ QRS) because there is less time for the drug to
dissociate form its receptor
What antiarrhythmics are most associated with use dependence? {{c1::Ic}} Use
Dependence → Cells discharging at an abnormaly high rate are preferentially
blocked. Use for SVT, A-fib, never use in ischemic heart disease. Class Ib has the
least use dependence (good for ischemic heart tissue)
Name 4 class III antiarrhythmics: {{c1:: Amiodarone Sotalol Dofetilide Ibutilide}}
K channel blockade (inhibit passive transport of potassium)
What antiarrhythmics cause significant QT prolongation and can lead to Torsade de
Pointes? {{c1::Ia & III}} Amiodarone has least risk for TdP amongst class Ia &
III antiarrhythmics
What are the two most common applications of Amiodarone? {{c1:: A-fib Ventricular
tachycardia}} technically a K-channel blocker, but has class I, II, and IV
effects
What antiarrhythmic is highly lipid soluble and has a long half life (58 days)?
{{c1::Amiodarone}} safe in renal disease; biliary excretion
What are the six main side effects of Amiodarone? {{c1:: Hyper and hypo-thyroidism*
↑ LFTs (asymptomatic) Skin sensitivity to sun Blue-grey skin discoloration Corneal
deposits Pulmonary fibrosis}} *thyroid issues bc it contains iodine = amiodarone
What is the most common cause of death with amiodarone? {{c1::Pulmonary fibrosis}}
"What will pulmonary fibrosis from amiodarone poisoning show pathologically and on
xray? {{c1:: foamy macrophages in air spaces ""honeycombing"" on CXR }}"
What atypical antiarrhythmic drug has receptors (purinergic) in AV nodal tissue and
vascular smooth muscle? {{c1::Adenosine}}
How does adenosine work in AV nodal cells? {{c1:: activates K channels
(hyperpolarization) blocks Ca influx}} both effects slow AV conduction
What IV antiarrhythmic has a short half life and is given for control of
supraventricular tachycardias? {{c1::adenosine}} usually AVNRT
What two substances block adenosine receptors? {{c1:: theophylline caffeine}}
adenosine is a sleep hormone → hence why coffee keeps you zooming at 2 am
What is the only time magnesium is used as an antiarrhytmic? {{c1::Acute Torsade de
Pointes}} blocks influx of Ca into cells - remember hypomagnesemia can cause TDP
-Also increase potassium efflux, causing hyperpolarization. OR normalizes potassium
levels
What atypical antiarrhythmic is used to treat bradycardia from AV block?
{{c1::Atropine}} muscarinic receptor antagonist: ↑ HR and AV conduction
What are the two major effects of Digoxin? {{c1:: ↑ contractility (for HF) ↓ AV
conduction (a-fib, vent tachy)}} ↑ contractility → inhibits Na/K ATPase →
intracellular Na & Ca buildup ↓ AV conduction→ ↑ parasympathetic (vagal) tone
What is the MOA of digoxin in increasing contractility? {{c1::inhibits Na-K-
ATPase}} traps sodium in cell, resulting in more Ca inside of cell
What is the MOA of digoxin in arrhythmias? {{c1::increased Vagal (parasympathetic)
tone}}
What is the cure for digitoxin toxicity? {{c1::Digibind}} aka renal probs,
hyperkalemia
What murmur(s) can you hear at the RUSB? {{c1::Aortic Stenosis }}
What murmur(s) can you hear at the LUSB? {{c1:: Pulmonic murmur PDA}}
What murmur(s) can you hear at the LSB (one costal space below pulmonic spot)?
{{c1:: Aortic regurg hypertrophic cardiomyopathy}}
What murmur(s) can you hear at the LLSB? {{c1:: Tricuspid murmurs VSD}}
What murmur(s) can you hear at the apex? {{c1::mitral murmurs}}
What is implied when there is a lateral shift of the apical impulse? {{c1::enlarged
heart}}
What murmur is a systolic crescendo-decrescendo ejection murmur? {{c1::Aortic
Stenosis}}
What are the three findings that indicate severe aortic stenosis? {{c1:: late-
peaking murmur Soft/quiet S2 Pulsus parvus et tardus}} 1. late peak → slow flow
across stenotic valve 2. soft/quiet S2 → stiff valve cant slam shut 3. pulsus
parvus et tardus → weak & small carotid pulse, delayed carotid upstroke
What murmur has the same character as aortic stenosis but is distinguished by
valsalva? {{c1::Hypertrophic cardiomyopathy}} louder HCM murmur softer A.S.
murmur
"What murmur is a diastolic decrescendo ""blowing"" murmur? {{c1::Aortic
Regurgitation}}"
What murmur is a holosystolic murmur heard best at the cardiac apex? {{c1::Mitral
regurgitaion}} Radiates to axilla. Often due to MI, MVP, or LV dilation
"What murmur is a diastolic ""rumbling"" murmur preceded by an ""opening snap""?
{{c1::mitral stenosis}}"
Most {{c1::right}} sided murmurs will get louder with inspiration carvallo's
sign: rIght sided murmurs increase with Inspiration lEft sided murmurs increase
with Exhalation
What murmur is a holosystolic murmur with similar character as MR? {{c1::VSD}}
small VSD → more turbulence → louder
"What murmur is a continuous ""machine-like"" murmur? {{c1::Patent Ductus
Arteriosus}}"
Most murmurs INCREASE with more preload (leg raise, squatting). Which two do not?
{{c1:: HCM MVP}} "At high volumes (preload) the thickened septum and ventricular
walls in HCM are more ""spread out"" which reduces the obstruction of outflow and
improves the murmur"
In murmur diagnosis, a young female who is otherwise healthy usually indicates what
murmur? {{c1::MVP}}
In murmur diagnosis, a heathly, young athlete with syncope usually indicates what
murmur? {{c1::HCM}}
In murmur diagnosis, a pregnant woman or immigrant usually indicates what murmur?
{{c1::Mitral stenosis}} infections!
In murmur diagnosis, IV drug abusers usually indicates what murmur? {{c1::Tricuspid
regurgitation}} most commonly Staph aureus acutely, also Pseudomonas and Candida
In murmur diagnosis, a patient with Turner syndrome or Aortic Coarctation usually
indicates what murmur(s)? {{c1:: Bicuspid AV}} can lead to aortic stenosis &
regurgitation
In murmur diagnosis, a patient with Marfan syndrome usually indicates what murmur?
{{c1::MVP}}
Does S2 split during inspiration or expiration? {{c1::inspiration}} increased
venous return delays P2
What two pathologies result in persistent S2 splitting? {{c1:: RBBB Pulmonary HTN}}
delayed pulmonic valve closure
What pathology causes fixed S2 splitting? {{c1::ASD}} systolic ejection murmur too
caused by flow across ASD → ↑ right sided flow
What 5 pathologies cause paradoxical S2 splitting? {{c1:: delayed closure of aortic
valve LBBB RV pacemaker LV systolic failure Aortic stenosis HCM}} paradoxicaL
= Left sided splitting
What cardiac pathology causes a very loud P2 sound? {{c1::Pulmonary HTN}}
forceful closure of pulmonic valve, can be heard at apex, and it aint
supposed to be heard at the damn apex
What pathology commonly causes an S3 heart sound? {{c1::acute heart failure}}
"can be due to Mitral Regurg; ↑ LA pressure → rapid early filling of LV may
be heard in normal hearts (young pts, pregnant - ""suckers"", not ""pushers"")"
How are S3 heart sounds best heard? {{c1:: Bell (low frequency) Expiration Loudest
at apex Lateral decubitus position }} BELL
What pathologies cause an S4 heart sound? {{c1::stiff left ventricle HTN HCM
Diastolic HF}} rapid late filling of LV due to atrial kick
What pathology causes a systolic non-ejection click? {{c1::MVP}} Late in systole,
AFTER carotid pulse
What is the most common cause of mitral stenosis? {{c1::rheumatic heart disease
from GABHS (pyogenes)}} "rumbling diastolic murmur after ""opening snap"" at apex"
{{c1::Intermittent claudication}} is a painful ischemic condition caused by
peripheral atherosclerosis of the arteries pain is triggered by walking &
relieved with rest
Septic shock will cause what two changes in normal CV physiologic values? {{c1:: ↑
CO ↓ SVR}} SVR is low because inflammatory mediators cause vasodilation
What hemodynamic abnormality is the pathophysiological hallmark of left ventricular
HF? {{c1::high LVEDP}} less blood pumped out → higher pressure
"What histological findings are found in heart failure? {{c1::Hemosiderin (iron)
laden macrophages (""HF cells"")}}"
Where in the heart do myxomas commonly occur? {{c1::left atrium }} attatched to
atrial septum, often at border of fossa ovalis
Myxomas may disrupt {{c1::mitral}} valve function "lead to mitral regurg & HF
OR sit in mitral valve (""ball in valve"") and cause mitral stenosis"
Where are cardiac rhabdomyomas found in the heart? {{c1::embedded in ventricular
wall}} Benign, usually in children (<1 year). Associated with tuberous
sclerosis. Hamartomatous histology.
90% of Cardiac Rhabdomyomas are assocaited with {{c1::Tuberous Sclerosis}}
tuberous sclerosis is caused by mutations in TSC1 (hamartin) and TSC2
(tuberin) which causes widespread tumor formation
What genetic abnormality causes tuberous sclerosis? {{c1::Autosomal dominant
mutations in TSC1 (hamartin) and TSC2 (tuberin)}}
"What are the most common presenting symptoms of tuberous sclerosis? {{c1:: 1.
Seizures ""Ash leaf spots"" Angiofibromas Mental Retardation}}"
What HTN drugs can cause hyperkalemia? {{c1:: Spirinolactone eplerenone Triamterene
Amiloride}} K sparing diuretics → act in cortical collecting tubule, used to treat
hypokalemia
What will the EF be in systolic vs diastolic HF? {{c1:: systolic will be reduced
diastolic be will normal}}
What symptoms are unique in systolic HF compared to diastolic? {{c1:: cool
extremities cachexia confusion}} """low flow symptoms"" → associated with very
low EF"
What kind of cardiomyopathy is seen in systolic compared to diastolic HF? {{c1::
systolic = eccentric (dilated) diastolic = concentric }} eccentric they grow in
series due to volume overload: increased mass of the left ventricle associated with
normal wall thickness and increased LV cavity size. Examples are Aortic
regurgitation, Mitral regurgitation, and ischemic (dilated cardiomyopathy).
concentric the grow in parallel due to pressure overload: increased mass of the
left ventricle associated with increased wall thickness and reduced LV cavity size.
Examples are aortic stenosis, HTN and HOCM
What is the most common cause of systolic heart failure? {{c1::Myocardial
infarction}} ischemic cardiomyopathy
What are the most common viral causes of nonischemic cardiomyopathy? {{c1::
COXSACKIE influenza adenovirus}} follow upper respiratory infx → myocarditis →
cardiomyopathy
What chemotherapy agents cause nonischemic cardiomyopathy? {{c1::anthracyclines →
doxorubicin, daunorubicin}} prevent with Dexrazoxane
What mutations are assocaited with familial causes of nonischemic cardiomyopathy?
{{c1:: sarcomere proteins beta myosin heavy chain alpha myosin heavy chain
troponin}} many autosomal dominant
"{{c1::Takostubo cardiomyopathy}} is ventricular apical ballooning (dilated
cardiomyopathy) caused by ↑ sympathetic stimulation and stressful situations
(""broken heart syndrome"")" Looks like anterior MI → resolves after 4-6 weeks.
Common in Japan
Wet beriberi (high output cardiac failure) can be a result of {{c1::thiamine (B1)}}
deficiency Dry → neuralgia, muscle weakness
What is the most common cause of subacute endocarditis? {{c1::viridans
streptococci}} small vegetations on congenitally abnormal or diseased valves.
often from dental procedures
What are the classic imaging findings in restrictive heart disease? {{c1:: normal
ventricles bi-atrial enlargement}} ↑ atrial pressure because of restricted filling
Restrictive cardiomyopathy leads to {{c1::right::right/left}} heart failure "↑ JVP
lower extremity edema liver congestion → cirrhosis (""nutmeg liver"") NO pulmonary
edema"
What is the classic cause of restrictive heart disease? {{c1::amyloidosis }} apple-
green birefringence
Thickened myocadium with low voltage on ECG is a classic finding in what two
pathologies? {{c1:: Amyloidosis Fabry disease}} thick myocardium with bad
electrical conductance → restrictive heart disease
What lysosomal storage disease leads to restrictive heart disease? {{c1::Fabry
disease}} deficiency of a-galactosidase A accumulation of ceramide trihexoside
Fabry disease is a lysosomal storage disease resulting in an accumulation of what
substrate? {{c1::ceramide trihexoside}} deficiency of a-galactosidase A
Hemochromatosis is a disease of iron excess that commonly causes what cardiac
pathology(s)? {{c1::Restrictive (classic) or Dilated Cardiomyopathy}}
Radiation therapy can lead to restrictive heart disease by what mechanism?
{{c1::extra-cellular matrix deposition of collagens and fibronectine}}
What heart pathology occurs acutely after radiation? {{c1::pericarditis}}
Radiation causes deposition of collagen and fibrous material in ECM.
{{c1::Loeffler's syndrome}} is a hypereosinophilic syndrome which can lead to
eczema, lung fibrosis, and restrictive cardiomyopathy Acaris lumbrocoides,
strongyloides; ↑ eosinophil count + eosinophilic infiltration of organs. Release of
MBP and other toxic eosinophil enzymes mediates damage.
What parasitic infection can lead to hypereosinophilic syndrome? {{c1::ascaris
lumbricoides}} Hypereosinophilic syndrome leads to restrictive cardiomyopathy.
Will show eosinophilic infiltrates in myocardium on biopsy.
Hypereosinophilic syndromes cause myocarditis acutely, which leads to chronic
{{c1::endomyocardial}} fibrosis and myocyte death Thrombus formation common →
embolic stroke
What is the classic cause of restrictive heart disease in infants?
{{c1::Endocardial fibroelastosis}}
Endocardial fibroelastosis results in proliferation of {{c1::fibrous (collagen)}}
and {{c1::elastic}} fibers in the endocardium, leading to restrictive
cardiomyopathy in infants
What drugs can cause acute exacerabations of heart failure? {{c1::NSAIDS}}
inhibit COX → ↓ prostaglandins ↓ renal perfusion → fluid retention
"What thiazide-like diuretic is used in combo with loop diuretics as a ""kick"" by
inhibting Na-Cl reabsorbtion in the distal tubule? {{c1::Metolazone}}" sometimes w/
loop diuretics, blocking sodium reabsorption in the thick ascending limb causes
reflex high absorption in the distal convoluted tubule
Combination therapy of {{c1::nitrates}} to reduce preload and {{c1::hydralazine}}
to reduce afterload is proven to reduce mortality in systolic acute and chronic HF
especially beneficial in black patients
Ionotropes are used to treat systolic heart failure by activating {{c1::Beta-1}}
pathways in myocytes, increasing HR and contractility many activate beta-2 pathways
in smooth muscle to cause vasodilation in peripheral arteries
What is the MOA of the ionotrope Milrinone? {{c1::inhibits PDE 3 to cause ionotropy
and vasodilation}} ionotropy: PDE3 breaks down cAMP in myocytes, inhibition →
↑ cAMP → contraction vasodilation: ↑ cAMP in vascular smooth muscle
What is the MOA of the ionotrope Dobutamine? {{c1::Beta-1 agonist increasing
ionotropy}} weak beta-2 agonist: vasodilation -Beta1 activation increases left
ventricular contractility and heart rate. With increased contractility, left
ventricular end systolic volume (LVESV) will fall. This change occurs any time
contractility increases. -Left ventricular end diastolic volume (LVEDV) will
decrease with dobutamine as a result of increased heart rate (less filling time).
{{c1::Low}} doses of dopamine cause vasodilation in the kidneys D1 action. D1= D2
> B > a
{{c1::Medium}} doses of dopamine cause it to act as a beta-1 agonist, increasing
ionotropy
{{c1::High}} doses of dopamine cause it to act as an alpha agonist leading to
vasoconstriction
{{c1::Low}} doses of epinephrine cause it to act as a beta-1 and beta-2 agonist,
increasing ionotropy and causing vasodilation
{{c1::High}} doses of epinephrine cause it to act as an alpha agonist leading to
vasoconstriction same as dopamine
What are the four effects (net result) of the renin-angiotensin system? {{c1:: ↑
salt/water retention → ↑ preload; ↑ TPR → ↑ afterload}} activated in chronic
systolic heart failure
what are two common side efects of both ACEIs and ARBs? {{c1:: hyperkalemia (↓
aldosterone) renal failure (↓ GFR)}} Remember that ATII stimulates adrenal
glomerulosa to produce aldosterone. Diminished ATII > low aldosterone >
hyperkalemia
What are two side effects unique to ACE inhibitors? {{c1:: dry cough angioedema}}
both due to bradykinin
What three beta blockers are proven to be beneficial in the treatment of chronic
systolic HF? {{c1:: Metoprolol (B1) Carvedilol (B1, B2, a1) Bisopropolol (B1)}}
What two drugs are used to block aldosterone in treatment of chronic systolic HF?
{{c1:: Spironolactone Eplerenone}} Potassium-sparing diuretics. Proven to improve
mortality
What aldosterone-blocking diuretic has the side effect of gynecomastia in men and
amenorrhea in women? {{c1::Spirinolactone}} blocks testosterone and activates
progesterone receptors. Eplerenone doesnt do this
What is the MOA of the chronic HF med Sacubitril? {{c1::inhibits neprilysin
(degrades ANP & BNP) → inhibition leads to ↑ ANP & BNP}} ANP and BNP cause
vasodilation (antagonists of RAAS system), sodium & water excretion, and reduced
sympathetic tone
"What is the MOA of chronic heart failure drug Ivabradine? {{c1::inhibits SA
""funny current"" → slows HR without decreasing contractility}}" used in patients
of max dose beta-blocker with ↑HR
What pathology will present with dextrocardia (right sided heart)? {{c1::
Kartagener syndrome (primary ciliary diskinesia)}}
In an aortic dissection, which layer of the aorta is torn? {{c1::intima }} "blood
gets in plane ""dissects"" between intima and media"
Type {{c1::A}} aortic dissections involve the ascending aorta and/or aortic arch
and are treated {{c2::surgically}} Ascending = proximal to left subclavian artery
Type {{c1::B}} aortic dissections involve the descending aorta and are treated
{{c2::medically}} control HTN & symptoms; no surg.
What are the 3 possible complications of an aortic dissection with propogation to
the aortic root? {{c1:: aoritc regurgitation pericardial effusion/tamponade
myocardial ischemia}} ischemia from obstruction of RCA origin
What are the 3 possible complications/symptoms of an aortic dissection with
propogation to the aortic arch? {{c1:: stroke (carotids) Horner's syndrome vocal
cord paralysis (LRL nerve)}}
Combining what two lipid lowering drug classes greatly increases the risk for the
side effect of myopathies (rhabdomyolysis)? {{c1::statins and fibrates
(gemfibrozil)}} -In the liver, gemfibrozil inhibits cytochrome P450 enzymes. This
reduces statin metabolism raising serum levels of the drug. -Muscle biopsy (in case
of statin's myopathy, though rarely done) shows myonecrosis and inflammatory cells
-Other drug that increases risk of myopathy (rhabdomyolysis) with statins is
cyclosporine.
Which lipid-lowering agents are first line to lower LDL? {{c1::Statins (HMG-CoA
reductase inhibitors)}} e.g. lovastatin, prevastatin -Statin drugs inhibit the
hepatic enzyme HMG-CoA reductase in the cholesterol synthesis pathway. This enzyme
catalyzes the conversion of HMG-CoA into mevalonate. When inhibited by a statin
drug, mevalonate levels will fall. As a result of decreased cholesterol synthesis,
the number of LDL receptors in the liver will increase to pull more cholesterol
from the plasma. It is important to understand that the cause of the decreased LDL
cholesterol in patients on statins is not from decreased synthesis but rather from
increased LDL receptors.
What type of ASD is associated with Downs Syndrome? {{c1::Primum type ASD}}
endocardial cushion defect
What congenital infection is associated with PDA? {{c1::Congenital Rubella}} mother
(usually immigrant) will have rash, fever, lymphadenopathy. baby will be deaf, have
juvenile cataracts, and PDA
What congential shunt causes a widened pulse pressure? {{c1::PDA}} due to low
diastolic pressure caused from loss of blood in arterial tree (shunt from aorta to
pulmonary artery)
What prostaglandin E1 analog is used to maintain a PDA? {{c1::Alprostadil}} use in
tetralogy of fallot and pulmonary atresia
What drug is used to close a PDA? {{c1::Indomethacin}} NSAID → inhibits COX
What syndrome occurs as a complication of uncorrected congenital shunts (ASD, VSD,
PDA)? {{c1::Eisenmenger's Syndrome}} RV hypertrophy and pulmonary HTN
What congenital heart defects are associated with fetal alcohol syndrome? {{c1::
ASD VSD Tetralogy of Fallot}}
Which class of lipid-lowering agents has the strongest effect on reducing
triglyceride levels? {{c1::Fibrates}} upregulate LPL → ↑ triglyceride clearance
activate PPAR-a → HDL synthesis
What type of necrosis is seen in ischemia and infarcts? {{c1::coagulative}} heart,
kidneys, lungs, but NOT brain (liquefactive)
What vasculitis is associated with Hepatitis B? {{c1::Polyarteritis nodosa}} type
III hypersensitivity. fever, anorexia, malaise, headache, GI issues, HTN,
neurological problems, cutaneous eruptions, renal damage, but spares lungs
"What is the triad of symptoms in Eisenmenger syndrome? {{c1:: late cyanosis
(""blue kid"") clubbing polycythemia (↑ Hgb) }}" presents in childhood (blue
kid, not blue baby), due to untreated L→R shunt (VSD, ASD, PDA)
What are the four abnormalities present in Tetralogy of Fallot? {{c1:: Pulmonary
Stenosis RV Hypertrophy Overriding Aorta VSD}} -PROVe
All abnormalities in Tetralogy of Fallot are due to anterior displacement of what
structure towards the right ventricle? {{c1::Infundibulum (Conus Arteriosus)}}
develops from bulbus cordis
What is the classic x-ray finding in Tetralogy of Fallot? {{c1:: Boot shaped
heart }}
What physical action improves symptoms in Tetralogy of Fallot? {{c1::Squatting}}
raises TPR and afterload → high LV pressure → less deoxygenated blood flowing
through VSD
Truncus Arteriosus (failure of aorta and pulmonary artery to divide) results from a
failure of {{c1::neural crest cells}} to drive formation of the aorticopulmonary
septum
What other congenital heart defect is almost always present with Truncus
Arteriosus? {{c1::VSD}}
What is the abnormal anatomic position of the aorta in Transposition of Great
Vessels (D type)? {{c1::Aorta is ANTERIOR and RIGHTWARD of pulmonary artery}}
What congenital heart defect is most commonly associated with maternal diabetes?
{{c1::transposition of the great vessels}}
In Tricuspid Atresia, no tricuspid valve is formed due to defects in what embryonic
structure? {{c1::endocardial cushions}} must have BOTH a R→L shunt AND a L→R
shunt to be compatible with life
{{c1::Ebstein anomaly}} is a congenital heart defect characterized by displacement
of tricuspid valve into the RV
Which congenital heart defect commonly presents with WPW syndrome? {{c1::Ebstein
anomaly}}
Ebstein anomaly is a congenital heart defect associated with prenatal
{{c1::Lithium}} exposure
What congenital heart defects are associated with 22q11 syndromes (DiGeorge)?
{{c1:: Truncus Arteriosus Tetralogy of Fallot Transposition of the GAs}} aka
conotruncal heart defects
What two complications can arise later in life from Coarctation of the Aorta?
{{c1:: Secondary HTN Brain (Berry) Aneurysms}} ↓ BP to lower extremities causes
RAAS overractivity so HTN will be in upper extremity (arms) and brain (aneurysms)
A murmur over the back between the scapula is indicative of what heart condition?
{{c1:: Coarctation of the Aorta}}
"What two x-ray findings are indicative of Coarctation of the Aorta? {{c1:: rib
notching & ""3 sign"" }}" 3 sign = coarctation Rib notching = very high UE BP
proximal to coarctation causes notching of ribs via pressure from intercostal
arteries
Which lipid-lowering agent increases HDL the most? {{c1::Niacin (vitamin B3)}}
inhibits hormone sensitive lipase in fat, reduces hepatic VLDL synthesis
What pathogens can cause dilated cardiomyopathy (leading to CHF)? {{c1:: Coxsackie
B Trypanosoma cruzi}} Coxsackie causes acute myocarditis and CHF, while
Trypanosoma cruzi (Chagas) has chronic onset CHF
What is the cause of endocarditis stigmata? {{c1::spetic emboli and immune
complexes}} Janeaway lesions & splinter hemorrhages are microthrombi. Osler nodes
(painful) are immune complexes.
What are the four components of endocarditis stigmata? {{c1:: Roth spots Osler
nodes Janeway lesions Splinter hemorrhages}} Janeway lesions & splinter
hemorrhages are caused by microthrombi; Osler nodes (painful) caused by immune
complexes.
What is the microbio classification of Staph aureus? {{c1:: gram + catalase +
coagulase +}} endocarditis → tricuspid valve regurgitation in IV drug users
What is the classic predisposing condition for Viridans Streptococci (S. sanguinis)
endocarditis? {{c1::Mitral valve prolapse}} affect damaged valves → damaged
valves create fibrin → bacteria synthesize dextran → dextran adheres to fibrin
Patients with endocarditis confirmed to be caused by Streptococcus Bovis must be
evaluated for what malignancy? {{c1::Colon cancer}} strongest association with S.
gallolyticus (S. bovis type 1)
What are the predisposing factors for Enterococcus Endocarditis? {{c1:: OLD men
GI/GU tract manipulation (abdominal surg, catheter, TURP)}}gram + cocci, Lancefield
group D
What is the microbio classification of Staph Epidermidis? {{c1:: gram + catalase +
coagulase - novobiocin sensitive}} normal skin flora, prosthetic valve
endocarditis
What two pathogens are classic causes of culture negative endocarditis? {{c1::
Coxiella burnetti Bartonella}}
How is Coxiella burnetti transmitted? {{c1::humans inhale aerosolized bacteria from
farm animals (cattle, sheep, goats)}} obligate intracellular zoonotic bacteria
What is the hallmark of Libman-Sacks Endocarditis (non-bacterial, thrombotic
endocarditis) on gross examination? {{c1::vegetations on BOTH sides of valve}}
- a form of non-bacterial thrombotic endocarditis that is characterized by
deposition of sterile platelet thrombi. - mitral valve most common - formed by
thrombus + immune complexes + starins of fibrin and mononuclear cells - The trigger
for formation of these lesions is unknown but endothelial injury in the setting of
a hypercoagulable state appears to be required - Contrast with bacterial
endocarditis: lesions consist of inflammatory cells (often macrophages) with
thrombus or platelets and fibrin.
What conditions predispose to Libman-Sacks Endocarditis (NBTE)? {{c1:: advanced
malignancy lupus}} aka hypercoagulable states → thrombus & immune complexes
A patient with bacterial endocarditis who develops an AV block suggests what...?
{{c1::abscess beneath valve annulus}}
What two drugs are given for endocarditis prophylaxis? {{c1:: Amoxicillin
Clindamycin (penicillin allergy)}} only for high risk pts: prosthetic valves,
prior endocarditis, heart transplant recipients who are undergoing high risk
procedures: dental work, respiratory surg, skin surgery
What is the microbio classification of Enterococcous (Group D)? {{c1:: gram +
catalase - gamma hemolytic grows in 6.5% NaCl}} gamma hemolytic means there is no
hemolysis → they grow in bile
What type of arteriosclerosis occurs when hypertension is severe (malignant HTN)?
{{c1::Hyperplastic arteriosclerosis}} onion-skin appearance vs pink, thickness
of hyaline arteriosclerosis
What is the most common cause of secondary HTN? {{c1::chronic kidney disease}}
sodium retention RAAS activation sympathetic activity
How do NSAIDs cause secondary HTN? {{c1::decrease PGE2}} PGE2 dilates afferent
arteriole so ↓ PGE2 causes constriction of the afferent arteriole, leading to ↓ RBF
and ↓ GFR = RAAS activation and↑ sodium/water retention
What nasal decongestant causes secondary HTN? {{c1::pseudoephedrine}} alpha-1
agonist
What two immunosupressants can cause secondary HTN? {{c1::Cyclosporines and
Tacrolimus}} Inhibit calcineurin
How do Cyclosporines and Tacrolimus cause secondary HTN? {{c1::inhibit calcineurin
→ renal vasoconstriction → salt/water retention}} Reversible renal
vasoconstriction (of the afferent and efferent arterioles) would result in
increased serum creatinine (due to dec in GFR caused by afferent arteriole
constriction) and HTN (due to activation of RAAS). BUN:Cr ratio would be >20:1.
Renal biopsy would show vacuoles within the tubular cells In addition to HTN and
nephrotoxicity, cyclosporine can also cause gingival hyperplasia, hirsutism and
hyperlipidemia
What drug would you give to treat secondary HTN caused by cyclosporine and
tacrolimus? {{c1::Diltiazem}} impairs metabolism of these drugs, allowing you to
use lower doses of cyclosporine and tacrolimus
What cause of secondary HTN often occurs with Adrenal adenomas (Conn's Syndrome)?
{{c1::primary aldosteronism}} can also occur due to bilateral idiopathic adrenal
hyperplasia
What are the three clinical features of primary aldosteronism? {{c1::resistant
HTN::blood pressure?}} {{c1::hypokalemia::serum potassium levels?}} {{c1::normal
volume status::volume status?}} Hypokalemia → aldosterone causes sodium
reabsorption and potassium excretion. If someone has HTN that will not respond to
normal treatments with hypokalemia, put Aldosteronism at the top of the
differential
What finding is diagnostic of primary aldosteronism? {{c1::renin-independent
aldosterone secretion}} low renin high aldosterone
What drugs would you use to treat primary aldosteronism? {{c1::spirinolactone,
eplerenone}} block aldosterone receptor in collecting duct
What would you prescribe to treat Liddle Syndrome? {{c1::Amiloride}} directly
inhibits ENaC
{{c1::Pheochromocytoma}} is a catecholamine-secreting tumor (epi, NE, dopa) arising
from the adrenal gland pts will have secondary HTN & episodic bouts of
palpitations, sweating, tachycardia.
What is the triad of symptoms in patients with pheochromocytoma? {{c1::
Palpiatations Headache Episodic sweating}} P.H.E.ochromocytoma catecholamines
released in fluctuating manner
How are pheochromocytomas diagnosed? {{c1:: Metanephrines Vanillymandelic acid
(VMA)}} catecholamine breakdown products
What is the cause of Cushing's Disease? {{c1::pituitary adenoma oversecretes ACTH}}
ACTH is secreted by corticotroph cells in the anterior pituitary. In
contrast, Cushing's Syndrome is caused by excess cortisol (corticosteroid
medications)
What is the key exam finding in renal artery stenosis? {{c1::renal bruit}} ↓
blood to kidney → ↑ renin & salt/water retention → HTN
Why are there no signs of volume overload in renal artery stenosis? {{c1::RA
stenosis is unilateral and the normal kidney compensates}}
What drugs can precipitate renal failure in the setting of renal artery stenosis?
{{c1::ACE inhibitors}} stenosis constricts afferent arteriole, so GFR depends on
Angiotensin II (AT-II preferentially constricts efferent arteriole, decreasing RPF,
increasing GFR, so filtration fraction increases). With lowered ATII, kidneys will
fail
"What vascular disease obstructs flow to the renal arteries by medial layer
fibroplasia, causing stenosis and aneurysms of vessels (""string of beads"")?
{{c1::Fibromuscular Dysplasia}}" demographic: women in 40's and 50's
Rheumatic fever is a type {{c1::II}} hypersensitivity reaction to the bacterial
{{c1::M}} protein of strep M protein is an antiphagocytic virulence factor that
resembles human proteins in the heart, joints, basal ganglia, etc Antibody-
dependant cellular cytotoxicity (antibodies attract NK cells and other WBCs which
secrete cytotoxic molecules) is believed to be the pathogenic mechanism of carditis
in rheumatic fever.
What are the signs/symptoms of rheumatic fever? {{c1:: Joints: polyarthritis (> 5
joints) Carditis Nodules (subcutaneous) Erythema marginatum (rash on trunk)
Sydenham chorea}} JONES criteria
Carcinoid heart disease is caused by the secretion of {{c1::serotonin}} by
carcinoid tumors of the intestines
What valves are affected by carcinoid heart disease? {{c1::tricuspid and pulmonic}}
seratonin is inactivated by the lungs, so left sided lesions are rare
What are the two causes of aortic stenosis? {{c1:: senile (wear and tear) bicuspid
aortic valve}} bicuspid valve causes aortic stenosis at a younger age
Supravalvular Aortic Stenosis (narrowing of the ascending aorta above the aortic
valve) is commonly seen in what genetic deletion syndrome? {{c1::Williams
Syndrome}} Due to Elastin defect (elastin comprises > 50% of aorta) caused by
deletion of the long arm of chromosome 7
What is the most common cause of pulmonic stenosis? {{c1::congenital defect in
children causing fused commissures with thickened leaflets}} rarely carcinoid
heart disease
What heart valve disease can cause extremely low diastolic pressure (ie 120/40) and
wide pulse pressure? {{c1::Aortic regurgitation}} blood from aorta leaks back
into the left ventricle during diastole
What is the most common cause of pulmonic regurgitation? {{c1::surgically repaired
Tetralogy of Fallot}} repair of RV outflow tract obstruction damages valve
What is the formula for blood pressure? {{c1::BP = CO x TPR}}
What are the main functions of beta-1 receptors? {{c1:: Heart: ↑ HR & contractility
Kidney: stimulate renin release}} ONLY found in heart and kidneys. Blockade will
lower CO, volume and decrease BP
What is the function of beta-2 receptors? {{c1:: muscle and liver: vasodilation
bronchodilation }} blockade does not lower BP
Which beta blockers are B1 selective and used for HTN? {{c1:: Atenolol Esmolol
Metoprolol}} all beta-blockers A-M are B1 selective except carvedilol and
labetalol
Which B1 selective beta blocker is uniquely used for systolic HF?
{{c1::metoprolol}}
What are the nonselective (B1 = B2) beta blockers that can be used for HTN? {{c1::
Propanolol Timolol Nadolol}}
Which beta-blockers are used to treat portal hypertension? {{c1:: Nadolol
Propanolol}} B1 block lowers BP B2 block lowers portal blood flow
Which beta blocker is used to treat glaucoma? {{c1::Timolol}} B2 blocking
properties lead to ↓ aqueous humor production
Which beta blockers block B1, B2, and a1 receptors? {{c1:: Carvedilol Labetalol}}
Which beta-blocker is used in hypertensive emergency to rapidly reduce BP?
{{c1::Labetolol}}
Which non-selective beta blocker is used to treat systolic HF by blocking
sympathetic stimulation of the heart? {{c1::Carvedilol}}
Which beta-blockers are beta agonists in low sympathetic activity and are beta
blockers in high sympathetic activity? {{c1:: Pindolol (B1 = B2 nonselective)
Acebutolol (B1 selective)}} aka partial agonists → intrinsic sympathomimetic
activity
Why are beta blockers contraindicated in patients with diabetes? {{c1::can cause
hypoglycemia because they block epinephrine, which raises glucose levels}}
symptoms of hypoglycemia: sweating, tachychardia. Symptoms masked by beta
blockers (can still sweat tho)
Nonselective beta blockers (B1 = B2) are uniquely contraindicated in patients with
what medical condition? {{c1::asthma/COPD}} B2 receptors = bronchodilators
What is the treatment for beta blocker overdose? {{c1::Glucagon}} activates
adenylate cyclase at different site than beta receptors: ↑ cAMP ↑ Ca = ↑
contractility & HR
What are four alpha-1 blocking drugs? {{c1:: Tamsulosin Alfuzosin Doxazosin
Terazosin}} a1 receptors in periphery vasoconstrict, so blocking them will lead to
vasodilation and ↓ TPR & BP
What is the main clinical use of a1 blockers? {{c1::BPH}} commonly cause
orthostatic hypotension, Tamsulosin has less hypotension
What MOA of the HTN drug clonidine? {{c1::a2 agonist → a2 is located on the
presynaptic terminal, and stimulation lowers NE release}}
What are the side effects of the a2 agonist clonidine? {{c1:: Rebound Hypertension
Sedation}} rebound HTN caused by abrupt cessation of clonidine
{{c1::Methyldopa}} is an a2 agonist used to treat HTN in {{c2::pregnancy}}
What is the key, but rare side effect of Methyldopa (a2 agonist)? {{c1::Hemolytic
anemia}} Specifically, warm autoimmune hemolytic anemia
What is the unique side effect of dihydropyridine calcium channel blockers
(nifedipine, amlodipine)? {{c1::edema}} causes pre-capillary vasodilation →
increased capillary hydrostatic pressure
What are two unique side effects of Verapamil? {{c1:: constipation
hyperprolactinemia}} blocking Ca channels in CNS → ↓ dopamine release →
hypogonadism, low libido, impotence
What drugs can cause the side effect of gingival hyperplasia? {{c1:: Calcium
channel blockers phenytoin cyclosporine}}
What is the MOA of Aliskiren and what is its unique effect? {{c1::direct renin
inhibitor → reduces Angiotensin 1 levels}}
What is the MOA of Nitroprusside (used in hypertensive emergency)? {{c1:: ↑ cGMP ↑
NO release venous AND arteriolar dilation net effect: ↓ preload ↓ afterload}}
What is the unique side effect associated with long term use of Nitroprusside?
{{c1::Cyanide toxicity}}
What is the MOA of Fenoldopam (used in hypertensive emergency)? {{c1:: D1 agonist
arteriolar dilation ↑ sodium/water excretion}} Fenol-DOPE-am
What HTN drugs are highly contraindicated in pregnancy? {{c1::ACE inhibitors, ARBs,
Aliskiren }} methyldopa, beta blockers, nifedipine, hydralazine are all SAFE
What drug is the first line treatment for septic shock? {{c1::norepinephrine}}
a1, a2, B1 agonist: ↑ HR & contractility (B1) ↑ vasoconstriction (a1)
What are the side effects of thiazide diuretics? {{c1:: metabolic alkalosis
hyponatremia hyperGlycemia hyperLipidemia hyperUricemia hyperCalcemia}} GLUC:
dont give to patients with diabetes because of the hyperglycemia
What is the drug of choice in treating PSVT? {{c1::Adenosine}} decreases AV node
conduction by hyperpolarizing K-channels and slowing Ca-channels. Quick, short
duration of action
{{c1::Cardiogenic}} shock is caused by a fall in cardiac output Obstructive and
hypovolemic shock will have low cardiac output, but only cardiogenic shock is
actually caused by low CO, usually due to fall in contractility from MI
{{c1::Hypovolemic}} shock is caused by a fall in intravascular volume which leads
to a fall in cardiac output hemorrhage -Activation of SANS: Vasoconstriction of
veins (alpha-1) to increase preload and cardiac ouput, vasoconstriction of
arterioles (alpha-1) to maintain blood pressure and increased contractility (beta-
1) to maintain cardiac output
{{c1::Distributive}} shock is caused by peripheral vasodilation septic shock,
anaphylactic
What is the Fick Equation for Oxygen consumed? {{c1::O2 consumed = CO * (Art O2 -
Ven O2)}}
What is the Fick Equation for Cardiac Output? {{c1:: O2 Consumption (Art O2 - Ven
O2)}}
What is the formula for SVR? {{c1:: SVR = MAP - RAP CO}}
In cardiogenic shock, the cardiac pressures will be {{c1::high}} and the SVR will
be {{c1::high}} i.e. myocardial infarction, advanced HF
What type of shock is the only type to have LOW SVR? {{c1::Distrubitve (septic)}}
diffuse vasodilation and/or endothelial dysfunction, because remember
infection and toxins cause increased vascular permeability, causing low SVR
Which type of shock is the only type of shock to commonly have high cardiac output?
{{c1::Distributive (septic)}}
Which type(s) of shock characteristically present with cold skin? {{c1::
Cardiogenic Hypovolemic}} ↑SVR & ↓CO
Which type(s) of shock characteristically present with warm skin?
{{c1::Distributive (septic)}} ↓SVR & ↑CO
Aside from cold skin, what physical exam findings are characteristic of cardiogenic
shock? {{c1:: ↑JVP (↑RAP) pulmonary rales (↑LAP)}}
What three pathologies are classic causes of obstructive shock? {{c1:: tamponade
tension pneumothorax massive pulmonary embolism}} obstruction to blood flow
from heart
Obstructive shock causes {{c1::low}} cardiac output and {{c1::high}} SVR CO is
low due to obstruction from pressure (tamponade, pneumothorax)
How do you treat cardiogenic shock? {{c1::ionotropes → Milrinone, Dobutamine}}
bc of fall in contractility
How do you treat distributive (septic) shock? {{c1::vasopressors → phenylephrine,
epinephrine, norepinephribe}} because of high vascular permeability (low SVR)
How do treat obstructive shock? {{c1::Treat obstruction!}} PE, tension pneumo,
tamponade
What is the hallmark of mitral regurgitation in PCWP tracings? {{c1::Giant V
waves}} PCWP is same as JVP for right atria (i.e. tricuspid regurg), but for
the left atrium
{{c1::Derealization}} is a symptom associated with panic attacks that causes the
patient to feel like items in a room look foggy and unreal, as well as feeling like
they are in a foreign place despite being at home
"{{c1::Depersonalization}} is a symptom associated with panic attacks that give the
patient an ""outer body experience"", like they are detached and looking at
themself from above"
Behaviors that achieve goals of the ego in OCD-patients (working really hard over
stressful project) are termed {{c1::Egosyntonic}} behaviorsobsessive-compulsive
personality disorder
How is acute stress disorder differentiated from PTSD? {{c1::Dissociative symptoms
and lasts less than one month}} both caused by recent trauma and cause
recurrent, intrusive memories. Treat with CBT
What lipid-lowering agent should be added to treatment of a patient with high LDL
that is poorly controlled by statins (first line)? {{c1::Bile acid resins
(cholestyramine, colestipol, colesevelam)}} prevent intestinal reabsorption of
bile acids, causing the liver to use cholesterol to make more
Benzodiazepines cause activation of {{c1::GABAA}} receptors by increasing the
{{c1::frequency}} of Cl- channel opening Allosterically bind GABAa receptors
Auditory hallucinations are a classic feature of {{c1::schizophrenia}}
Olfactory hallucinations are a classic feature of {{c1::aura in temporal lobe
epilepsy}}
What type of hallucinations are seen with alcohol withdrawal, cocaine, and
amphetamines? {{c1::tactile}} insects crawling on skin
What are the 4 major endocrine effects of anorexia nervosa? (sequentially) {{c1:: ↓
Leptin (loss of fat) ↓ GnRH secretion ↓ LH/FSH Amenorrhea}}"""functional
hypothalamic amenorrhea"""
What electrolyte abnormalities are associated with anorexia nervosa? {{c1::
hyponatremia low creatinine (↓ muscle mass)}} hyponatremia will cause free water
loss & volume depletion leading to ↓ GFR
Most fatalities from refeeding syndrome in anorexia treatment are caused by
{{c1::cardiac failure::organ dysfunction}} ↓ PO4 = ↓ ATP → poor contractility,
↓SV prevent with slow refeeding
What are the metabolic complications of purging seen in Bulimia Nervosa? {{c1::
metabolic alkalosis hypokalemia low urine chloride (<20)}} Low urine chloride with
the other two abnormalities is diagnositic of Bulimia/self induced vomiting. (I
totally forget why tho)
What is the first line treatment for Binge Eating Disorder? {{c1::Psychotherapy
(CBT)}} Binge Eating Disorder is binge eating without compensation (includes
purging and excessive exercise, which characterize bulimia)
In addition to SSRIs, what two drugs are given in the treatment of binge eating
disorder? {{c1:: Lisdexamfetamine (vyvanse) Topiramate (seizure med)}}
{{c1::Conversion Disorder}} is a psychiatric disorder involving voluntary
neurologic symptoms (inability to speak, blindness), suddenly following stressor
(death) despite normal neurologic workup "also called ""functional neurologic
symptom disorder"""
{{c1::La Belle Indifference}} is a component of conversion disorder in which the
patient shows lack of concern about symptoms
What separates malingering from Munchausen Syndrome? {{c1::done for SECONDARY
(external) gain}} miss work/school, get worker's compensation
Dissociative Identity Disorder almost always occurs with what other pyschiatric
disorders? {{c1:: PTSD Depression Substance Abuse}}
{{c1::Dissociative Amnesia}} is the inability to recall autobiographical memories
(past events, job, where they live) follows trauma/stress, reversible
{{c1::SSRIs}} are the first line drugs for atypical depression MAOis are older,
secondary
A hypomanic episode is similar to mania but less severe and has the key feature of
{{c1::little/no impairment in functioning}} more energy but leads to productive
activity and less irresponsible behavior
A hypomanic episode lasts at least {{c1::4}} days and has no {{c1::psychotic
symptoms}} mania does have psychotic symptoms
What is the difference between Bipolar I & II? {{c1:: Bipolar I: MANIA +/-
depression Bipolar II: hypomania + ≥ 1 MDD episode}} - BPI mania → psychotic
features and impaired function - BPII hypomania → no psychosis or impaired function
- Major depressive episodes ( ≥ 1) required for BPII diagnosis, BPI doesnt require
MDD episode, but its still common
What drugs are given to treat Bipolar Disorder? {{c1:: 1. Anticonvulsants (Valproic
acid, Carbamazepine, Lamotrigine) 2. Lithium 3. Antipsychotics}} avoid anti-
depressants → may cause MANIA
{{c1::Cyclothymic Disorder}} is a mood disorder with mild mania and mild depressive
symptoms (does not meet criteria for hypomania or MDD) symptoms come and go at
least two years
{{c1::Persistent Depressive Disorder (or Dysthymia)}} is a more chronic and milder
form of depression that lasts at least {{c1::2}} years.
What are the five stages of acute grief (Kubler-Ross model)? {{c1:: Denial Anger
Bargaining Depression Acceptance}}
Acute grief becomes persistent grief if it lasts longer than {{c1::6 months}}
 persistent grief interferes with functioning, may lead to major depressive
disorder
Postpartum blues is normal depressed mood and fatigue following childbirth and
resolves within {{c1::2 weeks}} treatment is supportive
Postpartum depression (15% of women) persists longer than two weeks and the
treatment is {{c1::CBT}} and {{c1::SSRIs}}
What are the two common presenting speech characteristics of disorganized thought
in patients with schizophrenia? {{c1:: Tangential speech (change topics quickly)
Circumstantial speech (long, weird answers to questions)}}
What are two classic physical pathologic findings in patients with schizophrenia?
{{c1:: Enlarged lateral brain ventricles Dendritic spine loss}}
Schizophrenia is caused by excess of {{c1::dopamine}}
{{c1::Delusional Disorder}} is a psychotic disorder characterized by one or more
delusions lasting at least one month with otherwise no abnormal behavior """My
next door neighbor is Tony Soprano and he's plotting to kill me"" In contrast,
patients with paranoid personality disorder will display a pattern of paranoid
behavior and many aspects of life. For example, they may feel like spouse is
cheating, their co-workers talk behind their back, ""everyone"" is judging them,
etc."
Postpartum psychosis is a rare psychiatric disorder than occurs within two weeks of
delivery and is most commonly associated with {{c1::bipolar disorder}} and
{{c1::discontinuation of psychiatric meds}} "delusions often involve baby -
""someone is trying to kill my baby"""
How do you manage a woman with postpartum psychosis? {{c1:: HOSPITALIZE (risk to
self and baby) Antipsychotics ECT}} personal or family history of postpartum
psychosis, first pregnancy are risk factors in addition to other psych disorders
and discontinuation of psych meds
{{c1::Reactive Attachment Disorder}} is a childhood disorder caused by early
deprivation of attachment in which the child is withdrawn, avoidant, and
unresponsive to comfort
{{c1::Disinhibited Social Engagement Disorder}} is a childhood disorder caused by
early deprivation of attachment in which the child has little or no reluctance to
interact with adults (hugs strangers, sits on laps of strangers)
What are the characteristic fracture red flags for child abuse? {{c1:: 1. Multiple
fractures in different stages of healing 2. Rib fractures 3. Long bone spiral
fractures}}
What are the classic red flags for head trauma in abused children? {{c1:: retinal
hemorrhages subdural hematoma (shaken baby syndrome)}}
Child Sexual Abuse is most common in {{c1::9-12 (pre-pubery)}} year olds and the
perpetrator is usually a {{c1::male}} known to child women are more common
perpetrators in physical abuse may present with STD
{{c1::Vulnerable Child Syndrome}} is when parents perceive their child to be highly
succeptible to disease, usually resulting in missed school or overuse of medical
services
What neurotransmitter abnormalities are associated with depression? {{c1:: ↓
seratonin ↓ norepinephrine ↓ dopamine}} antidepressants increase levels, which
improves symptoms
What is the MOA of tricyclic antidepressants? {{c1::block reuptake of seratonin and
norepinephrine}} amitriptyline, nortriptyline, imipramine, doxepin
What are the three characteristics of TCAs that cause side effects? {{c1::
Antihistamine Anticholinergic Alpha-1 bock}}
The {{c1::antihistamine}} effect of TCAs leads to the side effects of sedation,
weight gain, and confusion (especially in elderly) Aka do not give TCAs to
elderly patients
The {{c1::anticholinergic}} effect of TCAs leads to the side effects of blurry
vision, constipation, dry mouth and urinary retention
The {{c1::alpha-1 blocking}} effect of TCAs leads to the side effect of orthostatic
hypotension
Which class of TCAs has predominant anti-histamine (sedating) effects?
{{c1::tertiary amines}} Amitriptyline, Clomipramine, Imipramine, Trimipramine,
Doxepin
What class of TCAs has more prominent norepinephrine (activating) effects?
{{c1::Secondary amines}} protriptyline, nortriptyline, desipramine
TCA overdose can cause {{c1::seizures}} and {{c1::coma}} because they antagonize
GABA receptors at high doses TCA OD is potentially fatal
TCA overdose can cause {{c1::hyperthermia}} due to anticholinergic toxicity
Anticholinergic toxicity causes loss of sweating → hyperthermia. Other signs
of anticholinergic toxicity are skin flushing, dilated pupils, ileus, and urinary
retention.
The most prominent sign of TCA toxicity is {{c1::increased QRS interval}} because
TCAs block cardiac sodium channels at high doses same as class IC
antiarrhythmics → dont give to patients with arrhythmias! Can cause Torsades de
Pointes
How do you treat TCA overdose? {{c1::Sodium Bicarbonate}} extra sodium overcomes
TCA sodium channel blockade,
What two TCAs can be used to treat diabetic peripheral neuropathy? {{c1::
amitriptyline desipramine}}
What TCA is used in migraine prophylaxis? {{c1::Amitriptyline}} The others are
Beta-blockers, Calcium channel blockers, Valproate and Topiramate
What TCAs can be used to treat childhood bed-wetting (enuresis)? {{c1:: imipramine
amitriptyline desipramine}} BUT, desmopressin is actually first line
What TCA can be used to treat insomnia? {{c1::Doxepin}} tertiary amine →
sedation effects (antihistamine)
MOA-A inhibitors inhibit the breakdown of seratonin, norepinephrine, and dopamine,
but MAO-B inhibitors only prevent the breakdown of {{c1::dopamine}}
What are three non-selective MAOIs? {{c1:: tranylcypromine isocarboxazid phenelzine
}}
What MAOi is MAO-B selective? {{c1::selegiline}} remember MOA-B only deals
with dopamine
What is the main clinical use of the MOA-B inhibitor Selegiline?
{{c1::Parkinson's}} blocks conversion of dopamine to DOPAC
What are the only three clinical uses of MAO inhibitors? {{c1:: refractory
(atypical) depression anxiety Parkinson's (selegiline)}}
People taking MAOIs must avoid {{c1::tyramine}} to prevent serotonin syndrome
tyramine is found in aged cheese and wine → displaces other NTs (NE) into the
synaptic cleft → ↑ sympathetic stimulation
What is the classic triad of Seratonin Syndrome? {{c1:: Agitation Autonomic
hyperactivity Neuromuscular HyperActivity }} Hyperthermia is a serious
consequence of Autonomic hyperactivity. NM hyperactivity can cause tremor, clonus,
hyperreflexia, bilateral Babinski
What is the treatment for serotonin syndrome? {{c1::cyproheptadine}} serotonin
(5-HT) antagonist
The predominant side effect of SSRIs is {{c1::sexual dysfunction}} ↑ seratonin
effects in spinal cord → ↓ libido, anorgasmia, ED
SNRIs inhibit the reuptake of both {{c1::serotonin}} AND {{c1::NE}}
What SNRI can be given to treat fibromyalgia? {{c1::Duloxetine}}
What SNRI can be given to treat Diabetic Neuropathy? {{c1::Venlafaxine}}
What are the side effects of SNRIs? {{c1:: *↑ Blood Pressure* Nausea Sexual
dysfunction}} high BP due to Norepinephrine effects Venlafaxine has highest
rate of sexual dysfunction
What are the two indications for Bupropion? {{c1:: depression smoking cessation}}
Why is Bupropion is often given in combo with SSRIs to treat depression?
{{c1::improves sexual dysfunction caused by SSRI}} because it has no effect on
seratonin → only blocks NE and dopamine reuptake (stimulant properties)
Atypical antidepressant Mirtazapine causes more {{c1::norepinephrine}} and
{{c1::serotonin}} release by blocking presynaptic alpha-2 receptors a2 normally
receptors provide negative feedback to the presynaptic nerve, suppressing the
realease of NE and serotonin
Atypical antidepressant Mirtazapine indirectly activates {{c1::5-HT1}} receptors by
blocking postsynaptic 5-HT2 & 5-HT3 receptors
{{c1::Trazodone}} is a weak serotonin reuptake inhibitor (5-HT2 receptors) that is
mainly used to treat {{c2::insomnia}} low doses: serotonin antagonist high
doses: serotonin agonist
The believed MOA of Lithium is the inhibition of {{c1::inositol monophosphatase
(IMPase)}} ↓ inositol ↓ 2nd messengers: PIP2, IP3, DAG
Lithium is primarilly {{c1::renally}} extcreted reabsorbed in proximal tubule (like
Na), which is why low volume states (Thiazides) cause lithium toxicity
What three drug classes Increase the levels of Lithium? {{c1:: Thiazides NSAIDS ACE
inhibitors}} All affect kidney → any reduction in volume (diuretics) or
reduction in GFR (NSAIDs & ACEi's) cause more lithium to be reabsorbed with sodium.
THIAZIDES very high yield
What class of drug Decreases the levels of Lithium? {{c1::Potassium-sparing
diuretics}} In contrast, thiazides increase levels of lithium
What is the classic acute side effect of Lithium immediately after patient begins
taking it? {{c1::Tremor}}
What drug would you give to treat Nephrogenic Diabetes Insipidus caused by Lithium?
{{c1::Amiloride}} K-sparing diuretic → blocks ENaC channels of principal cells,
blocking lithium entry into renal cells
{{c1::Rett Syndrome}} is a neurodevelopment disorder of females with the hallmark
of regression of cognitive/motor skills over 1-2 years of age also will present
with repetetive hand motions
The {{c1::mesocortical}} dopamine pathway is responsible for the negative symptoms
in schizophrenia (apathy, anergia)
D2 blockade by First Generation Antipsychotics raises {{c1::cAMP}} inside of
neurons normally D2 receptors inhibit Adenylyl Cyclase, which breaks down cAMP.
By inhibiting D2, you promote Adenylyl Cyclase & raise cAMP
{{c1::Dystonia}} is an extrapyramidal symptom of antipsychotics that occurs acutely
(within hours/days) which causes involuntary contraction of muscles seen with
high potency antipsychotics (Haloperidol)
Benztropine is an anticholinergic drug that blocks {{c1::M1}} receptors to improve
dystonia
{{c1::Akathisia}} is the most common extrapyramidal side effect of antipsychotics
that occurs within days and causes restlessness and strong urge to move tx →
lower dose, propanolol, benzos
How do you treat Akathisia from antipsychotics? {{c1:: lower dose benzos
propanolol}} Akathisia: restlessness, overwhelming urge to move.
{{c1::Bradykinesia}} is an extrapyramidal side effect of antipsychotics that causes
slow movements (Parkinson-like) """drug-induced Parkinsonism"""
What is the treatment for Bradykinesia caused by antipsychotics?
{{c1::Benztropine}}
{{c1::Tardive Dyskinesia}} is an extrapyramidal side effect of antipsychotics that
causes choreoathetosis and takes months or years to first appear IRREVERSIBLE
patients will smack lips, grimace, twist and writhe
What are the three High Potency first generation antipsychotics? {{c1::
Trifluoperazine Fluphenazine Haloperidol}} Try to Fly High
Which division of first generation antipsychotics (high vs low potency) causes more
extrapyramidal side effects? {{c1::High Potency}} D2 > a1 > 5HT > H1
Which division of first generation antipsychotics (high vs low potency) causes more
non-neurologic side effects? {{c1::Low Potency}} a1 = 5HT > D2
What are the Low Potency first generation antipsychotics? {{c1:: Chloropromazine
Thioridazine}} Cheating Thieves are Low
{{c1::Neuroleptic Malignant Syndrome (NMS)}} is a dangerous reaction to
antipsychotics presenting usually a week later with FEVER and rigid muscles Treat
with Dantrolene or Bromocriptine
What are the symptoms of Neuroleptic Malignant Syndrome (NMS)? {{c1:: Myoglobinuria
Fever Encephalopathy Vitals unstable Enzymes ↑↑ Rigidity}} Malignant F.E.V.E.R.
What are the two treatments for Neuroleptic Malignant Syndrome (NMS)? {{c1::
Dantrolene (muscle relaxant) Bromocriptine (D2 agonist)}}
Which antipsychotic has the strongest association with prolonged QT interval?
{{c1::IV Haloperidol }} Haloperidol may block cardiac potassium channels
Which two antipsychotics are associated with ocular side effects? {{c1::
Chlorpromazine Thioridazine}} low potency
Which antipsychotic can cause corneal deposits? {{c1::Chlorpromazine}}
Which antipsychotic can cause retinal deposits? {{c1::ThioRidazine}} "resembles
retinitis pigmentosa, may cause ""browning"" of vision"
Why are second generation antipsychotics better at reducing psychosis without the
EPS side effects of the first generation? {{c1::5HT > D2 → stronger Serotonin
blockers than Dopamine}}
Many atypical (2nd gen) antipsychotics produce effects by blocking the {{c1::5-HT-
2A}} serotonin receptors This is the receptor that LSD stimulates to make you
trip
What drug class is first line for treating schizophrenia? {{c1::Atypical
Antipsychotics }} aripiprazole, clozapine, risperidone, ziprasidone
What two antipsychotics are the most common cuplrits of Metabolic Syndrome? {{c1::
Clozapine Olanzapine}} "all -""apine""s"
What are the symptoms of Metabolic Syndrome? {{c1:: weight gain hyperglycemia
hyperlipidemia}} "caused by atypical ""-apine"" antipsychotics (clozapine,
olanzapine)"
What are the unique side effects of the atypical antipsychotic Clozapine? {{c1::
agranulocytosis (↓ WBC count) seizures}} reversible when drug is stopped
What two atypical antipsychotics are most strongly associated with
hyperprolactinemia? {{c1:: Risperidone Paliperidone}} galactorrhea amenorrhea in
women gynecomastia in men
What is the unique MOA of the atypical antipsychotic Aripiprazole? {{c1::D2 partial
agonist}} some blockade, some agonist effects, but overall less EPS than 1st gen.
Most common side effect is Akathisia
People with {{c1::Paranoid}} Personality Disorder have extreme distrust (even
family), are suspicious, struggle to build close relationships, and project onto
others hallmark is projection → attributing unacceptable thoughts to others,
often accuse others of being suspicious
People with {{c1::SchizoTYPAL}} Personality Disorder have few friends, hold odd
beliefs or magical thinking (superstitious), and are open to challenges to beliefs
open to challenges to beliefs differentiates them from delusions in
schizophrenia
People with {{c1::Antisocial}} Personality Disorder have disregard for others,
impulsive, often break the law, and lack remorse more common in men. must be
18+, otherwise its conduct disorder
People with {{c1::Borderline}} Personality Disorder have unstable personal
relationships, fear of abandonment, impulsivity, and often self-harm more common
in women. breaking up & getting back together often. always either love or hate
someone, and these feelings swap often
{{c1::Splitting}} is the major defense mechanism in Borderline PD splitting →
black & white thinking (always/never, love/hate), cannot hold opposing views, p.
much everyone in 2017
The gold standard for treatment of Borderline Personality Disorder is
{{c1::Dialectal Behavioral Therapy}} weekly therapy for 1-2 years:
mindfulness, distress tolerance, emotion regulation
People with {{c1::Histrionic}} Personality Disorder always want to be the center of
attention, sexually provacative, and overly concerned about physical appearance
People with {{c1::Narcissistic}} Personality Disorder have an inflated sense of
self, lack empathy, loves praise, overreact to criticism
People with {{c1::Avoidant}} Personality Disorder avoid social interactions because
they feel inadequate and are afraid of embarassment differs from schizoid because
they want to socialize but cant
What distinguishes Obsessive-Compulsive Personality Disorder from regular OCD?
{{c1::OCPD: behaviors help to achieve goals}} i.e. making a to do list, vs
checking watch every 10 seconds in regular OCD
People with {{c1::Dependent}} Personality Disorder are clingy and have low self-
confidence always in a relationship, may be involved in abuse relationships
Which species of viridans group streptococci causes endocarditis? {{c1::Strep
sanguinis}} makes Dextrans that bind to fibrin-platelet aggregates on damaged
valves; subacute bacterial endocarditis (2-3 weeks)
For ADHD diagnosis, frequent symptoms of hyperactivity/impulsivity that impairs
function must be present in what three circumstances? {{c1:: present in 2+ settings
(school, home) persist for at least 6 months present before age 12}} excessive
for developmental level of child
What three drugs (or classes) are used in ADHD treatment? {{c1:: stimulants
Atomoxetine Alpha-2 agonists}} also behavioral interventions (rewards/timouts)
and behavioral therapy
Stimulants increase {{c1::dopamine}} and {{c1::NE}} in the CNS by blocking reuptake
{{c1::Atomoxetine}} is a non-stimulant treatment for ADHD less insomnia & loss of
appetite
ADHD drug Atomoxetine is a selective {{c1::norepinephrine}} reuptake inhibitor
no effect on dopamine → no dopamine euphoria or abuse potential
What alpha-2 agonists are 2nd line treatments for ADHD? {{c1:: Clonidine
Guanfacine}} also second line in Tourette Syndrome → increase prefrontal
cortex activity to regulate attention and behavior
What two genetic disorders are associated with autism? {{c1:: Fragile X Syndrome
Double Y Males (XYY)}}
What is the formula for Positive Predictive Value (PPV)? {{c1:: TP TP + FP}} PPV =
how many people who test postive actually have the disease
What kind of mutations occur in familial HCM? {{c1::single-point missense
mutations}} autosomal dominant → often genes for cardiac sarcomere proteins
What are the classic histological findings in HCM? {{c1:: Myocyte disarray
(excessive branching) Interstitial fibrosis}}
What two medications can be used to treat LV outflow obstruction in HCM? {{c1::
Beta blockers Calcium blockers (verapamil)}} ↓ contractility → less thickening.
Note that you'd never give dihydropyridine Calcium channel blockers (Amlodipine)
because HCM is worse with ↓ preload
What valvular disease often develops in HCM patients with LV outflow obstruction?
{{c1::Mitral regurgitation}} high velocity in LVOT tugs at mitral valve chords and
leaflets, causing systolic anterior motion (SAM) of mitral valve
What four abnormal heart sounds can be heard in HCM patients with LV outflow
obstruction? {{c1:: systolic ejection murmur (like A.S.) holosystolic murmur of MR
S4 Paradoxical S2 split}} MR commonly occurs secondary to HCM
Valsalva {{c1::decreases}} preload ↑ thoracic pressure → compression of veins → ↓
venous return → ↓ preload → smaller LV cavity → LOUDER HCM, softer aortic stenosis
Squatting {{c1::increases}} preload blood stored in legs returns to heart → preload
rises → size of LV increases → softer HCM
Which maneuvers increase and decrease the intensity of HCM? {{c1:: ↑ Valsalva,
Standing ↓ Sqautting, Leg Raise}}
Infantile transient HCM that resolves within a few months of age is associated with
{{c1::maternal diabetes}} usually thickening of IV septum
{{c1::Friedreich Ataxia}} is an autosomal recessive CNS disease that presents with
spinocerebellar symptoms and concentric left ventricular hypertrophy
trinucleotide repeat disorder (GAA) on chromosome 9
What are the 5 symptoms of Fabry Disease? (differentiate between early and late)
{{c1:: Early→ peripheral neuropathy, angiokeratomas, hypohidrosis Late → LV
Hypertrophy, renal disease}} X-linked recessive, deficiency of a-galactosidase A
Pompe Disease (type II GSD) is caused by a deficiency in the {{c1::acid alpha-1,4-
glucosidase}} enzyme causes HCM
What is the MOA of PCP (Phencyclidine)? {{c1:: 1. antagonist of NMDA receptors 2.
inhibits reuptake of dopamine, NE, 5-HT}}
What are the two treatments for PCP intoxication? {{c1:: Benzos Haloperidol}}
Ecstacy can cause the electrolyte abnormality of {{c1::hyponatremia}} leading to
increased fluid intake & secretion of ADH, which can cause seizures and death
can also cause hepatotoxicity → RUQ pain, ↑ ALT/AST
In cognitive orders with disorientation, rank person, date, and place from first
lost to last: {{c1::time → place → person (last)}} disorienation can be caused
by psych issues (dementia), fever, substance abuse, hypoglycemia, and electrolytes
What metabolic abnormality can cause reversible dementia? {{c1::Hypothyroidism}}
always check TSH
What are the two major effects of cocaine? {{c1:: local anesthetic (Na channel
blocker) inhibits monoamine reuptake}}
What three drugs can be given to patients to help with smoking cessation? {{c1::
Bupropion (antidepressant) Varenicline (partial nicotinic agonist)}}
Typical antipsychotics (eg; haloperidol, risperidone only control the
{{c1::positive}} symptoms of schizophrenia by blocking D2-receptors in mesolimbic
pathway -D2-receptors inhibit adenylyl cyclase → ↓ cAMP -Stimulation of the
mesolimbic dopamine pathway → increased positive symptoms of schizophrenia
(delusions, hallucinations)
The most common location of an ectopic thyroid is at {{c1::the base of the tongue
(lingual thyroid)}} presents as a mass in the tongue, detected during puberty
and pregnancy (increased hormone demand) -Removal may result in hypothyroidism if
it is the only thyroid tissue present
Both thyroid hormones (T3 & T4) are formed from a combination of {{c1::tyrosine}}
and {{c1::iodine}}
In the first step of thyroid hormone synthesis, Iodide reuptake occurs through the
{{c1::Na-Iodine Symporter (NIS)}} on the follicular cells perchlorate (ClO4-) and
pertechnetate (TcO4-) compete with iodide
What are the functions of thyroid peroxidase in thyroid hormone synthesis? {{c1::
1. Oxidation (iodide → iodine) 2. Organification (iodine + tyrosine from TG → MIT &
DIT) 3. Coupling of MIT & DIT}} MIT + DIT = T3 DIT + DIT = T4
T4 is converted to T3 by {{c1::5' deiodinase}} in peripheral tissues blocked by
PTU, propranolol
{{c1::Propylthiouracil (PTU)}} is a hyperthyroid medication that inhibits
{{c2::TPO}} and {{c2::5'-deiodinase}} TPO inhibition: ↓ T3/T4 from thyroid 5'DI
inhibition: ↓ T4 → T3 conversion
{{c1::Methimazole}} is a hyperthyroid medication that inhibits TPO only "PTU &
Methimazole are ""thioamides"""
Which beta-blocker is a weak inhibitor of 5'-deiodinase for the treatment of
hyperthyroidism? {{c1::Propanolol}} excellent in thyrotoxicosis → blocks
catecholamines and T4-T3 conversion
What is the regulatory mechanism by which the body prevents hyperthyroidism from
excessive iodide intake? {{c1::Wolff-Chaikoff Effect → excessive iodide inhibits
thyroid peroxidase (organification)}}
Large doses of I131 destroys thyroid tissue through {{c1::B-decay}} radiation
small doses used for imaging, large doses can be used as therapy for
hyperthyroidism
A deficiency of {{c1::Thyroxine-Binding Globulin (TBG)}} will result in less
available T4/T3 in tissues carrier protein for T4, produced in liver
What hormone raises TBG levels? {{c1::Estrogen}} pregnancy, birth control
users = ↑ total T4 (free T4 initially drops but normalizes in time)
How will liver failure alter TBG and T4 levels? {{c1:: ↓ TBG ↓ T4}} less
production of TBG: ↓ T4 levels
{{c1::HYPER}}thyroidism is a classic cause of hyperglycemiaThyroid hormone
increases carbohydrate metabolism (glycogenolysis, gluconeogeneis) → more glucose
How does thyroid hormone increase basal metabolic rate? {{c1::more Na/K ATPase
pumps}} more pumps → more ATP consumed → more oxygen demand → ↑ respiratory
rate, ↑ body temperature
Hyperthyroidism causes weight {{c1::loss}} ↑ Basal Metabolic Rate
Hypothyroidism will cause weight gain
Children with hypothyroidism are at risk for {{c1::cretinism}} which causes stunted
growth and mental retardation causes include: Iodine deficiency (3rd world) Thyroid
dysgenesis dyshormonogenesis (TPO dysfunction)
{{c1::Cretinism}} is the most treatable cause of mental retardation correct the
hypothyroidism
TSH (thyrotropin) released from the anterior pituitary binds to receptors on
follicular cells and activates the {{c1::cAMP/PKA}} second messenger system ↑ T3 &
T4 release
The hypothalamus releases {{c1::Thyroid Releasing Hormone (TRH)}} to tell the
anterior pituitary to release TSH when T3/T4 levels are lowhypothalamus senses
level of T3/T4 → excess will lead to inhibition of pathway
Early in pregnancy, {{c1::hCG}} stimulates the thyroid (like TSH) which will ↑ free
T4 and ↓TSH Only early in pregnancy, levels normalize with time (watch out for
this). hCG has same alpha subunit as TSH (as well as LH & FSH)
{{c1::Calcitonin}} is secreted by thyroid parafollicular (C) cells to lower serum
calcium used as therapy for hypercalcemia
The adrenal cortex is derived from {{c1::mesoderm}} and the adrenal medulla is
derived from {{c1::neural crest cells}}
Aldosterone promotes reabsorption of {{c1::sodium and water}} and excretion of
{{c1::potassium and hydrogen}} Aldosterone is a mineralocorticoid secreted by
the adrenal cortex
When is serum cortisol highest? {{c1::early morning (6 am)}} lowest one hour
after sleep onset
90% of serum cortisol is bound to {{c1::CBG}} CBG = Cortisol Binding Globulin,
estrogen increases levels
What are 5 effects that cortisol has on suppressing the immune system? {{c1:: ↓ T &
B cell plasma levels ↓ eosinophil count block histamine release from mast cells
inactivate NF-KB ↑ peripheral neutrophil count}}
Cortisol inactivates {{c1::NF-KB}} which is a key inflammatory transcription factor
that mediates response to TNF-a and controls synthesis of inflammatory mediatiors
inflammatory mediators: COX-2, PLA2, Lipoxygenase
Cortisol causes the liver to store more glycogen by increasing the synthesis of
{{c1::glycogen synthase}}
What effect does cortisol have on fat? {{c1::↑ total cholesterol & triglycerides →
adipocyte growth & fat deposition}} increases fatty acids by activating lipolysis
in adipocytes
How does Angiotensin II stimulate aldosterone production? {{c1::activates
aldosterone synthase}}
How does ACTH promote the synthesis of aldosterone? {{c1::stimulates Desmolase}}
Antifungal Ketoconazole is a potent inhibitor of {{c1::17,20 lyase}} in the testes
and adrenal cortex, leading to decreased andro & test which causes gynecomastia
The posterior pituitary is derived from {{c1::neural ectoderm (neural tube)}} and
contains axons and neurons that originate in the hypothalamus so they're
actually made in the hypothalamus and transfered via neurophysins (carrier
proteins)
What hypothalamic nuclei synthesize oxytocin and ADH? {{c1:: Oxytocin →
Paraventricular ADH → Supraoptic}}
The Anterior Pituitary gland is derived from {{c1::Rathke's pouch}} which is an
outgrowth of the oral cavity surface ectoderm in contrast to posterior pituitary,
which is an outgrowth of the basal forebrain (neural ectoderm)
Match the hypothalamic hormones with their anterior pituitary response: CRH →
{{c1::ACTH release}} TRH → {{c1::TSH release}} GnRH → {{c1::LH/FSH release}} GHRH →
{{c1::GH release}} Dopamine → {{c1::Prolactin inhibition}} Somatostatin → {{c1::GH,
TSH inhibition}}
↑ TRH (as seen in hypothyroidism) causes an increase in TSH as well as
{{c1::prolactin}} secretion
During pregnancy, {{c1::estrogen}} stimulates prolactin release from lactotrophs
pituitary can grow in size
During pregnancy, prolactin inhibits {{c1::GnRH}} release, resulting in cessation
of ovulation and menstruation
What drugs are used to treat prolactinomas? {{c1::Dopamine agonists →
Bromocriptine, Cabergoline}} inhibit prolactin release via D2 receptors
What visual field defect is seen with pituitary adenomas? {{c1::bitemporal
hemianopsia → compression of optic chiasm}}
What are the manifestations of hypopituitarism? {{c1:: ↓ ACTH → ↓ cortisol → shock
↓ TSH → hypothyroidism ↓ LH/FSH → hypogonadism}} causes by nonfunctional
adenomas, craniopharyngiomas, ischemia, brain injury
{{c1::Craniopharyngiomas}} are benign tumors in children derived from Rathke's
Pouch which lead to hypopituitarism and visual field defects
{{c1::Pituitary Apoplexy}} is a source of hypopituitarism that is caused by sudden
hemorrhage into the pituitary gland often due to a pre-existing adenoma or bleeding
risk factors (warfarin) sudden onset of severe headache, diplopia (pressure on
oculomotor nerve), shock (hypopituitarism)
{{c1::Sheehan Syndrome}} is an ischemic infarct of the pituitary following
postpartum bleeding presenting as shock (hypopituitarism) after delivery and
failure to lactate pituitary is enlarged in pregnancy, so it's vulnerable to
infarction during hypovolemic shock (giving birth)
What 3 things stimulate the release of growth hormone (somatotropin) from the
pituitary? {{c1:: GHRH exercise (deadlifts) sleep}}
What three things inhibit growth hormone (somatotropin) release from the pituitary?
{{c1:: Glucose Somatostatin IGF-1}}
Growth Hormone signals the LIVER to secrete {{c1::IGF-1 (somatomedin)}} which
mediates GH effects Measured in serum
Growth hormone {{c1::decreases}} glucose uptake by cells and {{c1::increases}}
lipolysis diabetogenic → raises blood sugar, causes insulin resistance lipolysis
→ activation of hormone senstive lipase
What is the most common cause of excessive growth hormone? {{c1::somatotroph
adenoma}} rare causes are GHRH secreting tumors → hypothalamic & carcinoid
tumors, small-cell lung cancer
What 3 tests are used to diagnose acromegaly/gigantism? {{c1:: serum IGF-1 oral
glucose tolerance test CNS imaging (MRI)}} glucose should suppress GH levels,
but with ↑GH patients, GH remains high. ** As a rule of thumb, most cases when
there is a secreting tumor, it will not be suppressed by whatever inhibits it
(gastrinomas don't respond to secretin, small cell lung carcinoma doesn't respond
to dexamethasone suppression test, and so on)**
{{c1::Octreotide}} is an analog of somatostatin used to suppress the release of
growth hormone goal is to lower IGF-1
{{c1::Proopiomelanocortin}} is a pro-hormone precursor of ACTH and Melanocyte
Stimulating Hormone produced by the pituitary - Also Beta-endorphins Excess
release of POMC (and subsequently MSH) results in hyperpigmentation
{{c1::Melanocyte Stimulating Hormone (MSH)}} stimulates melanocytes to produce
melanain, and causes hyperpigmentation in Cushing's Disease
What is the only hormone secreted by the intermediate lobe of the pituitary?
{{c1::Melanocyte Stimulating Hormone (MSH)}}
What drug can be given to induce labor or for post-partum bleeding? {{c1::Pitocin}}
Pitocin is synthetic oxytocin → causes uterine contraction
What are the indications for the somatostatin analog Ocreotide? {{c1:: Acromegaly
Carcinoid syndrome Glucagonoma/Insulinoma Upper GI bleeding Esophageal Varices}}
Remember that somatostatin suppresses growth hormone (acromegaly), insulin,
glucagon, gastrin (less acid, upper Gi bleed)
What is the cause of Laron Syndrome (Dwarfism)? {{c1::defective growth hormone
receptors}} ↑GH , ↓IGF-1
In all congenital adrenal hyperplasia syndromes, there are low levels of
{{c1::cortisol}} and high amounts of {{c1::ACTH}} ↑ ACTH causes the hyperplasia
→ can cause increased production of mineralocorticoids (aldosterone) or androgens
(testosterone)
What are the signs and symptoms of congenital adrenal hyperplasia (low cortisol) in
babies? {{c1:: hypoglycemia nausea & vomiting}}
In congenital adrenal hyperplasia, what will the result be if there are excess
androgens in a female (XX)? {{c1::Ambiguous genitalia}}
In congenital adrenal hyperplasia, what will the sexual result be if there are
excess androgens in a male (XY)? {{c1::precocious (early) puberty}}
In congenital adrenal hyperplasia, what will the result be if there are deficient
androgens in a female (XX)? {{c1::normal genitalia}}
In congenital adrenal hyperplasia, what will the result be if there are deficient
androgens in a male (XY)? {{c1::female or ambiguous genitalia}}
11-B Hydroxylase Deficiency causes excess buildup of {{c1::11-deoxycorticosterone}}
and androgens Exerts aldosterone-like effects (HTN, hypokalemia)
What are the clinical features of 11-B Hydroxylase Deficiency? {{c1:: low cortisol
symptoms hypertension hypokalemia}} like 21-A Hydroxylase Deficiency, ↑ androgens
(testosterone) will lead to ambiguous gentalia in girls and precocious puberty in
boys
How will 17-A Hydroxylase Deficiency alter the three adrenal cortex products?
{{c1:: ↑ Aldosterone ↓ Cortisol ↓ Androgens}} 17-a Hydroxylase is a cytochrome
P450c17 enzyme (CYP17A1) found in both adrenals and gonads → males will have female
or ambiguous genitalia
How does 17-a Hydroxylase Deficiency present in males and females (sexually)?
{{c1:: Males (XY): female or ambiguous genitalia Females (XX): lack secondary
sexual development → amenorrhea, ↓ estradiol at puberty}} both will have HTN and ↓
K+ due to excess aldosterone
Congenital Adrenal Hyperplasia is screened by measuring the level of {{c1::17-
Hydroxyprogesterone}} elevated in 21-a Hydroxylase deficiency (most common CAH)
Most forms of CAH are treated with {{c1::glucocorticoids}} replenishes cortisol and
lowers ACTH → stops overproduction of other hormones
What are the two ACTH-independent (↓ ACTH) causes of Cushing's Syndrome? {{c1::
Glucocorticoid therapy Adrenal Adenoma}}
What are the two ACTH-dependent (↑ ACTH) causes of Cushing's Syndrome? {{c1::
Cushing's Disease (pituitary tumor) Ectopic ACTH (small cell lung cancer)}} ↑ACTH
→ adrenal hyperplasia → ↑ cortisol
Skin Hyperpigmentation in patients with Cushing's Sydrome indicates what?
{{c1::ACTH-dependent (↑ ACTH) → pituitary tumor or small cell lung cancer}} ACTH
binds to MSH receptors
How do you diagnose someone with Cushing's Syndrome by the low dose dexamethason
suppression test? {{c1:: 1. 1mg dexamethasone before bedtime 2. morning blood test
3. cortsol high = Cushing Syndrome}} dexamethasone is synthetic cortisol and
should suppress normal ACTH release, meaning morning cortisol should be low. If
high → Cushing's Syndrome
What are the two treatments for Cushing's Syndrome? {{c1:: Surgery → remove tumor
Ketoconazole}}
How will Primary adrenal insufficiency (Addison's Disease) affect cortisol,
aldosterone and ACTH? {{c1:: ↓ Cortisol & Aldosterone ↑ ACTH}}
How will Secondary adrenal insufficiency affect cortisol, aldosterone and ACTH?
{{c1:: Normal Aldosterone ↓ ACTH & cortisol}} causes by failure of pituitary to
secrete ACTH → aldosterone is under the control of RAAS system (Ang II), so it
isn't affected
What are the low aldosterone associated symptoms of Adrenal Insufficiency? {{c1::
Hyperkalemia Acidosis Hypovolemia}} Low aldosterone? H-A-H
What are the causes of Addison's Disease? {{c1:: Autoimmune → antibodies to 21-
hydroxylase Infections → TB, fungal, CMV}}
{{c1::Waterhouse-Friderichsen Syndrome}} is a rare cause of acute adrenal
insufficiency caused by hemorrhage into the adrenal glands after meningitis -
Endotoxin-triggered coagulopathy Neisseria Meningitis is common cause. Look for
patient with meningitis + rash that develops shock and DIC
The most common cause of secondary adrenal insufficiency is {{c1::glucocorticoid
therapy}} "chronic suppression of ACTH → adrenal atrophy over time. Must ""ween""
patients off of steroids to prevent hypoadrenalism"
High ACTH with Low cortisol indicates {{c1::primary}} adrenal insufficiency
Low ACTH with Low Cortisol indicates {{c1::secondary}} adrenal insufficiency
How is the ACTH stimulation test (cosyntropin stim test) used to diagnose adrenal
insufficiency? {{c1:: Exogenous ACTH administered → cortisol should rise in 30-60
minutes Failure to rise → primary insufficiency Normal rise → secondary
insufficiency}}
Licorice overconsumption can present similary to hyperaldosteronism (HTN,
hypokalemia) because it contains the steroid {{c1::glycyrrhetinic acid}} which
inhibits renal {{c1::11-B-hydroxysteroid dehydrogenase}} cortisol can stimulate
aldosterone receptors, but cortisone does not. licorice blocks the conversion of
cortisol to cortisone, resulting in ↑ cortisol which stimulates aldosterone
receptors
Pheochromocytomas are catecholamine-secreting tumors arising from the
{{c1::chromaffin cells}} of the adrenal medulla which are derivatives of embryonic
{{c1::neural crest cells}}
Dopamine is metabolized by both {{c1::Monoamine Oxidase (MAO)}} and {{c1::Catechol-
O-methytransferase (COMT)}} to {{c2::Homovanillic Acid (HVA)}}
Epinephrine and Norepinephrine are both broken down by COMT and MOA to the final
product of {{c1::vanillylmandelic acid (VMA)}}
Before surgically removing a pheochromocytoma, the pre-op drug management includes
what two drugs? {{c1:: Phenoxybenzamine (irreversible a-blocker) Propanolol (non-
selective B-blockers)}} phenoxybenzamine MUST be given BEFORE propanolol to prevent
hypertensive crisis
{{c1::Paraganglioma}} is a catecholamine secreting tumor arising from sympathetic
ganglia that has a similar clinical presentation to pheochromocytomas
{{c1::Neuroblastoma}} is a tumor of primitive sympathetic ganglion cells that can
arise anywhere in the sympathetic nervous system (adrenal most common) and is only
found in children derived from neural crest cells 3rd most common childhood cancer
What are the unique presenting symptoms of neuroblastomas? {{c1:: mass effect →
abdominal pain Opsoclonus-myoclonus ataxia (OMA)::2?}}
{{c2::Opsoclonus-myoclonus ataxia (OMA)}} is a rare paraneoplastic syndrome
involving rapid eye movements, rhythmic jerking, and ataxia and 50% of OMA patients
also have a {{c1::neuroblastoma}}
How are neuroblastomas diagnosed? {{c1::urinary HVA & VMA levels}}
What is the most important risk factor for neuroblastomas prognosis? {{c1::Age at
diagnosis}} younger age (< 18 months) → better prognosis
What genetic abnormality is associated with neuroblastomas? {{c1::N-myc
amplification }} proto-oncogene, associated with poor prognosis
{{c1::Metaiodobenzylguanidine (MIBG)}} is a norepinephrine analog that is used to
diagnose pheochromocytomas & neuroblastomas concentrates in tumors and emits
radiation through radioactive iodine (I131)
When administering MIBG for pheochromocytoma & neuroblastoma diagnosis, you must
simulataneously administer {{c1::potassium iodide}} to protect the thyroid. non-
radioactive iodine → taken up by thyroid instead of I131
Describe the synthesis of insulin in Beta cells: {{c1:: 1. Preproinsulin made by
ribosomes on RER 2. Preproinsulin cleaved to proinsulin 3. Packaged into secretory
granules in Golgi 4. Proinsulin cleaved to insulin & C-peptide in granules}}
PROTEIN hormone
Insulin is composed of an alpha chain and beta chain connected by {{c1::disulfide}}
bridges C-peptide = connecting peptide, indicator for insulin production
What is the mechanism of insulin release in B-cells? {{c1:: 1. GLUT2 brings glucose
inside → Conversion glucose to G-6-P by enzyme glucokinase → 2. G-6-P metabolized
to ATP → Inc ATP/ADP ratio → 3. ATP closes ATP-dependent K-channels → accumulation
of K+ into cells causes depolarization of membrane → 4. Calcium channels open → Ca
influx → 5. Exocytosis of insulin}}
Production of insulin is inhibited by the action of {{c1::epinephrine}} on alpha-2
receptors fight or flight response → plasma glucose
What beta cell enzyme (found in liver and pancreas) is the 1st step of glycolysis
and is induced by insulin? {{c1::glucokinase}} ↑ KM → rate varies with glucose ↑
VM → can convert lots of glucose
The insulin receptor is what type of receptor? {{c1::Tyrosine Kinase Receptor
(TKR)}} insulin binds, tyrosines on receptor are phosphorylated, binds IRS-1 &
IRS-2 to induce PIK3 or RAS/MAP kinase pathways
What are the effects of the PIK3 insulin pathway? {{c1:: glycogen synthesis fatty
acid synthesis GLUT-4 transporter activation}} GLUT4 leads to increased glucose
uptake in muscle & fat
What are the effects of the RAS/MAP Kinase insulin pathway? {{c1::cell growth and
gene expression}}
What are the two insulin-dependent organs? {{c1::muscle and fat}} NEED GLUT4
for glucose uptake → need insulin to activate GLUT4
The brain and RBCs are insulin-independent organs that use {{c1::GLUT-1}} for
glucose uptake RBCs → no mitochondria (depend on glycolysis) Brain → no fatty
acid metabolism (depend on glucose/ketones
The liver, kidneys, and intestines are insulin-independent organs that use
{{c1::GLUT-2::glucose transporter?}} for glucose uptake
How does insulin promote glycogen synthesis? {{c1:: activates glycogen synthase via
dephosphorylation inhibits glycogen phosphorylase via dephosphorylation }}
How does insulin inhibit gluconeogenesis? {{c1:: ↑ PFK-2 activity leading to Inc
Fructose-2,6-bisphosphate inhibit Fructose-1,6-bisphosphatASE}} therefore, insulin
promotes glycolysis, breaking down glucose to reduce blood sugar
How does insulin increase fatty acid synthesis? {{c1:: activates acteyl-CoA
carboxylase::activates?}} {{c1::inhibits hormone sensitive lipase::inhibits?}}
{{c1::Hormone Sensitive Lipase}} is an enzyme that removes fatty acids from
triglycerides in adipoctytes
What activates and inhibits Hormone Sensitive Lipase? {{c1:: inhibits: insulin
activates: glucagon, epinephrine}}
What effects does insulin have on sodium and potassium? {{c1:: ↑ Na+ resorption in
nephron ↓ Potassium by enhancing NA-K ATPase}} Shifts potassium to intercellular
compartment. Insulin + Glucose are used to treat hyperkalemia
Describe the glucagon receptor function. {{c1::Gs → activates adenylyl cyclase → ↑
cAMP → activates PKA}} gylcogenolysis, gluconeogenesis, lipolysis, ketone
production
Glucagon receptors are found mostly in the {{c1::liver}} none in skeletal muscle
What are the two treatments for unconscious patient with hypoglycemia? {{c1:: IV
Dextrose IM Glucagon}} ↑ plasma glucose levels. IV dextrose preferred, but
obviously IVs are relegated to the hospital. IM glucagon often in school, work,
grocery store etc first aid kits in the setting of sudden hypoglycemic collapse
outside hospital setting.
{{c1::Insulinoma}} is a rare pancreatic islet-cell tumor in adults (~50)
characterized by fasting hypoglycemia and neuroglycopenic symptoms (confusion, odd
behavior) also presents with symapthetic activation from low glucose →
palpitations, diaphoresis, tremor
What are the clinical hallmarks of insulinoma presentation? {{c1:: fasting
hypoglycemia confusion & odd behavior sympathetic symptoms (palpatations)}} Will
have HIGH C-Peptide levels
How do you clinically differentiate exogenous insulin vs an insulinoma in patients
with fasting hypoglycemia? {{c1::insulinoma will have ↑ C-peptide, while exogenous
insulin will not}} both have high insulin (fasting hypoglycemia)
What class of oral diabetes drugs is most commonly associated with fasting
hypoglycemia? {{c1::2nd generation sulfonylureas (oral hypoglycemics)}}
Glimepride & Glyburide are long-acting and have ↑ risk of hypoglycemia than
Glipizide (short acting)
{{c1::Glucagonoma}} is a rare pancreatic tumor that leads to glucose intolerance
and elevated fasting glucose levels excess glucagon secretion → presents similar to
diabetes
Which MEN syndrome is associated with insulinomas and glucagonomas? {{c1::MEN Type
1}} mutations of MEN1 tumor supressor
What are the 7 symptoms of severe hypocalcemia (iCa <0.9 mmol/L)? {{c1:: Tetany
Twitching (Chvostek sign) Spasm (Trousseau sign) Seizures QT prolongation
Arrhythmias Hypotension }}
{{c1::Pseudohypoparathyroidism 1A (Albright hereditary osteodystrophy)}} is a
genetic disease causing the kidney to be unresponsive to PTH hypocalcemia
despite ↑ PTH, autosomal dominant defect in a-subunit of Gs PTH receptor
{{c1::Sarcoidosis}} is a pathology that can lead to activation of Vitamin D in the
absence of PTH stimulation in the PCT, leading to hypercalcemia
A once daily low dose of PTH leads to increased bone {{c1::formation}} eg,
Teriparatide used to treat osteoporosis
PTH stimulates osteoblasts to secrete both {{c1::M-CSF}} and {{c1::RANK-L}} which
activate osteoclasts - Macrophage colony-stimulating factor (M-CSF) is a
cytokine secreted by osteoblasts, in addition to RANKL, binds to surface on
precursor osteoclast cells to promote their proliferation and differentiation into
mature osteoclasts. Osteoclastic tissue degradation and osteoblastic tissue
formation contribute to a dynamic remodeling process that facilitates bone healing.
Which two tumors secrete large amounts of Parathyroid hormone-related protein
(PTHrP)? {{c1:: renal cell carcinoma squamous cell lung cancer}} leads to
hypercalcemia in malignancy
Primary hyperparathyroidism is most commonly caused by {{c1::parathyroid adenomas}}
inappropriate secretion of PTH not due to low calcium
how does primary hyperparathyroidism affect PTH, serum calcium, and urine calcium?
{{c1::↑ PTH, serum calcium, and urine calcium}} while high PTH causes calcium
reabsorption in the PCT, the serum calcium is too high to reabsorb it all
What are the two characteristic findings of osteitis fribrosa cystica caused by
prolonged hyperparathyroidism? {{c1:: subperiosteal bone resorption brown tumors
(giant osteoclasts in bones)}}
What are the two major risks of a parathyroidectomy to treat primary
hyperparathyroidism? {{c1:: recurrent laryngeal nerve damage post-op hypocalcemia}}
what is the most common cause of secondary hyperparathyroidism? {{c1::renal
failure}} - Chronically low serum calcium → ↑ PTH secretion - Note: High serum
phosphate levels in secondary hyperparathyroidism due to renal failure
{{c1::Renal Osteodystrophy}} is a consequence of renal disease leading to secondary
hyperparathyroidism and subperiosteal thinning of bones ↑PO4, ↓Ca2+, ↓Vitamin D
hydroxylation → bone pain, fractures, can lead to osteitis fibrosa cystica if
untreated
What is the cause of familial hypocalciuric hypercalcemia? {{c1::autosomal dominant
defect in calcium sensing receptors (CaSRs) in PT gland}} higher than normal set
point for calcium to suppress PTH
How will FHH affect PTH, serum calcium, and urine calcium levels? {{c1:: normal to
↑ PTH ↑ serum calcium ↓ URINE calcium}} Hypocalcuric Hypercalcemia
how will hypoparathyroidism affect PTH and calcium? {{c1::↓ PTH & Calcium}}
How is Autoimmune Polyendocrine Syndrome Type 1 (APS-I) inherited? (pattern and
gene) {{c1::autosomal recessive AIRE gene mutations}} strongly associated with
mucocutaneous candidiasis
What is the triad of symptoms of in APS-I? {{c1:: mucocutaneous candidiasis
autoimmune hypoparathyroidism Addison's disease}} Autosomal recessive defect in
AIRE gene
What inherited immunodeficiency syndrome causes hypoparathyroidism via failure of
3rd & 4th pharyngeal pouches to differentiate? {{c1::DiGeorge Syndrome }} -The
ventral wing of the third pharyngeal pouche gives rise to the thymus -The dorsal
wings of the third and fourth pharyngeal pouches give rise to inferior and superior
parathyroid glands
What is the cause of pseudohypoparathyroidsm 1A? {{c1::Autosomal dominant defect in
alpha subunit of GS PTH receptor → organs insensitive to PTH}}
What lab marker is used to diagnose carcinoid syndrome neoplasms? {{c1::5-
hydroxyindoleacetic acid (5-HIAA)}} 5-HIAA is a metabolite of seratonin, which
causes right sided heart murmurs, watery diarrhea, flushing
Describe the structure of Coxsackieviruses {{c1::small, naked, single-stranded +
sense RNA virus}} Picornavirus → most common cause of viral myocarditis. This comes
up a lot in Q banks.
What is the major skin manifestation exclusive to hypothyroidism? {{c1::myxedema →
facial/periorbital non-pitting edema}} hyaluronic acid deposits in dermis
What lab marker will be elevated in hypothyroidism? (aside from the usual)
{{c1::Creatine Kinase (CK)}} hypothyroid myopathy → weakness, cramps, myalgias
What is the first line treatment for hypothyroidism? {{c1::Levothyroxine (synthetic
T4)}} Liothryonine (synthetic T3) can cause hyperthyroidism because of rapid gut
absorption
{{c1::Thyroid Storm (thyrotoxicosis)}} occurs when someone with hyperthyroidism
experiences a massive catecholamine surge can cause death from arrhythmia
{{c1::Goiter}} is a cause of enlarged thyroid due to high TSH with an inability to
produce T3/T4 Grave's
A critically ill patient with low TSH, T3, T4 with high rT3 indicates
{{c1::euthyroid sick syndrome}} rT3 is synthesized from T4, not T3
What are the two unique findings of Grave's Disease hyperthyroidism? {{c1::
Exophthalmos Pretibial (shin) myxedema}} due to T-cell activation of fibroblasts
(contain TSH receptor), causing secretion of glycosaminoglycans that draw in water
→ swelling
What are the treatments for Grave's disease? {{c1:: 1. beta blockers, thionamides
2. radioactive iodine ablation or surgery}} thionamides → methimazole,
propythiouracil (PTU)
What are the side effects of thionamides (PTU, methimazole)? {{c1:: Skin rash
Agranulocytosis (↓ WBC) Hepatotoxicity Teratogen (methimazole) }}
What are the 4 treatments for thyroid storm? {{c1:: propanolol thionamides SSKI
(saturated solution of KI) steroids}} Steroids given to suppress autoimmune
damage
How do the results of radioactive iodine uptake (I131) help differentiate thyroid
nodules? {{c1:: hot nodule → takes up I131 → NOT cancer cold nodule → higher chance
of cancer}}
{{c1::Jod-Basedow Phenomenon}} is a cause of hyperthyroidism when iodine deficient
patients are given iodine often occurs in patients with toxic adenomas who are
given Amiodarone, CT contrast, potassium iodide
Type {{c1::I}} Amiodarone hyperthyroidism occurs in patients with pre-existing
thyroid disease because the iodine in Amiodarone causes excess hormone production
Type {{c1::II}} Amiodarone hyperthyroidism occurs in patients without pre-existing
thyroid disease because of excess T4/T3 release (no ↑ hormone synthesis)
How does Amiodarone cause hypothyroidism? {{c1::↑ iodine → Wolff-Chaikoff Effect
mimics T4 and inhibits 5'-diodinase }} "normal patients ""escape"" within a few
weeks, patients with pre-existing thyroid disease have ""failure to escape"" and
permanent hypothyroidism"
What antibodies are produced in Hashimoto's Thyroiditis? {{c1:: Antimicrosomal
Anti-TPO Anti-Thyroglobulin}}
What are the histologic findings in Hashimoto's Thyroiditis? {{c1:: lymphocytic
infiltrate of germinal centers Hurthle cells (big eosinophilic follicular cells)}}
Hashimoto's Thyroiditis predisposes patients to increased risk of what malignancy?
{{c1::Primary thyroid B-cell Lymphoma}} Form of non-hodgkins
{{c1::De Quervain's Subacute Thyroiditis}} involves granulomatous inflammation of
the thyroid in young females causing a tender, enlarged thyroid often following
recent illness (viral), hyperthyroid → euthyroid → hypothyroid
"{{c1::Riedel's Thyroiditis}} is caused by fibroblast activation and fibrous tissue
deposition in the thyroid, causing a ""rock hard"" thyroid"
What are the 3 extra-thyroid symptoms of Reidel's Thyroiditis? {{c1::
hypoparathyroidism RLN damage (hoarseness) difficulty breathing (trachea
compression)}} fibrous tissue deposition and rock hard thyroid
Riedel's Thyroiditis is related systemic disease involving what immunoglobulin?
{{c1::IgG4}} eg, autoimmune pancreatitis, retroperitoneal fibrosis, non-
infectious aortitis
What is the characteristic finding of thyroid follicular adenomas on biopsy?
{{c1::NORMAL follicular tissue completely surrounded by a fibrous capsule}} FNA
cannot distinguish between adenomas/cancer
{{c1::Papillary Carcinoma}} is the most common form of thyroid cancer strongly
associated with prior radiation exposure presents as thyroid nodule, excellent
prognosis
What are the three pathology findings in papillary carcinoma of the thyroid? {{c1::
psammoma bodies nuclear grooves Orphan Annie's Eye Nuclei}}
Follicular Carcinoma of the thyroid is similar to a thyroid adenoma except it
breaks through to fibrous capsule and spreads {{c1::hematogenously}}
{{c1::Medullary Carcinoma}} of the thyroid is a cancer of parafollicular (C) cells
which can lead to hypocalcemia (calcitonin secretion)
Which type of thyroid cancer can appear as amyloid deposits in the thyroid?
{{c1::Medullary Carcinoma of thyroid}}
Which MEN syndromes are associated with Medullary Carcinoma of the thyroid?
{{c1::MEN 2A and 2B}} caused by RET oncogene mutations
What thyroid pathology occurs in the elderly and causes dysphagia, hoarseness, and
dyspnea? {{c1::Anaplastic Carcinoma of thyroid}} similar presentation to
Riedel's, except these symptoms occuring in elderly points to anaplastic carcinoma
→ highly malignant, poor prognosis
Where are the two bodily locations that use sodium-dependent entry of glucose into
cells (absorbed from low → high concentration)? {{c1:: intestinal epithelium renal
tubules}} Unaffected by insulin concentration
In the intestines, glucose is cotransported with 2 Na+ by the {{c1::SGLT-1}}
transporter into the epithelium and from the epithelium → blood by {{c1::GLUT 2}}
What insulin-independent glucose transporter is bidirectional (gluconeogenesis)?
{{c1::GLUT-2}} liver, kidney, intestine, pancreas
In glycolysis, where does the conversion from a 6 carbon molecule to two 3 carbon
molecules occur? {{c1::Fructose 1,6 biphosphate → Aldolase → Glyceraldehyde-3-
phosphate}}
What 3 reactions in glycolysis are not reversible? {{c1:: Glucose → G6P F6P →
Fructose-1,6-Biphosphate Phosphoenolpyruvate → Pyruvate}} -Catalyzed by: 1.
Hexokinase/Glucokinase 2. Phosphofructokinase-1 3. Pyruvate kinase
The first step of glycolysis (glucose → G6P) is catalyzed by the enzyme
{{c1::hexokinase}} glucokinase in liver & pancreatic B-cells tho
hexokinase is inhibited by {{c1::G6P}} glucose → hexokinase → G6P
In the presence of F6P, {{c1::glucokinase regulatory protein (GKRP)}} transports
glucokinase to the nucleus to inactivate it High glucose competes with GKRP for
Glucokinase binding, transporting it to the cytoplasm and activating it The data
show a substance in liver cells that has a high concentration in the nucleus when
glucose levels are low, and a high concentration in the cytosol when glucose levels
are high. This is consistent with the behavior of glucokinase.
Glucokinase deficiency will result in {{c1::elevated ↑}} blood glucose levels
Pancreas is less sensitive to glucose; ↓ insulin release→ hyperglycemia.
{{c1::Phosphofructokinase-1}} is the rate limiting enzyme in glycolysis F6P →
F 1,6-P (uses ATP)
What are the key inhibitors of Phosphofructokinase (rate limiting enzyme in
glycolysis)? {{c1:: Citrate (TCA cycle) ATP}} high energy states
What are the key inducers of Phosphofructokinase 1 (rate limiting enzyme in
glycolysis)? {{c1:: AMP F 2,6 Biphosphate (insulin)}} low energy states
How does insulin regulate glycolysis? {{c1:: fed state: ↑ insulin → ↓cAMP/PKA →
↑PFK-2 → ↑F2,6-BP → induction of PFK-1 → promotes glycolysis}}
How does alanine affect glycolysis/gluconeogenesis? (describe the alanine cycle)
{{c1:: 1. Alanine transaminase (ALT) in muscle breaks pyruvate down into alanine 2.
Alanine enters liver and stimulates gluconeogenesis by ALT converting alanine to
pyruvate}}
What are the potential side effects of fibrates (gemfibrozil)? {{c1:: Myopathy
Cholesterol gallstones Hepatotoxicity}}
What is the most serious complication of Kawasaki disease? {{c1::coronary artery
aneurysms}} treat with IV immunoglobulin & aspirin
What three clinical scenarios would cause high levels of Lactate Dehydrogenase
(LDH)? {{c1:: Hemolysis Myocardial Infarction Tumors}} ↓ O2 → Pyruvate → LDH →
Lactate
How is Pyruvate Kinase Deficiency inherited? {{c1::autosomal recessive}}
How does Pyruvate Kinase Deficiency present? {{c1:: newborns extravascular
hemolysis splenomegaly}} no PK in RBCs → RBCs phagocytosed in spleen →
extravascular hemolysis & splenomegaly
How many ATPs are generated from glycolysis in tissues with oxygen and
mitochondria? {{c1:: 32 ATP = liver & heart → maltate-aspartate shuttle 30 ATP =
muscle → Glycerol-3P shuttle}}
How many ATPs are generated from glycolysis in tissues without oxygen or
mitochondria? {{c1::2 ATP }} 2 ATP + 2 Lactate + 2 H2O
In what two steps of glycolysis are ATP expended? {{c1:: glucose → G6P F6P →
F1,6BP}}
In what two steps of glycolysis are ATP generated? {{c1:: 1,3BPG → 3PG PEP →
pyruvate}} Easy if you understand that 1,3-Biphosphoglycerate obviously loses a
phosphate group (to ATP) to become 3PG
What is the main activator of pyruvate carboxylase in stimulating gluconeogenesis?
{{c1::Acetyl-CoA}} ↑ ATP → inhibition of TCA cycle → ↑ Acetyl-CoA →
gluconeogensis
How is pyruvate converted to phospoenolpyruvate in the first step of
gluconeogenesis? {{c1:: pyruvate ↓ pyruvate carboxylase + ATP + CO2 Oxaloacetate
(OAA) ↓ PEP carboxykinase + GTP PEP}}
What is the cofactor for pyruvate carboxylase in the conversion of pyruvate to OAA
in step 1 of gluconeogenesis? {{c1::biotin}} Biotin is a cofactor for ALL
CARBOXYLATION enzymes!! (pyruvate carboxylase, Acetyl-CoA carboxylase, Propionyl-
CoA carboxylase) -Def: Classic symptoms include dermatitis, nausea and loss of
appetite. The dermatitis of biotin deficiency typically involves a scaly rash on
the face and scalp similar to seborrheic dermatitis. -Massive consumption of egg
whites has been associated with biotin deficiency. Egg whites contain a protein
called avidin which binds intestinal biotin and prevents absorption.
How will pyruvate carboxylase deficiency present? {{c1:: failure to thrive in
infancy ↑ pyruvate & lactate Lactic acidosis}} -Def leads to accumulation of
pyruvate which is diverted into lactic acid causing lactic acidosis. Pyruvate can
also be converted to alanine leading to hyperalaninemia. The lack of oxaloacetate
stalls the TCA cycle and acetyl-CoA is shunted towards ketone production.
What is the rate limiting enzyme in gluconeogenesis? {{c1::Fructose 1,6-
biphosphatase 1}} converts F1,6BP → F6P in gluconeogenesis. Remember, this step is
irreversible in glycolysis
What enzyme converts G6P → Glucose in the final step of gluconeogenesis?
{{c1::Glucose-6 Phosphatase}} -In endoplasmic reticulum
Sex Hormone Binding Globulins (SHBGs) are produced by the {{c1::liver}} and bind to
{{c1::androgens}} with the highest affinity androgens > estrogens, so with ↑
SHBG, there will be more free estrogens compared to androgens
What are two causes of ↑ SHBG? {{c1:: estrogens (birth control) hyperthyroidism}}
↑ estrogen effects, leads to gynecomastia in men
What are three causes of ↓ SHBG? {{c1:: Androgens Hypothyroidism Nephrotic
Syndrome}} ↑ androgen effects, can cause hirsutism in women
GnRH acts on the pituitary via a {{c1::Gq}} protein receptor which uses an
{{c1::IP3}} second messenger system
{{c1::Leuprolide}} is a GnRH agonist with a D-amino acid substution for native L-
amino acid resistant to degradation, long half-life
Continuous administration of Leuprolide {{c1::suppresses}} LH/FSH release Used
for endometriosis, uterine fibroids, prostate cancer, precocious puberty. In
contrast, pulsatile administration of a GnRH agonist ↑ FSH/LH to treat infertility
{{c1::Kallman Syndrome}} is a disease of absent GnRH secretion from the
hypothalamus caused by impaired migration of GnRH from the {{c1::olfactory bulb}}
to the hypothalamus hypogonadism, ANOSMIA, delayed puberty, small gonads
LH, FSH, TSH, and hCG are all heterodimers that have the same {{c1::alpha}} chain
and different {{c1::beta}} chains Imporant → hCG very similar to LH → binds to LH
receptors in corpus luteum to continue progesterone release to prevent menstruation
& maintain pregnancy
{{c1::SIADH}} is a paraneoplastic syndrome characterized by severe hyponatremia and
↓ serum osmolality (<275) Small cell lung cancer
What malignancy is associated with SIADH? {{c1::Small cell lung cancer}}
ectopic ADH → hyponatremia, ↓ serum osmolality, normal volume status
Papillary Carcinoma of the thyroid is associated with mutations in what two genes?
{{c1::BRAF RET }} Both Oncogenes: - BRAF product: serine/threonine kinase - RET
product: receptor tyrosine kinase
Achondroplasia is an autosomal dominant form of dwarfism caused by one defective
copy of the {{c1::FGFR3}} gene associated with advanced paternal age
MEN 1 is a {{c1:: germline}} mutation in the MEN1 gene on chromosome {{c1::11q13}}
MEN2 - RET on chromosome 10
The MEN1 gene (11q13) codes for the protein {{c1::menin}} which is a {{c1::tumor
suppressor}} "classic example of 2 hit hypothesis → patients born with 1
abnormal MEN1 gene, second ""hit"" occurs in endocrine glands"
How does Zollinger-Ellison syndrome (gastrinoma) typically present? {{c1::multiple
peptic ulcers}} MEN1
What are the two tumors common to both MEN 2A and 2B? {{c1:: Medullary thyroid
carcinoma Pheocromocytoma (adrenal medulla)}} """medullary tumors"""
In addition to the medullary tumors, MEN 2A also presents with {{c1::parathyroid
hyperplasia}} no physical findings
In addition to the two medullary tumors, what two findings distinguish MEN 2B?
{{c1:: Mucosal neuromas Marfinoid appearance}} no parathyroid involvement
MEN 2A and 2B are autosomal dominant germline mutations in the {{c1::RET}} gene on
chromosome {{c1::10}} proto-oncogene, codes for receptor tyrosine kinase
Describe the RET gene mutation in MEN 2 syndromes: {{c1::RET is a proto-oncogene
coding for receptor tyrosine kinase → gain of function mutation → uncontrolled cell
growth}}
What are the classic symptoms of hyperglycemia (diabetes)? {{c1:: Polyuria (osmotic
diuresis from glucose) Polydipsia (thirst)}}
How do you diagnose gestational diabetes? {{c1::oral glucose tolerance test}}
Type 1 Diabetes is a Type {{c1::IV}} hypersensitivity autoimmune disorder t-cell
mediated destruction of pancreatic beta cells
How can Diabetic Ketoacidosis cause heart failure? {{c1::acidosis causes ↓phosphate
→ ↓ATP → ↓contractility}}
What are the 4 life-threatening complications of Diabetic Ketoacidosis? {{c1::
Mucormycosis (Rhizopus, Mucor) Cerebral edema}} {{c2::Arryhthmias (hyperkalemia)
Heart Failure (hypophosphatemia)}} Note that in DKA, total body potassium stores
are depleted, but the extracellular concentration of K is high due out a shift out
of cells.
what is the characteristic histological finding in Type 2 diabetes? {{c1::amyloid
deposits in islet cells}}
what is the characteristic histological finding in Type 1 diabetes?
{{c1::lymphocytic infiltrate of islet cells}}
{{c1::Hyperglycemic Hyperosmolar Syndrome}} is a life-threatening complication of
Type 2 DM caused by ↑ glucose (>600) and ↑osmolality (>320)similar to DKA, but has
neurologic deficits (seizures), no ketones, no acidosis
{{c1::Acanthosis Nigricans}} is hyperpigmented thickening of the skin in the axilla
or neck caused by insulin resistance (diabetes, obesity, cushing, cancer)
What are the two key underlying mechanisms of diabetic complications (cardiac
disease, renal failure, neuropathy, blindness)? {{c1:: non-enzymatic glycation
sorbitol accumulation}}
Hyaline arteriosclerosis of the efferent renal arteriole is unique to what
pathology? {{c1::diabetes}} causes hyperfiltration and microalbuminuria→ tx with
ACE inhibitors
What is the histopathological hallmark of nodular sclerosis of diabetic kidney
disease? {{c1::Kimmelstiel-Wilson Nodules}}
Chronic hypergylcemia (diabetes) can lead to an accumulation of sorbitol which is
involved in what 2 diabetic complications? {{c1:: cataracts (lens) neuropathy
(Schwann cells)}} sorbitol causes osmotic damage from drawing in fluid
Diabetic retinopathy is caused by {{c1::pericyte degeneration}} leading to
microaneurysms and hemorrhages also exudates, cotton-wool spots (nerve
infarctions), neovascularization (retinal ischemia)
Which endocrine hormones bind to intracellular receptors? {{c1:: Progesterone
Estrogen Test Cortisol Aldosterone T3, T4 Vitamin D}} PET CAT on TV
Thiazolidinediones (pioglitazone, rosiglitazone) activate {{c1::peroxisome
proliferator–activated receptors (PPARs}} to increase peripheral sensitivity to
insulin, decreasing blood glucose levels
A deficiency in what essential amino acid can cause hypothyroidism?
{{c1::phenylalanine}} Phenylalanine is a precursor for tyrosine (needed for
thyroxine) and catecholamines
What DM Type 2 drug class is associated with the side effects of flatulence,
diarrhea, and ↑ liver enzymes? {{c1::a-glucosidase inhibitors (acarbose,
miglitol)}}
Insulin hexamers have a {{c1::slower}} onset of action than insulin monomers
What are three rapid-acting insulin drugs? {{c1:: Lispro Aspart Glulisine}} use
pre-meal. reduced hexamer formation → rapid absorption, fast action
Which class of insulin drugs are best for managing post-prandial (meal)
hyperglycemia? {{c1::rapid acting (lispro, aspart, glulisine)}} taken right before
meal
What are the unique indications for regular insulin? {{c1:: DKA/HHS hyperkalemia}}
only type given IV
{{c1::Detemir}} is an insulin drug with a fatty acid side chain and binds
reversibly to albumin causes less weight gain
List the steps of glycogen synthesis {{c1::}}
Glycogen phosphorylase is stabilized by vitamin {{c1::B6}} breaks down glycogen
into glucose-1-phosphate, stops when glycogen branches decrease to 2-4 linked
molecules (limit dextrins), debranching enzyme cleaves limit dextrins
{{c1::Debranching Enzyme}} cleaves limit dextrins (2-4 linked glucose molecules) on
1-6 bonds So deficiency of Debranching enzyme = Cori Disease (GSD Type 3)
Glucagon and epinephrine phosphorylate what two enzymes to promote glycogen
breakdown? {{c1:: glycogen phosphorylase (activates) glycogen synthase (inhibits)}}
In contrast insulin de-phosphorylates these enzymes to promote the storage of
glucose as glycogen
{{c1::Von Gierke's Disease (Type I GSD)}} is caused by a deficiency of
{{c2::glucose-6-phosphatase}} IA: G6Pase IB: Glucose transporter deficiency
Pompe Disease (GSD type II) causes glycogen to accumulate in {{c1::lysosomes}}
Deficiency of Lysosomal acid a-1,4-glucosidase
McArdle's Disease (GSD Type IV) is caused by deficiency in {{c1::muscle glycogen
phosphorylase (myophosphorylase)}} Presents in adolescents/teens with exercise
intolerance and dark urine after exercise.
What are the two products synthesized in the HMP Shunt? {{c1:: NADPH Ribose 5-
phosphate (nucleotide synthesis)}} occur in cytosol
In the first step of the HMP shunt (oxidative), G6P is converted to 6
phosphogluconolactone by {{c1::G6P Dehydrogenase}} creates 1 NADPH
In the reductive step of the HMP shunt, Ribulose-5 phosphate is converted to F6P
(for glycolysis) by {{c1::transketolase}}, which uses {{c1::thiamine (B1)}} as a
cofactor Wernicke-Korsakoff syndrome
What are the 3 functions of NADPH? {{c1:: 1. cofactor in fatty acid & steroid
synthesis 2. phagocytosis 3. protects from oxidative damage}}
{{c1::Chronic Granulomatous Disease}} is caused by a loss of function of NADPH
Oxidase, meaning that phagocytes (neutrophils and macrophages) cannot generate H2O2
-In the absence of this enzyme, superoxide, hydrogen peroxide and
hypochlorous acid cannot be generated for bacterial and fungal killing. -Catalase
+ve organisms include: staphylococci, Pseudomonas cepecia, Aspergillus, Serratia
marcescens, and Nocardia. -Dihydrorhodamine is oxidized via the respiratory burst
to produce a green fluorescence within cells that maybe detected with flow
cytometry. Patients with CGD display poor fluorescence of activated phagocytes
(neutrophils and macrophages) when exposed to DHR.
Chronic Granulomatous Disease (CGD) can cause reccurent infections of what type of
bacteria? {{c1::Catalase positive (staph)}} Catalase(+) bacteria break down
H2O2 → host cells have no peroxide to use, unlike catale(-) bacteria which generate
peroxide
What six organisms cause almost all CGD infections? {{c1:: Burkholderia cepacia
Staph aureus Nocardia Aspergillus Pseudomonas Serratia marcescens}} Require
lifelong prophylactic antibiotics (TMP-SMX for catalase +ve infections). IFN-y
therapy can also reduce the incidence of serious infections. Bone marrow transplant
is the definitive treatment. B-SNAPS... all Catalase +
{{c1::G6PD deficiency}} is an enzymatic disorder of RBCs leading to hemolysis and
hemolytic anemia following oxidative stress G6PD needed to generate NADPH in
HMP shunt → NADPH degrades H2O2 in RBCs → oxidative damage & hemolysis
G6PD deficiency causes hemolysis because NADPH is required for the enzyme
{{c1::Glutathione Reductase}}, which generates glutathione to neutralize H2O2
How is G6PD deficiency inherited? {{c1::X-linked recessive → always males}}
How does G6PD deficiency present? {{c1:: hemolytic anemia following oxidative
stress back pain hemoglobinuria}} stressors → fava beans, sulfa drugs,
antimalarials, infections
What are the classic findings of G6PD deficiency on peripheral blood smear? {{c1::
Heinz bodies (precipitated oxided Hgb) Bite cells (phagocyte bites in spleen)}}
What drugs are triggers for G6PD deficiency? {{c1:: Antibiotics → sulfa, dapsone,
INH Anti-malarials → primaquine, quinidine Aspirin, acetominophen}} also fava
beans, infection
The Ureteric bud is an outgrowth of the {{c1::mesonephric (Wolffian) duct}}
The uteric bud gives rise to what 4 urogenital structures? {{c1:: ureter pelvis
calyxes collecting ducts}} outgrowth of mesonephric (wolffian) duct
The metanephric mesenchyme interacts with the uteric bud to give rise to what
urogenital structures? {{c1:: All nephron structures proximal to collecting duct}}
nephron minus collecting ducts (ureteric bud)
Wilms' Tumor is the most common renal malignancy of young children caused by
proliferation of {{c1::metanephric mesenchyme (blastema)}} metanephric mesenchyme =
embryonic glomerular structures
Renal Agenesis is caused by the failure of the {{c1::uteric bud}} to develop lack
of signals to mesenchyme
What congenital kidney pathology is strongly associated with vescicoureteral
reflux? {{c1::Duplex Collecting System}} two ureters → abnormal connection to
bladder → ↑ risk for UTIs
What are the six associations with Potter sequence? {{c1:: Pulmonary hypoplasia
Oligohydramnios (trigger) Twisted face Twisted skin Extremity defects Renal failure
(in utero)}} P.O.T.T.E.R. → causes include ARPKD, posterior urethral valves,
bilateral renal agenesis, chronic placental insufficiency
Horshoe Kidney is caused by the fusion of the inferior renal poles, which are
trapped lower in the abdomen by {{c1::inferior mesenteric artery}}
Urachal Remnants that do not obliterate to become to median umbilical ligament can
lead to what malignancy? {{c1::adenocarcinoma of the bladder}} Cancer at dome of
bladder. So if a question describes a patient with cancer at the dome of the
bladder, I'd bet they'd ask about the embryonic origin (urachus)
What is the formula for renal clearance of a given substance? {{c1:: Cx = (Ux * V)
Px}} Cx of inulin & creatinine determines GFR Cx of PAH determines RPF
The PCT absorbs 100% of what two substances? {{c1:: glucose amino acids}} 67% of
water, HCO3, NaCl, potassium, and phosphate also absorbed in PCT
{{c1::Hartnup Disease}} is an infant cause of tryptophan deficiency from absent
neutral amino acid transporters in the PCT, leading to a skin rash (plaques,
desquamation) Neutral amino acids in the urine. Tryptophan deficiency is just
the one that underlies the symptoms (pellagra d/t niacin def)
{{c1::Fanconi Syndrome}} is a disease caused by complete loss of proximal tubule
functions leading to excretion of all amino acids, glucose, bicarb, and phosphate
may result in metabolic acidosis
What are the presenting symptoms of Fanconi Syndrome? {{c1:: polyuria & polydipsia
w/ normal serum glucose metabolic acidosis (normal gap) hypokalemia
hypophosphatemia amino acids in urine}} cant reabsorb anything in PCT → presents
similar to diabetes but pts have normal glucose
What lysosomal storage disease presents with Fanconi Syndrome? {{c1::Cystinosis}}
also Wilsons disease, tyrosinemia
What are the acquired causes of Fanconi Syndrome? {{c1:: ischemia multiple myeloma
lead poisoning drugs (Cisplatin, ifosfamide, tenofovir)}}
What are the functions of the V1 and V2 ADH receptors? {{c1:: V1 → vasoconstriction
V2 → aquaporin 2 insertion}} -V1 is Gq-coupled -V2 is a GPCR cAMP system
How does ADH regulate urea in the nephron? {{c1::increases urea reabsorption (CD)}}
urea enters medullary interstitium to maintain osmolarity, recycled back into
tubular fluid by thin descending limb
Where is Erythropoetin (EPO) released from? {{c1::interstitial cells of peritubular
capillary}} renal failure will ↓ EPO release and lead to normocytic anemia
Ammonia (NH3) is synthesized from the amino acid {{c1::glutamine}} NH3
generated by kidneys when H+ is ↑
What two substances buffer H+ excreted into the urine? {{c1:: Phosphorus (H2PO4)
Ammonia (NH3)}} kidneys will secrete more titratable acids (phosphorus) and
ammonia in response to acidosis. Under acidotic conditions, kidney synthesizes
ammonia from glutamine.
What receptors are responsible for the absorption of galactose and fructose in the
intestines? glactose → {{c1::SGLT-1}} fructose → {{c1::GLUT-5}} GLUT-5 takes up
fructose through facilitated diffusion, both leave enterocytes by GLUT-2
Describe the metabolism of fructose and how it feeds into glycolysis {{c1::}}
Know the whole pathway
Essential Fructosuria is caused by a deficiency in {{c1::Fructokinase}} resulting
in the liver not being able to take up fructose fructose appears in urine;
identified by laboratory testing for the presence of urinary reducing sugars.
Standard urinalysis detects only glucose, and will be normal when isolated fructose
or glucose is present in the urine.
What are the symptoms of Hereditary Fructose Intolerance? {{c1:: hypoglycemia
vomiting hepatomegaly liver failure}} Occurs after baby transitions from
breastmilk to stuff with fructose.↓ ATP → ↓gluconeogenesis & ↓glycogen breakdown
When does Hereditary Fructose Intolerance present? {{c1::when baby stops
breastfeeding}} failure to thrive, hypoglycemia (seizures) afater feeding,
enlarged liver
Describe the pathway of Galactose metabolism {{c1::}}
Classic galactosemia is caused by a deficiency of {{c1::galactose-1-phosphate
uridyltransferase (GALT)}} leading to an accumulation of {{c1::galactose-1-
phosphate}}
In galactosemia, aldose reductase can convert excess galactose to
{{c1::galactitol}} which accumulates in the lens of the eye and causes cataracts
similar to sorbitol in diabetics, same polyol pathway Note that in
galactokinase deficiency (mild galactosemia), the ONLY symptom will be juvenile
cataracts
{{c1::Nelson's Syndrome}} is the development of an ACTH-secreting macroadenoma in
the pituitary in patients who have undergone bilateral adrenalectomies from prior
Cushing's disease
{{c1::Carney Complex}} is a rare autosomal dominant disorder presenting as myxomas,
hyperpigmentation, and endocrine hyperactivity mutations in PRKAR1A tumor
supressor
Which blotting technique is used to visualize DNA? {{c1::Southern blot}} DNA
sample enzymatically cleaved and separated via electrophoresis, then binds to
complimentary DNA in filter
Which blotting technique is used to visualize RNA? {{c1::Northern blot}}
Which blotting technique is used to visualize proteins? {{c1::Western blot}}
protein is separated via gel electrophoresis and labeled with antibody
Which blotting technique is used to visualize DNA-binding proteins?
{{c1::Southwestern blot}} DNA-binding proteins (i.e. transcription factors)
labeled with oligonucleotide probes
Describe the steps of ethanol metabolism and include where in the cell these steps
occur {{c1:: }}
Most biochemical problems associated with alcohol are due to high levels of
{{c1::NADH}} blocks TCA cycle blocks gluconeogenesis (shunts OAA to malate)
causes lactic acidosis (pyruvate→ lactate)
Alchohol causes accumulation of fatty acids in the liver because high levels of
NADH stall {{c1::beta oxidation}} also, stalling TCA cycle increases FA synthesis
Alcohol contributes to fatty acid synthesis because {{c1::citrate}} promotes
{{c1::Acetyl-CoA Carboxylase}}, the rate limiting enzyme in FA synthesis high
citrate from slowed TCA cycle
Alcoholics get ↑ triglycerides in the liver because {{c1::glycerol-3-phosphate}}
builds up and combines with FAs to form triglycerides
Alcoholic hepatitis results from inflammation due to the buildup of
{{c1::acetaldehyde}} after heavy boozing Chronically, scar tissue causes
cirrhosis. Don't get confused; Binge drinking causes acetaldehyde buildup and acute
hepatitis. Chronic alcoholism causes fatty change due to ↑ TGs via NADH inhibition
of B-oxidation.
{{c1::Fomepizole}} is a drug that inhibits alcohol dehydrogenase and is an antidote
for methanol or ethylene glycol overdose
{{c1::Disulfiram}} is a drug that inhibits aldehyde dehydrogenase acetaldehdye
rises, triggers catecholamine release → causes nausea, vomiting, sweating and
flushing
Alcohol flushing is linked to an inherited deficiency in {{c1::aldehyde
dehydrogenase 2 (ALDH2)}} most common in asian populations
Citrate synthase (1st step of TCA cycle) is inhibited by {{c1::ATP}} OAA (4C) +
Acetyl-CoA (2C) = Citrate (6C)
In the fasting state, {{c1::oxaloacetate}} is used for gluconeogensis, inhibiting
the TCA cycle and driving the conversion of Acetyl-CoA to {{c1::Ketone bodies}}
In the second step of the TCA cycle, citrate is converted to isocitrate by
{{c1::aconitase}} which is inhibited by {{c1::fluoroacetate::poison}}
fluoroacetate is rat poison
What is the rate limiting enzyme of the TCA cycle? {{c1::Isocitrate
Dehydrogenase }} Isocitrate → a-ketoglutarate generates CO2 and NADH
What inhibits and activates isocitrate dehydrogenase? {{c1:: activate: ADP, Ca2+
inhibit: ATP, NADH}}
What activates and inhibits a-ketoglutarate dehydrogenase? {{c1:: activate: ADp and
Ca2+ inhibit: Succinyl-CoA, NADH, ATP}}
{{c1::Succinate dehydrogenase}} is an enzyme in both the TCA cycle and the electron
transport chain Succinate → fumarate = FADH2 for electron transport chain
How do you calculate the expected pCO2 for a metabolic acidosis using the Winter's
Formula? {{c1::pCO2 = 1.5 (HCO3) + 8 +/- 2}} so, pH = 7.2, HCO3 = 9, pCO2 =? 1.5
(9) + 8 = 22 +/- 2
What diuretic is given for altitude sickness and metabolic alkalosis?
{{c1::Acetazolamide}} carbonic anhydrase inhibitor → augments HCO3- excretion
{{c1::Type 1 Renal Tubular Acidosis}} is caused by a defect in the ability of a-
intercalated cells in the distal tubule to secrete H+ urine pH > 5.5, hypokalemia,
metabolic acidosis (HCO3 < 10)
What are the key physical symptoms of Type 1 (distal) RTA? {{c1:: Chronic kidney
stones (CaP) Rickets Growth failure in children}} ↑ release of calcium from
bone
Positive urine anion gap in the setting of acidosis indicates {{c1::Renal Tubular
Acidosis}} UAG = Na + K - Cl
What is the treatment for Type I (distal) RTA? {{c1::sodium bicarbonate}} Type I
RTA is a failure of collecting duct to secrete acid (H+), so you'll have metabolic
acidosis and high urine pH.
{{c1::Type II (proximal) RTA}} is caused by a defect in proximal tubule HCO3
resorption urine pH < 5.5, hypokalemia, HCO3 = 12-20 (distal nephron can still
create acid to compensate)
What are the classic causes of Type II (proximal) RTA? {{c1:: Fanconi Syndrome
Carbonic Anhydrase Inhibitor (Acetazolamide)}} Fanconi → loss of ALL PCT function
Acetazolamide → blocks HCO3 reabsorption
{{c1::Type IV RTA}} is caused by a failure of the distal tubule to respond to
aldosterone, leading to ↓NH3 synthesis in PCT HYPERKALEMIA, urine pH < 5.4,
How do you treat Type IV RTA? {{c1::Fludrocortisone}} synthetic analog of
aldosterone
The glomerular basement membrane is composed of type {{c1::IV}} collagen and
negatively charged {{c1::heparan sulfate}} repels (-) molecules like albumin
only small molecules can pass thru
What are the first line drugs for UTIs? {{c1:: TMP-SMX Fluoroquinolones}}
concern with resistance developing to fluoroquinolones
What drug is used to treat UTIs in pregnant women? {{c1::Nitrofurantoin
(macrobid)}} can cause pulmonary fibrosis
What molecules activate and inhibit Acetyl-CoA carboxylase (RL enzyme in FA
synthesis? Activate: {{c1::Insulin, Citrate}} Inhibit: {{c1::Glucagon, Epinephrine,
Palmitoyl-CoA}} Acetyl-CoA → Acetly-CoA Carboxylase + Biotin + CO2 → Malonyl-CoA
Which step (enzyme) of FA synthesis requires NADPH? {{c1::fatty acid synthase}}
converts Malonyl-Coa to palmitate (16C FA)
What two areas in the body do not use fatty acids? {{c1:: RBCs (glycolysis only)
Brain (glucose & ketones only)}}
What are the symptoms of carnitine deficiency? {{c1:: Muscle weakness (exercise)
Cardiomyopathy Hypoketotic hypoglycemia}} due to malnutrition, liver failure,
hemodialysis, increased requirement (trauma, burn, pregnancy)
What are the symptoms of infantile primary systemic carnitine deficiency? {{c1::
encephalopathy hepatomegaly hyperammonemia (liver dysfx) hypoketotic hypoglycemia}}
mutation affecting carnitine uptake into cells → low carnitine EHHH?
{{c1::Medium Chain Acyl-CoA Dehydrogenase (MCAD)}} deficiency is an autosomal
recessive disorder of poor oxidation of 6-10 carbon fatty acids into acetly-CoA
What are the symptoms and metabolic abnormalities associated with MCAD deficiency?
{{c1:: Hypoketotic hypoglycemia (severe; hallmark of beta-oxidation disorder
involving fatty acid metabolism) Dicarboxylic acids (6-10C) in urine (these acids
are produced by omega oxidation of fatty acids which occur when beta oxidation
cannot proceed normally) ↑Acylcarnitine levels}} fatty acids cant be used to
generate Acetyl-CoA, so glucose is overused (hypoglycemia) and ketones cant be
synthesized
What is the cofactor to Methylmalonyl-CoA mutase (Methylmalonyl-CoA → Succinyl-
CoA)? {{c1::B12}} B12 deficiency will cause ↑Methylmalonyl-CoA; succinyl-CoA needed
for heme
{{c1::Methylmalonic Acidemia}} is caused by a deficiency in Methylmalonyl-CoA
mutase leading to anion gap metabolic acidosis and CNS dysfucntion fatal early
in life. ↑ BCAAs & FAs → metabolic acidosis, hypoglycemia, ketonuria,
hyperammonemia
What are the three basic amino acids? {{c1:: Arginine (strongest base) Lysine
Histidine}} His lys (lies) are basic
Histones are positively charged and bind to negatively charged phosphate backbone
of DNA because they contain {{c1::basic amino acids (lysine, arginine)}}
histidine has NO charge at body pH
What are the acidic amino acids? {{c1:: Aspartate Glutamate}} negatively charged
at body pH, proton donors
Sickle Cell Anemia results from the subsitution of polar {{c1::glutamate}} for
nonpolar {{c1::valine}} in hemoglobin -Valine is non-polar and hydrophobic
compared to glutamate which is polar and hydrophilic. Thus, the valine portions in
HbS display increased hydrophobicity compared to normal hemoglobin. These portions
bury themselves within nonpolar sections of the folded, globular hemoglobin protein
to avoid exposure to water within cells. This changes the conformation of
hemoglobin leading to the clinical features of sickle cell anemia.
Which amino acids are the main components of collagen? {{c1:: Glycine Proline
Lysine}} Vitamin C is necessary for hydroxylation of Proline and Lysine in
collagen synthesis
Which amino acids are purely Ketogenic? {{c1:: Leucine Lysine}} both essential,
converted to acetoacetate and Acetyl-CoA
Phenylalanine is converted to tyrosine by the enzyme {{c1::Phenylalaine
hydroxylase}}, which requires {{c1::Tetrahydrobiopterin (BH4)}} as a cofactor
What are the two causes of Phenylketonuria (PKU)? {{c1:: defective phenylalanine
hydroxylase deficiency BH4 cofactor}} ↑phenylalanine ↓tyrosine
What are the presenting symptoms of Phenylketonuria (PKU)? {{c1:: musty urine smell
(from phenylketones) CNS symptoms (retardation, seziures, tremor) light skin, hair
& eyes}} Pale skin, fair hair and blue eyes due to lack of tyrosine conversion
to melanin. Also, because catecholamine synthesis is disrupted, sites of
catecholamine synthesis will be pale on gross examination (eg, lack of dopamine
will cause lack of pigment in substantia nigra, like Parkinson's)
How do you treat Phenylketonuria (PKU)? {{c1:: restrict phenylalanine (foods high
in protein like chicken must be avoided) supplement tyrosine (now essential) no
aspartame (consituent of diet sodas) }}
BH4 Deficiency PKU leads to ↓ synthesis of NT's (including dopamine), which
presents as excess {{c1::prolactin}} in addition to normal PKU symptoms not
enough dopamine to inhibit prolactin secretion
In addition to phenylalanine restriction, what addition treatments are required for
BH4 deficient variant of PKU? {{c1:: supplement BH4 L-dopa, carbidopa (dopamine) 5-
HTP (serotonin)}}
What is the cofactor for tyrosine hydroxylase (tyrosine → DOPA)? {{c1::BH4}}
{{c1::Carbidopa}} is a drug that inhibits DOPA Decarboxylase to prevent L-DOPA
breakdown before it reaches the CNS
What is the cofactor for DOPA Decarboxylase? {{c1::Vitamin B6}}
What is the cofactor for Dopamine B-hydroxylase (Dopamine → NE)? {{c1::Vitamin C}}
What is the cofactor for Phenylethanolamine N-methyltransferase (NE → Epinephrine)?
{{c1::SAM (S-Adenosyl Methionine)}} donates methyl groups, composed of methionine
and ATP
Regenerating methionine for SAM (cofactor for PNMT) from homocysteine requires
{{c1::folate}} and {{c1::B12}}
Oculocutaneous Albinism (OCA) is caused by a defiency of what? {{c1:: Tyrosinase
(OCA Type 1) Tyrosine transporters (OCA Type 2)}} melanin is polymer of
tyrosine
{{c1::Alkoptonuria (ochronosis)}} is an autosomal recessive deficiency in
{{c2::homogentisic acid oxidase}} causing pigment deposits in connective tissue
Restrict tyrosine
What are the presenting symptoms of Alkaptonuria? {{c1:: Dark urine when left
standing Arthritis/Arthropathy/Arthralgias Black pigmented joints, cartilage
Calcified IV discs}}
What are the cofactors for Tryptophan Hydroxylase (Tryptophan → 5-HTP (serotonin))?
{{c1:: BH4 B6}} This is the reason for 5-HTP supplementation in BH4-deficient PKU
What are the products of tryptophan breakdown? {{c1::}}
What are the symptoms of niacin deficiency? {{c1:: Pellagra (hyperpigmented rash)
Red tongue Diarrhea dementia, encephalopathy}} Can be caused by Hartnup Disease →
loss of tryptophan in urine at PCT or B6 deficiency
What is the cofactor for Histidine Decarboxylase (histidine → histamine)?
{{c1::B6}}
All carbon and nitrogen in heme synthesis come from {{c1::Glycine}} and
{{c1::Succinyl-CoA}}
What are the three molecules derived from arginine? {{c1:: Creatine Urea Nitric
Oxide}} arginine for preworkout → NO & creatine pump
What are the two molecules derived from glutamate? {{c1:: GABA Glutathione}}
Glutamate Decarboxylase requires B6 to convert glutamate → GABA
Branched chain amino acids (leucine, isoleucine, valine) are metabolized by
{{c1::a-ketoacid dehydrogenase}} which requires {{c1::thiamine (B1)}} as a cofactor
deficiency → Maple Syrup Urine Disease
Classic Homocystinuria is caused by a deficiency in {{c1::Cystathione B Synthase
(CBS)}}
How do you treat Homocystinuria? {{c1:: Avoid methionine Supplement B6 INcrease
cysteine (now essential)}}
What are the three enzyme deficiencies that are causes of Homocystinuria? {{c1::
Cystathione Synthase (classic) Methionine Synthase MTHFR (defective folate/B12
metabolism)}}
{{c1::Cystinuria}} is a disease caused by ↓ reabsorption of cystine by PCT causing
kidney stones -Nephrolithiasis in young patients is a clue to this Dx.
-Prevention: methionine FREE diet (because cysteine is derived from amino acid
methionine) Low sodium intake also lowers cystine excretion, so a sodium restricted
diet is recommended in addition to low protein intake.
All aminotransferase enzymes (ALT, AST) require {{c1::B6}} as a cofactor
transfer nitrogen from amino acids to glutamate
What are the three components of urea synthesized in the liver to eliminate NH4+?
{{c1:: Ammonia (NH3) CO2 Aspartate}}
What is the first (and rate limiting) step in the urea cycle? {{c1::NH4+ + CO2 →
Carbamoyl Phosphate Synthetase 1 → Carbamoyl Phosphate}}
What is the allosteric activator of Carbamoyl Phosphate Synthetase 1? {{c1::N-
acetylgluatamate}} synthesized from glutamate & acetyl-CoA in fed state (↑
protein)
What is the second step of the urea cycle? {{c1::}} Also in MITOCHONDRIA
What antibody is specific for rheumetoid arthritis? {{c1::Anti-cyclic citrullinated
peptide (Anti-CCP) antibody}} product of urea cycle → incorporated into proteins in
inflammatory states. Rheumatoid factor (AB against Fc region of IgG) is not
specific
What are the treatments for hyperammoniemia? {{c1:: Limit protein Supplement
Arginine Lactulose Rifaximin Benzoate, Phenylacetate, Phenylbutarate}}
By what pattern is Ornithine Transcarbamylase (OTC) deficiency (most common urea
cycle disorder) inherited? {{c1::X-linked recessive}} ↑ carbamoyl phosphate,
ammonia, orotic acid
Citrullinemia is a urea cycle disorder caused by a deficiency of
{{c1::argininosuccinate synthetase}} ↑ citrulline, ↓ arginine, hyperammonemia
What are the five cofactors for the pyruvate dehydrogenase complex? {{c1:: Thiamine
pyrophosphate (B1) Lipoic acid CoA (B5) FAD (B2) NAD+ (B3) }} Tender Love Care
For None
Thiamine (B1) (thiamine pyrophosphate) is a cofactor for what FOUR enzymes? {{c1::
pyruvate dehydrogenase a-ketoglutarate dehydrogenase (TCA) a-ketoacid dehydrogenase
(BCAAs) Transketolase (HMP shunt)}}
What are the DRY Beriberi symptoms of thiamine (B1) deficiency? {{c1:: polyneuritis
(nerve pain) muscle weakness}}
What are the WET Beriberi symptoms of thiamine (B1) deficiency? {{c1:: tachycardia
high-output HF edema}}
PDH cofactor lipoic acid is inhibited by {{c1::arsenic}} arsenic makes breath
smells like garlic
What are the activators for the pyruvate dehydrogenase complex (PDH)? {{c1:: PDH
phosphatase ↑ NAD/NADH ↑ ADP Ca2+}} PDH phosphatase dephosphorylates PDH to
activate it, PDH kinase phosphorylates to inactivate
What are the inhibitors of the pyruvate dehydrogenase complex (PDH)? {{c1:: PDH
Kinase ↓ NAD/NADH ↑ Acetly-CoA ↑ ATP}}
How is PDH Complex Deficiency inherited? (pattern, gene, product) {{c1:: X-linked
mutations in PDHA1 gene codes of E1-alpha subunit}} pyruvate shunted to alanine
and lactate
What are the key symptoms of PDH complex deficiency? {{c1:: growth failure
developmental delay ↑ alanine lactic acidosis}} ↓ PDH results in the shunting of
pyruvate to alanine and lactate
How do you treat PDH complex deficiency? {{c1:: Thiamine, lipoic acid (optimize
remaining PDH) Ketogenic diet (high fat, lysine, leucine)}}
{{c1::Rotenone}} is an insecticide poison that inhibits Complex I in the electron
transport chain prevents electron transfer (reduction) to CoQ
{{c1::Antimycin A}} is an antibiotic that can inhibit Complex III (bc1 complex) in
the electron transport chain
What two poisons can inhibit complex IV in the electron transport chain? {{c1::
Carbon monoxide Cyanide}} CO→ binds a3 in Fe2+ state, competes with O2 Cyanide→
binds a3 in the Fe3+ state -This renders cytochrome unable to transport electrons
to generate protons in the intermembrane space. As a result, the electrochemical
gradient for ATP production falls.
What are the treatments for cyanide poisoning? {{c1:: Nitrites (amyl nitrite) +
thiosulfate hydroxocobalamin}} Nitrites convert Fe2+ → Fe3+ in hemoglobin
(methemoglobin), Fe3+ binds to cyanide to protect mitochondria
What three things are Uncoupling Agents which uncouple oxidative phosphorylation in
the electron transport chain? {{c1:: 2,4-Dinitrophenol (DNP) Aspirin overdose Brown
fat (uncoupling protein 1, thermogenin)}} all lead to production of HEAT
-Uncouplers of ETC disrupt ATP production by allowing protons to leave the
intermembrane space without generating ATP. Oxygen consumption via the ETC will
proceed normally as it is undisturbed by uncouplers. -Key point: Inhibitors shut
down ATP production by shutting down electron transport (and, therefore consumption
of oxygen). Uncouplers allow electron transport (ie; oxygen consumption) to proceed
normally but ATP production is inhibited through proton escape from the inner
membrane space.
{{c1::Oligomycin A}} is a macrolide antibiotic that inhibits ATP synthase (complex
V) to block oxidative phosphorylation in the electron transport chain
{{c1::Kwashiorkor}} is a disease of malnutrition from inadequate protein intake
causing hypoalbuminemia and edema
{{c1::Marasmus}} is a disease of malnutrition from inadequate total calorie intake
causing muscle and fat wasting Kwashiorkor without edema
Cholesterol is converted to cholesteryl esters in the ER of gut enterocytes by
{{c1::Acyl-CoA Cholesterol Acytransferase (ACAT)}} to be packaged into chylomicrons
Similar to LCAT (both make CE), but: 1. Location: - ACAT esterifies
cholesterol in enterocytes & hepatocytes - LCAT esterifies cholesterol in
bloodstream & peripheral tissues for more efficient transport 2. Substrate: - ACAT
uses acyl-CoA - LCAT uses phosphatidylcholine -Note: ACAT is important for
synthesis of cholesterol esters found in chylomicrons and VLDL but not HDL (High-
yield fact!)
Which apolipoprotein is found only on chylomicrons and is required for secretion
from enterocytes? {{c1::ApoB48}}
{{c1::Lipoprotein Lipase (LPL)}} is an extracellular enzyme anchored to capillary
walls which converts triglycerides to fatty acids & glycerol mostly found in
fat, muscle & heart. liver has hepatic lipase
Which apolipoprotein is required for activation of Lipoprotein Lipase (LPL)?
{{c1::Apo C-II}} found on chylomicrons, VLDL, IDL
Which apolipoprotein binds to liver receptors and is required for uptake of
chlyomicron remnants? {{c1::Apo E }} Apo C-II & E are from HDL
{{c1::Lecithin-cholesterol acyl transferase (LCAT)::enzyme}} packs esters densely
into the nascent HDL core to create mature HDL upon activation of apolipoprotein
{{c1::A-I}}
{{c1::Cholesteryl ester transfer protein (CETP)}} is an HDL enzyme that exchanges
esters (HDL) for triglycerides (VLDL) -Inhibition of CETP leads to accumulation
of cholesterol in HDL and decreased cholesterol in VLDL. Since VLDL goes on to form
LDL, serum LDL also decreases with CETP inhibition
Before picking up Apo C-II and Apo E from HDL, transport lipoprotein VLDL only
carries which apolipoprotein? {{c1::Apo B-100}}
{{c1::Hepatic Lipase}} is an enzyme in liver capillaries that releases fatty acids
to convert IDL → LDL
LDL receptors recognize the {{c1::B100}} apolipoprotein on LDL for transfer of its
high concentration of cholesterol & cholesteryl esters to cells -LDL has small
amount of triglycerides, high levels of cholesterol -The majority of plasma
cholesterol is associated with LDL regardless of overall health or fasting status.
LDL particles (and their associated cholesterol) are synthesized in the liver. The
liver secretes VLDL particles which are converted to IDL and then LDL. The majority
of plasma cholesterol (about 80%) is synthesized in the liver and secreted as VLDL
which becomes LDL. The remaining cholesterol (about 20%) comes from our diet. This
has clinical implications since some patients will have elevated plasma cholesterol
even if they eat a low cholesterol diet.
Abetalipoproteinemia is an autosomal recessive defect in {{c1::Microsomal
triglyceride transfer protein (MTP)}} aBETAlipoproteinemia → MTP forms/secretes
apo-B lipoproteins (B48 on chylomicrons from intestine, B100 on VLDL from liver)
How are each of the four familial dyslipidemias inherited? {{c1:: I & III:
Autosomal recessive II & IV: Autosomal dominant}}
Familial dyslipidemia Type I (Hyperchylomicronemia) will cause elevated blood
levels of what? {{c1:: ↑↑↑ Triglycerides (>1000) ↑↑↑ Chylomicrons}} LPL or ApoC-
II deficiency
Hyperchylomicronemia (FDL type I) is caused by a deficiency in {{c1::LPL}} or
{{c1::Apo C-II}} most commonly LPL, remember Apo C-II is required for LPL
activation
What are the clinical features of Hyperchylomicronemia (FDL type I)? {{c1::
pancreatitis hepatosplenomegaly eruptive xanthomas}} treat with low fat diet, no ↑
risk for atherosclerosis
Familial dyslipidemia Type II (Familial Hypercholesterolemia) will cause elevated
blood levels of what? {{c1:: IIa: LDL, cholesterol IIb: LDL, cholesterol, VLDL}}
absent or defective LDL receptors
Familial Hypercholesterolemia (FDL type II) is caused by a deficiency of {{c1::LDL
receptors}} heterozygotes have cholesterol ~ 300 homozygotes have cholesterol ~
700+
What are the symptoms of Familial Hypercholesterolemia (FDL type II)? {{c1::
accelerated atherosclerosis tendon (achilles) xanthomas corneal arcus}} can
have MI before age 20
Familial dyslipidemia Type III (Dysbeta-lipoproteinemia) will cause elevated blood
levels of what? {{c1:: Chylomicrons VLDL}} defective ApoE
Familial Dysbetalipoproteinemia (FDL type III) is caused by defective {{c1::ApoE}}
ApoE2 subtype → chylomicrons poorly cleared by liver
What are the symptoms of Familial Dysbetalipoproteinemia (FDL type III)? {{c1::
premature atherosclerosis (less severe than type II) tuberoeruptive xanthomas
palmar xanthomas}} caused by ApoE2 subtype
Familial dyslipidemia Type IV (Hypertriglyceridemia) will cause elevated blood
levels of what? {{c1:: VLDL TG}} Caused by hepatic overproduction of VLDL, can
cause acute pancreatitis (TGs > 1000)
Hypertriglyceridemia (FDL type IV) is caused by hepatic overproduction of
{{c1::VLDL}} associated with DM type II, obesity
What are the side effects of excess niacin (B3)? {{c1:: facial redness, flushing
hyperglycemia hyperuricemia}} Facial flushing d/t Prostaglandins → give with
aspirin
What is the main lipid-lowering effect of fibrates? {{c1::↓↓↓ Triglycerides }}
upregulates LPL to clear triglycerides, also activates PPAR-a to induce HDL
synthesis
Lipid-lowering agent Ezetimibe works by blocking {{c1::cholesterol}} absorption at
the {{c1::intestinal brush border}} results in ↑ LDL receptors in liver
What is the MOA of lipid-lowering PCSK9 inhibitors? {{c1::block PCSK9 degradation
LDL receptors}} Alirocumab, Evolocumab
What are the symptoms of Medullary Cystic Kidney Disease? {{c1:: small, shrunken
kidneys early onset gout renal failure}} Autosomal Dominant
Post-strep glomerulonephritis (PSGN) is a type {{c1::III}} hypersensitivity
reaction immune complexes = antigen-antibody (IgG) complexes activate
complement, attract neutrophils → ↓↓ serum C3 levels due to consumption
{{c1::Henoch-Scholnein Purpura}} is IgA nephropathy with extra-renal involvement
presenting with palable purpura on butt and legs, joint & abdominal pain Most
common childhood systemic vasculitis from diffuse IgA deposition. May lead to
intussusception
{{c1::Diffuse Proliferative Glomerulonephritis (DPGN)}} is the most common subtype
of SLE renal disease caused by immune complex deposition in glomeruli ICs →
inflammatory response. Can progress to membranous glomerolunephritis (nephrotic)
What three nephritic syndromes cause hypocomplimentemia (↓ serum c3)? {{c1:: Post-
strep GN Diffuse proliferative GN Membrano-proliferative GN}} Remember its ↓C3
caused by activation of alternative compliment pathway (C4 is normal or slightly
low)
{{c1::Rapidly Progressive Glomerulonephritis (RPGN)}} is a nephritic syndrome with
crescent moon shape on LM consisting of fibrin and plasma proteins with glomerular
parietal cells, monocytes, and macrophages
{{c1::Goodpasture Syndrome (RPGN I)}} is a nephritic syndrome caused by anti-GBM
antibodies and presents with a linear immunofluorescence staining
Goodpasture Syndrome (RPGN type I) is a type {{c1::II}} hypersensitivity with a
{{c1::linear}} IF staining caused by anti-GBM antibodies
Goodpasture's Syndrome is caused by antibodies to the {{c1::alpha-3}} chain of type
{{c1::IV}} collagen found in the GBM & alveoli Hemoptysis & nephritic syndrome,
type II HS
Which two nephritic syndromes can progress to RPGN (crescentic GN) Type II? {{c1::
Post-strep GN Lupus nephritis (DPGN)}} granular appearance on IF, type III HS
reaction
Alport Syndrome is a nephritic disease caused by a genetic defect in {{c1::type IV
collagen}} and is {{c1::X-linked}} inherited mutations in alpha-3,4,5 chains
found in BM in kidney, eye, ear
What is the classic triad of symptoms in Alport Syndrome (Hereditary Nephritis)?
{{c1:: Hematuria Hearing loss Ocular disturbances}} inherited X-linked genetic
defect in Type IV collagen
Minimal Change Disease causes effacement of podocytes (foot processes) via
{{c1::cytokine-mediated damage}} which may be secondary to {{c1::Hodgkins
Lymphoma::malignancy}} also triggered by recent infx, immunization, or immune
stimulus. excellent response to corticosteroids
{{c1::FSGS}} is the most common cause of nephrotic syndrome in blacks and hispanics
Membranous nephropathy is most common cause of nephrotic syndrome in white
people
Membranous Nephropathy is caused by {{c1::subepithelial::layer}} immune complex
deposition Nephrotic presentation of SLE renal disease
MPGN Type I can be secondary to what two infections? {{c1::Hep B & C}}
What are the three treatments for recurrent calcium stones? {{c1:: Thiazides
Potassium Citrate Low sodium diet}} Thiazides ↓ urine calcium Citrate binds calcium
but remains dissolved
What three UTIs can can Struvite stones (ammonium-magnesium-phosphate)? {{c1::
Proteus Staph Klebsiella}} All urease positive → hydrolize urea to ammonia,
making urine alkaline
Which stones are the only radiolucent stones? {{c1::Uric Acid stones}} not visible
on x-ray, but you can see them with CT. Form in acidic urine (lowest pH is in
distal tubule/collecting ducts)
In addition to hydration, what are the two medical treatments for uric acid stones?
{{c1:: Potassium bicarbonate (alkalize urine) Allopurinol}}allopurinol is a
xanthine oxidase inhibitor, which reduces uric acid production. NO SURGERY
REQUIRED, ever
Renal Cell Carcinoma commonly invades the {{c1::renal}} vein which can block
drainage of the {{c1::left spermatic}} vein, which would cause a left sided
varicocele spreads through venous system
What drug can been given to treat SIADH? {{c1::Demeclocycline}} ADH antagonist.
Vaptans (tolvaptan, conivaptan given for hyponatremia in heart failure)
Osmotic Demyelination Syndrome (CPM) is demyelination in the pons, leading to loss
of corticospinal & corticobulbar tracts due to {{c1::overly rapid correction of
hyponatremia}} quadriplegia → locked-in syndrome
Which amino acids are the nitrogen sources for purine synthesis? {{c1:: Aspartate
Glutamine Glycine}} A,G & G for Adenine & Guanine
What are the carbon sources for purine synthesis? {{c1:: CO2 Glycine
Tetrahydrofolate (BH4)}} key point → folate contributes to formation of
purines
What is the rate limiting enzyme in purine synthesis? {{c1::Glutamine-PRPP
amidotransferase}}
What are the inhibitors of Glutamine-PRPP amidotransferase? (RLEnzyme in purine
synthesis) {{c1::IMP, AMP, GMP}}
What two drugs inhibit IMP Dehydrogenase to block to conversion of IMP → GMP?
{{c1:: Ribavirin (antiviral) Mycophenolate (immunosuppressant)}} inhibits synthesis
of purine nucleotides (guanine)
What enzyme converts purines hypoxanthine and guanine to IMP & GMP in combination
with PRPP? {{c1::HGPRT (hypoxanthine-guanine phosphoribosyltransferase)}}
deficiency → Lesch-Nyhan Syndrome
What enzyme converts Adenine and PRPP to AMP? {{c1::APRT (Adenine
phosphoribosyltransferase)}}
{{c1::6-Mercaptopurine}} is a chemotherapy agent that mimics hypoxanthine/guanine
to inhibit purine synthesis (adenosine and guanosine). AZATHIOPRINE is an
immunosupressant that is converted to 6-MP to get the same result 6-MP competes for
binding with HGPRT.
Adenosine is broken down to Inosine by {{c1::Adenosine Deaminase}} before being
converted to hypoxanthine Adenosine Deaminase deficiency → autosomal recessive
SCID (severe combined immunodeficiency)
{{c1::Lesch-Nyhan Syndrome}} is an X-linked absence of HGPRT leading to excess uric
acid classic presentation → male child with motor symptoms (chorea), self-
mutilation, gout
What is the rate limiting step in Pyrimidine synthesis? {{c1::}} first step
What are the two components of a Pyrimidine ring (2N, 4C)? {{c1:: Carbamoyl
phosphate (1C, 1N) Aspartate (3C, 1N)}}
Orotic Aciduria is an autosomal recessive disease caused by a defect in {{c1::UMP
synthase}} Orotic acid + PRPP → UMP synthase → UMP -Deficiency leads to elevated
levels of orotic acid and under-synthesis of pyrimindine nucleotides → Impairs DNA
synthesis → megaloblastic anemia. -In children, this usually presents as delayed
development. -Next best test after with a normal BUN and elevated orotic acid is
RBC profile including measurement of Hct → megalobastic anemia
What are the key symptoms and findings of Orotic Aciduria? {{c1:: Orotic acid in
urine Megaloblastic anemia Growth retardation NO B12/folate response}} -In
megaloblastic anemia, RBC production is decreased resulting in decreased RBC count.
MCV is increased. Reticulocyte count should rise in the setting of anemia but does
not in orotic aciduria due to defective nucleotide synthesis. OMG NO → caused by
deficient UMP synthase. Tx with uridine
What is the treatment for Orotic Aciduria? {{c1::Uridine}} megaloblastic anemia is
usually corrected with B12/folate, but if not → orotic aciduria → give uridine
How do you differentiate between OTC deficiency and Orotic Aciduria, which both
have ↑carbamoyl phosphate & orotic acid in urine? {{c1::OTC deficiency will have
↑ammonia levels}} Ornithine Transcarbamylase is a urea cycle defect, leading to
hyperammonemia, which will cause encephalopathy
{{c1::Cytarabine (Ara-C)}} is a pyrimidine analog chemotherapy agent that inserts
into DNA strands leading to termination and inhibits DNA polymerase at high doses
mimics dCTP, CYTarabine can cause panCYTopenia
{{c1::Hydroxyurea}} is a cancer drug that blocks nucleotide synthesis by inhibiting
Ribonucleotide Reductase Ribonucleotide reductase converts UDP → dUDP (RNA to
DNA). used in polycythemia, essential thrombocytosis, sickle cell anemia -Dec DNA
synthesis leads to a megaloblastic anemia including a low red cell count and high
mean corpuscular volume (MCV).
How is dUMP converted to dTMP? {{c1::Thymidylate synthase → methylates dUMP with
N5, N10 Tetrahydrofolate}} Folate is a methyl donor
{{c1::5-Fluorouracil (5-FU)}} is a chemotherapy agent that mimics uracil and
inhibits thymidylate synthase covalently binds N5, N10-THF and thymidylate synthase
-Inhibition of thymidylate synthase by 5-FU decreases intracellular thymidine and
increases intracellular uridine.
What three drugs inhibit Dihydrofolate Reductase? {{c1:: Trimethoprim Methotrexate
Pyrimethamine}} TMP
What drug is given to treat the adverse reaction of myelosuppression caused by
Methotrexate? {{c1::Leucovorin (converted to THF)}}
What metabolites will be elevated in folate and B12 defiency? {{c1:: Both: ↑
homocysteine B12: ↑ Methylmalonic acid (MMA)}} Both folate & B12 deficiency will
have megaloblastic anemia and ↑homocysteine but only B12 deficiency will have high
MMA
{{c1::Xeroderma Pigmentosum}} is a disorder of extreme sensitivity to UV rays from
sunlight caused by defective nucleotide excision repair of DNA very high risk for
skin cancer
Rifampin is tuberculosis drug that inhibits {{c1::RNA polymerase}} in bacteria
RifamPin → RNA Polymerase
Describe the inheretiance pattern and genetics of hemochromatosis (pattern, gene,
chromosome) {{c1:: autosomal recessive HFE gene chromosome 6}} C282Y mutation.
can cause diabetes via iron deposition in liver (insulin resistance) and pancreatic
B-cells (insulin deficiency)
What is the primary effect of Metformin (Biguanides)? {{c1::↓ hepatic glucose
production}} inhibits gluconeogenesis, also increases peripheral sensitivity
to insulin
What is the main effect of Metformin (Biguanides)? {{c1::↓ hepatic gluconeogenesis
via Glycerol-3-phosphate dehydrogenase inhibition::process? due to which enzyme
inhibition?}} G3PD located in mitochondria; also increases peripheral insulin
sensitivity
What is the MOA of sulfonylureas? {{c1::close K channels in B-cell membrane}}
stimulates release of endogenous insulin, requires some islet function
List the sulfonylurea drugs by generation 1st: {{c1::chlorpropamide, tolbutamide}}
2nd: {{c1::glipizide, glyburide}} 3rd: {{c1::glimepiride}} increase potency with
generation
Which T2DM drug class has the same mechanism as sulfonylureas and is given
preferrentially because they do not cause sulfa allergy? {{c1::Meglitinides →
Repaglinide, Nateglinide}} given prior to meals
What is the MOA of Thiazolidinediones (TZDs) in T2DM treatment? {{c1::activate
PPAR-y to ↑ peripheral insulin sensitivity}} safe to use in renal impairment
What are the three potential mechanisms of TZD-PPARy induced insulin sensitivity?
{{c1:: ↑ GLUT-4 ↑ Adiponectin ↓ TNF-a}} TZDs = Pioglitazone, Rosiglitazone
What is the exact MOA of a-glucosidase inhibitors (miglitol, acarbose)? {{c1::↓
glucose absorption by inhibiting a-glucosidases in intestinal brush border}} ↓
postprandial hyperglycemia
What is the MOA(s) of Pramlintide (amylin analog)? {{c1:: ↓ glucagon release delays
gastric empyting}} always given with insulin
What two subcutaneous T2DM drugs mimic GLP-1 to stimulate insulin release? {{c1::
Exenatide Liraglutide}}
What is the MOA of DPP-4 inhibitors (Sitagliptin, Linagliptin)? {{c1::DPP-4
inhibition ↑ GLP-1}} DPP-4 inhibits release of GIP and GLP-1
What is the main side effect of Sitagliptin and Linagliptin? {{c1::infections
(urinary, respiratory)}} DPP-4 inhibitors
What are the two SGLT-2 inhibitors that reduce PCT glucose reabsorption? {{c1::
Canagliflozin Dapaglifozin}} glucose floze out on flozins
What are the symptoms of Vitamin B2 (riboflavin) deficiency? {{c1:: Cheilitis (lip
inflmm, cracks at mouth corners) Corneal Vascularization Dermatitis Glossitis}}
2 C's of B2
What are the risk factors for niacin (B3) deficiency? {{c1:: INH therapy Hartnup
disease Carcinoid syndrome}} INH → ↓ B6 activity Hartnup → ↓ tryptophan Carcinoid
→ tryptophan used for serotonin
Sideroblastic Anemia is a complication of vitamin {{c1::B6}} deficiency because it
is required to incorporate iron into heme
What drugs can cause Folate deficiency or disrupt its utlization? {{c1::
Methotrexate Trimethoprim Phenytoin}} MTX, TMP inhibit Dihydrofolate reductase
Phenytoin prevents absorption of folate in jejunum
What infectious organism can cause Vitamin B12 deficiency and megaloblastic anemia?
{{c1::Diphyllobothrium latum (fish tapeworm)}} -Adult tapeworm attach to the ileum
and consume dietary vitamin B12. -Cestode tapeworm caused by ingestion of larvae in
raw freshwater fish. -Shilling test: Radiolabeled B12 will not appear in urine
after oral B12 administration or after B12 administration with intrinsic factor.
-Tx with Praziquantel
What are the three indications for Vitamin A treatment? {{c1:: Acute Myelogenous
Leukemia (M3) Measles Psoriasis/acne}}
{{c1::Isotretinoin (accutane)}} is a Vitamin A derivative used in treatment for
acne and is highly teratogenic
Vitamin K-dependent activation of clotting factors via y-carboxylation is blocked
by warfarin because it inhibits {{c1::epoxide reductase}}
What are the four causes of Vitamin K deficiency? {{c1:: warfarin antibiotics
malabsorption newborn babies}} - malabsorption = crohns, etc - antibiotics ↓GI
bacteria which make Vit. K - newborns have sterile GI tract and dont get Vit. K
from breast milk. Risk of bleeding and cerebral hemorrhage without vitamin k shot.
{{c1::Acrodermatitis Enteropathica}} is an autosomal recessive disease caused by
zinc malabsorption which results in hyperpigmented dermatitis, poor growth, and
recurrent infections
What two lysosomal storage diseases are inherited X-linked recessive? {{c1::
Fabry's disease Hunter syndrome}} ALL other LSDs are autosomal recessive
What enzyme is deficient and what accumulates in Gaucher's Disease? Deficient
enzyme: {{c1::glucocerebrosidase}} Accumulation of: {{c1::glucocerebroside}} most
common → hepatosplenomegaly, pancytopenia, osteoporosis, femur necrosis
What are the symptoms of Gaucher's Disease? {{c1:: hepatosplenomegaly pancytopenia
osteoporosis dementia & ataxia (rare)}} deficiency of glucocerebrosidase,
accumulation of glucocerebroside
What is the characteristic histological finding in Gaucher's Disease? {{c1::Gaucher
cells → lipid-laden macrophages resembling crumpled tissue paper}}
What enzyme is deficient and what substrate accumulates in Niemann-Pick disease?
Deficient enzyme: {{c1::Sphingomyelinase}} Accumulation of: {{c1::Sphingomyelin}}
Pick = sPhingomyelin → progressive neurodegeneration
What are the symptoms of Niemann-Pick disease? {{c1:: neurologic degeneration
hepatosplenomegaly cherry-red macula}}
"What is the classic histological finding in Niemann-Pick Disease? {{c1::""Foam
cells"" (lipid-laden macrophage)}}"
What is the deficient enzyme and accumulated substrate in Krabbe's Disease?
Deficient enzyme: {{c1::galactocerebrosidase}} Accumulation of:
{{c1::galactocerebroside}} -Galactocerebroside will be shunted into a toxic
substance, galactosylsphingosine. As a result, the brain shows loss of myelin and
oligodendrocytes. This is a similar pattern to other demyelination diseases like
mutiple sclerosis. -Loss of myelin → neuropathy -Key point: Loss of myelin is a
major mechanism of the pathology of Krabb disease
What are the symptoms of Krabbe's Disease? {{c1:: Progressive weakness Peripheral
neuropathy Developmental delay Optic atrophy}} Presents in 3-6 months of life.
deficiency in galactocerebrosidase
What is the characteristic histologic finding in Krabbe's Disease? {{c1::Globoid
cells in neuronal tissue}}
What enzyme is deficient and what substrate accumulates in Tay-Sachs Disease?
Deficient enzyme: {{c1::hexosaminidase A}} Accumulation of: {{c1::GM2 ganglioside}}
heXosaminidase A → tAy-saX
What are the symptoms of Tay-Sachs Disease? {{c1:: neurodegeneration developmental
delay cherry-red macula}} NO hepatosplenomegaly (vs Niemann-Pick)
What is the classic histologic finding in Tay-Sachs Disease? {{c1::lysosomes with
onion skinning}}
What enzyme is deficient and what substrate accumulates in Metachromatic
Leukodystrophy? Deficient enzyme: {{c1::Arylsulfatase A}} Accumulation of:
{{c1::Cerebroside sulfate}} central and peripheral demyelination with ataxia &
dementia
What are the symptoms of Metachromatic Leukodystrophy? {{c1:: ataxia speech
problems dementia}} presents are 2 years of age, in contrast to Krabbe's (<6
months of age)
What enzyme is deficient and what substrate accumulates in HurLer's Syndrome?
Deficient enzyme: {{c1::a-L-iduronidase}} Accumulation of: {{c1::heparan & dermatan
sulfate}} presents in 1st year of life with coarse facial features, short
stature, mental retardation
What are the symptoms of HurLer's Syndrome? {{c1:: coarse facial features airway
obstruction recurrent infections corneal clouding hepatosplenomegaly}} Hurler Hurls
Corn Recurrently in the Air
What enzyme is deficient and what substrate accumulates in HunTer's Syndrome?
Deficient enzyme: {{c1::Iduronate sulfatase}} Accumulation of: {{c1::Heparan &
dermatan sulfate}} presents like mild Hurler's with later onset, aggressive
behavior and no corneal clouding
{{c1::Betamethasone}} is a corticosteroid drug given to stimulate surfactant
production in preterm delivery phospholipase A2 inhibitor. Dexamethasone also
given.
What are the risk factors for Neonatal Respiratory Distress Syndrome? {{c1::
prematurity maternal diabetes C-section}} deficient surfactant → alveolar collpase
What is the forumula for the Bohr method of measuring physiologic dead space (Vd)?
{{c1::}} Tv = Tidal Volume PeCO2 = exhaled air PaCO2 = blood CO2
What 4 things right shift the Oxygen-hemoglobin saturation curve? (easier to
release O2) {{c1:: ↑ CO2 ↑ Temp BPG ↓ pH}}
Hereditary Primary pulmonary HTN is associated with the inactivation of the
{{c1::BMPR2}} gene, which normally inhibits vascular smooth muscle proliferation
other cause of primary pulmonary HTN → young women secrete too much
endothelin, which causes chronic vasoconstriction
What is the formula of blood O2 content? {{c1::O2 content = (1.39 x Hb)(%sat) +
(.003 x PaO2)}} 2nd part is kind of irrelevant. Multiply by CO to determine how
much oxygen is being delivered to tissues
What is the formula for alveolar oxygen pressure? (PAO2) {{c1:: PiO2 - (PaCO2 /
0.8)}} Inhaled oxygen (PiO2 ≈ 150) minus diffusion across alveolar membrane
(PaCO2/0.8)
What are the findings in the congestive stage of lobar pneumonia? {{c1:: dilation
of alveolar capillaries bacteria exudate}}
What are the findings in the red hepatization stage (2) of lobar pneumonia? {{c1::
red-brown appearance exudate of RBCs, neutrophils, fibrin consolidation}}
What are the findings in the grey hepatization stage (3) of lobar pneumonia? {{c1::
gray, firm lobe exudate w/ neutrophils & fibrin dying bacteria}}
What three bacteria are the common causes of atypical pneumonia (walking
pneumonia)? {{c1:: Legionella pneumophila Mycoplasma pneumoniae Chlamydophila
pneumoniae}} interstitial infiltrates of CXR, mild, respiratory distress is
rare
What organisms are the common causes of pneumonia in neonates (< 4 weeks old)?
{{c1:: Group B Strep E. Coli}} same as meningitis
What bacterial cause of pneumonia is associated with outbreaks at hotels or
hospitals with contaminated water? {{c1::Legionella}} unilateral lobar pneumonia,
GI symptoms, neurologic abnormalities (bc of hyponatremia). Tx with macrolides or
fluoroquinolones
"What are the two serious complications that can come from Mycoplasma Pneumonia
infection? {{c1:: autoimmune ""cold"" hemolytic anemia Stevens-Johnson sydrome}}"
anemia → IgM antibody to RBC antigen
What three pathogens are the major causes of secondary pneumonia following
influenza virus infection? {{c1:: Strep pneumo Staph aureus H. influenzae}}
worseing symptoms after initial improvement
What pathogen causes pneumonia in transplant patients on immunosuppressive drugs?
{{c1::CMV}} """owl eye"" intranuclear inclusions. CMV lives latently within cells
throughout lifetime → reemerges when cell-mediated immunity is impaired
(immunosuppressive drugs, HIV, etc)"
What drugs are given for the treatment and prevention of RSV respectively? Treat:
{{c1::Ribavirin}} Prevent: {{c1::Palivizumab}} Ribavirin → blocks IMP
dehydrogenase (prevents conversion of inosine monophosphate to guanosine
monophosphate) Palivizumab → antibody against F protein
What pathogens are the common causes of aspiration pneumonia? {{c1:: Klebsiella
Staph aureus Anaerobes }} Clindamycin is first line
What pathogens are the common causes of lung abcesses? {{c1:: Anaerobes Staph
aureus Klebsiella}} Aspiration ASKs for Abcesses bugs same as aspiration pneumo
drugs same as aspiration pneumo (Clindamycin)
What are the oral drugs given for influenza prophylaxis? {{c1:: Oseltamivir
Zanamivir}} inhibit influenza neuraminidase → ↓ release of progeny virus
(amantidine is old flu prophylaxis but now only used in Parkinson's)
Sarcoidosis is associated with accumulation of {{c1::TH1 CD4+}} T cells ↑
CD4:CD8 ratio → non-caseating granulomas
In sarcoidosis, CD4+ TH1 cells secrete IL-2 and interferon-y. What do these
mediators do respectively? IL-2 → {{c1::TH1 proliferation}} IFN-y → {{c1::activates
macrophages}} both of these signals lead to granuloma formation (non-caseating)
What are the two classic pulmonary manifestions of sarcoidosis? {{c1:: Hilar
lymphadenopathy Pulmonary fibrosis}}
What is the classic skin manifestation of sarcoidosis? {{c1::Erythema nodosum}}
inflammation of fat cells under skin, tender red nodules, usually on both
shins
What are the two abnormal lab findings found in sarcoidosis? {{c1:: Hypercalcemia
High ACE levels}} hypercalcemia caused by elevated 1-a hydroxylase activity in
alveolar macrophages ↑ Vitamin D levels
Steroids are the mainstay treatment for sarcoidosis but many patients are weened
off long-term steroids and given what three other immunosuppressants? {{c1::
Methotrexate Azathioprine Mycophenolate}} """steroid sparing agents"""
What two muscaranic antagonists (M3) are used in the treatment of asthma and COPD?
{{c1:: Ipratropium (short acting) Tiotropium (long acting)}}
What two drugs asthma drugs block leukotriene receptors (CysLT1)? {{c1::
Montelukast Zafirlukast}} good for aspirin and exercise induced asthma
What asthma drug works by blocking 5-lipoxygenase pathway? {{c1::Zileuton}} blocks
conversion of arachidonic acid to leukotrienes → hepatotoxic
{{c1::Omalizumab}} is an anti-IgE antibody given for asmtha that inhibits the IgE
receptor (FceRI) on mast cells and basophils used in allergic asthma with ↑ IgE
levels resistant to inhaled steroids and long acting B2 agonists
{{c1::Cromolyn}} is a drug given for asthma prophylaxis that works by inhibiting
mast cell degranulation blocks release of histamines and leukotrienes
{{c1::Theophylline}} is an asthma drug that causes bronchodilation by inhibiting
phosphodiesterase, leading to ↑ cAMP metabolized by P450, blocks adenosine,
overdose → nausea, vomiting, seizures (think caffeine)
{{c1::Roflumilast}} is a COPD drug that inhibits PDE-4 to decrease inflammation and
relax airway smooth muscle
What is the hallmark of pulmonary embolism on ECG? {{c1::S1Q3T3}}
A fat embolism almost always occurs after {{c1::long bone fracture}} and presents
with pulmonary distress, neurological deficits & confusion, and petechiae
A woman who develops respiratory distress, ↓ O2, and hypotension shortly after
giving birth indicates what? {{c1::Amniotic fluid embolism}} can progress to
DIC, massive hemorrhage, and seizures due to the releases of thromboplastin (tissue
factor)
What are the Light Criteria (3) for determining if a pleural effusion is exudative?
{{c1:: pleural:serum protein ratio > 0.5 pleural:serum LDH ratio > 0.6 pleural LDH
> 2/3 of normal serum LDH}} malignancy, infection (pneumonia)
"Lymphatic pleural effusions (""chylothorax"") will show elevated levels of
{{c1::triglycerides}} in the pleural fluid" "TG usually > 100 mg/dL, fluid will
have ""milky"" appearance"
Smoking induced emphysema causes {{c1::centriacinar}} damage while a1-antitrypsin
deficiency emphysema causes {{c1::panacinar}} damage also, smokers get upper lung
damage, a1-antitrypsin peeps get lower lung damage
{{c1::Methacholine}} is a muscarinic (M3) agonist that causes bronchoconstriction
and is used in the diagnosis of asthma Methacholine test is used to exclude
asthma, but is not enough for a diagnosis
What are the two classic pathology findings in the sputum of asthmatics? {{c1::
Curschmann's spirals Charcot-Leyden crystals}}
What are the non-cardiac causes of pulsus paradoxus? {{c1:: asthma/COPD obstructive
sleep apnea croup}} ↓ amplitude of systolic BP by > 19 mmHg during inspiration
What are the risk factors for lung cancers? {{c1:: Cigs (PAHs) Radiation therapy
Asbestos Radon}}
{{c1::Lambert-Eaton syndrome}} is a paraneoplastic syndrome associated with small
cell lung cancer caused by antibodies against presynaptic calcium channels in
neurons, leading to weakness Small cell lung cancer also causes Cushings (ACTH)
and SIADH
What are the key pathology findings in Squamous cell carcinoma of the lungs? {{c1::
Keratin pearls Intracellular desmosomes (bridges)}} same as all squamous cell
cancers
What kind of lung cancer is a peripheral tumor commonly occuring in non-smokers and
women? {{c1::Adenocarcinoma}}
{{c1::Bronchioalveolar Carcinoma}} is a subtype of lung adenocarcinoma that
resembles pneumonia on CXR (lobar consolidation) nonsmokers, peripheral,
excellent prognosis
Bronchial Carcinoid tumors stain positive for {{c1::chromogranin A}} Chromogranin
A is positive in neuroendocrine tumors (eg, also small cell carcinoma). Rarely
actually causes carcinoid syndrome, super good prognosis, also non-smokers
What are the most common sites of metastases from lung cancer? {{c1:: Adrenals
Brain Bone (pathologic fractures) Liver (hepatomegaly, jaundice)}}
What is the hallmark of interstitial lung disease in differentiating causes of
restrictive lung disease? {{c1::low DLCO}} extra-pulmonary causes (obesity)
will have restriction with normal DLCO
Coal miner's pneumoconiosis commonly affects the {{c1::upper}} lobes of the lung
prolonged coal dust exposure → macrophages laden with carbon → inflammation
and fibrosis
What three environments/occupations are associated with Silicosis? {{c1:: foundries
sandblasting mines}} macrophages react to silica and activate fibroblasts to lay
down collagen
What 4 drugs are associated with interstitial lung disease? {{c1:: Bleomycin
Busulfan Amiodarone Methotrexate}}
Hypersensitivity Pneumonitis is a type {{c1::III/IV (mixed)}} hypersensitivity
reaction causing restrictive lung disease (often farmers and bird exposure)
How will secondary hyperparathyroidism (renal failure) affect PTH, ALP, serum
calcium and phosphorus? {{c1:: ↑ PTH, phosphate, ALP ↓ Ca }} Renal failure.
high PTH can't compensate for renal loss of Ca and renal retention of phophorus →
partially caused by inability to activate Vitamin D. **Think of it as
hypoparathyroidism with high PTH**
Why are Cystic Fibrosis patients infertile? {{c1::Absent vas deferens}} they
have capable swimmers, but no river to swim through
What is the pulmonary hallmark of primary tuberculosis? {{c1:: Ghon complex }}
What is the pulmonary hallmark of secondary (reactivation) tuberculosis? {{c1::
cavitary lesion in upper lobe }}
What drugs can cause reactivation of latent tuberculosis? {{c1::TNF-a inhibitors}}
adalimumab, infliximab, certolizumab, etanercept
What are the two key features that define an omphalocele? (in contrast to
gastroischisis) {{c1:: covered by peritoneum through umbilical cord}} caused by
failure of lateral fold closure
{{c1::Meckel's Diverticulum}} is the most common congenital GI anomaly, caused by
persistence of Vitelline duct TRUE Diverticulum → all 3 gut wall layers present,
often contains ectopic gastric tissue (stomach, pancreatic)
"{{c1::Duodenal atresia}} is caused by a failure of recanalization and presents as
a ""double-bubble"" sign on x-ray" Associated with Downs Syndrome
{{c1::Pilocarpine}} is a direct muscarinic agonist used to stimulate saliva
production in Sjorgren Syndrome M1=M2=M3 → Sjorgrens, open and closed angle
glaucoma
What pathogen is the most common cause of Sialadenitis (salivary gland infx)?
{{c1::Staph aureus (+ anerobes)}} often secondary to obstructing stone, tx with
piperacillin (staph) and something to cover anerobes
What are the two types of cells found in Mucoepidermoid Carcinoma salivary gland
tumors? {{c1:: squamous (epidermoid) cells mucus-secreting cells}} Malignant,
radiation biggest risk factor
An Indirect Inguinal Hernia enters the internal ring {{c1::lateral}} to the
inferior epigastric vessels and is covered by {{c1::all three}} layer(s) of
spermatic fascia goes into the scrotum, occurs in infants d/t failure of processus
vaginalis to close, more common in males
A Direct Inguinal Hernia enters the external ring {{c1::medial}} to the inferior
epigastric vessels and is covered by {{c1::external}} layer(s) of spermatic fascia
through Hasselbach's triangle due to weakness of transversalis fascia, never
bulges into scrotum, old men
What is the mechanism of bile's antimicrobial activity? {{c1::disrupts bacterial
cell membrane}}
What are the lab findings in Cholestasis (impaired bile flow to intestines)? {{c1::
↑ Direct (conjugated) bilirubin ↑ Alkaline Phosphatase (ALP)}} symptoms →
jaundice, pruritus, dark urine, clay colored stools
What antibiotic can cause acute cholestatic hepatitis and jaundice?
{{c1::Erythromycin}} ↑ ALP, normal bile ducts on imaging
Unconjugated bilirubin is conjugated with Glucuronic Acid in the liver by the
enzyme {{c1::UDP glucuronosyltransferase}}
Most urobilinogen is excreted in the feces as {{c1::Stercobilin}} and the minority
is excreted in the urine as {{c1::Urobilin}}
How will hemolysis present on lab inspection of bilirubin levels? {{c1:: ↑
unconjugated (indirect) hyperbilirubinemia ↑ urine urobilinogen}} hemolysis →
↑ indirect bilirubin overwhelms liver
How will biliary obstruction (cholestasis) present on lab inspection of bilirubin
levels? {{c1::↑ conj. (direct) hyperbilirubinemia urine bilirubin detected (dark
urine) absent urobilinogen}} dark urine → conjugated bilirubin is water soluble
absent urobilinogen → obstruction prevents bilirubin from reaching intestine
How will primary liver diseases present on lab inspection of bilirubin levels?
{{c1::↑ total bilirubin (mixed)}}
Which two drugs are common causes of hyperbilirubinemia? {{c1:: Rifampin
Probenacid}}
{{c1::Crigler-Najjar Syndrome}} is a hereditary pathology of hyperbilirubinemia
caused by severely reduced levels of UGT enzyme
Which second messenger systems (GPCRs) are used by the hormones that control acid
secretion? (ACh, gastrin, histamine, somatostatin, PGs) {{c1:: Gq → ACh, Gastrin
(+) Gs → Histamine (+) Gi → Somatostatin, PGs (-)}}
{{c1::Misoprostol}} is a PGE1 analog used to ↓ stomach acid production and ↑
gastric mucous barrier
{{c1::Pepsin}} is a gastric regulatory substance secreted by Chief cells in the
stomach to digest proteins pepsinogen (inactive) is converted to pepsin (active)
in the presence of H+ → secretion ↑ by vagal stimulation & local acid
How is the secretin test used to diagnose a gastrinoma (ZE syndrome)?
{{c1::Gastrinoma → gastrin level will rise after secretin administration}}
gastrin is usually suppressed by secretin
{{c1::Pernicious Anemia}} is caused by antiparietal cell and anti-IF autoantibodies
leading to the inability to absorb Vitamin B12 ↑↑ Gastrin levels
{{c1::Cholecystokinin}} is a hormone secreted by I cells in the duodenum & jejunum
to increase gallbladder contraction and pancreatic secretions CCK stimulates
vagus nerve to release ACh to stimulate pancreatic secretions
{{c1::Secretin}} is a hormone secreted by S cells in the duodenum to ↑ pH (↑
pancreatic HCO3 secretion & ↓ gastric acid secretion) in the small intestine -
Remember that pancreatic juice is an isotonic secretion, which normally contains
Na+ and K+ in the same concentrations as found in the plasma, a higher HCO3-
concentration than in plasma and a lower Cl- concentration than in plasma. As
pancreatic juice flow rates and secretin stimulation increase, the concentration of
HCO3- increases and the concentration of Cl- decreases
{{c1::Vasoactive Instestinal Peptide (VIP)}} is a Neurocrine hormone secreted by
parasympathetic neurons to relax smooth muscle of sphincters (LES), ↑ pH (like
secretin), and ↓ gastric acid secretion
What are the symptoms of a VIPoma? {{c1:: Watery Diarrhea Hypokalemia
Achlorhydria}} -Binding of VIP to intestinal epithelial cells leads to adenylate
cyclase activation and increased cAMP production, causing sodium, chloride and
water secretion into the bowel (secretory watery diarrhea, often >3 L/day). WDHA
syndrome -Somatostatin (octreotide) decreases the production of many GI hormones
eg; VIP, gastrin, glucagon, CCK.
A neonate with jaundice, dark urine, pale stools and an absent (or abnormal)
gallbladder on ultrasound is indicative of {{c1::Biliary Atresia}}
Describe the presentation of primary biliary cirrhosis {{c1:: women PRURITUS
fatigue jaundice}}
What are the abnormal lab findings associated with primary biliary cirrhosis?
(antibody & labs) {{c1::Anti-mitochondrial antibody ↑ ALP ↑ lipids}} Deficient
hepatic processessing of lipids can lead to (and present as) hyperlipidemia
stigmata (xanthelasmas, etc)
What is the only effective medical therapy used to treat primary biliary cirrhosis?
{{c1::Ursodeoxycholic acid}}
{{c1::Primary Sclerosing Cholangitis}} is an autoimmune disorder causing
inflammation, fibrosis, and strictures in the biliary tree
What extra-intestinal complication is unique to ulcerative colitis? {{c1::primary
sclerosing cholangitis}}
What are the lab findings in primary sclerosing cholangitis? {{c1:: p-ANCA + ↑ IgM
Cholestasis (↑ ALP, conj. bilirubin)}}
What is the histopathological hallmark of primary sclerosing cholangitis?
{{c1::Periductal fibrosis (onion-skin fibrosis of bile ducts)}} Remember, it's
intra and extra hepatic, where's primary biliary cholangitits only affects
intrahepatic bile ducts
{{c1::Cholangiocarcinoma}} is a rare cancer of bile duct epithelial cells,
presenting with symptoms of bile duct obstruction both Clonorchis sinensis and
Primary Sclerosing Cholangitis increase risk
What are the two key risk factors for Cholangiocarcinoma? {{c1:: Primary Sclerosing
Cholangitis (UC) Clonorchis sinesis}}
{{c1::Enterokinase/enteropeptidase}} converts trypsinogen to trypsin (active) at
the intestinal brush border -Enteropeptidase deficiency leads to both protein and
fat malabsorption as trypsin is required to activate enzymes required for both
lipid and protein digestion. The disease causes diarrhea, failure to thrive and
edema (due to hypoproteinemia)
Ingestion of Lye by children (household cleaners, Drano) causes injury to
esophageal mucosa via {{c1::liquefactive necrosis}}
Barrett's Esophagus is complication of GERD resulting in metaplasia of esophageal
stratified squamous epithelium to {{c1::nonciliated columnar epithelium with goblet
cells (intestinal ep.)}}
How will esophagitis from Candida appear on endoscopy? {{c1:: White membranes}}
pseudohyphae on biopsy, CD4 < 100
How will esophagitis from HSV-1 appear? {{c1::punched-out ulcers}}
How will esophagitis from CMV appear? {{c1::Linear ulcers}}CD4 < 100 (or < 50)
How will Eosinophilic Esophagitis appear on endoscopy? {{c1::Esophageal rings &
linear furrows}}
Achalasia is the inability to relax the LES due to loss of {{c1::Auerbach's
plexus}}
{{c1::Scleroderma esophageal dismotility}} is a cause of dysphagia due to
esophageal smooth muscle atrophy and ↓ LES pressure Achalasia is caused by ↑ LES
pressure
Esophageal Varices occur due to dilated {{c1::submucosal}} veins and are usually
caused by {{c1::portal hypertension (cirrhosis)}}
{{c1::Mallory-Weiss Syndrome}} is a cause of painful hematemesis due to damage of
the esophageal mucosa at the GE junction from severe, chronic vomiting (alcoholism,
bulimia)
{{c1::Boerhaave Syndrome}} is a transmural distal esophageal rupture presenting
with pneumomediastinum and and subcutaneous emphysema (air under skin in neck)
result of severe, violent vomiting or retching
What are the classic symptoms in Plummer-Vinson Syndrome? {{c1:: Beefy red tongue
Iron deficiency anemia Dysphagia Esophageal web}} The dude needs a plumber, the
dude aBIDEs
{{c1::Zenker's Diverticulum}} is a false diverticulum (mucosa & submucosa) through
the muscular layer at the pharyngoesophageal junction at Killian's Triangle due to
cricopharyngeal muscle dysfucntion, causes recurrent aspiration pneumonia
↑AST > ↑ALT on liver tests suggests {{c1::alcoholic hepatitis}}
↑ ALP plus ↑ {{c1::GGT}} confirms a hepatobiliary cause of ↑ ALP and rules out bone
disease GGT = gamma-glutamyl transpeptidase also elevated after binge drinking
Fatty infiltration in Alchoholic Liver Disease begins in Zone {{c1::III}} of the
liver Zone III also affected 1st by ischemia, contains cytochrome P-450 system,
most sensitive to metabolic toxins
{{c1::Mallory bodies}} are intracytoplasmic eosinpholic inclusions caused by
damaged intermediate filaments in hepatocytes caused by alcoholic liver disease
{{c1::Budd Chiari Syndrome}} is a liver pathology of centrilobular (zone III)
necrosis caused by thrombosis of the hepatic vein leading to abdominal pain,
ascites, and hepatomegaly
{{c1::Reye Syndrome}} is a rare cause of childhood liver failure and encephalopathy
associated with a viral infection (VZV, influenza B) that has been treated with
aspirin
How is a1 anti-trypsin deficiency inherited? (pattern) {{c1::autosomal co-
dominant}}
a1 Anti-trypsin polymers (in AAT deficiency) stain positive with {{c1::PAS}} and
resist digestion by {{c1::diastase}} glycogen (in glycogen storage disease)
also stains + with PAS but it is digested by diastase
What 4 pathogens are the common causes of Liver Abscesses? {{c1:: Staph aureus
Klebsiella (+ other gram neg rods) Entamoeba histolytica Echinococcus}} think
bacteria (Staph & Klebs) in developed countries; Entamoeba and Echinococcus in
underdeveloped countries
What two autoantibodies are present in Autoimmune Hepatitis? {{c1:: Anti-smooth
muscle ABs (ASMA) Anti-nuclear ABs (not specific)}} most common in women in 40s &
50s, treat with steroids and immunosuppressants
What is the treatment for tylenol (acetominophen) overdose? {{c1::N-
acetylcysteine}} replenishes glutathione which binds to NAPQI
{{c1::NAPQI}} is the primary toxic metabolite of acetaminophen that depletes
glutathione N-acetylcysteine to replenish glutathione which binds to NAPQI
How does Cirrhosis affect effective circulating volume (ECV) and total body water?
{{c1::↓ECV, ↑ total body water}}
Name the clinical sign, the portal vein, and the systemic vein implicated when
Esophagus anastomoses engorge in portal HTN Clinical sign → {{c1::esophageal
varices}} Portal vein → {{c1::left gastric}} Systemic vein → {{c1::esophageal →
azygos}}
Name the clinical sign, the portal vein, and the systemic vein implicated when
Umbilicus anastomoses engorge in portal HTN Clinical sign → {{c1::Caput medusae}}
Portal vein → {{c1::paraumbilical}} Systemic vein → {{c1::small epigastric}}
Name the clinical sign, the portal vein, and the systemic vein implicated when
Rectal anastomoses engorge in portal HTN Clinical sign → {{c1::internal
hemorrhoids}} Portal vein → {{c1::superior rectal}} Systemic vein → {{c1::middle &
inferior rectal}}
Portal HTN with a normal liver biopsy is highly suggestive of {{c1::Portal Vein
Thrombosis}} -As it is a pre-sinusoidal process. Normal histology of liver and
no ascites
How is the Serum Ascites Albumin Gradient (SAAG) used to determine the cause of
ascites? (formula, results) {{c1:: SAAG = serum albumin - ascites albumin SAAG >
1.1 → portal HTN SAAG < 1.1 → malignancy}}
What two drugs are used to treat Ascites? {{c1:: Spironolactone (1st line) Loop
Diuretics (2nd line)}} treatment always includes sodium restriction, paracentesis
for large volume ascites
What pathogens are the most common culprits of Spontaneous Bacterial Peritonitis
(ascites infection)? {{c1:: E coli Klebsiella}}
How is Spontaneous Bacterial Peritonitis diagnosed? {{c1::ascitic fluid absolute
neutrophil count > 250 }} treat with third gen cephalosporin (cefotaxime)
Hepatic stellate (Ito) cells in space of Disse store vitamin {{c1::A}} (when
quiescent) and secrete {{c1::TGF-B}} to produce extracellular matrix fibrosis in
cirrhosis
{{c1::Aspergillus}} is a fungal pathogen that produces an aflatoxin that can cause
Hepatocellular Carcinoma via p53 mutations can contaminate corn, soybeans,
peanuts, mostly in non-industrialized countries
What are three high yield clinical features & possible consequences of
Hepatocellular Carcinoma? {{c1:: Hypoglycemia Polycythemia Budd Chiari syndrome}}
obviously also ↑ LFTs, liver failure
What serum tumor marker will be elevated with Hepatocellular Carcinoma? {{c1::a-
fetoprotein}}
What are the two most common sites of HCC metastases? {{c1::Lung > bone}}
{{c1::Hepatic Adenomas}} are benign epithelial hepatic tumors usually presenting as
a solitary mass in the right lobe in young women (20s - 40s)
What are two risk factors for Hepatic Adenomas? {{c1:: birth control pills anabolic
steroids}} Can rupture during pregnancy. Benign, epithelial, solitary mass in
right lobe, most commonly in women.
{{c1::Hepatic (Cavernous) Hemangiomas}} are the most common benign liver tumor and
are composed of vascular spaces often filled with thrombus "Biopsy can cause fatal
hemorrhage (lots of blood). ""Mullberry-like"" purple-ish appearance on gross
examination."
{{c1::Hepatic Angiosarcomas}} are rare highly malignant hepatic tumors arising from
vascular endothelium
Exposure to what two toxins can cause Hepatic Angiosarcomas? {{c1:: Vinyl chloride
Arsenic }}
What are the most common origins of metastases to the liver? {{c1::colon >> stomach
> pancreas > breast > lung}} as always, will present as multiple nodules
Describe the inheritance & genetics of Wilson's Disease (pattern, chromosome, gene)
{{c1:: autosomal recessive chromosome 13 ATP7B gene}} "Wilson always had a crush on
13 in ""House"" but was too passive (recessive) to make a move"
What is the diagnostic hallmark of Wilson's Disease? {{c1::↓ ceruloplasmin}} will
also show low serum copper
What are the 3 treatments for Wilson's Disease? {{c1::Penicillamine Trientine
Zinc}} Penicillamine binds copper and promotes urinary excretion
Hereditary Hemochromatosis is most commonly due to a homozygous {{c1::C282Y}}
mutation
What two substances should be avoided in patients with Hemochromatosis? {{c1::
Alcohol (accelerates liver disease) Vitamin C (↑ Fe absorption)}}
What will lab tests for iron, ferritin, TIBC, and % saturation of transferrin show
in Hemochromatosis? {{c1::}} Complete opposite of iron deficiency. Iron overload
causes the body to downregulate TIBC
What are the treatments for Hemochromatosis? {{c1:: Phlebotomy Iron chelating
agents (Deferoxamine, Deferiprone, Deferasirox)}} DeFER____ = ferritin
{{c1::Hyperplastic Polyps}} are benign colonic polyps most common in the
rectosigmoid colon which may evolve into serrated polyps "progression towards
serrated polyp will have ""saw tooth"" or serrated pattern"
What morphology of adenomatous polyps have high malignant potential and are often
sessile? {{c1::Villous}}
{{c1::Juvenile Polyposis Syndrome}} is an autosomal dominant syndrome in children
causing numerous hamartomatous polyps which ↑ risk of cancer
{{c1::Peutz-Jeghers Syndrome}} is an autosomal dominant syndrome featuring numerous
hamartomous throughout the GI tract along with hyperpigmented mouth, lips, hands
and genitalia
The first step of the Chromosomal Instability Pathway is a mutation of the APC
gene. How does this mutation lead to ↑ risk of polyps? {{c1::Loss of APC (tumor
suppressor) → ↑ B-catenin → oncogene activation}} B-catenin activity is
regulated by the Wnt signaling mechanism.
List the step-wise progression (mutations) of the Chromosomal Instability Pathway
in the pathogenesis of colorectal carcinoma {{c1::}}
Describe the inheritance and genetics of Familial Adenomatous Polyposis (pattern,
chromosome, gene) {{c1:: autosomal dominant chromosome 5q APC gene}}
What are the presenting symptoms of Gardner's Syndrome? {{c1:: FAP Skin cysts
Hyperpigmentation of retina Osteomas (mandible) Impacted/supernumerary Teeth}}
After gardening, Gardners like to take a SHOT and FAP
Turcot Syndrome is a disease of familial adenomatous polyposis (FAP) combined with
{{c1::brain tumors}} mostly medulloblastomas and gliomas
Where do colorectal cancers from the Chromosomal and Microsatellite instability
pathways present, respectively? Chromosomal → {{c1::left}} Microsatellite →
{{c1::right}}
{{c1::Lynch Syndrome (HNPCC)}} is an autosomal dominant mutation of DNA mismatch
repair genes leading to microsatellite instability and colorectal cancer
NSAIDs may help prevent colorectal cancer because many CRCs overexpress {{c1::COX-
2}}
"What are the symptoms of right sided/ascending colon cancers? {{c1:: ""exophytic
tumors"" iron-deficiency anemia weight loss}}" microsatellite instability, HNPCC
What are the symptoms of left sided/descending colon cancers? {{c1:: LLQ pain Blood
streaked stool circumferential lesion change in stool caliber}}
{{c1::Carcinoembryonic Antigen (CEA)}} is a tumor marker that is good for
monitoring recurrence of colon cancer but should not be used for screening
Pigment gallstones are caused by a rise in {{c1::unconjugated bilirubin}} in bile
What are the risk factors for Pigment (bilirubin) gallstones? {{c1:: extravascular
hemolysis liver disease recurrent biliary infx (BROWN)}}
What is the classic physical exam finding in patients with acute cholecystitis?
{{c1::}}
What is the hallmark of chronic cholecystitis on x-ray? {{c1:: Porcelain
(calcified) gallbladder }} ↑ risk of gallbladder carcinoma
What two pathogens are the common causes of AIDS Cholangiopathy? {{c1::
Cryptosporidium CMV}}
What are the three components of the Charcot triad of ascending cholangitis?
{{c1::Jaundice, fever, RUQ pain}} Reynolds pentad adds confusion & shock labs
will be similar to cholestasis with ↑ WBCs
What are the common pathogens associated with ascending cholangitis? {{c1:: E coli
Klebsiella Enterobacter Clonorchis sinensis}} clonorchis sinensis will present w/
ascending cholangitis + peripheral eosinophilia (helminth), can lead to
cholangiocarcinoma
Air in the biliary tree is pathognomonic for {{c1::gallstone illeus}} gets stuck
in ILEUM (at ileocecal valve)
What bacteria can cause gallbladder adenocarcinoma? {{c1::salmonella typhi}}
{{c1::Curling ulcers}} is acute gastritis in burn patients due to hypovolemic
induced ischemia
{{c1::Cushing ulcers}} are acute gastritis and stomach ulcers due to increased
intracranial pressure
What are the three components of Helicobacter pylori triple-therapy treatment?
{{c1:: PPI (omeprazole) Clarithromycin Amoxicillin or Metronidazole}} -Synthesis
of HCl by parietal cells of the gastric mucosa is dependent on the H/K-ATPase,
which is known as a proton pump (primary active transport). This carrier transports
hydrogen ions into the gastric lumen in exchange for potassium ions. Omeprazole and
other PPIs inhibit the H/K-ATPase, thus decreasing the concentration of HCl in the
gastric lumen. These medications are used for treatment of PUD, GERD, and diseases
associated with increased gastrin secretion such as the Zollinger-Ellison syndrome
What is the key pathological finding in metaplastic atrophic gastritis? (pre-
stomach cancer) {{c1::Goblet cells in stomach}} should only be in intestines
What is the characteristic histological finding in Duodenal peptic ulcer disease?
{{c1::hypertrophy of Brunner's glands}} Located in submucosa of duodenum →
secrete basic fluid (HCO3) to neutralize acid
What are two complications of posterior duodenal ulcers? {{c1:: hemorrhage of
gastroduodenal artery pancreatitis}}
Any source of GI bleeding above the {{c1::ligament of Trietz}} is an upper GI bleed
and will result in hematemesis and dark (tarry) stools lower GI bleeding (below
LoT) will cause bright red stools (hemochezia)
Anterior duodenal ulcers may cause {{c1::perforation}} which would present as air
under the diaphragm and shoulder pain
Gastric ulcers on the lesser curvature of the stomach may rupture and cause
bleeding from the {{c1::left gastric}} artery
The Intestinal type of gastric adenocarcinoma is commonly located at the
{{c1::lesser curvature}} of the stomach and looks like {{c1::an ulcer with raised
margins}}
What is the histological hallmark of diffuse type gastric adenocarcinoma?
{{c1::Signet ring cells}}
What two cutaneous paraneoplastic syndromes are associated with gastric
adenocarcinoma? {{c1:: Acanthosis nigricans Leser-Trelat sign}}
{{c1::Krugenberg tumors}} are bilateral ovarian tumors most commonly arising from
metastatic gastric adenocarcinoma mucin-secreting signet cells seen on pathology
What are three ominous presentations (sites) of metastatic gastric adenocarcinoma?
{{c1:: Virchow node (left supraclavicular) Krukenberg tumor Sister Mary Joseph
nodule (periumbilical)}}
{{c1::Menetrier Disease}} is a precancerous hyperplasia of gastric mucosa leading
to achlorhydria and hypoalbuminemia achlorhydria results in protein loss because
acid is needed to activate pepsinogen → pepsin to digest proteins
What autoantibodies are present in Celiac disease? {{c1:: IgA anti-endomysial IgA
anti-tissue transglutaminase (tTG) anti-deaminated gliadin peptide}}
Celiac disease is a Type {{c1::IV}} hypersensitivity reaction associated with HLA
{{c1::DQ2}} and {{c1::DQ8}} 23 = 2, 4, 8
What are the three key histology features of Celiac disease? {{c1:: blunting of
villi crypt hyperplasia lymphocytes in lamina propria}}
Celiac disease can increase risk of what small bowel malignancy? {{c1::Enteropathy-
associated T-cell lymphoma (EATL)}} Celiac is a type IV hypersensitivity → T cells
→ T-cell lymphoma
{{c1::Dermatitis Herpetiformis}} is a skin condition associated with Celiac Disease
due to IgA deposition in dermal papillae Biopsy: Subepidermal clefting and
blistering other non-intestinal manifestations of Celiac can include iron-
deficiency anemia (celiac damages duodenum, iron absorbed in duodenum) and ↓ bone
density
Tropical Sprue is similar to Celiac Disease but has what two unique features?
{{c1:: can involve entire small bowel responds to antibiotics}} Because it can
involve the entire small bowel, it can cause B12 & folate malabsorption (ileum) and
megaloblastic anemia (celiac can't)
What is a non-intestinal manifestation of Tropical Sprue? {{c1::folate & B12
deficiency (megaloblastic anemia)}} Remember that Tropical Sprue can involve entire
small bowel, while Celiac can't. folate & B12 absorbed in jejunum/ileum → treat
with antibiotics (tetracyclines) and folate supplementation
What findings in biopsy of the small intestine confirm the diagnosis of Whipple's
Disease? {{c1::PAS(+) foamy macrophages in lamina propria}}
What are the three criteria for diagnosing acute pancreatitis? {{c1:: epigastric
pain (often radiates to back) ↑ amylase/lipase > 3x normal abnormal imaging }}
need 2/3
Autoimmune pancreatitis is a rare condition of reccurent attacks of acute
pancreatitis that is diagnosed by high levels of {{c1::IgG4 plasma cells}}
diffusely enlarged pancreas on imaging, treated with steroids
Pancreatic abcesses are commonly caused by infection of a pancreatic pseudocyst by
what bacteria? {{c1:: E coli Pseudomonas Klebsiella Enterococcus}} usual GI
culprits, usually occurs ~10 days into acute pancreatitis
Fat necrosis following acute pancreatitis can cause what two electrolyte
abnormalities? {{c1:: Hypocalcemia Hypomagnesemia}}
"What are the gross morphologic features of Ulcerative Colitis? {{c1:: friable
mucosa with ulcerations Pseudopolyps (healed ulcers) Loss of haustra (""lead pipe""
on imaging)}}"
What are the microscopic morphologic features of Ulcerative Colitis? {{c1:: crypt
abscesses (PMN infiltration) no granulomas}}
What are unique intestinal complications of Ulcerative Colitis? {{c1:: Toxic
Megacolon Fulminant colitis Perforation}}
Which antibodies are associated with the two IBDs? Crohn's → {{c1::ASCA}} UC →
{{c1::p-ANCA}} ASCA → anti-saccharomyces cerevisiae (yeast)
Which lymphocytes mediate the two IBDs? Crohn's → {{c1::TH1}} UC → {{c1::TH2}}
-The releaseof proinflammatroy cytokines by Th-1 cells (eg; IFN-y), activates
macrophages, which then cause local tissue damage, fibrotic scarring and the
formation of characteristic skip lesions. Macrophage activation leads to the
formation of non-caseating granulomas in CD Th1 = granulomas -Increased secretion
of IL-4 and IL-13 is the main underlying mechanism of UC.
What are the microscopic morphologic features of Crohn's Disease? {{c1::
Noncaseating granulomas Lymphoid aggregates}}
What are the unique extra-intestinal manifestations of Crohn's Disease? {{c1::
Migratory polyarthritis (large joints) Kidney stones (CaOx)}} malabsorption of
B12 & folate (pernicious anemia) is more common in Crohn's (primarily affects
ileum), but UC can infrequently reach the ileum and cause this too
{{c1::Sulfasalazine (5-aminosalicylic acid)}} is an effective anti-inflammatory
drug in the treatment of ulcerative colitis because it is not active until it
reaches the colon mesalamine is also a 5-Aminosalicylic acid drug
What are the side effects of Sulfasalazine (5-aminosalicylic acid)? {{c1:: GI upset
Sulfa allergy Oligospermia }} Mesalamine is 5-ASA alone → give to patients with UC
who have sulfa allergy
Chronic Autoimmune Gastritis is caused by {{c1::CD4+ T cells}} attacking parietal
cells in the body and fundus of the stomach T-cells, not B-cell antibodies to
IF, are the primary cause of pernicious anemia. ↑ risk of pernicious anemia due to
lack of B12 absorption secondary to loss of IF (from parietal cells)
What is the classic CT scan finding in Chronic pancreatitis? {{c1::calcification of
pancreas}}
What are the rare (non cancerous) complications of Chronic Pancreatitis? {{c1::
Splenic vein thrombosis Pancreatic insufficiency}}
{{c1::BRCA1 & BRCA2}} are tumor suppresor genes that code for DNA repair proteins
associated with breast, ovarian, and pancreatic cancer BRCA1 & BRCA2 mutations
with pancreatic cancer are commonly seen in Ashkenazi Jews
What two tumor markers can be measured in the serum to detect Pancreatic
Adenocarcinoma? {{c1:: CA 19-9 CEA}}
What genes are involved in the pathogenesis of pancreatic cancer? (4) {{c1:: K-RAS
(12p) BRCA2 CDKN2A DPC4/SMAD4 (18q)}} K-RAS = oncogene, others = tumor supp. K-
RAS → GTPase BRCA2 → DNA repair protein CDKN2A → p16, blocks G1 → S phase DPC4 →
Deleted in Pancreatic Cancer
Where do most acquired diverticula commonly occur? (tissue-level) {{c1::where vasa
recta perforate muscularis externa}}
{{c1::Diverticulosis}} is the presence of many diverticuli in the GI tract, usually
in the sigmoid colon caused by straining to pass stool (↑ pressure & wall
stress) as well as low fiber diets.
{{c1::Surgical Adhesions}} are the most common cause of small bowel obstruction
can lead to infertility in women
"{{c1::Intussusception}} is ""telescoping"" of a promixal bowel segment into a
distal segment, commonly at the ileocecal junction, causing ""currant jelly""
stools bleeding" mostly occurs in children < 1 year
What are the three most common lead points causing intussusception? {{c1:: Meckel's
diverticulum Lymphoid hyperplasia Tumors (adults)}} Rarely due to Henoch-
Schonlein Purpura or Rotavirus vaccine
What are the classic imaging findings of a volvulus at the sigmoid colon? Dilated
{{c1::sigmoid::GI part?}} Airless {{c1::rectum::GI part?}}
Hirschsprung's Disease is congenital megacolon caused by lack of nerve plexuses in
the distal colon due to {{c1::failure of neural crest cell migration}} presents
with bilious vomiting, failure to pass meconium, abdominal distention
{{c1::Rectal suction biopsy}} is the gold standard for diagnosing Hirschsprung's
Disease - Rectum always involved - suction needed to biopsy submucosa (cuz
there arent any ganglion cells in the mucosa in the first place, duh)
What is the classic x-ray finding of Necrotizing Enterocolitis? {{c1::Pneumatosis
intestinalis}} air in bowel wall from perforation of necrotic intestinal mucosa.
Hard AF to actually see
{{c1::Angiodysplasia}} is a pathology of abberant blood vessels in the GI tract
caused by high wall stress leading to lower GI bleeding old people →
constipation → ↑ wall stress. most common in cecum & right sided colon
{{c1::Hereditary Hemorrhagic Telangiectasia}} is an autosomal dominant small-vessel
vasculitis that results in telangiectasias throughout the GI tract (nose → rectum),
GI bleeds, and iron deficiency """Osler-Weber-Rendu syndrome"" was a stupid
name anyway, can rarely lead to AVMs (brain)"
What are the side effects of aluminum hydroxide antacids? {{c1:: Constipation
Hypophosphatemia}}
What are the side effects of magnesium hydroxide antacids? {{c1:: Diarrhea
(osmotic) Hypermagnesemia (hypotension, cardiac arrest)}}
What are the two clinical uses for Bismuth Salicylate & Sucralfate? {{c1:: H.
Pylori ulcers Traveler's diarrhea}} can form black stool (not a problem)
"What are two ""stimulant"" laxatives that work by stimulating enteric nervous
system to increase GI motility? {{c1:: Senna Bisacodyl}}" can cause melanosis coli
What laxative works as a stool softener by osmotically drawing water into stool?
{{c1::Docusate}}
{{c1::Ondansetron}} is a 5-HT3 receptor antagonist given to control vomiting in
cancer patients can lead to seratonin syndrome and QT prolongation & Torsades de
Pointes
What classes of drugs can cause Torsades de pointes? {{c1:: antiArrhythmics (IA,
III) antiBiotics (macros, quinolones) anti-Cy-chotics (haloperidol) antiDepressants
(TCAs) antiEmetics (ondansetron)}} ABCDE
What are three important contraindications to Metoclopramide? {{c1:: Seizure
disorder Parkinson's Bowel obstruction}} D2 antagonist → same side effects as
typical antipsychotics
{{c1::Theca}} cells in the ovarian follicle convert cholesterol into
androstenedione stimulated by LH via a cAMP 2nd messenger system
{{c1::Granulosa}} cells in the ovarian follicle convert androstenedione into
estradiol stimulated by FSH & also produce inhibin to ↓ FSH
{{c1::Mittelschmerz}} is transient mid-cycle ovulatory pain classically associated
with peritoneal irritation (eg, follicular swelling/rupture, fallopian tube
contraction) can mimic appendicitis
Menstruation occurs 14 days after ovulation when the corpus luteum degrades and
{{c1::progesterone}} levels decline
If fertilization occurs, the embryo will make {{c1::human chorionic gonadotropin
(hCG)}} which mantains the corpus luteum & progesterone production opposite of
menstruation. progesterone mantains ↓↓ LH/FSH
{{c1::Estrogen}} stimulates the endometrial proliferative phase after menstruation
 endometrial thickness increases (>10x)
{{c1::Progesterone}} stimulates the secretory phase of the uterine cycle after
ovulation by inhibiting endometrial proliferation
Mullerian Agenesis is a cause of primary amenorrhea due to the absence of
{{c1::upper vagina +/ uterus}} "Normal female (46 XX) with primary amenorrhea,
short vagina, normal ovaries, hormone levels, and secondary sexual development
(breast, hair) (also called ""Mayer-Rokitansky-Kuster-Hauser syndrome"", aka the
2nd worst name for a disease, after pseudopseudohypoparathyroidism)"
Elevated levels of {{c1::FSH}} are an early finding in women who are approaching
menopause loss of inhibin production from follicles
What are the clinical features of polycystic ovarian syndrome? {{c1:: Infertility
Acne Amenorrhea Hirsutism (facial hair) Obese females Bilateral follicular cysts }}
I Abhor And Hate O.B.
What are the pharmaceutical treatments for PCOS? {{c1:: OCPs Spironolactone
Metformin/TZDs Ketoconazole Clomiphene}} weight loss is #1 tho
What are the complications/risks of PCOS? (2) {{c1:: Diabetes Endometrial & Ovarian
cancer}} Endometrial cancer → unnoposed estrogen (↓ progesterone) increases risk
of endometrial hyperplasia
{{c1::Finasteride}} is a drug that blocks the conversion of testosterone → DHT by
inhibiting 5-a-reductase used to treat BPH & hair loss in men side effect:
8====D ~~~~ → 8==D~
{{c1::Aromatase}} is an enzyme in fat & Leydig cells that converts testosterone →
estradiol Aromatase inhibitors: anastrazole, letrozole, exemastane. Used for ER+
breast cancer
How does testosterone affect hematocrit/RBC count? {{c1::↑↑ (polycythemia)}} low T
can cause anemia; if a teen/young adult athlete or bodybuilder presents with ↑ Hct
+ normal platelets & WBCs = they're juicin
What are the three secretions of Sertoli cells and what are their functions? {{c1::
inhibin B → inhibit FSH AndroBP → maintain local levels of test MIF → suppress
paramesonephric ducts}} sum notes: - FSH stimulates Sertoli → neg feedback -
testicle test is 100x peripheral due to ABP - MIF = mullerian inhibitory factor =
AMH
What is the key risk factor for Acute Endometritis? {{c1::C-section}} Caused by
retained products of conception (placental/fetal tissue). Most often S. aureus, E.
coli, or gram (-) rods
What are the three causes of chronic endometritis? {{c1:: IUDs PID (chlamydia or
gonorrhea) Tuberculosis}} Will show plasma cells on biopsy. Actinomyces is
associated with IUD infections.
What is the histological hallmark of chronic endometritis on biopsy? {{c1::plasma
cells}} biopsy often done because of unexplained infertility → plasma cells
indicate chronic inflammation
{{c1::Endometrial Polyps}} are benign exophytic projections in the endometrium
composed of hyperplastic stromal tissue that can present as painless uterine
bleeding common near menopause → unnoposed estrogen → estrogen causes
endometrial proliferation
{{c1::Tamoxifen}} is a SERM that can lead to endometrial polyps and cancer
What are the most common locations for Endometriosis? (ectopic endometrial tissue)
{{c1:: pelvic peritoneum ovaries uterosacral ligaments rectovaginal septum}}
Endometriosis causes blood to POUR
What are the 4 theories describing the pathogenesis of Endometriosis? {{c1::
Retrograde flow Metastasis Metaplasia Stem Cells}}
{{c1::Cyclic pevlic pain}} is the classic symptom of endometriosis presents
with pain depending on the site of tissue: - dyspareunia → pain from sex -
dyschezia → pain with pooping - dysuria
How may the uterus appear on the physical exam in Endometriosis? {{c1:: Normal
sized and possibly retroverted uterus}} Adenomyosis will present similarly with
enlarged uterus
A chocolate (blood-filled) cyst on the ovaries is classically associated with
{{c1::endometriosis::disease}}
What are the pharmaceutical treatments for endometriosis? (4) {{c1:: NSAIDs OCPs
(progestin) Leuprolide (GnRH agonist) Danazol (steroid)}}
Squamous Cell Carcinoma of the vagina is a rare malignancy almost always secondary
to what two pathologies? {{c1:: HPV Cervical Squamous Cell Carcinoma}} often an
extension of Cervical SCC
The lower vagina is derived from the {{c1::urogenital sinus}} and drains into the
{{c1::inguinal}} lymph nodes
Clear Cell Carcinoma of the vagina (or cervix) is associated with maternal
{{c1::diethylstillbestrol (DES)}} usage
{{c1::Vaginal Adenosis}} is the presence of columnar epithelium in the vagina
(should be entirely squamous) associated with DES exposure in utero → can lead to
clear cell carcinoma
{{c1::Sarcoma Botryoides}} is a rare vaginal tumor of young girls that is derived
from embryonal rhabdomyoblasts (immature muscle cells)
How does Sarcoma botryoides present on physical exam? {{c1::clear, grape-like mass
growing from vagina}} ↓ nsfw ↓
Sarcoma Botryoides (and all other rhabdomyosarcomas) stain positive for
{{c1::Desmin}} Intermediate filament in muscle Z-disc
Cervical neoplasias arise from the basal layer of the {{c1::squamoucolumnar
junction (transitional zone)}} of the cervix
What are the risk factors for Cervical cancer? {{c1:: HPV Multiple sexual partners
(↑HPV) Sex at young age (↑ HPV) Immunodeficiency Smoking }}HPV 16 & 18 → 16 sex
partners by the time you're 18 ↑ risk of HPV cancer
Describe the steps in oncogenesis from the E6 and E7 genes of HPV E6: {{c1::p53}}
inhibition → dysplasia E7: {{c1::Rb}} inhibition → {{c1::E2F}} activation →
dysplasia
An endometrial {{c1::Leiomyoma (fibroid)}} is a benign tumor of the myometrium in
pre-menopausal women
What is the histologic appearance of an endometrial Leiomyoma (fibroid)?
{{c1::whorled pattern of smooth muscle}}
{{c1::Endometrial hyperplasia}} is abnormal endometrial gland proliferation caused
by excess and unopposed estrogen stimulation
{{c1::Atypical + complex}} histological architecture in endometrial hyperplasia
significantly increases the risk of squamous cell carcinoma transformation
complex + atypical > atypical > complex > simple
What is the classic presenation of Endometrial Carcinoma? {{c1::post-menopausal
woman with abnormal uterine bleeding}}
{{c1::Endometriod (type I)::subtype}} Endometrial Carcinoma is due to estrogen-
dependent hyperplasia most common, histology resembles endometrium. Usually
presents ~ 50-60, while serous subtype classically presents at 70+
{{c1::Serous Subtype (type II)::subtype}} Endometrial Carcinoma is due to estrogen-
independent hyperplasia
The most frequently altered gene in the serous subtype of endometrial carcinoma is
{{c1::p53 tumor suppressor}} Serous = serious = worse prognosis
What is the most common non-colon malignancy in females with Lynch Syndrome
(HNPCC)? {{c1::Endometrial carcinoma}}
What are the two layers of breast epithelium? Inner: {{c1::luminal epithelial cells
(secrete milk)}} Outer: {{c1::Myoepithelial cells (contractile)}}
Myoepithelial cells contract in response to oxytocin
{{c1::Estrogen::hormone}} primarily acts on breast ducts to increase breast size in
puberty, menstruation, and pregnancy ↑ prolactin in pregnancy also makes boobs
grow
During pregnancy {{c1::estrogen}} and {{c1::progesterone}} inhibit lactation
Prolactin rises during pregnancy but lactation suppressed by E & P. Fall in
hormones after delivery → milk production occurs.
{{c1::Epithelial Hyperplasia}} is a proliferative breast tissue change of ↑
luminal/myoepithelial cells in the terminal ducts or lobules ↑ risk of
carcinoma with atypical cells
{{c1::Sclerosing adenosis}} is a proliferative breast disorder characterized by
dense stroma, increased number of compressed acini, and calcifications
How do Intraductal Papillomas present? {{c1::bloody/serous nipple discharge}}
{{c1::Fibroadenoma}} is a common benign stromal breast tumor in young women
characterized by mobile masses of fibrous and glandular tissue well-defined &
hypoechoic on Ultrasound
{{c1::Phyllodes Tumor}} is a benign stromal breast tumor in older women
characterized by by leaf-like growths of stroma covered by epithelial tissue
Mammary Duct Ectasia is a benign inflammatory condition of the breast in older,
multiparous women characterized by {{c1::distension (ectasia) of subareolar ducts}}
What is the characteristic presentation of Mammary Duct Ectasia? {{c1::older woman
with breast mass and thick, white discharge}}
Fat Necrosis is a benign inflammatory breast pathology caused by {{c1::trauma
(surgery, sports)}}
Lactational mastitis (trauma, cracks on nipple) is a consequence of breastfeeding
that can result in bacterial infection with {{c1::Staph Aureus::pathogen}}
How is Lactational Mastitis treated? {{c1:: dicloxacillin or cephalexin AND
continue breastfeeding }}
Periductal Mastitis is inflammation of the {{c1::subareolar}} ducts and is strongly
associated with {{c1::smoking}}
Periductal Mastitis is caused by ductal metaplasia from {{c1::cuboidal}} to
{{c1::squamous}} cells, which obstructs the duct causing a red, tender, warm
periductal mass often secondary to Infx → give antibiotics, sometimes requires
I&D
What are two non-malignant breast pathologies that can cause micro-calcifications
on breast mammography? {{c1:: Sclerosing adenosis Fat necrosis}}
{{c1::Ductal Carcinoma in Situ}} is a malignant growth of epithelial cells of the
TDLU that fills the ductal lumen and is limited by intact basement membrane "↓
Cribiform DCIS w/ ""cookie cutter"" pattern ↓"
Comedocarcinoma (subtype of DCIS) is characterized by {{c1::central necrosis}} of
ductal carcinoma on biopsy higher risk than cribiform (cookie-cutter)
{{c1::Paget disease}} is the presentation of red, eczematous patches on the nipple
due to underlying breast malignancy may cause bloody nipple discharge
Lobular Carcinoma in Situ is proliferation of cells in TDLU that is distinguished
from DCIS by {{c1::discohesive growth::patholigcal process}} caused by loss of
{{c1::E-cadherin (adhesion protein)::cellular structure}} DCIS (A) vs LCIS (B)
Neither LCIS or DCIS usually lead to breast masses; how are they detected? DCIS:
{{c1::micro-calcifications on mammogram}} LCIS: {{c1::incindental finding on
biopsy}} LCIS is often bilateral and multifocal → risk factor for later invasive
carcinoma in both breasts
What is the unique presentation of the Inflammatory subtype of Invasive Ductal
Carcinoma? {{c1::Peau d'orange → breast skin looks like an orange peel}}
Infammatory Breast Cancer presents with Peau d'orange due to invasion of
{{c1::dermal lymphatic vessels}} blocked lymphatic drainage → swollen breast
(mimics infection) → high grade, poor prognosis
What class of receptor does HER-2 code for? {{c1::cell surface tyrosine kinase
receptor (EGF receptor)}} important because it differs from the other breast
cancer markers, ER & PR (intracellular receptors), which is helpful for selecting
medical therapy (Trastazumab for HER-2)
ER+ and PR+ breast tumors can be treated with {{c1::Tamoxifen (SERM)}}
HER-2 + breast tumors can be treated with {{c1::Trastuzumab}}
BRCA1 & BRCA2 are tumor suppressor genes that code for {{c1::DNA repair
proteins::product}}
{{c1::BRCA::gene}} mutations are the classic example of incomplete penetrance
What are the two key associations of Male Breast Cancer? {{c1:: Klinefelter
syndrome BRCA2 mutations}} Klinefelter (XXY) causes feminization so a female
cancer makes sense
What is the formula for drug Clearance with Vd? {{c1::Cx = Vd x Ke (elimination
constant)}} often used to calculate Ke : (Cx/Vd)
What is the formula for drug Half Life (t1/2)? {{c1:: t1/2 = (0.7 x Vd) clearance}}
What is the formula for drug Maintainance Dose? {{c1::Cp x CL x t F}}
What is the formula for drug Loading Dose? {{c1::Cp x Vd F}} only divide by F
if bioavailability < 100%
What are the two roles of the Sonic Hedgehog Gene (SHH)? {{c1:: Axial CNS
development Limb development }}
Wnt-7a is an embryonic gene produced in the AER that activates {{c1::LMX-1}} to
stimulate dorsal mesoderm development Ventrally, Engrailed1 represses Wnt-7
What 4 epileptic drugs are the strongest teratogens? {{c1::Valproic acid (↑↑ NT
defects) >> Phenytoin, Phenobarbital, Carbamazepine}}
What classes of chemotherapy agents are teratogens that can cause spontaneous
abortion and missing digits? {{c1:: Alkylating agents Antimetabolites}}
Alkylating agents → Busulfan, Cylcophosphamide (ifosfamide), Nitrosoureas
Antimetabolites → Azathioprine, 6-MCP, Cladribine, Cytarabine, 5-FU, Methotrexate
What is the main teratogenic effect of Methotrexate? {{c1::Neural tube defects (↓
foltate)}}
What are the teratogenic effects of Warfarin? {{c1:: Spontaneous Abortion Fetal
Hemorrhage Optic Atrophy Warfarin Embryopathy}} Stop Fucking On Warfarin
What are the teratogenic effects of Methimazole? {{c1:: Neonatal hypothyroidism
Aplasia Cutis }}
What drugs can teratogenically displace bilirubin from albumin, causing
kernicterus? {{c1::Sulfonamides}}
What historical drug used to treat AML caused teratogenic limb defects (phocomelia,
micromelia)? {{c1::Thalidomide}} "micromelia → short ""flapper"" limbs"
What are the three facial features of fetal alcohol syndrome that accompany
intellectual disability? {{c1:: smooth philtrum short palpebral fissures thin
vermillion border}} also ASD, VSD, ToF
What are the two teratogenic chemicals in cigarette smoke and what is their
teratogenic mechanism? {{c1:: nicotine → vasoconstriction CO → impaired O2
delivery}}
{{c1::Methylmercury}} is a teratogenic neurotoxin found in swordfish, shark,
tilefish, and king mackerel
Which inborn error of metabolism causes similar teratogenic effects as fetal
alcohol syndrome? {{c1::Phenylketonuria (PKU)}}
Which cranial nerves are derived from each pharyngeal arch? 1 → {{c1::V2 and V3}} 2
→ {{c1::VII}} 3 → {{c1::IX}} 4 → {{c1::X (superior laryngeal branch)}} 6 → {{c1::X
(recurrent laryngeal branch)}} Chew, smile, swallow stylishly, simply swallow,
speak
What is the muscular derivate of the Third Pharyngeal Arch? {{c1::Stylopharyngeus}}
which is innervated by the glossopharyngeal nerve
What are the muscular derivates of the Sixth Pharyngeal Arch? {{c1::instrinsic
laryngeal muscles except cricothyroid}} Larynx = 6 letters = 6th arch
Treacher Collins Syndrome is due to absent {{c1::neural crest cell}} migration to
the {{c1::first}} pharyngeal arch
"{{c1::Li-Fraumeni Syndrome}} is an autosomal dominant example of the ""two-hit""
hypothesis that results in multiple malignancies at an early age via loss of TP53
tumor supressor gene" SBLA → Sarcoma, Breast, Leukemia, Adrenal
McCune-Albright Syndrome is the classic example of genetic {{c1::mosaicism}}
What are two classic examples of diseases that display genetic Allelic
Heterogeneity? {{c1:: B-thalassemia Cystic Fibrosis}}
Cleft Palate is due to the failure of what embryonic structures to fuse?
{{c1::lateral palatal shelves (processes)}}
What are the derivatives of the 2nd through 4th pharyngeal Clefts? {{c1::Cervical
sinus}} should obliterate, but if not → branchial cleft cyst → most commonly
2nd cleft cyst below angle of mandible, anterior to SCM
In females, the paramesonephric ducts give rise to what structures? {{c1::
Fallopian tubes Uterus Upper 2/3 vagina}} due to absence of MIF (Sertoli cells) and
androgens (Leydig cells)
{{c1::Septate Uterus}} is the most common female uterine (Mullerian) duct
abnormality, caused by incomplete resorption of the setpum treatment: Septoplasty
{{c1::Unicornuate Uterus}} is a Uterine abnormality where the uterus only connects
to one ovary
{{c1::Bicornuate Uterus}} is a Uterine abnormality caused by incomplete fusion of
the Mullerian ducts <3 shaped uterus
Hypospadias is a congenital anomaly causing a ventral opening of the male urethra
due to failure of the {{c1::urethral folds}} to close
Epispadias is a congenital anomaly causing a dorsal opening of the male urethra due
to abnormal position/formation of the {{c1::genital tubercle }}
In utero, primary oocytes are arrested at which stage of the cell cycle until
puberty? {{c1::prophase of meiosis I}}
Starting with puberty, secondary oocytes are arrested in which stage of the cell
cycle? (degenerate if fertilization doesnt occur) {{c1::Metaphase of Meiosis II}}
if fertilization occurs, they complete meiosis II and form ovum (1n, 1c)
The {{c1::decidua basalis}} is the altered endometrium at the site of implantation
in the uterus that interacts with trophoblasts to create the placenta
{{c1::Syncytiotrophoblast}} is the outer layer of the fetal placenta that forms
villi for maternal blood exchange and synthesizes hCG
{{c1::Cytotrophoblast}} is the inner layer of the fetal trophoblast that
proliferates and secretes proteolytic enzymes to invade the syncytiotrophoblast
What are the 3 blood vessels in the umbilical cord and what are their functions?
{{c1:: 2 Umbilical Arteries → deoxygenated fetal blood to placenta 1 Umbilical Vein
→ oxygenated placental blood to fetus}} also...
The {{c1::urachus}} is a remnant of the allantois the connects the fetal bladder to
the umbilicus then obliterates to become the {{c1::median umbilical ligament}} in
adults EASY PATH CORRELATIONS: - Patent Urachus → urine discharge from
umbilicus - Urachal Cyst → partial failure to obliterate, can lead to infection &
bladder adenocarcinoma - Vesicourachal Diverticulum → slight failure to obliterate;
outpouching of bladder
What is the main mechanism by which the fetus is protected from maternal immunity
during pregnancy? {{c1::Trophoblasts DO NOT express MHC class I antigens}} also,
placenta secretions block immune response
How many chorions and amnions will be present in monozygotic twins who split during
days 1-3? {{c1:: 2 chorion 2 amnion}} may have two placentas
How many chorions and amnions will be present in monozygotic twins who split during
days 4-8? {{c1:: 1 chorion 2 amnion}} most common (75%)
How many chorions and amnions will be present in monozygotic twins who split during
days 8-12? {{c1:: 1 chorion 1 amnion}} chorion and amnion are already under
development
During pregnancy, syncytiotrophoblasts secrete {{c1::human placental lactogen}} to
block the effects of insulin & deliver more nutrients to the fetus also called
chorionic somatomammotropin
Supine Hypotension during pregnancy is caused the the baby compressing the
{{c1::IVC}} leading to a decrease in preload fall in CO, can cause reflex
tachycardia
What are two B2 agonists that relax the uterus to suppress contractions in women
during labor? {{c1:: Terbutaline Ritodrine}}
What two drugs are used to terminate pregnancy? {{c1:: Mifepristone Misoprostol}}
What are the 3 signs of ectopic pregnancy? {{c1:: lower than expected rise in hCG
amenorrhea pain (sudden, lower abdominal)}} often mistaken for appendicitis
What drug is used to terminate an ectopic pregnancy? {{c1::Methotrexate}}
Intraventricular Hemorrhage is a complication of low birth weight caused by poor
autoregulation of blood flow in the {{c1::germinal matrix}}hemorrhage into Lateral
ventricles → hypotonia, loss of spontaneous movement, seizures, coma
What are the four drugs safe to use in the treatment of Gestational HTN? {{c1::
Hydralazine a-Methyldopa Labetalol Nifedipine}} Hypertensive Moms Love Nifedipine
Preeclampsia is caused by abnormal transformation of sprial arteries from
{{c1::small resistance vessels}} to large capitance vessels, which leads to
endothelial dysfunction, vasoconstriction, and ischemia spiral arteries remain
as small, resistance vessels. pathogenesis:
What is the characteristic finding of placental biopsy in preeclampsia?
{{c1::Fibrinoid Necrosis (vessel walls thick & pink)}}
What are the diagnostic criteria for the clinical diagnosis of preeclampsia?
{{c1::New onset HTN > 20 weeks gestation with proteinuria or end-organ damage}}
"often presents with EDEMA (not ""diagnostic"", but always present)"
What are the treatments for preeclampsia and eclamplsia? {{c1:: Anti-hypertensives
(HMLN) IV Magnesium Sulfate (seizures) DELIVER THE BABY}}
What are the components of HELLP Syndrome (severe preeclampsia)? {{c1:: Hemolysis
Elevated Liver enzymes Low Platelets}}
What kind of anemia is seen in HELLP Syndrome? {{c1::Microangiopathic Hemolytic
Anemia}}
{{c1::Penile Fracture}} is a rupture of the tunica albuginea & corpus cavernosum
due to trauma My condolences
What disease can cause ischemic priapism? {{c1::Sickle cell anemia}} sickled RBCs
block venous drainage of corpus cavernosum
What are the risk factors for squamous cell carcinoma of the penis? {{c1::
uncircumcised penis HPV (16,18) Smoking}}
How does Placental Abruption (abruptio placentae) typically present? {{c1::Abrupt
painful bleeding in third trimester}} can also have abdominal pain, back pain,
and uterine contractions
{{c1::Placenta Previa}} is a placental complication in pregnancy caused by
placental attatchment to the lower uterus over the cervical os
Velamentous Umbilic Cords insert into the fetal membranes, which leaves the fetal
vessels exposed to possible rupture because {{c1::there is no protection from
Wharton's jelly }}
{{c1::Vasa Previa}} is a placental complication where the fetal blood vessels lie
in membranes near cervical os
The biggest risk factor for abnormal placental attachment (accreta, increta,
percreta) is {{c1::prior C-section}} also placenta previa, prior surgery
(inflammation)
What are the four causes of Postpartum Hemorrhage? {{c1:: 4 T's: Tone (uterine
atony) Trauma (lacerations, incisions, uterine rupt) Thrombin (coagulopathy) Tissue
(retained products of conception)}}
What are the key features of the first and second phases of Amniotic Fluid
Embolism? {{c1:: I: Respiratory distress, ↓ O2, hypotension II: Bleeding (DIC,
massive hemorrhage)}} seizures also often occur
{{c1::Hydatidiform Mole}} is a benign gestational neoplasm comprised of cystic
swelling of trophoblastic chorionic villi Dont forget; Choriocarcinoma → no villi
involvement
"How will a Hydatidiform Mole appear on pathology specimen and ultrasound? path →
{{c1::cluster of grapes}} U.S. → {{c1::""snowstorm appearance""}}"
What are the possible karyotypes for a Complete Hydatidiform mole? {{c1::46XX; 46
XY}} "fertilization of an ""empty"" egg → all chromosomes are paternal"
Complete Hydatidiform Moles will be p57-{{c1::negative}} on immunostaining p57
only expressed by maternal chromosomes → no maternal chromosomes in a complete mole
→ partial moles p57-positive
Which type of Hydatidiform Mole will have fetal tissue present? {{c1::Partial
mole}} Partial moles are caused by 2 sperm fertilizing an oocyte with egg.
maternal chromosomes needed for fetal tissue
What karyotypes are present in a Partial Mole? {{c1::69 XXX; 69 XXY >>> 69 XYY}}
one Normal egg is fertilized by Two sperm
How do Hydatidiform Moles present? {{c1:: Painless vaginal bleeding Uterine
enlargement more than expected Pelvic pressure/pain}}
What are the 4 hCG-mediated sequelae of Hydatidiform moles? (hCG >100k) {{c1::
Hyperemesis gravidarum Ovarian theca lutein cysts Early preeclampsia
Hyperthyroidism}} HOEs have High hCG
What are the treatments for Molar Pregnancy? (1 procedure, 2 drugs) {{c1:: Uterine
suction curettage Methotrexate or Actinomycin D}} Methotrexate or Actinomycin D
are only for high-risk patients with potential to develop choriocarcinoma (complete
moles)
{{c1::Choriocarcinoma}} is a rare gestational malignancy of trophoblastic tissue
that can follow a molar pregnancy or a normal pregnancy You must monitor hCG
levels after molar pregnancy. It should fall after treatment, but if it plateaus →
persistent disease (possible choriocarcinoma)
While hydatidiform moles and Choriocarcinoma present similarly, the key clinical
symptom of Choriocarcinoma is {{c1::hemoptysis}} others: ↑hCG, vaginal
bleeding, theca lutein cysts, hyperthyroidism
What chemotherapy agents are used to treat Choriocarcinoma? {{c1::Methotrexate &
Actinomycin D}} non-gestational choriocarcinoma is much more difficult to
treat/cure
What are the signs and symptoms of congenital Varicella Zoster Virus in newborns?
{{c1:: Microcephaly, hydrocephalus Dermatomal scars Occular problems (cataracts,
nystagmus) Limb atrophy & hypoplasia}} Micro Dudes Often Limp leads to mental
retardation long term (VZV not included in FA ToRCHeS section)
Which two ToRCHeS infections often result in hyrops fetalis? {{c1:: Parvovirus B19
Syphillis}} Parvovirus B19 infects RBC progenitors → fetus → expanding RBC volume,
shortened RBC life, immature immune systems → death
"The cause of the ""blueberry muffin"" rash seen in ToRCH infections is
{{c1::extramedullary hematopoeis}}"
"What 3 ToRCHeS infections can cause a ""blueberry muffin"" rash? {{c1:: Rubella
Toxoplasma CMV}}"
What are the two classic symptoms and findings specific to congenital CMV
infections? {{c1:: Sensorineural hearing loss Periventricular intracranial
calcifications}} less specific → blueberry muffin rash, seizures
Which type of ovarian cyst may delay menstruation due to continued production of
progesterone? {{c1::Corpus Luteal Cyst}}
Which type of ovarian cyst is associated with high B-hCG levels? {{c1::Theca-lutein
cyst}} Twins, molar pregnancy, choriocarcinoma
Ovarian surface epithelium is a single layer of simple cuboidal cells derived from
{{c1::coelomic epithelium::embryological structure}}
Most epithelial ovarian tumors present as an adenexal mass; what are four rare,
acute symptoms of these tumors? {{c1:: Bowel obstruction Ascites Pleural Effusion
Venous Thromboembolism}}
{{c1::Serous Cystadenomas}} are benign ovarian epithelial tumors, which are often
bilateral cysts with watery fluid, lined by a single layer of fallopian tube-like
cells Serous Cystadenocarcinoma is the malignant version. Both are the most common
benign & malignant ovarian tumors
What are the two key histological findings in an ovarian Serous Cystadenocarcinoma?
{{c1:: Growth of fallopian tube-like epithelial layer Psammoma bodies}}
Which type of epithelial ovarian tumors are characterized by many small
cavities/recesses (multiloculated) and mucus secreting epithelium? {{c1::Mucinous
cystadenoma & cystadenocarcinoma}} Goblet cells (or goblet-appearing cells?) in
the ovary → mucinous cystadenoma/carcinoma
Pseudomyxoma peritonei is an intraperitoneal accumulation of mucinous material from
which two types of cancers? {{c1:: Ovarian mucinous cystadenocarcinoma & Appenix
tumors}} """jelly belly"", ""mucinous ascites"" → may cause bowel obstruction"
"{{c1::Brenner Tumor}} is a rare, benign epithelial ovarian tumor that contains
bladder transitional cells and ""Coffee bean"" nuclei on H&E stain"
What four things Decrease ↓ the risk for ovarian neoplasms? {{c1:: Tubal ligation
Previous pregnancies Breastfeeding OCPs}} More ovulation = ↑ risk
What serum tumor marker is useful to monitor epithelial ovarian cancers? {{c1::CA-
125}}
What are the risk factors for ovarian neoplasms? (7) {{c1:: Old age Indertility
Endometriosis PCOS Family history BRCA 1/2 Lynch Syndrome}}more menstruation =
higher risk
{{c1::Granulosa Cell Tumors}} are malignant stromal ovarian neoplasms that secrete
estrogen and present with postmenopausal bleeding and breast tenderness
usually presents ~50-54; juvenile type (< 8) causes precocious puberty
{{c1::Fibroma}} is a benign stromal ovarian neoplasm that is a solid, white tumor
with no hormone activity composed of bundles of spindle-shaped fibroblasts
(wouldve made the card too easy)
What extra-ovarian clinical condition is associated with ovarian fibromas?
{{c1::Meigs Syndrome → ovarian fibroma, ascites, pleural effusion}}
{{c1::Thecoma}} is a stromal ovarian tumor that usually coexists with fibromas and
presents very similarly to ovarian granulosa cell tumors
{{c1::Mature Cystic Teratoma (Dermoid Cyst)}} is a benign germ-cell ovarian tumor
that containts hair, squamous cells, tooth-like material, and sebaceous (oily)
material most common ovarian tumor in women 10-30 years old
Ovarian Dermoid Cysts (MCTs) are usually removed surgically to avoid what 3
complications? {{c1:: Torsion Rupture → Peritonitis Sqaumous Cell Carcinoma}}
Struma Ovarii is a subtype of teratoma that contains mostly {{c1::thyroid tissue}}
hyperthyroidism + ovarian mass = Struma Ovarii
Immature Teratomas (malignant ovarian germ cell tumor) contain what two
characteristic types of tissue? {{c1:: Immature fetal tissue Neuroectoderm}} young
women < 20
What three enymes/hormones are tumor markers for ovarian Dysgerminomas? {{c1:: LDH
B-hCG ALP (placental)}} Malignant; germ-cell origin; adolescents
"What is the histologic appearance of ovarian Dysgerminomas? (and male seminomas)
{{c1::""fried egg"" → large cells with clear cytoplasm and central nuclei}}"
What tumor marker is elevated in Yolk Sac (Endodermal Sinus) Tumors? {{c1::AFP}}
How do ovarian & testicular Yolk Sac tumors typically present? {{c1::abdominal pain
in children less than 3 years old}} Yolk Sac tumors are large, solid masses with
necrosis and hemorrhage ↓. Would def hurt.
What is the histological hallmark of Yolk Sac (Endodermal Sinus) Tumors?
{{c1::Schiller-Duval bodies → resemble primitive glomeruli}}
"The ""nutcracker effect"" is a cause of varicocele due to compression of the left
renal vein between which two arteries? {{c1::Aorta & SMA}}"
"How will the prostate feel on DRE in patients with acute prostatitis? {{c1::warm,
large, tender ""boggy""}}" Conversely, prostate cancer will cause discrete
nodules. For prostatis, think E. coli in older men; in younger men, think STDs
(Chlamydia, N. gonorrhea).
Which a1-blocker is preferentially given to treat BPH because it is uroselective
(a1A) and does not cause hypotension? {{c1::tamsulosin}}
What tumor markers/lab values are indicative of prostatic adenocarcinoma? {{c1::↑
total PSA; ↓ free PSA}} PSA will rise in BPH (4-10 ish), but PSA of 11+ is
suggestive of cancer
Prostate cancer commonly metastasizes to the spine and causes purely
{{c1::Osteoblastic}} lesions old man with back pain, ↑ ALP & ↑ PSA → think
prostate mets
What are the two medical treatments for prostate cancer? {{c1:: Flutamide
Leuprolide}}
What 4 conditions/diseases can cause primary male hypogonadism? {{c1:: Klinefelter
Myotonic dystrophy Swyer sydrome (gonadal dysgenesis) Mumps}} primary: ↑ LH; ↓
Test
{{c1::Asherman Syndrome}} is a cause of secondary amenorrhea in females due to
adhesions/fibrosis of the endometrium from uterine curettage
{{c1::Primary Ovarian Insufficiency (premature ovarian failure)}} is a disease of
hypergonadotrophic hypogonadism (↑FSH & LH, ↓ estrogen) that presents with clinical
features of menopause before age 40
{{c1::Functional Hypothalamic Amenorrhea}} is a common cause of secondary
amenorrhea in young women caused by decreased GnRH secretion due to stress, weight
loss, eating disorders "young woman who's stressed or works out too much and stops
having their period. ""She Works Out Too Much"" - MGMT"
What are the two key risk factors for testicular germ-cell tumors? {{c1::
Cryptorchidism Klinefelter Syndrome}}
{{c1::Seminomas}} are testicular germ-cell tumors that present as homogenous masses
with no hemorrhage or necrosis
What two lab values may be elevated in Seminomas? {{c1:: ALP (placental) B-hCG}}
{{c1::Embryonal Carcinoma}} is a testicular germ-cell tumor that presents as a
painful mass with hemorrhage and necrosis
Why do testicular Seminomas have a better prognosis than other testicular germ-cell
tumors? {{c1::Seminomas spread lymphatically (slow); Non-seminoma GCTs spread
hematogenously (fast)}}
{{c1::Leydig Cell Tumors}} are non germ-cell tumors of the testes that produce
androgens and estrogens
How do Leydig Cell Tumors of the testes appear grossly and histologically? Gross →
{{c1::golden brown (↑ lipids)}} Histo. → {{c1::Reinke Crystals}}
{{c1::Diffuse Large B-cell NHL::Lymphoma subtype}} is the most common cause of
testicular lymphoma Most common testicular cancer in Men > 60
Extragonadal GCTs most commonly arise where in children and adults? children →
{{c1::Sacrococcygeal & intracranial}} Adults → {{c1::Anterior mediastinum}}
Extragonadal GCTs are caused by {{c1::failure of germ cell migration}} early in
fetal development
{{c1::Ovotesticular DSD (true hermaphroditism)}} is a DSD where both ovarian and
testicular tissue is present 46XX > 46XY
What are the two causes of 46XX females to be born with ovaries and ambiguous
external genetalia? {{c1:: Congenital Adrenal Hyperplasia Gestational
Hyperandrogenism (weeks 7-12)}} - CAH → 21-a hydroxylase deficiency -
Hyperandrogenism → exogenous androgens (progestin), luteomas (secrete DHT & test),
aromatase deficiency
What are three causes of Gestational Hyperandrogenism which will lead to
virilization or ambiguous genitalia in 46XX female babies? {{c1:: Luteoma (secrete
DHT & test) Exogenous androgens (progestin) Placental Aromatase Deficiency}} mother
will develop hirsutism and virilization
What are the three common causes of 46 XY DSD? (testes present w/ ambiguous
genitalia) {{c1:: Gonadal dysgenesis 5-a Reductase deficiency Androgen
Insensitivity}} rarely, CAH & testosterone synthesis defects
Swyer Syndrome is a DSD of XY gonadal dysgenesis due to lack of {{c1::Sertoli
Cells}}
How will 5-a Reductase Deficiency present? {{c1::Developement of male genitalia in
phenotypic female at puberty due to ↑ testosterone}}
{{c1::Endothelins}} are proteins that are potent vasoconstrictors released by
endothelial cells near the site of damage to prevent bleeding
{{c1::Tissue Factor (Thromboplastin)}} is a glycoprotein constitutively expressed
in sub-endothelial cells that acts as the major activor of the coagulation system
when exposed by endothelial damage
Factor VIII circulates bound to {{c1::Von Willebrand Factor (vWF)}} to increase its
plasma half life. - both produced by endothelial cells (NOT liver) - vWF cleaved by
thrombin (VIII-vWF → VIIIa) in response to vascular injury
Both multicomponent complexes (intrinsic and extrinsic Xase) require what two
molecules to function? {{c1::Phospholipids & Calcium}}
Factor {{c1::XIII}} crosslinks fibrin to stabilize the fibrin plug and requires
{{c1::calcium}} as a co-factor
How does Factor XII lead to the production of bradykinin? {{c1::}}
Activated Protein C primarily inactivates which two clotting factors? {{c1::Va &
VIIIa}} In factor v (Leiden) mutations, Va is resistant to protein C
degradation, so a person with FVL mutation will have coagulopathy that does not
correct with adding protein c
Which clotting factors are activated by Vitamin K? {{c1::2, 7, 9, 10, protein C &
S}}
{{c1::Thrombopoetin (TPO)}} synthesized in the liver tiggers the production of
platelets from {{c1::megakaryocytes}}
Where is von Willebrand Factor (vWF) stored in endothelial cells and platelets
respectively? Platelets → {{c1::alpha granules}} Endothelial cells → {{c1::Weibel-
Palade bodies}}
Adhesion: vWF on subendothelial collagen binds to {{c1::GPIb}} receptor on
platelets
Platelet Aggregation: Activated platelets express {{c1::GPIIb/IIIa}} to bind to
fibrinogen or vWF
Which substances are secreted from Alpha Granules in activated platelets? {{c1::
Fibrinogen vWF Platelet factor 4}} Antibodies to PF4 are the cause of Heparin
induced Thrombocytopenia
What substances are released from the Dense Granules in activated platelets? {{c1::
ADP Calcium Seratonin}}
Elevated levels of {{c1::homocysteine::amino acid}} cause a hypercoagulable state
Nephrotic Syndromes cause a Hypercoagulable state due to loss of {{c1::Antithrombin
III (ATIII)}} in the urine
What is the cause of hypercoagulability in Factor V Leiden Mutations? {{c1::protein
C cant inactivate factor V}} Too much activated factor V promotes fibrin formation
= hypercoaguable state. PTT Will not correct when protein C is added to serum
Describe the mutation involved in the Factor V Leiden disease. (mutation; not
result) {{c1::DNA Point mutation: Guanine → Adenine at position 506}}
Describe the actual mutation in the Prothrombin Gene Mutation disease:
{{c1::Guanine → Adenine at Prothrombin 20210 nucleotide}} ↑ Prothrombin → ↑ Venous
clots
What are the three acquired causes of Antithrombin III Deficiency? {{c1:: Liver
disease (↓ production) Nephrotic syndrome (lost in urine) DIC (consumption)}}
classically presents as Herparin Resistance → high doses of heparin wont
increase PTT because heparin activate ATIII
Protein C deficiency classically presents as thrombosis of skin tissue following
{{c1::warfarin}} therapy Warfin ↓ Vit. K, which activates Protein C
What three autoantibodies are associated with Antiphospholipid Syndrome? {{c1::
Anti-cardiolipin Anti-B2 glycoprotein Lupus Anticoagulant}}
How are Hemophilias inherited? (A, B and C) A: {{c1::X-linked Recessive}} B:
{{c1::X-linked Recessive}} C: {{c1::Autosomal Recessive}}
All Hemophilias will result in {{c1::PTT}} prolongation Vitamin K deficiency
will also have ↑ PTT but also ↑ PT (hemophilias will have normal PT)
List which clotting factors are deficient in each of the hemophilias: A:
{{c1::VIII}} B: {{c1::IX}} C: {{c1::XI}} All intrinsic pathway.. Treat by
replacing deficient factor and desmopressin (dDAVP) for A
Hemophilia A is treated with factor VIII concentrate and {{c1::desmopressin}}
-ADH activation of the V2 receptor on vascular endothelium causes release of
von Willebrand factor (vWF) and factor VIII
{{c1::Aminocaproic Acid}} is a drug that inhibits plasminogen (plasmin) activation
to supplement treatment of hemophilias
{{c1::Cryoprecipitate}} is a component of thawed FFP that contains factor VIII,
fibrinogen, factor XIII, and vWF not used for hemophilia A anymore, but is still
used as fibrinogen source for DIC & massive trauma
{{c1::Prednisone}} can be used to treat Coagulation Factor Inhibiting antibodies
produced by malignancy, autoimmune, or post-partum Mixing Study will not correct
PTT with Clotting Factor inhibitor antibodies (mixing study will correct PTT with
hemophilia)
The most sensitive lab test to detect Vitamin K Deficiency is elevated
{{c1::PT/INR}} ↑ PTT may be present, but less sensitive → Extrinsic pathway
(PT/INR) is dependent on factor VII, which also has the shortest half-life.
What are the three stop codons? {{c1:: UAA UAG UGA}} Stop codons do not translate
into amino acids, so here's an example mRNA sequence & corresponding tRNA: 5' -CCA-
UUG-UAG- 3' 3' -GGU-AAC- 5'
What vessel(s) derive from the First Aortic Arch? {{c1::Maxillary artery (br. of
external carotid)}} 1st arch is maximal (maxilla, mm. of mastication)
What vessel(s) derive from the Second Aortic Arch? {{c1::Stapedial & Hyoid Artery}}
remember the 2nd pharngeal arch gives rise to stapedius muscle and part of
hyoid bone
What vessel(s) derive from the Third Aortic Arch? {{c1:: Common Carotid Prox.
internal Carotid}} Three C's
What vessel(s) are derived from the Fourth Aortic Arch? {{c1:: true Aortic Arch
prox right subclAviAn}} 4 → AA;AA
What vessel(s) are derived from the Sixth Aortic Arch? {{c1:: Pulmonary Arteries
Ductus Arteriosus}} Sex (6) in public is PDA
Glanzmann's Thrombasthenia is an autosomal recessive platelet disorder caused by
deficiency of {{c1::GPIIb/IIIa receptors}} Remember that with qualitative
platelet disorder, there is no thrombocytopenia (will have normal platelet count)
In addition to prolonged bleeding time, what are the two characteristic lab
findings in Bernard-Soulier Syndrome? {{c1:: Thrombocytopenia Large platelets on
blood smear}}
What is the pathophysiologic cause of Immune (idiopathic) Thrombocytopenia Purpura?
{{c1::Anti-GpIIb/IIIa antibodies causing destruction by splenic macrophages}}
What are the treatments for Idiopathic/Immune Thrombocytopenia Purpura (ITP)?
{{c1:: Steroids IVIG Splenectomy}} IVIG blocks Fc receptor on splenic macrophages
→ macrophage wont consume/destroy platelet-antibody complex
Thrombotic Thrombocytopenia Purpura (TTP) is a disorder of small vessel thrombus
formation due to deficiency of {{c1::ADAMTS 13 (vWF metalloprotease)}}
What are the diagnostic lab findigns in TTP? {{c1:: MAHA: Schistocytes, ↑ LDH
Thrombocytopenia Normal PTT/PT}}
What lab test abnromalities are associated with (diagnostic of) DIC? {{c1:: ↑
PTT/PT ↑ D-dimer MAHA (schistocytes, ↑LDH) ↓ Platelets ↓ Fibrinogen}}
How is Von Willebrand Factor Disease diagnosed? {{c1::Ristocetin assay showing no
platelet aggregation}} ↑ Bleeding time, ↑ PTT (depends on severity), normal
platelet count, normal PT
What are the three treatments for Von Willebrand Factor Disease? {{c1:: vWF
concentrate Desmopressin Aminocaproic acid}}
Heyde's Syndrome is a disease of GI bleeding from Angiodysplasia due to
{{c1::aortic stenosis}} ↓ vWF
Why is aspirin preferred over other NSAIDs as an antiplatelet drug?
{{c1::IRREVERSIBLE inhibition of COX-1 & COX-2}} ↓ activity for entire
lifetime of platelet (7-10 days); other NSAIDs reversibly inhibit COX
What is the rare, serious side effect of ADP-inhibiting antiplatelet drugs?
(clopidogrel, prasugrel, etc) {{c1::Thrombotic Thrombocytopenia Purpura}}
{{c1::Ticagrelor}} is a reversible P2Y12 antagonist with the unique side effect of
{{c2::dyspnea}}
What is the MOA of antiplatelet drugs Cilostazol and Dipyridamole? {{c1::inhibit
PDE-3 → ↑ cAMP → ↓ platelet activation}} Also lead to vasodilation
Dipyridamole is an antiplatelet PDE3 inhibitor that also causes vasodilation by
blocking {{c1::adenosine}} uptake What ionotrope also inhibits PDE-3? Milrinone
What 3 antiplatelet drugs function by blocking GPIIb/IIIa receptors and inhibiting
aggregation? {{c1:: Abciximab Tirofiban Eptifibatide}} AB-CIX-imab: 2b x 3a =
ab CIX (6)
What are the extrinsic causes of hemolysis? {{c1:: Antibodies Mechanical trauma
(narrow vessels) RBC infection}}
How do you calculate the Corrected Reticulocyte Count? {{c1::(% of reticulocytes)
(Hct/45)}} ↑ Retic count = hemolysis
{{c1::Cords of Billroth (splenic cords)}} are vascular channels found in the
{{c1::red pulp}} of the spleen that trap old or damaged RBCs for macrophage
destruction
What commonly causes Intravascular Hemolysis in small vessels and large vessels
respectively? small → {{c1::thrombus (MAHA)}} large → {{c1::mechanical heart
valves}}
Low levels of {{c1::Haptoglobin}} are indicative of intravascular hemolysis can
also be low in extravascular hemolysis & cirrhosis
What 3 urinary findings are characteristic of intravascular hemolysis? {{c1::
hemoglobinuria hemosiderinuria urobilinogen }} no bilirubin → unconjugated
bilirubin (via hemolysis) is not water soluble
"{{c1::Parvovirus B19}} is a DNA virus that can cause an ""aplastic crisis"" in
patients with chronic hemolysis because the virus replicates in RBC progenitor
cells and decreases erythropoesis"
What is the hallmark of Acute Lymphoblastic Leukemia (ALL) in peripheral blood
smear and bone marrow biopsy? {{c1::↑↑↑ CD10+ and TdT+ Lymphoblasts}}
What two sites are the common locations for Acute Lymphoblastic Leukemia (ALL)
spread? {{c1::Testes & CNS}}
Which two translocations are most common in B-cell ALL and what do they indicate
about prognosis? {{c1:: t(9;22) → poor prognosis t(12;21) → good prognosis}}
Down Syndrome greatly increases the risk of what two cancers? {{c1::↑↑ ALL; ↑ AML}}
How does T-Cell ALL (less common) present? {{c1:: Young males (childhood - 20s)
Mediastinal mass SVC syndrome Tracheal obstruction}} CD2, CD3, CD4, CD5, CD7, CD8+
T-cell proliferation → big Thymus → mediastinal mass
What are the classic findings of Acute Myelogenous Leukemia (AML) on peripheral
blood smear? {{c1::Auer rods; myeloperoxidase(+) myeloblasts}}
What translocation defines Acute Promyelocytic Leukemia (APL)? {{c1::t(15;17)}}
Myelodysplastic Syndromes (MDS) are stem-cell disorders of ineffective
hematopoiesis often secondary to what 3 environmental exposures? {{c1:: Radiation
Chemo Benzene}} usually presents years after exposure; can transform into AML
Warm AIHA is due to {{c1::IgG}} antibodies to patient's RBCs Spherocytes on
blood smear
Cold AIHA is due to {{c1::IgM}} antibodies to patient's RBCs In Cold, RBCs
agglutinate and cause painful blue fingers and toes. Eg, Mycoplasma pneumonia
causes IgM attack of RBCs in cold (iced test tube) but dissociates at warm/central
body temps.
What conditions are associated with warm AIHA? Oh, and what drug can cause this?
{{c1:: SLE NHL CLL Methyldopa}}
What drugs can cause Direct Coombs-positive Hemolytic Anemia? {{c1:: Methyldopa
Penicillins Cephalosporins}} Penicillins mechanism of AIHA:
Cold AIHA will show a positive direct Coombs test for {{c1::anti-C3::not anti-IgM}}
antibodies IgM splits from RBCs in warmth, C3 stays
What conditions are associated with cold AIHA? {{c1:: Mycoplasma pneumonia Mono
(Ebstein-Barr) CLL}}
What conditions are associated with Microangiopathic Hemolytic Anemia (MAHA)?
{{c1:: DIC, TTP/HUS HELLP malignant HTN}} platelet disorders (DIC, TTP, HUS) →
thrombi in narrowed vessels → RBC damage HELLP, malignant HTN → endothelial injury
→ thrombus formation
What two pathogens infects RBCs and cause hemolytic anemia? {{c1::Malaria &
Babesia}}
Reed-Sternberg Cells (Hodgkins) are usually derived from {{c1::B-cell}} lymphocytes
and positive for {{c1::CD15 and CD30::CD markers}}
Why are B symptoms (night sweats, etc) more common in Hodgkin Lymphoma vs NHL?
{{c1::Reed-Sternberg cells release lots of cytokines}}
What electrolyte abnormality is a common presenting symptom of Hodgkin Lymphoma?
{{c1::Hypercalcemia}} RS cells activate macrophages, which contain 1-a-
hydroxylase → ↑ Vitamin D
"What is the hallmark of the rare Nodular Lymphocyte Predominant subtype of Hodgkin
Lymphoma on biopsy? {{c1::CD20+ ""popcorn cells""}}"
{{c1::Nodular Sclerosing}} HL is the most common subtype of Hodgkin Lymphoma and
often presents as a mediastinal mass on CXR
What normal protective proteins on the RBC membrane are absent in Paroxysmal
Nocturnal Hemoglobinuria? {{c1:: CD55 = DAF (decay acc. factor) CD59 = MAC
inhibitory protein}} Other features of PNH include thrombosis (the MCC of
death), abdominal pain, fatigue, jaundice and erectile dysfunction in men.
Paroxysmal Nocturnal Hemoglobinuria (PNH) is caused by an acquired mutation in stem
cells leading to loss of {{c1::glycosylphosphatidyinositol (GPI) anchor}} GPI
normally attaches CD55 (DAF)& CD59 to RBC membrane. These surface proteins protect
against complement activation and destruction. Without them - hemolysis.
What are the 4 presenting symptoms of PNH? {{c1:: Hemolysis at night Abdominal pain
Iron deficiency anemia Thrombosis (cause of death)}} I HAIT night
PNH increases the risk of what malignancy? {{c1::Acute Myeloid Leukemia (AML)}}
 PNH caused by stem cell mutations → AML
What is the gold standard test to confirm diagnosis of PNH? {{c1::Flow cytometry →
antibodies to GPI-anchored proteins (CD55/59)}}
{{c1::Eculizumab}} is an antibody to complement protein C5 used to treat PNH PNH is
caused by complement-mediated intravascular RBC lysis
Hereditary Spherocytosis is caused by an autosomal dominant defect in what 4
possible proteins? {{c1::Spectrin > Ankyrin, band 3, band 4.2}}
What test is the gold standard for confirming Hereditary Spherocytosis diagnosis?
{{c1::positive osmotic fragility test}} also.. ↓MCV; ↑MCHC; ↑RDW
What is the treatment for Hereditary Spherocytosis? {{c1::Splenectomy}} more
imporant stuff ↓
Non-Heme Iron is converted to the Fe2+ state by {{c1::Vitamin C}} before being
absorbed in the duodenum Heme iron is found in meats & easily absorbed. But,
this is why you'd want to avoid Vitamin C in Hemochromatosis
Describe iron storage in the body - which protein, cell type, and organs?
{{c1::Ferritin in macrophages of liver and bone}}
What are the clinical circumstances associated with iron deficiency caused by
inadequate GI uptake? {{c1:: Babies Malabsorption (PPIs, post-gastrectomy)
Malnutrion}}
How do pregnancy and OCP use affect serum iron parameters? {{c1::↑ Transferrin; ↓ %
saturation}}
What two protozoans can cause iron deficiency anemia? {{c1:: Anclystoma duodenale
Necator americanus}} hookworms → larvae penetrate skin, cause anemia by sucking
blood from intestinal wall. Treat with Bendazoles or Pyrantel Pamoate
What lab values are associated with Iron Deficiency Anemia? {{c1::}} Remember
that hemochromatosis (iron overload) is the complete opposite
What causes of anemia will have ↑ RDW? {{c1::iron, B12/folate deficiencies}} Useful
for distinguishig iron deficiency from mild thalassemia (thal. will have normal
RDW)
Which two causes of anemia will result in elevated protoporphyrin levels? {{c1::
Iron deficiency Lead poisoning}}
Anemia of chronic disease is a result of increased {{c1::hepcidin}} release by the
liver, which binds ferroportin to inhibit iron transport
What lab values are associated with Anemia of Chronic Disease compared to iron
deficiency? {{c1::}}
What are the most common causes of exposure to lead (lead poisoning) in children
and adults? {{c1:: Children: eating lead paint (old house) Adults: Inhalation
(battery factory)}}
Lead Poisoning inhibits what two enzymes in heme synthesis? {{c1:: ∆-aminolevulinic
acid (∆-ALA) dehydratase Ferrocheletase}} ↓ HEME
Lead poisoning can result in build-up of what two intermediates in heme synthesis?
{{c1:: Aminolevulinic acid Protoporphyrin}} Both in mitochondria...
sideroblasts
What is the characteristic finding of Lead Poisoning on peripheral blood smear?
{{c1::Basophilic stippling (accumulations pyrimidines/RNA)}}
What are the three treatments for Lead Poisoning? {{c1:: Dimercaprol Calcium
disodium EDTA DMSA (succimer)}} DMSA (succimer) used for chelation in Kids
Sideroblastic anemia is caused by failure to synthesize {{c1::protoporphyrin}}
leading to iron accumulation in {{c1::mitochondria}} of RBCs In BONE MARROW
What are the 4 reversible causes of Sideroblastic Anemia? {{c1:: Alcohol
(mitochondrial poison) B6 deficiency (INH; required for Aminolevulinic acid
synthase) Copper deficiency Lead poisoning (inhibits enzyme Aminolevulinic acid
dehydratase and Ferrochelatase) }}
The genetic form of Sideroblastic Anemia is an {{c1::X-linked}} inherited
deficiency in {{c1::ALA synthase}}
What lab findings are associated with Sideroblastic Anemia? {{c1:: ↑ iron -/↓ TIBC
↑ ferritin}} Low erythrocyte protoporphyrin levels (unless caused by lead
poisoning)
Chronic Myelogenous Leukemia is due to dysregulated production of
{{c1::granulocytes::cells}} ↑ neutrophils, basophils, eosinophils, myeloblasts ↑
basophils extremely rare → immediately think CML
How do you differentiate CML from a benign leukemoid reaction (infection)?
{{c1::CML → ↓↓ LAP}}
What chromosomal translocation is the genetic hallmark of CML? {{c1::Philadelphia
chromsosome: t(9;22) BCR-ABL fusion gene}}
Fusion of the BCL-ABL genes in the Philadelphia chromosome t(9;22) result in the
synthesis of {{c1::cytoplasmic tyrosine kinase::protein}} Rarely occurs in ALL;
indicates poor prognosis
What are the three BCR-ABL Tyrosine Kinase Inhibitors used to treat CML? {{c1::
Imatinib Dasatinib Nilotinib}} """-tinib = tyrosine kinase inhibitor ""-ib"" =
small molecule w/ inhibitory properties specifically"
Small Lymphocytic Lymphoma is a neoplastic proliferation with the same malignant
cells as CLL, but is differentiated by {{c1::lymphocyte count < 5000}} Both pretty
mild & asymptomatic. May see lymphadenopathy or B symptoms (only 10%)
What is the hallmark of Chronic Lymphocytic Leukemia on peripheral blood smear?
{{c1:: Smudge cells }} fragile lymphocytes disrupted during preparation of blood
smear
What are the three possible complications of Chronic Lymphocytic Leukemia? {{c1::
Hypogammaglobulinemia (↑bacterial infx) Autoimmune hemolytic anemia Diffuse Large B
cell Lymphoma }}
Hairy Cell Leukemia is a rare, chronic B-cell malignancy that expresses what cell
surface markers? {{c1:: CD103 (sensitive) CD19, 20, 22 (usual B cell stuff)}}
"What are the key unique features of Hairy Cell Leukemia presentation? {{c1::
splenomegaly (hairy cells in red pulp) ""dry tap"" on BM marrow biopsy}}"
{{c1::Cladribine (2-CDA)}} is a purine analog that inhibits adenosine deaminase and
is the preferred initial treatment for Hairy Cell Leukemia also IFN-a, pentostatin
Alpha Thalassemia {{c1::Minima (a-/aa)}} results in an asymptomatic carrier state
biggest problem is passing down gene if partner also has an alpha thalassemia
What two demographics commonly have Alpha Thalassemia Minor and what are their
respective genetic configurations (xx/xx)? {{c1:: Asians → cis (aa/--) Africans →
trans (a-/a-)}} Causes mild anemia, but Cis configuration (asians) carries high
risk to offspring
{{c1::HbH Disease}} is an alpha thalassemia with three deletions (a-/--) that
causes excess beta globin (ß4) production
How does HbH Disease present? {{c1::Microcytic anemia with extravascular hemolysis
(splenomegaly, etc)}} microcytic anemias (iron def) wont cause extravascular
hemolysis → key test clue
What test is used to diagnose HbH disease? {{c1::DNA testing}}
Alpha thalasemia with four deletions (--/--) causes {{c1::Hgb Barts (4 gamma
globins)}}, which leads to hydops fetalis Suspect in stillborn baby with massive
swelling (pleural effusion, ascites). Especially in Asian populations (most common
carriers of cis (--/aa) deletion)
What chromosomes contain the genes for Alpha & Beta globin chains, respectively? A
→ {{c1::16 (4 genes)}} B → {{c1::11 (2 genes)}}
What type of genetic defect causes alpha and beta thalassemias, respectively? Alpha
→ {{c1::Deletions}} Beta → {{c1::Point mutations in splice sites & promotor
sequences}}
Beta Thalassemias are most prevalent in what geographical population(s)?
{{c1::Mediterranean}}
Beta Thalassemia Minor (B/B) is typically asymptomatic and diagnosed by
{{c1::↑HbA2}} on electrophoresis
"What are the two physical skeletal manifestations of Erythroid Hyperplasia
(expansion of bone marrow) seen in Beta Thalassemia Major? {{c1::""crew cut""
skull; ""chipmunk"" faces}}"
Hepatosplenomegaly is often a consequence of Beta Thalassemia major due to
{{c1::extramedullary hematopoiesis}}
What are the findings of Beta Thalassemia Major on electrophoresis? {{c1:: ↓ HbA
(likely none) ↑ HbA2; ↑ HbF}} cant make HbA (a2B2) with no B.
Alpha and Beta Thalassemias are actually protective against what pathogen?
{{c1::Malaria (plasmodium falciparum)}} Still get infected, but much less severe
(for obvious reasons).
What drugs would you give to treat DVT in pregnancy? {{c1::LMWH → Enoxaparin,
Dalteparin}} LMWHs dont cross placenta, ↑ bioavailability, short elimination
times (can be stopped right before delivery). Only use thrombolytics (tPAs) for
life threatening emergencies in pregnancy.
Describe the mutation causing Sickle Cell Anemia {{c1::Point mutation; Glutamate →
Valine}} Valine (non-polar) alters the shape of beta-chains. Occurs via a
subsitution adenine → thymine at the 6th codon of the Beta gene
Sickle cell anemia is caused by HbS polymerizing (sickling) under what three
circumstances? {{c1:: low oxygen high altitude acidosis}}
"Which two RBC pathologies can cause extreme Erythroid Hyperplasia (↑↑ EPO)
resulting in ""chipmunk facies"" and ""crew cut"" appearance on skull xray? {{c1::
Sickle Cell Anemia Beta Thalassemia Major}}"
What are the five major clincal manifestations (consequences) of vaso-occlusion of
microvasculature caused by Sickle Cell Anemia? {{c1:: Dactylitis Acute pain crises
Spleen failure (infections) Acute chest syndrome Renal Dysfunction }} So if they
describe at pt with HbS and ask about the pathogenesis of these symptoms, just know
that they're caused by vaso-occlusion of sicked RBCs Dactylitis → pain & swelling
in hands/feet due to occlusion of microvasculature. Common initial symtpom among
children
Sickle Cell Anemia predisposes patients to increased risk of infections by what
bacteria? {{c1::Encapsulated: Strep pneumo >> H. influenza > Neisseria
Meningitidis}} SHiN; must vaccinate against these organisms because (even Strep)
can cause severe bacteriemia/sepsis and lead to Death -Deficient clearance of
bacteria due to functional asplenia. In most children with sickle cell dis,
recurrent splenic infarcation results in loss of splenic function by the age of 2-4
years. Consequently IgM production is decreased, which leads to ineffective
complemet activation and thus, impaired opsonization of bacteria. -Part of the
management of SCD is prevention of infections, which includes pneumococcal and
meningococcal vaccination, as well as daily prophylactic peniciliin from age 3
months until at least age 5.
Sickle Cell Anemia patients are predisposed to osteomyelitis from what bacteria?
{{c1::Salmonella}} "Salmonella is encapsulated & people with SCA are asplenic.
Also, avascular necrosis caused by micro-occlusion in SCA creates the ""perfect""
environment for osteomyelitis"
{{c1::Splenic Sequestration Crisis}} is a complication of SCA caused by vaso-
occlusion of the spleen, resulting in the pooling of RBCs, ↓Hgb, rapidly enlarging
spleen, and risk for hypovolemic shock
SCA causes renal papillary necrosis via vaso-occlusion of the {{c1::vasa recta in
the renal medulla}}
What are the treatments for Sickle Cell Anemia? {{c1:: Hydroxyurea (↑HbF)
Immunizations (encaps. bacteria) Transfusions Bone marrow transplant }}
Hydroxyurea increasing HbF is the most important takeaway point. BM
transplant is curative. Median survival is 42-48 years.
Sickle Cell Trait increases the risk for what malignancy? {{c1::Renal Medullary
Carcinoma}} Sickle Cell Trait is usually OK, but the renal medulla is still
vulnerable to sickling; may see loss of concentrating ability (polyuria)
While usually diagnosed by electrophoresis, HbS can be diagnosed by adding
{{c1::sodium metabisulphite}} to a blood sample (sickling test)
Hemoglobin C (HbC) is caused by what amino acid substitution in B-globin?
{{c1::Glutamic acid→ Lysine}} Unlike valine (HbS), Lysine is charged, so HbC
doesn't sickle because there are less hydrophobic interactions
What are the findings on peripheral blood smear in patients with HbC disease
(homozygotes)? {{c1::HbC crystals with target cells }}
{{c1::Epoetin Alfa}} in an EPO analog used to treat anemia in chronic kidney
disease Anemia from chronic kidney disease is a normocytic anemia caused by ↓
EPO release of peritubular capillaries in renal cortex. (Darbepoeitin alfa is also
used)
{{c1::Aplastic}} anemia is caused by loss of hematopoietic precursors in the bone
marrow, resulting in pancytopenia ↓ RBCs, WBCs, platelets; ↓ reticulocyte count;
↑ EPO
What are the 4 causes of Nonhemolytic, Normocytic Anemia? (retic count ≤ 2%) {{c1::
Aplastic Anemia Chronic Kidney Disease Anemia of Chronic Disease Iron Deficiency
(early)}} Açai doesnt actually make you smaller ≈ normocytic (sry dr oz)
What are the diagnostic findings of Aplastic Anemia on bone marrow biopsy?
{{c1::Hypocellular marrow with fatty infiltration (dry bone tap)}}
"""Idiopathic"" Aplastic Anemia is thought to be caused by {{c1::T-cell}} mediated
destruction of stem cells in bone marrow" We know this because it can be treated
with immunosuppression:
What two immunosuppressant drugs are used to treat Idiopathic (immune) Aplastic
Anemia? {{c1:: Antithymocyte globulin Cyclosporine}} Becuase these treatments are
effective, Idiopathic Aplastic Anemia is thought to be caused by T-cell mediated
destruction of BM
What Viruses can cause Aplastic Anemia? {{c1:: Hepatitis EBV HIV Parvovirus B19}}
Fanconi Anemia is an inherited cause of aplastic anemia due to {{c1::defective DNA
repair}} causing bone marrow failure
Fanconi Anemia is an inherited form of aplastic anemia that increases the risk of
which malignancies? {{c1:: Acute Myeloid Leukemia (AML) >> Myelodysplastic
syndromes Squamous carcinoma (head, neck, vulva)}}
Pure Red Cell Aplasia is a paraneoplastic syndrome strongly associated with
{{c1::Thymomas::malignancy}} Anemia with ↓↓ reticulocytes (normal granulocytes &
platelets)
Which inborn error of metabolism can cause Megaloblastic Anemia? {{c1::Orotic
Aciduria}}
What are the non-megaloblastic causes of Macrocytic anemias? (eg, not due to folate
or B12 deficiency) {{c1:: Liver disease Alcoholism Diamond-Blackfan Anemia}} It
takes Big Balls (macrocytic) to drink Alcohol on the Black Diamond
{{c1::Rituximab}} is a monoclonal CD20 B-cell antibody used to treat CD20+ B-cell
lymphomas (DLBCL, Follicular) Also treats CLL, RA, ITP, MS. Increases risk of
progressive multifocal leukoencephalopathy
The genetic hallmark of Follicular Lymphoma is a t{{c1::(14;18)}} translocation
causing overexpression of {{c1::BCL2}} Bcl2 stabilizes mitochondria, preventing
leakage of cytochrome C and apoptosis.
"How does Follicular Lymphoma present? {{c1::Older person with ""waxing and
waning"" lymphadenopathy}}" Average age at diagnosis is 65. Can transform to
DLBCL
The presence of {{c1::macrophages}} is indicative of reactive lymphadenopathy
(infectious) vs lymphoma
Mantle Cell Lymphoma is a B-cell malignancy that expresses what unique (or
abnormal) cell surface marker? {{c1::CD5}} remember that CLL also expresses
CD5 in addition to normal B-cell markers (eg, CD20)
The genetic hallmark of Mantle Zone Lymphoma is a t{{c1::(11;14)}} translocation
leading to overexpression of {{c1::Cyclin D1}}
Which type of NHL is often extranodal and is associated with chronic inflammatory
disorders? {{c1::Marginal Zone Lymphoma}}
"{{c1::Burkitt's Lymphoma}} type of lymphoma is associated with a ""starry sky""
appearance on lymph node biopsy" "white areas are composed of ""tingible-body""
macrophages"
Where do the endemic and sporadic forms of Burkitt's lymphoma present respectively?
endemic → {{c1::mandible mass}} sporadic → {{c1::abdominal mass}}
The genetic hallmark of Burkitt's Lymphoma is a t{{c1::(8;14)}} translocation
leading to overexpression of {{c1::c-myc}} C-myc is an oncogene transcription
factor
Adult T-Cell Lymphoma is caused by {{c1::HTLV-1}} infectionAssociated with IV drug
abuse in eastern/tropical countries. Can cause lytic bone lesions and hypercalcemia
(like Multiple myeloma) and skin lesions/rashes.
What is the unique, characteristic non-hematologic complication of Adult T-Cell
Lymphoma? {{c1::Lytic bone lesions w/ hypercalcemia}} (Multiple Myeloma wont have
the lymphadenopathy, lymphocytosis, skin lesions, and the patient prob wont be from
the endemic regions listed)
"{{c1::Mycosis Fungoides}} is a localized cutaneous T-cell lymphoma characterized
by slowly progressive patches, plaques, and tumors in a ""bathing trunk""
distribution" Scaly, pruritc, well-demarcated skin plaques and patches. In the
later stages of the disease, mushroom-shaped tumors develop within the plaque
lesions. -Leukemic dissemination of the neoplastic CD4+ T-cells results in Sezary
syndrome
{{c1::Sezary Syndrome}} is a widespread cutaneous T-cell lymphoma causing erythema
of the skin of the entire body
Multiple Myeloma is a malignancy of plasma cells & immunoglobulin proliferation
that is driven by {{c1::IL-6}} Primarily produces IgG (~50%), IgA (~20%),
Light chains only (~15%)
Excess light chain production in Multiple Myeloma leads to what two pathological
complications? {{c1:: Renal damage AL amyloidosis}}
What are the 4 clinical features of Multiple Myeloma? {{c1:: hyperCalcemia Renal
failure Anemia Bone lytic lesions (& vertebral fx)}} Bones & hypercalcemia: Renal
failure:
Bence Jones Proteins (Multiple Myeloma) in the urine are caused by
{{c1::immunoglobulin light chains}} combining with {{c1::Tamm-Horsfall mucoprotein
(THP)}}
What is the leading cause of death in Multiple Myeloma? {{c1::Infection}}
"What are the two characteristic findings of Multiple Myeloma on peripheral blood
smear? {{c1::Rouleaux (stacks of RBCs) Plasma cells w/ ""clock face"" chromatin}}"
{{c1::Monoclonal Gammopathy of Undetermined Significance}} is a plasma cell
disorder that is distinguished from Multiple Myeloma becuase it is asymptomatic and
bone marrow has <10% monoclonal plasma cells Can progress to Multiple Myeloma
"Waldenstrom Macroglobulinemia is a B-cell lymphoma that produces an ""M Spike""
due to overproduction of {{c1::IgM}}"
What fibril protein accumulates in each of the systemic amyloidosis diseases?
Primary → {{c1::AL (Ig Light chains)}} Secondary → {{c1::serum Amyloid A (AA)}}
Dialysis-related → {{c1::B2-microglobulin}} Note that serum amyloid A is an
acute phase reactant, which is why secondary amyloidosis (AA) occurs in chronic
inflammatory diseases (RA, IBD, protracted infection, etc)
The hereditary/familial forms of amyloidosis are caused by what abnormal fibrillin
protein? {{c1::Mutated Transthyretin (ATTR)}}
What is the normal function of Transthyretin (mutated in hereditary amyloidosis)?
{{c1::Transports Thyroid Hormone and Retinol (vitamin A)}} Synthesized in liver, so
liver transplant is treatment for hereditary amyloidsosis (caused by Mutated
transthyretin)
Amyloidosis is caused by aggregation of proteins into {{c1::B-pleated linear
sheets}}, which are insoluble and cause cellular damage Secondary structure.
Responsible for congo red staining.
Secondary (AA) amyloidosis occurs in the setting of chronic inflammatory conditions
because Serum Amyloid A (SAA) proteins are {{c1::acute phase reactants}} eg,
IBD, RA, familial Mediterranean fever, protracted infection
The major cause of death in Familial Mediterranean Fever is {{c1::Secondary (AA)
Amyloidosis}} Familial Mediterranean Fever is an inflammatory disease of
neutrophils involving recurrent episodes of fever and inflammatory serosal pain
(abdominal pain, pericarditis)
What is the treatment for Familial Mediterranean Fever? {{c1::Colchicine (inhibits
neutrophils)}} Familial Mediterranean Fever is an inflammatory disease involving
recurrent episodes of fever and inflammatory serosal pain (abdominal pain,
pericarditis)
What are the common symptoms of Dialysis-related Amyloidosis? {{c1:: Shoulder pain
Carpal tunnel syndrome}}
Chronic Myeloproliferative Disorders (polycythemia v., thrombocythemia) are
associated with {{c1::V617F JAK2}} mutations V617F (valine → phenylalanine)
makes bone marrow stem cells more sensitive to growth factors (EPO, TPO)
JAK2 is an oncogene located on chromosome {{c1::9}} that codes for cytoplasmic
{{c1::tyrosine kinase}} This is the basis for myeloproliferative disorders.
How will PaO2 and EPO levels change with the following: 1. Hypoxia 2. EPO secreting
tumor (RCC) 3. Polycythemia vera {{c1::}}
What are the two major mechanism that cause the symptoms of Polycythemia vera?
{{c1:: ↑ RBC mass Thrombosis}}
What are the three potential complications of Polycythemia vera? {{c1::
Myelofibrosis Leukemia (AML) Gout}}
Essential Thrombocytosis is characterized by a massive, malignant proliferation of
{{c1::megakaryocytes}} and {{c1::platelets}}
Primary Myelofibrosis is caused by megakaryocyte release of {{c1::PDGF}} and
{{c1::TGF-B}} to stimulate fibroblasts
What is the classic finding of Myelofibrosis on peripheral blood smear?
{{c1::Teardrop cells (Dacrocytes) }} RBCs deformed leaving fibrotic marrow.
Can also be seen with Thalassemias.
Langerhans Cell Histiocytosis is a malignancy of dendritic cells that stains
positive for what tumor markers? {{c1:: CD1a S100 CD207}}
What is the classic finding of Langerhans Cell Histiocytosis on electron
microscopy? {{c1:: Birbeck Granules }}
Hairy Cell Leukemia is a mature B-cell tumor that stains positive for {{c1::TRAP
(tartrate-resistant acid phosphatase)}}
While most heme synthesis occurs in the bone marrow, 20% of heme synthesis occurs
in the {{c1::liver}} to be used in {{c1::cytochrome P450 enzymes}} This is
important because CYP450 Inducers can precipitate A.I. Porphyria symptoms
How are both Porphyrias inherited? {{c1::Autosomal dominant}}
What are three succeptibility factors (worsen disease) for Porphyria Cutanea Tarda?
{{c1:: Alcohol Hepatitis C HIV}} Because 20% of heme synthesis occurs in the
LIVER for CYP450 enzymes
What are the two treatments for Acute Intermittent Porphyria? {{c1:: Hemin
(synthetic heme) Glucose}} Lowers production of ALA and Porphobilinogen
(accumulated substrates (neurotoxic) in AIP)
Where are the two attachments of the ACL? {{c1:: Lateral femoral condyle Anterior
tibia}} "resists anterior movement of tibia relative to femur → basis of
""anterior drawer"" test"
What are the two attachments of the Posterior Collateral Ligament (PCL)? {{c1::
Medial femoral condyle Posterior tibia}} resists posterior movement of tibia
relative to femur
A varus deformitity of the knee indicates a tear of the {{c1::lateral collateral
ligament (LCL)}}
A valgus (knock-knee) deformity of the knee indicates a tear of the {{c1::medial
collateral ligament (MCL)}}
The Lachman test is more sensitive for ACL injury than the anterior drawer sign.
What is different about it? {{c1::knee bent at 30 degree angle}} knee bent at 90
degrees for anterior drawer
"What is the classic cause of PCL tear/injury? {{c1::""dashboard injury"" → knee
into dashboard in MVA}}" from trauma (force directed posterior at knee),
whereas ACL injuries are often non-contact injuries. Test w/ Posterior Drawer sign
Pre-patellar Bursitis is often caused by {{c1::pressure from repeated kneeling}}
Why does Osgood-Schlatter Disease (Tibial tuberosity avulsion) occur in
children/adolescents? {{c1::Tibial tubercle is the secondary ossification center of
the tibia}} So, it's very succeptible to stress from overuse -First aid:
Which muscles function in ABduction the arm at each of the following angles
(degrees)? 0-15: {{c1::Supraspinatus (Suprascapular nerve)}} 15-100: {{c1::Deltoid
(Axillary nerve)}} >90: {{c1::Trapezius (Accessory nerve)}} >100: {{c1::Serratus
Anterior (Long thoracic nerve)}}
Supraspinatus Impingement occurs due to compression of the tendon between which two
bones? {{c1::Humeral head & Acromion process}} common in swimmers and throwers
(baseball pitchers)
What clinical test is used to identify supraspinatus injury? {{c1::Empty/full can
tests (pushing down on abducted arm)}}
List which nerve innervates the following muscles of arm abduction: Supraspinatus
(0'-15'): {{c1::Suprascapular}} Deltoid (15'-100'): {{c1::Axillary}} Trapezius
(>90'): {{c1::Accessory}} Serratus Anterior (>100'): {{c1::Long Thoracic}}
What nerve is commonly injured in anterior shoulder dislocation? {{c1::Axillary
nerve (C5, C6) }} -Other causes of axillary nerve injury include: Rotator cuff
surgery, fracture of surgical neck of the humerus sensory loss of deltoid & weak
shoulder abduction
What are the two major complications of proximal humerus fractures? {{c1::Avascular
necrosis of humeral head via axillary artery rupture & Axillary nerve damage}}
Lateral Epicondylitis (tennis elbow) will cause pain with resisted wrist
{{c1::extension}}
Medial Epicondylitis (golfer's elbow) will cause pain with resisted wrist
{{c1::flexion}}
What is the cause of Radial Head Subluxation (Nursemaid's Elbow)? {{c1::traction on
pronated forearm causes annular ligament to slip off radial head}}
What are the symptoms of a Musculocutaneous Nerve (C5-C7) Lesion? {{c1:: loss of
flexion (biceps) sensory loss of lateral forearm }}
What is the classic cause of Lower Trunk (C8-T1) Injury? (Klumpke Palsy)
{{c1::catching tree branch while falling (excessive abduction of arm)}}
damages median and ulnar nerves
What are the two common predisposing causes of Thoracic Outlet Syndrome? {{c1::
Cervical rib (C7) Pancoast tumor}}
Winged Scapula is caused by trauma to the {{c1::long thoracic (C5-C7)}} nerve which
innervates the {{c1::serratus anterior}} muscle
What autoantibodies are associated with Myasthenia Gravis? {{c1::Post-synaptic
Anti-Acetylcholine Receptor antibodies}} associated with HLA-B8, Thymomas, Type II
Hypersensitivity
What are the clinical features of Myasthenia Gravis? {{c1:: Muscle fatigueability
Diplopia and ptosis Improvement after Edrophonium}} fatigueability → muscles tire
with use. Can lead to dyspnea via respiratory muscle weakness
{{c1::Edrophonium (Tensilon)}} is a short-acting AchE inhibitor used to diagnose
Myasthenia Gravis Pyridostigmine and Neostigmine (AchE inhibitors) to treat
The Edrophonium test for Myasthenia Gravis may lead to salivation, abdominal
cramping, dyspnea, and bradycardia due to {{c1::increased parasympathetic
activity}}
What diseases are associated with Myasthenia Gravis? {{c1::Thymic Hyperplasia &
Thymoma}}
Lambert-Eaton Myasthenic Syndrome is a paraneoplastic syndrome of the NMJ
associated with what malignancy? {{c1::Small cell lung cancer}}
What autoantibodies are associated with Lambert-Eaton Myasthenic Syndrome?
{{c1::Anti-Voltage-Gated Calcium Channel (VGCC) antibodies }} Pre-synaptic →
prevents depolarization and ACh release, whereas Myasthenia Gravis targets the
post-synaptic nicotinic ACh receptor
What are the clinical features of Lambert-Eaton Myasthenic Syndrome? {{c1:: Slow-
onset proximal muscle weakness Autonomic dysfunction (dry mouth, ED) Improves with
muscle use}}
What are the two possible complications of scaphoid fracture? {{c1:: Avascular
necrosis non-union}}
Why does scaphoid fracture often cause avascular necrosis? {{c1::Radial artery
supplies distal scaphoid → proximal part relies on retrograde flow}} Fracture
prevents blood from distal scaphoid from perfusing proximal part of bone.
Lunate bone dislocation may result in {{c1::acute carpal tunnel syndrome}}
What are two RARE causes of Carpal Tunnel Syndrome? {{c1:: acromegaly dialysis-
related amyloidosis}} (ie, not pregnancy, RA, hypothyroid, or diabetes)
Guyon's Canal Syndrome (Ulnar neuropathy) is classically seen in what demographic?
{{c1::cyclists}} due to pressure from handlebars. Guyon canal spans between hook
of hamate and pisiform bones
A superficial laceration of the hand that results in paralyzed thenar muscles but
normal sensation of the thumb indicates damage of which nerve? {{c1:: Recurrent
branch of median nerve }} Recurrent Branch of the Median nerve provides only
motor innervation to thenar muscles, very superficial, so often damaged with
shallow cuts.
What nerve would be injured from a fracture at the medial epicondyle of the
humerus? {{c1::Ulnar nerve}} "Radial deviation of wrist with flexion. Ulnar claw
may not be seen (""Ulnar paradox"")"
What three intermediate filament proteins function to mechanically stabilize the Z
disc/line? {{c1:: a-actinin vimentin desmin}} Can be stained to identify tumors:
Vimentin → sarcomas, RCC, meningioma Desmin → rhabdomyosarcoma
{{c1::Titin}} is a cytoskeletal protein that tethers myosin to the Z disc
Ca2+ released from muscle sarcoplasmic reticulum binds {{c1::Troponic C}} to remove
tropomyosin blockade of the actin binding site
{{c1::Dihydropyridine receptors (DHPR)}} are L-type Caclium channels that connect
T-tubules and Sarcoplasmic Reticulum to open Ryanodine receptors Ryanodine
receptors release calcium from SR
What membrane-bound transporter is responsible for the reuptake of Ca2+ back into
the SR after muscle contraction? {{c1::Sarco-endoplasmic reticulum Ca2+-ATPase
(SERCA)}} Ca2+-ATPase → uses ATP for hydrolysis (high yield)
Describe the pathophysiology of Malignant Hyperthermia. {{c1::bad ryanodine
receptors → excessive Ca2+ release → ↑ ATP consumption from SERCA → heat → tissue
damage}}
In contrast to slow-twitch muscle fibers, fast twitch muscle fibers primarily
metabolize {{c1::glucose}} and {{c1::glycogen}} for energy slow-twitch have ↑
myoglobin = more oxidative phosphorylation, FA metabolism. Slow twitch muscle
fibers are predominant in tonic/postural muscles
The autosomal recessive (infantile) form of Osteopetrosis arises due to mutations
in {{c1::carbonic anhydrase type II}} Carbonic Anyhdrase is required to make
acid → osteoclasts need acid to break down bone. No acid = no bone breakdown =
excessive bone formation
What is the only potential cure for the infantile form of Osteopetrosis? {{c1::Bone
marrow transplant}} osteoclasts derived from monocytes/macrophages
Rickets (vitamin D deficiency in children) will cause thickening of the
{{c1::epiphysis (growth plates)}} of the bone due to accumulation of
{{c1::osteoid}} also will have bowed legs, swelling at costochondral junctions,
and a soft skull
What are the two classic x-ray findings of Osteomalacia? {{c1:: Pseudofractures
Looser zones}}
Serum level of which form of Vitamin D is the best indicator of deficiency?
{{c1::25-OH Vitamin D (Calcidiol)}} 25-OH Vitamin D → storage form produced by the
liver, constant production, long half-life, not regulated by PTH
What are the lab findings in Vitamin D deficiency? {{c1:: ↓ Calcium, phosphate ↑
PTH, bone ALP}}
{{c1::Paget's Disease (Osteitis Deformans)}} is a localized disorder of bone
remodeling in elderly due to ↑ osteoclast activity followed by ↑ osteoblast
activity
What are the two microscopic hallmarks of Paget's disease? {{c1:: Mosaic pattern of
lamellar bone Cement lines}}
What are the two serious complications that Paget's Disease patients are at risk
for developing? {{c1:: High output cardiac failure Osteosarcoma}} high output
cardiac failure due to AV fistula in new bone
What are the lab findings in Paget's Disease? {{c1::↑ Bone ALP}} Ultimately becomes
osteoblastic (last phase) and ALP is the best marker of osteoblast activity. PTH,
Ca, Phosphorus all normal
What are the two treatments for Paget's Disease? {{c1:: Bisphosphonates
Calcitonin}}
Osteoporosis predominately effects {{c1::trabecular}} bone
What is the mechanism by which anticonvulsants (phenobarbital, phenytoin,
carbamazepine) cause secondary osteoporosis? {{c1::↑ activity CYP450 enzymes which
↑ breakdown of Vitamin D }} And as you know... ↓ Vitamin D → ↓ Calcium→ ↑ PTH →
Bone resorption
What medical conditions can cause secondary Osteoporosis? (4) {{c1::
Hyperparathyroidism (duh) Hyperthyroidism Mutliple myeloma Malabsorption (↓ Ca &
Vit D)}}
What are the two diagnostic features of Osteoporosis? {{c1:: Fragility fractures(s)
T-score ≤ -2.5 on DEXA}} One time DEXA screening recommended in women ≥ 65
What is the main side effect of ORAL bisphosphonates (Alendronate, Risedronate)?
{{c1::Esophagitis}} ** Take with water on empty stomach and remain upright for
30 minutes
What are the three rare, but serious side effects of Bisphosphonate drugs? {{c1::
Esophagitis (oral) Atypical femur fracture (diaphyseal) Osteonecrosis of jaw}}
{{c1::Teriparatide}} is a recombinant form of PTH used to treat osteoporosis given
as a once daily subcutaneous injection once-daily bolus ↑ osteoblasts
What is the major risk of the recombinant PTH analog, Teriperatide?
{{c1::Osteosarcoma}} Avoid in Paget's pts, previous cancer pts, radiation
exposure. Teriperatide also causes transient hypercalcemia
{{c1::Raloxifene}} is a selective estrogen receptor modulator (SERM) drug
preferentially used to treat osteoporosis because it does not increase risk of
endometrial hyperplasia Does increase risk of thromboembolic events (DVT, PE)
{{c1::Denosumab}} is a monoclonal RANK-L antibody occasionally used to treat
osteoporosis Mimics osteoprotegerin (OPG), inhibiting osteoclast activation
Den-os-u-mab: O(s) = targets bone U = human source Mab = monoclonal antibody
Increase in cardiac contractility is mediated by sympathetic stimulation (Gs) to
increase {{c1::calcium}} entry into myocytes """Calcium-triggered calcium
release"". Cant recruit extra fibers like skeletal muscle."
Cardiac lusitropy (relaxation) is achieved by B1-mediated phosphorylation of
{{c1::Phospholamban}}, which inhibits SERCA Aka, inhibiting the inhibitor. So,
↑ contractility and lusitropy are mediated via B1 receptors, because the faster the
heart contracts, the faster it needs to relax to contract again. Phospholamban
normally inhibits SERCA (calcium reuptake = relaxation)
How do Osteoid Osteomas present? {{c1::Bone pain at night that is relieved by
NSAIDs}}
Where do Osteoid Osteomas occur? {{c1::cortex of long bones}}
{{c1::Osteomas}} are painless, palpable benign tumors on the surface of facial
bones that often occur with Gardener's Syndrome Middle aged men. May precede
colonic manifestation of Gardener's syndrome (FAP)
Ewing Sarcoma is a malignant bone tumor composed of undifferentiated primitive
{{c1::neuroectoderm}} cells Youngest age at presentation of all bone tumors.
Commonly white boys < 15 years old.
{{c1::Ewing Sarcoma}} is a malignant bone tumor of children that usually presents
similarly to osteomyelitis (warm painful bone mass, fever, leukocytosis)
Suspected osteomyelitis in young male (~10-15) with sterile blood culture and
mass asipiration → Ewing Sarcoma
What is the genetic translocation associated with Ewing Sarcoma? {{c1::t(11;22)
fusion protein EWS-FLI1}}
Giant Cell Tumors (osteoclastomas) are benign stromal bone tumors that express high
levels of {{c1::RANK-L}} RANK-L drives osteoclast activity in tumor → leads to
giant osteoclast cells
{{c1::Heteroplasmy}} refers to the presence of both normal and mutated mtDNA
resulting in variable expressivity in mitochondrial inherited diseases All
offspring of mother will show signs of disease, but heteroplasmy causes variable
expressivity. Eg, Mitochondrial myopathies, Leber Hereditary Optic Neuropathy
What is the most common cause of Genitofemoral (L1-L2) Nerve Injury?
{{c1::Retractor blades in abdominal surgery}} damn med students smh
What are the common causes of Lateral Femoral Cutaneous Nerve (L2-L3) injury?
{{c1::compression from tight clothing, obesity, pregancy}} Travels under inguinal
ligament; prone to compression
What are the motor and sensory functions of the Obturator (L2-L4) Nerve? Motor:
{{c1::thigh adductors }} Sensory: {{c1::medial thigh}} Damaged in pelvic
surgery (via trochar), pelvic ring fractures. Thigh adductors:
List the 4 structures (vessels/nerve/lymphatics) coursing through the femoral
region from lateral to medial: {{c1::NAVL: Nerve; Artery; Vein; Lymphatics}}
What are the two motor functions of the Common Peroneal Nerve (L4-S2 branch of
sciatic)? {{c1::Foot dorsiflexion & eversion}} "Injury (trauma, fibular neck fx) →
Foot Drop → inverted & plantar flexed; ""steppage gait"""
What are the common causes of Common Peroneal Nerve Injury? {{c1:: Compression
(prolonged bedrest) Leg casts Fibular neck fracture}}
What are the motor functions of the Tibial Nerve? {{c1::Foot plantarflexion,
inversion; toe flexion}}
What are the common causes of Tibial Nerve (L4-S3) Injury? {{c1:: Tarsal tunnel
narrowing Baker's cyst Trauma (rare) }}
What are the two landmarks for locating the Pudendal Nerve in a pudendal nerve
block? {{c1::Ischial spine of pelvis and Sacrospinous ligament}} -Pudendal nerve
block is sometimes used to provide anesthesia during surgical procedures involving
perineum (eg; episiotomy) or during the second stage of labor if epidural
anesthesia is no longer feasible.
Osteoarthritis is caused by mechanical wear and tear of {{c1::articular (hyaline)}}
cartilage which is composed of type {{c1::II}} collagen
Abnormal {{c1::chondrocytes}} mediate the degradation and inadequate repair of
articular (hyaline) cartilage in Osteoarthritis secrete proteases and cytokines
What is the synovial fluid WBC in Osteoarthritis compared to RA?
{{c1::Osteoarthritis (200-2k) << RA (2k-50k)}} Osteoarthritis is degenerative, not
inflammatory; RA is inflammatory, and joints will be swollen, warm, etc.
Which hand joints are involved in Osteoarthritis? {{c1:: DIP (Heberden nodes) PIP
(Bouchard nodes) 1st CMC}} Not MCP
What is the only modifiable risk factor for Osteoarthritis? {{c1::Obesity}} other
risk factors: advances age, female gender, joint trauma (knee, hip)
What 3 pathogens are the most common causes of Septic Arthritis? {{c1::Staph aureus
Strep pneumo Neisseria gonorrhea}} If someone has acute monoarthritis → get them
to a hospital now. Septic arthritis will have purulent synovial fluid with WBCs >
50,000 and system symptoms of infections (fever, chills)
{{c1::Eosinophilic Granuloma}} is a benign proliferation of Langerhans cells in the
bone, most commonly involving the skull
Smooth muscle contraction is caused by the binding of calcium to {{c1::Calmodulin}}
which complex to activate MLC Kinase [Ca2+] in the cell and MLC
phosphorylation are the two major regulators of smooth muscle contraction/tone
{{c1::IP3}} is a second messenger that causes calcium release from the SR to
stimulate contraction in smooth muscle H1, a1, V1, M1, M3
How do cAMP and cGMP respectively cause smooth muscle relaxation? cAMP → {{c1::MLC
Kinase inhibition}} cGMP → {{c1::MLC phosphatase activation}} Hence why it seems
paradoxical that Gs receptors (B2) induce smooth muscle relaxation and
vasodilation.
What are the 4 major stimuli for ↑ Nitric Oxide production from L-arginine in
endothelial cells? {{c1:: Blood flow/shear stress Acetylcholine Bradykinin
Substance P}} BABeS make you produce Nitric Oxide
Chronic Tophaceous Gout is a consequence of long-standing hyperuricemia leading to
uric acid collections (tophi) in what three locations? (most commonly) {{c1:: Ears
Tendons (achilles) Bursa (olecranon)}}
What are the two mechanisms by which Alcohol can trigger Gout? {{c1:: ↑ Lactic
acid; ↓ uric acid secretion (main mechanism) ATP (purine) breakdown }} -Ethanol
depletes cellular NAD+ and increases cellular NADH. This high ratio of NADH/NAD
drives synthesis of lactate from pyruvate leading to lactic acidosis, a common
finding among heavy alcohol users. Uric acid and lactic acid utilize (and compete
with each other) the transporter URAT1 (urate transporter-1) for excretion in the
proximal tubule of the nephron. -↑ Lactic Acid → Activation of URAT1 -ATP (A =
Adenine = purine) breakdown
What are the 3 most common causes of Gout due to ↓ Uric acid excretion? {{c1::
Renal failure Thiazides Volume depletion}} any reduction in GFR → ↓ uric acid
excretion and increased uric acid reabsorption in PCT
What are the 4 most common causes of Gout due to ↑ Uric acid production? {{c1::
Myeloproliferative disorders (p. vera) Lesch-Nyhan Syndrome Von Gierke's Disease
Tumor Lysis Syndrome }} - Myeloproliferative Dx & TLS → ↑ cell turnover - Lesch-
Nyhan → ↓ HGPRT (no purine salvadge; all hypoxanthise broken down into uric acid) -
Von Gierke → Lactic Acidosis; Lactate competes with uric acid for excretion via
URAT1 (same mech. as alcohol)
Describe the findings of gout (uric acid) crystals under polarized light: {{c1::
Negative Birefringence: yellow under parallel light blue under perpendicular
light}}
What are the three drugs given to treat acute Gout attacks? {{c1:: NSAIDs
Glucocorticoids Colchicine}} Colchicine is a microtubule inhibitor that prevents
neutrophil chemotaxis
What is the mechanism of action of Colchicine? {{c1::Binds tubulin to inhibit
microtubules → impaired neutrophil chemotaxis}} Side effects include GI symptoms
(common) and rarely agranulocytosis
What two Xanthine-Oxidase inhibitors are used in the treatment of chronic Gout and
what is the pharmacokinetic difference between the two? {{c1:: Allopurinol
(competetive inhibitor) Febuxostat (non-competetive)}} Can actually cause acute
gout attack (via abrupt change in serum uric acid level) → initiate treatment with
NSAIDS or Colchicine
Xanthine Oxidase inhibitors (Allopurinol, Febuxostate) may increase the toxicity of
what two Immunosuppressant drugs? {{c1:: Azathioprine 6-mercaptopurine}}
Normally, xanthine oxidase metabolizes 6-MP to inactive metabolites.
Inhibition of XO by allopurinol results in accumulation of 6-MP to toxic levels
leading to side effects of nausea, diarrhea and pancytopenia
{{c1::Pegloticase}} is an IV recombinant procine uricase that is used to treat
severe, refractory Gout Peglo = pegylated = attached to polyethylene glycol (PEG)
to ↑ t1/2 Uricase = degrades uric acid to allantoin
What are the four major electrolyte abnormalities that result from Tumor Lysis
Syndrome? {{c1:: Hyperkalemia Hyperphosphatemia → hypocalcemia Hyperuricemia }}
What are the two drugs given to prevent acute renal failure (ATN via hyperuricemia)
in Tumor Lysis Syndrome? {{c1:: Allopurinol Rasburicase}} Rasburicase:
{{c1::Probenecid}} is a sulfa drug given to treat chronic gout via blocking PCT
reabsorption of uric acid Also → blocks secretion of penicillin, can cause uric
acid stones
IV discs generally herniate posteriolaterally due to the relatively weak and thin
support of the {{c1::posterior longitudinal ligament}}
{{c1::Spondylolisthesis}} is the forward displacement (slippage) of one vertebra
over another may cause radiculopathy
Spinal stenosis radiculopathy is aggrivated by {{c1::extension}} and relieved by
{{c1::flexion}} eg, old man has leg pain while walking (extended), but pain is
relieved by leaning forward (flexion) on railing.
What are the motor functions of the Sciatic nerve (L4-S3)? {{c1::Hip extension &
knee flexion (hamstrings)}}
What three bones a formed by Membranous ossification? {{c1:: Calvarium (skull)
Facial bones Clavicle }} Woven bone laid down directly (without cartilage),
then replaced by lamellar bone
What is the pathophysiologic cause of Rigor Mortis (post-mortem sustained muscle
contraction)? {{c1::Dead people cant make ATP → myosin heads cant disengage actin}}
Seronegative Spondyloarthritis conditions are associated with which HLA subtype?
{{c1::HLA-B27}} P.A.I.R. → Psoriatic arthritis, Ankylosing spondylitis, IBD,
Reactive arthritis
What is the treatment for Polymyalgia Rheumatica? {{c1::Corticosteroids}}
{{c1::Tetrodotoxin}} is a potent toxin in pufferfish that binds to fast voltage-
gated Na+ channels to prevent depolarization -It inhibits passive transport of
sodium Symptoms include paresthesias (face), weakness, loss of reflexes, nausea and
diarrhea. Patients can become paralyzed but remain conscious. Tx is supportive.
{{c1::Astrocytes}} are glial cells that prolferate in reactive gliosis after neural
injury Derived from: Neuroectoderm Marker: GFAP Functions: Support of neurons,
remove excess NT, repair & scar formation, BBB, extracellular K+ buffer, glycogen
fuel reserve buffer.
What is the major functional difference between Oligodendrocytes (CNS) and Schwann
Cells (PNS)? {{c1::Each oligodendrocyte can myelinate many axons (~30); each
schwann cell can only myelinate 1 axon. }} Oligodendrocytes are the prominent
type of glial cell in white matter. Derived from neuroectoderm. Injured in MS, PML,
leukodystrophies
Which type of nerve fibers are small, myelinated fibers that carry sensations of
cold and pain? {{c1::A-delta}}
What are the three nerve cell body changes that occur during Axonotmesis (axonal
retraction following nerve injury)? {{c1:: Swelling Chromatolysis (Nissl bodies
disappear) Peripheral nucelus}}
How much time does it take for ischemia to result in irreversible damage to the CNS
neurons? {{c1::4-5 minutes}} Neurons more sensitive to ischemia than glial cells
(high energy demands, lack glycogen). Most sensitive neurons: Hippocampus,
Cerebellar Purkinje cells, Neocortex, Striatum (basal ganglia)
Neurons in which 5 areas of the CNS are most vulnerable to irreversible ischemic
damage? {{c1:: Hippocampus Cerebellum (purkinje cells) Neocortex Watershed areas
Striatum (basal ganglia)}} irreversible damage begins 5 minutes after hypoxia
What are the most important microscopic changes that can be seen at each of the
following time intervals following cerebral ischemia? 12-24 h: {{c1::eosinophilic
cytoplasm, red neurons}} 24-72 h: {{c1::necrosis, neutrophils}} 3-5 d:
{{c1::microglia}} 1-2 wk: {{c1::gliosis (astros), vasc. proliferation}} >2 wk:
{{c1::glial scar}}
Liquefactive necrosis of brain tissue occurs 24-48 hours after an ischemic event
due to {{c1::lysosomal enzyme release from neutrophils}} Early → cell debris &
macrophages Late → cystic spaces and cavitation due to tissue digestion by the
lysosomal enzymes
What CNS structure senses changes in osmolarity? {{c1::OVLT (organ vasculosum
lamina terminalis)}} Anterior wall of third ventricle
What causes Vasogenic cerebral edema after trauma, tumors, or stroke?
{{c1::Breakdown of blood-brain barrier due to destruction of endothelial cell tight
junctions}} BBB = tight junctions between nonfenestrated capillary endothelial
cells + basement membrane + astrocyte foot process
What are the components of the blood-brain barrier? {{c1:: 1. tight junctions
between continuous capillary endothelial cells 2. basement membrane 3. astrocyte
foot process}} - Nonpolar (lipid soluble) substances easily cross BBB via
diffusion. - Glucose & Amino Acids cross BB via carrier-mediated transport
Where is GABA (y-aminobutyric acid) synthesized in the brain? {{c1::Nucleus
accumbens (subcortex)}} inhibitory; ↓ anxiety, Huntington's
Where is Acetylcholine synthesized in the brain? {{c1::Basal nucleus of Meynert
(subcortex)}} ↑ REM sleep; ↓ Alzheimers, Hungtington's dx
A lesion to which area of the brain results in fluent speech but impaired
comprehension? {{c1::Wernicke area → superior gyrus of left temporal lobe}}
"""Fluent aphasia"" → Patient is speaking total nonsense & have no idea that
they're doing so. Meaningless senstences, no stuttering. -Wernicke aphasia is
associated with right superior quadrant visual field defect as a result of
involvement of the inferior fascicle of the left optic radiations (Meyer loop) in
the temporal lobe. Note: it's not enough to just know ""wernicke's area"";
questions will likely list ""superior gyrus of left temporal lobe"" as answer
choice."
A patient who has fluent speech and intact comprehension, but cant repeat phrases
implies damage to what structure in the brain? {{c1::Arcuate fasciculus; connects
Wernicke's to Broca's area}}
Where are each of the three synapses for nerves of the Spinothalamic tract (in
ascending order)? 1 → {{c1::Ipsilateral dorsal horn}} 2 → {{c1::VPL of thalamus}} 3
→ {{c1::1º Somatosensory cortex}} principle function is to carry pain & temp via
A∆ and C fibers. Decussates in anterior white commisure at same level it enters
Where are each of the three synapses for nerves of the Dorsal Column tract (in
ascending order)? 1 → {{c1::Ipsilateral nucleus gracilis/cuneatus in caudal
medulla}} 2 → {{c1::VPL of thalamus}} 3 → {{c1::1º somatosensory cortex}}
Pressure, vibration, fine touch, proprioception. Decussates via internal
arcuate fibers in caudal medulla
What physical exam finding would indicate that loss of lower extremity sensation is
due to peripheral neuropathy (eg, diabetic neuropathy) instead of a spinal cord
lesion? {{c1::Sensation improves further up the leg}} Spinal cord lesion:
neuropathy would be consistent at all levels below lesion
Why does Galactosemia present within the first few days of life, while fructose
intolerance doesn't present until a baby stops breastfeeding? {{c1::Breast milk
contains lactose (galactose + glucose), but does not contain fructose or sucrose}}
"Sucrose (fructose + glucose) is usually first introduced to a baby via fruit
or formula. So look for ""8 month old recently just started feeding with
applesauce"" or something like that (idk what babies eat) to hint at fructose
intolerance"
Polio is a single-stranded RNA virus that causes destruction of the {{c1::Anterior
Horn}} of the spinal cord Anterior horn = LMN cell bodies → pure LMN lesion
(flaccid paralysis, fasciculations) Classic presentation → unvaccinated child,
febrile illness, ascending paralysis starting 4-5 days later -Acute LMN weakness
that begins asymmetrically in the lower extremities. Patients can have pro-dromal
flu-like symptoms before the onset of weakness. Diaphragmatic involvement results
in resp failure and death. -CSF analysis: typically consistent with viral infection
i.e; lymphocytic pleocytosis, normal or slightly increased protein levels, and
normal glucose levels.
Describe the presenation of Werdnig-Hoffman Disease: {{c1::Symmetric
hypotonia/weakness in Newborn (floppy baby) with tongue fasciculations}} Same
type of lesion (anterior horn, pure LMN) as polio, but presents at birth and leads
to death within months. Also, polio is Asymmetric
"What is the inheritance pattern of Werdnig-Hoffman Disease (""floppy baby disease)
and what gene is involved? {{c1:: autosomal recessive SMN1 gene}}" - Baby with
symmetric hypotonia/weakness - SMN1 → Survival Motor Neuron Protein → chromosome 5
What neurologic deficits are seen in Amyotrophic Lateral Sclerosis (ALS)? {{c1::
UMN and LMN NO sensory/autonomic deficits}} Hand weakness is often the first
presenting symptom.
What is the most common cause of death in Amyotrophic Lateral Sclerosis (ALS)?
{{c1::Aspiration pneumonia}} UMN & LMN deficits → dysphagia → aspiration pneumo
(Klebs, anaerobes) → death usually within 3-5 years
Familial cases of Amyotrophic Lateral Sclerosis are caused by a deficiency of
{{c1::Zinc Copper Superoxide Dismutase 1 (SOD1)}} SOD1 neutralizes free
radicals → deficient SOD1 → free radical damage
What spinal cord lesion(s) will result from Tabes Dorsalis (tertiary syphillis)?
{{c1:: posterior columns dorsal roots}} progressive sensory ataxia (impaired
proprioception), loss of DTRs
What spinal cord lesion(s) will result from Syringomyelia? {{c1::spinothalamic
fibers decussating in anterior white commissure}} Bilateral loss of pain & temp
only at level of lesion (usually C8-T1 ~ arms, hands)
What are the first two neurologic manifestations of Syringomyelia that has
expanded/become larger? {{c1:: Muscle weakness (ant. horn) Horner's syndrome (lat.
horn)}} -Syringomyelia damages lower motor neurons in the anterior horn of the
spinal cord, which causes bilateral weakness that can progress to bilateral flaccid
paralysis and muscle atrophy. This would result in dec or absent biceps reflex.
-Further expansion of the syrinx can cause damage to the corticospinal tract, which
manifests as hyperactive reflexes, spasticity and muscle spasm of the lower
extremities due to disruption of descending inhibitory fibers from upper motor
neurons.
What spinal cord lesion(s) will result from Subacute Combined Degeneration (B12
deficiency)? {{c1:: Spinocerebellar tracts Corticospinal tracts Dorsal columns}}
S.C.D. → ataxia, parasthesia, impaired proprioception, UMN signs. Due to ↑
Methylmalonic Acid levels
What are the neurologic findings of Brown-Sequard Syndrome (hemisection of spinal
cord) at and below the level of the lesion? At level: {{c1:: ispilateral loss of
all sensation ipsilateral LMN signs}} Below level: {{c1:: ipsilateral UMN signs
ipsilateral loss dorsal column s. contralateral loss spinothalamic s.}}
The spinal cord ends at which vertebral level? {{c1::L2 (conus medullaris)}} spinal
nerves continue inferiorly (cauda equina)
What type of RNA is produced by eukaryotic RNA Polymerase I? {{c1::ribosomal RNA}}
18S, 5.8S, 28S; form essential ribosomal components
What type of RNA is produced by eukaryotic RNA Polymerase II? {{c1:: mRNA snRNA
micro RNA}} - small nuclear (sn)RNA: mRNA splicing and transcription regulation -
micro RNA: cause gene silencing via translation arrest or mRNA degradation
What type of RNA is produced by eukaryotic RNA Polymerase III? {{c1:: tRNA 5S
ribosomal RNA}} - tRNA: adaptor molecule linking codons with specific amino acids
- 5S rRNA: essential component of 60S ribosomal subunit
Where does the Olfactory Nerve (CN I) exit the skull? {{c1::cribiform plate of
ethmoid bone}}
Which cranial nerve is the only CN without thalamic relay to the cortex?
{{c1::Oflactory (CN I)}} Nerves pass through cribriform plate of ethmoid bone
→ synapse in olfactory bulb → piriform cortex. Can be damaged by skull fracture.
What are the adult derivatives of the Diencephalon? (posterior division of
forebrain) {{c1:: Thalamus Hypothalamus Optic Nerve (CN II) Third ventricle}}
Only CN I & II found outside of brainstem.
What abnormalities are seen with Occulomotor (CN III) nerve palsy? {{c1:: Eye down,
out, pupil dilated, ptosis }}
What drug is used to treat Trigeminal Neuralgia? {{c1::Carbamazepine}}
What are the signs and symptoms of Abducens Nerve (CN VI) palsy? {{c1::Diplopia,
affected eye can't move laterally (outward)}} Abducens nerve can be damaged due
to Cavernous Sinus Thrombosis
What area of the face would be paralyzed as a result from a LMN lesion to CN VII?
{{c1::Complete ipsilateral paralysis}} forehead not spared (in contrast to UMN
lesion)
What area of the face would be paralyzed as a result from a UMN lesion to CN VII?
{{c1::Contralateral face with forehead sparing}} forehead receives dual
innervation from both sides of brain
What are the symptoms of Facial Nerve (VII) Palsy? (excluding facial muscle
deficits) {{c1:: Loss of corneal reflex (motor part) Loss of taste (anterior 2/3
tongue) Hyperacusis (stapedius paralysis)}} Hyperacusis → can't tolerate
sounds. Stapedius muscle (paralyzed) normally stablizes stapes in ear. Just
remember branchial arches.
Bell's Palsy is the most common cause of peripheral facial palsy due to {{c1::HSV-1
reactivation}} Tx with corticosteroids and acyclovir. Other causes of peripheral
facial palsy include Lyme, Herpes zoster, Sarcoidosis, tumors (parotid), diabetes
What are the 5 most common causes of peripheral facial nerve (CN VII) palsy? (not
including Bells/HSV) {{c1:: Lyme disease Tumor (parotid) Herpes Zoster (Ramsay
Hunt) Sarcoidosis Diabetes Mellitus}} Her DaMn Lymes Taste Sour (MFW eating the
lime after a tequila shot ↓)
What are the motor and sensory functions of the Glossopharnyngeal Nerve (CN IX)?
{{c1:: Taste, sensation (post. 1/3 tongue) Salivation (parotid) Swallowing Monitor
carotid body/sinus Stylopharyngeus}} Taste, salivate, and swallow carots
stylishly Stylopharyngeus → elevation of pharynx/larynx
"Which cranial nerves can be tested by making the following sounds? ""kuh kuh kuh""
→ {{c1::CN X}} ""Mi Mi Mi"" → {{c1::CN VII}} ""La La La"" → {{c1::CN XII}}" X →
raises palate & cough reflex VII → moves lips (facial nerve) XII → moves tongue
What two cardiac pathologies can cause Recurrent Laryngeal Nerve (CN X) damage
(hoarseness)? {{c1:: Dilated Left Atrium (2º to MS) Aortic Dissection}}
What are the two phyiscal exam findings indicative of damage to the Accessory Nerve
(XI)? {{c1:: Can't turn head towards normal side (SCM) Shoulder droop (affected
side)}}
What are the afferent and efferent branches of the Lacrimation Reflex? Afferent:
{{c1::V1}} Efferent: {{c1::VII}} Note: loss of lacrimation reflex via V1 damage
does not preclude emotional tears
What is the only tongue muscle that is not supplied by the hypoglossal nerve (XII)
and which nerve innervates it? {{c1::Palatoglossus (CN X)}}
Which nerve(s) and/or vessel(s) exit the skull through the optic canal? {{c1::CN II
Ophthalmic artery}}
Which nerve(s) and/or vessel(s) exit the skull through the Superior Orbital Fossa?
{{c1::CN III, IV, V1, VI}} Just think which nerves have eye functions
Which nerve(s) and/or vessel(s) exit the skull through the Foramen Rotundum?
{{c1::V2}} V1, V2, V3 → SRO
Which nerve(s) and/or vessel(s) exit the skull through the Internal Auditory
Meatus? {{c1::VII, VIII}}
Which nerve(s) and/or vessel(s) exit the skull through the Foramen Spinosum?
{{c1::Middle Meningeal Artery}} Branch of Maxillary artery
Which nerve(s) and/or vessel(s) exit the skull through the Jugular Foramen? {{c1::
IX, X, XI Jugular vein}}
How do ischemic and hemorrhagic strokes differ in their initial presentation?
{{c1::ischemic stroke symptoms have slow onset over hours; hemorrhagic is sudden
onset}} best first test → non-contrast head CT
What is the best first test when evaluating a probable stroke patient? {{c1::Non-
contrast CT (to exclude hemorrhage)}} Must be done before tPA can be given for
thrombus/embolism.
Which imaging test is most sensitive for detecting the presence of ischemic stroke?
{{c1:: Diffusion-weighted MRI (3-30 mins)}} CT takes 6-24 hours to detect
ischemic changes. Non-contrast CT must always be done first to exclude hemorrhage
(so you don't give tPa and kill them)
What are the symptoms of a Middle Cerebral Artery (MCA) stroke and which symptoms
are unique in right vs left MCA strokes? (Assume left side is dominant) Both →
{{c1::Contralateral motor and sensory loss to face, upper extremity}} Left →
{{c1::Aphasia (Wernicke, Broca)}} Right → {{c1::Hemineglect}} Remember: - UMN
lesion to facial nerve will spare contralateral forehead. - Werkicke's area =
Temporal lobe - Broca's area = Frontal lobe
What are the symptoms of an Anterior Cerebral Artery (ACA) Stroke?
{{c1::Contralateral paralysis and sensory loss of lower extremity }}
What are the possible symptoms of a Posterior Cerebral Artery (PCA) Stroke? {{c1::
Contralateral Hemianopia w/ macular sparing Visual hallucinations Visual
agnosia/alexia Thalamic Syndrome}} Thalamic Syndrome:
What is the cause of Hemiballism (wild, flinging movements of extremities)?
{{c1::Contralateral lesion of Subthalamic nucleus (lacunar stroke)}} remember:
STN stimulates the GPi to inhibit the thalamus (suppress movement). So without STN
→ no indirect (inhibitory) basal ganglia pathway → wild flailing of contralateral
limb(s)
What is the classic triad of Lacunar Stroke presentation? {{c1:: Uncontrolled HTN
Unilateral pure motor or sensory loss Negative initial head CT}} "Lacuunar. Also no
""cortical signs"" (aphasia, agnosia, hemianopsia)"
What is the cause of Lacunar Strokes? (micro-infarcts to areas of brain)
{{c1::Hyaline arteriosclerosis 2º to uncontrolled HTN}} proposed mechanism
include lipohyalinosis and microatheromas (macrophages in blood vessel)
Deficiency of what Vitamin can cause ataxia via degeneration of the spinocerebellar
and dorsal column tracts? (not including B12) {{c1::Vitamin E}} Vitamin E →
antioxidant. Similar neurologic presentation as B12, but there will no be
megaloblastic anemia or ↑ Methylmalonic acid. May see hemolytic anemia. Deficiency
associated with Abetalipoproteinemia
Medial Medullary Syndrome is caused by a stroke of which artery? {{c1::Anterior
spinal artery}} Medial Medullary Syndrome 1. Corticospinal tract → contr.
paralysis of upper and lower limbs (Motor = medial) 2. Medial Lemniscus → ↓ contr.
proprioception (Medial = Medial) 3. Hypoglossal Nerve (CN XII) → ipsilateral
hypoglossal dysfx. Tongue deviates ipsilaterally. (XII = divisible by 12 = medial)
By rule of 4's, all are Medial structures + CN XII localizes to medulla.
Which arteries provide blood supply to the medial and lateral Midbrain? Medial →
{{c1::PCA (paramedian br)}} Lateral → {{c1::PCA}}
Which arteries provide blood supply to the medial and lateral Pons? Medial →
{{c1::Basilar}} Lateral → {{c1::AICA}}
Which arteries provide blood supply to the medial and lateral Medulla? Medial →
{{c1::ASA}} Lateral → {{c1::PICA}}
What cardiac abnormalities are most commonly associated with Downs Syndrome? {{c1::
ASD (primum) VSD}} Endocardial Cushion defects
Why does Alzheimer's Disease often occur early (~50) in patients with Down
Syndrome? {{c1::Amyloid Precursor Protein (APP) is found on chromosome 21}} "APP
breakdown forms beta amyloid → ""senile plaques"" of Alzheimer's"
Down Syndrome increases the risk of which two cancers? {{c1:: ALL AML (M7
subtype)}} M7 AML → Megakaryoblastic leukemia -M7 AML → before the age of 5 years
-ALL → after the age of 5 years
What genetic abnormality causes mild Down Syndrome? {{c1::Somatic mosaicism → post-
fertilization mitotic error in somatic cells}} 1% of cases. Some cells trisomy 21,
others normal. No association with maternal age.
What are serum marker abnormalities are associated with Down Syndrome in first
trimester maternal blood screening? {{c1:: ↓ PAPP-A ↑ B-hCG}} PAPP-A = Pregnancy
Associated Plasma Protein A
What serum marker abnormalities are associated with Down Syndrome in second
trimester maternal blood screening? {{c1:: ↑ B-hCG, Inhibin A ↓ AFP, Estriol }}
What non-skeletal defects are associated with Edward Syndrome (trisomy 18)? {{c1::
GI defects Congenital heart disease }} GI (75%) → Meckel's, malrotation,
omphalocele CV (50%) → VSD, PDA Most die in utero, the rest usually die < 1 year
What serum marker abnormalities are associated with Edward Syndrome in first
trimester maternal blood screening? {{c1::↓ PAPP-A, B-hCG}}Same as Patau. Down
Syndrome is only trisomy with ↑ hCG
What serum marker abnormalities are associated with Patau Syndrome in first
trimester maternal blood screening? {{c1::↓ PAPP-A, B-hCG}}Same as Edward Syndrome.
Down Syndrome is only trisomy with ↑ B-hCG in first trimester
What serum marker abnormalities are associated with Edward Syndrome in second
trimester maternal blood screening? (quad screen) {{c1::↓ AFP, Estriol, B-hCG,
Inhibin A}} Every single serum marker is low in Edward Syndrome.
What non-physical (internal) abnormalities are associated with Patau Syndrome
(trisomy 13)? {{c1:: Polycystic kidney disease Congenital heart disease}} PKD is
unique to Patau. Also holoprosencephaly, cutis aplasia, cleft lip/palate,
polydactyly
What serum marker abnormalities are associated with Patau Syndrome in the first
trimester maternal blood screening? {{c1::↓ PAPP-A, B-hCG}}All lab markers in the
second trimester (quad screen) will be normal. Patau is usually diagnosed by
ultrasound.
Genomic imprinting, the process by which one gene copy is silenced, occurs by what
mechanism? {{c1::Methylation of cytosine in DNA}} "Occurs during gametogenesis
(before fertilization). Genes ""marked"" as being parental/maternal origin → only
one allele is expressed in imprinted genes."
Prader-Willi and Angelman syndromes are both imprinting syndromes that involve what
chromosomal segment? {{c1::15q11-q13}} Prader-Willi → Maternal gene silenced
(imprinted), Paternal allele deleted or mutated Angelman → Paternal UBE3A gene
silenced (imprinted); Maternal allele deleted or mutated
Which genes (maternal vs paternal) are deleted or mutated in the two genomic
imprinting disorders? Prader-Willi → {{c1::Paternal PWS}} AngelMan → {{c1::Maternal
UBE3A}} Prader-Willi = Paternal AngelMan = Maternal
While most cases (75%) of Prader-Willi Syndrome are caused by paternal gene
deletion, what other genetic abnormality can cause this condition? {{c1::Maternal
uniparental disomy (25%)}} Angelman Syndrome rarely (5%) due to uniparental
disomy because paternal non-disjunction is much less common.
What are the symptoms of Prader-Willi Syndrome? (5) {{c1:: Obesity Hyperphagia
Hypotonia Hypogonadism Intellectual Disability (mild)}} """OHH, HI Prader-
Willi"". Tommy Wiseau definitely had some mild intellectual disability."
Deletion Syndromes (DiGeorge, Cri-du-chat, Williams) are usually due to what type
of replication error? {{c1::crossover error in meiosis}}
What congenital deletion causes Cri-du-chat Syndrome? {{c1::5p-}}
What congenital deletion causes Williams Syndrome, and what does this deleted
segment code for? {{c1::Partial deletion of long arm of chromosome 7 → codes for
Elastin}} """Elfin"" facies, intellectual disability, hypercalcemia, well-
developed verbal skills, extremely friendly, CV problems Think Will Ferrell in ELF"
List the input and output destination of the Thalamic Ventral Posterolateral
Nucleus: {{c1::Spinothalmic & Dorsal column (ML)::input}} ↓ VPL ↓ {{c1::1º
Somatosensory cortex::destination}} Relays all sensory → pain, temp, touch,
proprioception, vibration
List the input and output destination of the Thalamic Ventral Postero-Medial
Nucleus: {{c1::Trigeminal & gustatory::input}} → VPM → {{c1::1º Somatosensory
cortex::destination}} Postero-Medial = Post Meal (taste plus facial sensation)
List the input and output destination of the Thalamic Lateral Geniculate Nucleus:
{{c1::CN II::input}} → LGN → {{c1::Calcarine sulcus::destination}} CN II, optic
chiasm, optic tract → Lateral = Light
List the input and output destination of the Thalamic Medial Geniculate Nucleus:
{{c1::Superior olive & inferior colliculus::input}} ↓ MGN ↓ {{c1::Auditory cortex
of temporal lobe::destination}} Hearing; Medial = Music
List the input and output destination of the Thalamic Ventral Lateral Nucleus:
{{c1::Basal Ganglia::input}} → VL → {{c1::Motor cortex::destination}} Movement
What is the function of the Lateral nucleus of the Hypothalamus? {{c1::Hunger}}
Lesion → anorexia, failure to thrive in babies
What is the function of the Ventromedial nucleus of the Hypothalamus?
{{c1::Satiety}} Lesion → Hyperphagia, obesity
What is the function of the Anterior nucleus of the Hypothalamus? {{c1::Cooling}}
Lesion → Hyperthermia
What is the function of the Posterior nucleus of the Hypothalamus? {{c1::Heating}}
Lesion → inability to thermoregulate
What is the function of the Suprachiasmatic nucleus of the Hypothalamus?
{{c1::Circadian rhythm}} Side of melatonin action
Fever is triggered by inflammatory cytokine stimulation of {{c1::Prostaglandin E2}}
synthesis, which increases the anterior hypothalamus set point Fever inducing
cytokines: IL-1, IL-6, TNF-a
What are the two actions of Leptin in the hypothalamus? {{c1:: inhibits Lateral
nucleus stimulates Ventromedial nucleus}} """Leptin makes you thin"" → reduces
hunger (LN); promotes satiety (VMN). Released by adipocytes after eating."
Kluver-Bucy Syndrome can be caused by {{c1::HSV-1::pathogen}} encephalitis HSV-1
is the most common cause of sporadic encephalitis and targets the Temporal lobes →
KB Syndrome is caused by bilateral destruction of the amygdala (located in temporal
lobes)
What symptom would result from bilateral damage to the Hippocampus?
{{c1::Anterograde amnesia}} Can't make new memories. Like that Adam Sandler movie
with Drew Barrymore. Hippocampus is most sensitive to hypoxic damage; infarction of
hippocampal branches of PCA, anterior choroidal arteries
What is the classic pathology finding in a patient with Wernicke-Korsakoff Sydrome?
{{c1::Bilateral atrophy of mammilary bodies}} Associated with Thiamine (B1)
deficiency and alcoholism.
What is the triad of symptoms in Wernicke Encephalopathy? {{c1:: Confusion Ataxia
Nystagmus/visual probs}} C.A.N. of beer. Reversible with Thiamine (B1).
Korsakoff is distinguished by amnesia/confabulation and lack of response to
Thiamine. -MRI: Bilateral, symmetric hyperintensities are seen in the medial
portions of the thalamus (overlay)
What are the two psychiatric symptoms that distinguish Korsakoff Syndrome from
Wernicke's? {{c1:: Anmesia (anterograde > retro) Confabulation}} Confabulation →
Can't remember so they make things up. Irreversible.
Which two structures in the inner ear vestibular system detect Linear motion?
{{c1::Utricle & Saccule}} Eg, gravity, moving forward/backward. Contain
Otoliths (calcium carbonate crystals) that sit on top of hair cells and stimulate
action potentials when linear movement is detected.
Horizontal (L/R) and torsional nystagmus are caused by {{c1::peripheral}}
vestibular dysfunction Aka a problem with the vestibular apparatus itself.
Upbeat/downbeat nystagmus caused by central vestibular dysfunction (brainstem
lesions, strokes, tumors)
Vertical nystagmus (upbeat, downbeat) is caused by {{c1::central}} vestibular
dysfunction Central = BAD → Brainstem or cerebellar lesion, vertebrobasilar stroke,
TIA, posterior fossa tumor, etc.
What in-office positional maneuver can be done to reproduce & diagnose Benign
positional vertigo (peripheral)? {{c1::Dix-Hallpike Maneuver}} Seated pt, extend
neck and turn head to side, rapidly lie patient down on table and let head hang
over table.
Benign Positional Vertigo is a peripheral cause of vertigo occuring with head
turning/position that is caused by {{c1::Canalithiasis (calcium debris in
semicircular canal)}} Diagnose w/ Dix Hallpike Maneuver. Treat with Epley
Maneuver. IF DHP maneuver doesn't yield typical BPV results → consider CNS imaging
to look for central causes of vertigo
What is the cause of Meniere's Disease? {{c1::Endolymph accumulation causing
swelling of the labyrinthine system}} Benign, peripheral cause of vertigo.
Triad of symptoms → Tinnitus, Sensorineural hearing loss, Vertigo
What are the treatments for Meniere's Disease? {{c1:: Low salt diet Diuretics}}
Meniere's is caused by build-up of endolymph fluid → salt restriction &
diuretics → ↓ fluid. Antihistamines, Antiemetics, Anticholinergics sometimes used
for symptomatic relief.
What fundoscopic finding is indicative of Increased Intracranial Pressure?
{{c1::Papilledema}} Bilateral swelling of the optic disc, blurred margins of
optic disc on fundoscopy. Also seen in severe HTN. Causes → Tumors, cerebral edema
(stroke/trauma), hydrocephalus, Idiopathic
Decorticate posturing (arms flexed) commonly indicates {{c1::cerebral hemisphere}}
damage Above Red Nucleus
Decerebate posturing (arms extended) commonly indicates {{c1::brainstem}} damage
Decerebate = Below Red Nucleus
Cingulate (subfalcine) Herniations under the falx cerebri can compress the
{{c1::anterior cerebral artery}} Contralateral leg paraylsis. Subfalcine = below
falx
Uncal herniation is a displacement of the {{c1::medial temporal}} lobe through the
tentorium, which may compress the midbrain Ipsillateral CN III compression,
can collapse ipsilateral PCA, cerebral peduncle compression
What are the four structures that may be damaged/compressed as a result of an Uncal
Herniation? {{c1:: CN III (ipsilateral) PCA Cerebral peduncle (crus cerebri)
Basilar artery}} "Seein 3 at PCB - CN III → ""blown"" pupil ipsilateral - PCA →
Homonymous hemianopsia - C. Peduncle → contralateral or ipsilateral paresis
(compression of Kernohan's notch) - Basilar A. → duret hemorrhage of pons and
midbrain"
What type of herniation will cause loss of consciousness with small reactive pupils
that eventually become nonreactive? {{c1::Central (downward) Transtentorial
Herniation}} Thalamus, hypothalamus, medial parts of both temporal lobes
forced through tentorium → brainstem caudally displaced → loss of consciousness →
FATAL
Tonsillar Herniations are often caused by a posterior fossa mass forcing the
cerebellar tonsils downward through the {{c1::foramen magnum}} Labeled (4) in
image: Dont forget CN IX, X, XI exit skull thru foramen magnum
Why do cerebellar tonsillar herniations often cause death? {{c1::compression of
medulla damages centers for respiration & cardiac rhythm control →
cardiorespiratory failure}} Labeled (4) in image
Epidural Hematomas are caused by rupture of the {{c1::middle meningeal}} artery
often due to fracture of the {{c1::temporal}} bone Always due to trauma. Often
fracture at temporal bone part of Pterion
What is the special feature of Epidural Hematoma presentation? {{c1::Lucid
Interval}} Trauma (head injury) → Loss of consciousness → Lucid interval (aka,
wakes up and feels ok) → passes back out 30 mins later
Subdural Hematomas are caused by rupture of what vascular structure(s)?
{{c1::Bridging VEINS between dura & arachnoid space }} Veins → slowwww bleed
due to low pressure
How will a Subdural Hematoma appear on head CT? {{c1::Crescent-shaped bleed }}
What brain injury is associated with Shaken Baby Syndrome? {{c1::Subdural
Hematoma}} Rupture of bridging veins between dura and arachnoid mater. Slow bleed.
Crescent shaped on CT.
What is the classic presentation of a Subdural Hematoma? {{c1::Confusion/headache
weeks after head injury}} Rupture of bridging veins between dura and arachnoid.
Veins = low pressure → slow bleed → takes weeks to develop symptoms
How will Subarachnoid Hemorrhages appear on brain CT? {{c1:: White attenuation
(blood) in basal cisterns }}
"How does a Subarachnoid Hemorrhage present? {{c1::Sudden, ""thunderclap"" headache
(""worst headache of my life"") with fever and nuchal rigidity}}" Fever,
nuchal rigidity common. No focal deficits. Xanthochromia on spinal tap.
Which type of intracranial bleeding will show Xanthochromia (yellowing) on CSF
spinal tap? {{c1::Subarachnoid Hemorrhage}}
What 4 congenital medical conditions are associated with Saccular/Berry Aneurysms?
{{c1:: ADPKD Coarctation of Aorta Marfan Syndrome Ehlers-Danlos}} Get your
Berrys at ACME.
Hemorrhagic strokes most commonly occur in which areas of the brain? (5) {{c1::
Putamen (35%) Subcortex (30%) Cerebellum (16%) Thalamus (15%) Pons (5-12%)}}
Hemorrhagic stroke of Putamen → Lenticulostriate arteries
What are the symptoms of a Hemorrhagic stroke of the Putamen? {{c1:: Contralateral
hemiparesis & hemisensory loss with gaze deviation towards side of bleed}} So if
someone comes in with complete paralysis and sensory loss on the left side and
their eyes are deviated to the right, that right there my friend is a hemorrhagic
stroke of the putamen. Always affects more than just the putamen; - Internal
capsule damage → hemiparesis - Thalamic damage → hemisensory loss - Front Eye Field
→ Gaze deviation
What is the pathophysiologic cause of Neonatal Intraventricular Hemorrages?
{{c1::Reduced glial fiber support & poor autoregulation of BP}} Poor
autoregulation of BP to Germinal Matrix (highly vascularized area in primi's)
causes hemorrhage into Lateral Ventricles. Full term/mature babies have decreased
vascularity to germinal matrix, so it isn't a problem.
What are the 4 main risk factors for Berry aneurysms? (not including congenital
medical conditions) {{c1:: Old age HTN Smoking African Americans}}
What drug is given to prevent cerebral vasospasm after a Subarachnoid Hemorrhage?
{{c1::Nimodipine}} Calcium channel blocker; Vasospasms triggered by blood
occur days after initial hemorrhage and worsen neuro symptoms.
Where is the most common site of a Berry (saccular) aneurysm? {{c1::junction of
ACom + ACA}} ACom/ACA > PCom/PCA > MCA
What are the symptoms of compression and/or rupture of an ACom Berry Aneurysm?
{{c1:: Compression: bitemporal hemianopia Rupture: contralateral LE hemiparesis &
sensory loss}}
What are the symptoms of compression and/or rupture of a PCom Berry Aneurysm?
{{c1::Compression; unilateral headache, eye pain, CN III palsy}} "-PCom compressing
CN III results in ipsilateral pupillary dilation, drooping of the eyelid and gaze
that is directed ""down and out"" Remember that CN III palsies due to compression
will start with only the dilated pupil (no motor loss), because → parasympathetics
mediating pupil constriction are located in the outer/superficial nerve"
What does pupil sparing indicate when evaluating etiologies of CN III palsy?
{{c1::Diabetic ischemic neuropathy}} Diabetes causes disease of small vessels,
which course through the center of the nerve, where the motor fibers are located.
So, ischemia only to the center of the nerve will spare the parasympathetics (pupil
constrictors) on the outside of the nerve.
{{c1::Charcot-Bouchard Aneurysms}} are micro-aneurysms of the lenticulostriate
arteries to the basal ganglia, thalamus, etc Associated with chronic HTN. Not
visible on angiography (super small)
Alteplase (TPA) can be given for thrombolytic therapy of an ischemic stroke only if
administered within {{c1::3-4.5 hours}} of onset Contraindications → ANY
history of IC bleed, stroke or head trauma within past 3 months, BP > 185/110, INR
> 1.7, platelets < 100k, ↑ PTT. glucose < 50 mg/dL
The notochord secretes {{c1::Sonic Hedgehog Protein (SHH)}} to induce the overlying
ectoderm to differentiate into the neural tube and neural crest cells Notochord
becomes nucleus pulposus (IV discs)
{{c1::Spina Bifida}} is a neural tube defect caused by failure of the caudal
neuropore to close posteriorly Anencephaly → Rostral neuropore fails to close
Anteriorly
{{c1::Anencephaly}} is a neural tube defect caused by failure of the rostral
neuropore to close anteriorly No forebrain, open calvarium, mother will have
polyhydramnios in utero (can't swallow if you don't have a head)
What are the four major risks for Neural Tube Defects? {{c1:: ↓ Folic Acid Maternal
Diabetes Obesity Drugs }} Drugs → Valproic acid, Carbamazepime, Methotrexate,
Trimethoprim
Meningomyeloceles are severe NTDs that are almost always associated with what other
embryological defect? {{c1::Chiari II Malformations}} Chiari II → herniation of
vermis & tonsils (2 stuctures) through foramen magnum
What gestational finding is associated with Anencephaly? {{c1::Polyhydramnios}}
They have no head, so they can't swallow amniotic fluid.
{{c1::Encephalocele}} is a rare NTD where the brain or meninges herniate through a
skull defect (most commonly occipital bone)
What findings on amniotic fluid sampling are indicative of Neural Tube Defects?
{{c1::↑ AFP and AChE }} Measure serum AFP at 16 - 18 weeks gestation. If serum AFP
is high, check the amnionitc fluid. Spina Bifida occulta will have normal AFP tho.
Holoprosencephaly is a failure of the cerebral hemispheres to separate at 5-6 weeks
gestation thought to be caused by mutations in {{c1::Sonic Hedgehog Signaling
Pathway}} SHH gene → involved in AP axis patterning, CNS development, also
produced at base of limbs in zone of polarizing activity (Just google it if for
some reason you haven't seen this yet and you're curious)
What two conditions are associated with Holoprosencephaly? {{c1:: Patau syndrome
(trisomy 13) Fetal alcohol syndrome}} Patau syndrome will also have
polydactyly, cutis aplasia, Pkd
{{c1::Chiari I Malformation}} is a congenital displacement of the cerebellar
tonsils below the foramen magnum Usually fine at birth; manifests in adulthood
with headaches and cerebellar symptoms. Associated with Syringomyelia
{{c1::Chiari II Malformation}} is congenital herniation of the cerebellar vermis
and tonsils through the foramen magnum Chiari II = 2 structures. Cause
aqueductal stenosis (non-communicating hydrocephalus). Associated with
meningomyelocele
"How do Chiari I Malformations typically present? {{c1::""Cough Headache"" and
Ataxia starting around 18 years }}" """cough headache"" = meningeal irritation.
Also may see CN dysfunction due to brainstem compression."
What are the two major complications (symptoms) of a Chiari II Malformation? {{c1::
Hydrocephalus (aqueduct obstruction) Paralysis (below meningomyelocele)}}
Dandy Walker Malformation is congenital agenesis of the {{c1::cerebellar vermis}}
which leads to cystic enlargement of the {{c1::4th ventricle}} Cysts of 4th
ventricle → Hydrocephalus
Most adult brain tumors are located {{c1::above}} the tentorium, while most
childhood brain tumors are {{c1::below}} the tentorium Children = short =
infratentorial (& vice versa)
Brain cancer metastases usually originate from which 5 primary sites? (rank by
frequency) {{c1::Lung > breast > melanoma, colon, kidney}} Multiple, well-
circumscribed tumors at white/gray matter junction.
Which two brain tumors stain GFAP(+)? {{c1:: Glioblastoma (adults) Astrocytoma
(kids)}} GFAP = Glial Fibrillary Acidic Protein. Intermediate filament. Glial
origin. Derived from NCCs
Meningiomas are benign extra-axial brain tumors that arise from {{c1::arachnoid
cells}}
What is the biggest risk factor for development of a Meningioma? {{c1::Prior
radiation}} Childhood malignancies treated with radiation → 20 years of latency,
peace, and happiness → Meningioma as adult. Affects females > males
Schwannomas are classically located at the {{c1::cerebellopontine angle}} and cause
dysfunction of cranial nerves {{c1::VII and VIII (causes unilateral sensorineural
hearing loss and tinnitus, usteady gait)}} Can be anywhere along any
peripheral nerve. Vestibular Schwannoma = localzied to CN VIII in internal acoustic
meatus.
Schwannomas stain positive for what tumor marker? {{c1::S100}} Schwannoma ~ S100.
Neural crest cell origin. Other cancers that are S100+ include Melanomas and
Langerhans cell histiocytosis
What autosomal dominant disorder is assocaited with Bilateral Acoustic Schwannomas?
{{c1::Neurofibromatosis II}} NF2 = chromosome 22 = 2 schwannomas
What three CNS tumors are associated with Neurofibromatosis type II? {{c1::
Schwannomas (2x) Meningiomas Ependymomas}} MISME
Oligodendrogliomas are slow-growing adult brain tumors of {{c1::white matter}} most
commonly located in the {{c1::frontal}} lobe Oligodendrocytes = myelinate axons
in white matter
Pilocytic Astrocytomas are the most common brain tumor in children and are usually
located in {{c1::posterior fossa (cerebellum)}} Rosenthal fibers on histology
How do Pilocytic Astrocytomas appear on imaging? {{c1::Cystic and Solid mass in
posterior fossa }}
What is the classic histology finding of Pilocytic Astrocytomas? {{c1::Rosenthal
fibers → eosinophilic, corkscrew fibers}}
Medulloblastomas are malignant childhood brain tumors that usually occur in the
{{c1::cerebellum (midline)}} and present with {{c1::truncal ataxia}} Most common
malignant childhood brain tumor. Can compress 4th ventricle, causing non-
communicating hydrocephalus. PNET+
Medulloblastomas stain positive for what tumor marker? {{c1::PNET (primitive
neuroectodermal tumor)}} Most common malignant brain tumor in childhood, but
75% of children survive to adulthood via a combo of surgery, radiation and chemo.
Many complications.
What are the major complications of Medulloblastomas? {{c1:: Hydrocephalus
(compress 4th vent.) Metastases to dura of spinal cord}} Spinal cord mets in
dura. Will see multiple nodules. Tend to occur in lower spinal cord and can cause
cauda equina syndrome. Back pain, focal neuro lesions can occur
Ependymomas are childhood brain tumors that most commonly arise from the {{c1::4th
ventricle}} and present with {{c1::hydrocephalus}} Obviously Ependymal cell
origin. Poor prognosis
Hemangioblastomas are rare vascular tumors of the cerebellum that can secrete what
hormone? {{c1::EPO}} Causing polycythemia.
What autosomal dominant syndrome is associated with Hemangioblastomas? {{c1::Von-
Hippel Lindau disease}} Deletion of VHL (tumor suppressor) on chromsome 3. Causes
Hemangioblastomas in the retina, brainstem, cerebellum and spine, Angiomatosis,
bilateral RCC, and Pheochromocytomas
How do Craniopharyngiomas appear on CNS imaging? {{c1:: Calcified crystals in Sella
turcica }} "Remember; derived from Rathke's Pouch (outpouching of the pharyngeal
roof that develops into the anterior pituitary gland) = Ectoderm -Histopathologic
findings: cystic mass filled with dark, browinsh-yellow, oily fluid (""motor oil-
like"") -MRI:"
Which brain tumor can compress the pre-tectal area of the midbrain and consequently
cause Perinaud Syndrome? {{c1::Pinealoma}} Perinaud Syndrome → Paralysis of
upward gaze, Pseudo-Argyll-Roberston pupils, Hydrocephalus (via compression of
cerebral aqueduct)
What layers must be penetrated during a Lumbar Puncture (spinal tap)? {{c1::skin →
ligaments → dura → arachnoid → stop}} L4-L5. Target is subarachnoid space. Does
not pierce pia.
What are the four most serious complications of meningitis? {{c1:: Death (pretty
serious) Hydrocephalus Hearing loss Seizures}} - Mostly bacterial meningitis -
Hydrocephalus → post-meningitis scarring of arachnoid villi, leading to ↓ CSF
absorption = communicating hydroceph.
Describe the CSF fingings in Bacterial Meningitis: Cell type: {{c1::↑ PMNs}}
Protein: {{c1::↑}} Glucose: {{c1::↓}}
Describe the CSF fingings in Viral Meningitis: Cell type: {{c1::↑ Lymphocytes}}
Protein: {{c1::normal or ↑}} Glucose: {{c1::normal}}
Describe the CSF fingings in Fungal/TB Meningitis: Cell type: {{c1::↑ Lymphocytes}}
Protein: {{c1::↑}} Glucose: {{c1::↓}}
What are the three most common causes of meningitis in Newborns (0-6 months)?
{{c1:: Group B Strep (agalactiae) E. Coli Listeria }} Tx: Ampicillin + Gentamycin
What are the four most common causes of meningitis in Children (6mo-6yrs)? {{c1::
Strep Pneumo Neisseria meningitidis H. Flu type B Enteroviruses}} - tx:
ceftriaxone + vancomycin - Enteroviruses → Coxsackie, echovirus - H. Flu →
immigrant/unvaccinated
What are the four most common causes of meningitis in 6-60 year olds? {{c1:: Strep
pneumo Neisseria meningitidis Enteroviruses HSV-2}} - tx: ceftriaxone +
vancomycin - N. meningitis → #1 in teens
What are the three most common causes of meningitis in Elderly (60+)? {{c1:: Strep
pneumo Gram (-) rods Listeria}} - tx: ceftriaxone + vancomycin + Ampicillin
Why are newborns and elderly more succeptible to Listeria meningitis? {{c1::poor
cell mediated immunity}} gram (+) facultative intracellular rod.
What three demographics are at higher risk for Strep Pneumo meningitis? {{c1::
Asplenic patients Sickle cell (functionally asplenic) Alcoholics}} Strep pneumo
→ lancet-shaped gram (+) cocci in pairs, encapsulated → functioning spleen needed
to clear encapsulated organisms. Also often follows strep respiratory infection.
What is the major complication that can arise from Neisseria meningitidis
meningitis? {{c1::Waterhouse-Friderichsen Syndrome → adrenal insufficiency (primary
i.e; low cortisol, elevated ACTH), fever, DIC, shock}} - Polysaccharide capsule
and LOS endotoxin - Associated with younger people living in close quarters (army
barracks, college dorms) - Close contacts receive prophylaxis with Rifampin, cipro
or ceftriaxone.
How do you prevent the transmission of Group B Strep (Agalactiae) from the mother
to fetus during birth? {{c1::Ampicillin during labor }} This comes up pretty
often.
What E. coli virulence factor is most important for causing neonatal meningitis?
{{c1::K1 Capsular antigen}} Inhibits complement and other immune response. Allows
bacteria to evade host immunity. Also the causative factor in newborn pneumonia.
{{c1::Encephalitis}} is inflammation of the brain distinguished from meningitis by
altered mental status, motor or sensory deficits, and personality changes. If
these are present → Encephalitis (not meningitis) → HSV-1 is most common cause;
affects temporal lobes
What is the classic finding of Cryptococcus Neoformans Meningitis on MRI of the
brain? {{c1::Soap-bubble lesions}} Thiccck polysaccharide capsule. Culture on
Sabouraud agar, highlight with india ink (clear halo) and muscaramine (red inner
capsule). Latex agglutination test most specific. Treat with Amphotericin B +
Flucytosine followed by fluconazole
What pathogen causes retinitis in HIV patients with CD4 count < 100, characterized
by retinal edema and cotton-wool spots on fundoscopy? {{c1::CMV}} -
Valganciclovir is a first-line systemic therapy for CMV retinitis, a condition that
can cause blurring, vision loss, floaters, and photopsia (flashing lights).
The {{c1::inferior}} cerebellar peduncle is the major pathway into the cerebellum
from the spine Ipsilateral spinal cord proprioception information.
The {{c1::middle}} cerebellar peduncle is the major pathway into the cerebellum
from the Pons Contralateral pons
The {{c1::superior}} cerebellar peduncle is the major pathway OUT of the cerebellum
that carries axons from the {{c1::deep cerebellar nuclei}} All cerebellar outputs
originate from deep nuclei. Fibers travel to red nucleus and thalamus to regular
motor activity of cortex.
Purkinje Cells {{c1::inhibit}} the deep nuclei of the cerebellum by releasing
{{c1::GABA}} Regulate coordination of movements
The Dentate Nuclei of the cerebellum contains neurons that project to the
{{c1::contralateral VA & VL nuclei}} of the thalamus Most Lateral. All outgoing
cerebellar tracts exit through superior cerebellar peduncle
{{c1::Lateral}} Cerebellar lesions affect the extremities, while {{c1::Midline}}
lesions affect the trunk Lateral → hemispheres, dentate nucleus Midline →
vermis, EGF nuclei, floculonodular lobe
What are the 3 symptoms of Lateral Cerebellar Lesions? {{c1:: Dysmetria Intention
tremor Fall toward injured side}} - Lateral lesions affect ipsilateral
extremities - Dysmetria → under/overshoot target with finger/hand/leg (eg, finger
to nose)
What are the symptom(s) of Central (midline) Cerebellar Lesions? {{c1:: Truncal
ataxia Nystagmus, vertigo}} - Midline lesions affect trunk. - Vermis damage →
truncal ataxia (eg, can't stand independently, falls over when sitting) -
Flocculonodular lobe damage → nystagmus, vertigo (flocculonodular nuclei connect
cerebellum to vestibular nuclei)
Positive Romberg test indicates {{c1::Sensory}} ataxia NOT cerebellar; B12
deficiency, Tabes Dorsalis, etc. Cerebellar lesions will have ataxia even when eyes
are open.
What is the triad of symptoms associated with Ataxia-Telangiectasia? {{c1::
Cerebellar Ataxia Spider Angiomas (telangectasias) IgA deficiency}} Ataxia
presents within 1st year of life. Telangectectasias are dilated capillary vessels
near skin (ear, nose, face, neck). IgA deficiency results in repeated
sinus/respiratory infections. Ocular telangiectasias
Describe the genetic inheritance of Ataxia Telangectasia (inheritance pattern,
chromsosome, gene): {{c1:: Autosomal recessive Chromsome 11 ATM gene}} Caused by
DNA hypersensitivity to ionizing radiation. Ataxia-Telangiectasia Mutated (ATM)
gene → functions to repair double stranded DNA breaks. Mutation results in
defective Nonhomologous end-joining.
What is the normal function of the ATM gene in Ataxia-Telangiectasia and what is
the result of its mutation? {{c1::ATM detects double-stranded DNA breaks; DNA is
hypersensitive to ionizing radiation}} leads to defective non-homologous end-
joining
What two lab findings are associated with Ataxia-Telangiectasia? {{c1:: ↑ AFP ↓
IgA}} IgG and IgE may also be reduced.
What is the major risk/complication associated with Ataxia-Telangiectasia?
{{c1::Lymphomas and Luekemias}} AR mutation in ATM gene; results in failure to
detect DNA damage and hypersensitivity to ionizing radiation.
Describe the genetic inheritance of Friedrich's Ataxia (inheritance pattern,
chromosome, gene): {{c1:: Autosomal recessive Chromsome 9 Frataxin gene}}
Frataxin needed for normal mitochondrial function. GAA trinucleotide repeats.
Friedreich's Ataxia is associated with {{c1::GAA}} trinucleotide repeats on
chromosome 9 Encodes frataxin → mutation leads to impaired mitochondrial
function.
Frataxin is a mitochondrial protein expressed in high levels in which three organs?
{{c1::Brain, heart, pancreas}} - Friedreich's Ataxia symptoms → Ataxia,
nystagmus (due to degeneration of spinocerebellar tract)brain), hypertrophic
cardiomyopathy (heart), diabetes (pancreas)
What three spinal cord tracts are impaired in Friedreich's Ataxia? {{c1::
Spinocerebellar tracts Corticospinal tracts Dorsal colums }} Same as SCD (B12
deficiency) - Spinocerebellar → ataxia - Corticospinal → spastic paralysis - Dorsal
columns → ↓ vibratory sense, proprioception
What are the 4 main non-neurologic symptoms present in Friedreich's Ataxia? {{c1::
Kyphoscoliosis Pes Cavus Hypertrophic cardiomyopathy Diabetes (B-cell
dysfunction)}} Pes Cavus → high arch foot, also seen in Charcot-Marie Tooth
disease
What type of seizure involves one discrete part of the brain with no alteration in
consciousness? {{c1::Simple partial seizures}} Most commonly medial temporal lobe.
Can be motor, sensory, autonomic, psychic
What type of seizure involves one discrete part of the brain with impaired
consciousness? {{c1::Complex partial seizures}} Typically originate in medial
temporal lobe. often display automatisms.
Partial seizures most commonly originate in the {{c1::medial temporal}} lobe and
are often caused by {{c1::Mesial temporal sclerosis}} Neuronal loss in hippocampus
(also called hippocampal sclerosis). Can diagnose by MRI
What is the hallmark of Juvenile Myoclonic Epilepsy presentation? {{c1::myoclonic
jerks on awakening from sleep}} Shock-like, irregular movements of both arms.
JME starts as absence seziures (~5 years old) → Myoclonic seizures (~15 years) →
Grand mal seizures soon after
What is the classic EEG finding associated with Absence (petit mal) Seizures of
childhood? {{c1::3-5 Hz spike and wave activity}} Absence seizures → sudden
(few seconds) impairment of consciousness with no change in body/motor tone.
Usually remits by puberty. No post-ictal confusion. Treat with Ethosuximide.
What is the first line drug used to treat Absence (petit mal) Seizures and what is
its mechanism of action? {{c1::Ethosuximide → blocks thalamic T-type calcium
channels}} Valproic acid is 2nd line
Which drugs are used in acute and prophylactic treatment of Status Epilepticus,
respectively? Acute: {{c1::Lorazepam (benzos)}} Prevent: {{c1::Phenytoin,
Fosphenytoin}} Given concurrently. Add phenobarbital if benzos/phenytoin arent
working.
What drug is given to terminate Status Epilepticus seizures if the patient is still
seizing after benzo/phenytoin administration? {{c1::phenobarbital}}
Phenobarbital ↑ GABAA action
Which 3 anti-epileptic drugs are CYP450 Inducers? {{c1:: Carbamazepine
Phenobarbital Phenytoin}}
Which type of headache is the only type that causes bilateral pain? {{c1::Tension}}
Constant pressing/tightening pain that usually lasts 4-6 hours
Migraine headaches are thought to be caused by irritation of what 3 CNS structures?
{{c1:: CN V Meninges Blood vessels}}
Trigeminal nerve activation in migraine headaches leads to the release of what 3
vasoactive neuropeptides? {{c1:: Substance P Calcitonin gene-related peptide
Neurokinin A}}
What are the 3 drugs used for abortive therapy of acute migraine headaches? {{c1::
Triptans NSAIDs Dihydroergotamine}}
{{c1::Cluster}} headaches are characterized as excruciating, unilateral headaches
behind the eye Mostly men who are smokers. Can also present with lacrimation,
rhinorrhea, and autonomic dysfunction (Horner's syndrome)
What 3 symptoms characteristically accompany the excruciating, retro-orbital pain
of Cluster Headaches? {{c1:: Rhinorrhea Lacrimation Horner's syndrome}} Most
common in males who smoke
What are the acute and prophylactic treatments for Cluster headaches? Acute:
{{c1::Sumatriptan, 100% O2}} Prevent: {{c1::Verapamil}}
List the structures responsible for drainage of the ventricular system: Lateral
ventricles ↓ {{c1::Interventricular foramina (of Monro)}} ↓ Third Ventricle ↓
{{c1::Cerebral aqueduct (of Sylvius)}} ↓ Fourth Ventricle
What structure(s) produce CSF? {{c1::Ependymal cells of choroid plexus
(ventricles)}} - CSF absorbed by arachnoid villi - CSF drained into superior
sagittal sinus then to the venous system
Circulating CSF is absorbed by {{c1::arachnoid villi}} then drained to the
{{c1::superior sagittal sinus}} before entering the venous system Impaired
absorption by arachnoid villi causes communicating hydrocephalus (most commonly d/t
post-meningitis scarring)
Which type of hydrocephalus causes ↑ ICP and papilledema and can lead to
herniation? {{c1::Communicating Hydrocephalus}} ↓ CSF absorption by arachnoid
granulations, most commonly d/t post-meningitis scarring. All ventricles will be
dilated on CT.
What is the classic triad of symptoms associated with Normal Pressure Hydrocephalus
(NPH)? {{c1:: Urinary incontinence Gait disturbance Dementia}} """Wet, wobbly,
and wacky"". Symptoms due to ventricular compression of corona radiata. Reversible
with CSF shunt."
The symptoms of Normal Pressure Hydrocephalus are due to ventricular compression of
the {{c1::corona radiata}} "-Impaired absorption of CSF and resulting
ventriculomegaly ""Wet, wobbly, wacky"" → urinary incontinence, gait apraxia,
dementia. Affects elderly."
{{c1::Hydrocephalus ex vacuo}} is apparent ventricular enlargement secondary to
atrophy of the cortex seen in old age or some diseases (AD, Pick, HIV) Ventricles
look big because brain is shrinking. No symptoms.
Dural sinuses are large venous channels that drain the cerebral veins and CSF into
the {{c1::internal jugular}} vein Sagittal sinus receives CSF
Which 7 stuctures are located inside the Cavernous Sinus? {{c1:: Internal carotid
artery CN III, IV, V1, V2, VI sympathetic fibers to pupil}}CN VI is most
succeptible to injury
What are the three major causes of Cavernous Sinus Syndrome? {{c1:: Tumor
(pituitary) Septic thrombus Carotid-cavernous fistula}}
Inhaled anesthetics with high solubility will have {{c1::slow}} induction and
washout time
How does the blood/gas partition coefficient of inhaled anesthetics relate to their
solubility and induction time? {{c1::Higher PC → higher blood solubility, slower
induction time}}
Inhaled anesthetics with high lipid affinity have {{c1::higher}} potency Lipid
solubility = affinity of gas for lipids, based on oil/gas partition coefficient.
What does a low MAC indicate about the properties of an inhaled anesthetic? {{c1::↓
MAC = ↑ potency}} MAC (minimum alveolar concentration) → concentration of
anesthetic that prevents movement in 50% of subjects in response to pain. MAC is a
measure of potency → related to lipid solubility, not blood. MAC is lower in
elderly
What are the 5 physiologic effect of Inhaled anesthetics? {{c1:: myocardial
depression respiratory depression nausea/vomiting ↑ cerebral blood flow ↓ GFR}}
Just imagine doing a quick ROS → CV, resp, neuro, GI, renal Note that ↑
cerebral blood flow accompanies cerebral vasodilation, leading to ↑ ICP
What are the 2 unique side effects of Halothane? {{c1:: Hepatotoxicity Malignant
hyperthermia}} Hepatotoxicity → severe, life-threatening massive necrosis
Malignant Hyperthermia → inherited mutations in Ryanodine receptors leads to
excessive release of calcium, leading to high ATP (~heat~) from SERCA reuptake
What is the unique side effect of Methoxyflurane? {{c1::Nephrotoxicity}}
Breakdown products (fluoride & DCAA) toxic to kidneys
What is the unique side effect of Enflurane? {{c1::Seizures}} Lowers seizure
threshold
What is the unique side effect of the inhaled anesthetic, N2O? {{c1::Expansion of
trapped gas in body cavity}} Diffuses rapidly into air spaces and increases
volume. Cannot use in Pneumothorax or Abdominal distention
Thiopental is a barbiturate IV general anesthetic used in which two circumstances?
{{c1:: Induction of anesthesia Short surgical procedures}} ↑ lipid solubility (↑
potency) with rapid, short action that is quickly terminated by redistribution to
muscle and fat.
What is the antidote for Benzodiazepine overdose? {{c1::Flumazenil}} Competetive
inhibitor at benzodiazepine binding site of GABAA receptor, but it is not used
often bc Benzo overdose is rarely fatal and Flumazenil can cause withdrawal
seizures.
Midazolam is a Benzodiazepine IV general anesthetic used in what two clinical
circumstances? {{c1:: Procedural sedation (endoscopy) Anesthesia induction}} Short-
acting. Causes sedation, CV & resp depression, and amnesia
What is the mechanism of opioids (morhpine, fentanyl) on the Mu receptors in the
brain? {{c1::Hyperpolarization via increase K efflux from cells}}
Hyperpolarization → less pain transmission
What is the antidote for opioid overdose and what is its mechanism of action?
{{c1::Naloxone → competetive antagonist at Mu receptors}} Reverses effects within
minutes. Must be given IV (inactivated by liver if PO)
Prolonged usage of opioids leads to tolerance of most effects, with the exception
of which two? {{c1:: Constipation Miosis}} Constipation is most common and
persistent opioid side effect. Opioid stimulation of mu receptors in GI tract
decreases secretion and slows gastric motility. Recommend fiber and laxatives.
What is the MOA of Ketamine as an intravenous general anesthetic? {{c1::NMDA
receptor antagonist}} Sympathomimetic and Dissociative drug. Very popular amongst
the wookie jam-band music festival crowd.
What is the MOA of Propofol as an IV general anesthetic? {{c1::GABAA potentiation}}
Sedation, anesthesia; good for rapid anesthesia induction, short procedures,
ICU sedation
Local Anesthetics are weak bases that cross the cell membrane in the
{{c1::uncharged}} form and block sodium channels in the {{c1::charged}} form
{{c1::Acidic}} environments make local anesthetics less effective, requiring higher
drug concentrations to reach effect Acidic environments (infected tissue) have ↑
proton levels, which traps the local anesthetic (weak base) in the charged form
(BH+) thereby preventing it from crossing the cell membrane and exerting effects
Local anesthetics are often administered with {{c1::epinephrine}} to prevent
bleeding (via vasoconstriction) and prevent washout Vasoconstriction → less
washout → great local effect → less systemic concentration
List the order of differential blockade exhibited by local anesthetics by size and
myelination: {{c1::Small, myelinated fibers > small, unmyelinated > large,
myelinated > large, unmyelinated}} Myelinated fibers are easier to block due to
nodes of Ranvier → inhibiting one node blocks entire action potential transmission
List the order of differential blockade exhibited by local anesthetics based on
sensation modality: {{c1::Pain > temp > touch > pressure}} Pain & temp = free nerve
endings
Which local anesthetic displays the most risk for severe cardiotoxicity?
{{c1::Bupivacaine}} Local anesthetic (including bupivacaine) cardiotoxicity
causes hypotension, arrhythmia, bardycardia, heart block. Cocaine is the exception
→ HTN, vasoconstriction
Which local anesthetic carries the greatest risk for oxidizing iron to Fe3+ and
producing Methemoglobinemia? {{c1::Benzocaine}} Fe3+ cannot bind oxygen. All local
anesthetics can cause methemoglobinemia (plus nitric oxide and dapsone). Patients
will have Chocolate-brown blood. Treatment is Methylene blue
What drugs may be given to reverse the effects of non-depolarizing NMBAs?
{{c1::AChE Inhibitors (Neostigmine)}} AChE Inhibitors = Neostigmine,
physostigmine, pyridostigmine, edrophonium. Must be given with atropine or
glycopyrrolate to prevent muscarinic effects such as bradycardia
Familial form of Alzheimer's Disease is linked to mutations in which 2 genes?
{{c1::Presenilin-1 & 2}} - Familial form is only 10% - Most are simply
sporadic with the major risk factor being age - Down syndrome will cause early AD
due to APP on chromosome 21.
What three AChE inhibitors are used to treat Alzheimer's Disease? {{c1:: Donepezil
Galantamine Rivastigmine}} Dont Remember my Galentine Side effects → nausea,
dizziness, insomnia
What finding in the CSF is indicative on Creutzfeldt-Jakob Disease? {{c1::↑ 14-3-3
protein}} Periodic sharp waves on EEG and Spongiform cortex on biopsy.
What are the findings on microscopic examination of a brain with Creutzfeldt-Jakob
Disease? {{c1::spongiform cortex (intracellular vacuoles)}}looks spongy to me
Multiple Sclerosis is an autoimmune disorder caused by {{c1::T-cell}} reacting to
{{c1::Myelin Basic Protein (MBP)}} in the CNS Type IV Hypersensitivity. HLA-DR2
In multiple sclerosis, self-reactive T-cells release {{c1::IFN-gamma}} to recruit
{{c1::macrophages}} Type IV Hypersensitivity. HLA-DR2
What are the 4 classic symptoms of Multiple Sclerosis in addition to the relapsing-
remitting extremity neuropathies? {{c1:: Optic Neuritis MLF Syndrome (INO)
Pyramidal tract weakness Neurogenic bladder}} Any neuro symptom possible, but
these are classic: - Optic Neuritis → demyelination of optic nerve, painful
unilateral loss of vision - MLF Syndrome (INO) → one eye cannot move medially on
lateral gaze. Pt will complain of diplopia - Bladder dysfunction → spastic bladder,
overflow incontinence due to loss of UMN detrusor inhibition
{{c1::MRI}} is the gold standard diagnostic test to diagnose Multiple Sclerosis and
will show {{c1::Periventricular plaques}} plaques indicate oligodendrocyte loss and
reactive gliosis
What do periventricular plaques on MRI in Multiple Sclerosis indicate?
{{c1::Oligodendrocyte loss and reactive gliosis}} MS = T-cell attack on Myelin
Basic Protein → myelin synthesized by oligodendrocytes in CNS
What are the CSF findings in Multiple Sclerosis? {{c1:: ↑ IgG and MBP Oligoclonal
bands}} MS → attack of oligodendrocytes → oligoclonal bands
"What are the three ""disease-modifying"" therapy drugs given to slow the
progression of Multiple Sclerosis? {{c1:: B-interferon Glatiramer Natalizumab}}"
Treat acute flairs with IV steroids.
{{c1::Guillain-Barré syndrome}} is an acute inflammatory demyelinating disease
characterized by ascending muscle weakness over a period of days to weeks that
usually follows an infection Autoimmune attack of Schwann Cells. Sensory deficits
(paresthesias) are mild. Usually resolves over weeks to months.
Guillain-Barré syndrome is a post-infectious autoimmune attack of {{c1::Schwann}}
cells and inflammation of the {{c1::endoneurium}} of peripheral nerves Rapid,
ascending muscle weakness with some mild sensory deficits. Symptoms usually resolve
over weeks to months.
What two stimuli can reproduce/exacerbate Multiple Sclerosis symptoms? {{c1:: Neck
flexion (Lhermitte sign) ↑ temperature (Uhthoff phen.)}} 1. Lhermitte sign → neck
flexion causes electrical sensation down back/limbs 2. Uhthoff phenomenon →
symptoms worse after hot shower or exercise (↑ body temp) due to slowing of
neuronal conduction in unmyelinated nerves
What other symptoms are commonly present with Guillain-Barre Syndrome in addition
to the ascending muscle weakness? {{c1::Autonomic dysfunction (tachy, arrhythmias,
HTN, urinary retention, etc)}} Severe autonomic dysfunction can cause sudden
cardiac death
Guillain-Barre Syndrome has been proven to be triggered by which pathogens? {{c1::
Campylobacter jejuni CMV (and other viruses)}} GBS preceded by blood diarrhea →
Campylobacter jejuni GBS preceded by febrile illness in an immunosuppressed patient
(few months after transplant) → CMV
What CSF findings are associated with Guillain-Barre Syndrome? {{c1::↑ protein with
normal cell count (Albuminocytologic dissociation)}} -Albuminocytologic
dissociation results from a dysfunction of the blood-brain barrier. -Postinfectious
autoimmune reaction that generates cross-reactive antibodies against gangliosides
(eg; anti-GM1 antibodies) or other unknown antigens of peripheral schwann cells,
which leadds to segmental demyelination and axonal degeneration
How do you treat Guillain-Barre Syndrome? {{c1:: Respiratory Support Plasmapheresis
IV immunoglobulins}} Respiratory support is a must becuase ascending paralysis
causes weakness of resp muscles
Progressive Multifocal Leukoencephalopathy (PML) is a severe demyelinating disease
of the CNS caused by reactivation of latent {{c1::JC virus}} Destruction of
oligodendrocytes (white matter). Everyone carries this virus, but it classically
only affects AIDS patients with CD4 < 200
What areas of the brain are the primary sites of oligodendrocyte destruction in PML
(JC virus reactivation)? {{c1:: Parietal & Occipital (visual symptoms are common)}}
"Destroys oligodendrocytes (white matter) and has ""Multifocal"" in the name
→ demyelination of multiple white matter lesions on imaging"
{{c1::Acute Disseminated (postinfectious) Encephalomyelitis}} is a disease of
multifocal inflammation and demyelination after infection or vaccination Acute
onset of multifocal neurologic symptoms → rapid deterioration & hospitalization.
Charcot-Marie-Tooth disease is a group of progressive peripheral nerve disorders
caused by what? {{c1::defective production of peripheral nerve proteins or myelin
sheath}} Typically Autosomal Dominant caused by PMP22 gene duplication
The most common type of Charcot-Marie-Tooth disease (CMT1A) is an {{c1::autosomal
dominant}} inherited duplication of the {{c1::PMP22}} gene CMT = Hereditary motor &
sensory neuropathy (HMSN)
Parkinson's Disease involves damage to which basal ganglia structure(s)?
{{c1::Substantia nigra}} Substantia nigra plays a role in initiation of
voluntary movements. Damage to this area presents with bradykinesia, tremor and/or
rigidity.
{{c1::MPTP}} is a chemical used to cut heroin that destroys dopaminergic neurons in
the substantia nigra and causes Parkinson's MPTP = methy-phenyl-
tetrahydropyridine. Metabolized by MAO-B to MPP+ (active form)
"What kind of tremor is caused by Parkinson's Disease? {{c1::""pill-rolling""
tremor at rest}}" Other classic symptoms include cogwheel rigidity, bradykinesia,
postural instability, and shuffling gait
{{c1::Levodopa (L-Dopa)}} is a dopamine precursor that can cross the blood-brain
barrier for conversion to dopamine by {{c1::DOPA Decarboxylase}} Carbidopa given to
inhibit peripheral DOPA Decarboxylase so that L-DOPA can reach CNS and do its thing
{{c1::Carbidopa}} is a peripheral DOPA Decarboxylase inhibitor, allowing L-DOPA to
reach the CNS Can still get CNS dopamine side effects (anxiety, agitation,
insomnia) but won't get nausea/vomiting beause area postrema is outside the BBB.
Avoid Vitamin B6
What two Parkinsons drugs prevent dopamine/L-dopa breakdown by COMT? {{c1::
Entacapone (peripheral) Tolcapone (peripheral & CNS)}} COMT = catechol-O-
methytransferase
What are the 3 symptoms of non-ergot dopamine agonist toxicity? (pram, ropinirole)
{{c1:: impulse control disorder postural hypotension hallucinations/confusion}}
Which two antimuscarinic drugs are given to treat tremor-predominant symptoms of
Parkinson's Disease? {{c1:: Benztropine Trihexyphenidyl}} Tri to Park the Benz
Improve tremor and rigidity but little effect on bradykinesia. S/E's include
sedation, dry mouth
List the sequence of nucleotides implicated in each of the following Trinucleotide
Repeat Disorders: Huntington Disease: {{c1::CAG}} Myotonic Dystrophy: {{c1::CTG}}
Fragile X Syndrome: {{c1::CGG}} Friedreich's Ataxia: {{c1::GAA}} First Aid
menonics: CAG: Caudate has ↓ ACh and GABA CTG: Cataracts, Toupee, small Gonads CGG:
Chin (protruding), Giant Gonads GAA: Ataxic GAAit
What 3 neurotransmitter abnormalities are associated with Huntington Disease?
{{c1:: ↑ dopamine ↓ GABA, ACh}} Loss of GABA and ACh from caudate. Neuronal
death via NMDA-R binding and glutamate excitotoxicity
What abnormalities are seen in brain imaging of a patient with Huntington disease?
{{c1:: Ex vacuo ventriculomegaly (lateral) Atrophy of caudate and putamen Atrophy
of frontal and temporal lobes}} "Remember ""ex vacuo"" means apparent
enlargement due to atrophy of surrounding structures"
Describe the inheritance of Huntington Disease (inheritance pattern, chromosome,
gene): {{c1:: Autosomal dominant Chromosome 4 Huntingtin (HTT)}} (CAG)
trinucleotide repeat → anticipation
What is the pathophysiologic cause of the Huntington Disease? (not genetics)
{{c1::Neuronal death from glutamate toxicity}} Glutamate binds NMDA receptor →
excess influx of calcium → cell death. Like the brain is overdosing.
What three drugs are given to treat Huntington's Disease? {{c1:: Tetrabenazine
Reserpine Haloperidol }} Only treats CHOREA → blocking dopamine inhibits
chorea. Tetrab & Reserp → VMAT inhibitors
What is the MOA of Tetrabenazine and Reserpine? {{c1::Inhibit VMAT → ↓ dopamine
vescicle packaging and release}} Use for chorea (Huntington disease, Tardive
diskenesia, rheumatic fever) and Tourette's Disease
What are the neurological movement symptoms associated with Wilson's Disease?
{{c1:: Dysarthria Parkinsonism Wing-beating tremor}} WD causes accumulation of
copper in tissues, resulting in lesions to the putamen and globus pallidus (P + GP
= lentiform nucleus)
What are the two drugs given to treat Essential Tremors? {{c1:: Propanolol
Primidone}} Patients often self-medicate with alcohol
{{c1::Essential}} tremors are high-frequency tremors occuring with sustained
posture and worsened when anxious Eg, the first time u got to third base were
asked to do anything in the OR
Which type of tremor is characterized as slow, zigzag motion when
pointing/extending toward a target and what lesion causes it? {{c1:: Intention
tremor Cerebellar lesion}} Finger to nose
Restless leg syndrome is associated with {{c1::iron}} deficiency and {{c1::chronic
kidney}} disease Treat with dopamine agonists (pramipexole, ropinirole)
While the sympathetic nervous system predominantly constricts vascular smooth
muscle, sympathetic stimulation will vasodilate blood vessels in which two organs?
{{c1::Muscle and liver}} ↑ muscle vasodilation → preparation to fight or
flight. (Jack3d rip) ↑ liver vasodilation → glycogen that is being converted to
glucose can reach systemic circulation
Where are the sympathetic ganglia found? {{c1::Paravertebral T1-L5}} Hence why a
pancoast tumor at the top of the lung can compress the sympathetic ganglia to the
head & cause Horner's Syndrome
{{c1::Conductive}} hearing loss is caused by a defect in the transmission of sound
waves, usually due to obstruction, infection, or otosclerosis Obstruction → wax
Infection → otitis media Otosclerosis → bony overgrowth of the stapes (results in
immobility) -Congenital conductive hearing loss can occur as a result of a
development defect in the first branchial cleft (which gives rise to the external
auditory canal), the first branchial pouch (which gives rise to the middle ear
cavity and eustachian tube), the first branchial arch (which gives rise to the
malleus and incus) and/or the second branchial arch (which gives rise to the
stapes)
{{c1::Otosclerosis}} is bony overgrowth of the stapes, which results in conductive
hearing loss
{{c1::Sensorineural}} Hearing Loss is caused by failure of nerve transmission
(cochlea disease, acousitc neuroma, CN damage) Weber → localized to unaffected ear
Rinne → normal (air > bone)
Presbycusis is normal age-related sensorineural hearing loss due to degeneration of
{{c1::Organ of Corti}} Slowly progressive, symmetric, bilateral. Higher
frequencies lost first due to destruction of hair cells at the cochlear base
Presbycusis first causes hearing loss of {{c1::higher}} frequencies due to
destruction of hair cells at the cochlear {{c1::base}} Lower frequencies are
detected at apex
How do results of the Weber test differ in conductive vs sensorineural hearing
loss? Cond → {{c1::localize to affected ear}} Sens → {{c1::localize to good ear}}
How do results of the Rinne test differ in conductive vs sensorineural hearing
loss? Cond → {{c1::BC > AC}} Sens → {{c1::AC > BC (normal)}} Note that in
SensHL, both AC and BC are reduced, so AC still > BC
Noise-induced hearing loss that occurs after a sudden, loud noise (explosion) is a
caused by {{c1::tympanic membrane rupture (resulting in conductive hearing loss)}}
Long-term, progressive noise exposure → damage to ciliated hair cells of
Organ of Corti (high frequency lost first eg; beeping of microwave or birds
chirping) -In a normally functioning ear, sound waves are transmitted mechanically
through the tympanic membrane, via the ossicles, and through the oval window to the
perilymph-filled inner ear. The resulting vibrations are transmitted to the
cochlear hair cells, from where neurologic impulses are transmitted via the
vestibulocochlear nerve. -Rupture of the oval window is a cause of hearing loss
associated with barotrauma. Sudden decreases in pressure between the inner and
outer ear cause dissolved gasses to be released from the perilymphatic fluid in the
inner ear and results in rupture of the oval window. Patients with barotrauma will
have a recent history of diving or flying.
Cholesteatoma is an overgrowth of {{c1::desqamated keratin debris}} within the
middle ear space that may cause conductive hearing loss due to erosion of middle
ear structures May erode tympanic membrane, ossicles, mastoid air cells
What are the two major symptoms of cholesteatomas? {{c1:: Conductive hearing loss
Painless otorrhea}} Squamous (keratin) debris forming round pearly mass behind
TM. Caused by chronic negative pressure in the middle ear (infx, trauma, surg)
leading to retraction pockets
Parasympathetic preganglionic neurons arise from the {{c1::brainstem}} and
{{c1::Sacral spinal cord (S2-24)}} before synapsing on autonomic ganglia near/on
the effector organ(s) CN III, VII, IX, X and pelvic splanchnic nerves →→→ ganglia
→ target
Which 4 cranial nerves carry parasympathetic fibers? {{c1::CN III, VII, IX, X}}
III → pupil constriction VII → lacrimation, salivation (sublingual,
submandibular glands) IX → salivation (parotid gland) X → thoracoabdominal viscera
Which type of receptors are located at the first (postganglionic cell bodies) and
second (target organ) synapses of parasympathetic nerves, respectively? 1st synapse
→ {{c1::nicotinic ACh}} 2nd synapse → {{c1::muscarinic ACh}} All
parasympathetic transmission uses Acetylcholine as NT
The first synapse for all structures the sympathetic nervous system innervates uses
{{c1::Acetylcholine}} as the neurotransmitter on {{c1::nicotinic ACh}} receptors
Sympathetic innveration to sweat glands uses which neurotransmitter(s) and which
type(s) of receptor? NT(s): {{c1::ACh}} Receptor(s): {{c1::Muscarinic AChR}}
Sympathetic innveration to adrenal medulla uses which neurotransmitter(s) and which
type(s) of receptor? NT(s): {{c1::ACh}} Receptor(s): {{c1::Nicotinic AChR}}
Sympathetics to adrenal medulla do not synapse in paravertebral ganglia
{{c1::Hemicholinium}} is a research chemical that blocks the transfer of choline
into neurons, preventing the synthesis of acetylcholine
{{c1::Vesamicol}} is a chemical that inhibits choline acetyltransferase (ChAT) from
packaging ACh into vescicles in presynaptic neurons
{{c1::Botulinum}} is a toxin that blocks the exocytosis (release) of ACh from the
presynaptic nerve terminal at the neuromuscular junction Leads to descending
flaccid paralysis. Watch for babies who've ingested honey or adults who have eaten
canned foods
Activation of which two types of receptors inhibit the release of norepinephrine in
adrenergic synapses? {{c1::M2, a2}} Both Gi - M2 → parasympathetic mediated ↓ HR
and contractility of atria (CN X) - a2 → exert negative feedback by sensing NE in
the synaptic cleft
{{c1::Metyrosine}} is an antihypertensive drug given to treat pheochromocytomas by
blocking tyrosine hydroxlase in presynaptic adreneric nerves Tyrosine
hydroxylase (tyrosine → Dopa) is the rate limiting enzyme in catecholamine
synthesis
{{c1::Resperpine}} is a drug that works by blocking VMAT and subsequently
inhibiting dopamine vescicle packaging in presynaptic adrenergic neurons VMAT =
vescicular monoamine trasnporter. Tetrabenazine also a VMAT inhibitor. Used to
treat Chorea (huntington's dx, tardive dyskinesia)
What are the 3 functions of alpha-1 adrenergic receptors? {{c1:: ↑ vasc. smooth
muscle contraction ↑ mydriasis ↑ intestinal & bladder sphincter muscle tone}}
Direct Alpha-1 agonists - Midodrine → a1 only - Norepinephrine → a1 > a2 > B1
- Phenylephrine → a1 > a2 Alpha-1 Antagonists: - nonselective: phenoxybenzamine
(irreversible), phentolamine (reversible) - selective: Prazosin, terazosin, etc
(used for BPH and HTN)
{{c1::Nicotinic}} ACh receptors are ligand-gated Na/K channels Nn → autonomic
ganglia, adrenal medulal Nm → NMJ of skeletal muscle Muscarinic ACh receptors are
GPCRs
Gs receptors on vascular smooth muscle cause {{c1::relaxation}}, while Gi receptors
cause {{c1::contraction}} Important because Gs relaxes smooth muscle (B2, D1),
but stimulates cardiac muscle (B1)
Which 5 receptors use Gq G-protein class second messenger system? {{c1::a1, M1, M3,
H1, V1}}
Which 3 receptors use Gi G-protein class second messenger system? {{c1::a2, M2,
D2}}
Which 6 receptors use Gs G-protein class second messenger system? {{c1::B1, B2, B3,
D1, H2, V2}}
Fill in the blanks in the parasympathetic pathway of miosis (pupillary
constriction) from beginning to end: {{c1::Edinger-Westphal nucleus}} → CN III →
{{c1::ciliary ganglion}} → {{c1::short ciliary nerves}} → spincter pupillae
"Edinger-Westphal nucleus is located in the midbrain near CN III nucleus.
Loss of this tract produced dilation (""blown pupil"") seen in CN III lesions"
The where each of the 3 synapses occur in the sympathetic Mydriasis (dilation)
pathway (including where the pathway starts): Start: {{c1::posterior hypothalamus}}
1st: {{c1::ciliospinal center of Budge (C8-T2)}} 2nd: {{c1::Superior cervical
ganglia}} 3rd: {{c1::Dilator pupillae}} Sympathetic fibers exit spinal cord at T1
level and cross apical pleura of lung (pancoast tumors) and travel with the
cervical sympathetic chain near the subclavian
The third neuron in the sympathetic pathway to the eye travels with the
{{c1::internal carotid}} artery and enters the orbit as the {{c1::long ciliary}}
nerve Long ciliary nerve synapses on pupillary dilator muscles to cause mydriasis.
Sympathetic fibers to head also innervate smooth muscle of eyelids (minor
retractors) and sweat glands of forehead and face
What are the 4 most common causes of lesions to the sympathetic chain to the face
that may result in Horner's Syndrome? {{c1:: Pancoast tumor Aortic dissection
Carotid dissection Lateral Medullary Syndrome (PICA stroke)}} Others include
pontine hemorrhage, late-stage syringomyelia, Brown-Sequard syndrome, any spinal
cord lesion above T1
In the pupillary light reflex, light in either retina travels via CN II to the
{{c1::pretectal nuclei in the midbrain}}, which activates the Edinger-Westphal
nuclei bilaterally Light in one eye should cause pupils to constrict
bilaterally (direct and consensual reflex)
What physical exam finding characterizes Marcus Gunn pupil? {{c1::Swinging light
test to affected eye does not cause constriction}} Afferent (CN II) pupillary
defect. Because light in one eye does cause bilateral constriction, we know that
the efferent (parasympathetic) pathway is intact and there is an afferent defect in
the eye without proper response.
What is the classic cause of a Marcus Gunn Pupil (afferent pupillary defect)?
{{c1::Optic neuritis due to MS}} Painful unilateral vision loss
What physical exam findings characterize an Argyll Robertson Pupil (eg, tertiary
syphillis)? {{c1::Constricts to accomadation, but does not react to light}}
"""Prositute's pupil"" → accomodates, but doesnt react"
The lens of the eye is surrounded by a capsule with type {{c1::IV}} collagen Alport
Syndrome → hereditary defect in type IV collagen → cataracts, hereditary nephritis,
sensorineural hearing loss
The Lens of the eye is an avascular structure that obtains nutrients via diffusion
and relies on {{c1::anaerobic metabolism}} its principle source of energy Cause
of cataracts
In the resting state, ciliary muscles are {{c1::relaxed}}, zonules are pulled
tight, and the lens {{c1::flattens}} to focus on far objects
When focusing on near objects (accomodation), the ciliary muscles {{c1::contract}},
causing the zonules to relax and lens to become rounded
Presbyopia is age-related impairment of accomodation (focusing on near objects)
caused by which two processes? {{c1:: ↓ lens elasticity ↓ strength of ciliary
muscles}} Remember that accomodation requires the ciliary muscles to contract,
which loosens the zonule fibers and causes the lens to become rounder to focus on
near objects
{{c1::Myopia (nearsightedness)}} is a refractive error where the focal point is in
front of the retina due to the eye being too long or too much corneal curvature
Nearsighted = cant focus on far objects Treat with concave (diverging) lens
Which type of lens is required to correct Myopia (nearsightedness)? {{c1::negative
(diverging) lens}} Concave (diverging) lenses spread light refraction to
compensate for a focal point in front of the retina
{{c1::Hyperopia (farsightedness)}} is a refractive error where the focal point is
behind the retina due to a short eye or minimally curved cornea
What type of lens is required to correct Hyperopia (farsightedness)? {{c1::positive
(converging) lens}} Convex = converges
{{c1::Astigmatism}} is a refractive error of abnormal curvature of the cornea,
causing multiple focal points and blurry objects at all distances
Which two congenital systemic disorders are associated with Ectopia Lentis
(disclocation of the lens) and how do they differ? {{c1:: Marfan; up/out
Homocystinuria; down/in}}
What are the 8 congenital risk factors and conditions associated with cataracts?
{{c1:: Galactosemia & Galactokinase def. Trisomies (13,18,21) ToRCHeS (rubella)
Myotonic dystrophy Marfan syndrome Alport syndrome Neurofibromatosis 2}} 2
Gal's Tri Rubbing My M.A.N.
{{c1::Retinitis Pigmentosa}} in an inherited retinal disorder of painless,
progressive visual loss that first presents with night blindness and peripheral
visual loss Often presents in childhood. Associated with abetalipoproteinemia
What is the characteristic fundoscopy finding in Retinitis Pigmentosa? {{c1:: Bone
spicule-shaped pattern of pigmentation around retina }} peripheral vision and
night blindness (rods) are lost first
What are the hallmarks of Retinitis on fundoscopy? {{c1:: Retinal hemorrhages
Whitish appearance of retina }} Retinitis is characterized by retinal edema and
necrosis, usually caused by a virus (CMV, HSV, VZV) in immunosuppressed patients
"What 4 fundoscopy findings are associated with non-proliferative Diabetic
Retinopathy? {{c1:: Microaneurysms (1st sign) ""Dot-and-blot"" hemorrhages Cotton-
wool spots Hard exudates/macular edema}}"
Proliferative diabetic retinopathy is caused by {{c1::retinal ischemia}} triggering
neovascularization Retinal ischemi + neovascularization may lead to retinal
detachment and blindness
What are the 3 treatments for proliferative diabetic retinopathy? {{c1::
Photocoagulation Vitrectomy VEGF inhibitors}} Anti-VEGF drugs → Ranibizumab,
Bevacizumab
{{c1::Retinal Detachment}} is a process by which the retinal photoreceptor layer
peels away from the underlying support layer leading to ischemia and blindness
-Fundoscopy: a gray, detached, freely floating retina Blindness because
photoreceptor layer is stripped away form choroid (blood supply) in support layer
What condition often precedes retinal detachment? {{c1::Posterior vitreous membrane
detachment}} "Vitreous shrinks with age → pulls on retina → causes retinal
holes/tears → floaters (black spots) → flashes of light → ""curtain drawn down""
pattern of rapid visual loss → blindness"
Which ocular refractory disorder predisposes patients to retinal detachment?
{{c1::Myopia (near-sightedness)}} Myopia → larger eyes → thinner retinas Other
risk factors: prior eye surgery or trauma, proliferative diabetic retinopathy
What is the cause of Branch Retinal Vein Occlusion (BRVO)? {{c1::BRVs compressed by
nearby arterial atherosclerosis}} BRVO will show hemorrhage and venous
engorgement only in affected area (image below). In contrast, CRVO will involve
entire retina
What is the cause of Central Retinal Vein Occlusion (CRVO)? {{c1::thrombus}} -Focal
retinal hemorrhage and venous engorgement/edema involving entire retina
"What is the characteristic fundoscopy finding seen in Central Retinal Artery
Occlusion? {{c1:: ""cherry red"" macula (in the foveal region) }}" -
Ophthalmoscopy findings also include retinal pallor (pale, white retina) and narrow
retinal vessels with a cattle-trcuk appearance. -Characterized by sudden, painless
loss of vision and an afferent pupillary defect. Caused by carotid artery
atherosclerosis, cardiac thrombus, giant cell arteritis -Ophthalmologic emergency.
Therapeutic measures include eyeball massage, an inhalation of a mixture of 95% and
5% carbon dioxide and arterial vasodilators eg; sublingual nitroglycerin. A delay
in initiation of therapy can result in permanent loss of vision.
What are the three common causes of Retinal Artery Occlusion? {{c1:: Carotid artery
atherosclerosis Cardiac embolism (think afib) Giant cell arteritis}} internal
carotid → ophthalmic artery (GCA) → retinal artery
Age-related macular degeneration causes what two primary visually defects? {{c1::
Distortion (metamorphopsia) Scotomas (loss of central vision)}}
Dry Macular Degeneration is caused by the gradual deposition of drusen (yellow
extracellular material) between which two layers of the eye? {{c1:: Bruch's
membrane and Retinal Pigment Epithelium }} -These depositions cause
progressive atrophy of the central and/or pericentral retinal pigment epithelium,
resulting in painless central and/or peripheral visual impairment.
Wet Macular Degeneration causes rapid vision loss due to bleeding secondary to
{{c1::choroidal neovascularization}} -VEGF inhibitors (Ranibizumab) delivered
intravitreally are the first-line treatment for wet macular degeneration. Break in
Bruch's membrane → BVs form beneath retina → leakage/subretinal hemorrhage → rapid
vision loss -Presentation: Acute, painless, unilateral loss of central vision
(central scotoma), with history of gradual loss of central vision loss and
fundoscopic findings of subretinal hemorrhage and grayish-green retinal
discoloration
What are the two Anti-VEGF drugs that are given as injections to treat
proliferative diabetic retinopathy and wet macular degeneration? {{c1:: Bevacizumab
Ranibizumab}} Also limits vascular growth of tumors, depriving them of a blood
supply Bevacizumab = Blood Vessels
Pseudotumor Cerebri (idiopathic intracranial hypertension) can cause diplopia due
to CN {{c1::VI}} palsy CN VI nnervates lateral rectus (LR6SO4); affected eye
cannot abduct. Will also see papilledema (the margins of the optic discs are
blurred due to swelling of the optic nerve) on fundoscopy. vs Normal Papilledema
What visual field defect will result from a lesion to the optic nerve?
{{c1::Complete ipsilateral anopia}}
{{c1::Amaurosis Fugax}} is painless, ischemic transient vision loss in one eye that
is often caused by embolism to the retinal artery "Classically described as
""curtain shade"" over vision. Central retinal artery occlusion will not be
transient."
What visual field defect will result from compression of the optic chiasm?
{{c1::Bitemporal hemianopsia}} Remember that the nasal (medial) retina fibers
carry visual information from the temporal (lateral) visual fields of each eye.
What visual field defect will result from a lesion to the optic tract?
{{c1::Homonymous Hemianopsia}} Macular sparing with PCA stroke due to dual
blood supply from MCA and PCA
What visual field defect will result from a lesion to Baum's Loop in the Parietal
lobe (dorsal optic radiation)? {{c1::Contralateral lower quadrantanopia}}
What visual field defect will result from a lesion to Meyer's Loop in the Temporal
lobe (dorsal optic radiation)? {{c1::Contralateral upper quadrantanopia}}
Conjugate gaze (to the right) begins with the {{c1::right PPRF}} signaling the
right CN VI nucleus to stimulate the right lateral rectus muscle
In conjugate gaze, the {{c1::Medial Longitudinal Fasciculus (MLF)}} carries fibers
from the CN VI nucleus to the contralateral CN III nucleus to stimulate the medial
rectus muscle
Internuclear ophthalmoplegia (INO) is a horizontal gaze disorder of weak adduction
(medial movement) of one eye due to lesions of {{c1::Medial Longitudinal Fasciculus
(MLF)}} Left INO = Left eye cant adduct (move medially) when looking to the
right
What is the most common cause of Internuclear Ophthalmoplegia (INO)? {{c1::Multiple
Sclerosis}} MLF is highly myelinated
A lesion to the PPRF will result in paralysis of conjugate gaze to {{c1::same}}
side as the lesion Medial pons lesion
A PPRF lesion (paralysis of horizontal gaze) can occur as a result of a
{{c1::basilar}} artery stroke affecting the {{c1::medial pons}} Locked-in syndrome
→ Quadriplegia & loss of horizontal eye movements → vertical eye movement and RAS
are spared (preserved consciousness)
A lesion to the Frontal Eye Field will cause both eyes to deviate {{c1::towards}}
the side of the lesion FEF responsible for keeping normal gaze central (so your
eyes dont wander off) due to equal activation of FEF.
The sclera (white) and the cornea (clear) form the outer layer of the eye composed
of type {{c1::I}} collagen Blue sclera in osteogenesis imperfecta (defect in
type I collagen)
The {{c1::sclera}} is the avascular outer coating of the eye which serves as the
site of extraocular muscle insertion Type I collagen, nutrients from episclera
and choroid
Inflammation of the {{c1::sclera (scleritis)}} causes dark, red eyes and severe
pain with eye movement Pain w/ movement because sclera is the site of insertion
for extraocular muscles. Potentially blinding. Associated with systemic disease
(RA).
{{c1::Pseudomonas}} is a pathogen that commonly causes corneal abrasion and
keratitis in contact lens wearers due to biofilm productionPain, photophobia,
foreign body sensation. Visualized with fluorescein dye and blue light. Treat with
ciprofloxacin drops.
{{c1::HSV-1}} is a pathogen that can cause Keratoconjunctivitis, resulting in pain,
redness and discharge Usually reactivation.
Which pathogen is the most common cause of Viral conjunctivitis (pink eye)?
{{c1::Adenovirus}} Pink eye, watery discharge, swollen pre-auricular lymph
nodes. Adenovirus is very stable and able to survive easily on surfaces (highly
infective).
What are the characteristic symptoms of each of the following causes of
conjunctivitis? Allergic → {{c1::itchy, bilateral}} Bacterial → {{c1::purulent
discharge}} Viral → {{c1::watery discharge}} Bacterial → S. aureus, S. pneumo,
H. flu (adults); S. pneumo, H. flu, Moraxella catarrhalis (children) Viral →
Adenovirus, measles (unvaccinated)
Inflammation of which eye structure is strongly associated with system inflammatory
disorders (RA, JIA, HLA-B27 conditions, etc)? {{c1::Uvea (uveitis)}} Systemic
disorders → HLA-B27 conditions, Sarcoidosis, Rheumatoid arthritis, Juvenile
idiopathic arthritis, etc. May have hypopyon (accumulation of pus in anterior
chamber)
Aqueous Humor in the anterior chamber is produced by the {{c1::ciliary body
epithelium}} under the sympathetic stimulation of {{c1::B2}} receptors Beta
blockers, a2 agonists, and carbonic anhydrase inhibitors ↓ aqueous humor production
Aqueous humor is drained from the anterior chamber by the {{c1::Trabecular
meshwork}} into the {{c1::Canal of Schlemm}} to leave the eye via episcleral
vasculature
Stimulation of parasympathetic {{c1::M3}} receptors causes constriction of the
ciliary muscle, allowing aqueous humor to drain from the anterior chamber -For
distance vision, the ciliary muscle changes the shape of the lens in a process
called accomodation. Ciliary muscle changes also alter the flow of aqueous humor.
Contraction of the ciliary muscle increases the size of the pores in the trabecular
meshwork, leading to increased aqueous humor drainage. Relaxation of the ciliary
muscle decreases trabecular meshwork pore size, reducing aqueous humor outflow. M3
agonists: direct → pilocarpine, carbachol indirect → physostigmine, echothiophate
{{c1::Closed-angle glaucoma}} is a cause of ↑ IOP that presents with abrupt
painful, red eye, with blurred vision and halos around lights "Eye is ""rock""
hard. Fixed and mid-dilated pupil. Surgical emergency. Caused and/or exacerbated by
mydriasis. -Fundoscopy: Optic disc would appear edematous or hyperemic"
What drug is first-line for treatment of closed angle glaucoma while awaiting
surgery? {{c1::Pilocarpine (muscarinic agonist)}} Others include Acetazolamide,
Mannitol, Timolol.
What are the three risk factors for open angle glaucoma? {{c1:: Age African-
American race Family history}} Causes include uveitis, trauma, steroids,
retinopathy
What fundoscopic finding(s) are characteristic of glaucoma? {{c1::Optic disc
atrophy with cupping}}
What 5 classes of drugs are used to treat chronic glaucoma? {{c1:: M3 agonists A2
agonists Diuretics B blockers Prostaglandins}} MAD BP
Which two alpha-2 agonists are used to treat chronic glaucoma? {{c1:: Apraclonidine
Brimonidine}} ↓ Aqueous production; can have ocular side effects → blurry
vision, redness, itchiness, foreign body sensation
{{c1::Epinephrine}} is an alpha-agonist that can be used to treat open-angle
glaucoma, but is absolutely contraindicated in closed-angle glaucoma Causes
mydriasis via a1 stimulation
List the five layers of the epidermis from superficial to deep: {{c1:: Stratum
Corneum Stratum Lucidum Stratum Granulosum Stratum Spinosum Stratum Basale}}
Which layer of the epidermis contains stem cells? {{c1::Stratum basale}}
The Stratum {{c1::Granulosum}} of the epidermis contains keratohyalin granules
which form keratin filaments This is where the process of keratinization happens →
cells die, organelles disintegrate, resulting in interlocked dead cells full
keratin
{{c1::Hyperkeratosis}} is a dermatologic lesion characterized by ↑ thickness of the
stratum corneum Stratum cornum = ↑ keratin. Eg, psoriasis, calluses
{{c1::Parakeratosis}} is a dermatologic lesion characterized by retention of nuclei
in the stratum corneum Stratum corneum should not have nuclei. Indicates
hyperproliferation. Seen in skin diseases (psoriasis) and malignancies
{{c1::Hypergranulosis}} is a dermatologic lesion characterized by ↑ thickness of
the stratum granulosum classic feature of Lichen planus
{{c1::Spongiosis}} is a dermatologic lesion characterized by fluid accumulation
(edema) of the epidermis seen in eczema (Note that urticaria is caused by
edema in the dermis; dermal edema is not spongiosis)
{{c1::Acantholysis}} is a dermatologic lesion characterized by loss of connections
(desmosomes) between keratinocytes "Key feature of pemphigus vulgaris. ""Rounded""
keratinocytes detached and floating freely in the epidermis."
{{c1::Acanthosis}} is a dermatologic lesion characterized by epidermal hyperplasia
and thickening of the straum spinosum Rete ridges are elongated
What are the two major causes of Acanthosis nigricans? {{c1:: Insulin resistance
(DM, Cushing's) Gastric adenocarcinoma}}
Scales are secondary derm lesions caused by peeling/flaking of the {{c1::stratum
corneum}} Psoriasis, eczema, SCC
{{c1::Tight junctions (Zone occludens)}} are epithelial cell junctions that seal
two membranes together to prevent paracellular movement between cells near the
apical membrane Composed of occludin and claudin
{{c1::Adherens Junctions (Zonula Adherens)}} are epithelial cell junctions that
form a belt around cells to anchor adjacent cells to one another
{{c1::Desmosome (Macula Adherens)}} are spots of cell-to-cell attachment most
commonly found in the skin Attached to keratin intermediate filaments found in
cell cytoplasm, linked by cadherins
Desmosomes are spot-junctions between epithelial cells composed of cytoplasmic
{{c1::keratin (intermediate)}} filaments linked by cadherins
{{c1::Hemidesmosomes}} are epithelial cell junctions that attach epithelial cells
to basement membrane
Hemidesmosomes are composed of cytoplasmic keratin (intermediate) filaments linked
by {{c1::integrins}} to the basement membrane Integrins attach to laminin (basal
lamina) and collagen in basement membrane
Gap Junctions are communication channels between cells composed of {{c1::connexin}}
proteins Connexons are too small for proteins, nucleic acids to pass through.
Only allows passive of small molecules (Na in myocytes)
Pemphigous vulgaris is a serious autoimmune skin disorder caused by antibodies
against which type of epithelial cell junction? {{c1::demsomes}} specifically, IgG
against Desmoglein. So, it's a type II hypersensitivity
Bullous pemphigoid is an autoimmune skin disorder caused by IgG antibodies against
which type of epithelial cell junction? {{c1::hemidesmosomes}} Less severe than
PG, both Type 2 HS
Which five tumors can secrete EPO and cause Polycythemia? {{c1:: Pheochromocytoma
Hepatocellular carcinoma Renal cell carcinoma Hemangioblastoma Leiomyoma}} Please
Help Reduce Hematocrit Levels
{{c1::Cutibacterium acnes}} is an anaerobic bacteria in the normal skin flora that
uses sebum as a growth medium to cause acne Comedones refer to debris blocking
sebaceous gland ducts, creating a lipid-rich environment for bacteria to grow,
because the bacteria use triglycerides in the sebum as feul. (Formerly called
Priopionibacterium)
What are the four (usmle relevant) treatments for acne? {{c1:: Benzoyl peroxide
Clindamycin Tetracyclines Isotretinoin (Vitamin A)}} Benzoyl peroxide (topical)
breaks down keratin to unblock pores. Bactericidal to C. acnes Vitamin A
(retinoids) decrease production of keratin and sebum
While the pathogenesis of Seborrheic dermatitis is poorly understood, what are the
two associations with this condition? {{c1:: Parkinson's Malassezia furfur}} common
in infants and adults
{{c1::Pseudofolliculitis barbae (razor bumps)}} are firm papules/pustules that
occur after shaving due to inflammation from trapped hairs (common in black men)
{{c1::Psoriasis}} is a chronic inflammatory skin disorder characterized by well-
demarcated pink/salmon colored plaques with silverly scaling on the extensor
surfaces
{{c1::Auspitz sign}} is pinpoint bleeding spots from exposure of dermal papillae
when scales are scraped off in psoriasis
{{c1::Rosacea}} is an inflammatory skin condition that manifests as elevated
papules and pustules commonly located on the nose and cheeks No comedones. May
be associated with facial flushing in response to external stimuli (alcohol, heat)
{{c1::Phymatous rosacea}} is hypertrophy of this skin (most commonly around the
nose) as a consequence of untreated rosacea
What are the histologic hallmark of Seborrheic keratosis neoplasms? {{c1::Keratin-
filled cyst (horn cyst)}}
{{c1::Erythema Nodosum}} is a type IV hypersensitivity reaction characterized by
painful inflammation of subcutaneous fat (panniculitis) on the shins Causes
include IBD (Crohns), sarcoidosis, streptococcal infections, coccidiodes,
histoplasmosis, TB, leprosy
What two autoimmune conditions are known triggers for Erythema Nodosum? {{c1::
Sarcoidosis IDB (Crohns)}} Infectious causes → streptococcal infx,
coccidioidomycosis, histoplasmosis, TB, leprosy
What 5 infectious causes are known triggers for Erythema Nodosum? {{c1::
Streptococcus Coccidioidomycosis Histoplasmosis Tuberculosis Leprosy}} "Easy way to
remember this; each pathogen has something in common with the one below. 1 -
""cocci"" - 2 - fungal lung infx - 3 - lung - 4 mycobacterium - 5. Other causes →
IBD (crohn's), Sarcoidosis"
What is the hallmark pathology finding in Erythema Nodosum? {{c1::Septal
panniculitis}} Inflammation between subdermal fat lobules, not inflammation of
the actual fat lobules themselves
Lichen planus is chronic, inflammatory skin disorder of itchy plaques and is
strongly associated with {{c1::chronic Hepatitis C}} 6 P's → Pruritic, Purple,
Polygonal, Planar, Papules and Plaques
What are the 6 characteristics of Lichen Planus lesions? {{c1::Pruritic, Purple,
Polygonal, Planar, Pustules and Plaques}} But if you forget all that mess → they're
super itchy, flat, purple lesions. Strongly associated with Hep C.
What are the two unique presentation characteristics of Lichen Planus? {{c1::
Mucosal involvement Wichham straie }} Wickham striae → reticular white lines in
oral LP that represent hypergranulosis
Wickham straie of oral lichen planus are reticular white lines caused by
{{c1::hypergranulosis}}
What are the characteristic pathology findings of Lichen Planus?
{{c1::Hypergranulosis and sawtooth infiltrate of lymphocytes at dermal-epidermal
junction (rete ridges)}}
"{{c1::Pityriasis Rosea}} is a skin condition that begins as a single salmon-
colored lesion (Herald patch) followed weeks later by multiple lesions in a
""christmas tree"" distrubution on the trunk" Self-resolving (6-8 weeks)
{{c1::First}} degree burns affect the epidermis only and blanch with pressure
Painful, red, no blisters. Heal within 7 days.
{{c1::Second}} degree burns extend to the dermis and cause blisters. Painful and
blanch with pressure plus blisters (1st degree wont blister; heal within 1-3 weeks.
{{c1::Third}} degree burns extend through the hypodermis, are yellow/white, painful
only to pressure, do not blanch, and scar with healing generally painless
because superficial nerves are burned off.
Which forms of UV radiation are associated with sunburn, tanning beds, and skin
aging, respectively? Sunburn: {{c1::UVB (280-320 nm)}} Tanning bed: {{c1::UVA (320-
400 nm}} photo-aging: {{c1::UVA}} Both UVA & UVB ↑↑ risk of skin cancer
What is the pathophysiologic mechanism by which UV rays cause sunburn? {{c1::UV →
DNA mutations → apoptosis of keratinocytes}} Sunburn involves damage to the
epidermis and dermis. Also causes vasodilation and release of inflammatory
mediators. Remember that xeroderma pigmentosum arises from defective nucleotide
excision repair of UV damage
What are the two risk factors for Breast Angiosarcomas? {{c1:: Radiation therapy
Lymphedema post-mastectomy}} Women who previously had breast cancer. Radiation can
damage endothelial blood vessel lining. Chronic lymphedema can cause lymph vessels
(also endothelial) to swell, triggering neoplasia.
{{c1::Angiosarcomas}} are malignant tumors of blood vessels that arise from the
dermis in the head and neck (sun exposure) Blood vessels are derived from
endothelium. No BVs in epidermis. Usually elderly white males. Aggressive, poor
prognosis.
{{c1::Bacillary angiomatosis}} is a proliferation of vascular skin papules due to
Bartonella infection in AIDS patients Has neutrophilic infiltrate (kaposi
sarcoma does not)
{{c1::Kaposi sarcoma}} is a malignant angioproliferation in the skin, mouth or GI
tract, due to HHV-8 infection in HIV patients (resembles bacillary angiomatosis)
Violaceous skin lesions in a HIV patient--> Kaposi sarcoma Lymphocytic
infiltrate (inflammation) on biopsy, no neutrophils (BA)
How do you differentiate between Kaposi Sarcoma and Bacillary Angiomatosis? KS →
{{c1::lymphocytic infiltrate}} BA → {{c1::neutrophil infiltrate}} Easy; KS is
a viral infection (lymphocytes) and BA is a bacterial infection (neutrophils)
{{c1::Pyogenic granulomas (lobular capillary hemangiomas)}} are benign tumors of
blood vessel hyperplasia in the skin classically stimulated by {{c2::pregnancy}}
and {{c2::trauma}} BLEED profusely
{{c1::Cherry Hemangiomas}} are very common benign capillary hemangiomas that occur
on the trunk with aging ↑ with age, do not regress. Histologically; congested
capillaries in the dermis.
Cystic Hygroma is a congential lymph-filled cyst on the back of the neck associated
with {{c1::Downs Syndrome}} and {{c1::Turner's Syndrome}} Often identified on
fetal ultrasound. Increases risk of miscarriage and fetal death.
Glomus Tumors are benign growths of {{c1::modified smooth muscle cells}} at tips of
toes, fingers and under nailbeds that are extremely painful when exposed to cold
Smooth muscle cells of the thermoregulatory glomus body
{{c1::Strawberry Hemangiomas}} are very common, benign proliferations of blood
vessels that appear in newborns and regress within a few years of life
{{c1::Nevus Flammeus}} is a malformation of dermal capillaries and venules that
presents in newborns as unilateral, blanching, pink-red patch (port-wine stain)
Sturge-Weber
Melanocytes are derived from what embryonic origin? {{c1::Neural crest cells}}
This is high yield. Melanocytes are specialized secretory cells in basal
layer of the epidermis.
What are the two causes of ↓ melanin production in Oculocutaneous Albinism (OCA)?
{{c1:: ↓ tyrosinase activity defective tyrosine transport}}Normal number of
melanocytes
"{{c1::Melasma (""pregnancy mask"")}} is an acquired hyperpigmentation of sun-
exposed areas of the face due to a change in hormone levels in women (OCPs,
pregnancy)" More common in women with darker complexion at baseline. Treat with sun
protection and hydroquinone (inhibits tyrosinase)
Vitiligo is an acquired, localized pigment disorder of depigmented (white)
macules/patches due to {{c1::autoimmune destruction of melanocytes}} So you'd
treat with steroids +/- immunosuppressants
While vitiligo will have obvious areas of depigmentation in dark-skinned
individuals, how will light-skinned individuals with vitiligo present?
{{c1::Failure to tan in a localized region}}
Actinic Keratosis are premalignant skin lesions caused by sun-induced growth of
{{c1::atypical epidermal keratinocytes}} Actinic keratosis → increasing degrees of
dysplasia → squamous cell carcinoma
What are the three major histology findings in Actinic Keratosis? {{c1::
Hyperkeratosis Parakeratosis Epidermal cell dysplasia}} Parakeratosis = retained
nuclei in corneum
Actinic keratosis are small, rough red-brown plaques in sun-exposed areas of the
skin that are premalginant for {{c1::sqaumous cell carcinoma::malignancy}}
{{c1::Squamous cell carcinoma}} is a skin cancer that presents as red, scaling
plaques that may ulcerate most commonly on the lower lip, ears and hands 2nd
most common skin malignancy. 5% metastasize to lymph nodes, hardly any metastasize
beyond that.
What is the classic pathology finding in Squamous Cell Carcinoma? {{c1:: Keratin
pearls }}
"{{c1::Keratoacanthoma}} is a benign variant of SCC that appears as a ""dome-
shaped"" nodule with central hyperkeratosis which grows rapidly (4-6 weeks) and
slowly regresses over time"
Rank the three major forms skin cancer from most common to least: {{c1::Basal cell
> squamous cell > melanoma}} Highest potential for recurrence/metastases: Melanoma
>>> sqamous > basal
"{{c1::Basal Cell Carcinoma}} is a skin cancer that presents as a ""pearly"" papule
or nodule commonly with rounded, thickened borders, telangiectasias, and central
crusting or ulceration"
Superficial subtype Basal cell carcinoma presents as a {{c1::light red/pink
plaque}} most commonly on the {{c1::trunk}} So it basically looks like every
other skin lesion in existence.
What are the five phenotypic characteristics of melanoma? {{c1:: Asymmetrical
Irregular Border Color variation Diameter > 6 mm Evolving over time}}
{{c1::Superficial spreading}} is the most common subtype of melanoma ABCDE
phenotype
{{c1::Nodular melanoma}} is a very aggressive subtype of melanoma that grows
vertically 15-30% of melanomas, but 50% of melanoma deaths
{{c1::Lentigo maligna melanoma}} is a subtype of melanoma in the elderly that grows
slowly within the epidermis for years before darkening and invading the dermis
{{c1::Acral lentiginous melanoma}} is the least common subtype of melanoma that
occurs at the palms, soles, and under the nails in dark skinned patients (Asians &
AAs)
What tumor marker is used to identify melanomas? {{c1::S100}} S100 = calcium
binding protein in nucleus. Highly specific, low sensitivity
What parameter is used to assess the risk of metastasis of melanoma? {{c1::Depth of
tumor (Breslow thickness)}} Breslow thickness → distance from granular layer of
epidermis to deepest tumor cells
Melanoma metastasizes hematogenously and lymphatically to which three organs most
commonly? {{c1::Lungs, liver, brain}} Brain mets → most common cause of death.
Must excise with wide margins.
Most sporadic melanomas are caused by a {{c1::V600E}} mutation of the {{c1::BRAF}}
gene BRAF → proto-oncogene, codes for serine/threonine kinase → triggers cell
proliferation on RAS activation
BRAF is a proto-oncogene that codes for {{c1::serine/threonine kinases}}
Melanoma (V600E mutation), Non-hodgkin lymphoma, papillary thyroid carcinoma,
serrated polyps & CRC
What causes freckles (ephelis)? {{c1::↑ number of melanosomes}} Normal # of
melanocytes
What is the most common demographic affected by SLE? {{c1::African
American/Hispanic women of reproductive age (~15-40)}} Think lupus if an
individual of this demographic presents with rash (malar), joint pain, and fever
Which 3 antibodies are associated with SLE, and which are sensitive/specific? (not
including antiphospholipid syndrome Abs) {{c1:: Anti-nuclear (sensitive) Anti-dsDNA
(specific) Anti-smith (specific)}} - Anti-dsDNA → associated with disease activity
(↑ in flares) and associated with renal involvement (DPGN) - Anti-smith → directed
against snRNPs
While most SLE symptoms are the result of a type III hypersensitivity, which SLE
symptoms are caused by a type II hypersensitivity reaction? {{c1::cytopenias}}
Direct antibody attack of cells → Anemia, Thrombocytopenia, Leukopenia
What are the three most common causes of death in patients with SLE? {{c1:: Renal
failure (#1) Infection Cardiovascular disease (accelerated)}} Renal failure →
glomerular deposition of DNA-anti-DNA immune complexes. Can be rephritis (DPGN) or
nephrotic (membranous nephropathy)
What are the two symptoms of neonatal lupus? {{c1::Rash (red, circular lesions on
the face and scalp) and Congenital Heart Block}} Heart block (heart rate in
50s) does not respond to steroids → child may need permanent pacemaker. Remember
that neonatal lupus is associated with Anti-SSA (Ro) and Anti-SSB (La) antibodies
from SLE or Sjorgrens syndrome
Immunosenesence is a process of aging characterized by decreased {{c1::T}}-cell
production and impaired {{c1::cell-mediated}} immunity Impaired cell-mediated
immunity thereby results in the decreased production of antibodies & B-cell class
switching.
Which blistering skin disorder is unique due to its involvement of the oral mucosa?
{{c1:: Pemphigus vulgaris }} Life threatening type II hypersensitivity due to
autoimmine IgG antibodies directed against desmoglein (component of desmosomes,
which connect keratinocytes in the stratum spinosum)
What is the pathologic hallmark of Pemphigus vulgaris? {{c1::Acatholysis → loss of
connections between keratinocytes}} Note that this is occuring in the stratum
spinosum due to anti-desmoglein (desmosome) antibodies
Pemphigus vulgaris is caused by IgG autoantibodies against {{c1::desmoglein}} in
the stratum {{c1::spinosum}} Desmoglein is a component of desmosomes, which are
found in the spinosum. Causes ancothlysis and flaccid intraepidermal bullae
{{c1::Pemphigus vulgaris}} is a blistering skin disorder characterized by flaccid
intraepidermal bullae with oral involvement Caused by antibody destruction of
desmosomes in stratum spinosum → limited by basement membrane → intraepidermal
What three pathologies can cause a postivie Nikolsky Sign (skin slips off with with
gentle tug)? {{c1:: Pemphigus vulgaris Staph scaled skin (child) Stevens-Johnson
syndrome}} Peel Scalded Skin Slowly All caused by loss of connections in
epidermis.
How does Pemphigus vulgaris most commonly present? {{c1::Painful chewing and
swelling inside of mouth}} Usually 30-60 years old. Oral pain d/t oral bullae
and ulcerations. In PV, there won't many classically appearing intact bullae, most
will be ruptured and scabbed (see image).
What is the classic finding on immunofluorescence staining of Pemphigus vulgaris?
{{c1::IgG in reticular (net-like) pattern }} D/t IgG against desmoglein. Tx with
immunosuppressants.
{{c1::Bullous pemphigoid}} is a blistering skin disorder characterized by tense,
subepidermal blisters which spares the mouth Most bullae will be intact. In
contrast, pemphigous vulgaris blisters are usually ruptured with scabs
(intraepidermal = weaker). Typically a disease of the elderly
What is the classic finding on immunofluorescence staining of Bullous pemphigoid?
{{c1:: Line at epidermal-dermal junction (hemidesmosomes) }}
What is the classic pathology finding in Bullous pemphigoid biopsy?
{{c1::Eosinophils & lymphocytes between dermal-epidermal junction }}
{{c1::Dermatitis Herpetiformis}} is an itchy papular/vescicular rash occuring on
the extensor surfaces in patients with celiac disease Biopsy: Subepidermal clefting
and blistering Most commonly at the elbows. IgA deposits at dermal papillae. treat
with dapsone and gluten-free diet
Dermatitis Herpetiformis is caused by {{c1::IgA}} deposition in the {{c1::dermal
papillae}} Biopsy: Subepidermal clefting and blistering Occurs with celiac disease
(IgA = gut), will see microabscesses at tips of papillae.
Impetigo is a highly contagious superficial skin infection caused by
{{c1::neutrophils}} collecting beneath the stratum {{c1::corneum}} "Macules →
papules → rupture → dried sebum → ""honey-colored"" crust. Most commonly due to
Staph aureus or Strep pyogenes"
Staph aureus causes bullous impetigo via Exfolatin-mediated cleavage of
{{c1::desmoglein-1 complex}} in the stratum {{c1::granulosum}} Exfolatin =
Exfoliative exotoxin. Also causes scalded skin syndrome.
{{c1::Erysipelas}} is a skin infection of the superficial dermis characterized by a
rash with clear demarcation Patient will also have systemic symptoms of acute
onset (fever, chills). Usually caused by Strep pyogenes.
How do erysipelas and cellulitis infections differ based on location? (skin layers)
Erysipelas: {{c1::upper dermis & superficial lymphatics}} Cellulitis: {{c1::deep
dermis & subcutaneous fat}} Erysipelas has a distinct demarcation between
infected tissue and normal, while Cellulitis has an ill-defined, spreading border
{{c1::Cellulitis}} is a skin infection of the deep dermis characterized by a
painful, warm rash with an ill-defined, spreading border Middle-aged and elderly
(rarely children). Strep pyogenes or Staph aureus
Skin abcess is defined as a collection of {{c1::pus (neutrophils and bacteria)}}
walled-off in the dermis or subcutaneous space. Always staph aureus. Requires I&D
(abx cant penetrate bc its walled-off)
{{c1::Necrotizing Fasciitis}} is a deep tissue infection of muscular fascia and
subcutaneous fat that causes destruction (necrosis) of all tissue above the fascia
d/t anaerobes or strep pyogenes
List which pathogen(s) are associated with the following skin infections: Impetigo:
{{c1::Staph, Strep}} Bullous Impetigo: {{c1::Staph}} Erysipelas: {{c1::Strep}}
Cellulitis: {{c1::Strep, Staph}} Abscesses: {{c1::Staph}} Nec. Fasciitis:
{{c1::Strep, anaerobes (bacteroides)}} Strep = Pyogenes Staph = aureus
The NF1 gene (mutated in NF1) codes for the {{c1::neurofibromin (tumor
suppressor)}} protein which normally functions to restrict {{c1::RAS}} activity
Mutation → RAS overactivity → uncontrolled growth → cafe-au-lait spots,
cutaneous neurofibromas, optic gliomas, pheochromocytomas, Lisch nodules
Which 3 symptoms of NF1 present within 2 years of life? {{c1:: Cafe-au-lait spots
Bone abnormalities Optic gliomas }} Optic gliomas in an infant is a dead giveaway.
Develop Lisch nodules in developmental delay around 2-6 years old, then cutaneous
neurofibromas in adolescence
What are the four components of Neurofibromatosis II? {{c1:: Bilateral acoustic
schwannomas Juvenile cataracts Meningiomas Ependymomas}} NF2 affects 2 ears, 2
eyes, 2 parts of brain
NF1 and NF2 are on which chromosomes? NF1 → {{c1::17}} NF2 → {{c1::22}}
Important note: NF1 has 100% penetrance but displays variable expressivity
(every carry affected, but to a different degree). Card on this is genetics deck.
-Neurofibromatosis=17 letters (type 1) -NF2=22
Tuberous Sclerosis is mutations in TSC1 and TSC2 genes; which chromosome are they
located on and what product do they code for? TSC1: {{c1::Chr 9; Hamartin::chr;
product}} TSC2: {{c1::Chr 16; Tuberin::chr; product}} Twoberin, Two digits (16)
What is the normal function of Hamartin (TSC1) and Tuberin (TSC2)? {{c1::inhibit
mTOR (kinase enzyme)}} TS = mutation → mTOR overactivity → cell growth (especially
in size) mTOR = mechanistic target of rapamycin.
Tuberous Sclerosis can present as hydrocephalus due to the development of
{{c1::Subependymal giant cell astrocytomas}} at the {{c1::interventricular
foramen}} Low grade astrocytoma. May also have ungual fibromas (beneath nailbed)
What are the three potential risks/complications of Renal Angiomyolipomas in
Tuberous Sclerosis? {{c1:: Hemorrhage (pain) HTN (renin secretion) Chronic Kidney
Disease}} Most frequent renal manifestation. Always multiple/bilateral. Caused by
a proliferation of epithlial cells around vessels. Compress normal renal tissue
(CKD)
All Neurocutanoues disorders are inherited {{c1::autosomal dominant}} except for
{{c1::Sturge-Weber Syndrome}} SW → spontaneous gene mutation causing congenital
vascular disorder of capillaries
Sturge-Weber Syndrome is caused by a sporadic {{c1::somatic}} mutation of
{{c1::GNAQ}} gene Somatic mutation = occurs after fertilization → Mosaicism
Leptomeningeal angiomas in Sturge-Weber Syndrome cause {{c1::seizures}} in 80% of
patients and occur on the {{c1::same}} side as the port-wine stain
Leptomeninges = pia & arachnoid Angioma = capillary venous malformation May
also cause seizures, headaches.
What is the normal function of the VHL gene (deleted in von Hippel-Lindau disease)?
{{c1::tumor suppressor → ubiquitination of hypoxia-inducible factor 1a}}
Ubiquitination is a post-translational modification that tags proteins for
destruction in a proteasome. Cells behave as if they're hypoxic → blood vessel
growth → hemangioblastomas
{{c1::Hemangioblastomas}} are benign, bright red vascular tumors that occur in VHL
Disease No invasion or metastasis, but can present as compression of other
structures or hemorrhage.
Hemangioblastomas are most commonly located in which 4 locations in VHL Disease?
{{c1:: Brainstem Cerebellum Retina Spinal Cord}} Highly vascular w
hyperchromatic nuclei:
Urticaria is an allergic skin reaction caused by {{c1::mast cell}} degranulation
and {{c1::histamine}} release Type 1 Hypersensitivity. Antigen binds to IgE on mast
cells. IgE on mast cells aggregate, triggering degranulation.
Urticaria causes edema due to {{c1::histamine::mediator?}} increasing the
permeability of blood vessels in the {{c1::dermis}} No changes to epidermis.
Dilation of lymph vessels for fluid drainage in dermis.
{{c1::Atopic Dermatitis (Eczema)}} is a skin hypersensitivity disorder
characterized by recurrent pruritic rashes triggered by environmental antigens
Often at flexures (elbows). Associated with other atopic diseases; asthma,
allergies, etc.
Atopic Dermatitis (Eczema) is associated with increased levels of serum {{c1::IgE}}
Most ppl with eczema will also have another atopic disease (asthma,
allergies). Appears on face in babies/infants and in elbow crease in children and
adults
{{c1::Contact Dermatitis}} is an allergic skin reaction that is localized to the
area of skin in contact with the allergen -Presensitized CD4+ Th-cells are
involved. These cells bind to MHC II on antigen-presenting cells via the T-cell
receptor and release cytokines, causing inflammation and cellular injury. Type 4
Hypersensitivy, often caused by poison ivy, nickel (jewelry), copper, cosmetics
laundry detergets, neomycin.
Stevens-Johnson Syndrome is a severe type {{c1::4}} hypersensitivity skin reaction
to drugs characterized by necrosis of the {{c1::epidermis (keratinocytes)}}
Characteristic dermatologic manifestations are widespread blisters and
erosions of the skin and mucosal surfaces Nikosly sign (+). Prodrome with fever,
flu-like symptoms → face/chest lesion → symmetric spread → progresses into
vescicles/bullae → sloughing of skin
{{c1::Toxic Epidermal Necrolysis}} is a more severe form of Stevens-Johnson
Syndrome that marked by involvement of > 30% of the skin Higher mortality.
Sloughing of skin → lost water (dehydration) & infections
Erythema multiforme is a skin disorder associated with which two infections? {{c1::
Herpes Simplex Virus Mycoplasma pneumonia}} HSV is most common. Also associated
with sulfa drugs, NSAIDs, phenytoin, cancers, autoimmine diseases
What is the hallmark lesion of Erythema Multiforme? {{c1:: Target lesion
(dark/dusky center surrounded by red ring) }} "Can present as macules, papules,
vescicles → differs between patients (""multiforme"")"
While they may present similarly, how do you differentiate between Erythema
Multiforme and SJS based on location of lesions? SJS → {{c1::starts on face}} EM →
{{c1::starts on back of feet/hands}} "Both may have target lesions and follow
the use of drugs, but EM (often preceded by HSV) will start on the back of the hand
or feet and move towards the trunk and towards the face (""centripital spread"")"
Atopic Dermatitis is often associated with mutations in the {{c1::filaggrin}} gene
Can be familial. Look for multiple family members having hx of asthma,
allergies, etc.
What are four major differences that distinguish Rheumatoid Arthritis from
Osteoarthritis? {{c1:: Systemic symptoms (fever) Symmetric Morning stiffnes > 1
hour Spares DIP }} Classically affects MCP and PIP joints. Also importantly,
RA improves with use.
What are rheumatoid factor antibodies directed against? {{c1::Fc portion of IgG
antibody}} RF = IgM. Not specific. Positive in Sjogren's, Lupus, endocarditis, Hep
B, Hep C.. Anti-citrullinated peptide antibody is specific
Which autoantibody is the most specific for Rheumatoid Arthritis? {{c1::Anti-
citrullinated peptide antibody}} -Pathophysiology of RA appears to be
inflammation of the synovium (soft tissue that lines the joint spaces of
diarthrodial joints, bursae and tendon sheaths), followed by synovial hypertrophy
and joint erosion. RA will have ↑ ESR & CRP. HLA-DR4.
Felty Syndrome is a possible complication of long-term rheumatoid arthritis
characterized by {{c1::neutropenia}} and {{c1::splenomegaly}} Neutropenia in
Felty's syndrome often improves after splenectomy. Always in someone with severe
disease (joint deformity, extra-articular disease)
Caplan Syndrome is definied as {{c1::pneumoconiosis}} and {{c1::pulmonary
rheumatoid nodules}} in the setting of rheumatoid arthritisRA + neutropenia +
splenomegaly = Felty Syndrome
What are 10 most common extraarticular manifestations of rheumatoid arthritis? :
( {{c1:: Caplan Syndrome Interstitial lung disease Pleuritis Pericarditis Anemia of
chronic disease Felty syndrome AA Amyloidosis Sjogren syndrome Scleritis Carpal
tunnel}} PAPAS Felt SICC
Scleroderma (Systemic Sclerosis) is initiated by endothelial damage causing
{{c1::fibroblast}} activation and {{c1::excess collagen}} deposition The
pathophysiology of scleroderma appers to be antibody-mediated fibroblast
activation, which leads to excess collagen deposition Widespread fibrosis &
sclerosis most commonly visible on the skin. Commonly involves women 30-50 years
old
What are the two initial signs of Diffuse Scleroderma? {{c1:: Raynaud's phenomena
Skin thickening}} Raynaud's is 1st sign and often precedes other signs and symptoms
(renal, GI, CV) by a year.
Diffuse Scleroderma leads to early/rapid progression of what visceral symptoms?
{{c1:: GI dysmotility Renal failure Interstitial lung fibrosis Pulmonary HTN
Myo/peri-carditis Joint/muscle pain}} Most feared long-term complication of
diffuse scleroderma is renal failure Gonna RIP My Joint Heart manifestations can
also include conduction diseases (bundle branch blocks, AV blocks)
Scleroderma Renal Crisis is a life-threatening complication of diffuse scleroderma
that responds to treatment with {{c1::ACE Inhibitors}} Person with diffuse
scleroderma presenting with marked HTN and acute worsening of renal function → ACE
inhibitors ASAP
What are the five major features of Limited Scleroderma (crest syndrome)? {{c1::
Calcinosis cutis Raynaud phenomenon Esophageal dysmotility Sclerodactyly (thick
skin) Telangiectasia}} Skin involvement limited to fingers and face. Diffuse
scleroderma can have all these symptoms as well. Calcinosis cutis → calcium
deposits in subcutaneous tissue on elbows, knees, fingers. Can break and leak white
liquid. visible on xray Calcinosis occurs in the subcutaneous tissue of elbows,
knees, fingers - can break skin and leak chalky white liquid - xray of hands may
show soft-tissue calcifications Raynaud syndrome may lead to digital ulceration /
critical ischemia Esophageal dysmotility is caused by collagen deposition in the
esophagus, causing atrophy of smooth muscle - this leads to LES hypotonia
(incompetent LES) - leads to acid reflux and dysphagia --> stricture, barrett
esophagus, aspiration Sclerodactyly is fibrosis of the skin of the hands (fingers
are puffy, hard to bend) - skin is thickened (can't pinch), becomes shiny and loses
wrinkles - once it gets severe, patients have hands like claws Telangiectasias are
skin lesions that result from dilated capillaries - presents on the face, hands,
mucous membranes (inside the mouth) - women tend to have it more on face
Which autoantibody is specific to Limited Scleroderma (Crest syndrome)? {{c1::Anti-
centromere AB}} - anti-centromere = crest - anti-nuclear antibody = elevated in
both forms, non-specific
What is the first line treatment for Raynaud's Phenomenon? {{c1::Dihydropyridine
Calcium channel blockers (amlodipine)}} etiologies include CREST syndrome, SLE,
mixed connective tissue disease, idiopathic.
What four autoantibodies are associated with Sjogren's Syndrome? {{c1:: Anti-
nuclear (ANA) Rheumatoid factor Anti-SS-A (Ro) Anti-SS-B (La)}} Rheumatoid factor
→ 1º or 2º disease Anti-SS-A (Ro) → neonatal lupus Anti-SS-B (La) → neonatal lupus
Anti-nuclear (ANA) → nonspecific
What salivary gland biopsy finding confirms the diagnosis of Sjogren's Syndrome?
{{c1:: Focal lymphocytic sialadenitis }} Also need to have antiribonucleoprotein
antibodies (SS-A, SS-B)
Type I Hypersensitivity reactions are due to {{c1::preformed IgE antibodies}}
cross-linking on the surface of mast cells to trigger degranulation within minutes
of exposure Degranulation of histamine results in symptoms like wheezing, uticaria-
an itchy, red, raised plaque in the skin. First exposure to allergic antigen
(pollen, cats) → Th2 → IL-4 → B-cells → IgE → second exposure →
hypersensitivity/allergies IgE does NOT activate compliment About six hours after
early symptoms of type I HSR, late symptoms develop. These are caused by influx of
inflammatory cells like macrophages, neutrophils, and eosinophils which release
cytokines. Lesions will turn firm and indurated when this occurs.
{{c1::Anaphylaxis}} is a severe, systemic type I hypersensitivity reaction tiggered
by food, drugs, bee stings, etc Tx with Epinephrine → Urticaria,
Bronchoconstriction (resp distress), Hoarseness (laryngeal swelling/edema),
vomiting, cramps, shock, death.
What are the four functions of PGE2 in T1HS reactions? {{c1:: Redness
(vasodilation) Edema (permeability) Fever (hypothalamus) Pain (nerves)}}
Bradykinin and PGE2 are the two mediators of pain in inflammatory responses
What are the two functions of Leukotrienes (E4, C4, D4) in T1HS reactions? {{c1::
Bronchoconstriction Inc vascular permeability}} - Montelukast and Zafirlukast block
leukotriene receptors (CYSLT1) in aspirin and exercise-induced asthma. - Zileuton
blocks the syntheses of leukotrienes by blocking 5-lipoxygenase - note that LTB4
functions in neutrophil and eosinophil chemotaxis, not bronchoconsctriction
What are the four major molecules released from Mast Cells upon degranulation in
T1HS? {{c1:: Histamine Heparin Tryptase ECF-A}} - ECF-A → Eosinophil chemotactic
factor of anaphylaxis - Tryptase (and chymase) → neutral proteases, markers of mast
cell activation
Desensitization (allergy shots) gradually alter the body's immune response to an
antigen by what mechanism? {{c1::IgE → IgG}} IgE causes the allergic reaction.
With enough exposure to antigen, response switches to IgG antibodies that can block
mediator release
What are the three mechanisms of Type II (IgG and IgM) Hypersensitivity disorders?
{{c1:: Phagocytosis Complement-mediated lysis Antibody-dependent cytotoxicity }}
{{c1::Serum sickness}} is a systemic T3HS disorder caused compliment-mediated
inflammation 1-2 weeks after exposure to trigger -Antibody-antigen complexes
form after exposure to nonhuman protein antigens (eg; venom anti-toxins, microbial
anti-toxins). If these complexes are inadequately cleared by the mononuclear
phagocyte system, they can deposit in tissues and cause serum sickness due to the
resulting inflammatory response. This response includes complement activation and
consumption, which results in a decreased serum complement concentration Immune
complexes in plasma (IgG, IgM) → systemic → skin, kidneys, joints → compliment
activation → activation of macrophages and neutrophils via Fc receptors →
neutrophil lysosomal enzymes → tissue destruction
What three substances are rarely associated with serum sickness-like reactions?
{{c1:: Rabies or tetanus anti-toxin Penecillin (hapten) Monoclonal antibodies
(rituximab, etc)}} Type III HS → presents with urticaria, fever, arthralgia,
proteinuria, lymphadenopathy 1-2 weeks after administration of drug
{{c1::Arthus Reaction}} is a subacute localized T3HS reaction that occurs when
injected antigens form immune complexes with preformed antibodies (IgG) in the
dermis ICs deposition describes mechanism of Arthus reaction. ICs trigger
localized vasculitis and fibrinoid necrosis by activating the classical complement
pathway. These intradermal ICs cause swelling, induration, necrosis due to
compliment activation around 4-10 hours after injection.
What type of hypersensitivity reaction causes swelling, redness hours after skin
injections (TDaP, insulin)? {{c1::Localized Type III HS (Arthus reaction)}}
Hypersensitivity pneumonitis (farmer's lung) is also has a localized T3HS
component due to preformed antibodies to environmental antigen (in farmers lung)
{{c1::Autograft}} is a type of transplant where the graft is taken from self and
commonly occurs in {{c1::Bone Marrow}} transplants Leukemias, lymphomas → remove
bone marrow from patient → administer high dose chemo to kill remaining cell lines
→ replace (give back) bone marrow
{{c1::Syngenetic Graft (isograft)}} refers to a transplant in which the graft is
taken from an identical twin
{{c1::Xenograft}} refers to a transplant in which the graft is taken from a
different species
{{c1::Allograft}} refers to a transplant in which the graft is taken from a
different person of the same species Most transplants (kidney, lung, etc)
What are the three elements of a good graft match for organ transplant? {{c1:: Same
blood type Same (close) MHC I & II Negative cross-matching screen}} - Cross-
matching screen → test of donor cells against recipient plasma, make sure there
arent any host antibodies waiting to attack a potential graft - MHC I → expressed
on all donor cells, CD8+ rxn if different from recipient - MHC II → can be carried
along in vascular endothelial cells from donor
Genes coding for Human Leukocyte Antigens (HLA Types) are located on chromosome
{{c1::6}} MHC I → HLA- A,B,C MHC II → HLA-DR, -DM, -DP, DQ
What is the likelihood that a sibling is a perfect match to a patient in terms of
HLA antigens? {{c1::25%}} "HLA antigens are inherited as groups of alleles.
Father and mother both have two sets → child inherits one ""set"" from each
parent."
What are the three most important HLA genes for solid organ transplant matching?
{{c1:: HLA-A HLA-B HLA-DR}} """6 out of 6 match"" if they all match."
Graft Versus Host Disease is mostly a complication of which two organ transplants?
{{c1:: Bone Marrow Liver}} "BM and Liver are rich in lymphocytes → grafted
immunocompetent T cells proliferate in immunocompromised host and attack
""foreign"" host proteins"
{{c1::Graft Versus Host Disease}} is a transplant complication where the Donor T-
cells (CD8) attack recipient (host) proteins -CD8+ T-cells bind to MHC class I
on somatic cells via the T-cell receptor and induce target cell death Often from BM
and Liver transplant. Causes rash, diarrhea, abdominal pain, liver dysfunction
(↑LFTs, ↑ bilirubin)
Graft Versus Host Disease is actually a favorable reaction in the setting of bone
marrow transplant to treat {{c1::leukemia}} Graft versus tumor effect. Grafted
CD8 T-cells see host's leukemic cells as foreign and attacks them
List the timing associated with each of the three types of transplant rejection:
Hyperacute: {{c1::within minutes}} Acute: {{c1::weeks to months}} Chronic:
{{c1::months to years}}
Hyperacute rejection occurs due to {{c1::preformed antibodies}} attacking donor
{{c1::ABO or HLA}} antigens Antigen-antibody binding activates complement,
leading to thrombus formation and graft ischemia. Presents with graft swelling and
deterioration of organ function within 48 hours of transplant. T2HS → Antibodies
already exist from prior exposure to antigen, so they attack ASAP. Occurs with
pregnancy, blood transfusion, previous transplantation. Prevent with cross-matching
and ABO group matching screen. Immunosuppression will not prevent hyperacute
rejection, since this form of rejection is caused by antibodies that have already
formed.
"What are the features of Hyperacute rejection on a cellular and tissue level?
(what is actually happening to host/graft) {{c1::Fibrinoid necrosis & thrombosis of
graft vessels leading to ischemia/necrosis (""white rejection"")}}" Remove graft
ASAP → transplant was a failure and there's nothing that can be done to salvage the
graft.
Acute transplant rejection occurs due to delayed {{c1::T-cell (CD8 and/or CD4)}}
attack against donor MHCs The absence of C4d staining (a marker of antibody-
mediated damage) and the presence of inflammatory infiltrate indicate acute
cellular rejection not humoral Cell-mediated immune reaction (T4HS). There is also
a humoral component, but antibodies develop after transplant.
What are the microscopic features of Acute transplant rejection? {{c1::Vasculitis
with interstitial infiltrates of lymphocytes/mononuclear cells}} Treatable with
immunosuppression
{{c1::Chronic}} transplant rejection is a caused by recipient CD4 T-cells secreting
cytokines to induce vascular smooth muscle proliferation, parenchymal atrophy and
fibrosis Dominated by arteriosclerosis. Both cellular (T4HS) and humoral (T2HS)
components
What is the result of chronic rejection of a lung transplant? {{c1::Bronchiolitis
obliterans → fibrosis and narrowing of small bronchioles}} Will cause dyspnea,
wheezing. Most common cause of death in lung transplant patients.
What is the result of chronic rejection of a heart transplant? {{c1::Accelerated
atherosclerosis (narrowing of coronary arteries)}} Recipeint CD4 T cells →
cytokines → proliferation of vascular smooth muscle, interstitial fibrosis,
arteriosclerosis
What is the gold-standard test and finding in diagnosis of (Temporal) Giant Cell
Arteritis? {{c1::Focal granulomatous inflammation on temporal artery biopsy}}
Do not wait for biopsy results → treat with high dose steroids ASAP to avoid
ophthalmic artery occlusion (blindness)
{{c1::Takayasu's Arteritis}} is a large-vessel vasculitis caused by granulomatous
thickening of the {{c2::aortic arch and proximal great vessels}} Classic
demographic: Asian females < 40 Remember that GCA (the other large-vessel
vasculitis) is also due to granulomatous inflammation
What is the hallmark physical exam finding in Takayasu's Arteritis? {{c1::Weak
pulses in one arm}} "Also present with systemic symptoms (fever, night sweats,
arthritis) and occular disturbances. ""Pulseless disease"" → granulomatous
inflammation (narrowing) of aortic arch and proximal great vessels → BP discrepancy
between arms/legs + bruits over arteries"
Kawasaki Disease must be recognized early and treated with {{c1::Aspirin and IVIG}}
to prevent the feared complication of {{c1::coronary artery aneurysms}} Can
lead to thrombosis (myocardial infarction) and rupture of CA aneurysm. Also
remember that Aspirin in children can cause Reye Syndrome. Kawasaki is like the
only exception
{{c1::Buerger Disease (Thromboangiitis obliterans)}} is a medium-vessel necrotizing
thrombosing vasulitis seen in male smokers that causes intermittent claudication of
the fingers and toes "It is segmental. Called thrombosing because thrombi
develop (thrombi are ""inflammatory"", composed of inflammatory elements including
neutrophils and giant cells which occlude blood vessels), leading to vessel
inflammation (vasculitis); non-atherosclerotic disorder, ischemia develops due to
thrombus formation May lead to gangrene, autoamputation of fingers/toes, and
superficial nodular thrombophlebitis (painful nodules that follow venous
distribution)."
Which vasculitis disease is caused by a Immune Complex deposition (T3HS)?
{{c1::Polyarteritis Nodosa}} Associated with Hepatitis B (HBsAg), attacks pretty
much every bodily system except the lungs. PAN spares the lungs.
What findings on biopsy of blood vessels indicate Polyarteritis Nodosa?
{{c1::Transmural inflammation of medium-sized vessels with fibrinoid necrosis}}
"Lesions are often in various stages of healing. Transmural inflammation and
fibrinoid necrosis are early → progress to fibrosis and ""string of pearls""
appearance on imaging over time"
Henoch-Schonlein Purpura (IgA vasculitis) commonly occurs in children following
{{c1::URI}} Child + URI → develop melena, hematuria, palpable purpura on
buttocks/legs, arthralgias
What is the treatment for all small-vessel vasculitis diseases? {{c1::Steroids +
Cyclophosphamide}} - Also PAN. - Large-vessel (GCA, Takayasu) = steroids -
Buerger = smoking cessation - Kawasaki = IVIG, Aspirin
What abnormal lab finding is found in both large-vessel vasculitis diseases (GCA,
Takayasu)? {{c1::↑ ESR}} - Churg-Strauss = eosinophilia, ↑ IgE, p-ANCA -
Microscopic polyangiitis = p-ANCA - Wegener's = c-ANCA
B and T cells in the blood enter the lymph nodes through {{c1::high endothelial
venules}} in the paracortex Paracortex houses T-cells and enlarges in cell-
mediated immune response (viral infections)
{{c1::Medullary sinuses}} of lymph nodes contain macrophages and reticular cells to
filter lymph (phagocytosis) before it exits through efferent lymphatic vessels
{{c1::Medullary cords}} of lymph nodes contain closely packed lymphocytes and
plasma cells that secrete antibodies into the efferent lymphatic flow
What are the three important structures located within the White Pulp of the
spleen, and which type of cells predominate in each structure? {{c1::Marginal
zone}} {{c2::(Macrophages)::cells?}} {{c2::Follicles}} {{c1::(B cells)::cells?}}
{{c1::PALS}} {{c2::(T cells)::cells?}} The marginal zone is the portion of the
spleen between the red pulp and white pulp. Its major role is the removal of
antigens (ie; debris) from the blood, and exposure of antigens to antigen-
presenting cells like macrophages and dendritic cells PALS = Periarteriolar
lymphocyte sheaths
"What is the special structure of splenic red pulp sinusoids that allows them to
filter old/defective RBCs? {{c1::fenestrated ""barrel hoop"" basement membrane}}"
Abnormal RBCs can't deform and pass through fenestrated sinusoid membrane and
become trapped in Cords of Billroth where they are devoured by macrophages. Think
SCD, hemolysis disorders, etc.
Why are patients with splenic dysfunction (asplenia, SCD) at increased risk for
infection from encapsulated organisms? {{c1:: ↓ marg. zone macrophages (↓
phagocytosis) ↓ IgM (↓ C3b opsonization and compliment)}} Strep pneumo is
predominant pathogen for sepsis (death in >50% of patients); Others H.influ,
N.meningi
What is the major function of the CH2 (second constant heavy chain) region of the B
Cell receptor? {{c1::Complement binding}}
What are the three interactions that must take place between B and T cells in the
process of T-cell Dependent B-cell activation and class switching? B-cell component
↔ T-cell component {{c1:: MCH II ↔ TCR (CD4) CD40 ↔ CD40L B7 ↔ CD28}} B7 ↔ CD28 =
Tcell activation (2nd step) and cytokine secretion
What are the three major conjugate vaccines for encapsulated bacteria? {{c1:: Strep
pneumo (PCV13) H. influenza type B Neisseria meningitidis}}SHiN → bacteria with
polysaccharide capsule are conjugated with protein antigen (toxoid), which promotes
T-cell activation and cell mediated immunity → class swtiching, production of
memory, overall stronger immune response
Antibody class is determined by the {{c1::Fc}} region Fc = Constant, Carboxy
terminal, Compliment binding, Carbohydrate side chains
Staph aureus virulence factor {{c1::Protein A}} binds to the {{c1::Fc portion (CH2)
of IgG antibodies}} to prevent opsonization and compliment activation
{{c1::IgG}} is the only immunoglobulin isotype that crosses the placenta to provide
infants with passive immunity IgA secreted in Breast Milk
What two changes/processes occur during transcytosis of IgA from the serum to GI
and respiratory lumen? {{c1::gains secretory component & dimerizes}} - Secretory
component → protects Fc region of IgA from proteases in intestinal/resp lumen -
Dimerizes → monomers held together by J chain to prevent attachment of bacteria and
viruses to mucous membranes
IgA Protease is a virulence facor secreted by which three pathogens? {{c1:: Strep
pneumo H. influenza Neisseria (both types) }} SHiN bacteria. IgA protease cleaves
IgA secretory component allowing bacteria to adhere to and colonize mucous
membranes
What are four examples of Passive Immunity? {{c1:: IgA in breast milk IgG crossing
placenta Antitoxin (rabies, etc) Humanized monoclonal antibody }} Passive
immunity → recieving preformed antibodies. Rapid onset. Short half-life. -Human
immunoglobulin against a viral proetin is used for post-exposure prophylaxis in
suspected cases of rabies.
Describe the genetics of Duchenne Muscular Dystrophy (inheritance pattern, gene,
product): Pattern: {{c1::X-linked recessive}} Gene: {{c1::DMD}} Product:
{{c1::Dystrophin}} Becker is the same except it is due to a non-frameshift
deletion in dystrophin gene (partially functional).
Dystrophin (mutated in DMD) is a protein that connects intracellular {{c1::actin}}
to {{c1::a/b-dystroglycan}} in the muscle membrane a/b-dystroglycan connected to
ECM proteins (laminin)
Duchenne and Becker muscular dystrophies are due to deletion mutations in the
dystrophin (DMD) gene - how do these mutations differ and why is Becker less
severe? {{c1:: Duchenne: frameshift mutation Becker: non-frameshift mutation}}
Frameshift → deletion disrupts reading frame, early stop codon, truncated or
absent dystrophin protein Non-Frameshift → deletions of multiples of 3 nucleotides
= some functioning protein
Loss of dystrophin in DMD leads to what pathological process in muscle cells?
{{c1::myonecrosis}}
What two enzymes are elevated in the serum of a patient with Duchenne muscular
dystrophy? {{c1:: Creatine Kinase Aldolase}} Loss of dystrophin leads to
myonecrosis, causing muscular enzymes to spill into the blood
What are the findings on muscle biopsy in a patient with DMD? {{c1::Fibrofatty
replacement of muscle}} """Pseudohypertrophy"" of calf muscles"
What is the most common cause of death in patients with Duchenne Muscular
Dystrophy? {{c1::Dilated Cardiomyopathy}} ↓ LVEF, systolic HF, myocardial fibrosis,
AV block, arrhythmias
The {{c1::alternative}} compliment pathway involves the spontaneous conversion of
C3 → C3b via microbe surface molecules C3b binds amino and hydroxyl groups
commonly found on the surface of pathogens
{{c1::Factor H}} is a plasma glycoprotein synthesized in the liver that blocks the
alternative pathway on host cells Accelerates decay of C3 convertase (C3bBb) and
inactivates C3b. Some cancers and bacteria (H. flu, N. men, Strep, pseudomonas) use
Factor H as virulence factor
Hereditary Angioedema is a caused by a deficiency in {{c1::C1 esterase inhibitor}}
which leads to elevated levels of {{c1::bradykinin}} C1 inhibitor normally breaks
down bradykinin → ↑ bradykinin → swelling of skin, GI tract, upper airway beginning
in childhood → treat with C1 inhibitor concentrate and never give ACE inhibitors
What lab abnormality is diagnostic of C1 Esterase Inhibitor Deficiency (Hereditary
Angioedema)? {{c1::↓ C4 (consumption)}} Never give ACE Inhibitors
Which glomerular disease is associated with C3 Nephritic Factor autoantibodies?
{{c1::MPGN type II (dense deposit disease)}} C3 Nephritic factor is an IgG
autoantibody that stabilizes C3 convertase leading to persistent compliment
activation and ↓ C3 levels
{{c1::Fragile X Syndrome}} is the most common cause of inherited intellectual
disability and the 2nd most common genetic cause of intellectual disability Down
Syndrome is most common cause of genetic intellectual disability, but DS is 95% not
inherited.
Describe the genetics of Myotonic Dystrophy Type 1 (inheritance pattern, gene,
chromosome): {{c1::Autosomal Dominant}} {{c1::DMPK gene}} {{c1::chromosome 19}}
- CTG trinucleotide repeat. - Type 2 = CNBP gene
Myotonic Dystrophy Type 1 is caused by {{c1::CTG}} expansions in the DMPK gene
which codes for {{c1::myotonic dystrophy protein kinase}} DMPK gene is transcribed
but not translated
Myotonic Dystrophy Type 2 (less common) is due to a mutation in the {{c1::CNBP}}
gene due a {{c1::CCTG (tetranucleotide)}} repeat Less severe than type one.
X-Linked (Bruton) Agammaglobulinemia is caused by a defect in {{c1::Bruton Tyrosine
Kinase (BTK)}} resulting in a failure of B-cell maturation Failure of B-cell
precursors to become B-cellsAbsence of CD19 B cells (mature B-cells) Light chains
are not produced → B cell precursors fail to become mature B cells → symptoms begin
~ 6 months old (loss of maternal antibodies) Few or no germinal centers. On
physical exam, this results in small or absent tonsils and lymph nodes.
What are the 3 major findings in patients with X-Linked (Bruton)
Agammaglobulinemia? {{c1:: No B cells on peripheral smear ↓ Ig of ALL classes ↓
germinal centers in lymph nodes}} - Hypoplasia of the tonsils is a finding in
Bruton agammaglobulinemia Treat with IVIG
Which immunodeficiency syndrome can present with Anaphylaxis to Blood Transfusion?
{{c1::Selective IgA deficiency}} T1HS reaction against plasma proteins in
transfused blood.
Which immunodeficiency syndrome can cause false postive B-hCG test? {{c1::Selective
IgA deficiency}} People with IgA deficiency produce heterophile antibodies → 30%
of women with IgA def test (+) for B-hCG
What 3 lab findings are indicative of Common Variable Immunodeficiency (CVID)?
{{c1:: Normal B cell count ↓ plasma cells ↓ Immunoglobulins (usually IgG)}} CVID
due to a defect in B cell differentiation → they're present, but cant mature and
secrete antibodies
What are the three key presentation features that distinguish CVID from Brutons
(XLA)? {{c1:: Affects females (not X-linked) Later onset (~20-45) ↑ rate of
lymphoma & autoimmune disease}} - Both → deficient IGs, recurrent bacterial and
enteroviral infections - Bruton → X-linked (males), presents around 6 months, not
associated with lymphomas or AI diseases
What are the three B-cell immunodeficiency disorders? (not combined) {{c1:: X-
linked (Bruton) agammaglobulinemia Selective IgA deficiency Common variable
immunodeficiency}} - All will have recurrent sinopulmonary and GI infections -
Bruton's is only one with ↓ B cell count
{{c2::Hyper-IgE (Job) Syndrome}} is a T-cell disorder caused by deficiency of
{{c1::CD4+ Th17}} cells due to {{c1::STAT3}} mutation which leads to {{c2::impaired
neutrophil chemotaxis}} STAT3 → signal transducer and activator of transcription
that is activated by cytokines. Leads to overproduction of IgE and loss of IFN-y
What three lab findings are associated with Hyper-IgE Syndrome (Job syndrome)?
{{c1:: ↑ IgE and eosinophils ↓ IFN-y}} Due to defective Th17 caused by STAT3
mutations
Chronic Mucocutaneous Candidiasis is a T-cell (cell-mediated) disoder caused by
defects in {{c1::AIRE (autoimmune regulator)}} genes -Th1 cytokines: Dec IL-2 and
IFN-y -Inc IL-10 (anti-inflam) -Not due to antibody/B-cell disorder AIRE function 1
→ associates with Dectin-1 to respond to Candida antigens AIRE function 2 →
promotes self-antigen production in thymus for negative selection
The most common type of SCID is due to an {{c1::X-linked recessive}} inherited
mutation of {{c1::IL-2RG}} gene IL-2RG → IL-2 receptor gamma subunit Cytokine
receptor deficiency
List which gene is mutated in the two most common forms of SCID: XR: {{c1::IL2RG}}
AR: {{c1::Adenosine deaminase}} XR IL2RG mutation is most common (XR = boys)
Newborns are screened for SCID by measuring levels of what? {{c1::TRECs (T-cell
recombinant excision circles)}} TRECs → circular DNA formed in normal T-cells
in the thymus. Can't just check T-cell count because maternal T-cells may falsely
indicate normal counts.
Which two immunodeficiency syndromes will show absence of thymic shadow on CXR?
{{c1:: DiGeorge (22q11 deletion) SCID}} DiGeorge will also have facial
abnormalities, hypocalcemia, and heart defects. SCID wont.
Adenosine Deaminase deficiency (AR SCID) leads to excess {{c1::dATP}} which
inhibits {{c1::ribonucleotide reductase}} ↓ DNA synthesis → B/T cell dysfunction
Remember that Hydroxyurea is a drug that inhibits ribonucleotide reductase to treat
myeloproliferative disorders (CML, PV)
ATM gene mutations (Ataxia-telangiectasia) lead to hypersensensitivity to ionizing
radiation due to defects in {{c1::Nonhomologous end joining}} NHEJ → DNA repair
process that repairs double strand DNA breaks, with no requirement for homology (vs
homologous recombination)
What is the pathophysiological cause of Hyper-IgM syndrome? {{c1::Defective B-cell
class switching due to defective CD40L on T-cells}} BnB: Recurrent bacterial
infections, mostly caused by encapsulated bacteria (due to loss of IgG
opsonization) and opportunistic infections eg; pneumocystis, cryptosporidium and
histoplasmosis B cells make IgM only (↑↑) All other antibodies are absent. -Caused
by a defect in T-cell receptor signalling (most commonly from a defect in CD40
ligand) that renders T-cells unable to activate class switching in B-cells.
What is the normal function of the Wiskott-Aldrich Syndrome protein (WASp)?
{{c1::maintenance of T-cell cytoskeleton}} "- Mutation of the WAS gene leads
to the inability of T-cells to organize the actin cytoskeleton (abnormal actin
polymerization) Think of it as forming an ""immunologic synapse"" → without WASp,
T-cells cant properly react to APCs"
Leukocyte Adhesion Deficiency (type 1) is a disorder of phagocyte dysfunction
caused by a defect in {{c1::LFA-1 integrin (CD18)}} protein on phagocytes
Autosomal recessive defect in CD18, a subunit of the adhesion molecule, beta-
2 integrin. Inability of neutrophils to migrate to the site of infection LFA1 →
Lymphocyte Function associated Antigen-1 → forms beta subunit of several integrins
(adhesion molecules) -LAD1 is diagnosed using flow cytometric measurement of
surface molecules such as CD11b or CD18. The treatment for mild to moderate cases
is mainly supportive, with early treatment of infections and prophylaxis with TMP-
SM, if needed, but severe cases require definitive therapy with hematopoietic stem
cell transplantation
What are the three major symptoms of Leukocyte Adhesion Deficiency presentation?
{{c1:: late separation of umbilical cord recurrent skin infx w/ no pus impaired
wound healing}} Cord stump usually falls off in 2-3 days, delayed (30+ days) in
LAD, often gets infected (omphalitis) Special note: In actual practice, the most
common reason for delayed cord separation is excessive cleaning by the baby's
caregivers (eg; with alcohol) which prevents bacterial colonization and neutrophil
migration to the stump.
Infants with Leukocyte adhesion deficiency will have elevated levels of
{{c1::neutrophils}} in the blood LFA-1 integrin (CD18) protein functions in
neutrophil migration → defect → no neutrophils at infection sites and ↑ neutrophils
in blood
Chediak-Higashi syndrome is a phagocyte disorder caused by a defect in
{{c1::lysosomal trafficking regulator gene (LYST)}} which leads to microtubule
dysfunction Microtubule dyfunction in phagosome-lysosome fusion
Chediak-Higashi syndrome leads recurrent pyogenic infections from which two
pathogens (most commonly)? {{c1:: Staph Strep}} LYST gene defect leads to a
microtubule dysfunction and a failure of phagosome-lysosome fusion
What is the classic finding of Chediak-Higashi syndrome on peripheral blood smear?
{{c1::Giant granules in granulocytes}} Due to defective lysosomal trafficking
caused by microtubule dysfunction. Also associated with pancytopenia.
What aggrivates and relieves the sharp pain of pericarditis? Aggrivates:
{{c1::inspiration, lying supine}} Relieves: {{c1::sitting up, leaning forward}}
These are buzzwords for pericarditis. Patients will also have a friction rub
on auscultation
What are the two characterisitc ECG findings associate with pericarditis? {{c1::
Diffuse ST elevation PR depression}}
What is the classic physical exam finding in pericarditis? {{c1::pericardial
friction rub}} scratchy sound heart throughout systole and diastole
What are the three treatments for pericarditis? {{c1:: NSAIDs Steroids Colchicine}}
Colchicine disrupts microtubule polymerization and inhibits neutrophil
chemotaxis. Lowers risk of pericarditis recurrence. Used in gout, pericarditis, and
familial mediterranean fever
{{c1::Cardiac Tamponade}} is an accumulation of pericardial fluid that leads to
high pericardial pressure and restriction of cardiac filling
What is the characteristic CXR finding in cardiac tamponade? {{c1:: Water bottle
sign }} Looks more like a canteen you'd see in some old western movie
Why does pulsus paradoxus occur in Cardiac Tamponade? {{c1::Insipration ↑ RV volume
→ ↑ RV pressure bulges septum → ↓ LV size → ↓ CO}} Defined as ↓ in amplitude of
systolic BP by > 10 mmHg during inspiration
Pulsus paradoxus is defined as a decrease in amplitude of systolic BP by {{c1::>
10}} mmHg during {{c1::inspiration}} Insipration ↑ RV volume → ↑ RV pressure
bulges septum → ↓ LV size → ↓ CO
What are the five etiologies of pulsus paradoxus? {{c1:: Cardiac tamponade
Pericarditis Asthma, COPD Obstructive sleep apnea Croup}} However, respiratory
causes of PP are due to pulmonary pressure fluctuations, not pericardial
restriction (tamponade)
What are the three common ECG findings assocaited with Cardiac Tamponade? {{c1::
Sinus tachycardia Low voltage QRS electrical alternans}} "electrical alternans →
variation in QRS amplitude due to ""swinging"" movement of heart in large effusion"
The 47 XXY (most common) karyotype of Klinefelter Syndrome arises through what
aberrant genetic process? {{c1::Meiotic nondisjunction of either parent}} One X
chromosome will be inactivated (Barr body)
Somatic mosaicism refers to the presence of genetically distinct cell lines in an
individual due to mutations during {{c1::mitosis after conception}} Examples -
Klinefelter → 46 XY & 47 XXY - Turner → 46 XX & 45 XO - Sturge-Weber - McCune
Albright - Down's Syndrome (rarer form)
Men with Klinefelter Syndrome will have primary hypogonadism with small, firm
testes due to what two cellular abnormalities? {{c1:: Seminiferous tubule
dysgenesis Abnormal leydig cell function}} ↓Inhibin B → ↑FSH LCs: ↓test → ↑ LH
How will Klinefelter syndrome affect sex hormones (test, estradiol, FSH, LH)?
{{c1:: ↑ FSH, LH, estradiol ↓ testosterone}} Primary Hypogonadism → small firm
testes → loss of negative feedback due to lack of testosterone and inhibin B
production → ↑↑ gonadotropins
Men with Klinefelter syndrome have long legs and arms partially due to having an
extra copy of the {{c1::SHOX}} gene SHOX (short stature homeobox) gene is located
on both X & Y chromosomes and causes short stature when present in only one copy. -
Turner Syndrome (XO = 1 sex chromosome) = 1 SHOX gene = short stature - Klinefelter
& Double Y Males (XXY, XYY) = 3 SHOX genes → tall stature
What molecular process causes the inactivation of an X chromosome (Barr Body)?
{{c1::Lyonization → extra X chromsome condensed into heterochromatin with
methylated DNA}} Normal females (XX) and Klinefelter (XXY)
What genetic phenomenon is responsible for mild forms of Turner and Klinefelter
syndromes? {{c1::Somatic mosaicism}} - D/t mitotic nondisjunction after
fertilization. - Turner: some cells XO, some XX - Klinefelter: some cells XXY, some
XY
Short stature in females born with Turner syndrome may be preventable with
{{c1::growth hormone}} therapy They're short because they only have one SHOX
gene (XO)
How will the ovaries appear in a female with Turner syndrome? {{c1::streak ovaries
→ fibrous tissue seen in expected location of ovaries}} Primary Hypogonadism due
to gonadal dysgenesis. No or very few follicles. Pregnancy is possible in some
cases with IVF
{{c1::Turner Syndrome (XO)}} is the most common cause of primary amenorrhea in
females """Menopause before menarche"" → streak gonads cant synthesize
estrogen, can treat with estrogen to induce puberty."
What are the three cardiovascular abnormalities associated with Turner Syndrome
(XO)? {{c1:: Bicuspid aortic valve Coarctation of aorta HTN in childhood}} HTN in
childhood may be primary, due to coarctation of aorta, or due to kidney
malformations
What two renal abnormalities are often present in females with Turner Syndrome?
{{c1:: Horseshoe kidney abnormal collecting ducts}}
What are two causes of X-linked recessive diseases presenting in females? {{c1::
Homozygosity Skewed lyonization}} Skewed lyonization → good X chromosome is
inactivated (Barr body) while mutated chromosome is expressed Homozygosity → father
has disease & mother is a carrier
What are the two key features of X-linked Dominant disorders? {{c1:: 1. No male-to-
male transmission 2. All daughters of affected male have disease}} - All
daughters get X chromosome from father - All sons get X chromosome from mother and
only Y chromosome from father
Mitochondrial inherited disorders mostly affect the CNS and skeletal muscle because
these organs rely on {{c1::aerobic metabolism}} for energy production
Mitochondrial myopathies → weakness, CNS disease, lactic acidosis
What are the three symptoms common to all mitochondrial myopathies? {{c1:: Weakness
(myopathy) CNS disease (confusion) Lactic acidosis}} CNS and skeletal muscle rely
heavily on aerobic metabolism for energy production → bad mitochondria → disease
What is the classic finding on muscle biopsy of patients with mitochondrial
myopathies? {{c1:: Red, ragged fibers (accumulation of diseased mitochondria) }}
Patients with type A/B blood produce anti-A/B antibodies of which immunoglobulin
class? {{c1::IgM}} Cannot cross placenta → Reason why type A mother carrying a
type B baby is OK (and vice versa)
Rh-negative individuals may develop anti-D antibodies under which two
circumstances? {{c1:: Pregnancy (delivery) Transfusion}} Pregnancy → Rh(-) mother
carries Rh(+) fetus and exposed to fetal blood during delivery.
Rh(-) mothers carrying Rh(+) fetus may develop {{c1::IgG anti-D}} antibodies on
exposure to fetal blood during delivery IgG can cross placenta: mother develops
anti-D IgG after delivering first baby, then transmits antibodies to fetus during
second pregnancy if second baby is also Rh(+)
{{c1::Rh}} hemolytic disease of the newborn causes HDN in the fetus anti-D IgG
(from 1st pregnancy) crosses the placenta and attacks fetal RBCs → hydrops fetalis
{{c1::Packed RBCs}} are used as blood transfusion therapy to ↑ Hgb and O2 carrying
capacity while minimizing volume given to patient Used in acute blood loss,
severe anemia.
What are the two classic findings on venous pressure tracing in patients with
Cardiac tamponade? {{c1:: Prominent x descent Absent y descent}}
What is the hallmark constrictive pericarditis on imaging? {{c1:: Calcification of
pericardium }} Fibrous, calcified scar in pericardium from chronic pericarditis,
chest radiation, heart surgery, etc
Pericardial knock is a sharp, high pitched early diastolic heart sound most
commonly associated with what cardiac pathology? {{c1::Constrictive pericarditis}}
Similar to S3, due to rapid early diastolic filling halted when LV volume
hits threshold of expansion from stiff, calcified pericardium
What is Kussmaul's Sign? {{c1::↑ JVP with inspiration (paradoxical)}} Inspiration
causes venous blood to drain into right side of heart which should lower the JVP.
Kussmaul's sign occurs when RA/RV is too stiff and causes pressure to rise in JVs
What are the three common etiologies of Kussmaul's Sign (↑ JVP on inspiration)?
{{c1:: Constrictive pericarditis Restrictive cardiomyopathy RV infarction}} NOT
seen in cardiac tamponade → heart is surrounded by fluid so it has room to move to
accomodate for venous return, whereas constrictive/restrictive heart diseases
cannot accomodate
What is the classic venous pressure wave finding associated with constrictive
pericarditis? {{c1::Rapid/prominent y descent}} Myocardium is adherent to
pericardium
{{c1::Cyclins}} are regulatory proteins that bind and activate {{c1::Cyclin
Dependent Kinases (CDKs)}} to phosphorylate regulatory proteins to allow
progression through the cell cycle Form Cyclin-CDK complex, CDKs alone are always
present in cells but inactive p53 → p21 → CDKs → hypophosphorylation (activation)
of Rb → inhibiton of E2F → inhibition at G1 → S
At the G1-S checkpoint, Cylcin-CDK complexes activate {{c1::E2F (transcription
factors)}} to prepare the cell for S phase - TF → bind DNA promoter regions -
E2F normally inhibited by Rb protein - CDKs phosphorylate (inhibit) Rb
E2F proteins are tonically inhibited by {{c1::retinoblastoma (Rb) proteins}} to
prevent the cell from progressing from G1 → S phase Inhibition released by CDK
phosphorylation of Rb (tumor suppressor)
Which two pathways halt the progression from G1→ S phase in response to single and
double stranded DNA breaks, respectively? SS breaks → {{c1::ATR pathway}} DS breaks
→ {{c1::ATM pathway}} - Both lead to phosphorylation of p53 - ATM → Ataxia
Telangiectasia Mutated
Describe the pathway of cell cycle inhibition in response to DNA breaks at the G1 →
S checkpoint: DNA damage → {{c1::ATM/ATR phosphorylate p53 → p21 → ↓CDK activity}}
→ progression halted
Describe the genetics of Li-Fraumeni syndrome (inheritance pattern, chromosome,
gene): {{c1:: Autosomal dominant Chromosome 17 TP53 gene }}Sarcomas, breast,
leukemia, adrenal
Which tumors stain positive for Desmin? {{c1::Muscle tumors → rhabdomyoma/sarcoma,
leiomyoma/sarcoma, Sarcoma botryoides}} Desmin and vimentin are part of the Z-
disks in sarcomeres
{{c1::Lamins}} are intermediate filaments that form the nuclear envelope Dont
get it confused with laminin (extracellular protein)
Cilia and flagella are cellular motility structures composed of {{c1::microtubules
and dynein}} Cilia (shorter)→ fallopian tubes, resp tract Flagella (longer) →
sperm
How is Kartagener Syndrome (1º ciliary dyskinesia) inhereted and which genes are
mutated? {{c1::Autosomal recessive::inheritance pattern}} {{c1::Dynein
genes::Defective gene/structure}} Dextrocardia, chronic sinusitis,
bronchiectasis, and infertility
{{c1::Nissl Bodies}} are the rough endoplasmic reticulum in neurons which function
to synthesize neurotransmitters
The golgi apparatus modifies {{c2::N-oligosaccharides}} on {{c1::asparagine}}
The golgi apparatus adds O-Oligosaccharides to which two amino acids? {{c1:: Serine
Threonine}} Defects in N-glycosylation and O-glycosylation play important roles in
the pathogenesis of tumors. Interesting read that no one has time for:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4396820/
The golgi apparatus adds {{c1::mannose-6-phosphate}} to proteins that are destined
for {{c2::lysosomes}} M6P added to acid hydrolase enzymes on N-linked
oligosaccharides to trigger packaging in the trans-Golgi → lysosomes
{{c1::I-Cell Disease (Inclusion cell disease)}} is a lysosomal storage disorder
caused by a failure of the golgi apparatus to target proteins to lysosomes
Deficiency in N-acetylglucosaminyl-1-phosphotransferase resulting in a
failure to tag lysosomal proteins with M6P → these proteins do not reach the
lysosome and are instead secreted outside of the cell
What enzyme is deficient in I-Cell Disease and what is this enzyme's normal
function? {{c1::N-acetylglucosaminyl-1-phosphotransferase; phosphorylate mannose
residues::enzyme; function}} In its absence, these proteins are secreted outside
of cell
{{c1::Acid hydrolases}} are the predominant lysosomal enzymes and work best in
{{c1::acidic}} environments 40+ types → nucleases, proteases, lipases, etc etc
{{c1::Peroxisomes}} are small membrane-enclosed organelles that contain many
oxidative enzymes which generate hydrogen peroxide (H2O2) Functions: - ß-oxidation
of VLCFA - α-oxidation - catabolism of BCFAs, AAs, ethanol - synth of cholesterol,
bile acids, plasmalogens
What are the 4 major functions of peroxisomes? {{c1:: 1. ß-oxidation of VLCFA 2. α-
oxidation 3. catabolism of BCFAs, AAs, ethanol 4. synth of cholesterol, bile acids,
plasmalogens}} - a-oxidation only occurs in peroxisomes - plasmalogens:
important membrane phospholipid, especially in white matter of brain
{{c1::Proteasomes}} are barrel-shaped protein complexes that degrade damaged or
ubiquinated proteins - require ATP - defects implicated in cases of Parkinson's
disease
Defects in ubiquinated protein degradation in lysosomes is believed to play a role
in {{c1::Parkinson's Disease::pathology}} Leads to toxic accumulations of proteins
(a-synuclein) in neurons
{{c1::Signal recognition particles (SRPs)}} are ribonucleoproteins in the cytosol
that recognize signal sequences and move proteins from the cytosol to the RER
- signal sequences → short peptides on the N-terminal of proteins undergoing
synthesis (translation)
Describe the pathways of vescicular trafficking proteins, COPI and COPII COPI:
{{c1::Golgi}} → {{c1::ER}} COPII: {{c1::ER}} → {{c1::Golgi}} """Two (COPII)
steps forward (anterograde); one (COPI) step back (retrograde)"
Which bodily structures are composed of Type I collagen? {{c1:: Bone (organic
comp.) Skin Tendons, ligaments Cornea}} Also dentin (teeth), fascia, late wound
repair. Type 1 collagen is the primary component of osteoid. Decreased production
in osteogenesis imperfecta
Describe the genetics of Osteogenesis imperfecta type 1 (inheritance pattern,
genes, product): {{c1::autosomal dominant::inheritance pattern}} {{c1::COL1A1,
COL1A2::gene(s)}} {{c1::Type 1 collagen::product (defective)}} Decreased
production of type 1 collagen; produced type 1 collagen is normal, theres just not
a lot of it
What do the COL1A1/2 genes encode normally? {{c1::Alpha chains of type 1 collagen}}
Osteogenesis imperfecta → COL1A1/2 mutations → Abnormal/absent alpha chains →
can't form triple helix
What are the four major clinical features of Osteogenesis imperfecta? {{c1::
Fractures Blue sclera Tooth abnormalities Hearing loss}} B (bone): fx w no trauma
I (eye): ↓ CT over veins T (teeth): pale teeth (↓dentin) E (ear): abnormal ossicles
Collagen post-translational modification begins with synthesis of {{c1::pre-pro-
alpha collagen chains}} in the RER which are directed into the ER lumen by
{{c1::signal molecules}} Heading into the ER lumen, signal sequence (pre-) is
cleaved resulting in pro-a-chains
Pro-a-chains undergo what three post-translational modifications in the RER after
the signal sequence has been cleaved? {{c1:: Hydroxylation of Pro & Lys
Glycosylation of hydroxylysine Assembly of procollagen 3x-helix}}
In the RER, three pro-alpha chains are combined and stabilized by {{c1::disulfide
bonds}} and exocytosed into the extreceullar space as {{c1::procollagen (triple
helix)}}
What is the first extracellular modification of collagen precursors after being
exocytosed from the cell? {{c1::Terminal (N and C) propetides cleaved by
procollagen peptidases to form Tropocollagen}}
Collagen synthesis is complete when tropocollagen molecules are cross linked by
{{c1::covalent lysine-hydroxylysine}} bonds to form collagen fibrils
**Tropocollagen is 1st insoluble precursor
What enzyme is responsible for tropocollagen cross-linking and what cofactor is
required for this enzyme to function? {{c1::Lysyl oxidase + copper}} Collagen
fibers are bundles of collagen fibril triple helices
Osteogenesis imperfecta (type I) is caused by a failure to form {{c1::procollagen
triple helices}} in the RER Due to glycine substitution for bulkier amino acids
leading to defective alpha chains
Describe the genetics of the classic type of Ehlers Danlos syndrome (inheritance
pattern, genes, product): {{c1:: autosomal dominant COL5A1/2 Type V collagen}}
Often a de novo mutation → meaning the parent may not have it, but when the
child acquires the mutation, they will subsequently pass down the mutation to
future children in autosomal dominant fashion
Describe the genetics of the vascular type of Ehlers Danlos syndrome (inheritance
pattern, genes, product): {{c1:: Autosomal dominant COL3A1 gene Type III collagen}}
fragile blood vessels (aorta), muscles, organs → all prone to rupture
What cardiac defect is often present in the classic (skin and joint) type of Ehlers
Danlos? {{c1::MVP}} Due to COL5A1/2 mutations coding for type 5 collagen →
joint hypermobility, stetchy skin, easy bruising, MVP
"What are the unique complications and risk factors in patients with vascular type
Ehlers Danlos syndrome? {{c1:: Rupture of arteries (aorta, circle of willis),
muscles, ""hollow"" organs}}" "- life-threatening - Berry aneurysm rupture (30-40s)
- ""Hollow organ"" rupture → intestinal perforation, uterus rupture during
pregnancy"
{{c1::Menkes Disease}} is a rare disorder of defective collagen caused by impaired
copper absorption and transport "- defective Menkes protein (ATP7A) - ↓ lysyl
oxidase (requires copper) - results in brittle, ""kinky"" hair, growth retardation,
hypotonia"
Describe the genetics of Menkes Disease (inheritance pattern, gene, product) {{c1::
X-linked recessive ATP7A gene GI ATPase (copper uptake)}} Impaired copper
absorption → deficiency → ↓ lysyl oxidase activity (requires copper as cofactor) →
defective collagen
Menkes Disease is caused by {{c1::copper}} deficiency which leads to decreased
activity of {{c1::lysyl oxidase}} - can't cross link tropocollagen into collagen
fibrils - ATP7A gene → ATPase involved in GI copper uptake and transport - male
child with spare, brittle (kinky) hair
"Describe the classic presentation of Menkes Disease: {{c1::Infant male with
sparse, brittle (""kinky"") hair and CNS/growth retardation}}" Plus low body
temperature, hypotonia, osteoporosis and fractures
Describe the genetics of Marfan Syndrome (inheritance pattern, chromosome, gene):
{{c1:: Autosomal dominant Chromosome 15 FBN1 gene (fibrillin-1)}} Fibrillin is
secreted into the extracellular matrix by fibroblasts and becomes incorporated into
the insoluble microfibrils, which appear to provide a scaffold for deposition of
elastin
What are the three major cardiovascular manifestations of Marfan Syndrome? {{c1::
MVP (too floppy) Aortic aneurysms & dissections}} Aortic complications due to
cystic medial necrosis of aorta (cysts and necrosis in medial layer)
Name the DNA repair mechanisms associated with single strand and double strand DNA
repair, respectively: SS: {{c1::nucleotide excision, base excision, mismatch
repair}} DS: {{c1::homologous & non-homologous end joining}}
{{c1::Base Excision repair}} is a process of ssDNA repair that is important in
repair of spontaneous/toxic deamination and occurs throughout the cell cycle
Recognizes specific base errors → deaminated bases, oxidized bases, open
rings.
What is the first step in base excision repair? {{c1::DNA glycosylases remove
damaged base}} creates a baseless (apurinic or apyrimidic) nucleotide by
breaking glycosidic bond between nucleotide base and sugar backbone
Which enzymes remove nucleotides in the second step of base excision repair, and
which ends of the nucletotide do they cleave? {{c1:: AP-Endonuclease: 5' end AP-
Lyase: 3' end}}
Following base and nucleotide excision, {{c1::DNA polymerase-ß}} adds new,
complimentary nucleotide to the {{c1::3-OH}} terminus to fill the gap in base
excision repair Which is then sealed by DNA ligase
"{{c1::Nucleotide Excision Repair}} is a process of ssDNA repair that removes
""bulky"" DNA damage (multiple bases) commonly caused by UV radiation" - defect =
Xeroderma pigmentosum - DNA damage = pyrimidine dimers - G1 phase specific (prior
to DNA synth) - Endonucleases remove multiple nucleotides
UV Radiation causes DNA damage and accumulation of {{c1::pyrimidine dimers}} which
are removed and replaced via nucleotide excision repair - Endonucleases remove
multiple nucleotides
List the phase of the cell cycle that corresponds to the activity of each of the
methods of ssDNA repair: BER: {{c1::throughout}} NER: {{c1::G1}} MMR: {{c1::S}}
(BER = base excision repair; NER = nucleotide excision repair; MMR = mismatch
repair)
{{c1::Endonucleases::enzymes}} excise bulky oligonucleotides (pyrimidine dimers) in
the first step of nucleotide excision repair Per usual, DNA polymerase fills the
gap and Ligase seals it
Xeroderma Pigmentosum is a disorder of extreme sensitivity to UV rays caused by a
defect in what cellular process? {{c1::Nucleotide excision repair}} removal of
UV-induced pyrimidine dimers
{{c1::Mismatch repair}} is a process of ssDNA repair that identifies and repairs
incorrectly placed bases/nucleotides that arise during DNA replication "-
insertions, deletions, incorrect matching. - Defect = Lynch synd. (HNPCC) - Mostly
S phase (some G2). - ""plan B"""
HNPCC (Lynch syndrome) is caused germline mutations in {{c1::MLH1 and MSH2}}
causing failure of {{c1::DNA mismatch repair}} Leads to microsatellite instability
due to failure to recognize and repair DNA slippage. Right sided colon cancer.
"{{c1::Ziehl-Neelsen stain}} is the ""acid fast"" stain that contains
{{c1::carbolfuchsin}} to detect mycolic acids in mycobacterial cell walls"
Carbolfuchsin → heat → alcohol (decolorizer) → methylene blue (counter
stain). Acid-fast organisms (mycobacteria and Nocardia) will remain red even after
alcohol & methylene blue
How do you diagnose myc. Leprosy? {{c1::Skin biopsy OR PCR}} NEVER choose
culture, it cannot be cultured. CAN cause false (+) VDRL
What are the treatments for tuberculoid and lepromatous leprosy, respectively? TBL:
{{c1::Dapsone + Rifampin}} LPL: {{c1::add clofazamine}}
Dapsone is a drug used to treat leprosy and pneumocystis jiroveci that acts by
competing with bacterial {{c1::PABA}} and inhibiting {{c1::dihydropteroate
synthase}} - PABA: para-aminobenzoic acid - can trigger G6PD - can cause
Agranulocytosis
IL-12 receptor deficiency can be treated with {{c1::IFN-y}}IL-12 (from antigen-
presenting macrophages) → immature Th-cells → Th1; Th1 → IFN-y → macrophage
activation -If IL-12 receptors on naive T-cells are defective, T-helper cells will
not transform to Th-1 cells and will not release IFN-y; lack of IFN-y means that
macrophages will not be activated. Without macrophage activation, kids w/ IL-12
receptor deficiency are succeptible to nontuberculous mycobacteria and disseminated
salmonella.
{{c1::Micro RNA (miRNA)}} binds (via base pairing) to 3' end of mRNA to block
protein translation Abnormal expression of miRNAs contributes to certain
malignancies (eg, by silencing an mRNA from a tumor suppressor gene).
{{c1::small interfering RNA (siRNA)}} are dsRNA sequences similar to miRNA that
inhibit the translation of specific mRNAs Eg, can inhibit a specific oncogene
(KRAS, nmyc, etc). Research underway. cool stuff
{{c1::Promoters}} are non-transcribed DNA regions upstream from gene locus that
bind RNA poly II and transcription factors to initiate transcription Promoter ≠
primer (RNA)
What are the three major promoter regions (sequences) that have been described?
{{c1:: TATA Box (TATAAA..) CAAT Box (CCATT..) GC Box (GGGCGG..)}}
{{c1::Enhancers}} are DNA sequences that increase the rate of transcription via
binding of transcription factors called {{c1::activators}} May be upstream,
downstream, or even within (in an intron) the gene whose expression it regulates.
Because of DNA coiling, many are geometrically close but many nucleotides away from
gene they enhance
{{c1::Silencers}} are DNA sequences that decrease the rate of transcription via
binding of transcription factors called {{c1::repressors}} Prevent RNA polymerase
from binding. Same location characteristics as enhancers.
{{c1::Hetergeneous nuclear RNA (hnRNA)}} is the initial RNA transcript from DNA
that is modified to become mRNA hnRNA → 5' capping, 3' tail, and intron
splicing → mRNA → leaves nucleus and enters cytosol for translation
5' capping is the addition of {{c1::7-methylguanosine}} to the 5' end of pre-mRNA
Introns (spliced from RNA) always have which two nucleotides at 5' and 3' ends? 5'
→ {{c1::GU}} 3' → {{c1::AG}}
Primary pre-RNA transcripts combine with {{c1::snRNPs}} and other proteins to form
the spliceosome Forms lariat (loop of mRNA) with intron which is spliced out,
then exons are joined.
snRNPs are short RNA polymers which contain high amounts of {{c1::Uridine}}
Sometimes called U-RNAs, five different U-RNAs defined → U1, U2, U4, U5, U6
(note: anti-U1 RNP antibodies produced in mixed connective tissue disease
What are two antibodies that target snRNPs? {{c1:: Anti-smith Anti-U1 RNP}} Anti
smith → SLE Anti-RNP → MCTD
Mixed Connective Tissue Disease is an autoimmune disorder associated with what
autoantibodies? {{c1::anti-U1 RNP (speckled ANA)}} MCTD → features of SLE,
systemic sclerosis, and/or polymyositis
What is the 3' polyadenylation sequence added at the end of RNA transcription to
stimulate transcription termination? {{c1::AAUAAA-(10-30 nucleotides)-CA}}
Which two RNA binding proteins bind to the AAUAA and CA sequences at the 3'
polyadenylation sequence to terminate DNA transcription? AAUAA: {{c1::CPSF}} CA:
{{c1::CstF}} - CPSF: Cleavage/polyadenylation specificity factor - CstF:
Cleavage stimulation factor
3' Polyadenylation is complete when {{c1::Poly-A-polymerase (PAP)}} adds ~200
adenosine nucleotides to the 3' end of mRNA
How does miRNA modify gene expression? {{c1::Base pairs with mRNA, removing poly-A-
tail and exposing mRNA to endonucleases for degradation}} Ultimately inhibits
translation; not transcription
A gene that has been transcribed into mRNA can be moved into {{c1::cytoplasmic
processing bodies (P-bodies)}} to sequester and/or degrade mRNA P-bodies contain
endonucleases, decapping enzymes, and miRNAs; the mRNA may be translated at a later
time.
How does Strep pyogenes acquire the erythrogenic toxin? (not present in genome)
{{c1::Gene for toxin transferred by lysogenic bacteriophage}} -Via specialized
transduction ET (like TSST from staph) cross-links ß region of TCR to MHC-II →
Polyclonal T-cell overactivation → massive release of cytokines (IL-2, IFN-y, and
TNF-a) → Toxic-shock like syndrome, scarlet fever
What are the two classic pathology findings in Rheumatic Fever? {{c1:: Aschoff
bodies (granulomas) Anitschkow cells (owl-eye macroph)}}
Which two strains of viridans group streptococci cause dental carries? {{c1:: Strep
mutans Strep mitis}} Think mutans & mitis infect the mouth
What are the three unique features of Enterococcus UTIs? {{c1:: Catheters in
hospital Removing cath may cure infx NEGATIVE for nitrites}}
Which two causes of UTIs are negative for nitrites? {{c1:: Enteroccocci Staph
saphrophyticus}} UTI symptoms and labs without nitrites → it's one of these two
Describe the withdrawal effects experienced by alcoholics at each of the following
intervals (in hours) after their last drink: 3-36: {{c1::tremor, GI, agitation}} 6-
48: {{c1::seizures (tonic-clonic)}} 12-48: {{c1::hallucinations (visual)}} 48-96:
{{c1::delirium tremens}} Treat: Benzos
What are the three FDA approved drugs given to reduce the risk of relapse in
alcoholism therapy? {{c1:: Disulfiram Naltrexone Acamprosate}} Disulfiram is
antabuse → triggers catecholamine release and makes them feel like dying if they
drink (classical conditioning)
Naltrexone is a {{c1::long-acting opioid antagonist}} given to reduce cravings in
the treatment of alcohol cessation
{{c1::Acamprosate}} is a drug that modulates NDMA receptors to treat alcohol
cessation once abstinence has been achieved. causes diarrhea
What is the common side effect of Acamprosate? {{c1::Diarrhea}} Acamprosate
modulates NMDA receptors to treat alcohol cessation and should be given to maintain
abstinence once it has been achieved.
What is the classic and unique presentation of Benzodiazepine overdose? {{c1::CNS
depression with normal vitals}} Altered mental status, slurred speech, ataxia,
etc... but they wont have HTN or hypotension, tachycardia or bradycardia, etc..
"What gives tRNA its characterstic ""cloverleaf"" shaped secondary structure?
{{c1:: Base pairing within the molecule }}"
tRNA contains a(n) {{c1::anticodon}} loop that functions to pair with complimentary
mRNA to bring in the correct amino acids
The D Loop of tRNA contains {{c1::dihydrouridine}} residues for recognition by
aminoacyl-tRNA synthetase
The T-loop of tRNA contains what unique RNA sequence? {{c1:: T → Ribothymidine Ψ →
Pseudouridine C → Cytidine }} Needed for tRNA ribosome binding
What sequence of nucleotides is found at the amino acid acceptor site of tRNA?
{{c1::5'-CCA-3'}}
Where do amino acids attach to tRNA? {{c1::Hydroxyl (OH) of A (5'-CCA-3')}}
Hydrolic editing is the process by which {{c1::aminoacyl-tRNA synthetase::enzyme}}
hydrolyzes mischarged (incorrect) amino acids from AMP or tRNA increases accuracy
of tRNA charging
Protein synthesis always occurs such that new amino acids are added to the {{c1::C
terminal (COOH)}} end of an existing AA
The ribosomal {{c1::A}} site binds to amino acids on charged tRNA
The ribosomal {{c1::P}} site will hold and stabilize tRNA attached to growing
protein chain
Initiation of protein synthesis always begings with the {{c1::AUG}} codon on mRNA
which codes for the amino acid(s) {{c1::methionine or N-formylmethionine}}
Methionine = eukaryotes N-formylmethionine = bacteria
Met/fMet bind directly to the {{c1::P}} site on ribosomes to begin protein
synthesis Usually removed later by protease enzymes
What are the elongation factors used by bacteria and eukaryotes, respectively?
Bacteria → {{c1::EF-Tu, EF-G}} Eukaryotes → {{c2::EF1, EF2}} - Hydrolyze GTP →
GDP - EF2 targeted by diphtheria toxin and psuedomonas toxin A
{{c1::Peptidyl transferase}} catalyzes the linkage between growing peptide (P site)
and amino acid (A site) Peptidyl peptidase is part of ribosome made up of RNA (not
proteins)
{{c1::Releasing factors}} bind to ribosomes when a stop codon is encountered at the
A site to terminate translation Hydrolyzes bonds between tRNA (P-site) and the
last AA of polypeptide chain to create the -OH end of protein
{{c1::Heat shock proteins}} are chaperone proteins constitutively expressed to
stabilize proteins in stressful environments (heat, pH shift, hypoxia) Chaperone
proteins → proteins that bind to other proteins to facilitate proper folding
Clostridium perfringens causes a late onset (8-22 hrs) food poisoning due to
ingestion of bacterial {{c1::spores}} Spores ingested from undercooked meats
which produce the toxin (later). In contrast, Staph aureus and B. cereus occur
early due to ingestion of preformed toxin
Diphtheria gains its exotoxin via {{c1::ß-prophage}} Lysogenic phage →
incorporates DNA into bacteria → toxin inactivates EF-2 via ADP-ribosylation
{{c1::Granulomatosis Infantiseptica}} is a severe in utero infection from
{{c1::Listeria}} that leads to disseminated abscesses and/or granulomas in the
liver, lungs, kidneys, brain Skin lesions (papules, ulcers), most babies stillborn
or die soon afer birth.
What are the distinctive findings on evaluation of the placenta in Granulomatosis
Infantiseptica? {{c1:: Chorioamnionitis Villitis Abscess formation}} GI is an in
utero infection from Listeria that causes disseminated abscesses and/or granulomas
in multiple organs (liver, spleen, lungs, brain) and skin lesion (papules, ulcers)
ultimately leading to fetal death
Emetic type of Bacillus cereus infection is caused by direct ingestion of
{{c1::Cerulide toxin}} Vomiting like 1-5 hours after a meal (rice)
Where is Actinomyces normally found? {{c1:: oral flora female genital tract}}
- Oral flora → pus-draining abscess of head and neck (classic presentation),
aspiration pneumonia - Female UG flora → IUD INFECTIONS
Rank the major cardiac conduction tissues from fastest to slowest: {{c1::Purkinje >
Atrial muscle > Ventricular mm > AV node}} AV node (slow): 0.05 m/sec
In high flow states (eg, secretin in response to duodenal acid), the pancreatic
fluid contains high levels of {{c1::bicarbonate}} and low levels of
{{c1::chloride}} Both isotonic solutions. Sodium (high) and Potassium (low) are
always constant → concentration in pancreatic fluid does not vary with flow rates
How do uterine leiomyomas typically present? (demographic and symptoms)
demographic: {{c1::AA women ~20-40}} symptoms: {{c1::pain and heavy menstrual
bleeding}} Benign smooth muscle tumor, most common tumor in females, can result in
endometrial venous ectasia → miscarriages and iron deficiency (bleeding)
Which coronary artery supplies the AV node? {{c1::Posterior descending (PDA)}}
- branches from LCX if Left dom. - Also: posterior 1/3 of interventricular
septum, posterior 2/3 walls of ventricles, and posteromedial papillary muscle
{{c1::Type I (a)}} error is a false positive error, meaning the study finds a
difference when one does not truly exist in reality
{{c1::Type II (b)}} error is a false negative error, meaning the study finds no
difference when one does truly exist in reality Incorrectly accepting the null
hypothesis
The four outcomes of hypothesis testing have a probability of being correct based
on what three factors? {{c1:: Difference between means Scatter of data Number of
subjects}} 4 outcomes: Correct: - accept H0 = no difference exists - accept H1 =
difference exists Incorrect (error): - (a) accept H0 = difference exists - (b)
accept H1 = no difference exists
Cross-Sectional studies measure {{c1::prevalence}} Ex: You send a one-time
survey to all college girls asking if they are in a relationship and if they think
Saturdays are for the boys: - 75% single girls believe SAFTB - 8% of taken girls
believe SAFTB So you can say that being in a relationship is associated with less
chance of girls' believing SAFTB, but you can't technically say being controlling
taken caused this mindset
The main outcome of cohort studies is measured by {{c1::Relative Risk}} Ex:
Cohort study determined that medical students who live alone were 5 times more
likely (risk) to depression vs those who lived with roommates.
What is the major problem with cohort studies? {{c1::They dont work for rare
diseases}} Do case-control instead
Case-control studies compare groups with and without a(n) {{c1::disease}}
Opposite of cohort. Better for rare diseases.
The main outcome measure of Case-control study is {{c1::Odds ratio}} OR: odds of
disease in exposed vs odds of disease in unexposed
What practice is used to reduce confounders in case-control studies?
{{c1::Matching}} Ex: A group of 200 men is found to have erectile dysfunction and
we want to determined what the odds are that they watch porn daily. Matching means
that we'd select another 200 men without ED (controls) who are as close to those
with ED (cases) as possible. So we'd try to make sure they all have similar age,
BP, lipid levels, free testosterone levels, etc.
{{c1::Gluconeogenesis}} becomes the principal source of blood glucose after 12-18
hours of fasting Glycogenolysis is major source within 12-18 hours
Which blood vessel runs in close proximity to the radial nerve near the midshaft of
the humerus? {{c1::Deep brachial artery}} Midshaft humerus fracture = Radial nerve
+ deep brachial artery
{{c1::Odds}} ratio does not change with number of cases Risk ratios are
dependent on number of cases/controls → RR not valid for case-control study (except
in rare diseases)
What is the rare disease assumption and how does it relate to a 2x2 contingency
table? {{c1::OR = RR when B>>A and D>>C}} Meaning that pretty much no one (exposed
plus unexposed) has disease. Very few diseases.
What prevalence value of a certain disease is the cutoff to accept it as a rare
disease (in rare disease assumption)? {{c1::< 10%}} Means that you can calculate
relative risk in case-control study
What are three common long-acting benzodiazepines? {{c1:: Chlordiazepoxide Diazepam
Flurazepam}} Never give for anxiety
What is the mechanism of topical prostaglandins in glaucoma treatment?
(Latanoprost) {{c1::↑ aq. humor outflow through uveoscleral pathway}} May cause
iris hyperpigmentation
How does primary Osteoporosis affect PTH, calcium, phosphorus levels? {{c1::It
doesn't. All normal}}
Which two bacteria are PYR positive? {{c1:: Strep pyogenes Enterococci}}
How are incidence and prevalence affected by chronic diseases? {{c1::Prevalence >>
incidence}} Chronic (diabetes, HTN) → way more cases in the total population than
new cases (incidence) at a given time
How are incidence and prevalence affected by rapidly fatal diseases?
{{c1::incidence = prevalence}}
How are incidence and prevalence affected by new primary prevention programs that
decrease rate of disease? {{c1::↓↓ incidence and prevalence}}
How are incidence and prevalence affected by a new drug/intervention that improves
survival? {{c1:: prevalence increases incidence unchanged}}
PPV and NPV are highly dependent on {{c1::prevalence}} Sensitivity and
specificity are not altered by prevalence
{{c1::Attrition bias}} is a type of {{c1::selection}} bias where patients are lost
to follow-up unequally between groups patients who don't follow up are
selecting to be out of trial
{{c1::Berkson's bias}} is a type of {{c1::selection}} bias when hospitalized
patients are chosen as treatment or control arm Hospitalized pts may have more
severe symptoms, better access to care, etc → alters results of study
What are the three strategies used to reduce confounding bias? {{c1:: Matching
Crossover studies Multiple/repeated studies}}
{{c1::Effect modification}} is when a third factor increases the impact of an
exposure on an outcome Drinking → blackout Drinking + tequila → blackout You can
still black out easily from drinking something other than tequila (i.e. it's not a
confounder), but people who drink tequila might black out more (effect modifier)
Which three enzymes (steps) of the TCA cycle generate NADH from NAD+? {{c1::
Isocitrate Dehydrogenase a-Ketoglutarate Dehydrogenase Malate Dehydrogenase}}
Succinate dehydrogenase genererates FADH2 from FAD
Which enzyme in the TCA cycle synthesizes GTP? {{c1::Succinyl-CoA synthetase (succ.
thiokinase)}} Succinyl-CoA → succinate + GTP. GTP is then used by PEPCK in
gluconeogenesis to generate PEP from oxaloacetate
Enteropeptidase is a duodenal brush border enzyme that activates {{c1::trypsin}}
Trypsin then activates all other pancreatic enzymes. Deficiency of
enteropeptidase leads to protein and fat malabsoprtion, causing diarrhea, FtT,
edema
How do you calculate Number Needed to Treat? NNT = {{c1::1/ARR}} ARR = control
event rate - exp. rate
{{c1::Likelihood ratio}} is a statistical measure that tells us how much a person's
probability of having disease shifts with (+) or (-) test Eg, person has pre-test
probability of having a disease of 30% based on risk factors. If a test is
positive, they'd have a higher likelihood ratio (i.e. 80%) of having disease, and
vice versa
What is the formula for likelihood ratio from a positive (+) test?
{{c1::Sensitivity/(1-specificity)}} Like sensitivity and specificity, likelihood
ratios do not vary with prevalence. Need to know pre-test probability to use LRs
What is the formula for likelihood ratio from a negative (-) test? LR(-) = {{c1::
(1-sensitivity)/specificity}}
List the three key obligate aerobe bacteria: {{c1:: Pseudomonas Mycobacterium
tuberculosis Nocardia}} Use O2-dependent system to generate ATP (superoxide
dismutase)
What are the byproducts of Obligate Anaerobe fermentation (energy generation)?
{{c1:: Gases (CO2 and H2) Short-chain FAs (foul smell) }} SCFAs → Acetic acid,
isobutyric acid, etc
List four key Obligate Anaerobes: {{c1:: Clostridium Bacteroides Fusobacterium
Actinmyces israelii}} Anaerboes Cant Breathe Fresh Air
Which oral anaerobes are the common culprits of aspiration pneumonia? {{c1::
Peptostreptococcus Fusobacterium Bacteroides fragilis Prevotella}} Tx:
Clindamycin
What are three most important Obligate Intracellular bacteria? {{c1:: Rickettsia
Chlamydia Coxiella}} - Use host ATP. - Dont gram stain well. - Chlamydia dx:
N.A.A.T. - Rickettsia dx: clinical/serology
List the five steps (chemicals, etc) in the process of gram staining: {{c1::}}
- Gram(+) = purple = retain crystal violet in cell wall - Gram(-) = do not
retain CV, take up safranin counter stain
Mycobacteria (TB) do not gram-stain well becuase they have high {{c1::lipid
(mycolic acid)}} content in cell wall Use Ziehl-Neelsen stain (carbol fuschin)
for acid fast bacteria
Which two bacteria are difficult to gram-stain because they have no cell wall?
{{c1:: Mycoplasma Ureaplasma}} Mycoplasma contains sterols (cholesterol)
Chlamydia does not gram-stain well because they are intracellular and they lack
peptidogylcan because of {{c1::↓ muramic acid}}
What five pathogens are visualized via Giemsa stain? {{c1:: Plasmodium Trypanosomes
Chlamydia Rickettsia Borrelia}} Intracellular (mostly). Giemsa is mixture of
methylene blue, eosin, and Azure B that enters cells and stains nucleic acids
Which three pathogens are visualized via Silver Stain? {{c1:: Fungi (pneumocystic,
etc) Legionella Helicobacter pylori}} (pneumocystic jiroveci)
"Actinomyces israelii produces orange-yellow ""sulfur"" granules which are composed
of {{c1::filaments of bacteria}}"
Which non-streptococcus bacteria have the special feature of being beta-hemolytic
on blood agar? {{c1:: Staph aureus Pseudomonas}} Pseudomonas distinguished by
greenish-metallic appearing colonies d/t pyoverdin and pyocyanin
Bordet-Gengou agar used to culture Bordetella pertussis is prepared from
{{c1::potato extract (starch)}} B pertussis can also grow on Regan-Lowe medium
(charcoal, blood, antibiotic)
C. diphtheria produces {{c1::gray-black}} colored colonies on {{c1::Tellurite
media}} C.dip reduces potassium tellurite to tellurium. Can also use Loeffler's
Media for CD
Lowenstein-Jensen agar is a selective media for {{c1::mycobacterium
tuberculosis::pathogen}} Contains eggs, flour, glycerol, salt. SLOW growing
(weeks)
Eosin-methylene blue (EMB) plated with E. coli will grow as {{c1::green metallic or
blue-black}} colored colonies Bacteria that don't ferment lactose are
clear/colorless
Sorbitol Mackonkey agar is a specific growth media for {{c1::E. coli O157:H7}},
which produce colorless colonies O157:H7 CANNOT ferment sorbitol (other E. coli
can and produce pink colonies)
Sulfonamide antibiotics inhibit {{c1::dihydropteroate synthase}} Bacteriostatic
alone, bactericidal with TMP
What two structural properties of Sulfonamide antiobiotics lead to high rates of
hypersensitivity reactions? {{c1:: Arylamine (NH2) at N4 Nitrogen ring attached to
N1}}
Endotoxin (LPS) release upon gram(-) lysis leads to the activation of what three
immune system components? {{c1:: Macrophage Complement Tissue factor}}
LPS endotoxin activates macrophages via binding to what receptor? {{c1::CD14}}
Lipooligosaccharides are bacterial endotoxins released by {{c1::Neisseria
meningitidis::pathogen}} Similar to LPS, without O-antigen. Primary virulence
factor in causing meningococcemia
How do Shiga toxin and Shiga-like toxin (EHEC) inhibit protein synthesis?
{{c1::inactivate 60s ribosome by removing adenine from rRNA}} However, Shigella
causes disease via invasion of GI mucosal cells (non-toxigenic strains still cause
significant disease)
What is the major virulence difference between EHEC and Shigella? {{c1::Shigella is
invasive, EHEC is not}} Shigella invades GI mucosal cells, causing damage and blood
diarrhea. EHEC attaches to GI epithelial cells and causes disease via toxin release
Which three bacteria produce an exotoxin that acts by increasing fluid secretion?
{{c1:: ETEC Bacillus anthracis Vibrio cholera}} Amount of Cl- secreted = amount of
water in GI tract.
Fluid secretion in the GI tract is regulated by {{c1::CFTR}} transmembrane protein
which is activated by {{c1::Gs}} receptors ETEC (LT), cholera → Gs → ↑ cAMP →
↑Chloride (and H2O) secretion in gut via CFTR → watery diarrhea
What is the mechanism of Pertussis toxin? {{c1::Inhibits GI → ↑ cAMP in neutrophils
→ ↓↓ phagocytosis}} "Whooping cough → child coughs on expiration, ""whoops"" on
inspiration"
C. tetani's tetanospasmin toxin causes rigidity by preventing release of inhibitory
NTs (GABA, glycine) from {{c1::Renshaw cells in spinal cord}} Spastic paralysis,
risus sardonic, trismus (lockjaw) -CSF analysis is typically normal in tetanus
because it is a toxin-mediated disease -Denatured C. tetani toxoid is used as a
vaccination against tetanus. The still intact receptor binding site of the toxoid
induces antibody production and memory cell formation (active immunity).
Postexposure prophylaxis should include vaccination with DTaP and human
immunoglobulin (TIG), as well as antibiotics and intensive care treatment.
Which two bacterial toxins function by lysing cell membranes? {{c1:: Alpha toxin (C
perfringens) Streptolysin O (Strep pyogenes)}}
C. perfringen's alpha toxin is a {{c1::phospholipase (lecithinase)}} enzyme that
degrades {{c2::phosphatidylcholine and sphingomyelin}} Causes muscle breakdown
(myonecrosis) → creates anaerobic environment
{{c1::Streptolysin O}} is the toxin that causes B-hemolysis in Strep pyogenes
Anti-Streptolysin O (ASO) antibodies used to diagnose rheumatic fever
The most important statistical measure of a screening test is {{c1::sensitivity}}
Screening tests must be highly sensitive
What is the mechanism of action of Clomiphene? {{c1::Blocks estrogen receptors in
hypothalamus → causing release of LH/FSH}} Remove's estrogen's negative
feedback, used to stimulate ovulation (PCOS)
{{c1::Transduction}} is the transfer of DNA between bacteria via a bacteriophage
Virus picks up DNA and infects another bacteria
{{c1::Transposons}} are DNA segments within bacterial DNA that can be excised and
reintegrated at new locations in DNA Once excised, transposons can be moved to
a plasmid (transposition). Important for antibiotic resistance
What is the bacterial structure of Moraxella catarrhalis? {{c1::Gram-negative
diplococci}} Colonizes airways, causes otitis media, COPD exacerbations
Imipenem is always given with {{c1::cilastatin}} to inhibit {{c1::dehydropeptidase
I}} to decrease breakdown of drug in the renal tubules Only imipenem; other
carbapenems don't need cilastatin
Which carbapenem antiobiotic has the lowest risk for seizures? {{c1::Meropenem}}
Carbapenems inhibit GABA receptors in CNS at high doses or with renal
failure. Meropenem is safest
{{c2::Aztreonam}} is a monobactam antiobiotic that binds to {{c1::PBP-3}} in only
{{c1::gram-negative rods}} bacteria PBP-3 = penicillin-binding protein 3.
Synergistic with aminoglycosides
Aztreonam is synergistic with {{c1::aminoglycosides}} Can use in penicillin-
allergic patients
{{c1::Cefazolin}} is an antiobiotic used prior to surgery to prevent S. aureus
wound infections 1st generation cephalosporin
{{c2::Ceftaroline}} is a 5th gen cephalosporin that is specific for coverage
against {{c1::MRSA and VRSA}} because it inhibits {{c1::PBP2a}}
What are the symptoms of classic Dengue fever? {{c1:: Break-bone fever (flu + pain)
Retro-orbital pain Rash}} Tropica. Aedes mosquito. SS-RNA virus (flavivirus). 4
serotypes. 2nd infection (different serotype) can lead to hemorrhagic fever.
What are the symptoms of Hemorrhagic dengue fever? {{c1:: Thrombocytopenia
Bleeding, shock Positive torniquet test}} Aedes mosquito. Caused by repeat
infection with different Dengue serotype. Torniquet test → petechiae after BP cuff
inflation for 5 mins
Which two protein-synthesis (30s/50s) inhibiting antibiotics are bactericidal?
{{c1:: Aminoglycosides Linezolid (variable)}} Aminoglycosides → Gentamicin,
Neomycin, Amikacin, Tobramycin, Streptomycin
{{c1::Neomycin}} is an aminoglycoside given prior to bowel surgery to decrease
colonic bacteria Poorly absorbed so it stays in gut. Can also be given to treat
hyperammonemia
What is the major mechanism of resistance to aminoglycosides? (details)
{{c1::Aminoglycoside inactivated by enzymes via phosphyorylation, adenylation,
acetylation}} Phosphorylation → AG kinase Adenyl/acetylation → transferases
{{c1::Aminoglycoside}} antibiotics can cause neuromuscular blockade by blocking the
release of Ach at NMJs AGs also cause ototoxicity, nephrotoxicity, and are
teratogenic
What is the mechanism of Macrolide resistance? {{c1::Methylation of 23s rRNA }}
 component of 50s ribosome → macrolides can't bind Linezolid resistance is
caused by point mutations in rRNA
{{c1::Democlocycline}} is a tetracycline antibiotic used to treat SIADH via ADH
antagonism Causes nephrogenic DI to reverse SIADH
{{c1::Tetracycline}} antibiotics cannot be taken with milk (Ca), antacids (Ca, Mg)
or iron-containing preparations because these divalent cations chelate the abx and
prevent absorption
What is the mechanism of Tetracycline resistance? {{c1::↓uptake or ↑efflux out
of bacterial cells by plasmid-encoded transport pumps.}}
Chloramphenicol blocks {{c1::peptidyl transferase}} at the 50s ribosomal subunit
Macrolides block elongation at P site
Chloramphenicol causes Gray baby syndrome because babies lack {{c1::liver UDP-
glucuronyl transferase}} required for metabolism/excretion of drug. Skin turns
ashy/gray. Hypotension. often fatal
What is the mechanism of Chloramphenicol resistance? {{c1::Plasmid-encoded
acetyltransferase inactivates drug}}
What are the three major side effects of Linezolid (oxazolidinones)? {{c1:: BM
suppression (thrombocytopenia) Peripheral neuropathy Serotonin syndrome}}
Linezolid used to treat MRSA and VRE by preventing formation of initiation
complex at 50s
What is the mechanism of Linezolid resistance? {{c1::Point mutation of rRNA}}
{{c1::Quinuspristin and Dalfopristin (streptogramins)}} are antiobiotics that block
50s ribosome to treat VRE
Quinolones (-floxacin) inhibit what two enzymes? {{c1:: Topoisomerase IV DNA gyrase
(Top II)}} Bactericidal Gyrase → makes double-stranded break and repairs it Top IV
→ separates daughter chromosomes (decantenation)
What is the mechanism of Vancomycin's Red man syndrome? {{c1::Direct mast cell
activation and histamine release}} Prevent by sloowww infusion
Plasmodium spp. (malaria) are transmitted by {{c1::female Anopheles}} mosquito
bites and travel to the liver in the {{c1::sporozoite}} form Sporozoites =
infectious. Asymptomatic for up to one month.
List the form of Malaria in each of the following stages of the life cycle: Bite →
{{c1::sporozoites}} → hepatocytes → {{c1::schizonts}} → rupture →
{{c1::merozoites}} → infect RBCs → {{c1::trophozoites}} Trophozoites (ring form)
mature into schizonts again in RBCs, form merozoites again, then lyse RBCs
{{c1::Recombination}} is a viral exchange of genes between 2 chromosomes by
crossing over within regions of significant homology Eg, HSV1 and HSV2, one
acquires resistance to acyclovir
In RBCs, trophozoites mature into {{c1::schizonts}} which digest RBC proteins
(hemoglobin) and excrete breakdown products toxic to RBCs Merozoites formed
(again) → RBC lysis. occurs at regular intervals (48hrs, 72hrs). Chloroquine
inhibits this process.
Plasmodium vivax & ovale have a dormant {{c1::hypnozoite}} form in the liver which
is treated with {{c1::Primaquine}} Recurring infection months after resolution
List the fever pattern associated with each Plasmodium species: vivax/ovale:
{{c1::48-hr}} falciparum: {{c1::irregular}} malariae: {{c1::72-hr}}
Plasmodium {{c1::falciparum}} can invade RBCs of any age, while all other species
can only invade {{c1::reticulocytes}} Hence why falciparum is much more severe
"Plasmodium falciparum occludes capillaries by forming sticky ""knobs"" composed of
{{c1::PfEMP1 parasite proteins}} on RBC surfaces, which bind to endothelial cells"
PfEMP1 = P. falciparum erythrocyte membrane protein 1
What are the three major complications of capillary occlusion from P. falciparum?
{{c1:: Cerebral malaria Renal failure (blackwater fever) ARDS}} "Occlude
capillaries via ""sticky knobs"" of parasite proteins on RBC surface which bind to
endothelial cells in capillaries"
{{c1::Duffy antigen}} on the surface of RBCs is necessary for P. vivax infection
Absence of Duffy is protective
Chloroquine blocks {{c1::plasmodium heme polymerase}} in the RBC
{{c1::trophozoite}} form of malaria species Chloroquine is a weak base and
accumulates in food vacuoles (acidic) in RBC trophozoites
Which two IV drugs are given to treat severe malaria infections? {{c1:: Artesunate
Quinidine}} Mefloquine = resistance Primaquine = liver (v & o)
Dermatophytes are fungi that require {{c1::keratin}} for growth Hence they cause
tinea infections (fungal skin/nail infx)
Dermatophytes exist only in what form? {{c1::Molds with hyphae}}
KOH (potassium hydroxide) is used to diagnose fungal infections because it
dissolves {{c1::epidermal keratinocytes}} allowing fungi to be visible Used for
dermatophyte infections, tinea versicolor, superficial candida
List where the following tinea infections occur: capitis: {{c1::scalp}} corporis:
{{c1::torso}} cruris: {{c1::inguinal }} pedis: {{c1::feet}} unguium: {{c1::nails}}
How does Malassezia cause tinea versicolor? {{c1::Degrades lipids → acids → damages
melanocytes → hypopigmented skin }}
In addition to normal topical antifungals, what drug is used to treat tinea
versicolor and what is its MOA? {{c1::Topical selenium sulfide → promotes shedding
of stratum corneum}} Random fact: selenium is a required cofactor for glutathion
peroxidase
Sporotrichosis is caused by skin penetration of {{c1::spores}} which form a papule
before traveling proximally via {{c1::lymph channels}} """Ascending
Lymphangitis"""
What are the two treatments for Sporothrix schenckii? {{c1:: Oral itraconazole
SSKI}} SSKI = saturated solution of potassium iodide
Chronic mucocutaneous candidiasis is ultimately caused by {{c1::Th17}} dysfunction
Presents with recurrent, noninvasive C albicans infections of the skin,
mucous membranes and nails Mutations in AIRE gene. Defects in IL-17 or IL-17R. T-
cells don't react to candida. Presents as child with recurrent thrush, diaper rash
Describe the immunologic pathogenesis of ABPA: {{c1::↑ Th2 CD4+ cells → ↑ IL-4, IL-
5 → ↑ eosinophils and IgE production}} Occurs predominantly in asthma and CF
patients. It's an allergic (HS) reaction to aspergillus antigens
{{c1::Latex agglutination test}} is the most specific test for C. neoforman and
detects {{c1::polysaccharide capsular antigen}} Sample w/ CN + latex beads covered
with anti-capsular antibodies → clumping & agglutination = positive Also can use
Sabouraud's agar and india ink stain
Rhizopus and Mucor sp. cause mucormycosis in DKA patients because they contain the
enzyme {{c1::ketone reductase}} High glucose & ketones in serum stimulate
growth
"Fever and chills (""shake and bake"") is an acute adverse effect of Amphotericin B
administration caused by {{c1::prostaglandin}} release" Can treat/reduce with
NSAIDs or diphenhydramine
What are two ways to decrease the risk of Amphotericin nephrotoxicity? {{c1::
Excessive hydration Liposomal Amphotericin B}} - Amp B causes renal
vasoconstriction and is toxic to tubules (inserts pores into cell membrane). -
Liposomal = AmpB dissolved in lipids
Under what circumstance is Amphotericin B given intrathecally? {{c1::funal
meningitis}} Always supplement K+ and Mg+ because of alterations in renal
tubule permeability
Which two electrolyte abnormalities are associated with Amphotericin B? {{c1::
Hypomagnesemia Hypokalemia}}
Flucytosine blocks fungal DNA/RNA synthesis after being converted to {{c1::5-
fluorouracil}} by {{c1::cytosine deaminase}} Cytosine deaminase only present in
fungi
What is the major side effect of Flucytosine? {{c1::Bone marrow suppression}}
Some spontaneous conversion to 5-FU. Results in leukopenia, thrombocytopenia.
Only given with AmpB to treat cryptococcal meningitis
Which metabolic processes occur strictly in the mitochondria? {{c1:: Fatty acid (ß)
oxidation Acetyl-CoA production TCA cycle Ketogenesis Oxidative phosphorylation }}
FAT KOp
Which metabolic processes occur strictly in the cytoplasm? {{c1:: Glycolysis HMP
shunt Synthesis of steroids, proteins, FAs, Cholesterol, nucleotides}} Both = Heme
synthesis, Urea cycle, gluconeogenesis
Endotoxin (LPS) binds to {{c1::CD14 (TLR4)}} receptor on macrophages to trigger
cytokine release IL-1, IL-6 → Fever TNF-a → fever & hypotension N.O. → hypotension
Peptidoglycan can bind to {{c1::NOD receptors (intracellular)}} in macrophages to
trigger cytokine expression NOD = nucleotide-binding oligomerization domain
{{c1::Lipoteichoic acid}} on gram-positive bacteria can be recognized by the innate
immune system to trigger cytokine release LTA → IL-1, TNF-a
Which two cytokines activate cellular endothelial adhesion molecules? {{c1::IL-1;
TNF-a}} Promoting neutrophil adhesion/migration to inflammed tissue
How does TNF-a cause cachexia in malignancy? {{c1::Inhibits Lipoprotein Lipase in
fat tissue, reducing utilization of FAs}} LPL degrades TGs circulating in
chylmocrions and VLDL
{{c1::IL-6::cytokine}} stimulates production of acute phase proteins (CRP) from the
liver in response to inflammation - Other important functions of IL-6 include
differentiation of myeloid stem cells and terminal differentiation of B-cells into
plasma cells, as well providing positive feedback to Th-17 cells and negative
feedback to regulatory T cells. ESR increases in the setting of inflammation
largely due to increased levels of fibrinogen which causes red cells to stick
together. Also fever Positive acute phase proteins: 1. Fibrinogen 2. Ferritin, 3.
Serum amyloid A, 4. Hepcidin and 5. C-reactive protein Negative acute phase
proteins: 1. Albumin, 2. Transferrin and 3. Transthyretin
What are the four major enzymes in neutrophil specific granules? {{c1:: Collagenase
ALP Lysozyme Lactoferrin}} CALL specific neutrophils. Can fuse with phagosomes
and can also be released into extracellular space
What are the three major enzymes in neutrophil azurophilic granules (lysosomes)?
{{c1:: MPO Acid phosphatase B-glucuronidase}} Fuse with phagosomes only (no e.c.
release)
What are the 5 major neutrophil chemotactic agents? {{c1:: Kallikrein Platelet
activating factor C5a LTB4 IL-8}} N-formylmethionine (via LTB4) and Endotoxin
(via C5a)
How will estrogen (pregnancy, OCPs) affect thyroid hormone levels? {{c1::↑ Total T4
and T3}} Estrogen transiently increases TSH, but also upregulates TBG. This
means that total T3/T4 being produced is increased, but most is bound to TBG,
meaning normal free T3/T4
Which cells of the innate immune system destroy human cells with absent/reduced MHC
I? {{c1::Natural Killer Cells}} Part of the innate immune system that do not
require prior sensitization/activation to have a cytotoxic effect. Target cell
lines with downregulated MHC I molecules, which allows them to act as anti-viral
and anti-cancer surveillance systems vs cytotoxic T-cells that must be activated by
MHC I molecules some viruses block MHC I
Natural Killer Cells express which two unique cell surface molecules? {{c1:: CD16
CD56}} CD16 binds Fc of IgG for antibody-dependent cell-mediated cytotoxicity
NKCs kill cells via antibody-dependent cell-mediated toxicity via {{c1::CD16}}
binding to {{c1::Fc region of IgG}} Eosinophils also kill parasites via ADCC
Which two cells of the innate immune system are capable of killing cells via
antibody-dependent cellular cytotoxicity (ADCC)? {{c1:: Natural killer cells
Eosinophils}} NKCs: CD16 + Fc IgG Ephils: bind Fc IgE on parasites
{{c1::Natural Killer Cells}} are the only lymphocytes of the innate immune system
But they have no memory and dont require antigen presentation by MHC (in
contrast to B-cells and T-cells)
Eosinophil granules stain red on Wright stain due the {{c1::postive}} charge of
{{c1::Major Basic Protein}} Eosin dye has negative charge
T-cells can only recognize {{c1::peptides}} presented on MHCs on APCs Cannot react
to any antigens in body. Must be phagocytosed, processed, and presented on MHC
molecules. This prevents autoimmunity.
What are the three components of the T-cell receptor? {{c1:: Alpha chain Beta chain
CD3 complex}} A&B chain bind to antigen from MHCs. CD3 transmits signal into
cell.
MHC II binds to {{c1::invariant chain}} in the {{c1::ER}} to prevent binding of
intracellular proteins Releases invariant chain after antigen loading in acidified
endosome
What are the three major cytokines secreted from Th2 cells? {{c1:: IL-4 IL-5 IL-
10}} - IL-4: ↑Th2 + IgE - IL-5: ↑Eosinophils + IgA - IL-10: ↓Th1, major inhibitor
What are the major functions of the following Th2 cytokines? IL-4: {{c1::↑Th2 + IgE
}} IL-5: {{c1::↑Eosinophils + IgA }}
What are the major functions of IL-10 secreted from Th2 and Tregs? {{c1:: ↓ APC MHC
expression ↓ Th1}} Anti-inflammatory. No pro-inflammatory effect. IL-10 and
TGF-B are the major anti-inflammatory cytokines TGF-B secretion by regulatory T-
cells prevents autoimmunity by inhibiting B-cells and macrophages and activating
regulatory T-cells and Th-17 cells. IL-10 from regulatoryT-cells downregulates the
expression of MHC class II molecules, inhibits the secretion of Th-1 cytokines, and
suppresses activated macrophages and dendritic cells. These mechanisms prevent
autoimmune disease by maintaining tolerance to self-antigens.
Which cytokines activate and inhibit Th1 cells? Activate: {{c1::IFN-y, IL-12}}
Inhibit: {{c2::IL-4, IL-10 (Th2)}}
Which cytokines activate and inhibit Th2 cells? Activate: {{c1::IL-2, IL-4}}
Inhibit: {{c1::IFN-y (Th1)}}
Th1 cells are extremely important for immune defense against which two infections?
{{c1:: M. tuberculosis Listeria}} TB → intracellular macrophage infx Listeria →
intracellular; weak Th1 response responsible for succeptibility in newborns,
eldery, and immunocompromised
Describe the 4 steps in the pathogenesis of granulomas: {{c1::Th1::cell}} →
{{c2::IFN-y::cytokine}} → {{c1::macrophage activation::cell}} → {{c2::TNF-
a::cytokine}} → granuloma formation Blockade of IFN-y receptors lead to impaired
phagocytosis and impaired granuloma formation, which increases the risk of
disseminated mycobacterial infection. TNF-a plays an important role in the
sequestration of M.Tb in granulomas. Inhibition of TNF-a results in the breakdown
of granulomas and release of mycobacteria, which can also increase the risk of
disseminated mycobacterial infection
CD8 T-cells can lyse and induce apoptosis in bacteria by inserting
{{c1::granulysin}}
Regulatory T-cells (Tregs) are identified by expression of what four surface
markers? {{c1:: CD25 CD3 CD4 FOXP3}} IPEX: genetic deficiency of FOXP3 →
autoimmunity -Autoimmune endocrinopathy is a feature of immune dysregulation,
polyendocrinopathy, enteropathy, X-linked syndrome (IPEX syndrome), which is caused
by a mutation in the FOXP3 gene. FOXP3 encodes a transcription factor required for
the normal development of regulatory T-cells; impaired functionality of the FOXP3
protein leads to a loss of tolerance to self-antigens. Present in the first 6
months of life with enteropathy, skin conditions (eg; eczema, erythroderma,
psoriasis), type I diabetes mellitus (the most common endocrine disorder in IPEX
syndrome), and autoimmune thyroid disease.
Positive selection occurs in the thymic {{c1::cortex}} where T-cells are tested for
binding to self-MHC complexes on {{c1::thymic epithelial cells}} Weak binding:
apoptosis (need to be strong)
Negative selection occurs in the thymic {{c1::medulla}} and tests for
{{c1::autoimmunity}} Passed positive selection, meaning they're good soldiers.
Negative selection makes sure that they don't friendly fire.
Alkylating agents add alkyl groups to {{c1::N7 nitrogen of guanine}} which
ultimately inhibits {{c2::DNA strand cross linking}} Cell cycle non-specific
All ecosanoids (luekotrienes, PGs, etc) are synthesized from {{c1::membrane
phospholipids}} by {{c1::phoshpolipase A2}} Phospolipids ↓ PLA2 ← steroids ↓
Arachidonic acid
What are the two adverse effects associated with selective COX-2 inhibitors? {{c1::
Thrombosis Sulfa allergy}} Celocoxib is the only selective COX-2 inhibitor.
Reversible.
How do Cyclosporine and Tacrolimus differ in their mechanisms of NFAT inhibition?
Cyclosporine: {{c1::binds cyclophilins}} Tacrolimus: {{c1::binds FK506 BP}}
FK506BP = FK506 Binding Protein = FKBP
Mycophenolate reversibly prevents purine synthesis by inhibition of {{c1::IMP
dehydrogenase type II}} Type II only found in lymphocytes → selectively prevents
synthesis of B & T cells
Muscarinic {{c1::M2}} receptors in the heart reduce contractility and HR by
inhibiting {{c1::calcium}} entry into cells Anticholinergic poisoning causes
Bradycardia
How does muscarinic agonism cause smooth muscle relaxation (vasodilation)? ACh →
{{c1::endothelial cells → NO release → diffuses into smooth muscle → activates
cGMP}} → smooth muscle relaxation Just remember that this is an indirect effect
through NO; does not directly act on vascular smooth muscle
List the common indications for the following ACh agonists: Bethanechol:
{{c1::Ileus, urine retent.}} Carbachol: {{c2::glauc., pupil constrict.}}
Pilocarpine: {{c1::glauc., Sjogrens}} Methacholine: {{c2::Asthma testing}}
How are incidence and prevalence affected by a new screening/diagnostic test that
has imroved sensitivity? {{c1::Both increase}}
Myasthenia gravis exacerbations will muscle function improvement on Edrophonium
testing indicates what? {{c1::Insufficient dose of AChE inhibit; ↑ dose}} No
improvement: ↓ dose
Myasthenia gravis exacerbations with no improvement in muscle function on
Edrophonium testing indicates what? {{c1::Cholinergic crisis; ↓ dose}} Cholinergic
crisis arises when too much AChE medication (pyridostigmine) is given, causing the
muscles to be refractory to ACh
Cholinergic medication (ACh agonists and AChE inhibitors) can cause exarcerbation
of which two conditions? {{c1:: COPD/Asthma Gastric ulcers}} M3 → Gq →
bronchoconstriction M3 → Gq → activate parietal cell ATPase → acid secretion →
ulcers
What is the treatment regiment for organophosphate poisoning? {{c1::Atropine +
Pralidoxime}} -The initial treatment is atropine, which quickly reverses
bradycardia and bronchoconstriction. Regeneration of acetylcholinesterase by
pralidoxime is slow. So, it should be administered after atropine. Atropine:
muscarinic antagonist Pralidoxime: regenerates AChE -Because atropine does not act
on nicotinic receptors, it cannot reverse any neuromuscular dysfunction caused by
organophosphate poisoning. Pralidoxime, a cholinesterase reactivator, is also
effective in treating the nicotinic effects of organophosphates.
Which three muscarinic antagonists are used to produce mydriasis and cycloplegia?
{{c1:: Atropine Homatropine Tropicamide}}
Which muscarinic antagonist is used to treat motion sickness? {{c1::Scopolamine}}
First gen antihistamines are also used to treat vestibular nausea
Which muscaranic antagonist is used to reduce pre-op airway secretion?
{{c1::Glycopyrrolate}} Also used for drooling & peptic ulcers
Which two muscarinic antagonists are used as antispasmodics to treat irritable
bowel syndrome? {{c1:: Hysocyamine Dicyclomine}}
Motion sickness (vestibular nausea) is caused by overstimulation of which two
receptors? {{c1::M1, H1}} Treat: M1: scopolamine H1: Meclizine, Dimenhydrinate
In addition to scopolamine, which drugs are used to treat vestibular nausea (motion
sickness)? {{c1:: Meclizine Dimenhydrinate Diphenhydramine}} Reversible H1
inhibitors
What is the major indication for Phentolamine (a-blocker)? {{c1::Reversal of
hypertensive crisis when pts on MOA inhibitors eat tyramine}} Can cause
orthostatic hypotension, reflex tachycardia
{{c1::Poxviruses}} are the only DNA viruses that replicate in the cytoplasm All
other DNA viruses replicate in nucleus
In addition to mental retardation and hypotonia, what are three key physical exam
findings of cretinism (neonatal hypothyroidism)? {{c1:: Coarse facial features
Enlarged tongue Umbilical hernia}} Must give levothyroxine by two weeks of age.
Otherwise, may be irreversible
{{c1::Salk (inactivated)}} is the major poliovirus vaccine used in the US,
delivered by injection and generates a systemic antibody response Cannot cause
vaccine-associated polio
What are the four components of the SBAR communication method? {{c1:: Situation
Background Assessment Recommendation}} 1. Situation: what is happening? -
patient has fever 2. Background: who is pt? - elderly woman w cancer 3. Assessment:
Vitals? Labs? 4. Recommendation: What is needed? - I need to know if you want to
start antibiotics
Which pathogens require contact precautions? {{c1:: C. difficile MRSA Any
infectious diarrhea (noro/rota-virus)}} Easily spread by contact. Gloves + Gown.
Which pathogens require droplet precautions? {{c1:: Neisseria meningitides
Respiratory viruses (RSV, flu) Bordetella pertussis}} Droplet: infection spreads by
speaking, coughing, or sneezing Gloves + Gown + Facemask
Which pathogens require respiratory precautions? {{c1:: TB Measles Chickenpox}}
Gloves + Gown + Fit tested mask or respirator
{{c2::Rotavirus}} infections lead to destruction and atrophy of the small
intestinal villi leading to decreased absorption of {{c1::sodium}} and
{{c1::potassium}}
What are the three major uses of PCR? {{c1:: Amplification of small amount
Determine presence of DNA Determine amount of DNA}} Amount → lots of DNA
amplifies rapidly, low amount of DNA amplifies slowly
{{c1::Real Time (Quantitative) PCR}} is PCR done in the presence of a
{{c2::fluorescent dye}} used to determine the quantity of DNA - Amount of DNA
proportion to dye - More DNA = more fluorescence - ongoing; rapid increase in
fluorescence = lots of DNA in sample
What are the two major clinical uses of PCR? {{c1:: HSV encephalitis HIV viral
load}} HIV is RNA virus, but reverse transcriptase is used to create cDNA,
which is amplified to determine viral load
What are two major cinical uses of Southern blot procedures? {{c1:: RFLP Sickle
cell anemia}} RFLP (Restriction fragment length polymorphism) → restriction
nucleases cut DNA at specific base sequences. Analyze fragments with southern blot.
Determines gene polymorphisms in family; which family members are heterozygous
carriers (Aa)? which are AA? aa?
{{c1::Right ventricle}} is the most commonly injured cardiac chamber in penetrating
chest trauma Makes up majority of anterior surface of heart. Often presents as
tamponade (↑ JVP, hypotension, distant heart sounds)
Which structures are immediately anterior and posterior the esophagus,
respectively? (eg, transesophageal echocardiogram) Anterior: {{c1::Left atrium}}
Posterior: {{c1::Aorta}}
Describe the anatomic location of the SA node: {{c1::Right atrial posterolateral
wall near SVC}} SA node is supplied by right coronary artery in most patients
Describe the anatomic location of the HIS bundle: {{c1::Interventricular septum
near tricuspid valve}}
{{c1::Cytotoxic edema}} is an increase in intracellular fluid within neurons, glia
and endothelial cells due to loss of Na/K-ATPase following cerebral ischemia
Vasogenic edema is due to breakdown BBB (tight junctions between endothelial
cells) d/t tumor, stroke, trauma.
Two functions of interferons alpha and beta are: {{c1::1. Increased expression of
MHC class I proteins on surface of virus-infected cells}} {{c2::2. Activation of
various enzymes that promote the antiviral state of cell (by downregulating protein
synthesis to resist potential viral replication}} Ribonuclease L is an enzyme
that mediates the degradation of cellular and viral RNA and thereby inhibits viral
protein synthesis. The enzyme is only activated upon binding to double-stranded
RNA, which ensures that breakdown of intracellular RNA occurs preferentially in
virus-infected cells.
Cathepsin is a lysosomal enzyme released by {{c1::neutrophils}} during type III
HSR, such as vasculitis and serum sickness
Findings on peripheral blood smear in patient with splenic dysfunction or
asplenectomy {{c1:: }}
Effects of IL-1 and TNF-alpha: Both increases {{c1::endothelial adhesion molecules;
allows neutrophils to enter inflamed tissue}} IL-1 acts as {{c2::Endogenous
pyrogen, acts on hypothalamus and causes fever}} TNF-alpha can cause {{c2::
Vascular leak, septic shock; Cachexia (inhibits lipoprotein lipase in fat tissue,
reducing utilization of fatty acids; Can cause intravascular coagulation leading to
DIC}}
Avascular necrosis of femoral head is a common problem in patients with lupus,
especially those who take {{c1::steroids}} . Vascular damage to the bone blood
supply leads to necrosis of bone marrow elements and ultimately mechanical failure
of the hip joint. The process is progressive with joint failure usually occuring
within a few years, necessitating hip replacement surgery. Mechanism of association
between glucocorticoids and AVN is unclear. It may involve {{c2::increases in bone
marrow adipocyte size, which blocks venous outflow}}
Following the first dose of vaccination, antigens generate a relatively weak immune
response. There is production of {{c1::IgM}} antibodies, some {{c1::IgG}}
antibodies and memory B-cells. The time required to reach peak production of
{{c1::IgG}} antibodies is relatively {{c1::long}}, since prior to the first
exposure there are no memory cells present. Following the second vaccination,
antigens are recognized by memory B cells. These rapidly differentiate into
{{c2::IgG}}-secreting plasma cells that lead to an increased quantity of
circulating {{c2::IgG}} antibodies. The time required to reach peak antibody
production is also {{c2::decreased}}
SLE is an example of type {{c1::III}} hypersensitivity "-SLE occurs when self-
reactive lymphocytes produce antibodies to host nuclear antigens. The immunologic
process of reacting to self-antigens is called loss of tolerance, meaning that
immune cells are unable to ""tolerate"" self-antigens as they should, and therefore
generate an immune response."
BnB Qs immuno
Under stimulation by T-cell cytokines, B-cells undergo two processes in the lymph
node (germinal center) in response to activation: {{c1::1. Class switching and 2.
Somatic hypermutation}} -Class switching is the mechanism whereby a B-cell changes
production of antibody from one class to another (eg; stops synthesizing IgM and
starts synthesizing IgG). -In somatic hypermutation, B-cells develop point
mutations in genes for the variable region of B-cell receptor. This slightly
modifies the B-cell receptor, which may result in stronger antigen binding. If an
altered variable region binds antigen more avidly than the original B-cell
receptor, cells with the altered variable region will proliferate more. As a
result, the immune response becomes stronger and more targeted to an antigen over
time
Central tolerance, also known as negative selection, is the process of elimination
of B-cells that react with self-antigens (autoreactive B-cells). These events occur
early in B-cell development, before B-cells move to the periphery. Immature B-cells
that react with self-antigens in the {{c1::bone marrow}} undergo apoptosis
Even a two haplotype match where all major histocompatibility complex antigens are
the same can elicit some degree of immune response. This is due to {{c1::minor
histocompatibility antigens}} that differ between donor and recipient. Even with a
two haplotype matched donor organ from a sibling, immunosuppression will be
required. The only exception is when the organ comes from an identical twin, in
which case, all major and minor histocompatibility antigens should be identical and
immunosupression is generally not required
Laboratory findings in a HIV patient who is not receiving treatment or who has
failed treatment (eg; due to medication non-compliance or drug resistance) : 1.
CD4+/CD8+ ratio {{c1::decreases}} 2. HIV RNA {{c1::increases}} 3. HIV antibody test
{{c1::positive}}
{{c1::Dead neutrophils}} are the primary cellular component of the purulent exudate
(eg; pus; thick, white liquid) found in an abscess.
The most likely cause of an isolated oculomotor nerve palsy in a patient with
uncontrolled diabetes mellitus is diabetic mononeuropathy, which occurs as a result
of {{c1::microangipathic ischemia}} -Ptosis occurs in patients with oculomotor
nerve palsy because levator palpebrae superioris is innervated by the oculomotor
nerve. Whereas patients with oculomotor nerve palsy due to compression usually show
dilated pupils, those with diabetic mononeuropathy normally do not have pupillary
involvement because the microangiopathy typically involves the vaso nervosum within
the oculomotor nerve, while the pial blood vessels (which supply the superficial
parasympathetic fibers) are usually spared.
Eczematous dermatitis: {{c1::Acute::acute/chronic}} {{c1::allergic contact}}
dermatitis Type {{c2::IV}} HSR, due to {{c2::CD4+ Th-}}cell activation, which leads
to inflammatory response in {{c2::24}} hours after {{c2::re-exposure::exposure/re-
exposure}} -Light microscopy: 1. Spongiosis (accumulation of edema fluid in the
inter-cellular spaces in the epidermis) 2. Maybe marked to form intra-epidermal
vesicles 3. +/- peri-vascular infiltrates of lymphocytes and eosinophil (either in
superficial dermis or deeper) -On chronic exposure, lesion become less edematous,
weepy, which results in thickening of stratum spinosum and stratum corneum, to form
plaques
{{c1::NMDA glutamate}} receptors are targeted by antibodies in anti-{{c1::NMDA}}
encephalitis, which is a type of paraneoplastic encephalitis (presents with
cognitive defects, personality changes, speech impairment, involuntary limb
movements and autonomic instability eg; tachycardia, hypotension), that is
typically associated with ovarian teratoma. -Patients with PEm can have a
prodrome of fever, headache and fatique lasting weeks to months before the onset of
features of CNS damage. -CSF analysis: lymphocytic pleocytosis with inc protein
concentration.
Parasympathetic activation of {{c1::M3 (coupled with Gq)}} receptors, located on
the detrusor muscle of the bladder, trigger contraction of the detrusor, forcing
urine into the urethra. Activation of {{c1::M3}} receptors also causes relaxation
of the internal urethral sphincter, allowing urine to flow.-The external urethral
sphincter is under voluntary (somatic) control and must relax for urination to
occur. -Alpha-1 receptors cause contraction of the internal sphincter during
bladder filling. -Beta-3 receptors cause relaxation of the detrusor during filling.
-Volatile anesthetics interfere with the autonomic nervous system, causing bladder
atony (lack of muscle tone or strength). Narcotic medications such as fentanyl
cause urinary retention by inhibiting acetylcholine release from parasympathetic
sacral neurons that innervate the detrusor muscle. Because anesthetics and
narcotics inhibit bladder function, urinary retention is common after surgery.
Treatment for postoperative urinary retention includes catheterization.
Administration of low-dose naloxone, an opioid antagonist, may reverse urinary
retention induced by opioids.
Prolonged paralysis after administration of succinylcholine can be seen in patients
with a rare condition known as {{c1::butyrylcholinesterase}} deficiency. -
Butyrylcholinesterase (formerly called pseudocholinesterase) is an enzyme that
breaks down succinylcholine. The typical duration of action of succinylcholine is
approximately ten minutes. In case of this enzyme def, the patient will be
paralyzed even after 1 hour of administration of succinylcholine. This is
consistent with an abnormal genetic variant of the butyrylcholinesterase enzyme.
In primary active transport, the carrier molecules are enzymes that hydrolyze ATP
(ATPases) and use the energy released to transport ions and molecules against their
concentration gradients. Examples of such carriers are: {{c1::N-K ATPase H-K ATPase
Calcium ATPase }}
-Receptive relaxation is a reflex that allows the {{c1::gastric fundus}} to dilate
in anticipation of food passing through the pharynx and esophagus -Postprandial
alkaline tide is defined as an increase in plasma {{c1::HCO3-}} and decrease in
plasma {{c1::Cl-}} secondary to the surge of acid within the gastric lumen.
Supplementation for breastfed infants: {{c1:: }} -All vitamins and trace
minerals are present in adequate amounts except vitamins D and K. Vitamin K is
supplemented by an intramuscular injection at delivery to prevent hemorrhagic
disease in the newborn. -Regular sunlight exposure typically provides sufficient
vitamin D. However, infants are generally shielded from direct sunlight due to
sunburn risk. In addition, infants with dark skin pigmentation require more
sunlight exposure to produce adequate vitamin D. Melanin is a natural sunblock and
prevents ultraviolet rays from reaching the skin for vitamin D synthesis. Prolonged
vitamin D insufficiency can lead to rickets (inadequate bone and cartilage
mineralization). Therefore, all exclusively breastfed infants should receive
vitamin D supplementation to prevent rickets. Formula-fed infants do not require
supplementation as formula is fortified with adequate amounts of vitamin D.
-Although breast milk has low iron content, the bioavailability of iron in
breastmilk is considerably higher than supplemental iron and is sufficient for
infants until age 4 months. Due to decreasing iron concentration in breast milk
over time, supplementation is recommended for breastfed infants at age >4 months
until solid food intake provides an adequate amount.
Two-thirds of lightning-related deaths occur within the first hour following
injury; the most common causes {{c1::fatal arrhythmias and respiratory failure}}
-Finding of an unconscious person on wet ground or under tress during a
thunderstorm suggests a lightning injury. Lichtenberg figures: Erythematous
cutaneous marks in a fern-like pattern (caused by local hyperemia) confirm the
suspiciom. -Lightning-related complications:
Fats and amino acids can be used as substrates for gluconeogenesis in the liver
through conversion into {{c1::succinyl-CoA}} - A number of non-carbohydrate
substances can be converted to glucose in the liver via succinyl-CoA. These include
odd chain fatty acids and some amino acids. Once converted to succinyl-CoA, thy can
be metabolized into succinate which can enter the TCA cycle. Through the TCA cycle,
succinate is metabolized to oxaloacetate which can enter gluconeogenesis.
What changes are expected compared to normal state (i.e; adequate food intake) with
a fasting state, for hepatocyte levels of: 1. Fructose 2, 6 bisphosphate levels
{{c1::decreased::increased/decreased}} 2. Pyruvate kinase activity
{{c1::decreased::increased/decreased}} 3. Glucose-6-phosphatase
{{c1::increased::increased/decreased}} "-Under prolonged fasting/starvation
conditions, fatty acids stored in adipose tissue will be metabolized in the liver
into acetyl-CoA for entry into the TCA cycle. Increased levels of acetyl-CoA will
activate gluconeogenesis and inhibit glycolysis. -Pyruvate kinase catalyzes the
final step in glycolysis. Activity will be decreased in the fasting state. -
Fructose 2,6 bisphosphate is a regulator of glycolysis. Its level is an ""on-off
switch"" for glycolysis and will be low when gluconeogenesis is activated during a
fast. -Glucose-6-phosphatase catalyzes the final step of gluconeogenesis in the
liver, the conversion of glucose-6-phosphate into glucose. Its activity will be
high in the fasting state."
Major absorption sites in small intestine: 1. In duodenum, {{c1::iron, copper and
vitamin B1}} 2. In jejunum, {{c1::vitamins ADEK, lipids, vitamin C and folate}} 3.
In ileum, {{c1::viatmin B12 and bile salts}}
Examples of electron transport inhibitors: 1. Complex I by {{c1::rotenone}} 2.
Complex III by {{c1::antimycin A}} 3. Complex IV by {{c1::cyanide, carbon monoxide
and azides}} -An electron transport chain inhibitor will halt both ATP
production and oxygen consumption -Key point: Inhibitors shut down ATP production
by shutting down electron transport (and, therefore consumption of oxygen).
Uncouplers allow electron transport (ie; oxygen consumption) to proceed normally
but ATP production is inhibited through proton escape from the inner membrane
space.
Myocytes contain {{c1::phosphocreatine}} which serves as a reservoir for phosphate
groups -When ATP is hydrolyzed to ADP for muscle contraction, phosphocreatine
donates phosphate groups to ADP to re-generate ATP. The supply of phosphocreatine
is depleted within 8-10 seconds.
What changes are expected compared to normal state (i.e; adequate food intake) with
a fasting state, for hepatocyte levels of: 1. Pyruvate dehydrogenase activity
{{c1::decreased::increased/decreased}} 2. Pyruvate carboxylase activity
{{c1::increased::increased/decreased}} 3. Oxaloacetate concentration
{{c1::increased::increased/decreased}} 4. Acetyl-CoA concentration
{{c1::increased::increased/decreased}} -In fasting state, beta oxidation of
fatty acids leads to increased levels of acetyl-CoA in liver cells. High acetyl-CoA
levels inhibit pyruvate dehydrogenase (PDH) activity by activating kinase enzymes
that phosphorylate PDH to render it less active. -High levels of acetyl-CoA also
activate pyruvate carboxylase (PC) which diverts pyruvate towards gluconeogenesis.
Pyruvate is converted into oxaloacetate, the first step towards liver synthesis of
glucose. -Final effect of increased acetyl-CoA is the synthesis of ketones by the
liver
High doses of which vitamin are associated with peripheral neuropathy:
{{c1::Vitamin B6}}
DSM-5 diagnostic criteria for Narcolepsy include.. 1. Recurrent lapses into sleep
or naps ({{c1::3 or more than 3 times/week for 3 months::attacks/week and
duration}}) 2. 1 or more than 1 of the following: a. {{c1::cataplexy}}: Brief loss
of muscle tone precipitated by strong emotions (eg; laughter, excitement) b. Low
cerebrospinal fluid levels of {{c1::hypocretin-1/orexin-A}} c. {{c1::Shortened}}
REM sleep latency -Associated features include: 1. Hypnagogic or hypnopompic
hallucinations 2. Sleep paralysis
Determine the correlation coefficient of following: A. {{c1::No correlation, r=0}}
B. {{c1::Perfect fit, r=1}} -r is always between −1 and +1. The closer the
absolute value o r is to 1, the stronger the linear correlation between the 2
variables. -Positive r value Ž positive correlation (as one variable ↑, the other
variable ↑). -Negative r value Ž negative correlation (as one variable ↑, the
other variable ↓).
Determine the correlation coefficient of following: A. {{c1::r= -0.2}} B. {{c1::r=
-0.8}} -r is always between −1 and +1. The closer the absolute value o r is to
1, the stronger the linear correlation between the 2 variables. -Positive r value
Ž positive correlation (as one variable ↑, the other variable ↑). -Negative r
value Ž negative correlation (as one variable ↑, the other variable ↓).
What changes are expected compared to normal person with a patient of DKA, for
hepatocyte levels of: 1. Acetyl CoA levels {{c1::increased}} 2. TCA cycle NADH
generation {{c1::decreased}} 3. Beta-oxidation of fatty acids {{c1::increased}}
-In DKA, insulin levels are extremely low. Liver behaves as if in the fasting
state despite the presence of hyperglycemia. As a result, fatty acid metabolism via
beta-oxidation increases. This generates high levels of acetyl CoA in hepatocytes.
Normally, much of this acetyl CoA would be metabolized by the TCA cycle. In DKA,
however, the TCA cycle is stalled and acetyl CoA is shunted toward ketone
synthesis. Levels of Ketones may become so high that a life-threatening acidosis
occurs. -The TCA cycle stalls in DKA because oxaloacetate is depleted. OAA is
diverted towards gluconeogenesis even though glucose levels are high. In addition,
fatty acid metabolism generates NADH which favors conversion of OAA to malate,
further decreasing the pool of OAA for the TCA cycle. Thus, the TCA cycle generates
decreased amounts of NADH in the setting of DKA.
Driving pressure across pulmonary system is calculated as: {{c1::Mean pulmonary
artery pressure}} - Left atrial pressure -To calculate mean pulmonary pressure
from the pressure in the pulmonary artery, remember that mean pressure is diastolic
pressure plus 1/3 (systolic - diastolic) -To obtain the pulmonary vascular
resistance (PVR), we can apply the following equation: (delta) P = Flow (cardiac
output) * PVR OR PVR = (delta) P / cardiac output Note: same principles apply for
driving pressure across the total body (systemic circulation) and total peripheral
resistance (TPR)
"Athlete's hearts undergo non-pathological cardiac changes as a result of endurance
exercise (""the athlete's heart""). These changes include: 1. Resting
{{c1::bradycardia::tachycardia/bradycradia}} 2. {{c1::dilated LV cavity::LV cavity
size}} 3. {{c1::Eccentric hypertrophy::type of hypertrophy}}" -Hypertrophy in
atheletic hearts allows for higher cardiac output with exercise compared to non-
athletic hearts.
Differences between von Gierke disease and Cori disease: 1. Age of Dx -
{{c1::Newborn}} vs {{c1::Child}} 2. Fasting hypoglycemia - Severe vs Mild 3.
Hepatomegaly - {{c1::Yes in both cases}} 4. Muscle involvement - Only in {{c1::Cori
disease}}, not in {{c1::von Gierke}} 5. Enzyme - G-6-Phosphatase vs Debranching
eznyme 6. Accumulation - {{c1::Glycogen}} vs {{c1::Limit dextrins}}
Compared to normal liver, which of the following are expected in a patient with
alcoholic fatty liver for hepatocyte's levels of: 1. Malonyl-CoA: {{c1::increased}}
2. Glycerol-3-phosphate: {{c1::increased}} -Metabolism of ethanol generates
high levels of NADH. Recall that NADH is normally high when cells are replace with
energy. Thus, high NADH triggers energy storage by the liver including synthesis of
fatty acids. Fatty acids accumulate leading to alcoholic fatty liver disease.
-Malonyl CoA is produced by the rate-limiting enzyme of fatty acid synthesis,
acetyl-CoA carboxylase. Activity of this enzyme is increased among chronic alcohol
users leading to increase levels of malonyl CoA. -Glycerol is normally metabolized
into glycerol-3-phosphate in the liver for entry into glycolysis. In the setting of
high NADH from alcohol consumption, glycerol metabolism is inhibited. Glycerol-3-
phosphate levels increase leading to production of triglycerides which contribute
to fatty acid buildup in the liver.