Medicine Revision E6.5 (Medicalstudyzone - Com)

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CVS REVISION 1 ----- Active space -----
Aortic Valve Disorder 00:02:49
• Lesser the no. of leaflets → chances of stenosis (Unicuspid > Bicuspid).

• More the no. of leaflets → chances of regurgitation (Quadricuspid).
Aortic Stenosis (AS) : 00:04:43

Etiology :
Degeneration / Calcification on Progresses
Aortic Sclerosis Aortic stenosis
top of Tricuspid / Bicuspid valve
Bicuspid aortic valve (M>F) Tricuspid aortic valve (M>F)

Young patient. Elderly patient > 60 yrs.
• Associated with NOTCH 1 defect (endothelial NO -
synthase defect).
• High chance of aortopathy.
Aortic Sclerosis :
• Major cause of Aortic stenosis.
• Gradient < 20 mmHg.
• Associated with Atherosclerosis.
Note :
• Rheumatic etiology is very rare in Aortic stenosis.
• Acute Rheumatic fever : May develop valvulitis. (MR (M/c) > MR+AR).
15 - 20 yrs later
Rheumatic heart disease : (MS + MR (M/c) > MS + AR > AR + AS).
Hemodynamics :
Normally Aortic valve opening produces no sounds
Sometimes Bicuspid aortic valve can produce ejection clicks.
Ventricular systole in aortic stenosis :
Degeneration and Calcification → Incomplete aortic valve opening → Creates a
gradient between LV and Aorta (Gradient > 40 mmHg).
Gradient ∝ Severity of the disease.
Medicine Revision • v1.0 • Marrow 6.5 • 2023

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2 01 Medicine
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----- Active space -----

40/4/1 rule : Seen in severe aortic stenosis.
• Mean Transvalvular pressure gradient > 40 mm Hg.
• Peak flow velocity across the valve > 4 m/s.
• Aortic valve surface area < 1 cm2.
Compensation :
• Concentric LV Hypertrophy at the expense of cavity size To maintain
• Left Ventricular mass Cardiac output
Symptoms :
• Mild / Moderate AS → Usually asymptomatic.
• Severe AS → Symptomatic.
• Very severe AS → LV Failure.
ASD 5/3/2 rule : Chances of survival if surgery not done,

• Within 5 years from the onset of Angina (1st symptom) → Unlikely to survive.
• Within 3 years from onset of syncope → Unlikely to survive.
• Within 2 years from onset of dyspnea → Unlikely to survive.
Note : Aortic stenosis → Pressure overload condition (Palpitation not

seen as it is seen in volume overload conditions).
Associated conditions :
1. Atrial Fibrillation (AF) : Fatal in patients with Aortic stenosis (Cardiac output is
severely compromised).
2. Systemic Hypertension : Can mask Aortic stenosis.
Uncontrolled Hypertension → Aortic pressure → Falsely low pressure
gradient. Hence, Strict control of blood pressure is needed.
Investigations :
• Trans Thoracic Echocardiogram (IOC) : 40/4/1 rule.
• Angiogram : Detect atherosclerotic changes in Coronaries.
• CT Aortogram in bicuspid valve patients : To r/o Aortopathy.
• Dobutamine Stress ECHO : Differentiate b/w Mild AS and Very severe AS.
Note : In very severe AS, LV fails → Low Flow Low gradient AS.

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Clinical findings : ----- Active space -----
Components Findings
Pulse • Slow rising pulse.
• Severe AS → Pulsus tardus.
• Very severe AS → Pulsus parvus et tardus.
BP • Associated with Left ventricular hypertrophy.
• High BP → Mask aortic stenosis.
JVP • Normal.
• May be elevated in very terminal stages only.
Apex Heaving apex : High amplitude sustained apex.
Heart sound • S1 : Normal.
• S2 : a. Loud S2 : Bicuspid.
b. Soft S2 : Elderly.
c. Reverse/Paradoxical split, P2-A2: Severe AS
• S3 : (+) → Very severe AS (LV Systolic failure).
• S4 : (+) → Seen only in Aortic Stenosis.
Murmurs Mixed frequency murmurs : Harsh Ejection systolic
murmur + Late systolic accentuation → Best heard in
Aortic area and sitting position.
a. Low frequency : Radiated to the carotid.
b. High frequency (soft blowing musical) →
Radiated to the apex (Gallavardin phenomenon).
Note : Production of heart sounds.

• S3 : Normal/less than normal filling of non compliant dilated ventricle OR
of hypercompliant ventricle (Physiological S3).
• S4 : Healthy atria across a non stenosed valve contract vigorously in sinus
rhythm into a hypertrophic non-compliant non-dilated ventricle.
Treatment :
Symptomatic
Aortic Valve
Severe AS Gradient > 50mmHg Replacement (AVR).
Asymptomatic
Observation &
Gradient < 50mmHg
follow-up.
• If bioprosthetic valve is used → No anticoagulation needed .
• Recent update : TAVI → Trans catheter aortic Valve Implantation.

4 01 Medicine

Aortic Regurgitation (AR) : 00:34:34
Acute aortic regurgitation :

Seen in :
• Aortic Dissection.
• Infective Endocarditis.
• Rupture of sinus of Valsalva.
Presentation :
• Acute Pulmonary edema ± Cardiogenic Shock.
• Acute AR + Chest pain → Suspect Aortic Dissection.
• Acute AR + Right heart failure → Suspect Rupture of Sinus of Valsalva.
Management :
• NTG/ Nitroprusside : Dilate the aorta.
• Aortic Valve replacement : Definitive Management.
Chronic aortic Regurgitation :

Etiology :
Valve Leaflet issues Root issues

• Rheumatic cause. • Syphilis.
• Quadricuspid valve. • Marfan syndrome.
• Takayasu arteritis. • Ehlers Danlos syndrome.
• Ankylosing spondylitis. • Takayasu arteritis.
• IgG4 related disease ( Large vessel
vasculitis).
• Behcet’s disease Variable vessel
• Cogan’s disease vasculitis
Note :
• Takayasu arteritis → Involve both root and the leaflets.
• Cogan’s disease → Interstitial keratitis + Aortitis + Sensorineural hearing
loss.
Hemodynamics :
1. Diastolic pressure gradient :
• Normal ventricular diastole :
Aorta diastolic pressure = 80 mm Hg
High gradient present.
LV diastolic pressure = 10 mm Hg
Competent aortic valve → No back leak despite High pressure gradient.
• Ventricular diastole in AR :
Aortic valve incompetence → Blood flow from Aorta to LV.
2. Vasodilatation : Pressure in aorta → Pressure gradient → Less Leak. ----- Active space -----
• Exercise → Lead to Vasodilation → Make patient better.
• NTG/ Nitroprusside → Used in Rx of Acute Aortic Regurgitation.
3. Systemic HTN : Pressure in aorta → Pressure gradient → More leak.
4. Nocturnal angina. : Bradycardia at night → filling → Diastole prolonged →
More blood leak (Blood stolen from the Coronaries).
Compensation :
• Eccentric Hypertrophy with dilatation.
• Ejection fraction (EF) : Normal to .
• LV End Diastolic Pressure (LVEDP) : Normal.
• End Systolic Volume (ESV) : Normal.
Presentation :
• Mild/ Moderate AR → Occasional palpitation.
• Severe AR → Dyspnea, S3.
Clinical Findings :
Components Findings
Pulse • Collapsing pulse (High volume pulse).
• Pulsus Bisferiens.
BP Wide Pulse pressure (Hills sign).
JVP • Normal.
• May be elevated in very terminal stages only.
Apex Hyperdynamic (Down and out).
Heart sound • Soft S1 : Premature closure.

• S2 : a. Loud S2 : Root causes.
b. Soft S2 : Leaflet causes.
c. Delayed A2. Sometimes P2-A2 also seen.
• S3 : (+) → LV Systolic failure.
• S4 : Absent.
Murmurs End Diastolic murmur : High pitched, soft blowing murmur.
• Decrescendo murmur : Gradient → Murmur .
• Austin Flint murmur → Displacement of anterior mitral leaflet (Asso-
ciated low pitched murmur).
• Cole cecil murmur → Murmur radiating to the axilla.
Treatment :
• Symptomatic Severe AR : Aortic Valve Replacement.
• Asymptomatic Severe AR : 55/50 Rule.
Ejection fraction < 55 %
LV End Systolic Diameter > 50 mm Aortic Valve replacement

6 01 Medicine

Mitral Valve Disorder 00:52:19
Mitral Stenosis (MS) :

Etiology :
Rheumatic Heart disease → Commissural fusion (Fish mouth abnormality).
Rx : Percutaneous balloon mitral valvotomy/ commissurotomy.
Acute rheumatic fever 15 - 20 yrs Rheumatic heart disease
(with valvulitis) (MS+MR > MS+AR)
Hemodynamics :
During diastole → Incomplete valve opening → LAP.
• Mild / moderate case (No Symptoms) : LAP not transmitted to the
pulmonary vein.
• Severe cases : PCWP → Pulmonary hypertension → Hypertensive Tri-
cuspid Regurgitation (TR).
Classification of Mitral Stenosis : On basis of Valve Surface area.

• Severe MS ( <1.5 cm2) : Asymptomatic or symptomatic.
• Very severe MS (<1 cm2).
• Progressive MS (>1.5 cm2).
Symptoms :
• Mild MS : Asymptomatic.
• Moderate MS : Dyspnea on exertion (1st symptom).
• Severe MS : Dyspnea at rest + Pulmonary Hypertension (RVH + TR).
• Very severe MS : Left Ventricular Failure.
Other symptoms :
• Hemoptysis.
• Ortner’s Syndrome : compression of the Recurrent Laryngeal nerve.
• Hoarseness of voice.
• Dysphagia.

Clinical Findings : ----- Active space -----
Components Findings
Pulse Normal.
BP Normal.
JVP Elevated→ Due to RVH.
Apex Tapping apex : Loud S1.
Heart sound • S1 : Loud S1→ Depends on
a. Velocity of closure.
b. Position of leaflets at the end of diastole.
c. Timing (Delayed closure→ Loud sound).
• S2 : Loud palpable P2.
Note : A2-P2 widening→ seen in P. HTN + RV failure.
• Opening snap : seen in Organic MS ( LAP).
Note : Higher LAP → Opening snap occurs earlier.
• S3, S4 : Not heard.
Murmurs Low pitched Mid Diastolic murmur + Pre systolic accentuation.
Note : Presystolic accentuation → Lost in AF.
.
Severity of the Mitral stenosis depends on :
• Long duration of the murmur.
• Short S2-OS gap.
Treatment :
• Control tachycardia→ Beta blockers/ Verapamil/ Diltiazem.
• Anticoagulation→ Oral Vitamin K Antagonist (Risk of Embolization / LA clots).
• Percutaneous Mitral Balloon Valvulotomy/commissurotomy → If it fails,
Mitral Valve Replacement.
• Calcific MS or Associated moderate to severe MR + LA Clot → Mitral valve
Replacement.
Note : Mandatory to do Transesophageal ECHO → To detect LA Clot.
Mitral Regurgitation (MR) : 01:10:35
Acute Mitral Regurgitation :

• Papillary muscle dysfunction /Papillary muscle rupture .
• Inferior Wall MI→ RCA involvement → Posteromedial Papillary muscle
rupture.
8 01 Medicine

Chronic Mitral Regurgitation :
Primary MR Secondary MR
Problem with leaflets. Due to Annular Dilatation
Causes :
• Rheumatic heart disease LV Dysfunction
(MS + MR) : M/c in
Annular Dilatation
developing countries.
MR Begets MR
• Mitral valve prolapse : m.c in 2 Mitral Regurgitation
�
developed countries.
• SLE/ RA LV Remodeling
Hemodynamics :
• Issue in LV Systole.
• When Afterload → Blood Moves from Left ventricle to left atria.
Factors improving and worsening MR :

• Nitrates/ NTG/ Nitroprusside : pressure on the aortic site (Some amount
of blood flow into the aorta).
• S. Hypertension in MR : pressure on the aortic site → More resistance
(Blood moves to the Left atria).
Compensation :
Eccentric Hypertrophy with dilatation of the Left Ventricle.
Mild to Moderate MR Severe/Decompensated MR

Presentation Asymptomatic + On and off LV failure (+) →
palpitation. Predominantly dyspnea.
LV End Diastolic Pressure Normal.
LV End Systolic Volume Normal.
Ejection fraction Normal or Normal to

Clinical Findings : ----- Active space -----
Components Findings
Pulse • Pseudo collapsing pulse.
• LV failure : Pulsus alternans/ pulsus dicroticus.
BP Normal.
JVP Normal.
Apex Hyperdynamic apex : Displaced down and out.
Heart sound • S1 : Soft S1
a. Poor coaptation of the valve leaflets.
b. dp/dt of isovolumetric contraction not good.
• S2 : Early A2 and Normal P2→ Wide Split S2.
• S3 : Heard even without failure.
• S4 : Not heard.
Murmurs Pan Systolic murmur : High pitched , seen in apex, Soft blowing murmur,
Radiates to the axilla.
Note :
• Myxomatous Degeneration : MVP ± MR.
• MVP : can produce Click + Murmur on Hyperdynamic auscultation.
• LV Size → Chordae stretch → Prolapse (Click will move closer to S1 → Long
duration murmurs).
• Valsalva and Standing :
a. HCM → Intensity of murmur
b. MVP → Duration of murmur
Treatment :
Surgical repair is tried first → If it fails → Replacement.
Indications of surgical repair :
• Symptomatic cases.
• Asymptomatic patient : 60/40 rule.
a. Ejection fraction : ≤ 60%.
b. LV End systolic Diameter : ≥ 40 mm.

10 02 Medicine
----- Active space ----- CVS REVISION-2
Physiology of Pulse 00:00:11
Wave Coincides with

Percussion wave S1
P wave Peak
Tidal wave Aortic recoil
Dicrotic notch S2
Dicrotic wave Peripheral
(Reflected wave) resistance (PR)
Applied aspect :
Central/Augmented Systolic BP is Best indicator of Target Organ Damage (TOD).
NOTE :
• Pulse apex deficit : Atrial Fibrillation (A-fib).
• Radio femoral delay : Coarctation of aorta.
Abnormalities in Pulse 00:04:30
Rate abnormalities :
Relative Bradycardia : For every 1˚F → in HR by 1o bpm. If in HR is < than
this, then it’s said to be relative bradycardia.
Causes : Infectious : Typhoid, Q-fever, Legionnaires’, Brucellosis.
Non infectious : Lymphoma, Drug fever.
Note : Leptospirosis, Dengue & malaria are very rare causes.
Rhythm abnormalities :
Irregularly irregular : A-fib.
Regularly Irregular : VPC (Ventricular Premature Complex).
Volume abnormalities :
High volume ( Stroke volume) Low volume ( Stroke volume)
Collapsing pulse AR Hypokinetic pulse LV dysunction
Pseudo-collapsing pulse MR Pulsus tardus Severe AS
- Pulsus parvus et tardus Very severe AS

Contour abnormalities : ----- Active space -----
1. Pulsus bisferiens 2. Pulsus dicroticus

Systolic peak + Prominent dicrotic peak.
Seen in LV systolic failure.
HCM d/t SAM. Severe AR ± Mild AS

3. Pulsus alternans 4. Pulsus bigemini
Regular alternate high & low volume Irregular alternate high & low volume
pulse. pulse.
Seen in LV systolic failure. Seen in VPC.
HCM : Hypertrophic Cardiomyopathy; SAM : Systolic Ant. Motion of mitral valve; VPC : Ventricular Premature Complex
Note : Brockenbrough sign : In HCM → Pulse volume after post VPC pause d/t SAM.
Variations in pulse with respiration :
Reverse Pulsus
Pulsus Normalis Aggregans/ Pulsus paradoxus
paradoxus
SBP falls by > 10 mmHg with inspiration. SBP with inspiration
Seen in : Seen in :
• Cardiac Tamponade (M/c) • IPPV.
• I/3rd cases of CCP. • HCM.
• Hyper inflated lung.
• SVC Obstruction.
• Pulmonary Embolism.
Note : very rare in Restrictive cardiomyopathy.
CCP : Chronic Constrictive Pericarditis; IPPV : Intermittent Positive pressure ventillation
Jugular venous pulse 00:13:53
Normal JVP waveform :
waveform Corresponds to
a wave RA contraction. Measures active filling of diastole (30% of filling).
x descent Atrial relaxation
Upward bulge of Tricuspid valve into atrium.
c wave
Coincides with S1.
v wave Atrial filling. Coincides with S2
Emptying of Atria.
y descent
Measures passive filling of diastole (70% of filling)

12 02 Medicine

JVP abnormalities :
Abnormality Conditions
Prominent a waves Pulm HTN, Rt. atrial thrombus/mass, TS, RVH.
Cannon a waves Complete AV block, AVNRT junctional rhythm, Vent. tachycardia.
Absent a waves Atrial fibrillation
Absent x descent Severe TR, RV failure.
Prominent/Rapid X
Cardiac tamponade (CT), Chr. constrictive pericarditis (CCP)
descent
Dominant v waves TR, ASD, Vena caval pressure.
Prolonged y descent Tricuspid stenosis (TS)
Prominent y descent CCP, isolated severe TR, RCM
Absent y descent Cardiac tamponade.
Note :
Kussmaul’s Sign :
• Inspiratory rise in JVP.
• Seen in : CCP, Restrictive cardiomyopathy, Right ventricular MI, TS.
• Not seen in cardiac tamponade.
Abd. Jugular reflex (>3cm or >15 s) : Marker of impending Right Heart Failure.
Heart sounds 00:34:36
Mixed murmur Low pitched murmurs Low pitched heart sounds

1. Aortic stenosis : 1. MS 1. S3
Carotids (low pitch) 2. TS 2. S4
Apex of heart (High pitch) 3. Austin flint murmur 3. Tumor plop
Rest all are high pitched sounds.
S1 & S2 :
S1 S2 (A2-P2)
• Occurs just prior to isovolumetric contraction (IVC). • A2 -P2 closure interval is called
• Due to coaptation of mitral & tricuspid valves Hangout Interval (HI).
• Normally A2 occurs prior to P2.
1. Soft S1 1. Loud A2 :
• MR. • Bicuspid aortic valve producing
• Good filling of heart. AS.
• AR. • Root pathologies in AR.
2. Loud S1 2. Soft A2 :
• MS. • Elderly AS.
• Valve pathologies in AR.
3. Loud P2 : Pulmonary HTN.
4. Soft P2 : Pulmonary stenosis.
Split S2 : ----- Active space -----
Wide variable split Wide fixed split Paradoxical split

Early A2 or Split fails to move P2 first followed by A2.
delayed P2. with respiration. Commonly accompanied by loud P2.
Cause : Causes : Causes :
• MR. • RV failure. • AR.
• ASD. • AS.
S3 :
• S3 in AS/AR is always with heart failure.
• S3 in MR can be heard with or without heart failure.
• Never heard in MS.
S4 : Seen only in AS.

Added diastolic sounds :
Mnemonic : OP Time 3-4.
1. Early diastolic sound :
• Opening snap (High pitch) :
a. Snapping open of mitral valve.
b. S2-OS gap shortens with severity of MS/↑ left atrial pressure.
• Pericardial knock (High pitch).
• Tumor plop (Low pitch).
2. Middiastolic sounds : S3 (Low pitch).
3. Late diastolic sound : S4 (Low pitch).
Added systolic sounds :

1. Ejection clicks :
• Aortic ejection click : Seen in bicuspid aortic valve.
• Pulmonary ejection click.
Note : All right sided heart sounds ↑ with respiration → Carvallo’s sign, except
pulmonary ejection click.
2. Non ejection clicks :
• Seen in mitral valve prolapse.

14 03 Medicine
----- Active space ----- CVS REVISION 3
Heart Failure 00:00:27
Structural or functional impairment of the ventricle to pump out/fill itself with blood.
Classification :
• HF with reduced EF (HFrEF) (< 40%) : Guideline based management.
• HF with preserved EF (HFpEF) (> 50%) : Comorbidity based management.
• HF with mid range EF (HFmEF) (40-50%).
Staging of HF :
• A : Only risk factors present. Best prognosis.
• B : Risk factors + Structural abnormalities. M/c cause of mortality :
• C : Present or prior symptoms. Sudden cardiac death
• D : Advanced HF (Mortality cause is pump failure).
NYHA grading of symptoms : For angina, palpitation & dyspnea.
Class 1 Symptoms at exertion, no limitation.
Class 2 Mild symptoms at ordinary physical activity, slight limitation.
Class 3 Symptoms at less than ordinary physical activity, marked limitation.
Class 4 Symptoms at rest, severe limitation.
Symptoms :
LV systolic failure LV end diastolic pressure Increase in RVEDP
• Cachexia (TNFα). • ↑ LAP → ↑ PCWP → • Abdomino jugular reflex
• ↓ Urine output (Cardiorenal Dyspnea → Orthopnea → (AJR) → Impending RV
syndrome). PND → Acute pulmonary failure.
• Altered sensorium. edema. • JVP.
• Cold extremities. • O/E : Rales & S4. • Ascites.
• Narrow pulse pressure. • Hepatomegaly.
• O/E : S3 & cardiomegaly. • Edema.
Framingham criteria :
Major symptoms :
1. Dyspnea/orthopnea/PND. 5. JVP.
2. Acute pulmonary edema. 6. AJR.
3. Rales. 7. Cardiomegaly.
4. S3.
Note : No ascites, edema, hepatomegaly in major Framingham criteria.
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1. Dyspnea : ----- Active space -----

Types of dyspnea :
Bendopnea Trepopnea
• Seen in advanced HF (left & right HF). • Preferred to lie on right side.
• A/w ↑ JVP & PCWP. • Pleural effusion more on right side.
• Along with dyspnea, crepitations (Fine gravitational creps a/w cold
extremities) + S4 can be seen.
2. Angina : D/t ↑ LV mass or LVOT obstruction (not a mandatory symptom of HF).
3. Palpitations : D/t cardiomegaly.
4. Syncope : D/t LVOT obstruction.
Diagnosis :
ECG :
Other symptoms :
• Low voltage in limb leads.
• Sinus tachycardia → ↑ mortality. • High voltage in chest leads.
• JVP (RHF) : ≥ 3 cm elevated from sternal angle. • Poor R wave progression.
• AJR (Impending RHF). Echo : To evaluate ejection fraction.
• Edema, Ascites. Cardiac MRI : Gold standard for EF.
Decompensation :
Factors that precipitate acute HF in a patient with underlying HFrEF/HFpEF :
• Patient related (Non compliant/diet). • Arrhythmias (A. Fib).
• Infection related (Infective endocarditis). • MI.
• Anemia. • NSAIDs & beta blockers.
Mx of HFrEF :
1. Block SNS ( decrease HR & FOC) 2. Block RAAS
• β blockers. • ARNI (Angiotensin II receptor
• Metoprolol/carvedilol/bisoprolol. blocker + Neprilysin inhibitor).
• Bisoprolol (β1 selective) : 1.25 mg - 10 mg. eg. Valsartan + Sacubitril.
• Started at lowest dose. • ARNI > ACE inhibitors > ARBs.
• Patient should not have edema. 4. SGLT 2 antagonist
3. Mineralocorticoid receptor antagonist (MRA)
• Dapagliflozin/empagliflozin.
• Spironolactone/eplerenone/finrenone.
• Produce natriuresis & diuresis
• Side effects : Hyperkalemia,gynecomastia.
without tachycardia.
FOC : Force of contraction.
Mortality benefit : β blockers > ARNI > MRA > Hydralazine + nitrate.
Note : Hydralazine + nitrate is used in renal failure patients with heart failure.

16 03 Medicine

Other drugs :
Diuretics : For symptomatic relief.
Ivabradine :
• Used only if HR > 70 bpm & patient on maximum dosage of β blockers.
• MOA : Inhibits funny currents (Na+).
• S/E : Visual field abnormalities.
No role :
• ACE inhibitor + Neprilysin inhibitor : Omapatrilat.
• Digoxin.
Dysfunction of ventricles 00:29:29
Systolic dysfunction Diastolic dysfunction

Pumping defect Filling defect
Left sided issues Right sided issues (RV > LV)
Always followed by diastolic dysfunction Normal systole possible.
Diastolic dysfunction with normal systole.
Constrictive Restrictive (more severe)

Chronic constrictive pericarditis Restrictive cardiomyopathy
Diastolic dysfunction : ↑ RVEDP → ↑ RAP → Transmitted to SVC, IVC → Right

sided HF (Ascites precox, edema, JVP & hepatomegaly). It has a chronic course.
Acute pericarditis (D/d for MI)

• Clinical features : Elevated ST + chest pain.
• ECG : Global ST elevation (Concave) except lead V1, no reciprocal changes,
PR depression.
• Cause : Post viral (Coxsackie virus), uremia.
Multiple relapses → Rigid, calcific, thickened pericardium with adhesions (Rock
like pericardium) → Chronic constrictive pericarditis.

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Chronic Constrictive Pericarditis (CCP) Restrictive cardiomyopathy ----- Active space -----
Causes : Causes :
• Multiple relapses of acute pericar- • Intercellular accumulation :
ditis. Amyloidosis (Most important cause).
• Post viral > TB. • Intracellular accumulation : Iron
Features : Chronic RHF symptoms. (Hemochromatosis), glycosphingolipids
• Cachexic + malnourished (TB) with (Fabry’s disease) and glycogen
ascites, edema, hepatomegaly. (Pompe’s disease).
• Transmyocardial filling pressure • No accumulation : DM, scleroderma.
= Intracavitary pressure - Intra Features :
pericardial pressure. It is reduced • Stiff hypertrophic, non compliant, non
in CCP. dilated ventricle.
Diastolic dysfunction → Slow, chronic RHF symptoms.
Normal systole. Normal chamber size.
ECG : Low voltage complexes.
Kussmaul sign (↑ in JVP on inspiration) : Fall in intrathoracic pressure is not
transmitted to heart chambers d/t pericardial issue (normally JVP falls with
inspiration).
JVP : JVP :
• Sharp prominent rapid x descent. • Holodiastolic restriction → No y
• Sharp prominent rapid y descent : descent, no square root sign.
Frederichs sign. • Atrial relaxation not adequate → x
Ventricular pressures during diastole descent not prominent.
: Fall → rise → abrupt halt : Square
root sign.
Elevation & equalisation of diastolic Elevation & equalisation of diastolic
pressures after 1/3 of diastole.
rd
pressures not seen.
Pulsus paradoxus seen in 1/3 of rd
Pulsus paradoxus absent.
patients.
Pericardial knock can be heard. S3 can be heard.
Broadbent sign : Indrawing of 11th & No pericardial knock.
12th ribs (systolic retraction of apex).
Ix : MRI (IOC). Ix : Echo.
Rx : Pericardiectomy. Rx : Medical management
(Manage cardiomyopathy/HF).

18 03 Medicine

Cardiac tamponade 00:57:25
Cause : Acute post traumatic event.

Features :
• Acute rise in intrapericardial pressure.
• Presentation : Obstructive shock (Hypotension + shock + disproportionate
dyspnea + tachycardia).
• Beck’s Triad : Hypotension + muffled heart sounds + ↑JVP.
• JVP : Holodiastolic restriction → Absent y descent, no square root sign, no
pericardial knock.
Systolic phase of venous return (Coupled constraint) : X descent is
prominent.
• Holodiastolic elevation & equalisation of diastolic pressures present.
• Transmission of pressure to cardiac chambers can be seen → ↓JVP on
inspiration → No Kussmaul sign.
• Small chambers (as compressed from all sides).
• Pulsus paradoxus (Fall of SBP > 10 mm Hg on inspiration).
ECG : Low voltage complexes (Electrical alternans).
Rx : Emergency pericardiocentesis.

CVS REVISION 4 ----- Active space -----
Cardiomyopathy :
Myocardial disease in which heart is structurally & functionally abnormal in the
absence of valvular heart disease, congenital heart disease, CAD & HTN.
Classification of cardiomyopathy :
1. Dilated cardiomyopathy (DCM).
2. Hypertrophic cardiomyopathy (HCM).
3. Restrictive cardiomyopathy (RCM).
4. Unclassified.
Dilated cardiomyopathy 00:00:12
Autosomal dominant.
Thin walled dilated LV → Has poor contractility.
Symptoms :
1. Systolic heart failure symptoms :
• Cachectic.
• Cold extremeties.
• Altered sensorium.
• Renal failure symptoms.
• Narrow pulse pressure.
• S3 +ve.
2. Diastolic failure symptoms : Dyspnea.
3. Right sided failure symptoms : JVP, ascites, edema, hepatomegaly.
Causes :
1. 30% genetic : Truncated variant (Tv) Titin mutation (M/c) > myh7 mutation.
2. Peripartum cardiomyopathy :
• Best prognosis.
• D/t anti-angiogenic factors : SFLT 1.
• Risk factors :
a. ↑ Age at pregnancy.
b. HTN with pregnancy.
c. Multiple pregnancy.

20 04 Medicine

3. Alcohol induced cardiomyopathy :
• Good prognosis (Reversible).
• Patients with ACE polymorphism are at ↑ed risk.
• Precipitated by : Selenium deficiency (Keshan’s disease), thiamine
deficiency & magnesium deficiency.
4. Drug induced cardiomyopathy :
• Worst prognosis.
• Attributed to high dose Anthracycline.
5. Autoimmune : Sarcoidosis & hemochromatosis (DCM > RCM).
6. Endocrine : Pheochromocytoma, thyrotoxicosis & acromegaly.
7. Myocarditis :
• Acute post inflammatory DCM which can occur along with the infection/post
infection period.
• Good prognosis.
• M/c cause : HHV 6 > Chagas disease.
Investigations :
1. ECG findings : Triad
a. Low voltage in limb leads.
b. High voltage in chest leads.
c. Poor ‘R’ wave progression.
2. Echo : Global LV hypokinesia.
3. MRI :
• Gold standard for ejection fraction.
• To look for ischemia vs infract.
4. Angiography.
Restrictive cardiomyopathy 00:14:30
Seen in amyloidosis of heart.

Bad prognosis.
Types of amyloidosis :
1. Primary amyloidosis
2. Secondary amyloidosis : No cardiac involvement.
3. Transthyretin induced
a. Senile systemic amyloidosis (Wild type) → Seen in elderly with carpal
tunnel syndrome.
b. Familial amyloid polyneuropathy (Mutant type) → Severe ANS
symptoms + cardiac symptoms seen.
Features : ----- Active space -----

• Biatrial enlargement.
• Biventricular hypertrophy.
• Interatrial septal thickening.
• Low voltage complexes.
Investigations :
• IOC : Cardiac MRI (Glittering of myocardium).
• ECG : Pseudo infarct pattern (Infarct pattern on ECG with normal echo).
Unclassified cardiomyopathy 00:17:02
Takotsubo cardiomyopathy :
Aka stress induced cardiomyopathy/neurogenic myocardial stunning/transient
apical ballooning.
M/c : Middle aged females.
Cause : Sympathetic overactivity.
Presents with : ACS like presentation.
Investigations :
• ECG : ST elevation.
• Trop I elevated (Not as much as in ACS).
• NT Pro BNP is high.
• On angiography :
a. Normal coronary arteries.
b. Base is hypercontractile.
c. Bulging apex.
Prognosis :
• Short term complications same as MI.
• No long term complications.
Hypertrophic cardiomyopathy 00:20:12
M/c genetic cardiovascular disease.

Autosomal dominant.
Myosin heavy chain mutation > myosin binding protein C mutation.
Males = females (Females have poorer prognosis).

22 04 Medicine

Course of HCM :
• 95% -99% → Stable course.
• 1% - 5% → Develop complications like :
1. Progressive heart failure.
2. Arrhythmias (Atrial fibrillation).
3. Sudden cardiac death.
Note : Pompe’s disease mimics HCM.
Features of hypertrophy :
• LV thickness ≥15 mm with no cause & no dilatation .
• Asymmetric hypertrophy : Only septum + anterior wall hypertrophies.
• Inappropriate hypertrophy : Absence of any factor causing ↑ in afterload.
• Concentric LVH → ↓ Cavity size → ↑ LVEDP.
Left ventricular outflow tract (LVOT) obstruction :
• First 1/3rd : Fixed obstruction.
• Second 1/3rd : No obstruction.
• In last 1/3rd : Dynamic obstruction.
Pathophysiology :
1. Diastolic dysfunction with normal systolic function :
Concentric LVH → ↓Cavity size → ↑ LVEDP → ↑LAP → ↑PcWP → Dyspnea
(M/c symptom). A-fib
2. Systolic motion of anterior mitral leaflet (SAM) :
• Asymmetrical septal hypertrophy → LVOT obstruction → ↑ Velocity of
blood across the obstruction → Low pressure zones across the outflow
tract → Anterior mitral leaflet sucked into septum (Occurs in mid to late
systole).
• SAM will lead to 2˚ MR.
3. Angina (2nd m/c symptom) with normal coronaries : D/t microvascular
dysfunction.
Factors influencing obstruction :

• ↑ Preload →↓Gradient ↓ LVOT obstruction
• ↑ Afterload →↓Gradient
• ↑ Force of contraction →↑ Gradient → ↑ LVOT obstruction.
Clinical features :
• Most patients are asymptomatic.
• Atrial fibrillation.
• Angina, syncope, & dyspnea (Features of LVOT obstruction).
Findings : ----- Active space -----

• Pulse : Pulses bisferiens ( In HCM p wave > t wave).
• JVP : Normal
• Apex : Double /triple apex (d/t SAM).
• S1 : Normal
• S2 : Normal/reverse split.
• S3 : May be heard.
• S4 : May be heard.
• Murmurs :
a. Lower left sternal border : Ejection systolic murmur (D/t SAM).
b. Apex : Pan systolic murmur (D/t 2˚ MR).
• Biopsy : Myofibre disarray.
Dynamic auscultation :
All the murmurs in cardiology ↓se with valsalva or standing except :
1. MVP : ↑Duration of murmur.
2. HCM : ↑ Intensity of murmur.
To differentiate b/w MVP & HCM
Post VPC pulse volume
Increased Decreased (Brocken brough sign)
MVP HCM
Rx :
• DOC : β blockers (Propranolol).
• 2nd DOC : Verapamil > diltiazem.
• If no adequate response : Add Disopyramide (Class 1a).
Side effects of disopyramide :
a. QT prolongation.
b. Anticholinergic side effects.
c. Reduce ejection fraction by 5% - 10%.
• If medical Mx fails → Surgery : Septal myomectomy.
• If family h/o sudden cardiac death or spontaneous sustained VT → Im-
plantable cardioverter-defibrillator (ICD).

24 05 Medicine
----- Active space ----- CVS REVISION 5
Myocardial Infarction (MI) 00:00:20
Coronary circulation :
Dominance of coronary circulation :

Based on origin of posterior descending
artery (which supplies Inferior wall) :
• Right dominant (80%) : If arises
from right coronary artery (RCA).
• Left dominant (20%) : If arises
from left circumflex artery (LCX).
Origin of Acute marginal artery (AMA)

demarcates RCA into Proximal & Distal
segments.
Acute marginal art. supplies RV free
wall. Occlusion of AMA → RVMI.
Inferior wall MI (IWMI), Right ventricular MI (RVMI), Posterior wall MI (PWMI) :
Inferior Wall MI Can occur d/t Occlusion of Proximal RCA, Distal RCA or LCx.
Involvement of Post. Descending artery : IWMI ± PWMI.
In a right dominant person :

• Proximal RCA occlusion : RvMI + IWMI ± PWMI.
• Distal RCA occlusion : IWMI ± PWMI.
Posterior wall can be supplied by obtuse marginal artery (branch of LCx), hence
can be spared in RCA occlusion.
In a left dominant person :

• LCX occlusion : Definitely IWMI + PWMI.
• Proximal RCA occlusion : Only RvMI.
• Distal RCA occlusion : No MI.

IWMI & RVMI Features : ----- Active space -----

• SA nodal branch → Bradycardia.
• Clear lungs, ↑ JVP, hypotension in RVMI.
• Posteromedial papillary muscle rupture → 20 MR.
• ST elevation : II, III, aVF (Inferior wall).
Identifying site of occlusion in IWMI :

ST ↑ ST ↓
RCA Lead III > II aVL > aVR
LCX Lead II > III aVR > aVL
RVMI : V1 shows ST ↑ (or) flat/depressed ST which is discordant with V2, V3, V4.
Findings :
1. ST elevation in leads II, III, aVF. IWMI
2. Reciprocal changes in V2,V3,V4.
3. ST ↑ in III > II
RVMI with
& ST ↓ in aVL > aVR proximal RCA
4. ST in V1 discordant to V2, V3.
Diagnosis : IWMI + RVMI with proximal RCA occlusion.
Anterior wall MI (AWMI) : 00:09:30
Left coronary artery (LCA) branches into : Left anterior descending (LAD) & LCX.
Blood supply Area Corresponding leads

LAD (D1) or LCX High lateral wall I, aVL
LAD (S1) Septum V1 >> V2
LAD (D2) Anterior wall V2, V3, V4
LAD (D3) or LCX Lateral wall V5, V6
Findings :
1. ST elevation in V2, V3, V4.
2. Reciprocal changes in leads II, III, aVF.
3. ST ↑ in V1 → Above S1.
4. ST ↑ in I & aVL → Above D1.
Diagnosis : Extensive antero high lateral MI.

26 05 Medicine

Acute coronary syndrome Mx algorithm :
Golden hour : 6 hours.
First medical contact
Diagnosis (preferably <10 mins)
24 hour PCI capable center Centre not capable for PCI
PCI within 60 mins

Shift for PCI, if PCI Can’t shift within 120 mins
possible in < 120 mins
Thrombolysis (Tenecteplase
0.5 mg/kg as bolus)
Shift to PCI capable center

Repeat ECG within 60-90 minutes
Resolution No resolution
Plan PCI within 2 to 24 hours Rescue PCI
Note : Pharmacoinvasive approach : PCI within 2 - 24 hours following successful
thrombolysis.
Medical management after initial stabilisation :
• Aspirin 300 mg.
• Clopidogrel 300 mg.
• For a patient planned with PCI : Ticagrelor/Prasugrel & Clopidogrel 600 mg.
• Statin 20-40 mg.
• Anticoagulation 30 mg s/c (Before PCI).
• ACE inhibitors & β blockers started within 24 hours.
• Life long aspirin & statin.
• 2nd antiplatelet for 1 year.
Arrhythmias 00:19:32
Narrow QRS tachycardia Slight wide QRS tachycardia Wide QRS tachycardia
QRS < 0.12 s QRS 0.12-0.16 s QRS > 0.16 s
Origin : Above bundle of His. Origin : Above bundle of His. Origin : Ventricles.
• Atria : Atrial tachycardia (focal/ But, conducted with a • Ventricular tachycardia.
multifocal). bundle branch block
• AV node : Junctional tachycardia.
• AVNRT, AVRT, AF, atrial flutter.
Note : Paroxysmal atrial tachycardia with AV block (d/t Digoxin).

Narrow QRS tachycardia : ----- Active space -----
Regular RR interval Irregular RR interval

AVNRT : • Atrial fibrillation.
• No P waves. • Multifocal atrial tachycardia.
• P wave just outside QRS, with short RP & long
PR interval (only in 1/3rd patients).
AVRT :
• P wave just outside QRS, with short RP (> 80 to
100 ms) & long PR interval.
Focal atrial tachycardia :
• Long RP, short PR interval with morphologically
abnormal P waves.
M/c narrow QRS tachycardia : Sinus tachycardia.

Findings :
1. Narrow QRS tachycardia
(Rate > 150/min).
2. P wave just before QRS
complex → Long RP & short
PR.
Diagnosis : Atrial tachycardia.
Findings :
1. Narrow QRS tachycardia.
2. P wave just after T wave.
Diagnosis : Atrial tachycardia.
Management :
1. AVNRT :
• Adenosine.
• In COPD → Verapamil → no response → Metoprolol. Defibrillation done in :
• Pulseless VT.
• Synchronised DC cardioversion.
• Ventricular fibrillation.
2. Atrial tachycardia : Verapamil, β blockers. • Polymorphic VT.
Multifocal atrial tachycardia :

• 3 different morphologically abnormal P waves can be identified.
• Can be precipitated by Theophylline

28 05 Medicine
----- Active space ----- Atrial fibrillation (AF) : 00:35:27
Findings :
1. Irregular RR interval.
2. Fibrillatory waves.
3. No identifiable P waves.
Diagnosis : AF.
Valvular AF : AF seen in MS (or)
prosthetic mitral valve.
Types :
1. Paroxysmal : Lasts for < 7 days. Reverts back spontaneously (or) with drugs.
2. Persistent : Lasts for > 7 days.
3. Permanent : LA dilatation > 4 cm. Rhythm can’t be reverted back to normal.
Complications : Thromboembolism.
Management :
Hemodynamically unstable : DC cardioversion (100 J → 100 J).
Hemodynamically stable
Transthoracic echo
Normal
Duration of AF
LA > 4 cm
Indicates : > 48 hours < 48 hours
Structural heart disease (or) unknown
Rhythm control :
Rate control : CCBs. Transesophageal echo (or) • Ibutilide.
cardiac CT to visualise clot • Amiodarone (Structural
If clot + heart disease)
3 weeks anticoagulation f/b
Rhythm control f/b 4 weeks
anticoagulation
Wide QRS tachycardia :
Ventricular tachycardia :
• Sustained VT , rate > 100/min.
• ≥ 3 VPCs.
• Capture beat, fusion beat maybe present.
Management Monomorphic VT
.
Unstable Stable
Synchronised DC cardioversion • Procainamide.

(100 J → 100 J → 100 J → 60J) • Amiodarone in structural heart disease.
• Lignocaine : Post MI.

Polymorphic VT + prolonged QT : Torsades de pointes. ----- Active space -----

Precipitating factors
• Class Ia, Ic, III anti arrhythmic
drugs.
• Terbinafine.
• Macrolides.
• Hypokalemia, hypocalcemia,
hypomagnesemia.
• Hypothermia.
Torsades de pointes
Mx (All patients unstable) :
Defibrillation (200 J) + 2g I/v MgSO4.
Hyperkalemia : 00:45:20
Causes :
• Renal failure (M/c).
• Hypoaldosteronism.
• Pseudo hypoaldosteronism : RTA type IV.
• Spironolactone.
ECG findings Serum K+
(mEq/L)
Tall T waves 6-7
ST segment ↓, 7-8
PR segment ↑
Wide QRS 8-9
P wave absent >9
Mx of hyperkalemia : Calcium gluconate.
Hypokalemia : 00:47:22
Findings :
1. Sagging of ST segment.
2. Prominent U waves.
Mx : I/v KCl.

30 06 Medicine
----- Active space ----- RESPIRATORY SYSTEM REVISION 1
Weibel’s generation of airways :

• Total 23 generations of airway.
• First 16 generations → Conducting zone (Upto terminal bronchioles).
• Last 7 generations → Respiratory zone
(Respiratory bronchioles + alveolar ducts + alveoli = Acinus).
Classification of Lung Diseases 00:02:47
Lung diseases
Obstructive lung diseases Vascular Restrictive lung disease

• COPD : • Pulmonary hypertension.
Chronic bronchitis. • Pulmonary thromboembolism.
Emphysema.
Small airway disease (<2mm). Intraparenchymal Extraparenchymal
• Bronchial asthma (BA). Interstitial lung • Neuromuscular (NM) disorders :
• Bronchiectasis except disease (ILD) Myasthenia, ALS, GBS.
tractional bronchiectasis. ALS : Amyotrophic Lateral Sclerosis.
• Bronchiolitis. GBS : Guillain Barre Syndrome.
• Cystic fibrosis (CF). • Chest wall issues :
Kyphoscoliosis, obesity.
• Filling disorders + Parenchymal destruction : Lung abscess (Necrotizing pneumonia).

• Pleural disease : Pleural effusion
Note : Lung parenchyma is Alveoli + alveolar interstitium + vascular interstitium.
Interstitial Lung Disease (ILD) :
• Diffuse lung parenchymal fibrosis.
• Early stage :
Hypoxia Type 1 respiratory failure (RF).
(↓PaO2) Pulmonary vasoconstriction → Pulmonary hypertension.
• Late stage : More lung parenchyma is involved → Hypoxia + Hypercarbia →
Type 3 RF.
COPD (Chronic Obstructive Pulmonary Disease) :

Larger airway + Smaller airway + Parenchymal + Vascular involvement.
Chronic bronchitis : Type 2 RF.
Pulmonary hypertension.
Lung parenchyma involved
Right ventricular failure (Cor pulmonale).
Emphysema : Alveolocapillary membrane involved → Type 1 RF.
Www.Medicalstudyzone.com RS Revision 1 06 31
Respiratory failure 00:18:32 ----- Active space -----
Types Physiology PaO2 PaCO2 P(A-a)O2 Examples

Type 1 Diffusion failure Normal • Alveolar filling disorders :
Pneumonia.
Diffuse Alveolar Hemorrhage.
ARDS.
• ILD.
• Vascular disorders.
• Emphysema.
Type 2 Ventilatory failure Normal Pump :
Neuromuscular disorders.
Chest wall issues.
Effector organ : Chronic bronchitis.
Generator : Brainstem disorders.
Type 3 Combined ILD (Type 1 → Type 3).
diffusion & Type 2 → Type 3 RF is rare.
ventilatory failure
Spirometry 00:21:17
FEV1 /Forced Expirato-

ry Volume in 1 second :
Amount of FVC exhaled in
1st second.
FVC = 5L
Volume (l)
FEV1 = 4L
FEV1 /FVC > 80%.
Time (sec)
Lung volumes in obstructive and restrictive lung disease :
Obstructive lung disease Restrictive Lung disease
Elastic recoil pressure (ERP) is low There is ventilation issue.
d/t loss of alveolar attachments ERP is high d/t fibrosis → Difficult to
→ Hyperinflation→ Dynamic inflate alveoli.
compression of airways.

32 06 Medicine
----- Active space ----- Obstructive lung diseases Restrictive lung diseases
Vascular
Hyperinflation Air trapping Intra Extra parenchymal lung
phase phase parenchymal diseases
1 FEV 1 ↓↓ ↓↓ Normal to ↑ Normal
FVC
2 FEV 1 ↓↓ ↓↓ Normal Normal
3 FVC Normal ↓↓ ↓↓ Normal
4 DLCO Emphysema = ↓↓ ↓ Normal Very low
NM Chest
issues wall
5 RV ↑↑ ↑↑ ↓ Normal Normal Normal
6 TLC ↑↑ Normal ↓↓ ↓↓ Normal Normal
7 RV/ TLC - - - ↑↑ Normal -
Lung volumes in smaller airway disease :

• FEV 1 /FVC : Normal
• Forced expiratory flow 25-75% (FEF 25-75) /
Volume (l)
Maximal Mid Expiratory Flow Rate (MMEFR) is
used to identify small airway disease.
Time (sec)
DLCO 00:45:30
Measurement of lung’s ability to transfer gas (O2) across alveolocapillary

membrane.
• Normal Value of DLCO : 20-30 ml/min/mm Hg.
• Normal Value of DLCO : 70 to 140 %.
Carbon monoxide/CO used for measuring DLCO because :
• CO affinity to hemoglobin is very high.
• CO is diffusion limited gas.
• There is negligible amount of CO in the blood.
Alveolocapillary membrane : Diffusion takes place across

1. Alveolar epithelium + Basement membrane.
2. Interstitium.
3. Capillary endothelium + Basement membrane.
Surface area of alveolocapillary membrane : 70 m2
Thickness of alveolocapillary membrane : 0.2 - 0.5 micrometre.
Factors affecting DLCO : ----- Active space -----
Factors that increase DLCO Factors that decrease DLCO

• ↑ Blood volume : Supine position, ↑cardiac output, • Valsalva maneuver.
congestive cardiac failure, polycythemia. • Smoking (↑ CO Hb).
• ↓ PaO2 : High altitude. • High flow O2 therapy (↑ OxyHb).
• Exercise and Obesity. • Anemia.
• Left to right cardiac shunts.
Clinical application of DLCO :

Diseases with ↑ DLCO Diseases with↓ DLCO
Diffuse alveolar hemorrhage: Helps in early diagnosis of ILD in
Sensitive indicator for early rheumatological disorders:
bleeding into alveoli. Eg: • Rheumatoid arthritis (RA)
• Goodpasteur disease • Scleroderma
• Wegener granulomatosis • Mixed connective tissue disease
• Microscopic Poly Angiitis • Polymyositis
• Dermatomyositis
In asymptomatic patients → DLCO falls >15%
within 6 months. → marker of progression of ILD
Bronchial asthma Pulmonary vascular diseases
Bronchitis Bleomycin toxicity
Emphysema
Pleura 01:00:42
Fluid in pleural cavity Detected

10 -30 mL Normal fluid in pleural cavity.
50 mL USG.
60- 80 mL Chest X-ray Lateral view.
200 mL Chest X-ray PA view.
300 mL Clinically.
Pleural effusion :
Light’s criteria distinguish transudates from exudates :
• The fluid is considered as exudative pleural effusion if any one of the
following are found :
1. Ratio of pleural fluid to serum protein ≥0.5.
2. Ratio of pleural fluid to serum LDH ≥0.6.
3. Pleural fluid LDH ≥2/3rd of the upper limits of normal serum LDH.
• The fluid is considered a transudate if all the above are absent.
34 06 Medicine

Causes of transudative pleural effusion :
• Congestive heart failure. • Hypoalbuminemia.
• Cirrhosis. • Budd Chiari Syndrome.
• Nephrotic syndrome. • Urinothorax.
• Superior vena cava obstruction. • Peritoneal dialysis.
• Hypothyroidism.
Can cause Transudative/Exudative effusion :
• Chronic constrictive pericarditis. • Pulmonary infarction.
• Pulmonary embolism. • Acute pancreatitis.
Note : Methotrexate causes HSP.
Pleural fluid analysis :
• Cells : 1700 cells/μl (75% macrophages, 25% lymphocytes, < 1% mesothelial cells).
• LDH : <50 % of Serum LDH.
• Protein : 1 to 1.5 g/dL.
• Glucose : Same as Serum glucose.
Causes of eosinophilc effusion ( >10 % eosinophils in pleural fluid) :
• Hemothorax /Pneumothorax. • Drugs.
• Parasitic : Paragonimus westermani. • Eosinophilic Granulomatosis with
• Histoplasmosis/Coccidioidomycosis. Polyangiitis (EGPA).
• Asbestosis. • Pulmonary infarction.
Pleural fluid abnormalities and associated diseases :
1. Empyema : 2. RA :
• LDH >1000 U/L • pH <7.2
• Neutrophils in pleural fluid • Glucose <30 mg/dL
• pH < 7.2 • Macrophages and multinucleate
• Glucose 30 -60 g/dl giant cells (tadpole cells)
3. Malignancy :
• Glucose 30-60 mg/dL
Community acquired pneumonia associated pleural effusion :
Effusion Pathology Investigations
LDH
Simple parapneumonic Culture
Inflammation → ↑ vascular permeability. Normal
effusion Glucose
pH
Complicated Simple parapneumonic effusion + bacterial LDH increased.
parapneumonic effusion invasion ( fibrin deposition & septation). Culture +.
Complicated parapneumonic effusion + Glucose reduced.
Empyema pH < 7.2.
Macroscopic pus in pleural cavity.
Empyema : Any pneumonia not responding to antibiotics within 72 hours

Clinical features : Fever not responding to antibiotics, Pleuritic pain,
Pleuritic tenderness, tachycardia, clubbing.
Investigations : Chest x-ray → D sign/pregnant belly sign. ----- Active space -----
IOC : CECT → Split Pleura Sign (Differentiates empyema from
necrotising lung abscess).
Treatment : Intercostal drainage (ICD). No role for intrapleural antibiotics.
D Sign/Pregnant belly sign USG : Septations in empyema Split pleura sign
Indications of ICD :
• Empyema (Absolute indication).
• Pleural fluid pH < 7.2.
• Organism in culture.
• Loculated pleural effusion.
• Massive effusion.
Massive pleural effusion
Pleural TB :
• If left untreated → pulmonary TB/extrapulmonary TB within 5 years.
• Gene Xpert/CBNAAT/Pleural fluid ADA/ pleural fluid culture → Inconclusive in
pleural TB.
• Pleural biopsy (Medical thoracoscopy/wax guided) is conclusive
ADA (Adenosine DeAminase) :

Pleural fluid ADA Interpretation
< 40 U/L Not suggestive of TB.
>70 U/L + lymphocytes + exudative effusion Highly suggestive of TB.
40 to 70 U/L Lymphoma, empyema, malignancy, brucellosis, TB.
Note : Mesothelial cells→< 5% in TB. (Normal <1%).

Connective tissue disorder related to pleural effusion :
• Most important lung manifestation of SLE and RA : Pleuritis ± effusion.
Chylous vs. pseudochylous pleural effusion :
Chylous pleural effusion Pseudochylous pleural effusion
Usually after trauma or tumor Usually after RA/TB.
• Triglycerides : High.
• Chylomicrons present.
• Milky lymphocytic exudative effusion. • Contains cholesterol crystals
• Normal glucose.
• Low LDH.

36 07 Medicine
----- Active space ----- RESPIRATORY SYSTEM REVISION 2
Pulmonary thromboembolism 00:00:22
Causes of pulmonary thromboembolism :

• Venous thromboembolism (VTE) from suprapopliteal veins → femoral vein
(Pelvic veins in pregnancy).
• Inherited cause : Factor V Leiden mutation (M/c).
• Acquired causes : Antiphospholipid antibody syndrome (M/c), nephrotic syn-
drome, post orthopedic surgery, malignancy (Adenocarcinoma), COPD.
Note : M/c site of DVT : Deep veins of calf.
Types of pulmonary thromboembolism :

1. Massive, 2. Submassive & 3. Non-massive.
Massive Submassive Non-massive
Hypotension. No hypotension. No hypotension.
D/t RV dilatation → RV dilatation + markers of RV No RV dilatation or
septum pushed to ischemia ↑ (NT proBNP, trop I). biomarker rise.
left → small LV → If both markers are ↑ : High risk. Presents with
↓ CO (Cardiac out- If any one ↑ : Low risk. recurrent pneu-
put). monia.
Evaluation of pulmonary embolism :

Clinical :
Symptoms Signs
• Unexplained dyspnea with clear lung fields. • Tachycardia, tachypnea.
• Syncope. • S3, ↑ JVP : Acute right
• Chest pain (Pleuritic). heart failure.
• Cough with hemoptysis (Non-massive). • Clear lung fields.
• Sudden cardiac death. • ↓ breath sounds, rales
Investigations :
ABG : Hypoxemia, respiratory alkalosis, widening of (A-a) O2 gradient.
ECG : T inversion in V1 to V4 correlates with severity.
S1Q3T3.
Echo : ----- Active space -----

Findings seen in echo :
• RA & RV dilatation, septal push, small LV.
• Cardiac tamponade.
• Mc Connell’s sign : Hypocontractile RV free wall
+ hypercontractile apex. CTPA : Saddle thrombus.
Imaging : IOC -CTPA (CT pulmonary angiography).

• Clot.
• Pulmonary artery dilatation.
• RV dilatation.
• Polo mint sign : Thin rim of contrast persists
around a central filling defect d/t thrombus.
CTPA : Saddle thrombus.
Well’s score :
Parameter Score
Clinical signs of DVT. 3
Alternate diagnosis less likely than 3
pulmonary embolism. After interpretation of
Well’s score :
Heart rate >100/min 1.5
High risk → CTPA.
Recent surgery or immobilisation. 1.5
Low risk → D-dimer.
Previous pulmonary embolism or DVT. 1.5
Score ≤4 : PE unlikely.
Hemoptysis. 1
Malignancy. 1
Management :
Start anticoagulation : Unfractionated heparin (80 U/kg) or low molecular
weight heparin (1 mg/kg s/c) followed by warfarin to maintain INR of 2-3.
If massive (or) submassive high risk :
• Thrombolysis (Alteplase 100 mg i/v over 2 hours x 14 days).
• If thrombolysis is C/I : Embolectomy.
After thrombolysis → Anticoagulation : Newer oral anticoagulants (NOAC) better
than warfarin.
If submassive low risk (or) non-massive : Continue anticoagulation.
If patient is not a candidate for NOAC : IVC filter.

38 07 Medicine

Pulmonary hypertension 00:19:29
Pulmonary hypertension : Resting mean pulmonary artery pressure ≥20 mmHg

with right sided heart catheterisation.
Types :
A. Due to ↑ pulmonary vascular resistance (PVR) B. Due to ↑Left atrial

Type 1 Pulmonary artery hypertension (PAH). pressure (LAP)
Plexiform arteriopathy d/t remodelling/ Type 2 D/t cardiac
vasoconstriction/thrombosis. causes.
Type 3 Lung related causes : ILD, c/c bronchitis.
Type 4 C/c thromboembolic pulmonary hyper-
tension.
Pulmonary vascular resistance (PVR)
Note : PVR <3 Wood units in type 2.
PVR >3 Wood units in other types. = Change in pressure/ flow
Rt. heart pressure - Lt. heart pressure
=
Cardiac output
Type 1 : PAH
Idiopathic : Should be termed idiopathic after ruling out
• Limited systemic sclerosis.
• Toxins : Rapeseed oil.
• Serotonergic substances : Fenfluramine. Molecular pathogenesis :
• BMPR-2 mutation. • Endothelin ↑.
• Infections : HIV, Schistosomiasis. • Nitric oxide ↓.
• Portal hypertension. • Prostacyclin ↓.
O/E : Clinical presentation of PAH :
• Loud, palpable P2. Fatigue (M/c symptom).
• Parasternal heave. Breathlessness.
• Epigastric pulsations. Chest pain (RV ischemia).
• 2 ICS pulsations.
nd
• High pitched pansystolic murmur along left sternal border which ↑ on

inspiration 20 to PAH : Hypertensive tricuspid regurgitation.
• High pitched early diastolic murmur d/t pulmonary regurgitation or
pulmonary artery dilatation : Graham steel murmur.

Evaluation : ----- Active space -----

Echo : Pulmonary artery dilatation, RV function, TR.
PFT : FEV1/FVC normal, FVC normal, DLCO ↓.
Polysomnography & HRCT : To rule out obstructive sleep apnea syndrome & ILD.
V/Q scan : To rule out c/c thromboembolic PAH (Rx : Pulmonary
endarterectomy).
6 minute walk test : Predictor of survival.
Management :
Supportive care :
• Avoid pregnancy.
• Oral anticoagulants.
• Long term oxygen therapy.
• Diuretics for RHF.
Specific therapy :
• CCB.
• Endothelin receptor antagonists (ERA).
• PDE 5 inhibitors.
• Prostanoids.
• Guanylyl cyclase stimulants.
Vasoreactivity test
Positive Negative
CCB No role for CCB
(Nifedipine 240 mg)
Class 1 to 3 symptoms Class 4 symptoms
Ambrisentan (ERA) + Prostanoids (Epoprostenol,

Tadalafil (PDE 5 inhibitor) Troprostinil)
Note : If prostanoids fail in class 4 symptoms → Atrial septostomy (or) lung

transplantation.
Interstitial lung diseases (ILD) 00:36:38
Parenchyma : Alveoli + alveolar interstitium + vascular interstitium.

ILD : Diffuse parenchymal lung fibrosis.
Mediator : TGFβ, PDGF.
40 07 Medicine
Idiopathic interstitial pneumonia :

Forms of idiopathic interstitial pneumonia :
1. Idiopathic pulmonary fibrosis (IPF) :
• M/c.
• Histological counterpart : Usual interstitial pneumonia (UIP).
2. Non specific interstitial pneumonia (NSIP).
3. Cryptogenic organising pneumonia (COP).
4. Respiratory bronchiolitis associated ILD (RB-ILD).
5. Desquamative interstitial pneumonia (DIP). ILD a/w smoking
6. Diffuse alveolar damage : • RB-ILD.
• Acute interstitial pneumonia. • DIP.
• Poor prognosis. • LCH.
• Eg : COVID pneumonia. • Rheumatoid arthritis
7. Lymphocytic interstitial pneumonia (LIP). associated ILD (RA-ILD).
Patterns of ILD :
Pattern Seen in Onset Treatment
UIP RA (Majority : Idiopathic) Chronic. Anti PDGF : Nintedanib.
NSIP Connective tissue diseases, Subacute. Steroid + MMF
drugs. (Mycophenolate mofetil)
COP Polymyositis, dermatomyositis, Subacute. Steroid + MMF.
anti synthetase syndrome.
LIP Sjogren’s syndrome, HIV.
Clinical features : CTD a/w ILD

Symptoms : • Diffuse systemic sclerosis.
• Dyspnea on exertion. • MCTD.
• Dry, non productive cough. • Sjogren’s syndrome.
• Compliance/hypoventilation • Polymyositis, dermatomyositis.
(Type 3 respiratory failure). • IgG4 related disease.
Signs : • Ankylosing spondylitis.
• Clubbing.
• Velcro crackles : B/L, bibasal, end
inspiratory to early expiratory, fine
crackles, not varying with cough.

Investigations : ----- Active space -----

PFT :
• FEV1/FVC : ↑ (FVC ↓ & FEV1 normal).
• DLCO : ↓.
IOC : HRCT.
HRCT findings :
CXR : Shows B/L, bibasal,
Non specific : Reticular & linear shadows.
subpleural reticulonodular infiltrates.
Pattern HRCT findings
UIP Honeycombing, cystic spaces, loss of lung architecture, traction
bronchiectasis.
NSIP Ground glass opacities (GGO).
COP Consolidation.
Reverse halo sign : GGO surrounded by consolidation.
Reverse halo sign

LIP NSIP + nodules + cysts.

42 07 Medicine
Conditions causing cysts in lungs :

• LCH : Langerhans cell histiocytosis.
• LAM : Lymphangioleiomyomatosis.
• LIP.
LCH
Young male smoker.
LAM
Upper lobe ILD (Nodules + cysts).
Young females with tuberous
Associated with diabetes insipidus.
sclerosis.
CD1a cells ≥5% : Birbeck granules,
Cysts in lungs.
tennis racquet shaped.
Pneumothorax.
LCH LAM
Drug induced ILD : Causes of upper lobe ILD :
1. Amiodarone. • Ankylosing spondylitis.
2. Bleomycin. • Sarcoidosis.
3. Busulfan. • Silicosis.
4. Cyclophosphamide. • Coal worker’s pneumoconiosis.
5. Mitomycin. • ABPA : Allergic bronchopulmonary
6. Methotrexate. aspergillosis.
Rare causes. • Hypersensitivity pneumonitis.
7. Anti TNFα drugs.
• Berylliosis.
• TB.
• LCH.
Occupational lung diseases 01:11:26
Pneumoconiosis :
1. Silicosis.
2. CWP. Complicated
3. Asbestosis.
4. Berylliosis. → Uncomplicated

Silicosis : Caused by exposure to SiO2 (Quartz) in rock cutting, slate cutting, sand ----- Active space -----
blasting & mining industries.
1. Acute silicosis :
Seen when there is large exposure to SiO2 (crystalline silica) within 2 years.
Symptom : Dyspnea on exertion.
Findings : Crazy pavement
• PAS +ve macrophages. pattern
• Milky white bronchoalveolar lavage. • Acute silicosis.
• CT : Crazy pavement pattern (GGO + nodules + • Diffuse alveolar
cysts). hemorrhage.
Poor prognosis. • Pulmonary alveolar
proteinosis.
2. Chronic silicosis :
M/c pneumoconiosis.
10-30 years of exposure.
Cell affected : Pulmonary alveolar macrophage (PAM) → Reactivation of TB.
A/w autoimmune conditions (Scleroderma).
Pleural involvement : Nil.
Parenchymal involvement :
• Upper lobe ILD.
• B/L upper lobe nodules : Nodules
join together → conglomerate
nodules (Angel wing sign). Egg shell calcification
• Hilar adenopathy with peripheral
calcification (Egg shell calcification).
• Cavitation ±.
• Lung signs in 25%.
• Dyspnea & cough.
• Mixed pattern on spirometry.
Coal worker’s pneumoconiosis (CWP) :

Cell affected : PAM → But, no risk of TB reactivation.
A/w autoimmune conditions : Caplan’s syndrome (RA + active synovitis + nodules
+ IgA rheumatoid factor +ve).
• No hilar lymphadenopathy.
• No egg shell calcification.
• Nodules.
• Upper lobe fibrosis.
• Cavitation ±.

44 07 Medicine

Berylliosis :
Ceramic industry.
• Upper lobe infiltrates.
• Non caseating granulomas.
• Thickening of bronchovascular bundles.
• Hilar adenopathy.
• NSIP pattern.
Note : Smoking is a risk factor in silicosis, CWP & berylliosis.
Asbestosis :
Serpentine (90%)
2 types of fibres Crocidolite
Chrysotile (10%)
• Around 10 years of exposure. Amosite (Most dangerous)
Pleural involvement :
• Pleural manifestations are not related to smoking.
• Parietal pleural thickening (M/c) : Pleural plaques with
calcification → Seen as Holly leaf sign/table mountain
sign/candle drip sign in CXR.
• Earliest : Benign asbestos related pleural effusion (BAPE)
→ exudative, eosinophilic with mesothelial cells.
Pleural plaques
• Lower lobe ILD : Diffuse massive fibrosis.
• Infiltrates result in dyspnea.
• No lung signs.
• Restrictive pattern in spirometry.
Malignancy Holly leaf sign

Pleural mesothelioma Ca lung

• Unrelated to smoking. • Related to smoking.
• Occurs after 30 years of exposure. • Occurs 10-30 years after exposure.
• Epithelioid type is m/c. • Adenocarcinoma.
• Markers : Pan cytokeratin, calreticulin. • Symptoms : Cough with hemoptysis.
• Symptoms : Chest pain (or) mass.

RESPIRATORY SYSTEM REVISION 3 ----- Active space -----
Airway diseases :
• No parenchymal involvement.
• Type 1 respiratory failure (Normal PaCO2).
Eosinophilic lung disease 00:02:05
Defined by :
a. BAL eosinophilia >25% (or)
b. Lung tissue eosinophilia (or)
c. Peripheral eosinophilia + Lung infiltrates.
Causes :
Known causes Unknown causes
1. Parasite 1. Eosinophilic granulomatous polyangiitis
a. Loeffler’s syndrome : Hypersensitivity to (EGPA).
ascaris. 2. Acute eosinophilic pneumonia (ARDS like
b. Lung fluke invasion. presentation).
2. Drugs : Nitrofurantoin. 3. Chronic eosinophilic pneumonia/CEP
3. Tropical pulmonary eosinophilia (d/t (Reverse batwing : Photographic negative
microfilaria). of pulmonary edema on radiology).
4. Allergic bronchopulmonary aspergillosis (ABPA) 4. Idiopathic hyper eosinophilic syndrome.
Note :
HSP (Hypersensitivity pneumonitis).
Bronchial asthma (A/w eosinophilia). Not eosinophilic lung diseases.
Pulmonary eosinophilic granuloma diseases.
BAL eosinophilia with > 40% : CEP & Tropical Pulmonary eosinophilia.
Aspergillus in lung 00:06:56
Organism : Aspergillus fumigatus with septate hyphae (Forms mucus plug).

Not a highly contagious disease.
Presentations of aspergillus infection :
1. ABPA : Eosinophilic lung disease.
2. Aspergilloma : Seen in old tuberculosis cavity.
3. CCPA (Chronic cavitary pulmonary aspergillosis) : Thick walled cavities +
bronchial wall invasion in COPD patients.
46 08 Respiratory System

4. Invasive aspergillosis :
• Neutropenic patients.
• CT : Halo sign (consolidation surrounded by ground glass opacities).
ABPA :
A. fumigatus colonizes airways in bronchial asthma or cystic fibrosis patients
(Acute/remission/exacerbations/steroid dependent asthma/fibrosis).
Type 1 + Type 3 hypersensitivity (type 1 > 3).
Lung findings seen in 20% patients.
Pathology :
Bronchiectasis : Proximal bilateral cylindrical symmetrical central type.
C/F of ABPA :
• Fever and cough with brownish thick mucosal plugs.
• Rarely gets converted to ILD (Involves upper lobe).
Investigation :
• IgE >1000 (Part of obligatory criteria + used for Tram track lines in CXR
follow up).
• Precipitin +ve.
• Imaging :
a. Chest Xray :
- Transient irregular parenchymal infiltrates.
- Atelectasis.
Finger in glove appearance
- Tram track appearance. (d/t mucoid impaction
- Finger in glove appearance. in distal bronchi)
b. CT : Tree in bud appearance.
Treatment :
a. Steroids for 12 weeks (DOC).
b. Steroid non responders : Itraconazole for 16 weeks.
c. Omalizumab (Monoclonal antibody against IgE). HRCT showing
central bronchiectasis
(tree in bud pattern)
Hypersensitivity pneumonitis (Extrinsic allergic alveolitis) :

Inflammatory disorder of the lung involving the alveolar wall & terminal airways.
Repeated exposure to organic dust Type 4 + Type 3 HS Involves
airway > Parenchyma.

Characterised by : ----- Active space -----

• IgE/eosinophil absent + Precipitin +ve + Non caseating granuloma & infiltrates.
• If parenchyma is involved : Non fleeting Interstitial infiltrates.
• Subacute form (M/c) : A/w response to steroids.
• No systemic symptoms.
HRCT : Mosaic/Head cheese pattern

(Different kind of densities seen).
Rx : Steroids . Mosaic attenuation/

Head cheese pattern
Organic dust :
Microorganisms serve as antigen in dust/animal proteins/chemicals :
Disease Exposure Antigen
Farmers lung Moldy hay Thermophilic actinomycete
Bagassosis Moldy sugarcane (M/C antigen) :
Mushroom worker’s lung Moldy compost/mushroom Thermoactinomycetes vulgaris
Malt workers lung Barley
Aspergillus clavatus
Tobacco workers lung Mold on tobacco
(2nd m/c)
Compost lung Compost
Wood workers lung Wood pulp
Bird fancier’s lung (Obstructive/ Avian droppings
emphysematous pattern) (Pigeon, parrot, chicken)
Chemical workers lung Polyurethane foams
(Isocyanates)
Note :
Disease Antigen
Hot tub lung, or humidifier or
Cladosporium, MAC
air conditioner lung
Wood trimmers lung Rhizopus
Familial HP/wood workers Bacillus subtilis

----- Active space ----- Hypersensitive reactions to Aspergillus

Extrinsic allergic
Asthma ABPA
alveolitis/HSP
Colonization of airways, Lymphocytic infiltration of
Hypertrophied
Pathology viscid mucoid impaction, interstitium, noncaseating
mucus gland
tissue eosinophilia granuloma
Radiographic features
Migratory peripheral
Normal Diffuse alveolar
Early infiltrates, atelectasis,
hyperinflation interstitial infiltrates
bronchiectasis
Normal Reticulonodular
Late Fibrosis
hyperinflation interstitial opacities
Skin test reactions to Aspergillus antigens
Immediate Positive Positive Positive
Delayed Negative Positive Positive
Other findings
Peripheral
Negative Positive Negative
eosinophilia
IgG aspergillus
Positive Positive Positive
precipitins
Normal or
Serum IgE levels Marked elevation Normal
mildly elevated
BAL lymphocytosis :
CD4/CD8 (>2 : 1) : Sarcoidosis.
CD8/CD4 (>2 : 1) : HSP.
Bronchiectasis 00:23:50
Obstructive type of airway disease.

Abnormal irreversible dilatation of bronchi + obliterative fibrosis of bronchioles.
D/t destruction of smooth muscles and elastic tissue of lung.
Types of dilatation : Tubular, cylindrical (M/C), varicose & cystic dilatation.
Cystic dilatation : Seen in children & a/w clubbing.
Traction bronchiectasis (Part of ILD) : Restrictive type.
Causes for loss of smooth muscles & elastic tissue :

1. Idiopathic (30%).
2. Tuberculosis (40-50%).
3. Genetic causes : Alpha-1 antitrypsin deficiency.
4. Childhood infections : Measles & pertussis.
5. Genetic syndromes : Yellow nail syndrome, William Campbell syndrome.
Pathophysiology : ----- Active space -----
• Lt lobe > Rt; F > M; 50-70 yrs.

• Dry bronchiectasis (Sicca) : Tuberculosis .
• Right middle lobe bronchiectasis :
K/a Brocks syndrome (d/t lymph node in TB).
• Middle lobe bronchiectasis : D/t MAC.
C/F :
• Chronic cough.
• Foul smelling sputum.
• Hemoptysis.
• Early & mid inspiratory coarse crackles.
• Diffuse rhonchi.
Imaging :
1. Volumetric multidetector helical CT scan (Best) : Absence of bronchial
tapering.
2. Airway dilatation (Parallel lines or ring shadows) : 1-1.5 times adjacent vessel
diameter : Signet ring sign.
3. Tram track sign.
4. Tree in bud pattern.
5. Central distribution, upper lobe
& fibrotic band : ABPA.
Bronchiectasis : Signet ring in CT s/o cylindrical bronchiectasis

Rx :
1. Airway clearance with physiotherapy and postural drainage (Cornerstone of
therapy).
2. Nebulized 7% hypertonic saline or steam inhalation to clear secretions .
3. Recombinant DNase for cystic fibrosis associated bronchiectasis .
4. Resection : If localized bronchiectasis with recurrent infection unresponsive
to drugs .
5. Prophylaxis : Macrolides (Azithromycin) for 6-9 months.
M/c organism causing infection : Pseudomonas .


Chronic obstructive pulmonary disease (COPD) 00:36:00
Acinus (Respiratory unit) : Respiratory bronchiole + Alveolar ducts + Alveoli .

COPD has 2 diseases :
1. Chronic bronchitis (clinical) : Cough with sputum for 3 months for 2 consecutive
years.
2. Emphysema (Pathological) : Dilatation of airspace distal to terminal bronchiole
followed by destruction of walls of airspaces .
Types of emphysema :
Centriacinar Panacinar Paraseptal

• Most common. • Complete involvement. • Young, male, smokers.
• Respiratory • Young, non smoker, α-1 • Associated with
bronchiole involved. antitrypsin deficiency & pneumothorax.
• Smoker & males . liver disease.
• Upper lobe • Lower lobe
predominant. predominant.
α-1 antitrypsin Phenotypes :
1. Pimm : Normal phenotype.
2. Pizz : Severe deficiency.

Chronic bronchitis Emphysema ----- Active space -----
Structure involved Parenchymal +++ Airway +++

Gaseous changes PaO2 PaO2
PaCO2 Normal PaCO2
Type of Respiratory failure Type 2 Type 1
Hypoxia More Less severe
Pulmonary HTN/ More common Less common
RV failure/ Infection
Prognosis More mortality Better outcomes
Complications :
V/P mismatch (Characteristic of COPD)
Severe chronic hypoxia

Muscularization
Intimal hyperplasia
Pulmonary hypertension Fibrosis
Obliteration
Cor pulmonale Edema
Death
Rx : Based on categories.
mMRC 0-1, CAT< 10 mMRC ≥2, CAT ≥10
0 to 1 moderate Group A Group B
exacerbations A bronchodilator A long acting
(Not leading to (Short acting bronchodilator
hospital admission) bronchodilator) Dyspnea (LABA or LAMA)
Exacerbation
≥2 moderate Group D
exacerbations Group C LAMA or
or LAMA LAMA + LABA
≥ 1 leading to (Long acting ± ICS
hospitalization anti-muscarinic drugs) (If eosinophils ≥ 300).
mMRC : modified medical research council dyspnea questionnaire ;
CAT : COPD assessment test.
For exacerbations : SABA + Short oral steroid therapy for 5-10 days.

----- Active space ----- LTOT (Long term oxygen therapy) :

• Given for 14-18 hrs/day.
• After exacerbation is over.
• Indications :
a. PaO2 <55 mmHg.
b. PaO2 of 55-60 mmHg if patient has pulmonary HTN/ RV failure.
Lung transplant : Last option.
Localised emphysema : Lobe resection (If not much cardiac problem & FEV1 >20%)
Pneumonia Management 00:53:34
CURB score :
Score of 1 to each point. Score 0, 1 : Outpatient management.
C : Confusion. Score 2 : Inpatient management.
U : Urea > 42 mg/dl. Score 3 : ICU management.
� : Respiratory rate >30/min.
B : <90/60 mm of Hg.
Age : ≥ 65 years.
Outpatient Mx :
Amoxicillin 1 gm TDS/Amoxiclav 625 mg BD (If risk factors like DM is present)
+ Azithromycin 500mg OD /Doxycycline 100mg BD.
Inpatient Mx :
a. Severe (ICU) : Beta-lactam + Macrolide (or) Beta lactam + Levofloxacin.
b. Non severe :
• Beta-lactam (Ampicillin-sulbactum 1.5-3gm Q6h).
+ Macrolide (Azithromycin 500mg OD) (or)
• Levofloxacin 750 mg OD alone.

Rheumatology Revision 1 09 53
RHEUMATOLOGY REVISION 1 ----- Active space -----
Localization of Disease in Rheumatology 00:02:43
Step 1. Intraarticular vs extraarticular pathology :

Intraarticular pathology Extraarticular pathology
Involves : Involves :
• Synovium. • Ligaments & tendons.
• Hyaline cartilage. • Muscle & fascia.
• Intraarticular joint capsule.
Rheumatological problem. Orthopaedic problem.
Diffuse, deep seated pain . Localised, superficial pain.
Pain on active & passive movement. Pain on active movement.
Swelling, crepitus & deformity seen. Localised swelling away from joint.
Step 2. Intraarticular pathologies : Synovitis vs Articular cartilage involvement.
Synovitis Articular cartilage involvement
Seen in Rheumatoid arthritis. Osteoarthritis.
Pathogenesis Inflammatory. Non inflammatory.
Associated Synovial hypertrophy→ • Loss of joint space.
features Pannus → Bone erosion • Osteophytes.
• Subchondral sclerosis.
Step 3. In Synovitis :
a. Only Synovitis :
Seen in RA, SLE, SLE like arthritis (Sjogren’s/polymyositis/dermatomyositis).
Rheumatoid arthritis SLE/SLE like arthritis
• Erosions seen as juxtaarticular • Erosions not seen.
osteopenia. • Non erosive deformity due
• Deformity due to erosions. to laxicity A/k/A Jaccoud’s
arthropathy.
Note :
• Jaccoud’s arthropathy : Also seen in acute rheumatic fever.
• Erosive & Non erosive arthritis.

54 09 Medicine
----- Active space ----- Erosive arthritis Non erosive arthritis

• Rheumatoid arthritis. • SLE & SLE like arthritis.
• Psoriatic arthritis (PsA). • Acute rheumatic fever.
• Chronic crystal arthritis (MSUM > • Acute crystal arthritis.
CPPD). • Relapsing polychondritis (RPC).
• Multicentric reticulohistiocytosis.
Note :
• If erosions (+) in SLE → Rhupus syndrome (RA + SLE overlap).
• MAGIC Syndrome → Mouth and Genital ulcer (Behcet’s disease) + Inflammed
cartilage ( RPC).
b. Spondyloarthritis(SpA) : Synovitis + Enthesitis + Dactylitis.

• Axial predominant SpA → Ankylosing spondylitis (Bilateral sacroilitis)
• Peripheral predominant SpA
Symmetrical polyarthritis (>5 joints)
1. Psoriatic arthritis :
Assymetrical oligoarthritis (2-4 joints)
2. Reactive arthritis.
c. Crystal arthropathy : Synovitis due to crystals.
• Monosodium urate monohydrate crystal (MSUM)/Gout : 1 st MTP > Knee
joint.
• Calcium pyrophosphate dihydrate crystal (CPPD)/Pseudogout : Knee joint.
Note :
Symmetrical polyarthritis of small joints of upper limb.
1. Acute (<6 weeks) : Acute monoarthritis.
• Post viral (parvovirus B19). 1. Knee : septic arthritis > CPPD.
• Undifferentiated arthritis. 2. 1st MTP : MSUM.
2. Chronic (>6 weeks) :
• Rheumatoid arthritis. Assymetrical oligoarthritis : Peripheral SpA.
• SLE/ SLE like arthritis. 1. Reactive arthritis.
• Psoriatic arthritis. 2. Psoriatic arthritis.
Rheumatoid arthritis 00:25:40
M/c chronic inflammatory multisystem autoimmune connective tissue disease.

Peak : 40-60 yrs.
Female : male ratio → 3 : 1.
Note :
• 2nd M/c connective tissue disorder : Sjogren’s syndrome.
• M/c Arthritis : Osteoarthritis.

Etiology : ----- Active space -----
Genetic factors Environmental factors

1. HLA associated factors : 1. Smoking :
• HLA-DRB1*04 → QKRAA aminoacid motiff (AkA • Strongest risk factor.
shared epitope). • Associated with bad prognosis.
• HLA-DRB1*13 : Protective. • risk of ILD in RA.
• expression of PADI-4 in
airway.
2. Non HLA associated factors : 2. Infection : Chronic periodontitis.
• PADI-4 (Peptidyl arginine deaminase 4) Caused by Porphyromonas
Citrulline gingivalis.
Arginine PADI-4
(Normal Aminoacid) (Abnormal aminoacid)
3. Alcohol/OCP : Mild protection.
• PTPN 22
Note : Smoking associated ILD is seen in :
• Desquamative interstitial pneumonia.
• Langerhans cell histiocytosis.
• ILD in rheumatoid arthritis.
• Respiratory bronchiolitis associated ILD.
Pathogenesis :
1. Environmental & genetic factors → abnormal protein modification
(citrullination).
2. Abnormal proteins→ presented by APC (Langerhans dendritic cells) to T cells
→ 20 activation of B cells & neutrophils → Migration to joint.
3. Synovial hypertrophy (Type A> type B synoviocytes)→ Pannus formation →
Bone erosion.
Autoantibodies in RA :
Antibody Features
Anti CCP/anti citrullinated poly- • Seen in 80-90% cases of RA.
peptide/mutated citrullinated • Specificity : 95% for RA.
vimentin. • Best marker for Preclinical infection
• ↑ risk of extrarticular features
Anti CarP Associated with palindromic rheumatism.
Anti PADI-4 antibody -
Rheumatoid factor (RF) • IgM directed against Fc portion of IgG.
• ↑ titre a/w ↑ disease activity.
• Specificity : 75-80%.
• Also +ve in :
a. Sjogren’s.
b. Cryoglobulinemia type 2 & 3.
c. Polyarticular JIA.
Note : Markers for relapse in RA → ESR& CRP (Anti-CCP and RF hold no value).

56 09 Medicine
----- Active space ----- Clinical features :

Articular manifestations :
• Duration : > 6 weeks.
• B/l symmetrical.
• Intraarticular.
• Inflammatory (Indicated by morning stiffness > 45 mins).
• Peripheral small joint, upper limb polyarthritis.
• Disease starts at distal radioulnar joint. Joints Joints spared
• Joints involved/spared rheumatoid arthritis. involved
Note : • MCP. • DIP.
DIP joint is involved in : • Wrist. • 1st CMC, 1st
• Psoriatic arthritis • PIP. MTP.
• C-spine • Thoracolum-
(Erosive arthritis : wrist, MCP, DIP, PIP). bar & sacral
• Osteoarthritis (Wrist and MCP joint spared). spine.
• Juvenile idiopathic arthritis.
• Multicentric reticulohistiocytosis.
Progression of disease :
Deformities Features
Reversible
1. Zigzag deformity. Radial deviation of wrist + Ulnar
deviation of MCP.
2. Subluxation of MCP joint.
3. Piano key styloid. Rupture of ulnar collateral ligament.
4. Hitchhiker thumb Abduction + Hyperextension of thumb.
deformity
Irreversible
1. Boutonniere deformity. Flexion of PIP + Hyperextension of DIP.
2. Swan neck deformity. Hyperextension of PIP + Flexion of DIP.
3. Opera glass hand. Arthritis mutilans.

Other joints involved/deformities :
• TM joint. • 5 th MTP : M.c involved
• C1-C2 joint : Odontoid process erosion. • Pes planus.
• Cricoarytenoid : Change in voice. • Forefoot varus.
• Ankle valgus.

Extra-articular Manifestations : ----- Active space -----
Involvement Features
Rheumatoid nodules • m/c extraarticular manifestation : 40% cases.
• 20% develop within 1 yr of onset of RA.
• M/c site : Olecranon.
• Non tender nodules.
• ↑association in Smokers, Anti CCP/RF +ve, Early onset & long duration RA.
• Granulomatous reaction : Type 4 hypersensitivity.
• Size↓on treatment.
Neuro ocular CNS • No brain parenchymal involvement.
manifestations • C1-C2 myelopathy.
• Entrapment neuropathy.
PNS • RA related small fibre peripheral neuropathy.
Ocular • M/c : Dry eyes (Keratoconjunctivitis sicca).
• Episcleritis > scleritis.
• Thinning of sclera (scleromalacia perforans).
• Uveitis not a feature.
Hematological • M/c : Anemia of chronic disease.

manifestation. • Normal WBC count (In SLE : Leukopenia or lymphopenia)..
• Thrombocytosis.
• Rapidly progressive anemia → Warm IgG AIHA.
• ↑ risk of diffuse large B cell lymphoma.
• LGL leukemia.
Felty syndrome :
• Seen later in the disease.
Large granular • Nodules, deformities +ve ; RF +ve, HLA-DRB1*04 +ve.
lymphocytes (LGL) • Antibody against citrullinated histones +ve.
• Features : RA + Neutropenia + Splenomegaly.
Lung manifestations Pleuritis ± exudative effusion (Low sugars, Low pH).
ILD : Usual interstitial pneumonia (UIP).
• Fibrosis.
• Traction bronchiectasis.
• Honeycombing.
• Loss of lung architecture.
• Cyst in the lung.
Honeycomb app.
Caplan syndrome : RA + nodules in lung + coal workers pneumoconiosis.
(seen in UIP) • Seen in active synovitis and RF +ve.
CVS manifestations M/c cause of death in RA : MI (accelerated atherosclerosis).
M/c presentation : Pericarditis w/o tamponade.
M/c valvular disease : Mitral regurgitation.
Renal manifestations M/c manifestation : 20 amyloidosis.
GIT GI vasculitis.
Vasculitis in RA • Immune complex mediated small vessel vasculitis.
• M/c lesion : Purpura.
• Histology : Leucocytoclastic vasculitis.
• Dangerous forms :
a. Medium vessel involvement : Gangrene.
b. GI vasculitis. Rx : Rituximab
c. Mononeuritis multiplex.

58 09 Medicine
----- Active space ----- Involvement Features

Others • Flexor tendon tenosynovitis.
• Bursitis.
• Hypoandrogenism.
• Osteoporosis.
• Pyoderma gangrenosum.
Note : ILD and Vasculitis in RA are more common in males.
Presentation of RA :
Presentation Features
Preclinical RA • Genetic & environmental risk factors +ve.
• Autoantibodies of RA +ve.
• Symptoms without clinical evidence of RA.
Chronic symmetrical small joint Symptoms : Pain & inflammation.

polyarthritis (M/c). D/d :
• SLE/SLE like illness.(No erosion).
• Psoriatic arthritis (No DIP involvement.
• CPPD (Pseudo RA) : Waxing & waning, non erosive.
Palindromic rheumatism • Intensely painful brief episodes of monoarticular
arthritis.
• Mimics gout.
• Antibody involved : Anti CarP.
Early morning stiffness of small joints + Normal examination & Xray findings.
suspect
Post viral arthritis (M/c : Parvo virus).
If symptoms persist If symptoms <6

> 6 weeks. weeks.
Suspect Undifferentiated arthritis. Diagnosis confirmed.
Remission in Persists as UA Evolve into RA

1/3 rd cases. or progress to 1/3rd cases.
other disease
in 1/3rd cases.

Scoring factors determining undifferentiated arthritis evolving into RA : ----- Active space -----
• Age.
• Sex.
• Joint distribution.
• Morning stiffness.
• Tender & swollen joints.
• Markers : CRP, RF & anti CCP.
Score >8 : Treat as RA.
Management :
DMARDS Biologic agents Small molecules
• Methotrexate (Mtx). • Anti TNF-α : Etanercept. • JAK 1/3
• Leflunomide. • Anti CD20 : Rituximab. inhibitor :
• Sulphasalazine. • Anti IL-1 : Anakinra. Tofacitinib.
• Hydroxychloroquine • Anti IL-6 : Tocilizumab. • JAK 1/2
(HCQ). • CTLA4/Fc IgG fusion inhibitor :
molecule : Abatacept. Baricitinib.
1. Start DMARD :
Methotrexate (Mtx) : 5mg weekly dose may go upto 25 mg weekly dose.
CBC, LFT monitored.
Side effects :
• Mucositis (m/c).
• Dose dependent bone marrow supression.
• Hypersensitivity pneumonitis
• ↑ size of nodules in 10% cases.
2. Remission assessment by Boolean score :
• Clinical assesment ≤ 1.
• Tender joint ≤1.
• Swollen joint ≤1.
• CRP ≤ 1mg/dl.
3. If no remission → Combination therapy used :
• Mtx + Sulphasalazine + HCQ or
• Mtx +TNF-α inhibitor or
• Mtx + JAK inhibitors.

60 10 Medicine
----- Active space ----- RHEUMATOLOGY REVISION 2
Systemic Lupus Erythematosus 00:00:57
General features :
• Female : Male = 9 : 1 (Males → Severe disease).
• Family history +.
• Renal involvement in SLE :
a. Adult SLE : 40% renal involvement.
b. Childhood SLE : 100% renal involvement.
c. Post-menopausal SLE : Mild disease with renal sparing.
• M/C cause of death :
a. First 5 years : Infection/lupus nephritis.
b. After 5 years : Accelerated atherosclerosis/MI.
Risk factors :
Genetic factors :
1. Non HLA & 2. HLA
Non HLA HLA
• C1q (early complement) deficiency. • C2, C3 deficiency.
• TREX gene on chromosome 3. • HLA -DR2/DR3.
• Genes on X-chromosome : Klinefelter syn-
drome has ↑risk.
Environmental factors :
• ↑ estrogen (OCPs, HRP), EBV, UV-B.
Pathogenesis :
Defective clearance of apoptotic/NETosis debris → Innate immune system
activation by IFN-α, IL-4 & Th2
Immune complex deposition (Type 3 HS reaction) in :

Vessel wall → Vasculitis
Synovium → Synovitis
Glomeruli→ Glomerulonephritis

Antibodies in SLE : Note : ----- Active space -----

1. Anti-nuclear antibodies (ANA) : Conditions with 100% ANA positivity :
• SLE : 97% +. 1. Drug-induced lupus erythematosus.
• Sjogren’s syndrome : 85% 2. Type 1 autoimmune hepatitis.
+ (least positivity among CTD). 3. Mixed connective tissue disorder.
ANA testing :
• Screening test for CTD.
• Method : Indirect immunofluorescence using Hep-2 cell line.
• Positive titre : ≥ 1/80.
• Patterns :
Pattern Antibody Specific disease
Homogenous Anti-ds DNA SLE
Anti-histone Drug-induced lupus
Dense fine speckled Rules out CTD
Fine speckled Anti-Ro/SS-A & SS-B Sjogren’s syndrome
Coarse speckled Anti-smith SLE
Anti-U1RNP Mixed connective tissue disorder
Nucleolar Anti-Pm-Scl-70 Sytemic sclerosis-dermatomyositis
overlap syndrome
Cytoplasmic Anti-Jo-1 Polymyositis & Dermatomyositis
ANA-negative SLE (3% cases) : Anti-Ro/SS-A & anti-La/SS-B +.
ANA profile : Done for ANA + patients.
2. Anti-ds DNA & 3. Anti-smith :

• Specificity for SLE : Anti-smith > anti-ds DNA.
• Anti-ds DNA is more clinically important : Titres measured by ELISA correlate
with risk for nephritis/vasculitis.
4. Anti-Ro/SS-A & 5. Anti-La/SS-B :
• Indicates secondary Sjogren’s syndrome.
• If + in pregnancy → Neonatal lupus with complete heart block.
• Associated with better prognosis → ↓ risk for nephritis/vasculitis.
• Associated with sub-acute cutaneous lupus.
• Associated with shrinking lung syndrome.
6. Anti-phospholipid : Seen in 1/3rd of SLE patients.
7. Anti-RBC : Warm antibody (IgG) autoimmune hemolytic anemia.
8. Anti-platelet : 2° ITP (Idiopathic thrombocytopenic purpura).
62 10 Medicine

9. Anti-glutamate (aka anti-neuronal) :
• M/C antibodies in CNS lupus.
• M/C manifestation in CNS lupus : Cognitive dysfunction.
10. Anti-ribosomal-P : Pyschosis/depression in CNS lupus.
Factors correlating with disease activity in SLE : Anti-ds DNA titres, ↓ C3 &
C4,↑ ESR & ↓ CRP.
Note :
Overlap syndrome : Presence of features of > 1/6 CTD.
1. SLE. 4. Dermatomyositis.
2. Sjogren’s syndrome. 5. Systemic sclerosis.
3. Polymyositis. 6. Rheumatoid arthritis.
Mixed connective tissue disorder :

• Overlap syndrome. • 100% ANA +.
• Anti-U1RNP +.
Diagnostic criteria for SLE : SLICC.
Clinical features :
Musculoskeletal manifestations :
• Chronic, inflammatory, b/l symmetrical polyarthritis of small joints in the up-
per limb.
• Jaccoud arthropathy : Non-erosive + deforming arthritis.
Mucocutaneous manifestations :
A. Acute cutaneous lupus erythematosus (ACLE) :
Malar rash/butterfly rash :
• Photosensitive.
• Erythematous.
• Scaling ±.
• Non-scarring.
• Associated with non-scarring alopecia.
• Associated with hard palate ulcers.
• Spares the nasolabial fold.
• Non-premalignant.

B. Subacute cutaneous lupus erythematosus (SCLE) : ----- Active space -----

Annular (M/C) & psoriasiform SCLE.
• Highly photosensitive.
• Non-scarring.
• A/w anti-Ro/La.
• A/w HLA-DR3.
• ↓ risk for nephritis/vasculitis.
• Spares the mid-facial region.
C. Chronic cutaneous lupus erythematosus (CCLE) : Discoid rash (M/C).
• 5% of patients with discoid rash have SLE.
• 20% of patients with SLE have discoid rash.
• Seen on the face, scalp and neck.
• Circular erythematous + dermal atrophy + follicular
plugging.
• Premalignant lesion for squamous cell carcinoma.
• A/w scarring alopecia.
• Carpet track sign.
CNS manifestations : .
• Small fibre neuropathy +, axial skeleton spared.
Ocular manifestations :
• 2° Sjogren’s syndrome (M/C), absence of uveitis.
Hematological manifestations :
• Anemia of chronic disease, warm antibody AIHA.
• Leukopenia, thrombocytopenia : 2°ITP, risk for DLBCL +.
Lung manifestations :
• Pleuritis ± effusion (exudative effusion with normal sugars).
• Diffuse alveolar hemorrhage : Marker of high disease activity.
CVS Manifestations :
Cardiac :
• Pericarditis without tamponade, mitral regurgitation, libmann-Sacks endo-
carditis.
Vascular :
• Risk for acute coronary syndrome after 5-10 years.
• Vasculitis :
a. Immune-complex mediated small vessel vasculitis → Leukocytoclastic
vasculitis.
b. GI & CNS vasculitis : Dangerous.
64 10 Medicine

Renal manifestations :
Class Type Remarks
1 Minimal mesangial No treatment required
2 Mesangial proliferative
3 Focal
4 Diffuse • M/C and most dangerous form
• Immunofluorescence : Full house effect (IgG, IgM, IgA,
C1q, C3)
• Electron microscopy : Hematoxylin bodies of Gross
• Rx : Aggressive immunosuppression.
5 Membranous • Refractory to steroid therapy
• Rx : Mycophenolate mofetil + calcineurin inhibitors
• Low risk for CKD
6 Advanced sclerotic
Treatment of SLE :
Mild (Constitutional symptoms/mild arthritis/rash) and moderate SLE :
• Oral steroid + Hydroxycloroquine + Methotrexate (If arthritis +) + Belimumab.
Note : Belimumab → B lymphocyte stimulation inhibitor.
Severe SLE (major organ involvement/life threatening disease) :

IV methyprednisolone → Oral methylprednisolone + IV Cyclophosphomide OR oral
mycophenolate mofetil (MMF)
Reassess after 3 months
Good response Poor response
3 years maintenance therapy Change cyclophosphomide to

with low dose steroids + MMF > MMF or vice versa
azathioprine
No response by the end of 6
months → resistant lupus
Rituximab
Indications for plasmapheresis in SLE :
• CNS vasculitis.
• Diffuse alveolar haemorrhage.
Spondyloarthritis 00:39:46 ----- Active space -----
• HLA-B27 +.
• RF -.
• Sacroilitis +.
• M/C extra-articular manifestation : Asymmetrical, alternating, acute, anterior uveitis.
• Central pathogenic cytokine : TNF-α.
• Age : < 40 years.
• Males > females.
Types :
Axial predominant Non-radiographic spondyloarthritis
Radiographic spondyloarthritis (Ankylosis spondylitis)
Peripheral predominant Reactive arthritis
Psoriatic arthritis
IBD arthritis (Enteropathic arthritis)
Juvenile onset spondyloarthritis
Radiographic spondyloarthritis :
Male : Female = 3 : 1.
Age : Late teens - early 20s.
Pathogenesis :
Calcification of peripheral fibers of annulus fibrosus → Thin, marginal & sym-
metrical syndesmophytes → Bony ankylosis → Bamboo spine
C/f :
1. Onset of symptoms < 45 years of age.
2. Symptom duration : > 3 months.
3. Inflammatory deep lower back/buttock pain (D/t B/l symmetrical ascending sacroilitis)
• Alternating. • Nocturnal awakening due to pain.
• Early morning stiffness > 30 mins. • Improves with activity.
4. M/C complication : Vertebral fracture at C5-C6.
5. Enthesitis :
• Achilles tendonitis & plantar fasciitis.
• Costocondral/manubriosternal joint : Chest pain.
6. Root joint involvement : Hip & shoulder joint arthritis
7. Extra-articular involvement :
• Uveitis. • Renal : 2° IgA nephropathy.
• Lung : B/L upper lobe fibrosis. • Osteoporosis.
• Cardiac : Aortic regurgitation.
Clinical test : Modified Schober test.

66 10 Medicine

Investigations :
X-ray (IOC) findings :
• Sacroilitis.
• Bone erosions → Romano sign.
• Bone fusion (ankylosis) → Bamboo spine.
• Square wave vertebra.
• Secondary sclerosis → Shiny corners sign.
• Interspinous ligament calcification → Dagger sign.
• Apophyseal joint capsule calcification → Trolley track sign
MRI : STIR sequence to detect sacroilitis.
Non-radiographic spondyloarthritis :
• Symptoms +.
• MRI : Sacroilitis.
• HLA B-27 +.
• X-ray : Normal.
• 5-10% of patients develop radiographic spondyloarthritis after 5-10 years.
Treatment of radiographic & non radiographic spondyloarthritis :

• NSAIDS : Indomethacin (reverses the progression of disease).
• Physiotherapy.
• TNF-alpha inhibitors.
• 1L-17 inhibitors : Secukinumab .
Note :
Diffuse Idiopathic Skeletal Hyperostosis (DISH) :
• Ligamentous calcification → Flowing candle wax appearance .
• Intervertebral disc space preserved.
• No sacroilitis.
Reactive arthritis :
• Occurs 2-4 weeks post infection :
Infection of Organism M : F ratio
Genito-urinary tract Chlamydia trachomatis (M/C 9:1
worldwide)
Gastrointestinal tract Shigella flexneri (M/C in India) 1:1
Upper-respiratory Beta-hemolytic streptococcus
tract Chlamydia pneumoniae
Note : Neisseria and E. coli do not cause reactive arthritis
• HLA-B27 + : Indicates risk for chronic reactive arthritis (seen in 15-20%).
• Arthritis : Acute onset + sterile/non-purulent.


• Peripheral predominant spondyloarthritis : Asymmetrical (LL > UL), additive,
painful oligoarthritis.
• Axial arthritis (30% cases) : Asymmetrical sacroilitis + thick/non-marginal/
coarse/fluffy/asymmetrical syndesmophytes.
• Enthesitis.
• Dactylitis : Sausage digits.
• Mucocutaneous manifestations :
a. Oral ulcers.
b. Keratoderma blenorrhagica.
c. Circinate balanitis.
• Extra-articular manifestations : Aortic regurgitation
Rx :
• NSAIDS : Indomethacin.
• Sulfasalazine : Used in chronic reactive arthritis.
Keratoderma blenorrhagica Circinate balanitis Dactylitis

IBD arthritis :
• Crohn’s disease > Ulcerative colitis.
• M : F = 1 : 1.
• Peripheral predominant arthritis : Seen in 25% cases.
• Ankylosis spondylitis like arthritis :
a. HLA-B27 +.
b. Seen in 10% cases.
Types :
Type 1 (LMAP) Type 2 (SMAP-U)
Large joint (knee) predominant, migratory, Small joint predominant, migratory, aggressive
asymmetrical, pauciarticular arthritis , polyarticular arthritis + uveitis
Correlates with bowel disease activity Does not correlates with bowel disease activity
Self limiting
DOC : TNF-alpha inhibitors.

68 10 Medicine

Psoriatic arthritis :
• Male = females.
• Develops after 40 years of age.
• HLA-Cw*0602 +.
• 60/20/20 rule :
a. 60% : Develop psoriasis followed by arthritis.
b. 20% : Develop psoriasis and arthritis together.
c. 20% : Develop arthritis followed by psoriasis.
Features :
1. Articular manifestations :
• Peripheral predominant arthritis : Commonly seen in plaque psoriasis > pus-
tular psoriasis (Severe destructive arthritis seen in HIV patients).
• Enthesitis.
• Dactylitis.
• Arthritis mutilans.
2. Extra-articular manifestations :
• Nail changes :
a. Pitting (M/C). e. Chronic B/L posterior uveitis.
b. Onycholysis. f. Aortic regurgitation.
Arthritis mutilans
c. Oil drop sign.
d. Yellowish nail margin.
e. Horizontal ridging.
Classification of psoriatic arthritis :
1. Symmetrical polyarthritis (M/C). Nail pitting Onycholysis Oil drop sign
2. Asymmetrical oligoarthritis.
3. Axial arthropathy :
• Cervical spine involvement +.
• Thick, non-marginal, asymmetrical, coarse, fluffy
syndesmophtes +. Psoriatic arthritis
4. Pure DIP arthritis.
X-ray findings :
• Ray pattern (Characteristic) : Involvement of DIP, PIP & MCP joints.
• Marginal erosion with adjacent bony proliferation → Whiskering.
• Pencil-in-cup deformity.
• Ivory phalanx.
• Arthritis mutilans.
Rx :
• 1st line : TNF-alpha inhibitors.
• 2nd line : Methotrexate.
Pencil-in-cup deformity
• Others :
a. IL-17 inhibitors : Secukinumab. c. JAK inhibitors : Tofacitinib, baricitinib.
b. IL-12/23 inhibitors : Ustekinumab. d. PDE-4 inhibitors : Apremilast.

Ankylosing Reactive arthritis IBD arthritis Psoriatic arthritis
spondylitis
Features • B/l sacroilitis • Asymmetrical • B/l sacroilitis • Asymmetrical
• Thin marginal involvement • Thin marginal involvement
symmetrical • Thick non symmetrical • Thick non
syndesmophyte marginal syndesmophyte marginal
asymmetrical asymmetrical
syndesmophyte syndesmophyte
Enthesitis + +++ - +++

Dactilitis - +++ - +++
Skin & - Mucocutaneous - Nail changes +
nail manifestation
changes • Keratoderma
blenorrhagica
• Circinate bal-
anitis
Summary of arthritis 01:15:35
1. Chronic symmetrical small joint arthritis :

• Rheumatoid arthritis. • Psoriatic arthritis (DIP joint +).
• SLE/SLE-like arthritis. • Calcium pyrophosphate deposition disease (CPPD).
2. Acute asymmetrical oligoarthritis :
• Reactive arthritis, psoriatic arthritis.
3. Monoarthritis :
• Crystal arthritis (MTP joint +), septic arthritis (Knee +).
4. Non-inflammatory arthritis :
• Osteoarthritis.
• Asymptomatic CPPD, calcium oxalate crystal disease, Calcium hydroxyapatite
deposition disease.
5. Inflammatory non-erosive arthritis :
• SLE, SLE-like arthritis.
6. Erosive arthritis :
• Rheumatoid arthritis. • Chronic tophaceous gout.
• Peripheral spondyloarthritis.

70 11 General Medicine
----- Active space ----- RHEUMATOLOGY REVISION 3
Vasculitis 00:00:37
Classification of vasculitis
(based on size of predominant vessel involved)
Large vessel Medium vessel Small Variable Single organ Secondary

• Giant Cell Arteritis • Kawasaki. vessel • Behcet’s • Cutaneous leukocytoclastic vasculitis
(GCA). • Poly Arteritis disease. angiitis/Hypersensitivity
• Takayasu arteritis. Nodosa (PAN). • Cogan’s vasculitis (HSV).
syndrome. • Cutaneous PAN (Arteriole).
• Primary CNS Vasculitis.
• Isolated aortitis.
ANCA Immune-complex mediated
• Granulomatosis with Poly Angiitis • IgA vasculitis (Henoch-Schönlein Purpura).
(GPA). • Cryoglobulinemic vasculitis (CAV).
• Microscopic Poly Angiitis (MPA). • Good Pasture syndrome (GPS).
• Eosinophilic Granulomatosis with • Hypocomplementemic urticarial vasculitis
Poly Angiitis (EGPA). (HUV) : Anti C1q antibodies.
Note :
Most prominent vessel involved : Venules.
Cogans syndrome → Aortitis + interstitial keratitis + vestibulitis (SNHL).
Secondary vasculitis :
Causes :
1. Connective tissue diseases :
• Immune-complex (IC) mediated small vessel vasculitis (M/c).
• Medium vessel involvement : RA (Gangrene or GI vasculitis)
SLE (CNS vasculitis or GI vasculitis).
2. Aortitis : IgG4 related disease.
3. Drugs :
• Immune Complex mediated vasculitis.
• Anti Neutrophilic Cytoplasmic Antibody (ANCA) : Hydralazine, Propylthiouracil
(PTU), Minocycline & Levamisole.
4. Infections :
• HBV (Similar to PAN).
• HCV (Similar to Cryoglobulinemia).
5. Lymphoproliferative malignancy.

Temporal arteritis and takayasu arteritis 00:08:52 ----- Active space -----
Pathogenesis : Granulomatous vasculitis :

• Fragmentation of internal elastic lamina. • GPA.
• Transmural inflammation with mononuclear cells, • EGPA.
few giant cells ± granulomas. • Temporal arteritis.
• Characterized by HLA DRB104. • Takayasu arteritis.
Temporal arteritis • RA.
• Cogan.
• CNS vasculitis.
Temporal arteritis/Giant Cell Arteritis (GCA) Takayasu arteritis
• > 50 years. • < 40 years.
Seen in • Median age : 72 yrs. • Median age : 25 yrs.
• F : M → 2 : 1. • F : M → 9 : 1.
Superficial temporal (M/c) > Vertebral >
Left subclavian artery (M/C),
Arteries Ophthalmic > Posterior ciliary artery (also
aorta, mesenteric & coronary
involved cause altitudinal hemianopia & is a/w
artery.
Anterior Ischemic Optic Neuropathy).
Typical GCA (M/C) :75 % cases
• New onset Headache.
• Elevated ESR. • Upper limb claudication.
• Jaw claudication. • Asymmetric pulse & BP.
• Temporal artery tenderness. • Carotid/Aortic bruit.
Clinical • Visual symptoms. • Renovascular hypertension
features • Poly Myalgia Rheumatica (PMR). (RVH) especially in young
Atypical GCA : 25 % cases Indian female .
• PUO (Pyrexia of Unknown Origin). • Renal & pulmonary
• Non specific : Fatigue, weight loss, malaise. involvement can be seen.
• C5 radiculopathy.
• Throat pain + Cough.
• IOC : Temporal artery biopsy (Skip lesions). • IOC : CT angiogram.
Investigation • Doppler ultrasound. • Best : MR angiogram.
• PET scan to rule out aortitis. • Gold standard : Arteriography.
• Steroids started immediately when GCA is
Steroids ±
Rx suspected → To avoid loss of vision.
Surgical revascularization.
• Relapse : Tocilizumab (IL6 inhibitor).
Polymyalgia rheumatica :
• Seen in patients with GCA.
• Pain and stiffness of hip, shoulder & pelvic girdle.
• Elevated ESR (> 50).
• Good response to low dose steroids.


ANCA vasculitis 00:20:18
D/t antibodies against Proteinase-3 or Myeloperoxidase (MPO) present inside

the granules of the neutrophil.
Screening test : Indirect immunofluorescence (IIF).
Confirmatory test : ELISA.
Cytoplasmic pattern Perinuclear pattern

c-ANCA positive. p-ANCA positive.
True positive c-ANCA : True p-ANCA positive : False p-ANCA positive :

Antibodies against Antibodies against MPO +ve. Antibodies against MPO -ve.
Proteinase-3. Causes : Causes :
Causes : • Renal limited vasculitis • Autoimmune hepatitis (Type 1).
• GPA (Maximum). (Maximum). • Primary Sclerosing Cholangitis.
• MPA. • MPA. • RA.
• Renal limited vasculitis. • EGPA. • Inflammatory Bowel Disease.
• EGPA. • GPA. • Infective Endocarditis.
• Drugs (Hydralazine). • Cystic Fibrosis.
• Goodpasture syndrome.
GPA vs MPA vs EGPA vs PAN :

GPA/ Wegener’s MPA (Microscopic EGPA/ PAN (Polyarteritis
disease Polyangiitis) Churg strauss nodosa)
syndrome
ANCA c-ANCA > p-ANCA p-ANCA > c- ANCA - Negative.
Vasculitis Necrotizing small vessel vasculitis Eosinophils ± Focal necrotizing
(Neutrophils) with fibrinoid necrosis. fibrinoid inflammation.
necrosis.
Granulomas Present. Absent. Extravascular. Absent.
Immuno- Pauci-immune. - -
fluorescence
Age > 40 years. Elderly people. - -
Vessels Small vessels. Small & Medium Medium vessels.
involved vessels.

GPA/ Wegener’s EGPA/Churg strauss ----- Active space -----

MPA PAN
disease syndrome
Consti-
Present (Weight
tutional Absent Present Absent
loss ≥ 4 kgs)
symptoms
URT (95%) URT (30%) URT
• Sinusitis (Staph. aureus). Allergic
• SNHL. manifestation (+)
• Sub glottic stenosis. Asthmatic phase Present.
• Serous otitis media. followed by
• Midline nasal deformities. Vasculitic phase.
Major LRT (90%) LRT (30%) LRT
manifes-
tations • Thick walled • Diffuse
Fleeting lung
cavitating nodules. infiltrates Lung parenchyma
alveolar
• Diffuse alveolar (Asthma like : Never involved.
hemorrhage.
hemorrhage (DAH). presentation).
Renal (60%) Renal (100%) Renal
Rapidly Progressive
Very rare (If Renal parenchyma
Glomerulonephritis RPGN type 3.
present very mild) : Never involved
(RPGN) type 3.
1. Ocular manifestations
Scleritis. Absent. Absent. Absent.
2. Skin manifestations
+ ++ (purpura) + Absent.
3. Neurological manifestations
++ (Cranial neurop-
Minor
++ + athy /Mononeuritis +
manifes-
multiplex).
tations
4. Other Mainfestations
• Bronchial artery
• Eosinophilic : (Hemoptysis)
gastroenteritis • Testicular artery
- - • Eosinophilic : Tenderness/
myocarditis : (M/c pain
cause of death). • Renal artery :
RVH
• Steroids + Oral or I/v Cyclophosphamide/ Rituximab.
Treatment • Maintanence : Azathioprine > Mycophenolate Mofetil.
• EGPA : Mepolizumab (IL-5 Antagonist).


Poly Arteritis Nodosa :
Other features :
• Features of medium vessel involvement in PAN → Nodules, ulcers, gangrene
& mononeuritis multiplex/polyneuropathy, livedo reticularis.
• Associated with Hepatitis B positivity (30 : 1)
& Hairy cell leukemia.
• Micro aneurysms can be seen (MR Angiogram
preferred more than CT Angiogram to detect
microaneurysm).
Diffuse Alveolar Hemorrhage
• Overall prognosis : Very poor.
Immune complex mediated small vessel vasculitis 00:37:28
IgA vasculitis (Henoch Schonlein purpura) Cryoglobulinemia associated vasculitis

Histology Leukocytoclastic vasculitis with immune complexes (+) & no ANCA positivity.
Age • Children < 5 years (M/c in boys). Middle to late middle aged females.
• Adult (More severe renal involvement).
Types • Type 1 : Monoclonal IgM.
- A/w Waldenstrom’s disease.
• Type 2 : Monoclonal IgM &
polyclonal IgG with Rheumatoid
factor (RF) +ve.
• Type 3 : Polyclonal IgG with RF +ve.
Skin • Non thrombocytopenic palpable purpura • Confluent purpura.
on lower limb (IgA) : 100% cases. • Ulcer/gangrene : Medium vessel
involvement.
GIT • Abdominal angina (M/C) : Presents Hepatitis C Virus (HCV) associated
with severe abdominal pain. (Type 2,3).
• Intussusception (most dangerous).
• Testicular torsion.
• Scrotal swelling.
• Blood in stools.
Joints KLMNO arthritis : (Knee joint SLE like arthritis &
predominant Large joint Migratory associated myalgia.
Non-deforming Oligoarthritis).
Renal • IgA nephropathy (Self-limiting). Membranoproliferative
• RPGN presentation in Adults. Glomerulonephritis (MPGN).
Rx Steroids (For joints & GIT manifestations). Management of HCV
Prognosis : Good in children. Severe cases : Rituximab.

RHEUMATOLOGY REVISION 4 ----- Active space -----
IgG4 related Disease 00:01:05
IgG4 :
• Doesn’t bind complement.
• Bi-specific antibody (Binds & sequesters antigen).
• Prevents interaction b/w IgG1 & C1q needed for complement cascade.
• Not an inflammatory molecule.
Chronic antigenic stimulation (Galectin 3)
Pathogenesis :
↓
↑↑ IgG4
↓
Activates myofibroblasts
↓ TGF-b
Fibrosis.
Characteristic findings :
• Tumefactive lesions/lymphadenopathy.
• Storiform fibrosis (Swirling/cartwheel appearance).
• Obliterative phlebitis.
• Mild eosinophilia (Background of atopy).
Clinical features :
M > F.
Subacute onset.
Constitutional symptoms like fatigue, weight loss.
Not seen : Fever, fibrinoid necrosis, granuloma, arthritis.
Major manifestations :
1. Type 1 Autoimmune Pancreatitis (AIP) : M/C manifestation.
• Obstructive jaundice.
• Exocrine & endocrine insufficiency (Type 3C DM).
• Enlarged, sausage-shaped pancreas with irregular/feathery borders.
2. Submandibular gland involvement :

• Painless, asymptomatic, B/L symmetrical swelling.
• Minor sicca symptoms.
3. Lacrimal gland involvement : Painless, asymptomatic, B/L symmetrical swelling.
4. Retroperitoneal fibrosis : Presents as B/L obstructive nephropathy.
76 12 Medicine
Sausage-shaped pancreas Storiform fibrosis Submandibular gland swelling

Note : Lacrimal + Submandibular + Parotid glands swelling → Previously called
Mikulicz syndrome.
Minor manifestations :
Organ system Manifestations
• Lymphocytic hypophysitis (Post partum).
CNS
• Pachy-meningitis without brain parenchymal involvement.
Orbit Orbital pseudotumour (Painful inflammatory mass).
Thyroid Reidel’s thyroiditis.
• Thickening of bronchovascular bundle.
Lungs • NSIP (Risk of ILD).
• Paravertebral mass.
Vascular Proximal aortitis (Only condition to involve aorta in vasculitis).
IgG4 sclerosing cholangitis. Previously → Primary sclerosing cholangitis
Biliary tract
(PSC).
• Tubulo-interstitial nephritis (M/C).
Kidney
• Membranous nephropathy (Low complements).
Investigations :
S. IgG4 : Normal in 40% cases.
Biopsy : IgG4/IgG ratio is more valuable in diagnosis.
Management :
First line : Steroids (Excellent response within 2 weeks).
Relapse : Rituximab (Steroid sparing agent).
Sarcoidosis 00:19:00
Features of sarcoidosis :
• F = M.
• Age : >18 years.
• HPE : Non-caseating granuloma with epitheloid cells in the centre and
T-lymphocytes in the periphery.
Immune paradox : Granulomas contain large numbers of lymphocytes but blood
picture shows lymphopenia.
Risk factor : Burning firewood. ----- Active space -----
Outcomes :
• 50% : Spontaneous resolution.
• 25% : Chronicity (Involving eyes, skin & lungs).
• 5% : Mortality.
Acute sarcoidosis
2 forms :
1. Lofgren’s syndrome.
2. Heerfordt-Waldenstrom syndrome.
1. Lofgren’s syndrome :
Good prognosis.
Clinical features :
• Fever (+/-).
• Uveitis (+/-).
• Arthritis.
• Hilar lymphadenopathy. Triad
• Erythema nodosum.
Arthritis (Misnomer) : Acute onset B/L ankle joint
tenosynovitis (Painful).
Garland sign
Garland sign :Right & left hilar lymphadenopathy + Right
paratracheal lymphadenopathy.
Erythema nodosum : 3 Ps.

• P : Painful.
• P : Pre-tibial. Without pigmentation
• P : Papule.
2. Heerfordt-Waldenstrom syndrome :
Clinical features : Erythema nodosum
• Acute B/L symmetrical anterior uveitis
• Parotitis. Triad
• B/L LMN 7th nerve palsy.
• Fever (+/-).
D/d for uveitis :
1. Spondyloarthritis : Acute anterior alternating asymmetrical uveitis.
2. Sarcoidosis : Acute B/L symmetrical anterior uveitis.
3. Bechet’s disease : Posterior uveitis.

78 12 Medicine

Chronic sarcoidosis
Features :
Eyes :
• Chronic uveitis.
• Panuveitis.
• Retinal vasculitis.
Skin : Lupus pernio (Maculopapular/nodular).
Lung : Lupus pernio
• Bilateral Hilar lymphadenopathy.
• Upper lobe ILD (NSIP) : M/C cause of death.
• Thickening of broncho-vascular bundle (Most characteristic).
• Associated with : Small airway diseases & endobronchial obstruction.
• No paravertebral mass.
Clinical paradox : Disease worsens as hilar lymphadenopathy ↓.
Scadding scoring system :

Based on chest X-ray.
Stage Findings X-ray
• B/L hilar lymphadenopathy

1
• No infiltrates
• B/L hilar lympadenopathy

2
• Pulmonary infiltrates present
• No B/L hilar lymphadenopathy

3
• ↑↑ Pulmonary infiltrates
4 Pulmonary fibrosis

Other manifestations : ----- Active space -----

Organ system Manifestations
CNS • M/C : B/L LMN 7 nerve palsy.
th
• Acute transverse myelitis.

• Central diabetes insipidus.
• Leptomeningeal enlargement.
Orbit Maybe present but not typical of sarcoidosis.
Eye Any compartment maybe involved.
Salivary glands Parotitis ± Swelling.
CVS • Dilated cardiomyopathy (DCM).
• Conduction blocks.
Vasculitis Immune complex mediated small vessel vasculitis (No aortitis).
Joints • Arthritis.
• Bone cysts.
• Bone erosions.
Liver Intra-hepatic cholestasis.
Kidney • Pre-renal AKI (D/t hypercalcemia).
• CKD (D/t tubulo-interstitial disease).
Bone marrow Pancytopenia + Splenomegaly (Rare).
Hypercalcemia in sarcoidosis :
Granuloma → Secretes 1a hydroxylase → ↑ 1,25-OH D3 → ↑ Ca2+.
Investigations :
IOC : PET scan.
Best : Endobronchial USG (EBUS) + Transbronchial biopsy.
Management :
1st line : Steroids (Oral/IV).
2nd line : Methotrexate, Azathioprine. Hydroxychloroquine, Leflunomide.
3rd line : TNF-a inhibitors.
Therapeutic paradox : TNF-a inhibitors cause sarcoidosis-like lesions.
Sjogren’s syndrome 00:38:37
2nd M/C multiorgan autoimmune connective tissue disease.

Incidence : Middle aged females.
F : M = 9 : 1.
80 12 Medicine

Features :
• Dry mouth, dry eyes.
• Parotid swelling :
a. Mediated by IL-18.
b. Sicca symptoms +++ (Not steroid responsive).
c. Asymmetric painful glandular swelling → Suspect marginal zone B-cell
lymphoma.
• Dental caries.
• 50% patients have extra-glandular manifestations.
M/C extra-glandular manifestation : Arthralgia/arthritis (SLE-like).
Raynaud’s phenomenon can precede sicca symptoms in 1/3rd patients.
Associated with : HCV.
• M/C cause of secondary Sjogren’s : Rheumatoid arthritis (SLE is another
cause).
Investigations :
Biopsy :
• Gold standard investigation.
• Shows CD4 T-cell infiltrates.
Antibodies :
1. Anti-Ro :
• Early onset disease.
• Long duration disease.
• ↑ Risk for extra-glandular disease & lymphoma.
2. Anti-La.
Sjogren’s manifestations in other organs :
Organs Sjogren’s
CNS Ganglionopathy
Ocular Dry eyes
Salivary gland Parotid swelling
Endocrine Thyroid disorders
NSIP-LIP
Lungs
(GGO + Nodular cysts)
Vasculitis Small vessel vasculitis
CVS Pericarditis
Primary biliary
Liver
cirrhosis
Kidney Distal RTA
GGO : Ground glass opacities

Systemic Sclerosis 00:49:03 ----- Active space -----
Scleroderma + Systemic manifestations.

Scleroderma mimics :
• Scleredema. • Eosinophilic fasciitis.
• Sclermyxedema. • Nephrogenic systemic fibrosis.
Risk factors :
1. Genetic factors.
2. Environmental factors like drugs :
• Silicosis.
• Vinyl chloride.
• Bleomycin.
• Pentazocine.
• Contaminated L-tryptophan.
Pathogenesis :
Risk factor
↓
Immune dysregulation
↓
Vasculopathy (Small vessel endothelial injury)
↓
Thrombosis
↓
Capillary hypoxia
↓
Mesenchymal differentiation
↓
Activates myofibroblasts
↓
Produce TGF-b
↓
Fibrosis
ESR, CRP : N/↓ (No inflammation).
M/C cause of death :
• Diffuse SSc : ILD.
• Limited SSc : Pulmonary arteriolar HTN.
82 12 Medicine

Presentation :
1. Raynaud’s phenomenon (RP) :
• Episodic vasoconstriction in response to cold/stress/
vibration.
• Phases : Pallor → Cyanosis → Redness.
• Secondary RP shows : Raynaud’s phenomenon

a. Critical limb ischemia.
b. Nail fold capillaroscopy → Dilatation & dropout of capillaries.
• D/d of secondary RP :
a. SSc.
b. MCTD.
c. Sjogren’s syndrome.
d. Anti-synthetase syndrome.
• RP in limited SSc is long standing, more painful & severe
with ↑sed chances of critical limb ischemia (Compared
to diffuse SSc).
2. Musculo-skeletal involvement :
a. Arthralgia, myalgia, joint contractures (Diffuse SSc). Critical limb ischemia
b. Tendon friction rub :
• Coarse crepitations on joint movements.
• Seen in diffuse SSc.
• Poor prognosis.
• Antibodies : Anti-RNA polymerase 3, Scl-70.
c. Calcinosis :
• Ca2+ hydroxyapatite crystal deposition in subcutaneous & soft tissues.
• M/C seen in sites of trauma.
• Seen in : SSc, juvenile dermatomyositis.
d. Acral osteolysis : D/t erosive arthritis.
Types of systemic sclerosis (SSc) :

1. Diffuse SSc : Skin lesions anywhere on the body.
2. Limited SSc : Limited to face & area distal to the elbow.
3. Sine scleroderma : No skin lesions.

Limited SSc : ----- Active space -----

Skin tightening less.
Telangiectasia seen.
Less/absent cardiac & renal involvement, ILD, tendon friction rubs.
Consider CREST syndrome :
• Calcinosis cutis. • S : Sclerodactyly.
• Raynaud’s phenomenon. • T : Telangiectasia.
• Esophagitis.
GIT involvement :
• Esophagitis (M/C) : D/t loss of tone of Lower Esophageal Sphincter (LES).
• GAVE (Gastric Antral Valve Ectasia) : Watermelon stomach.
• Pneumatosis intestinalis.
• Small Intestine Bacterial Overgrowth (SIBO).
Diffuse SSc :
Short lasting RP.
Middle aged females.
F : M = 5 : 1.
Presentation :
• Severe alopecia.
• Severe dryness of skin.
• Hyperpigmentation.
• Loss of body oil.
Salt & pepper skin
↓
Salt & pepper skin
↓
Mask facies :
• Microstomia.
• Pursed lips.
• Puckered mouth.
Masked fascies
Lung fibrosis, cardiac & renal involvement and tendon friction rub seen.
Antibodies :
1. Anti-topoisomerase-1 (Scl-70) : Seen in diffuse SSc.
2. Anti-centromere : Seen in CREST syndrome (Limited SSc).
3. Anti-RNA polymerase 3 (Anti-RNAP-3) :
• Scleroderma renal crisis (Most specific).
• Rapidly progressing skin lesions.
• GAVE.
• Malignancy.
• Tendon friction rub.

84 12 Medicine

4. PM/Scl-70 :
• Seen in both polymyositis and scleroderma.
• Shows nucleolar pattern.
Scleroderma renal crisis :

Seen in diffuse SSc.
Antibodies : Anti-RNAP-3 > Anti-topoisomerase-1.
Pathogenesis : Thrombotic microangiopathy of small vessels of kidney.
Presentation :
• Secondary Hypertension + Microangiopathic Hemolytic Anemia (MAHA) +
Thrombocytopenia.
• Secondary HTN usually presents as hypertensive emergencies.
• Occurs in first 4 years of disease.
Early treatment of diffuse SSc with steroids favors development of scleroderma
renal crisis.
Use of ACE inhibitors → ↓ Mortality.
Investigations :
Chest X-ray.
HRCT chest : GGO pattern → NSIP.
NSIP
Inflammatory Muscle Disease 01:13:31
Mononuclear cell infiltration into muscles + Systemic features.
Includes :
1. Polymyositis (PM).
2. Dermatomyositis (DM).
3. Juvenile DM.
4. Inclusion body myositis (IBM).
5. Immune mediated necrotising myopathy.
6. Cancer induced myositis.
7. Amyopathic DM.

Comparison b/w PM and DM : ----- Active space -----
Features PM DM
Age 40-60 years
Gender F > M (F : M = 2 : 1)
Incidence Adults only Juvenile group also seen
Occurrence Only in overlap syndromes Independently/Overlap
syndromes
Skin features Not seen Present
LMN weakness :
• B/L symmetrical
• Over a span of 3-6 months
• LL >>> UL
Presentation
• Proximal weakness
• No sensory findings
• Reflexes preserved
• Bowel & bladder normal.
• No necrosis • No necrosis
• CD8+ T cells • CD4+ T cells and B cells
Muscle biopsy • Endomysial & perimysial • Perivascular inflammation
(Gold standard) inflammation • Perifascicular atrophy
• Endomysial & perimysial
inflammation
CPK Positive (Usually)
Skin manifestations in DM :
Heliotrope rash
Gottron’s papule
Linear erythema Shawl sign

Holster sign
86 12 Medicine
V sign
Calcinosis cutis Periungual telangiectasia
Anti-synthetase syndrome :
Seen in both PM & DM.
Antibody : Anti-Jo-1.
Features : Fever + 1. Arthritis (SLE like)
2. ILD (NSIP)
3. Mechanic’s hand
4. RP Mechanic’s hand
Mechanic’s hand : Crusting & erosion of radial aspect of index & middle fingers.
Inclusion body myositis :

Seen in elderly males.
Chronic course.
Features :
• Asymmetrical weakness.
• Small muscles involvement.
Cancer-induced myositis :
DM (20-30%) > PM (10%) > IBM.
Antibodies :
• Anti-TIF-1g.
• Anti-NXP2.

Hematology Revision 1 13 87
HEMATOLOGY REVISION 1 ----- Active space -----
Hematology 00:01:33
Hematopoiesis :
Pleuripotent hematopoietic stem cell
Common Myeloid Progenitor (CMP) Common Lymphoid progenitor (CLP)

• RBC • B Lymphocytes
• Platelet • T Lymphocytes
• Neutrophil • NK Cells
• Eosinophil
• Basophil
• Monocyte → Macrophage (tissues)
Note :
• Erythropoietin (EPO) : Synthesized from peritubular interstitial fibroblast
(cortex and outer medulla).
• Supra-vital stains for reticulocyte identification : New methylene blue/
Brilliant cresyl blue.
Anemia 00:07:55
Reference range :
• Male : Hb < 13 g/dL
• Female : Hb < 12 g/dL • Male : Hb > 16.5 g/dL
• Pregnancy : Hb < 11 g/dL Needs evaluation • Female : Hb > 16 g/dL
• CKD : Hb < 10 g/dL
Laboratory parameters :
Decreases ( production of RBC)
• Retic count :
Increases (excessive destruction of RBC)
Note : Retic count is measured in %.
• Corrected retic count = Retic count x (Hb of the patient/desired Hb).

Desired Hb : Male : 15 g/dL & female : 13g/dL

88 13 Medicine

• RPI (Reticulocyte Production Index) : RPI = Corrected Retic count/2
Hypoproliferative : RPI <2.5 Hyperproliferative : RPI >2.5

Note : RPI is best.
• MCV (Mean Corpuscular Volume) : Average volume of an RBC.
Normal Range : 80 - 100 fL.
MCV > 100 : Macrocytosis
Megaloblastic Non megaloblastic

Hypo-proliferative anemia : 00:14:30
Symptoms duration : 2-3 months.
RPI : < 2.5, MCV normal to low.
Causes :
• Iron deficiency anemia.
• Megaloblastic anemia (vitamin B12, folate deficiency).
• Non megaloblastic macrocytic anemia.
• Anemia of chronic disease.
• Sideroblastic anemia.
• Thalassemia trait/thalassemia minor.
Increased MCV Macrocytosis
RPI < 2.5
Normal / MCV
Iron deficiency Sideroblastic Anemia of chronic Thalassemia

anemia anemia disease trait
Iron deficiency anemia 00:18:41
Iron metabolism :
1. Iron absorption :
Dietary iron
2/3 rd 1/3 rd
Heme iron : Fe2+ state Non Heme Iron

→ Transported via : Fe3+ state →
heme transporter Transported via
Divalent Met-
al Transporter
(DMT-1)

2. Iron storage : ----- Active space -----

Iron stored inside Ferritin (major)
the cell : Fe3+ state Hemosiderin (minor) : Macrophages
Note : Iron stores are detected using prussian blue (mainly hemosiderin).
3. Iron transport :
Note : In Brain
Iron in Fe 2+ state transported out via ferroportin
conversion of
Hephaestin in basolateral membrane converts Fe → Fe 3+ Fe 2+ → Fe 3+
2+
done by
Fe 3+ binds to transferrin (transport form)
ceruloplasmin
Fe 3+- transferrin complex
4. Iron uptake :
Marrow → Soluble transferrin receptors : Bind Fe-transferrin complex
Transferrin released into circulation Fe3+ taken up for erythropoiesis

Note : Iron stores in the body → Bone marrow, macrophage, liver, brain,
duodenal enterocytes.
Investigations :
Iron Indices :
Iron indices Normal value Comments
Serum ferritin 30-300 ng/mL • Reflective of Iron stores in the body.
• Earliest marker of Fe deficiency anemia.
• High S. ferritin (acute phase reactant)
cannot rule out Fe deficiency.
Serum iron 50-150 μg/dL Amount of transferrin bound Fe in circula-
tion.
TIBC (Total iron 300-360 μg/dL Indirect measurement of S. Transferrin
binding capacity)
TSAT (Transferrin Around 33 % or TSAT = (S. Fe/TIBC) x 100
Saturation) 1/3rd of TIBC
Peripheral smear : Microcytic hypochromic anemia.
RDW : Red cell Distribution Width (assessed from peripheral smear).
• Measures the degree of anisopoikilocytosis.
• Normal range : 11-14.5 %.

90 13 Medicine

Lab findings of IDA discussed below in a comparative table of other
hypoproliperfative anemia.
Note :
• Earliest marker of Fe deficiency : S. Ferritin.
• Most specific & sensitive marker : Soluble Transferrin Receptor assay (STFR)
or log ferritin.
• Free erythrocyte protoporphyrin : (lack of Fe to bind to protoporphyrin).
Clinical features : Fatigue, tiredness, palpitation & pallor on examination.

Additional symptoms to watch out for :
a. PICA symptoms : Especially pagophagia (craving for ice).
b. Restless leg syndrome.
c. Epithelial changes :
• Nails : Flattening, koilonychia.
• Tongue : Soreness, papillary atrophy, absence of filiform papillae.
• Mouth : Angular stomatitis.
• Hypopharynx : Dysphagia, esophageal webs → Plummer Vinson
syndrome.
• Stomach : Achlorhydria, gastritis.
d. Growth related issues, neuropsychiatric issues in growing
child.
e. Hair loss.
Severe iron deficiency
Evaluation : anemia → Microcytic
Fe deficiency anemia hypochromic
Female Male
Menstrual loss (mainly) GI blood loss unless proved otherwise
Note : Anemia in males usually evaluated with colonoscopy and upper GI

endoscopy to rule out GI bleed.
Other causes CKD on erythropoietin therapy (with EPO resistance)
of Fe deficiency Nutritional deficiency
anemia
Celiac disease : Malabsorption
• Anti-Ttg �b, anti-endomysial ab → Used to detect celiac disease.
• EPO therapy should be started only after replenishing iron stores.

Management : ----- Active space -----

Fe requirement = 2.2 x body wt x (Desired Hb- Patient Hb) + 1000
Daily requirement (adult Fe) :
• Adult male → 1 mg
• Adult female → 2 mg
• Pregnancy → 3 mg
Note : Usually 10 % of the Fe provided is absorbed
For adequate replenishment IV iron is the treatment of choice.
Ferric carboxymaltose Iron isomaltose
1 g/500 mg preparation
Effects of Fe injections :
• Retic count → Increase in 5-7 days and peaks around 2 weeks.
• Hb → Begins to rise around 2 weeks and increases by 2 g/dL by around 1
month.
Lab findings in hypo-proliferative anemia :
IDA Chronic Thalassemia Sideroblastic anemia

disease trait (α or β)
MCV/MCH or N or N (congenital)
N (acquired)
S. Iron N
TIBC N or N N or
Transferrin N
saturation
S. Ferritin N or N
S.TFR N N N or
S. Hepcidin N
BM iron stores N or N N or
Erythroblast iron N Ring forms
Blood picture on NCNC/ NCNC Microcytes Dimorphic
PS microcytic
hypochromic
NCNC : Normocytic Normochromic.

Note : Microcytic hypo-chromic anemia is also seen in miliary TB & RA.

92 13 Medicine
----- Active space ----- Anemia of chronic disease : 00:48:33

Functional iron deficiency → Problem in mobilization of Fe from the
stores. • Inflammation : IL-6 St imu
• Activin lat
e
inhibit
Hepcidin Ferroportin
bit
• Erythroferon inhi
• Hypoxia
Note : Gene controlling hepcidin → HFE gene on chromosome 6.
Sideroblastic anemia : 00:53:35

Problem with Protoporphyrin synthesis.
ALA synthase protoporphyrin
Heme synthesis : Succinyl CoA + Glycine ALA Heme
PLP
Causes :
• Congenital cause : X-linked ALA synthase defect (m/c).
• Acquired causes : Myelodysplastic syndrome (m/c), lead poisoning, copper
poisoning, chloramphenicol , pyrazinamide, alcohol (rare).
Electron microscopy : Pappenheimer bodies.
Peripheral smear : Dimorphic blood picture + Ringed sideroblast.
Ringed siderobast
Note : Ineffective erythropoiesis → Body will iron absorption.
Thalassemia trait/thalassemia minor : 00:58:59
Types of β thalassemia :
Thalassemia major βo βo
Intermediate β+ β+
Thalassemia trait/Thalassemia minor β β0 or β β+
Usually asymptomatic.
Hb : Usually around 10-11 g/dL.
Confirmatory test : Serum electrophoresis → HbA2 : 4.5-8.5 % (normal : 1.5-3%).
RDW : Normal (no aniosopoikilocytosis).
Note : Mentzer index = (MCV/RBC count).

• Thalassaemia trait : < 13.

Macrocytic anemia : Classification 00:00:10
Macrocytic anemia : Hypoproliferative anemia (RPI < 2.5) with MCV > 100 fL.
Macrocytic anemia
Megaloblastic Normoblastic
• B12 deficiency. • Liver disease (M/c) : Target cells
• Folate deficiency. can be seen.
• Drugs which directly inhibit DNA • Aplastic anemia.
synthesis : Cytarabine, 5-FU, 6-MP. • COPD.
• Thiamine deficiency. • Scurvy.
• Orotic aciduria. • Hypothyroidism. Target cells
• Post hemolysis.
• Alcohol.
Note : Nuclear maturation lags behind cytoplasmic maturation in megaloblasts.
B12 deficiency & folate deficiency 00:05:26
Vitamin B12 :
Body stores is 2-5 mg, RDA is 3-7 μg/day. Hence dietary deficiency is a rare
cause for B12 deficiency.
M/c cause : Autoimmune.
Absorption : Adenosocobalamine (or) Methylcobalamine
Stomach Combines with R factor (Haptocorrin)
D2 R factor & B12 complex is broken down
D2/D3 B12 + Intrinsic factor (IF) complex formation

Ileum Complex binds to cubam receptor
B12 absorbed into blood
Blood B12 + transcobalamin II Tissues
Note : R factor is present in saliva.
IF is produced by parietal cells in stomach.

94 14 Medicine

Causes of B12 deficiency :
• Pernicious anemia (autoimmune disorder).
• Ileal pathologies : Crohn’s disease, TB, tropical sprue.
• Small intestinal bacterial overgrowth (SIBO).
• Congenital deficiency of cubam receptor : Imerslund Grasbeck syndrome.
Folate deficiency : 00:10:50

Causes :
• Nutritional.
• ↑ Requirement : Pregnancy, myeloproliferative neoplasms, hemolysis.
• Drugs : Methotrexate, Triamterene, Pyrimethamine, PPI, Phenytoin,
anticonvulsants.
Absorption :
Polyglutamate (Dietary folate)
At Intestinal lumen
Monoglutamate (5 methyl THFA)
Homocysteine
B12
Methionine
In Epithelial cell
THFA
Methylmalonyl CoA B12 Succinyl CoA
THFA is required for 1 carbon transfer & DNA synthesis.
B12 deficiency Folate deficiency B12 + Folate deficiency

Methylmalonic acid ↑ Methylmalonic acid : N Methylmalonic acid ↑
Homocysteine ↑ Homocysteine ↑ Homocysteine ↑
Folate ↑ (Folate trap) Folate ↓ Folate ↓
In B12 deficiency, red cell folate levels are checked d/t their high levels.
Evaluation of B12 deficiency :
B12 < 200 pg/mL → B12 deficiency.
B12 200-300 pg/mL → Look for methylmalonic acid & homocysteine → if ↑ →
B12 deficiency.
Peripheral smear :
• Earliest finding : Hypersegmented neutrophils.
• Megaloblasts.
Hypersegmented neutrophils

• Dyserythropoeisis : ----- Active space -----

a. Howell Jolly bodies.
b. Cabot ring.
c. Basophilic stippling.
• Pancytopenia (In 20% cases).
Pernicious anemia : Megaloblasts Howell Jolly body

> 60 years, female > males.
Antibodies against :
• Parietal cell (Sensitive).
• Intrinsic Factor (IF) (Specific).
Features :
• Hypergastrinemia.
• Gastrin secreting tumors. Cabot ring Basophilic stippling
• Other autoimmune illnesses :
(Addison’s disease, type 1 DM, vitiligo, thyroid illness).
Note : Antral sparing is seen in pernicious anemia.
Symptoms :
1. Neurological : Order of parts affected.
• Nerve (neuropathy).
• Dorsolateral portion of spinal cord : Posterior column (Washbasin sign,
sensory ataxia) > lateral spinothalamic tract > corticospinal tract.
• Cerebrum : Optic atrophy, dementia.
2. GI : Gastritis, gastrin secreting carcinoid, intestinal type gastric
adenocarcinoma (Tumors are more common in men).
3. Less sensitive : Angular cheilitis, atrophic glossitis with red beefy tongue.
Rx : 1000 μg I/M of Hydroxycobalamin once weekly for 6 weeks (F/b once every 3 months).
Reticulocyte ↑ by 2-3 days, peaks by 6-8 days.
Hyperproliferative anemia 00:23:58
Hemolytic anemias → hyperproliferation : Reticulocytosis/macrocytosis.

Hemolytic anemia
Inherited causes Acquired causes

1. Hemoglobinopathies : 1. Immune :
• Sickle cell anemia. • Autoimmune.
• Thalassemia. • Alloimmune : HDN, FHTR.
2. Enzyme defects : • Drugs.
• G6PD deficiency. 2. Non immune :
• Pyruvate kinase deficiency. • Drugs/toxins.
• 5’ nucleotidase deficiency. • Infections.
3. Membrane defects : • PNH.
• Hereditary spherocytosis. • Fragmentation hemolysis.
96 14 Medicine

HDN : Hemolytic disease of newborn.
FHTR : Febrile hemolytic transfusion reaction.
All inherited causes are intracorpuscular defects, except familial HUS.

All acquired causes are extracorpuscular defects, except PNH.
Intravascular hemolysis Extravascular hemolysis
Features : Features :
• Hemoglobinuria. • Moderate splenomegaly.
Dark urine
• Hemosiderinuria. • Iron stores ↑.
• LDH ↑↑. • Jaundice ↑↑.
• Haptoglobin ↓. • Urobilinogen in urine ↑.
Causes : Causes :
• PNH (M/c). • Autoimmune hemolytic anemia
• Infections : Malaria, sepsis. (AIHA : Warm antibody).
• Paroxysmal cold hemoglobinuria • Hereditary spherocytosis.
(PCH). • Sickle cell anemia.
• Acute G6PD deficiency. • Thalassemia.
• Microangiopathic hemolytic anemia
(MAHA).
• Blood transfusion related hemolysis.
Drug induced immune hemolytic anemia :

1. Drug Modifying cell membrane : Cephalosporins.
2. Drug forming Auto antibody : Quinidine, Rifampicin, INH.
3. Drug forming Antibody against RBC : Methyldopa.
AIHA : 00:36:50
Destruction of RBCs :
• RBCs coated with warm antibody → in spleen.
• RBCs coated with complement → in peripheral circulation (Acrocyanosis,
Raynaud’s phenomenon).
Presentation :
• Symptoms over 4 weeks.
• Progressive fatigues, tiredness, palpitation.
O/E : Moderate splenomegaly.
Investigations :
Blood picture :
• Progressive decrease in Hb.
• TLC & platelet count : Normal.
DAT (Direct antiglobulin test) positive.
Note : AIHA + thrombocytopenia : Evan’s syndrome.

Direct Coomb’s test : ----- Active space -----
DCT
IgG +, C3 ±. IgG -, C3 +.
Coomb’s Cold
reagent
Warm
RBCs from (anti-human Coomb’s reagent Smear Agglutination
a patient with antibodies) binds to autoantibodies
hemolytic anemia are on RBCs and causes
containing added agglutination
surface antibodies
If smear does not show agglutination → Look for Donath Landsteiner antibody → If +ve → PCH.
PCH :Sudden onset of acute intravascular hemolysis.
RBC binds to antibody at 4 0C → Hemolysis at 37 0C.
Antibody : IgG antibody; Antigen : P antigen.
Donath Landsteiner test +ve.
Associated with syphilis.
Rx : Supportive care.
Warm AIHA Cold agglutinin disease PCH
Antibody IgG IgM IgG
Temperature at 37 0C 4 0C 4 0C
which antibody is
max active
Mechanism of Opsonisation Complement Complement
hemolysis
Site of hemolysis Extravascular Extra + intravascular Intravascular
PS Spherocytes Agglutination Combined
DAT +ve +ve +ve
(IgG +, C3 ±) (IgG -, C3 +) (IgG -, C3 +)
Donath - - +ve
Landsteiner test
Antigens Panagglutinin I antigen P antigen
Associations SLE/PAN/ IMN, mycoplasma, Syphilis
lymphomas (CLL)/ IgM secreting
RA/HIV tumors (Waldenstrom
macroglobulinemia).
Rx Steroid + splenec- Rituximab -
tomy + Rituximab

98 14 Medicine

Non immune hemolysis :
Causes :
• Infections : Malaria, babesia.
• Drugs.
• PNH.
• Fragmentation hemolysis.
Paroxysmal nocturnal hemoglobinuria : 00:50:30
Pathogenesis : Acquired mutation of PIGA gene.

PIGA gene on X chromosome → GPI anchor proteins → anchors complement
regulatory proteins (CD 55 & CD 59) to RBCs.
CD 55 : Decay accelerating factor (DAF).
CD 59 : Membrane inhibitor of reactive lysis (MIRL).
PIGA mutation → RBCs are sensitive to hemolysis (PNH III RBCs)

IOC : Flow cytometry (It determines the % of PNH III RBCs).
Presentation :
• M/c cause of acquired Intravascular hemolysis.
• Thrombosis (D/t defective urokinase plasminogen activator receptor, UPAR) :
Budd Chiari syndrome, cerebral venous thrombosis.
• Pancytopenia : Hypercellular marrow.
• Refractory anemia.
• Aplastic anemia (20%).
Note : Diseases with low LAP : PNH, CML.
Rx : Eculizumab (Anti C5).
Fragmentation hemolysis 00:54:30
Microangiopathy Macroangiopathy
• HUS. • Cardiac (Prosthetic
• TTP. valves).
Hemolytic uremic syndrome (HUS) :

Pathogenesis :
Endothelial injury → vWF released → thrombus formation + platelet trapping
→ RBCs pass through the injured vessel & form schistocytes.


• Microangiopathic hemolytic anemia (MAHA).
• Thrombocytopenia.
• Renal failure.
2 types :
1. Childhood type (D+) :
Dysentery +.
Causative organism : Shigella dysenteriae type 1 (Shiga toxin) or EHEC O157 : H7
(Shiga like toxin or verocytotoxin).
Presents with rapid progressive renal failure (Days to weeks).
Rx : Supportive care (excellent prognosis).
2. Adult type (D-) :
A/w alternate complement pathway activation (↓ C3 & normal C4).
Presents with hypertensive crisis.
Familial type Acquired type
Causes D/t defect in alternate complement • Drugs : Mitomycin,
pathway. Cisplatin, Calcineurin
• Complement factor H mutation (M/c). inhibitors, Ticlopidine,
• Complement factor B : Poor prognosis. Clopidogrel.
• Membrane cofactor P mutation : • HIV.
Good prognosis. • Post HSCT.
Rx : Plasmapheresis.
If recurrence in renal transplant : Rituximab + Eculizumab.
TTP :
Pathogenesis : (95%) Antibody against vWF metalloproteinase (ADAMTS 13).
Excess vWF → traps platelets.
Features :
• MAHA.
• Thrombocytopenia.
• CNS features.
• GIT features.
• Fever.
Rx : Plasma exchange (PLEX) + Rituximab.

100 15 Medicine
----- Active space ----- HAEMATOLOGY REVISION 3
Myeloproliferative Neoplasm (MPN) 00:00:08
Common features of MPN :

• No dysplasia (d/t mature cell expansion).
• Extramedullary hematopoiesis (EMH) → Hepatomegaly, Splenomegaly.
• Hyperviscosity & thrombosis.
• Fatigue ± Systemic features (weight loss, fever, myalgia).
• Can transform into one another/into Acute Myeloid Leukemia (AML).
MPN
Phenotypic Heterogeneity
BCR-ABL mutation : JAK2 mutation :
Reciprocal translocation t(9,22). Deletion of chr 9p.
• Chronic Myeloid Leukemia (CML). • Polycythemia Rubra Vera (PCRV) : 100% JAK2 +.
• Chronic Neutrophilic Leukemia (CNL). • Primary MyeloFibrosis (PMF) : 50-60% JAK2 +.
• Chronic Eosinophilic Leukemia (CEL). • Essential Thrombocytosis (ET) : 50-60% JAK2 +.
Approach to polycythemia :
Male : Hb > 16.5 g/dl, PCV > 49%
Female : Hb > 16 g/dl, PCV > 48%
RBC mass Normal RBC mass
Absolute erythrocytosis Relative erythrocytosis

(Fall in plasma volume)
EPO : Normal to low EPO : Increased • Post dengue.
(< 4 or upto 10) (> 10) • Dehydration.
Primary polycythemia : Secondary polycythemia

Mx : Hydration.
PCRV.
Hypoxia + No hypoxia
• COPD. Paraneoplastic polycythemia :
• Smoker. • Renal cell Carcinoma.
• Obstructive sleep • Hepatoma.
apnea. • Cerebellar hemangioblastoma.
• CO poisoning. • Uterine leiomyoma.
• Pheochromocytoma

Haematology Revision 3 15 101
Polycythemia Rubra Vera (PCRV) : 00:04:18 ----- Active space -----
Presentation :
• > 50 years.
• Female > Male.
Specificity Presentation
RBC Non specific to Systemic HT, vertigo, headache, thrombosis.
PCRV
WBC Basophilia (Aquagenic pruritis), Transcobalamin-1 ( Vit B12
Specific to PCRV binding capacity), hyperuricemia, risk of AML.
Platelet Acquired Von Willebrand Disease (VWD), Microvascular
thrombosis → Erythromelalgia (Burning pain in hand & feet).
Lab investigations :
• CBC : Hemoglobin, WBC, Platelet, Microcytic erythrocytosis.
• ESR : Very low.
Note : Microcytic erythrocytosis is seen only in
Thalassemia, PCRV & hypoxia.
WHO criteria for diagnosis of PCRV :
Major criteria :
1. Men : Hb > 16.5 g/dl, PCV > 49%.
Women : Hb > 16 g/dl, PCV > 48%.
2. Presence of JAK2 mutation : V617F mutation (M/C).
Minor criteria :
Erythromelalgia
Normal to low erythropoietin (EPO). (Red hands)
Diagnosis : 2 Major + 1 Minor criteria.
Treatment : Mx of PCRV
< 60 yrs/ > 60 yrs/

No evidence of thrombosis. Evidence of thrombosis +
Aspirin + Aspirin + Phlebotomy +
Phlebotomy (Target Hb : 12-13 g/dl). Ruxolitinib (JAK 1/2 inhibitor).
Primary Myelofibrosis (PMF) : 00:12:53
Mutations :
• JAK2 mutation (M/c)
• Calreticulin mutation Triple negative : Very poor
• MPL mutation (Thrombopoietin) prognosis.
Phases of PMF :
Initial phase : Hypercellular marrow.
Late phase : Fibrosed marrow. Hypercellular Megakaryocyte dysplasia
TGF β Bone marrow
marrow. (Cloud megakaryocyte) fibrosis.

102 15 Medicine

Presentation :
• 60-70 years.
• Male = Female.
• Has poor prognosis.
• Risk of thrombosis & AML (risk is PCRV > PMF).
• BM fibrosis Tear drop cells
Pancytopenia : Fatigue (M/c).
Leukoerythroblastic blood picture (Tear drop RBCs : Dacryocytes).
Hepatomegaly & Massive splenomegaly.
Bone pain. (d/t extramedullary hematopoiesis).
Skin : Sweet syndrome
Note : Massive splenomegaly : PMF, CML.
Moderate splenomegaly : PCRV.
Mild or no splenomegaly : ET.
Treatment :
• Bone marrow transplantation.
• If not fit for BM transplant : Ruxolitinib.
Essential thrombocytosis (ET) : 00:17:25
Presentation :
• 50-60 years.
• Female = Male.
• Has good prognosis.
• Risk of EMH, AML : Nil.
Risk of thrombosis & splenomegaly : Mild.
• Bleeding (Acquired VWD).
Lab investigations :
• Platelet > 4,50,000 (detected incidentally).
• Large mature platelets.
• Giant megakaryocytes with hyper lobulated nucleus & mature cytoplasm
(Staghorn megakaryocyte).
Note :
• Giant megakaryocyte : Idiopathic Thrombocytopenic Purpura.
• Small platelet : Wiscott-Aldrich syndrome.
• Pawn ball : MDS. Mx of ET
Treatment :
< 60 yrs/ > 60 yrs/
No evidence of thrombosis. Evidence of thrombosis +
Aspirin. Aspirin + Hydroxyurea > IFN α >

Anagrelide (risk of leukemia +).

Bone Marrow Failure Syndromes 00:20:46 ----- Active space -----
• Aplastic anemia.
• Myelodysplastic Syndrome (MDS).
• Pure Red Cell Aplasia (PRCA).
• Secondary myelofibrosis (Myelophthisis) : Secondary to drugs/toxins.
Approach to pancytopenia :
Pancytopenia
Hypocellular marrow. Hypercellular marrow.
• Aplastic anemia (Chronic). • AML/ALL (Acute).

• MDS (Hypocellular variant). • MDS.
• Aleukemic leukemia. • PMF.
• PNH (Paroxysmal Nocturnal • PNH.
Hemoglobinuria) : Rare. • Hairy cell leukemia.
• Lymphoma with BM involvement.
• Megaloblastic anemia (Rare).
• TB, SLE, HIV, Sarcoidosis.
Aplastic anemia : 00:24:56
Pancytopenia + Hypocellular marrow.
Causes :
Inherited causes :
• FANCA mutation : Fanconi anemia.
• Dyskeratosis congenita (DC).
• Ribosomopathy : Schwachman-Diamond syndrome. Hypocellular bone marrow
Polydactyly in Fanconi anemia Abnormal skin pigmentation in DC. Nail dystrophy in DC.
Acquired causes :
• Idiopathic (M/C).
• NonA-NonB-NonC hepatitis virus (Transient failure).
• Drugs : Chloramphenicol, NSAIDS, d-Penicillamine.
• Eosinophilic fasciitis (scleroderma mimic).

104 15 Medicine

Presentation :
• > 60 years.
• Very poor prognosis.
• Bleeding (M/c).
• Fatigue.
• Significant neutropenia → More prone to invasive aspergillosis.
Treatment :
• Allogenic Hematopoietic Stem Cell Transplantation (AHSCT).
• If not fit for transplantation :
equine Anti-Thrombocyte Immunoglobulin (e-ATG) + Cyclosporine.
Pure Red Cell Aplasia :

• RPS-19 gene mutation.
• Associated with Diamond-Blackfan syndrome & thymoma/CLL.
• Giant pro-erythroblast is seen in Parvo B19 infection.
• Hereditary spherocytosis + Parvo B19 infection → Aplastic crisis.
Myelodysplastic Syndrome (MDS) : 00:31:17
Myeloid cell dysplasia → Ineffective myelopoiesis → Pancytopenia.

Presentation :
• > 60 years.
M/c in India.
• 5q deletion MDS
40-60yrs.
Female > Male.
Respond well to lenalidomide.
• Anemia (M/c) : Macrocytic > Microcytic anemia.
Lab investigation :
• BM : Hypercellular > hypocellular marrow.
• RBC : Ringed sideroblast, megaloblast, macrocytic normoblast.
• WBC : 5-19% blast (Risk of ALL), Pseudo Pelger Huet cells (< 2 lobes in
nucleus), Dohle bodies, Toxic granules.
• Platelet : Pawn ball megakaryocytes.
Dysplastic megakaryocyte Pseudo Pelger Huet cells Ringed sideroblast

Treatment : ----- Active space -----

AHSCT.
• Trilineage
involvement Not fit for AHSCT Hypomethylating agents : Azacitidine/Decitabine.
5q deletion +ve Lenalidomide.

• Single lineage
(Anemia) 5q deletion -ve Erythropoietin.
• Newer drug in MDS : Luspatercept → Inhibits SMAD signaling pathway.
Plasma cell dyscrasia 00:37:26
Normal Plasma cells : Polyclonal.

Plasma cell dyscrasias : Monoclonal.
1. Multiple myeloma.
IgG with monoclonality/light chain restriction (M/c). Hence, called IgG myeloma.
M-component → Monoclonal protein (IgG).
2. Waldenstrom macroglobulinemia.
3. AL (Amyloid Light chain) amyloidosis.
4. Heavy chain disease.
Multiple Myeloma (MM) : 00:41:09
MGUS (Monoclonal Smoldering Multiple

Gammopathy of myeloma myeloma
Undetermined (Asymptomatic (MM)
Significance) myeloma)
M protein concentration <3g/dl ≥ 3g/dl ≥ 3g/dl
BM plasma cells < 10% ≥ 10% ≥ 10%
Myeloma defining event Absent Absent Present
MGUS has 1% chance of transforming into myeloma.
Myeloma defining events : SLIMCRAB
1. Sixty (≥ 60%) : Bone marrow plasma cells.
2. Light chain ratio : κ/λ or λ/κ > 100.
3. MRI : Atleast one focal lesion.
4. Ca > 11mg/dl : Hypercalcemia.
2+
5. Renal failure : Creatinine > 2mg/dl.

6. Anemia : Hb < 10g/dl.
7. Bone : Lytic lesion ≥ 1
Diagnosis of Myeloma : 1 out of 7 events + M-protein + BM plasma cells.

106 15 Medicine

Presentation :
• > 70 yrs.
• Male > Female.
• Bone pain or unexplained fracture.
• Anemia + ESR + Reversal of albumin globulin ratio.
• Hypogammaglobulinemia → Risk of infection (Recurrent pneumonia/UTI).
• Acute Kidney Overflow proteinuria.
Injury Proximal Renal Tubular Acidosis.
Renal failure in elderly.
Light Chain Cast Nephropathy (LCCN) : M/c type (λ > κ).
Light chain deposition disease (κ > λ).
• Radiculopathy.
High risk MM :
• Del 17p.
• t (14 ; 16). M-spike
Very poor prognosis.
• t (14 ; 20).
• t (4 ; 14).
Serum Protein Electrophoresis
Investigations :
• Serum Protein Serum Immuno + Serum Free Light Followed
+ by
BM biopsy.
Electrophoresis (SPEP) Electrophoresis (SIFE) Chain ratio (SFLC).
• Flow cytometry : CD 38 +ve, CD 138 +ve, CD 19 -ve.
Treatment :
Low & Moderate risk MM High risk MM
3 cycles of 3 cycles of
Autologous Autologous
Bortezomib + Followed Carfilzomib + Followed
Stem Cell Stem Cell
Dexamethasone + by Dexamethasone + by
Transplant Transplant
Lenalidomide. Lenalidomide.
• Autologous stem cell transplant is not curative → Relapse can occur.

• Newer drug in MM : Daratumumab (CD 38 monoclonal antibody).
Lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia :
Lymphoplasmacytic cells (IgM bearing memory B cell) proliferation in BM.
Presentation :
• Myd 88 mutation.
• No lytic bone lesions or renal lesions.
• IgM related hyper viscosity syndrome :
a. Cryoglobulinemia.
b. Cold Agglutinin disease.
Treatment : Plasmapheresis (PLEX).
Maturation of B cell 00:01:09
In bone marrow :
Common lymphoid progenitor CD 34, HLA DR Precursor B cell ALL :
• Pro B cell ALL.
Pro B cell CD 19, CD 34, HLA DR
• Pre B cell ALL (M/c) :
Pre B cell CD 10 (CALLA antigen), TdT Early pre B cell ALL → Best prognosis.
CD 19, CD 20, CD 21, CD 22, • Immature B cell ALL.
CD 79a, CD 79b,
Immature B cell CD 19, CD 20, CD 21, CD 22, CD 79a, CD 79b, SIgM

In blood :
Immature B cell
CD 19, CD 20, CD 21, CD 22,
Naive B cell
Majority Few CD 79a, CD 79b, SIgM, CD 5±
Apoptosis Lymph node

Failure of apoptosis
Monoclonal naive B cell expansion
Chronic lymphocytic leukemia
CD 19, CD 20, CD 21, CD 22,
CD 79a, CD 79b, SIgM, CD 5,
CD 23
In lymph node : CD 19, CD 20, CD 21, CD 22,
B cell reaches interfollicular area CD 79a, CD 79b, SIgM, SIgD
(Acquires SIgD)
Pre germinal center Germinal/activation/
(Mantle zone) maturation center
CD 19, CD 20, CD 21,
Mantle cell lymphoma • Diffuse large B cell lymphoma (DLBCL) (M/c). CD 22, CD 79a, CD
CD 19, CD 20, CD 21, CD 22, CD 79a, • Burkitt’s lymphoma. 79b, SIgM, SIgD, CD
CD 79b, SIgM, SIgD, CD 5, cyclin D1 • Follicular lymphoma.
10, CD 23, BCL-6.
Note : Markers of maturation/activation are CD 10 & CD 23.

108 16 Medicine

Germinal center B cell
ABC DLBCL Marginal

Activated B cell Marginal zone
(Poor zone
(Plasmablast) (Post germinal center)
prognosis) lymphoma
Plasma cell dyscrasias Memory B cell
• Multiple myeloma. • Small lymphocytic lymphoma (SLL).

• Heavy chain disease. • Waldenstrom macroglobulinemia.
• AL amyloidosis. • Hairy cell leukemia (HCL).
• Hodgkin’s disease.
Note : No additional markers in marginal zone (CD 19, CD 20, CD 21, CD 22, CD
79a, CD 79b, SIgM, SIgD).
Immunophenotyping : Plasma cell → CD 19, CD 38, CD 138.
T cell neoplasms 00:19:33
Precursor T cell leukemia/lymphoma (T-cell ALL) :

Few cells mature in thymus (Causing mediastinal widening), hence it is also
termed as lymphoma.
Mature T cell neoplasms :
1. Cutaneous T cell lymphoma (Mycoses fungoides)/Sezary syndrome.
2. Anaplastic large cell lymphoma (CD 30, ALK +ve) : Seen in people with breast
implants.
3. Angioimmunoblastic lymphoma : Midline deformities.
4. Large granular lymphocytic leukemia (In rheumatoid arthritis).
5. Enteropathic T cell lymphoma : A/w celiac disease.
6. Extranodal NK/T cell lymphoma : Presents with nasal mass.
7. Adult T cell leukemia/lymphoma : A/w HTLV 1.
Causative agents 00:22:41
1. EBV : EBV association

• Hodgkin’s disease. • 100/70/40/20 rule of classical Hodgkin’s disease :
• Burkitt’s lymphoma. 100% : Lymphocyte depleted.
• Primary CNS lymphoma. 70% : Mixed cellularity.
• Post transplant lymphoma. 40% : Nodular sclerosis.
• Extranodal NK/T lymphoma. 20% : Lymphocyte rich.
• No EBV association in lymphocyte predominant non
classical Hodgkin’s disease.

2. HIV : ----- Active space -----

• DLBCL.
• Burkitt’s lymphoma.
3. H. pylori : MALToma (M/c extranodal marginal zone lymphoma).
4. HHV 8 :
• Primary effusion lymphoma.
• Castleman’s disease.
5. HTLV 1 : Adult T cell leukemia/lymphoma.
6. HCV association:
• Waldenstrom macroglobulinemia.
• Splenic marginal zone lymphoma.
Acute lymphocytic leukemia (ALL) 00:26:28
ALL
B cell ALL T cell ALL
Pro B cell Pre B cell Immature Precursor T cell

ALL ALL B cell ALL ALL/lymphoma
B cell tumors T cell tumors
Prevalence More common. Less common.
Age group Children < 10 years. Mostly adolescent.
Adolescents.
Adults > 60 years.
Presentation Bone marrow involvement. Mediastinal widening.
B cell ALL
Symptoms of B cell ALL :

• Pancytopenia.
• Bone pain (D/t rapid proliferation in marrow).
• High count phase : Testes involvement,
CNS involvement, hyperviscosity.
Mediastinal widening Blasts in bone marrow
Morphology : ≥ 20% blasts in marrow.
Cytology : PAS, acid phosphatase +ve.
Immunophenotyping : CD 10, TdT.

110 16 Medicine

Molecular genetics :
• Hyperdiploidy : Good prognosis.
• Hypodiploidy : Poor prognosis.
Prognostic factors :
Good prognosis Bad prognosis
Race White Black
Age 2-9 years < 1 or > 10 years
Sex Female Male
CNS involvement - +
Testes involvement - +
HSM, lymphadenopathy - +
Mediastinal mass - +
Type L1 L2, L3
Molecular genetics Hyperdiploidy Hypodiploidy
Immunophenotype B cell, early pre B T cell
Translocation t (12, 21) t(9, 22), t(4, 11), t(1,19)
Notch 1 gene
Treatment :
Induction : To achieve minimal residual disease (< 0.01% blasts in BM).
Drugs used :
• Steroid.
• L Asparaginase (In children).
• Vincristine.
• Daunorubicin.
• High dose Methotrexate (also used in osteosarcoma).
Hyper CVAD (Cyclophosphamide, Vincristine, Adriamycin, Dexamethasone)
regimen is used in adults.
Consolidation : Given for 2 cycles.
Maintenance : Oral Methotrexate, 6-Mercaptopurine (6-MP). Given for 2 years.
If remission not achieved on induction then give newer drug : Blinatumomab (CD
19/CD 23 antagonist).
CLL 00:38:52
Monoclonal expansion of naive B cell (> 5000 cells/μL) d/t failure of apoptosis.
CD 5, CD 23 +ve.
Seen at 65-85 years.
Male > female.
Note : CLL → from blood, SLL → from lymph node.
Diagnosed incidentally on routine checkup.

Blood picture : ----- Active space -----

TLC : 70,000-80,000.
Absolute lymphocyte count : ↑↑↑.
Hb and platelet count : Normal.
Rai & Binet staging : Smudge cell
Stage 0 : Lymphocytosis alone.
Stage 1 : Lymphocytosis + lymphadenopathy. Peripheral smear in CLL :
Indications to treat : Small, blue round lymphocytes.
• Development of B symptoms : Fever, night sweats, weight loss.
• Lymphadenopathy.
• BM involvement.
• Richter’s syndrome : Low grade tumors (CLL, SLL) transforms to high grade
tumor (DLBCL).
• Autoimmune hemolytic anemia (Warm antibody mediated).
Bad prognosis
• Zap 70 expression.
• β2 microglobulin.
• Unmutated immunoglobulin heavy chain.
Treatment :
FCR regimen (Fludarabine, Cyclophosphamide, Rituximab) : Not fit for elderly.
BR regimen (Bendamustine, Rituximab) : Preferred regimen.
If not fit for above drugs (or) in case of relapse :

• Ibrutinib : Tyrosine kinase inhibitor.
• Venetoclax : BCL 2 inhibitor.
• Idelalisib : PI3K inhibitor.
Lymphomas 00:46:43
Low grade High grade

• Follicular lymphoma. • DLBCL.
• Marginal zone lymphoma (MZL). • Burkitt’s lymphoma.
• Hairy cell leukemia. • Mantle cell lymphoma
• SLL. (MCL).
• Waldenstrom macroglobulinemia.

112 16 Medicine

Common features :
> 60 years (Except Burkitt’s lymphoma which has childhood predominance).
Male > female (Except MZL, where female > male).
B symptoms are less common.
Non contiguous involvement.
Asymptomatic lymphadenopathy.
Extranodal involvement : GIT (M/c), Waldeyer’s ring, oropharynx.
Mantle cell lymphoma :

Aggressive.
BM, GIT, Waldeyer ring involvement, lymphomatoid polyposis.
R CHOP regimen (Routinely given for NHL) is not enough for MCL.
Immunophenotyping : CD 5, cyclin D1 +ve (CD 10 -ve, CD 23 -ve).
Cytogenetics : t(11, 14).
Molecular genetics : SOX 11 upregulation (Good prognosis).
Follicular lymphoma :
Key markers : CD 10, CD 23, BCL-6, aberrant BCL-2 expression.
Cytogenetics : t(14, 18) (Ig heavy chain gene on chr 14 & BCL on chr 18).
Rx : Rituximab for low grade. R-CHOP for advanced disease.
MZL :
Extranodal involvement :
• GIT : MALToma (A/w non atrophic pangastritis of H. pylori).
• Salivary gland : Sjogren’s syndrome is a risk factor.
• Spleen : A/w HCV.
Translocation : t(11, 18).

Markers : CD 19, CD 20, CD 21, CD 22, CD 79a, CD 79b, SIgM, SIgD (CD 5 -ve, CD 10
-ve, CD 23 -ve).
Female > male, d/t autoimmune association.
Responds to H. pylori therapy.
DLBCL : 00:56:24
Rapid growth of lymph nodes.

B symptoms + organ compression symptoms.
BM involvement ±.
Extranodal involvement :
• Primary CNS lymphoma.
• Body cavity lymphoma.
• Effusion lymphoma.

Markers : CD 10, CD 23, BCL-6, aberrant BCL-2. ----- Active space -----
ABC DLBCL (Mum 1 antigen positive) has poor prognosis.
Double hit lymphoma : High grade lymphoma with rearrangement of c-myc +
BCL-2 (or) BCL-6.
Triple hit lymphoma : High grade lymphoma with rearrangement of c-myc +
BCL-2 and BCL-6.
Both have poor prognosis.
Rx : R CHOP regime (Rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin
(vincristine), prednisone).
Burkitt’s lymphoma :
Ki67 index +++.
Chemosensitive.
Varieties :
Age group EBV Presentation
Endemic Child 100% Jaw mass/axillary mass
Sporadic Adult 70% Abdominal mass
Translocations : t(2, 8), t(8, 14), t(8,22) (c-myc on chr 8).

HPE : Starry sky pattern (Star → macrophages, sky → tumor cells).
Note : Waldenstrom’s macroglobulinemia secretes IgM (Myd 88 mutation).
Hairy cell leukemia : Bone marrow

Memory B cells undergo BRAF 1 mutation → Hairy cells
Spleen
Presents with pancytopenia + massive splenomegaly.
Markers of hairy cells : CD 11C, CD 25, CD 103, CD 123, TRAP +ve, Annexin +ve.
Bone marrow : Fried egg appearance + fibrosis.
Complication :
• Atypical mycobacterial infection. D/t monocytopenia &
• Aspergillus infection. neutropenia.
Rx : Cladribine (or) Pentostatin.

114 16 Medicine

Hodgkin’s disease : 01:03:41
Memory B cells undergoes aberration on PDL1 gene → Reed Sternberg cell in

appropriate inflammatory background → Hodgkin’s disease.
Hodgkin’s disease v/s NHL :
Hodgkin’s disease Non Hodgkin lymphoma
Bimodal peaking (15-34 years) Elderly
Contiguous Non contiguous
Nodal disease. Extranodal disease (Mostly)
Posterior cervical > supraclavicular >
axillary
B symptoms more common, B symptoms less common
highly a/w EBV.
Classification
Classical Hodgkin’s disease Non classical Hodgkin’s

(CD 15 +ve, CD 30 +ve) disease (CD 20 +ve)
• Lymphocyte rich : Scanty RS cell. Lymphocyte predominant
• Nodular sclerosis : Lacunar RS cell. : Classical popcorn RS cell
• Mixed cellularity : Classical RS cell. (EBV -ve)
• Lymphocyte depleted : RS cell absent
(100% EBV +ve).
M/c type in World : Nodular sclerosis.
M/c type in India : Mixed cellularity.
Note : HIV association is seen in mixed cellularity.
Mixed cellularity is more common in paediatrics & elderly (70 % EBV +ve).
Nodular sclerosis is more common in females (Mediastinal widening) (40% EBV
+ve).
Lymphocyte rich has good prognosis (20% EBV +ve).
Rx of classical HD : ABVD (Adriamycin, Bleomycin, Vincristine, Dacarbazine) regimen.
Newer drug → Brentuximab : Anti CD 30 (When first phase Rx does not suffice).

Endocrinology Revision 1 17 115
ENDOCRINOLOGY REVISION 1 ----- Active space -----
Classification of hormones 00:05:10
On the basis of structure :

1. Amino acid (AA) derivatives
Tyrosine derivatives Tryptophan derivatives
• T3, T4 . • Serotonin : Produced by
• Catecholamines : Enterochromaffin (EC) cells
Adrenaline (80%), Noradrenaline (Main source) and Raphe nuclei
(20%) and Dopamine. in brainstem.
Produced from adrenal medulla. • Melatonin : From Pineal gland.
2. Peptide hormones
Small peptide Large peptide Glycoproteins
hormones (<50 AA) hormones (>50 AA) (Protein > carbohydrate)
• Posterior pituitary • GH (191 AA) • FSH
hormones • Prolactin (199 AA) • LH
• Hypothalamic • Insulin • TSH
hormones • PTH (Share same α subunit).
• ACTH • Renin
3. Vitamin derivatives
Vitamin A Vitamin D
4. Steroid hormones
Adrenal cortex hormones Sex steroids
• Aldosterone : Zona glomerulosa • Testosterone.
(15% of cortex) • Estrogen.
• Cortisol : Zona fasciculata • Progesterone.
• Adrenal androgens : Zona re-
ticularis
Note : Most abundant androgen is
DHEAS > Androstenedione.

116 17 Medicine

On the basis of mechanism of action :
Group Receptor Property Examples

Intracellular receptor : • Signals mediated Type 1 hormones :
1. Type 1 : Cytoplasmic by : Receptor- • Adrenal cortical
receptor hormone complex. hormones.
(Homodimeric • Effector action : • Sex steroids.
receptor). Gene transcription.
2. Type 2 : Nuclear Type 2 hormones : Vit
receptor A, vit D and thyroid
Group 1
(Heterodimeric hormones.
receptor).
SF 1, DAX 1
Constitutive
(Gonadotroph cells)
Orphan receptors activation without a
and HNF4α (MODY
ligand.
type 1)
Cell membrane • Signal mediated
receptors : by : 2nd messen-
1. G Protein Coupled ger.
Receptor. • Effector
Group 2. Tyrosine Kinase action : Protein
2 Receptor. translocation/
3. Cytokine receptors protein channels.
(Janus kinase).
4. Serine threonine
kinase receptors.
Group 2 hormones receptors :

1. G-protein coupled receptor (GPCR) : 2nd messenger
cGMP (Gt) IP3/DAG (Gq) cAMP (Gs or Gi)
Action Vasodilation Vasoconstriction Vasoconstriction
Activates Ca2+
cAMP PKA pathway
Transducin Calmodulin
Pathway → protein
mediated pathway & Protein
phosphorylation
Kinase C

cGMP IP3/DAG cAMP ----- Active space -----
Hypothalamus
TRH, GnRH CRH
Anterior pituitary
- FSH, LH, ACTH, TSH
Posterior pituitary
V1 & V3 receptor,
V2 receptor
oxytocin
Hormones NO, ANF GIT
Secretin, glucagon
CCK and gastrin and somatostatin,
PTH and calcitonin.
ANS
α1 receptors α2 and β
Ach receptors. (CAMP (Gi) : α2 and
somatostatin.)
2. Tyrosine kinase receptor (Intracellular dimerization) : Insulin, all growth
factors (Except TGF β).
3. Janus kinase receptor : Growth hormone, prolactin and EPO.
4. Serine threonine kinase receptor : Inhibin, activin, BMP 7, TGF β.
Pituitary gland 00:24:32
Development :
Development of anterior and posterior pituitary is independent of each other.
Pituitary dysplasia : M/C cause for congenital hypopituitarism (Only related to
anterior pituitary).
Development
Anterior pituitary Oral ectodermal derivative (Rathke’s pouch).
Posterior pituitary and stalk Neuroectodermal derivative.

118 17 Medicine

Hormones produced by anterior pituitary :
Lateral portion Central portion
Hormone produced GH, PRL ACTH, TSH
Somatotrophs (Most abun- Thyrotrophs (Least abundant
Types of cells
dant cell), Mamotrophs cell), Corticotrophs
Vascular insult (Eg : Growth or mass (lymphocytic
Affected by
Sheehan syndrome) hypophysitis)
Size Major portion Minor portion
Note :
20% of thyroid hormone synthesis is independent of TSH.
Entire gland produces FSH and LH (Gonadotrophs).
Somatotrophs and Mammotrophs are acidophilic cells. Rest are basophilic cells.
Thyro-
Corticotrope Somatotrope Lactotrope Gonadotrope
trope
Tissue
specific Prop-1, Prop-1,
T-pit Prop-1, Pit-1 5F1, DAX-1
transcription Pit-1 Pit-1, TEF
factor
POMC :
• ACTH.
• MSH.
• β Lipotro-
Hormone GH PRL TSH FSH, LH
pins (Most
important
derivative :
Endorphins).
Glyco-
Glycopro-
Polypep- Polypep- protein
Protein Polypeptides tein : α, β
tides tides : α, β
subunits
subunits
POMC : Pro-opiomelanocortin.
Note :
• Prop-1 (M/C cause) > pit-1 : Mutation leads to congenital hypopituitarism..
• GATA-3 : Responsible for transcription of SF-1 and DAX-1.
• First cell to appear : Corticotroph. ----- Active space -----

• Last cell to appear : Lactotroph/Mammotroph.
• 4 hormones of happiness → DOSE :
a. Dopamine : Pleasure hormone.
b. Oxytocin : ↑sed by touch.
c. Serotonin : Regulates the Mood.
d. Endorphins : Pain killer.
Relation of hypothalamus to pituitary gland :

Anterior pituitary Posterior pituitary
Hypothalamo-hypophyseal
Known as Neurohypophyseal system.
portal system.
Type Blood connection Axonal connection
Superior hypophyseal Inferior hypophyseal artery (Mets
Blood supply
artery from breast Ca → Central DI).
Note : Metastasis (M/c Breast Ca) is carried straight to the posterior pituitary
through the Inferior Hypophyseal Artery → Diabetes Insipidus.
Stalk effect :
On T1 weighted sagittal MRI :
• Anterior pituitary : Iso-dense.
• Posterior pituitary : Hyper-dense.
Tumor displacing
stalk
T1 weighted MRI

120 17 Medicine
----- Active space ----- Pituitary Tumor
Hormonal effect Stalk effect Mass effect
Functional tumors : • ↑ ICT symptoms.

• ↑PRL : Prolactinoma (M/c and • Optic chiasma compression
microadenoma). → Heteronymous/
• ↑ GH : GH secreting tumor Bitemporal hemianopia.
(Macroadenoma). • Cavernous sinus thrombosis.
• ↑ACTH : ACTH secreting adenoma • VIth nerve palsy.
(Microadenoma). • Temporal lobe compression.
Disruption of the stalk → loss

of hypothalamic connection →
Leads to :
1. Hypopituitarism.
2. hyperprolactinemia : d/t
loss of inhibition of PRL.
3. Central DI : d/t disruption
of posterior pituitary.
Prolactinoma 00:45:34
Prolactin :
PRL levels
(microg/L or Conditions
ng/mL)
< 25 (At fasting) Normal value
Physiologically seen in REM sleep, stress, pregnancy, chest
25-40
wall stimulation.
• Drugs → Dopamine antagonists :
a. Typical antipsychotics, Risperidone, TCA, SSRI.
40-100 b. Metoclopramide.
• VIP and oxytocin, Estrogen, 1o hyperthyroidism.
• Systemic conditions : CKD, CLD, PCOS.

PRL levels Conditions ----- Active space -----
(microg/L or
ng/mL)
Tumor suspected, size corresponds to PRL level.
Circulating macroprolactin (Inactive form) → No symptoms or
> 100 tumor but ↑ PRL.
Hook effect : Normal PRL levels with symptoms and tumor →
Repeat the test in serial dilution.
> 200 Definite diagnosis of tumor.
Presentation :
M/C age of presentation : >25-30 yrs
If +ve in <20 yrs → Genetic cause :
3. MEN 1 syndrome (10 - 15%).
4. Carney’s complex.
5. McCune Albright syndrome.
Microadenoma Macroadenoma
Size <1 cm >1 cm
Incidence More common Less common
F:M 20 : 1 1:1
Presenta- In females :
tion Galactorrhea-amenorrhea complex (Hormonal effect) :
↑ PRL → ↓Hypothalamopituitarygonadal axis → Hypogonadism :
1. 20 amenorrhea.
2. Infertility.
3. Hot flushes.
Osteoporosis : Spine M/c.
Insulin resistance.
In males :
• Loss of libido
• Erectile dysfunction
• Non specific symptoms.
Present late → Giant adenoma (>4 cm) with stalk and mass
symptoms.

122 17 Medicine

Investigations :
Screening test : Fasting PRL.
IOC : Gadolinium enhanced MRI (Microadenoma does not take up the contrast
→ Hypodense, normal gland surrounding tumor → Hyperdense).
Treatment :
Medical management :
Indications :
1. All macroadenoma.
2. Symptomatic microadenoma.
3. Compression symptoms/enlarging microadenoma.
4. Hypopituitarism.
Asymptomatic accidentally detected microadenoma → Followed up with MRI
after 3-6 months.
Drugs → Dopaminergic agonist :

• Cabergoline (DOC) :
a. Long T1/2 and ↓ side effects.
b. Dose : 0.25 mg, 2/weekly.
• Bromocriptine (Pregnancy).
Medical Rx given irrespective of size of tumor
Follow up after 1 month → PRL levels.
↓↓ PRL ↑↑ PRL ↑↑ PRL with S/E of

↓ ↓ drugs present
Continue Rx for ↑se dose to 2 mg /week. ↓
2 years. (S/E : TR and ILD). Dopamine agonists
resistance (20%)
Surgical management : ----- Active space -----

Transspehnoidal tumor resection/hypophysectomy.
Indications :
1. Dopamine agonist resistance.
2. Pituitary apoplexy.
3. Pregnancy.
4. Persistent compression symptoms.
Growth hormone 01:02:27
T1/2 : 5-20 min, pulsatile → Levels cannot be checked directly.

Mode of action :
• Directly.
• Indirectly : Via Somatomedin-C/IGF-1 (Produced in liver) → Peripheral
actions.
↑ production in stage 2,3 and 4 NREM sleep.
Stimulators : Hypoglycemia (Most important), Ghrelin, GHRH.
Inhibitors : Somatostatin, obesity, hypocaloric state/malnutrition (GH resistance).
Measurement : Measured through IGF + IGFBP-3 (Insulin like growth factor
binding protein-3).
Actions :
GH IGF 1
Bone, epiphyseal growth +++ +++
Anabolic effect on protein +++ +++
Effect on carbohydrates Diabetogenic Anti-diabetogenic
Effect on fats Lipolysis Anti-lipolytic
Salt and water retention + -
Actions of GH independent of IGF 1 :
B : Bone growth.
E : Epiphyseal growth.
A : Adipose tissue : Lipolysis.
M : Muscle protein synthesis.
S : Salt and water retention.
Acromegaly 01:10:13
Causes :
Growth Hormone secreting adenoma (Accounts for 98% of acromegaly cases).
GH secreting ectopic tumor : Pancreatic islet cell tumor.
GHRH secreting hypothalamic tumor : Hypothalamic hamartoma.
GHRH producing ectopic tumor : Bronchial carcinoid.

124 17 Medicine

Salient features :
Generally macroadenomas.
Males > females.
Age > 40 years.
If +ve in < 20 yrs → Genetic cause :
1. MEN 1 syndrome.
2. Carney’s complex Acral enlargement
3. McCune Albright syndrome
20 % tumors associated with → ↑ PRL.
Clinical features :
Acral enlargement : Enlargement of peripheral parts.
All organs enlarge except brain.
Coarse facies :
• ↑ Thickening of lips, tongue, face. Frontal bossing
• Frontal bossing.
• Prominent supraorbital ridges.
Enlarged soft tissue growth.
Features of McCune Albright syndrome :
• Cafe-au lait spots.
• Polyostotic fibrous dysplasia → Asymmetric face.
• Precocious puberty.
• Tumors.
McCune Albright syndrome
Complications :
Structure/system Complication
Nerve Entrapment neuropathy.
Muscle Myopathies
Hypertriglyceridemia
Hypercalcemia (↑ 1α hydroxylase).
Metabolic Hypercalciuria
Hyperphosphatemia.
Diabetes (Uncontrolled, short duration).
Ophthalmic Angle closure glaucoma
Respiratory system OSAS, PAH.
M/C cause of death.
Asymmetrical LVH → HF with prEF.
CVS
↑ incidence of CAD.
HTN
Thyroid Goiter (IGF 1)
GIT Non-malignant colonic polyps
Renal Salt and water retention, renal stones (↑Ca2+)
Menstrual abnormality Oligomenorrhoea

Work-up : ----- Active space -----

Screening test : IGF-1 levels.
Confirmatory test : Glucose induced GH suppression test → 75 g of oral glucose
→ GH levels checked after 1 hr
• <1 ng/mL : Normal.
• >1 ng/mL : Confirmatory.
• >40 ng/mL : Poor prognosis.
IOC : Gadolinium enhanced MRI → Macroadenoma shows heterogenous
enhancement.
Management :
Surgical management :
TOC : Transsphenoidal Surgery
Immediate post-op GH :
• Undetectable : Good prognosis.
• Detectable → ↑ chances of relapse → Medical therapy started and
imaging repeated after 12 weeks.
Medical management (2nd line) :
• Somatostatin Receptor Ligands (SSRL) :
a. Octreotide
b. Lanreotide
c. Pasireotide
• Bromocriptine/Cabergoline.
• Pegvisomant : GH receptor antagonist.
On relapse : 2nd Sx done, curated as much as possible.

If pt unfit for Sx : Gamma knife stereotactic RT.

126 18 Medicine

ENDOCRINOLOGY REVISION 2
Acquired Hypopituitarism 00:00:18
Stalk effect :
Triad : Hypopituitarism + Central diabetes insipidus + Hyperprolactinemia.
Causes : Functional → Macroadenoma (GH secreting)

• Tumors :
Non functional → Rathke cleft cyst, craniopharyngioma.
• Trauma related/Surgery related.
• Infection : HIV, histoplasmosis, toxoplasmosis, tuberculosis.
Langerhans cell histiocytosis
• Infiltration : Sarcoidosis
Hemochormatosis
Pituitary hormones :
Hormone Effects of decreased hormones
• Asthenia, weight loss, fatigue, loss of appetite.
• Repeated episodes of hypoglycaemia/hypotension.
ACTH
• Euvolemic hyponatremia.
Note : Hypovolemic hyponatremia seen in aldosterone insufficiency.
• Cold intolerance, constipation, bradycardia.
TSH Note : 20 % thyroid hormone synthesis independent of TSH. (Frank
hypothyroidism features → Usually not present).
GH Centripetal obesity, hypertriglyceridemia, endothelial dysfunction
PRL Involved only in lactating mothers.
Hypogonadism features : Muscle wasting, dispropotionate
fractures.
FSH, LH
• Male : Loss of libido.
• Female : Irregular cycles, hot flushes, secondary amennorhoea.
Note :
Eosinophils inversely ∝ Cortisol rhythm.
• Cushing syndrome : Eosionopenia.
• ACTH insufficiency : Hypereosinophilia.

Aldosterone insufficiency features not seen with ACTH deficiency. ----- Active space -----
• Aldosterone (Mineralocorticoid) secretion → Controlled by RAAS axis.
• Aldosterone insufficiency features : Salt wasting, postural hypotension,
dehydration and hyperkalemia, hyponatremia (Hypovolemic).
Hormone measurement :
• FSH, LH, TSH, PRL : Direct measurement available.
• GH :
a. IGF -1
b. Growth hormone provoctive test : L-Dopa, glucagon (Preferred),
arginine, clonidine.
Note : Insulin tolerance test (Gold standard) : 0.1 U/kg iv → Induce hypoglycemia
and detect the level of GH, ACTH in response to it.
Pituitary Apoplexy : 00:10:06
Acute intrapituitary hemorrhage.

Etiology :
• Tumor (Adenoma).
• Necrosis (Sheehan syndrome).
• Normal gland (Risk factors : Diabetes mellitus, HTN,
sickle cell anemia).
Presentation :
• Headache ± Meningeal signs ± Ophthalmoplegia.
• Severe hypotension and severe hypoglycaemia.
Management :
Pulsatile methylprednisolone 500 mg, followed by decompression surgery.

128 18 Medicine
----- Active space ----- Sheehan syndrome vs Lymphocytic Hypophysitis : 00:15:15
Sheehan syndrome Lymphocytic hypophisitis

Post partum pituitary
Post partum inflammatory
ischemic necrosis.
Etiology mass : IgG4 containing
Lateral zone affected >
lymphoplasmacytic cells.
Central zone.
• Hypogonadism • Stalk effect
Effects
• ACTH failure. • mass effect.
• ADH (N) • ADH
Hormone • Prolactin, GH • Prolactin
profile • ACTH, TSH
• LH, FSH
• Can present immediately after • Pituitary enlargement.
delivery : Lactational failure. • Headache.
• 3-6 months post delivery : • Visual disturbance.
1. H/o post partum hemorrhage • Hypopituitarism.
with hypotension, shock and DIC → • Hyperprolactinemia.
Needing blood transfusions/fluid • Associated autoimmune
management. disease.
2. Menstrual irregularity, 2o • Diabetes insipidus.
C/F
amenorrhoea, breast atrophy,
decreased libido, genital and
axillary hair loss.
3. Diabetes insipidus.
4. At least 1 anterior pituitary
hormone deficiency.
5. Empty/severely damaged sella
turcica.
Rx Complete hormone replacement. Responds to steroids.
Image
Necrosed gland Inflammatory mass

Empty sella : 00:17:12 ----- Active space -----
Primary Empty sella Secondary empty sella

Tear in the dura : CSF sweeps • Part of necrosis/tumor.
Etiology
across to collect in the sella. • Sella empty.
Benign intracranial HTN
Seen in Sheehan syndrome
(Increased ICT)
Hypopituitarism Absent Present
Anti Diuretic Hormone 00:19:44
Stimuli for ADH release :
Osmotic stimuli (Major) Non osmotic stimuli (Minor)

Osmolality → ADH + Thirst Effective circulating
stimulation volume → ADH.
S. Osmolality = 2 x S. Na+ + (Blood glucose/18) + (BUN/2.8)
Note : ADH doesn’t cause hypernatremia as there is a compensatory in thirst.

Exceptions : Head injury & Intubated patients.
Action of ADH on vasopressin receptors :
Receptors Site & action
• Blood : Vasoconstriction, platelet aggregation.
v 1 receptors :
• Glycogenolysis.
(IP3 DAG pathway).
• Heart : Myocardial thickening.
V2 receptors : • Endothelium : vWF release.
(cAMP protein kinase A pathway). • Cortical collecting duct : Free H2o absorption.
v3 receptors :
• Pituitary : ACTH release.
(IP3 DAG pathway).
ADH binds to basolateral
Note :
membrane
AQP3, AQP4 are expressed on
(V2 receptor)
the basolateral membrane.
Activates cAMP protein kinase A

pathway
Aquaporin (AQP2) expression

on luminal membrane
Free H2O reabsorption

130 18 Medicine
----- Active space ----- Hyponatremia : 00:25:58
Disorder of H2O metabolism.

Psychogenic polydipsia : Intake of >15-20 L H2O/day.
Solute reabsorption at DCT, thick ascending limb
Causes :
(Furosemide < Thiazide diuretics).
Excess ADH release.
Severity of hyponatremia :
• Very severe : S. Na+ → <100 mEq/L → ICT symptoms.
• Severe : S. Na+ → 100-119 mEq/L → CNS symptoms other than
increase in ICT such as ataxia, confusion.
• Moderate : S. Na+ → 120-129 mEq/L → GI symptoms, lethargy.
• Mild : S. Na+ → 130-134 mEq/L → GI symptoms.
Pseudohyponatremia : Normal to osmolality with low Na+.
• Translocational causes : Glucose, mannitol, glycine, maltose (effective
solutes).
• Paraproteinemia.
• Hypertriglyceridemia.
Approach to hyponatremia :
1. Rule out pseudohyponatremia (Normal to osmolality).
2. Evaluate true hyponatremia ( osmolality).
i. Rule out psychogenic polydipsia and diuretic overuse based on clinical history.
ii. Evaluate causes of excess ADH :
Excess ADH (Anti diuretic hormone)
Appropriate Inappropriate
Hypovolemic Hypervolemic Euvolemic
hyponatremia hyponatremia hyponatremia
Low ECF Volume. Low effective SIADH.
Hypovolemic : volume : Note : ADH is usually
(Volume lost via) : • CCF. released when
• GIT. • Cirrhosis. tonicity is and
• Kidney. Excess Volume seen → volume is low.
• 3 space loss. outside the cell.
rd

SIADH (Syndrome of Inappropriate ADH) : ----- Active space -----
Causes :
• Trauma.
• Drugs → Vincristine, NSAIDs, oxytocin, TCA, SSRI, 5 C’s : Chlorpromazine,
Cyclophosphamide, Carbamazepine, Clofibrate, Chlorpropamide.
• Paraneoplastic syndrome (Small cell Lung ca, duodenal tumor, thymus
tumors).
• Acute intermittent porphyria.
• Necrotizing pneumonia.
• Meningoencephalitis.
Clinical criteria for diagnosis :
• Euvolemic.
• Low serum osmolality. Urine
• Urine osmolality.
• Urine Na > 20mEq/L.
Absence of thyroid illness (Hypothyroidism), pituitary problem, adrenal
problem (Hypocortisolism), liver/renal disease.
Cerebral Salt wasting syndrome vs SIADH :

Cerebral salt wasting syndrome SIADH
Hypovolemia Euvolemia
Loss of adrenergic tone →
Mainly d/t trauma, drug induced
Suppressed RAAS
Urine Na
Natriuresis : Present
S. Uric acid : S. Uric acid : (<2 mg/dl)
S. K+ : S. K+ : N or
Diabetes Insipidus : 00:42:23
Name changed to :
• AVP-d : Arginine Vasopressin deficiency (Central DI).
• AVP-r : Arginine Vasopressin resistance (Nephrogenic DI).

132 18 Medicine
----- Active space ----- Polyuria :

> 3L urine/24 hours (Or) >40 ml urine/kg/24 hours.
Water diuresis. Solute diuresis.
Causes :
• Diabetic Patients
Passing > 7 L urine/24 hrs.
• Mannitol therapy.
• Diuretic.
• Post obstruction : Relieve obstruction.
Urine osmolality : Urine osmolality :
<300 mOsmol/kg. > 600 mOsmol/kg.
Note : Urine osmolality → 300-600 mOsmol/kg (Can be both water

diuresis/solute diuresis).
Urine dipstick : Negative. Urine dipstick : Positive.
Nocturnal craving for cold H2o
-
Urine specific gravity : 1.010
Hypotonic polyuria :
Polyuria + Urine osmolality < 600 mOSM/L.
AVP-D : Central DI AVP-r : Nephrogenic DI
Etiology : Deficiency of AVP Etiology : Resistance to action of AVP.
Causes : Causes :
• Vasopressin deficiency. • Fibrosed receptor d/t chronic tubulo
• Genetic causes : AD > AR > XLR. interstitial disease : IgG4, Sjogren’s,
• Pregnancy. sarcoidosis.
• Drugs : Lithium, demeclocycline,
cisplatin, foscarnet.
• Hypercalcemia/hyperuricemia/
hypokalemia.
• Sickle cell anemia (Occlusion of vasa
recta).
• Pregnancy.
Note :
Wolfram syndrome/DiDMOAD syndrome (Autosomal recessive) :
Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy, and Deafness.

Plasma copeptin assay : ----- Active space -----

It has replaced water deprivation test.
Hypotonic polyuria
Unstimulated random plasma copeptin
> 21.4 pmol/L ≤ 21.4 pmol/L

Nephrogenic
diabetes insipidus Arginine stimulation test :
Measure stimulated copeptin levels.
≥ 3.8 pmol/L : < 3.8 pmol/L :

Psychogenic Central diabetes
polydipsia insipidus
Treatment :
Diabetes Insipidus Drug
Desmopression 10-20 mcg intranasally.
Central Diabetes Insipidus
Desmopressin 0.1-0.8 mg daily once.
Peripheral Diabetes Insipidus Thiazides : Best option.
Lithium induced Diabetes Insipidus Amiloride/Triamterene.
SIADH vs Diabetes Insipidus :
SIADH Diabetes Insipidus

Presentation Hyponatremia Polyuria
Plasma volume Euvolemic
Serum Hypotonic Hypertonic
Serum Na
Urine volume Voluminous
Urine osmolarity Relatively high Relatively low
Urine Na >30 mEq/L Normal or variable
Chronic : Fluid restriction +
Treatment Vaptans. Supportive DDAVP
Na < 120 : Hypertonic saline.

134 19 Medicine
----- Active space ----- ENDOCRINOLOGY REVISION 3
Adrenal cortex Hormones produced

Zona glomerulosa Aldosterone.
Zona fasciculata Cortisol.
Zona reticularis Dehydroepiandrosterone (DHEAS), Androstenedione.
Primary Hyperaldosteronism (PHA) 00:01:02
Aldosterone secretion Primary hyperaldosteronism

from adrenal gland Renin (Hyporeninemic hyperaldosteronism).
Renal perfusion pressure/ 2˚ RAS

Aldosterone. 2˚ hyperaldosteronism.
Intra vascular volume activation
Causes of PHA :
Acquired causes Inherited causes
• Micronodular b/l adrenal hyperplasia Familial hyperaldosteronism (Autosomal
(M/C). Dominant) : Type 1 → GRA
• U/L adrenal adenoma (Conn’s syndrome). (Glucocorticoid Remediable Aldosteronism).
Presentation : Basolateral
Lumen
• 20 to 60 years. Principal cell membrane
H2O
• Male = Female. ADH
Aquaporins
• Triad :
1. Hypertension (HTN) with disproportionate K+/H+ 2Na+
target organ damage. ENaC AIP 2K+
Aldosterone
2. Hypokalemia : Weakness. Na +
AIP : Aldosterone
3. Metabolic alkalosis. Induced Protein
PHA (Acquired/GRA).
Note : Hypokalemia + HTN + DDx Cushing syndrome.
Metabolic alkalosis Apparent Mineralocorticoid Excess (AME).
Liddle syndrome.

Management : Screening test ----- Active space -----

Plasma Aldosterone Concentration (PAC) : ≥ 10 ng/dl.
Plasma Renin Activity (PRA) : < 1 ng/ml/hr.
Positive
Confirmatory test
Saline infusion test : 2L of NS over 4hours.
PAC ≥ 10 ng/dl.
Positive
CT adrenal
U/L adenoma B/L hyperplasia
< 35 years > 35 years
U/l adrenalectomy Adrenal Venous Sampling (AVS)

from left & right renal vein
Compare Aldosterone/Cortisol ratio
of both sides
Ratio > 4 : 1 → Lateralization No lateralization
Surgery Medical Mx
(Adrenalectomy) Aldosterone antagonist :
• Eplerenone.
• Finerenone.
• Spironolactone.
Adrenal Cortical Insufficiency/Addison’s Disease 00:11:48
10 Adrenal insufficiency 20 Adrenal insufficiency

Cause Adrenal cortical cause. Pituitary cause/
(Autoimmune > TB) Abrupt steroid withdrawal (M/C).
ACTH (Hyper pigmentation).
Aldosterone Normal
Cortisol, DHEAS, Androstenedione
Salt craving, postural + -

hypotension
Loss of axillary hair + +
Vitiligo + -
S. Potassium High. Normal.
S. Sodium Low.

136 19 Medicine

Primary adrenal insufficiency :
Acquired causes :
• Autoimmune (M/C) : Autoimmune Polyendocrine Syndrome (APS)/
Polyglandular Autoimmune syndrome (PGA) → APS 1/2 :
Produce Anti 21-OH antibody.
• Tuberculosis.
• Waterhouse friderichsen syndrome.
Inherited causes :
• AAA syndrome : Alacrimia, Achalasia cardia, Addison’s disease → Aladin
mutation.
4A syndrome : AAA syndrome + Autonomic nervous system dysfunction.
• X-linked adrenoleukodystrophy → Very long chain fatty acid.
Presentation :
• Cortisol insufficiency Weakness, weight loss, asthenia, fatigue.
Repeated hypoglycemia & hypotension.
Hyponatremia.
Note : Cortisol insufficiency : Euvolemic hyponatremia.
Aldosterone insufficiency : Hypovolemic hyponatremia.
• Aldosterone insufficiency Salt wasting.
Dehydration.
Hyperkalemia.
Postural hypotension.
• Sex steroid insufficiency → Dry skin.
• ACTH → Hyperpigmentation of skin.
• Eosinophilia.
• Normal or small or asymmetrical adrenal gland on CT scan.
• Non-adrenal calcification.
Note : Secondary addison’s : No symptoms of
aldosterone insufficiency & ACTH.
Investigations : Fasting cortisol
< 3 μg/dl 3-20 μg/dl > 20 μg/dl
10 Addison’s disease. Synacthen stimulation test. Addison’s disease

( Synthetic ACTH 250 μg IV/IM). is ruled out.
< 20 μg/dl > 20 μg/dl
10 Addison’s disease. Addison’s disease is ruled out.

Addisonian crisis : ----- Active space -----

Acute abdominal pain + Hypotension + Shock.
Addisonian crisis.
3 to 4L of NS over 8-12 hrs.

100 mg I/V Hydrocortisone Stat.
50 mg I/V Hydrocortisone 6 hrs apart.

Total dose on 1st day : 300 mg.
Gradually taper the dose of I/v hydrocortisone

& Switch to oral hydrocortisone.
Cushing Syndrome 00:23:27
Cortisol (active) : 11 beta hydroxy steroid Cortisone (inactive) :

Has glucocorticoid + dehydrogenase type 2 (11 βHSD-2) Has only
mineralocorticoid activity. glucocorticoid activity.
Deficiency of 11 βHSD-2 Hypercortisolism

Inherited deficiency Apparent Mineralocorticoid Excess.
Acquired deficiency In cushing syndrome.
In excessive licorice consumption.
Causes : Hypercortisolism
Endogenous Exogenous
ACTH dependent : 90% ACTH independent : 10% Steroid intake
ACTH secreting pituitary • Adrenal adenoma : M/C in ACTH

Micro-adenoma : independent.
Cushing disease (M/C overall). • Adrenal carcinoma (Toddlers).
• Mc Cune Albright syndrome (Infants).
Paraneoplastic syndrome (PNS) : • Macronodular adrenal hyperplasia.
• Small cell lung carcinoma. • Micronodular adrenal hyperplasia
• Carcinoid. (Primary Pigmented Nodular Adrenal
• Medullary thyroid carcinoma. Disease : PPNAD).

138 19 Medicine

Presentation of hypercortisolism :
Action Presentation
1 Protein Catabolism : Muscle : Myopathy.
Amino acid uptake in all Bone : Osteoporosis.
tissues except liver. Collagen : Violaceous purplish striae.
Platelet : Bruising.
2 Carbohydrate Alanine in blood : Substrate Gluconeogenesis.
for gluconeogenesis.
3 Fat Redistribution of body fat ± Buffalo hump, moon facies,
minimal lipolysis. centripetal obesity.
4 Mineralocorticoid Increased. Salt & water retention.
Hypokalemia.
Metabolic alkalosis.
5 Sex steroid Increased. Acne, hirsutism.
6 CNS - Steroid psychosis.
Other presentation :
• Eosinopenia. • Deep vein thrombosis.
• Risk of infection. • Menstrual : Amenorrhea or oligomenorrhea.
Presentation with high discriminatory value :

1. Proximal myopathy. 4. Bruising.
2. Facial plethora. 5. Young onset short stature/Osteoporosis.
3. Cutaneous striae. 6. Disproportionate HTN/DM.
Note : Centripetal obesity (M/c symptom) has poor discriminatory value.
Diagnosis & Management :
1. Midnight serum cortisol > 1.8 μg/dl.
To diagnose endogenous hypercortisolism,
2. Midnight salivary cortisol > 5.5 mmol/l
2 out of 3 following criteria should be positive
3. ONDST (OR) LDDST (Specific test) > 1.8 μg/dl.

Midnight serum cortisol ----- Active space -----

Midnight salivary cortisol
positive negative
8 AM plasma cortisol Cushing syndrome

is ruled out
> 1.8 μg/dl. Too low
Exogenous hypercortisolism
Endogenous hypercortisolism is suspected
Suspected cushing syndrome Suspected pseudocushing/Obesity/

Hyperestrogenism/PCOS/on Oral Contaceptive pills
Over Night Dexamethasone Suppression Test (ONDST)
1 mg oral dexamethasone at 11pm Low Dose Dexamethasone Suppression Test
(LDDST) 0.5 mg Q6H for 2 days
Next day 8 AM plasma cortisol
> 1.8 μg/dl.
< 1.8 μg/dl. > 1.8 μg/dl. Endogenous hypercortisolism
Normal Endogenous hypercortisolism
ACTH
< 1o pg/ml > 1o pg/ml
ACTH independent : ACTH dependent

Adrenal cause
1o - 100 pg/ml > 100 pg/ml
CT adrenal
U/L adenoma (M/c) Pituitary cause/PNS Paraneoplastic syndrome (PNS)
U/L adrenelectomy PET scan
MRI brain with gadolinium
≥ 6 mm mass < 6 mm/no mass

Pituitary adenoma Inferior petrosal sinus sampling
Trans-sphenoidal hypophysectomy Petrosal/ peripheral ACTH ratio
>2 : significant Negative
Trans-sphenoidal hypophysectomy PET scan
Drug used in Cushing syndrome : Ketoconazole.

140 19 Medicine

Pheochromocytoma 00:47:54
It is a neural crest cell tumor producing catecholamines or metabolites of

catecholamines.
Hormones produced in adrenal medulla Metabolites
Adrenaline (80%) Metanephrine, Vanillylmandelic acid (VMA).
Noradrenaline (20%) Normetanephrine.
Dopamine Homovanillic acid (HVA).
Phenyl ethanolamine
Nor-Adrenaline Adrenaline
N-methyltransferase (PNMT)
Adrenal pheochromocytoma (M/C) :

Produces adrenaline > Nor adrenaline.
Extra-adrenal pheochromocytoma :
• Also known as paraganglioma (25%).
• Produces only noradrenaline as PNMT is present only in adrenal gland.
• Types :
Sympathetic (Functional) : From organ of Zuckerkandl.
Parasympathetic (Non functional) : From carotid body > jugular bulb.
Association :
• 40 % : Hereditary (MEN-2, Von Hippel Lindau disease, NeuroFibromatosis-1).
• 40 % : Bilateral (MEN-2, Von Hippel Lindau disease).
• 50 % : Malignant → Surest sign of malignancy is metastasis.
Associated mutation : SDH-B mutation (Succinyl Dehydrogenase B).
Note : Pheochromocytoma in NF-1 is unilateral.
Presentation :
• M/c presentation : Panic attack.
• Triad : Severe episodic headache (M/c symptom) + tachycardia + profuse
sweating.
• M/c sign : Episodic hypertension.
Disease of 6 Ps and 1 W :
• Pain (Abdominal pain d/t hypercalcemia). • Perspiration.
• Pallor (Suggestive of malignancy). • Postural hypotension.
• Panic attack. • Weight loss (DM).
• Palpitation.
Investigations : ----- Active space -----

• Screening test:
24-hour urine fractionated metanephrine : 98% sensitivity & specificity ±
Plasma fractionated metanephrine : 100% sensitivity, but low specificity.
• IOC for adrenal pheochromocytoma : MRI abdomen.
IOC for extra-adrenal pheochromocytoma : Gallium DOTATATE PET Scan.
Treatment :
Surgery : Laparoscopic retroperitoneal adrenalectomy.
Days before surgery Drug
10 days Liberal I/V fluids.
7 to 10 days α-Blockers Phenoxybenzamine (m/c used).
(Any one drug given)
Prazosin.
Nicardipine/Metyrosine.
2 to 3 days β-Blockers Atenolol.
HTN crisis during surgery : Sodium nitroprusside/Nicardipine.
Multiple Endocrine Neoplasia (MEN) 00:59:13
• Autosomal dominant.
• Male = Female
MEN 1 :
• Mutation of Menin gene on chr 11q (tumor suppressor gene).
• M/c method of mutation : Intron inversion.
Manifestations of MEN 1 :
3 Major manifestations :
1. Parathyroid manifestation (Primary hyperparathyroidism) : 100%.
Primary hyperparathyroidism in MEN 1 Primary hyperparathyroidism
< 20 years > 50-60 years.
Male = Female. Female >> Male.
Symptomatic : Painful bones, renal stones, abdominal Asymptomatic.
groans, psychotic moans, fatigue overtones.
Asymmetric hyperplasia of all 4 glands. Adenoma (M/C).
2. Entero-pancreatic neuroendocrine tumors : 50-70%.

• M/c cause of death in MEN 1.
• Gastrinoma (M/c).
142 19 Medicine

3. Pituitary manifestation : 30-50%.
Aggressive macro prolactinoma → Presenting feature in 10-15%.
Minor manifestations :
• M/c skin manifestation : Angiofibroma. Others : Collagenoma, lipoma.
• M/c neurological tumor : Meningioma.
• M/c tumor : Adrenocortical tumor (30%).
• Pheochromocytoma in MEN 1 : < 1%.
• PNET(Primitive neuroectodermal tumour) : Thymic & foregut carcinoids.
MEN 2A :
Point mutation of RET proto oncogene mutation on 10q.
Divided into 4 types :
1. Classical MEN 2A.
2. MEN 2A with cutaneous lichen amyloidosis.
3. MEN 2A with Hirschsprung’s disease.
4. Familial Medullary Thyroid Carcinoma (FMTC).
Classical MEN 2A :
3 manifestations :
• Medullary thyroid cancer (100%).
• Pheochromocytoma : Inherited, bilateral (50%).
• Parathyroid hyperplasia (25%).
MEN 2B :
• Medullary thyroid carcinoma.
• Pheochromocytoma.
3/4 M’s :
• Marfanoid habitus.
• Mucosal & intestinal ganglioneuromatosis.
• Myelinated corneal nerve fibres.
• Megacolon (rare).
MEN 4 :
Due to Cyclin Dependent Kinase 1B (CDKN1B) mutation.
• Parathyroid involvement.
• Pituitary involvement.
• Ovarian/testicular tumor.
• Renal/adrenal tumor.

MEON 01:08:43 ----- Active space -----
MEON : Multiple Endocrine and Other Organ Neoplasia syndrome

Syndromes Inheritance/ Genes Endocrine Neoplasia
Mutation manifestation
Hyperparathyroidism Parafibromin Hyperparathyroidism Ossifying fibroma of the jaw.
– Jaw tumor (CDC 73). due to parathyroid
syndrome carcinoma.
Carney’s Complex PRKAR 1A. PPNAD AKA Lean Atrial myxoma.
Cushing.
Acromegaly.
Prolactinomas (rare).
Autosomal
Von Hippel Lindau VHL gene on Pheochromocytoma. • Renal cell cancer.
Dominant
disease (VHL) Chr 3. • Cerebellar
Hemangioblastoma.
NF 1 Neurofibrin Pheochromocytoma. Optic nerve sheath tumors.
on Chr 17.
Cowden syndrome PTEN. Autoimmune • Hamartomatous polyps of GIT.
Hypothyroidism. • CA breast.
Mc Cune Albright Post Zygotic Post Zygotic Adrenal Cushing. Polyostotic fibrous dysplasia.
syndrome Gs α subunit mutation of Acromegaly.
defect GNAS gene. Prolactinoma (rare).
Polyglandular Autoimmune Syndrome (PGA) 01:13:34
Also called �utoimmune Polyendocrine Syndrome (APS).

Features APS-1 APS-II
Age Childhood. Adult.
Skin, nail changes & Candidiasis Present. Absent.
Association APECED gene mutation. HLA-DR3 and DR4 associated.
Inheritance Autosomal recessive. Polygenic.
Gender association Male = Female. Female > Male.
Antibodies Anti 21-OH antibody -
(M/c cause for Addison’s).
Major manifestation Primary Hypoparathyroidism + Addison disease + Hashimoto
Graves > Hashimoto thyroiditis. thyroiditis> Graves.
Minor manifestations Addison disease. Type 1 DM.
Type 1 DM. Hypogonadism.
Hypogonadism.
APECED : Autoimmune Poly Endocrinopathy with Candidiasis & Ectodermal Dystrophy.

144 20 Medicine
----- Active space ----- ENDOCRINOLOGY REVISION 4
Hypercalcemia 00:01:12
Adjusted total Ca2+/Normal S. Ca2+ : 8.6-10.3 mg/dL.

Adjusted total Ca2+ = Measured Ca2+ + 0.8 x (4 - S. Albumin).
Pathophysiology :
↑ S. Ca2+
Inhibition of CaSR (Calcium Sensing Receptor)

(In parathyroid & thick ascending limb of loop of Henle)
↓ Ca2+ reabsorption
↑ Ca2+ excretion
Renal stones formation
Causes :
a. PTH-related : Normal PTH = 50-100 pg/mL.
1. Primary hyperparathyroidism (M/C).
2. Tertiary hyperparathyroidism.
3. Li-induced hyperparathyroidism.
4. Familial hypercalcemia with hypocalciuria (FHH).
5. Paraneoplastic hypercalcemia.
Primary hyperparathyroidism :
Parathyroid adenoma Parathyroid hyperplasia
• 60-80 years • Young
• F>M • F=M
• ↑↑ PTH (500 pg/mL) • Associated with MEN-1, MEN-2A
• ↑ Ca2+
• ↓ PO4

Tertiary hyperparathyroidism : ----- Active space -----

• Consequence of long-standing secondary PTH.
• ↑↑↑ PTH (> 1000 pg/mL). Note : Lithium can also cause
• ↑ S. Ca2+. • Primary hyperparathyroidism.
• ↑ S. PO4. • Nephrogenic DI.
• Seen in advanced CKD. • Chronic tubulointerstitial disease.
• Hypothyroidism
Familial hypercalcemia with hypocalciuria :
Loss of function mutation of CaSR → ↑ Ca2+ reabsorption → Hypercalcemia +
Hypocalciuria.
Paraneoplastic hypercalcemia :
• Aka Humoral Hypercalcemia of Malignancy (HHM).
• Seen in squamous cell carcinoma.
• Pathology : ↑ PTHrp leads to ↓ PTH (<50 pg/mL) and ↑↑ Ca2+.
b. Vitamin D related :
Active form of vitamin D : Calcitriol/1,25-dihydroxy D3.
Functions :
• ↑ Ca2+ absorption (Through calbindin in small intestine).
• Inhibits PTH.
2 forms of vitamin D :
• 1,25-dihydroxy D3 (t1/2 = 6-8 h).
• 25-hydroxy D3 (t1/2 = 2-3 weeks).
Work up :
• Both forms of Vitamin D ↑ : Hypervitaminosis D.
• 1,25-dihydroxy D3 ↑ + 25-hydroxy D3 normal :
a. Sarcoidosis.
b. Acromegaly.
c. Lymphomas.
c. Osteolytic hypercalcemia : d. Endocrine conditions :
• Multiple myeloma. • Pheochromocytoma.
• Ca breast. • Addisonian crisis.
e. Drugs : • Thyrotoxicosis.
• Thiazides. • Acromegaly.
• Lithium.
f. Milk alkali syndrome : Consumption of Ca2+ >4g/day.

146 20 Medicine

Presentation :
Clinical features :
• Painful bones : Seen in osteolytic hypercalcemia.
• Renal stones : Sometimes it is the only presentation.
• Abdominal groans (Pain) : Seen in sarcoidosis, Addisonian crisis.
• Psychotic moans.
• Fatigue overtones : Paraneoplastic hypercalcemia may present with only
fatigue.
O/E : Pseudo clubbing (Normal Lovibond angle).
Investigations :
1. ECG : Short QT interval.
2. X-ray : Shows bone changes.
• Sub-periosteal resorption.
• Rugger jersey sign.
• Diffuse bone resorption.
• Acral osteolysis.
• Osteitis fibrosa cystica.
• Salt & pepper skull. Short QT interval
3. Tc99 Sestamibi scan.
Tc99 Sestamibi scan Subperiosteal resorption

Hyperactive parathyroid glands
Management :
Acute management :
• Hydrate the patient (To prevent nephrogenic diabetes insipidus).
• Bisphosphonates.
• Calcitonin.
Definitive management :
Adenoma : Removal of adenoma.
Hyperplasia : Removal of 3 & 1/2 glands.

Hypocalcemia 00:21:03 ----- Active space -----
Presentations :
1. Arrhythmia : Prolonged QT interval.
2. Pseudotumour cerebri :
• ↑ ICT with seizures, papilledema (or)
• Calcification.
3. Neuromuscular irritation :
• Circumoral tingling.
• Numbness, paresthesia. Prolonged QT interval
• Bronchospasm, laryngospasm (Fatal).
• Latent tetany.
Latent tetany Basal ganglia calcification

Work up :
↓ S. Ca2+
Rule out hypomagnesemia (Gitelman syndrome, PPI use)
↓S. PO4
S. PTH
↑ S. PO4 ↑ S. PO4 ↑ S. PO4

↑ PTH ↓↓↓ PTH Normal PTH
Secondary True hypoparathyroidism Rhabdomyolysis

hyperparathyroidism. Tumour lysis syndrome
E.g : CKD.
Genetic Acquired
Di George syndrome Autoimmune Polyglandular Syndrome-1 (APS-1)

148 20 Medicine

Secondary hyperparathyroidism :
It is a response to hypocalcemia.
Seen in CKD.
Causes for hypocalcemia :
• Inhibition of 1a hydroxylase.
• ↓ Calcitriol.
Biochemistry :
• ↓ S. Ca2+.
• ↑↑ PTH.
• ↑ S. PO4 (↓ Excretion).
Pseudohypoparathyroidism :
↑↑ PTH → Resistance to action → ↓ Ca2+, ↑ PO4.
Types :
1. Type 1 : 1a, 1b.
2. Type 2.
3. Pseudo-pseudo hypoparathyroidism.
GNAS gene mutation :

• Seen in Type 1a & pseudo-pseudo hypoparathyroidism.
• GNAS gene defect → GSa defect → Bone mineral changes.
• Bone mineral changes : Short 4th metacarpal (Albright hereditary
osteodystrophy), short stature.
• Other features : Round facies, mental retardation.
Biochemistry :
1. Type 1 : ↓ S. Ca2+, ↑ PO4, ↑ PTH (Complete resistance).
2. Type 2 :
• Partial resistance.
• ↑ cAMP in urine on administering PTH.
• No bone mineral changes.
3. Pseudo-pseudo hypoparathyroidism : Normal biochemistry.
Treatment :
Acute : 10 mL 10% calcium gluconate over 10 minutes.
Long term : Calcium supplementation.

Thyroid Disorders 00:32:07 ----- Active space -----
Hormone synthesis :
Steps :
1. Sodium-Iodide symport (Basolateral membrane) : Tc99 & I123 use this channel.
2. Iodide-Chloride antiport (Pendrin) : On apical membrane.
3. Organification : I- → I2. Mediated by TPO/DUOX.
4. Iodination : Iodination of Tyrosine residues → MIT, DIT.
5. Coupling (TPO mediated) :
• MIT+ DIT → T3.
• DIT + DIT → T4.
6. Re-uptake into epithelial cells.
7. Proteolysis and release of hormones.
At peripheries : Deiodinase-2 inhibitors :

• Propyl thiouracil.
T4 Deiodinase-2 T3. • Amiodarone.
• Propranolol.
T4 Deiodinase-3 Reverse T3 (rT3). • Steroid.
Properties of thyroid hormone :
• T4 is secreted abundantly but is converted to T3.
• 80% of thyroid hormone in blood is T3.
• Bound to :
a. Thyroid binding globulin (TBG) (60-70%).
b. Albumin (20%).
c. Transthyretin (10%).
Sick euthyroid syndrome :

• Seen in sick patients (Fasting, systemic illness, ICU).
• T4 to T3 conversion is inhibited → T4 is converted into rT3.
• Aka Low T3 syndrome.
• Biochemistry :
a. T4 : Normal to ↑. c. rT3 : ↑↑.
b. T3 : ↓↓. d. TSH : Normal.
• As disease progresses, there is rapid clearance leading to :
a. T4 : ↓. c. rT3 : ↑.
b. T3 : ↓. d. TSH : ↓.

150 20 Medicine

Approach to hyperthyroxinemia :
↑ T3
Hyperthyroxinemia
↑ T4
↑ Free T3 (fT3) RTH Normal fT3, fT4

↑ Free T4 (fT4)
Euthyroid
Thyrotoxicosis hyperthyroxinemia
(Symptomatic) (Asymptomatic)
Overworking gland Stored hormone D/t ↑ TBG :

release • Pregnancy.
Hyperthyroidism • OCPs.
Subacute thyroiditis • Chronic active hepatitis.
• Tamoxifen.
RTH (Resistance to �hyroid Hormone) :

• ↑ fT3 & fT4 but receptors are insensitive → Clinically euthyroid.
• ↑↑ TSH.
↑↑ TSH Normal TSH
↓ TSH
(> 5 mIU/L) (0.5-5 mIU/L)
(<0.5 mIU/L)
1. Symptomatic : Pituitary
Primary hypothyroidism Hypopituitarism
cause.
↓↓ fT3 & fT4 (Autoimmune condition) (Inappropriate
2. Asymptomatic : Last
Hashimoto’s thyroiditis. normal)
stage of sick euthyroid.
Normal fT3 & fT4 Subclinical hypothyroidism. - -
1. Toxic : TSH secreting
↑↑ fT3 & fT4 pituitary adenoma. - Thyrotoxicosis
2. Euthyroid : RTH.
Effects of thyroid hormone :

1. ↑ BMR.
2. ↑ CO, ↑ BP.
3. ↑ Responsiveness to catecholamines.
4. Catabolic action : ↑ Proteolysis seen as muscle wasting, osteopenia/
osteoporosis, hypercalcemia, stones formation.
5. Clearance of cholesterol.

6. ↑ Gluconeogenesis and glucose utilization. ----- Active space -----

7. ↑ O2 consumption except brain and gonads.
8. Thermogenesis : Acts as an uncoupler.
9. Bone growth.
10. Myelination of CNS.
11. Conversion of b carotene to Vitamin A.
12. Stimulation of erythropoiesis.
Hypothyroidism 00:52:31
Types :
1. Primary.
2. Secondary : Acquired hypopituitarism.
3. Congenital : Pediatric population.
4. Consumptive : D/t hemangiomas.
Primary hypothyroidism :
Causes : Features :
• Surgical removal. • Heterogenous, irregular, firm
• Iodine deficiency. enlargement, painless (Nodules
• Li-induced. absent).
• IFN-a. • Incidence : F > M; 45-65 years.
• Amiodarone. • HLA : HLA-DR3/DR4.
• Autoimmune conditions :
a. Hashimoto’s.
b. APS-1 << APS-2.
Thyroid autoantibodies : Evaluation :

• TPO-Ab (90-100%). • ↓/N fT3.
• Thyroglobulin Ab (80-90%). • ↓/N fT4.
• TSH receptor Ab (10-20%). • ↑↑ TSH.
• Antibodies +ve → Hashimoto’s.
Histology :
• Oxyphil metaplasia.
• Follicular atrophy.
• Germinal centre formation.
• Lymphocytic infiltration.
Pre-malignant : MALTOMA (Marginal zone lymphoma) > Papillary thyroid cancer.
152 20 Medicine

Presentation :
1. Slowing of metabolic processes : 2. Accumulation of matrix GAGs :
• Fatigue. • Puffiness.
• Weight gain. • Macroglossia.
• Slowing of speech/hoarse voice. • Non-pitting edema/myxedema.
• Constipation. • Periorbital edema.
• Dryness of skin.
3. Others :
• ↓ HR.
• Poor concentration.
• Cold intolerance.
• Hair loss.
Note : False hypothyroidism seen in
• Menorrhagia/infertility.
Addison’s disease.
• Delayed deep tendon reflexes.
Treatment : Levothyroxine : 1.6-1.8 mg/kg/day.
Myxedema coma :
Presents with ↓ consciousness & seizures.
Findings : Trigger : Infections.
• Profound bradycardia.
• Pericardial effusion. Treatment : IV Levothyroxine + IV steroids.
• Hypothermia.
• Hypoventilation.
• Hypoglycemia.
• Hyponatremia.
Hyperthyroidism 01:02:42
Types :
1. Primary :
a. Diffuse enlargement : Graves disease (Autoimmune).
b. Nodular enlargement : Toxic multinodular goiter.
2. Secondary : TSH secreting pituitary adenoma.
Grave’s disease : Antibodies :

20-40 years. • TSH receptor Ab (80%).
F > M. • TPO Ab (50-80%).
Associated with smoking & HAART. • Thyroglobulin Ab (50-70%).

Presentation : ----- Active space -----

1. ↑ fT3 & fT4 :
• Restlessness, anxiety, tremors. • Proximal myopathy.
• Tachycardia, palpitations. • ↓ Bone mineral density → Fractures.
• Arrhythmia : Atrial fibrillation. • Apathetic thyrotoxicosis.
• Hypokalemic periodic paralysis. • Diarrhoea.
2. TSH receptor Ab → ↑ GAG : Seen only in Grave’s disease.
Ophthalmopathy
Dermopathy : Pretibial myxedema Acropachy
Management :
First line : Carbimazole 5 mg TDS + Propranolol 40 mg QID.
Relapse (50%) → Definitive Rx : Radio-iodine ablation (or) Surgery.
Subacute/De quervain’s thyroiditis :

Aka viral/granulomatous thyroiditis.
Presentation : Fever + Sore throat + Painful thyroid.
Findings :
• ESR ↑↑.
• Low uptake.
Initially presents with toxicosis but it may proceed to hypothyroid state.
Treatment :
• Aspirin (TOC).
• NSAIDS.
• Steroids.
Painless thyroiditis :
Aka Post-partum/silent thyroiditis.
ESR is normal.
Anti-TPO Ab present.
Associated with underlying autoimmune disorder : Type 1 DM (M/C).
No role for steroids.
Propranolol may be used.
Riedel’s thyroiditis :
Chronic thyroiditis.
IgG4 related disease.
Thyroid profile : Normal.
Dense, hard thyroid.

154 20 Medicine

Diabetes Mellitus 01:12:58
Classification :
Type Features
• Autoimmune destruction of pancreas (T & B cell mediated).
1 • ↓↓ Fasting C-peptide.
• Rx : Insulin.
Pathogenesis : Insulin resistance & ↑ lipolysis.
Complications :
• Macrovascular (M/C : Cardiac) : Unrelated to control of diabetes.
2 • Microvascular :
a. Ophthalmopathy.
b. Neuropathy.
c. Nephropathy.
1.5 KPD Type 2 DM behaving like type 1 DM.
• Type 1 DM behaving like type 2 DM.
1.5 LADA
• Antibodies positive.
3 Brain DM/Double DM/Alzheimer’s disease.
Pancreatic DM :
• Tropical chronic calcific pancreatitis.
3c • Hemochromatosis.
• IgG4 related disease.
• Cystic fibrosis.
Drug induced :
• L-asparagine.
3d
• Growth hormone.
• Tacrolimus.
• Elderly patients.
4 • ↑ T regulatory cells.
• Minimal symptoms.
• Seen across generations.
MODY • Good prognosis.
• M/C : MODY 3 (HNF-1a mutation).
KPD : ketosis Prone DM.
LADA : Latent Autoimmune Diabetes in Adults.
MODY : Maturity Onset Diabetes in Young.

Work up : ----- Active space -----

1. Continuous blood glucose monitoring.
2. HbA1c.
3. Ophthalmic evaluation.
4. Nerve conduction studies.
5. Urine routine examination.
6. Treadmill test If +ve Angiography.
Treatment :
Insulin :
Indications : Types of insulin :
• HbA1c ≥ 9.5. 1. Ultra short acting : Lispro.
• Microvascular complications. 2. Short acting : Regular insulin.
• H/o macrovascular events. 3. Intermediate acting : NPH.
• Diabetic ketoacidosis. 4. Long acting : Glargine.
• Type 1 DM/Type 1.5 LADA. 5. Ultra long acting : Degludec.
Target : HbA1c = 7.
Initial regimen :
• Total insulin to be given = 40 U.
• 24U of regular insulin (8 U × 3 times/day) + 16U Glargine (daily)/Degludec
(alternate days).
Oral Hypoglycemic Agents (OHAs) :

1. Metformin :
• MOA : ↑ AMP kinase.
• Dose : 500 mg BD (Upto 1g TDS).
• C/I : GFR <40 mL/minute → ↑ Chances of lactic acidosis
• Advantages :
a. ↓ HbA1c by 1.5%.
b. No hypoglycemia.
c. Promotes weight loss.
d. Helps with insulin resistance.
e. CVS neutral.

156 20 Medicine

Add-on to metformin :
• For comorbidity control.
• Given in :
a. Atherosclerotic vascular disease (ASVD) : GLP-1 analogue/SGLT2
inhibitor.
b. Heart failure with reduced EF : SGLT2 inhibitor.
c. CKD : SGLT2 inhibitor.
2. SGLT2 inhibitor :
• Drugs :
a. Dapagliflozin (10 mg).
b. Empagliflozin (25 mg).
• Advantages :
• ↑ Risk for :
a. Promotes diuresis & natriuresis.
a. Mycotic UTI.
b. No tachycardia.
b. Ketosis.
c. Inhibits RAAS.
d. Prevents proteinuria.
3. GLP-1 analogue & DPP-4 inhibitor :

GLP-1 analogue (Preferred) DPP-4 inhibitor
Liraglutide (S/c)
Drugs Gliptins (Oral)
Semaglutide (Oral)
CVS Benefit Neutral
Weight Weight loss Neutral
4. Sulfonylureas :
• Not used anymore d/t CVS mortality.
• Gliclazide may be tried.
Standard prescription :
• Start with : Metformin 500 mg BD (Can be increased upto 1g TDS).
• Add SGLT2 inhibitor/Liraglutide 0.6-1.8 mg s/c.

Www.Medicalstudyzone.com CNS Revision 1 21 157
CNS REVISION 1 ----- Active space -----
Headache 00:01:34
2 types :
Primary headache (90-95%) Secondary headache Pain insensitive
Recurrent. Causes : structures
No structural cause. • Infection (M/c : Meningitis). • Choroid plexus.
• Tumors : Rare. • Ependyma.
Dangerous headache
• First episode >55 years (Suspicion of
giant cell arteritis).
• Increasing severity over weeks.
• Early morning headache → Disturbed ↑ ICT : Perform fundoscopy
sleep associated with vomiting.
to rule out papilledema.
• Blurring of vision.
• ↑ on bending/lifting/coughing
(Meningeal inflammation).
IOC for ↑ ICT headache → MRI + MRA/MRV.

D/ds for ICT headache :
1. Space occupying lesions (M/c) :
• Tumor/tuberculoma/neurocysticercosis.
• Lesions affecting stalk : Tumor, infiltrative lesions (Sarcoidosis, Langerhans
Cell Histiocytosis (LCH), hemochromatosis, lymphocytic hypophysitis).
2. Cerebral venous thrombosis :
• Inherited cause : Factor V Leiden mutation.
• Acquired cause : Postpartum, Antiphospholipid Antibody Syndrome (APS).
Benign intracranial hypertension :

Previously called as pseudotumor cerebri.
Seen in middle aged obese females.
Slow ↑ in ICT over 3-6 months.
Sixth nerve palsy : False localising sign.
Imaging : Normal.
Opening pressure of CSF : ↑↑.
Rx : Repeated lumbar puncture to relieve pressure.
Topiramate (or) Acetazolamide.

158 21 Medicine

Primary headaches :
Tension type headache (TTH) > Migraine > SUNCT.
1. TTH :
• M/c cause of primary headache. • Female > male.
• No ↑ ICT signs. • 30-50 years.
• Does not affect activities of daily living. • 1/3rd cases are a/w depression.
• Perceived as a band/tightness/fullness. • No vomiting/photophobia/phonophobia.
Most effective in preventing daily attacks : TCA (Amitriptyline).
2. Migraine :
00:14:14
Female >> male.
Teenage.
↑ intensity with age.
Periodic in nature.
2 types : Classical Common
20% 80%
A/w aura : Visual aura (15 mins to 1 hour). No aura.
(Bright zig zag lines on periphery of visual field called as fortification spectra).
1-2 days prior, patient has low mood & irritability.

Properties of headache :
• Throbbing or pounding or pulsatile headache. • Duration : 4-72 hours.
• U/L (B/L in due course of time). • Location : Temporal.
• Vomiting ±.
• A/w photophobia, phonophobia (Patient prefers to sit quietly in a dark room).
• Post headache lethargy : Lasts for 1-2 days.
• Usually involves a trigger (Sleep deprivation : M/C).
Pathogenesis : Intracerebral vasoconstriction followed by vasodilatation.
Prophylaxis → Combat vasoconstriction.
Treatment → Combat vasodilatation.
DOC for :
• Mild to moderate attacks : NSAID.
• Moderate to severe attacks : 5 HT1B/1D agonists → Triptans.
• Severe to very severe attacks : 6 mg S/c Sumatriptan.
Triptans are contraindicated in ischemic heart disease.
Prophylaxis : Class I drugs → Propranolol, Valproate, Topiramate.
Trigeminal autonomic cephalalgia (TAC) :
Headache Any one of the I/L ANS symptoms :
• U/L. • Conjunctival congestion.
• Very severe. • Eyelid edema.
• Stabbing (or) + • Nasal congestion.
boring. • Rhinorrhea.
• Short lasting. • Lacrimation

TAC includes : ----- Active space -----

• Cluster headache (M/C).
• Paroxysmal hemicrania.
• SUNCT : Short lasting unilateral neuralgic headache
with conjunctival injection & tearing.
• Hemicrania continua.
Cluster headache : 00:23:04
Young males.
Periodicity +.
Properties of headache :
• 1-8 attacks/day.
• Duration : 15 min to 3 hours.
• Location : Periorbital.
• Alcohol is a trigger.
• Can have migrainous features.
Aborted by : 6 mg s/c Sumatriptan (or) 100% O2 at 12-15 mL/min for 15-20 mins.
Prophylaxis :
• Short term : Steroid (or) Verapamil.
• Long term : Verapamil.
Other TAC :
Paroxysmal hemicrania SUNCT Hemicrania continua
• Female = male. • Male > female. • Female > male.
• Less severe attacks. • Cutaneous trigger. • Elderly.
• Less periodicity. • No refractory period • U/L continuous head-
• Nocturnal headache absent. following the cutane- ache.
• Alcohol is not a trigger. ous trigger. • Responds to
• 1-20 attacks/day. • Prevention : Lamo- Indomethacin.
• Duration : 2-30 mins. trigine. • ANS symptoms ++.
• Responds to Indomethacin.
Trigeminal neuralgia :
Middle aged to elderly.
Neuralgic pain along the distribution of V2 & V3.
Episodic pain.
If U/L : Compression of superior cerebellar artery.
If B/L : Demyelination (Multiple sclerosis).
Cutaneous trigger → refractory period → Tic douloureux (Severe pain).
Rx : Medical → Carbamazepine > Lamotrigine.
Not responding to medical Rx : Decompression Sx.
Note : Carbamazepine is C/I in HLA B1502.

160 22 Medicine
----- Active space ----- CNS REVISION 2
Lower motor neuron lesions 00:00:34
Lower motor neuron

Symptoms Diseases
structure
*Anterior horn cell (α and γ • Degenerative motor neuron disease → Amyotrophic lateral
motor neurons in the grey Purely motor sclerosis (UMN +LMN).
matter of the spinal cord) • Syringomyelia.
• Sjogren’s syndrome (Asymmetrical truncal + UL sensory
Dorsal root ganglion ataxia).
Purely sensory
• Para-neoplastic syndrome (Anti Hu antibody +).
• Cisplatin/taxanes.
• Radiculopathy → Disc compression → Inter-vertebral
disc prolapse : M/c (Brief electric shock-like pain, motor
Spinal nerve root/radicle
weakness, loss of reflexes along the distribution of the
root).
• B/L polyradiculoneuropathy → Guillain Barre syndrome.
Plexus • Tumours.
• Mononeuropathy → Carpal tunnel syndrome (D/t
amyloidosis).
Sensory > • Mononeuritis multiplex :
motor • Leprosy (M/c).
• Polyarteritis nodosa.
• Cryoglobulinemia.
Nerve
• Polyneuropathy :
• Acquired :
a. Large fibre → Vit B12 (SACD)/Vit E/Copper
deficiency.
b. Small fibre → Diabetes.
• Inherited → Charcot-Marie-Tooth disease.
Neuromuscular junction • Myasthenia gravis (Diurnal variation of fatiguability, ptosis).
• Lambert-Eaton myasthenic syndrome.
• Intermittent weakness :
• Channelopathies.
• Mitochondrial myopathies .
Purely motor • Persistent weakness :
Muscle • Inherited → Dystrophies.
• Acquired :
a. Polymyositis, dermatomyositis.
b. Drugs/toxins.
c. Endocrine → Thyrotoxicosis, Cushing’s disease.
Cranial nerve nuclei in
the brainstem + muscles
supplied :
• Midbrain : CN 3, 4.
• Pons : CN 5, 6, 7, 8.
• Medulla : CN 9, 10, 11, 12.
*Note : In AHC lesions → Asymmetric muscle wasting, fasciculations, DTR ++.

Large fibre V/S small fibre neuropathy : ----- Active space -----
Large fibre neuropathy Small fibre neuropathy

Tract/
Posterior column/Aα fibres. Spinothalamic tract/Aδ & C fibres.
fibres
Acquired : Inherited :
• Diabetes mellitus. • Fabry’s disease.
• Guillain-Barre syndrome (B/L
• Drugs. • Tangier’s disease.
polyradiculoneuropathy).
• Porphyria.
• Vit B12/vit E/copper deficiency.
Causes • Amyloidosis.
• Pyridoxine toxicity.
• Vasculitis.
• Taxanes.
• Uremia.
• Frederich’s ataxia.
• HIV.
• Leprosy.
Mostly axonal.
Mostly demyelinating.
Chronic axonal involvement.
Acute demyelinating
Sensory >> motor symptoms.
polyradiculopathy.
Distal → proximal progression.
Sensory + motor symptoms.
Motor weakness minimal.
Features Distal + proximal involvement.
Reflexes preserved (Except ankle jerk).
Motor weakness prominent.
NCS : Amplitude affected.
Reflexes lost.
Stocking and glove pattern.
NCS : Conduction velocity
In DM, amyloid, porphyria : ANS involvement
affected.
(M/c : Erectile dysfunction).
Tingling.
Positive Burning pain.
Cotton wool sensations.
symptoms
Paresthesia/dysesthesia.
Loss of pain/temperature/crude touch/
Sensory ataxia. pressure :
Negative
Numbness. • Non-healing ulcers.
symptoms
• Charcot joints.
• Burns.
Note : Vit B12/vit E/copper deficiency → Posterolateral cord syndrome + nerve

involvement.
Causes of combined neuropathies :

Combined large and small fibre neuropathy : Motor predominant neuropathy :
• Vincristine. • GBS.
• Carcinomatosis. • Porphyria.
All chronic neuropathies are axonal except Chronic Inflammatory Demyelinating

Polyneuropathy (CIDP).

162 22 Medicine

Guillain Barre syndrome :
Types :
1. Acute inflammatory demyelinating polyradiculoneuropathy (AIDP) (M/c) :
• Males > females.
• Demyelinating fibres :
• Aα → Large/sensory-motor fibres.
• B → Preganglionic ANS fibres → ANS symptoms (Postural hypotension/arrhythmias).
• Mean age : 40 years.
• Characteristics :
• Acute monophasic : Lasts < 4 weeks .
• Inflammatory autoimmune : Anti-GM1 antibodies +nt. (Trigger → C. jejuni infection)
• Ascending polyradiculoneuropathy : LL → UL → brainstem (B/L LMN
7th CN palsy).
Symptoms :
Rubbery legs + tingling/cotton wool sensations/dysesthesia + transient blad-
der dysfunction → Rapidly progressive proximal to distal LL weakness → B/L
areflexic flaccid paraparesis.
2. Acute motor axonal neuropathy (AMAN) : Anti-GD1a antibody +nt
3. Acute motor sensory axonal neuropathy (AMSAN).
4. Miller Fisher syndrome :
• Demyelinating > axonal.
• Triad :
1. Ophthalmoplegia.
2. Arreflexia.
3. Ataxia.
Anti-GQ1b antibody +nt.
Treatment : Diagnostic tests :
• IVIG : 0.4g/kg for 5 days. • CSF : Albuminocytological dissociation.
• PLEX (Plasma exchange). • NCS : Demyelination.
Chronic inflammatory demyelinating polyneuropathy :

Duration : > 8 weeks.
Onset : Insidious.
Antecedent infection : 30% cases.
Presentation : Relapsing neuropathy with motor > sensory features.
• Motor : Proximal + distal LL predominant weakness.
• Sensory : Prominent symptoms + signs.
• ANS : Not involved.
Associated with :
• Cranial nerves : Not involved.
• HIV.
Treatment : • Myeloma.
• Steroids. • POEMS syndrome.
• PLEX.
CNS REVISION 3 ----- Active space -----
Myasthenia gravis 00:00:17
Ocular myasthenia (15-20%) Generalised myasthenia (80-85%)

Fatiguability on repeated activity. Features of ocular myasthenia.
Diurnal variation. Pharyngeal muscle involvement.
Ophthalmoplegia + ptosis. Proximal muscles of lower limb involvement.
Autoimmune disease.
Age group affected : 20-40 years.
Female > male.
Males have a severe phenotype.
Associated diseases : Type-1 DM, vitiligo, pernicious anemia, Addison’s disease.
Pathogenesis :
Blocking antibodies against postsynaptic acetylcholine receptors (AChR).
AChR antibodies Anti musk antibodies
• Most specific. • Seen in 50% patients who are -ve for
• Seen in 80%. antibody against AchR.
• 70% have thymic hyperplasia, • Females without thymus involvement.
10% have thymoma. • Absent in ocular myasthenia.
• Tongue fasciculations.
• Unresponsive to pyridostigmine.
Double negative (AChR antibody -ve & anti musk antibody -ve) : Have anti LRP4 antibody.
Symptoms :
• 2/3rd patients start with ocular symptoms :
a. Asymmetric ptosis with B/L pupil sparing diplopia.
b. M/c muscle involved : Medial rectus.
• 10% have limb symptoms.
• Rest of the patients have pharyngeal muscle involvement : Nasal twang of
voice, dysarthria, dysphonia, dysphagia.
Note : Chronic progressive external ophthalmoplegia (CPEO) → B/L symmetrical
ptosis with no diplopia.
164 23 Medicine

Workup :
Icepack test.
Edrophonium test. Improvement
Neostigmine test.
Repetitive nerve stimulation test (RNST) :
• Baseline → Compound muscle action potential (CMAP) → Normal.
• Low frequency (3 Hz) repetitive stimulation → Decremental response.
Most sensitive test : Single nerve fibre electromyography.

Most specific test : AChR antibody.
Lambert Eaton myasthenic syndrome :

Antibodies against presynaptic V/Q Ca2+ channels.
Paraneoplastic syndrome : A/w small cell lung cancer.
Proximal lower limb weakness ++.
Diplopia, ptosis : Mild.
ANS symptoms ++.
RNST :
• Baseline CMAP : ↓↓.
• High frequency : Very high incremental response.
Treatment of myasthenia gravis :

DOC : Pyridostigmine 30-60 mg QID.
Followed by steroid and azathioprine to prevent relapse.
For myasthenic crisis : I/v steroid + IVIG.
Motor neuron disease 00:11:40
3 types :
1. Pure UMN : Primary lateral sclerosis.
2. UMN + LMN : Amyotrophic lateral sclerosis (ALS).
3. Pure LMN : Spinal muscular atrophy. Degenerating structures in ALS
ALS : • Anterior horn cells (AHC).
90% : Sporadic. • Cranial nerve nuclei in brainstem.
10% : Cu-Zn superoxide dismutase. • Corticospinal fibres upto AHC.
Seen in > 60 years. • Corticobulbar fibres upto cranial
Degenerative disease. nerve nuclei.
Clinical features : ----- Active space -----

• Higher mental functions : Normal.
• Sensory symptoms : Nil.
• ANS : Normal.
• Cerebellum : Normal.
• Asymmetric involvement of upper limb → Wasting & atrophy → fascicula-
tions & cramps → exaggerated DTR.
• Distal + proximal involvement (Distal > proximal).
• Weakness.
• Can have either bulbar (40%) or pseudobulbar palsy (25%).
Bulbar palsy vs pseudobulbar palsy :
Bulbar palsy Pseudobulbar palsy

LMN involvement of cranial nerve nuclei UMN findings
in brainstem (9, 10, 11, 12) Involvement of corticobulbar fibres.
• Nasal twang. • Gag reflex +++.
• Nasal regurgitation. • Dysphonia.
• Flaccid tongue. • Small & spastic tongue.
• Flaccid dysarthria (Bulbar • Spastic dysarthria (Pseudobulbar
dysarthria). dysarthria).
• Jaw jerk ++.
• Emotional incontinence.
Spinal cord 00:18:43
Anatomy :
45 cm long & extends upto L1-L2. Origin of spinal cord segments
31 segments (C8, T12, L5, S5, C1). L4 to S2 From epiconus
Note : Cauda equina → L2 to C1. S3 to C1 From the conus (Bilaterally)
Arrangement of tracts in spinal cord :

Spinal cord tracts Arrangement of segments
(Medial to lateral)
Corticospinal tract (In lateral funiculus)
Spinothalamic tract (In lateral funiculus) C→T→L→S
All extrapyramidal tracts (In anterior funiculus,
except rubrospinal : Lateral funiculus)
Posterior column (In posterior funiculus) S→L→T→C
166 23 Medicine

Compressive myelopathy :
Intramedullary Extramedullary
Causes Ependymoma. Intradural : Neurofibroma, meningioma.
Syringomyelia. Extradural : Vertebral causes (Fracture,
mets, TB, etc), Vascular aneurysms.
Pain Funicular dull aching Root pain.
pain Tightness/band like (If posterior compres-
sion).
Sensory Spinothalamic tract +. Radiculopathy/Brown Sequard syndrome.
Posterior column spared. Posterior column symptoms (Upper limb >
Aka Dissociated sensory lower limb).
loss.
Bowel & ++ -
bladder
Motor Minimal motor involve- +++
ment (Lower limb > upper limb).
Sacral sparing.
AHC LMN + LMN -
Glove & stocking neuropathy : Sensory Brown Sequard syndrome

involvement in upper limb, motor • I/L pyramidal tract involvement.
involvement in lower limb. • I/L posterior column involvement.
• C/L spinothalamic tract involvement.
Conus medullaris v/s cauda equina :
Conus medullaris Cauda equina syndrome

S3 to C1 L2 to C1
B/L symmetrical involvement. Asymmetrical : Root pain.
No motor symptoms. Variable motor symptoms.
Anal/bulbocavernous reflexes lost. Variable reflex loss.
LMN bladder. Bladder involvement : Absent.
Saddle anaesthesia. Sensory : Saddle anaesthesia or other patterns.

Non compressive myelopathy : 00:35:34 ----- Active space -----

Causes :
Mneminc : “ VITAMIN ”
• Vascular (Anterior spinal artery infarction).
• Inherited (Fredrich’s ataxia).
• Toxins (Arsenic).
• Autoimmune (Sarcoidosis).
• Metabolic (B12, Vit E, Cu deficiency).
• Infections (TB, HIV).
• Neoplasia.
Acute transverse myelitis :

• Infectious trigger.
• Clear level : Band like sensation.
• Bowel/bladder : +++.
• At level → Hyperaesthesia & below level → UMN findings.
• Rx : Steroid.
Note : In GBS, there is no clear level & bowel/bladder involvement is absent.
Vitamin B12, vitamin E & Cu deficiency :

• Involvement of posterolateral cord + nerve + cerebrum (Sometimes).
• Posterior column → lateral spinothalamic tract → corticospinal tract →
large fibre neuropathy.
• Reflexes are lost late in the disease.
• Ankle jerk & knee jerk reflexes are absent (D/t neuropathy).
• Plantar reflex : Extensor.

168 24 CNS Revision 4
Dementia 00:00:48
Major cognitive impairment→ Daily activities affected.
Diagnostic criteria : More than one of the following functions are affected :
1. Memory → Medial temporal lobe / Hippocampus.
2. Language → Brocas (inferior frontal) & Wernicke (superior temporal).
3. Executive function → Dorsolateral prefrontal cortex.
4. Social cognition → Orbital prefrontal cortex.
5. Perceptual motor (praxicon) → Superior parietal lobule.
6. Complex attention → Orbital prefrontal cortex.
Functions of Prefrontal cortex

Prefrontal cortex
Medial Orbital Dorsolateral

Energisation and motivation Associated with : Executive function
Note : Lack of energisation • J : Judgement
and motivation → Apathy • I : Insight
• P : Personality
• F : Fluency
• A : Abstract thinking,
Attention
Causes :
Alzheimer’s Dementia (M/C) > Diffuse Lewy Body Dementia > Vascular dementia.
Other causes :
• Fronto temporal dementia (Picks disease)
• Normal Pressure hydrocephalus.
• Prion disease.
Note : 10 % of the dementia causes are reversible → Drugs , Vitamin B 12
deficiency, Chronic Meningoencephalitis, Normal pressure hydrocephalus,
Autoimmune conditions.

Rapidly progressive dementia : ----- Active space -----

• Frontotemporal dementia
• Prion disease Also cause young onset dementia
• Diffuse Lewy body dementia
• HIV
• Whipples disease.
Note : In every young patients always rule out Chronic Meningoencephalitis &
Autoimmune pathology.
Alzheimer’s dementia 00:08:23
Also called → Tauopathy.

Pathogenesis :
APP gene on Chromosome 21 mutated
Amyloidogenic pathway
Aβ Amyloid
Aβ 40 → Cerebral amyloid angiopathy Aβ 42 → Alzheimer’s disease

Amyloid deposition :
Outside neuron →
Both composed of
Amyloid plaque
Aβ Amyloid Hyperphosphorylated tau
Inside neuron → (cause neuronal toxicity)
Neurofibrillary tangle
Note : No proven risk factors are present for Alzheimers disease.
Stages of Alzheimers disease :

1. Stage of amnesia.
2. Stage of anomia :
3. Stage of visuospatial disorientation (Non dominant parietal lobe affected)
4. Executive dysfunction (Prefrontal cortex affected)
Note :
• Lesions of angular gyrus → Gerstmann syndrome :
a. Acalculia
b. Finger anomia
c. Right to Left disorientation
d. Alexia with agraphia


• Alexia without agraphia → Splenium of corpus callosum is involved.
• Visuospatial disorientation, constructional apraxia, dressing apraxia, hemispa-
tial neglect → Involvement of non dominant parietal lobe.
Treatment : Rivastigmine/ Donazepil/ Tacrine ( Cholinesterase inhibitors) +
Memantine (NMDA Antagonist).
Other causes of demetia 00:18:02
Frontotemporal dementia :
Frontotemporal dementia Alzheimers disease
Taupathy Taupathy
MAPT gene on Chromosome 17 • Presenilin 1 (Chr 14)
Early onset
(loss of function) • Presenilin 2 (Chr 1)
• Apo E4 → Late onset.
Young onset (40-50 yrs) Late onset (>60 yrs)
30 % genetic 5 % genetic
Rapidly progressive Slow progression
Prefrontal cortex functions lost. Prefrontal cortex involved in the later
stages only.
Diffuse Lewy Body Dementia : 00:19:44

AKA Parkinson plus syndrome.
Subcortical dementia.
Characterized by Lewy bodies (α synuclein) in the neuronal cytoplasm.
Note : α synucleinopathies.
• Parkinsons disease
• Diffuse Lewy Body Dementia
• Multisystem Atrophy
Clinical features :
• REM Sleep disorders and ANS dysfunction (earliest symptom).
• Dementia > Rigidity > Tremors.
• Fluctuating alertness/ consciousness.
• Visual hallucination.
• Worsening of symptoms on starting antipsychotics.
• No response to L- Dopa.
Note : Cortical dementia v/s Subcortical dementia.

Cortical Dementia Subcortical Dementia ----- Active space -----
Diseases • Alzheimers disease • Diffuse Lewy body dementia

• Frontotemporal • Progressive supranuclear palsy
Dementia • Normal Pressure hydrocephalus
Severity Severe Less severe
Apraxia/ Aphasia/ Agnosia (++) (-)
Extra pyramidal symptoms (-) (+++)
Corticobulbar involvement (-) (++)
Emotional involvement (-) (+)
Creutzfeldt jakobs disease : 00:26:58
It is a prion disease.
• Young onset dementia.
• β pleated sheet of prion.
• PrPsc → Protein involved.
• Rapidly progressive.
Clinical presentation :
Dementia + Myoclonus + High voltage sharp waves in a low slow background on EEG.
Pathological changes → Ribboning / spongiform changes in the cortex.
Vascular Dementia : 00:28:38
1. Post stroke Vascular dementia : Multi infarct state.

• Stepwise decline in cognitive function
2. Small vessel stroke : Lacunar stroke
• Risk factor : Systemic Hypertension.
• Pathogenesis : Lipohyelinosis.
• White matter disease → Binswangers disease( subcortical involvement).
• Characterised by :
1. Emotional fibres affected (corticobulbar)
2. Gait issues.
3. Urinary incontinence.
Normal Pressure Hydrocephalus : 00:31:19

Defective CSF absorption. G : Gait issues
( Apraxia → Ignition foot phenomenon)
Characterized by ventriculomegaly. U : Urinary incontinence
Clinical features : Hakim’s triad. D : Dementia ( subcortical)
Rx : Surgery.

Movement Disorder 00:34:13
Controlled by Extrapyramidal system.
Hyperkinetic Hypokinetic
• Chorea • Parkinson’s disease
• Athetosis • Atypical Parkinson’s disease
• Hemiballismus
• Dystonia
Hypokinesia : Slowness or Paucity of movement + No evidence of weakness/ spasticity.
Parkinson’s Disease : 00:37:40

Usually present >60 yrs.
PARK 1 → Autosomal Dominant ( Chrom 4)
Young onset Parkinsons
PARK 2 → Autosomal Recessive ( Chrom 6)
80 % patients → Tremor predominant Parkinsons.
20 % patients → Akinetic rigid syndrome ( poor outcome).
Cardinal features :
• Tremor :
a. Asymmetric, distal pill rolling tremor
b. 4-6 Hz tremor
c. Micrographia(+)
d. Brought on by concentration.
e. Resting tremors.
• Akinesia/bradykinesia.
• Rigidity.
Other features :
• Glabellar tap sign (+)
• Lead pipe (elbow)/ Cog wheel rigidity (wrist)
• Hypomimia.
• Hypophonia.

Atypical Parkinsonism : 00:42:45 ----- Active space -----
α Synuclenopathies Tauopathy
• Diffuse Lewy body Dementia • Progressive supranuclear palsy
• Multisystem atrophy • Corticobasal degeneration
Common symptoms :
• Rapidity of progression.
• No response of L- Dopa.
• Absence of tremors.
Multi system Atrophy ( MSA) vs Progressive Supranuclear palsy (PSP)

Multi system atrophy Progressive supranuclear palsy ( Steel
Richardsons syndrome)
Pathogenesis α Synnuclenopathy. Taupathy
Clinical features • ANS symptoms → (+++) • Max Bilateral Symmetrical axial
• REM Sleep disorders → ( ++) rigidity.
• Bilateral akinetic rigid Sym- • Wide based gait
metrical symptoms (axial) • Postural instability
• Supranuclear palsy → down gaze
palsy.
• Procerus sign : Wrinkling/ Furrowing
of the forehead
• Applause sign.
MRI findings Hot cross bun sign Humming bird sign/Morning glory sign
Types of MSA :
• MSA-P → Parkinson type
• MSA-A → Autonomic (Shydrager syndrome)
• MSA-C → Cerebellum
Corticobasal degeneration : 00:52:10

Tauopathy.
seen in elderly.
Clinical features :
• Asymmetrical
• Triad of → Apraxia + Myoclonus + Cortical dementia
• Hemiballismus /Parkinson features → ( Basal ganglia involvement).
Alien Limb phenomenon : Not using 1 limb and using the other limb.

174 25 Medicine
Approach to hemiplegia 00:00:44
Upper Motor Neurons (UMN) : Descending motor pathways.

1. Corticospinal tract.
Travel from cortex to the anterior horn cell.
2. Extrapyramidal tracts.
3. Corticobulbar tracts → upto cranial nerve nuclei in brainstem.
Causes of hemiplegia related to
Cortex Subcortex Brainstem
Cortex :
Corticospinal tract in cortex arises from :
• Motor cortex (Area 4) : 30 % fibres.
• Premotor cortex : 30% fibres.
• Sensory cortex (Area 3, 1, 2) : 40% fibres.
Frontal & parietal lobe Temporal lobe Occipital lobe
Supplied by : Supplied by : PCA.
M2 inferior division
Incongruent C/L homonymous
C/L hemiplegia Wernicke’s aphasia. macular sparing hemianopia.
Note : For motor weakness → Vessels involved :
• M1 (In sylvian fissure).
• M2 superior division.
• ACA (occlusion).
Features of cerebral lobes :

Frontal lobe Features of ACA occlusion :
Contains : • Lower limb > upper limb weakness.
• Prefrontal cortex. • Gait issues.
• Frontal eye field : • Bowel/bladder involvement.
To look to opposite side.
Note : B/L ACA occlusion → Severe apathy,
• Broca’s area.
akinetic rigidity, abulia.

Parietal lobe : ----- Active space -----
Dominant Non-dominant
Areas : Features :
• Angular gyrus → Gerstman syndrome : • Visuospatial disorientation.
a. Acalculia, anomia. • Constructional apraxia.
b. Left to right disorientation. • Dressing apraxia.
c. Alexia with agraphia. • Hemispatial neglect (Severe
• Superior parietal lobule → Apraxia. form is c/a anosognosia).
• Supramarginal gyrus with association
areas : Visual agnosia.
Inferior quadrantanopia is seen in parietal lobe lesions.
Temporal lobe :
Medial Lateral
Functions : Areas :
• Memory. • Auditory cortex.
• Epileptogenic. • Auditory association areas → Auditory agnosia.
• Wernicke’s area.
Superior quadrantanopia is seen in temporal lobe lesions.
Limbic cortex (In temporal lobe) → Kluver Bucy syndrome.
Aphasia : 00:14:20
Fluency
No Yes
Motor aphasia Sensory aphasia
Comprehension + Comprehension - Comprehension + Comprehension -
Rep + Rep - Rep + Rep - Rep + Rep - Rep + Rep -

Transcortical Broca’s Isolation Global Nominal Conduction Transcortical Wernicke’s
motor aphasia aphasia/ aphasia aphasia aphasia sensory aphasia
aphasia echolalia aphasia
Note : Naming is affected in all aphasias.

176 25 Medicine

Subcortex :
Corticospinal tract passes through anterior 2/3rd of posterior limb of internal
capsule in close association with the corticobulbar fibres.
Features of internal capsule lesions :

• C/L dense hemiplegia.
• C/L UMN 7th nerve palsy.
• Hemisensory loss.
• Homonymous hemianopia.
Brainstem :
Crossed hemiplegia is seen in brainstem lesions : C/L hemiplegia + I/L cranial
nerve palsy.
Midbrain syndromes : 00:20:34
Corticospinal tract passes through middle 3/5 of crus cerebri.

th
Vessel involved : P2 segment of PCA.

Ventral midbrain syndromes
Weber syndrome Claude syndrome Benedict syndrome
Lesion : Base of mid- Lesion : Tegmentum. Features :
brain. Features : • Weber +
Features : • I/L 3 nerve palsy.
rd
Claude.
• I/L 3rd nerve palsy. • C/L ataxia (Dentato rubro • C/L
• C/L UMN hemiplegia. thalamo cortical fibres). hemiballismus.
Dorsal midbrain syndromes (Cause : Pinealoma)

Parinaud syndrome Nothnagel syndrome
Lesion : Tectum. Features :
Features : • I/L LMN 3rd nerve palsy.
• Vertical upgaze palsy → sunsetting • Gaze palsy.
sign. • C/L ataxia (Superior
• Overactive levator palpebrae superioris cerebellar peduncle).
→ lid retraction (Collier’s sign).
• Pretectal nucleus → Accommodation
reflex present, pupillary reflex absent.
• Convergence retraction nystagmus.
• Skew deviation of eyes.

Pontine syndromes : 00:26:45 ----- Active space -----
Ventral pontine syndrome Dorsal pontine Lateral pontine syndrome

(Millard Gubler syndrome) syndrome (Foville (Marie fox syndrome)
syndrome)
F : I/L facial nerve palsy. F : I/L facial nerve A : I/L ataxia.
S : I/L sixth nerve palsy. palsy. S : C/L pain & temperature
H : C/L hemiplegia. G : Gaze palsy. loss (Spinothalamic tract).
H : C/L hemiplegia. H : C/L hemiplegia.
Medullary syndromes : 00:28:42
Lateral medullary syndrome Medial medullary syndrome

(Wallenburg syndrome) (Dejerine’s syndrome)
Vessel involved : V4 segment of vertebral artery 4 M’s :
> PICA • Motor nucleus of 12th nerve → I/L
Cranial nerves : LMN 12th nerve palsy.
• 5 : Spinal nucleus → I/L loss of sensation
th
• Motor fibres of pyramidal tract →
of face. C/L hemiplegia.
• 7th : NTS → Taste sensation. • Medial lemniscus → C/L posterior
• 8th : Vestibulocerebellar fibres → ataxia, column findings.
dizziness, vertigo. • Medial longitudinal fasciculus →
• 9th, 10th : Nucleus ambiguus → Dysarthria, Internuclear ophthalmoplegia.
dysphagia.
• 10th : Dorsal nucleus of vagus → Autonomic
features.
• 13th : Horner’s syndrome.
Sensory : C/L pain & temperature loss
(Spinothalamic tract).
Cerebellum : I/L ataxia (Spinocerebellar fibres).
No motor deficit.

178 25 Medicine

Stroke 00:34:50
Blood supply of brain :

> 22 mL/100 g/min : Normal.
< 10 mL/100 g/min : Infarct.
10 - 22 mL/100 g/min : Penumbra.
Transient ischemic attacks (TIA) :

The neurological deficit comes back to normal within 24 hours, generally within
an hour.
ABCD2 score : Predictor of risk of stroke.
Rx : Dual antiplatelet for 21 days.
Management of stroke :
In clinical practice :
High risk of stroke → Admit → CT brain (to detect bleed) + CT angio (to localise
large vessel involved).
Candidate for thrombolysis Contraindications for thrombolysis

• > 18 years. • Bleeding episode.
• < 4.5 hours from onset of stroke. • ICH.
• No bleed. • Surgery in last 14 days.
• No edema which is >1/3rd of the • GI bleed in last 21 days.
brain territory. • BP >185/110 mm Hg despite treatment.
If available at centre, mechanical thrombectomy is preferred over thrombolysis.

Thrombolysis → Alteplase (aka TPA) 0.9 mg/kg given :
• 10% as bolus.
• 90% as infusion over one hour.
Thrombectomy :
• Done if M1 (or) PCA are the vessels involved.
• Can be done upto 24 hours.
Most ideal line of Mx of stroke : Diffusion weighted MRI + CT brain.

Diffusion weighted MRI (DW MRI) : ----- Active space -----

• Shows changes in form of hyperintensities from 30 mins to 6 hours after
onset of stroke.
• Apparent diffusion co-efficient sequencing shows hypointensities in stroke.
• Normal DW MRI means stroke is less likely.
DW MRI flair :
• It shows changes after 6 hours.
• Used in early morning stroke, where the exact time of onset of stroke can
not be determined.
MR angio : Detects main vessel occlusion.

Perfusion MRI : Detects penumbra.
Summary :
Assessment of risk of stroke
CT brain + DW MRI with ADC sequence If ADC sequence is
not available, add
MR angio to locate site of lesion perfusion MRI
First order lesion Unaccessible lesion

Mechanical
thrombectomy Presents within Presents after
4.5 hours 4.5 hours
Thrombolysis Medical Mx
Medical management :
• Aspirin (75 mg) within 48 hours → continued lifelong.
• No role of statins & dual antiplatelet agents.
• Anticoagulation : Only for cardioembolic stroke.
Warfarin : In valvular heart diseases, AF, mechanical heart valve.
Dabigatran : In other conditions.
• If BP > 220/110 mm Hg → Treat hypertension
Carotid endarterectomy :
• If carotid atherosclerosis > 70% (or)
• If carotid atherosclerosis is 50-70% with symptoms.

180 26 Medicine
----- Active space ----- NEPHROLOGY REVISION 1
Syndromes in nephrology
Chronic kidney disease Renovascular hypertension Hematuria related Nephritic syndrome

diseases
• Diabetic nephropathy. • Large vessel related : • Porphyria. • PSGN (Post Streptococcal

• Chronic glomerulonephritis. Renal artery stenosis. • Rhabdomyolysis. Glomerulonephritis).
• Vascular CKD. • Small vessel related : • Paroxysmal nocturnal • IRGN (Infection Related
• Chronic tubulo-interstitial Thrombotic microangiopathy. hemoglobinuria. Glomerulonephritis).
Disease. • Glomerular diseases.
Chronic Kidney Disease (CKD) 00:01:44
Pathogenesis :
Interstitial fibrosis-Tubular atrophy-Glomerulosclerosis (IF-TA-GS).
In CKD : ↓ No. of functional nephrons → Compensatory ↑ in single nephron GFR
→ ↑ Intra-glomerular pressure → Proteinuria (Tubulotoxic) → Interstitial fibro-
sis (↑ TGF β).
Causes :
1. Diabetic nephropathy (M/C).
2. Chronic glomerulonephritis (CGN) : IgA nephropathy.
3. Vascular CKD (Ischemic nephropathy).
4. Chronic Tubulo-Interstitial Disease (CTID).
Presentation :
Diabetic CGN Vascular CKD CTID
nephropathy
Pathogenesis - End stage Renal artery Slow b/l fibrosis of
complication of stenosis → CKD. tubulointerstitium.
glomerular disease
(IgA nephropathy).
Onset Insidious. - Elderly. Slow.
History - - H/o smoking/ H/o autoimmune,
CAD/POVD. inherited diseases,
drug intake.
Edema Progressive Present. Absent. Absent.
extravascular.
Frothing of Present. Present. Absent. Absent.
urine

Nephrology Revision 1 26 181
Diabetic CGN Vascular CKD CTID ----- Active space -----

nephropathy
Proteinuria Nephrotic Proteinuria +. Urine : Albumin → Urine albumin :
range trace to 1+, No RBC. Trace to 1+.
>3.5 g in 24
hrs.
Hypertension Present. Present. Profound HTN. Absent.
USG Normal size to Small kidney or Small kidney. B/L small kidney.
enlarged kid- 8-10 cm with loss
ney with loss in CMD.
in CMD
Symptoms - • Fatigue - • Asyptomatic
(Anemia). (M/c).
• Sudden • Polyuria &
onset of uremic nocturia.
symptoms : • Fatigue
Vomiting. (Disproportionate
anemia).
• Water diuresis.
Other Diabetic S. Creatinine • Peripheral pulse : • Renal Tubular
presentation retinopathy. around 7.5 mg/ Absent. acidosis type IV.
dL. • Bruit +. • Disproportionate
hyperkalemia.
POVD : Peripheral occlusive vascular disease, CMD : Cortico Medullary Differentiation.
CTID :
Causes :
• Drugs : Lithium, Calcineurin inhibitors, Proton pump inhibitors.
• Autoimmune : IgG4 nephropathy, sarcoidosis, Sjogren disease.
• Inherited : Autosomal Dominant Polycystic Kidney Disease (ADPKD),
Medullary Cystic Disease of kidney (MCDK).
• Reflux nephropathy.
• Obstruction.
• Metabolic : Hypercalcemia, hypokalemia, hyperuricemia, hyperoxaluria.
Investigations :
• eGFR : Calculated using MDRD/CKD-EPI equation (Better).
Following parameters are taken into consideration,
a. Age. c. Sex.
b. S. Creatinine. d. Race.

182 26 Medicine

Grading of CKD based on eGFR :
Grade eGFR
G5 < 15 mL/min (End stage renal disease).
G4 15 to 29 mL/min.
G3 30 to 59 mL/min.
G2 60 to 89 mL/min.
G1 > 90 ml/min + Histological/biochemical/radiological evidence of kidney disease.
• USG : Kidney < 8 cm or 8 to 10 cm with loss in CMD.
CKD with normal size to enlarged kidney : DM, HIV, amyloidosis.
Renovascular hypertension 00:29:55
Vascular kidney disease :

• Large vessel related : Renal Artery Stenosis (RAS).
• Small vessel related :
Thrombotic Micro Angiopathy (TMA) → Hemolytic Uremic Syndrome (HUS).
Present as thrombocytopenia, MAHA (Micro Angiopathic Hemolytic Anemia)
& renal failure.
Renal artery stenosis :
Cause :
• M/c overall : Atherosclerosis.
• M/c in young :
Worldwide → Fibromuscular Dysplasia (FMD).
India → Takayasu arteritis (F : M ratio → 9 : 1).
String of bead appearance
• M/c in young male : Poly Arteritis Nodosa (PAN). in FMD
Presentation :
• Significant HTN crisis/emergency with complications like panic attack/
dyspnea/Posterior Reversible Encephalopathy Syndrome (PRES).
• Significant vascular disease & comorbidities.
• No edema.
• No significant proteinuria.
• USG : Normal sized kidney.
Note : Small kidney + Vascular disease → CKD (Ischemic nephropathy).
Diagnosis :
CT Renal Angiography (CTRA) or MR Angiography (MRA).
Management :
Angioplasty and stenting.

Hematuria related diseases 00:40:22 ----- Active space -----
Approach to hematuria :
Hematuria + Normal RFT
Urine dipstick
Positive for blood Negative for blood
Centrifugation of urine (1600 rpm for 5 mins) Porphyria

Look for supernatant at end of 5 mins
Clear High coloured

(D/t RBC)
Check after sometime
Isomorphic RBC. ≥ 40% dysmorphoric RBC or
≥ 5% acanthocytes or High coloured Clear
No proteinuria. (D/t Myoglobin)
(D/t Hb)
No acanthocytes. 1 single RBC cast +
No RBC cast. Proteinuria. ↑ Creatine
Acquired intravascular phosphokinase
Urological cause (90%) : Glomerular cause. hemolysis : Paroxysmal
Bladder mass. Young : IgA nephropathy. nocturnal hemoglobinuria Rhabdomyolysis
Renal cell Ca. (Episodic hematuria). : Muscle pain d/t
Urethral malignancy. undue muscle
exertion.
Nephritic syndrome/acute glomerulonephritis/

nephritis 00:48:50
Post Streptococcal Infection Related Glomerulonephritis

Glomerulonephritis (PSGN) (IRGN)/post infectious
glomerulonephritis
Age Children (2 to 7 years). Adult.
Organism Group A β-hemolytic streptococci. MRSA infection.
Incubation 3 to 5 weeks. No incubation period.
period
M/c in Immunocompetent. Immunocompromised (Diabetic foot).
Prognosis Excellent prognosis. Poor prognosis.
Presentation • Acute onset of high colored urine • Acute onset of high colored urine.
following skin >> throat infection. • HTN.
• HTN. • Profound renal failure requiring
• Renal failure (Mildly altered RFT). dialysis.
184 26 Medicine

Post Streptococcal Infection Related Glomerulonephritis
Glomerulonephritis (PSGN) (IRGN)/post infectious
glomerulonephritis
RBC cast + -
Edema Mild edema .
Proteinuria, Proteinuria 1+,
S. albumin S. albumin : Normal.
Immunofluorescence Starry sky pattern : IgG + C3 Rope or garland pattern : IgA + C3
deposits along capillary wall. deposits
Light microscopy Endocapillary (M/c) & mesangial Diffuse Proliferative
exudative (Neutrophil) diffuse Glomerulonephritis (DPGN) +
proliferative glomerulonephritis + No Crescent = Rapidly proliferating
crescent. glomerulonephritis (RPGN).
Electron microscopy Subepithelial camel hump deposits. -
Complications of PSGN :
• Hypertensive crisis. • Pulmonary edema (D/t overactivity of ENaC
• Hyperkalemia d/t renal failure. channel causing intravascular volume overload).
Indications of biopsy in PSGN :

• If C3 level fails to normalize in 8 weeks → C3 glomerulonephritis.
• Recurrence.
Granular deposits in PSGN DPGN Crescentic glomerulonephritis
Nephrotic v/s nephritic syndrome :

Nephrotic syndrome Nephritic syndrome
Onset Insidious. Acute.
Proteinuria Nephrotic range of proteinuria. Mild proteinuria.
Edema Extravascular edema. Intravascular edema.
RFT Normal. Abnormal.
Albumin Hypoalbuminemia. Normal albumin.
Lipid level Hyperlipidemia. Normal.

NEPHROLOGY REVISION 2 ----- Active space -----
Classification of acute renal disease :

Vascular Glomerular Tubulo-interstitial
• Reno-vascular HTN • Asymptomatic. • Acute tubular necrosis (ATN) :
(Hypertensive crisis). • Nephritic syndrome. Presents with AKI.
• TMA (RPRF). • Macrohematuria. • Acute Interstitial Nephritis (AIN) :
• Nephrotic syndrome. Presents with AKI/RPRF.
• RPGN (RPRF).
D/d for acute renal failure :
• AKI (Developing over hours to days).
• RPRF (Developing over days to weeks).
Rapidly Progressive Renal Failure (RPRF) 00:00:10
Causes :
1. RPGN (Rapidly Progressive Glomerulo-nephritis) :
• Glomerular RPRF.
• Clinico-pathological diagnosis : RPRF + crescents.
2. AIN (Acute Interstitial Nephritis) :
• Tubulo-interstitial disease.
• Caused by : Infections, drugs.
3. TMA (Thrombotic Microangiopathy) :
• Vascular cause of RPRF.
• Caused by :
a. Adult HUS. c. HELLP syndrome.
Crescentic glomerulus
b. APLA syndrome. d. Scleroderma.
RPGN :
Type Features
Type 1 Linear IgG + C3 deposits along GBM (Seen in Goodpasture syndrome).
1. Fullhouse effect : SLE.
2. IgA + C3 : IRGN (IgA dominant Infection Related Glomerulonephritis).
Type 2
3. Adult HSP (Henoch Schönlein Purpura).
4. MPGN (Membrano-Proliferative Glomerulonephritis).
Type 3 • Pauci-immune condition.
(Most common overall) • ANCA vasculitis : Microscopic polyangiitis (MPA) (M/C cause).
Type 4 Double positive (ANCA + Anti-GBM positive).
Type 5 Double negative.
In age 1-20 years : Type 2 > Type 3.

186 27 Nephrology

Nephrotic syndrome 00:12:50
Definition :
1. Nephrotic range proteinuria :
>3.5 g/24 h (or) Urine PCR ≥200mg/g (or) >50 mg/kg/day.
2. Edema.
3. Hypoalbuminemia.
4. Hyperlipidemia (Lipiduria).
Nephrotic syndrome in children :

Presentation :
• Edema (Extravascular).
• Subacute onset.
• Normal RFT.
• No h/o hematuria.
• Normal BP.
M/C cause : Minimal Change Disease (MCD).
If hematuria is seen : Focal Segmental Glomerulosclerosis (FSGS).
Management :
First line : Steroid
2 mg/kg/day (or) 60 mg/m2/day
90-95% 5-10%
↓ ↓
Respond Steroid Resistant Nephrotic
Syndrome
(Proteinuria persisting for 4
weeks after steroid intiation)
↓
Biopsy
Genetic FSGS Steroid resistant

↓ MCD
Transplant ↓
DOC : Calcineurin
inhibitors
(Tacrolimus)
Outcome in steroid responders : ----- Active space -----

1. 25% : Cured.
2. 25% : Infrequent relapses → Managed with steroids.
3. 50% : Frequently Relapsing Nephrotic Syndrome (FRNS).
• Steroid Dependent Nephrotic Syndrome (SDNS) : ≥2 replapses within 14 days
of stopping/tapering steroids.
• Management :
a. First line : Oral Cyclophosphamide (or) Oral Mycophenolate mofetil.
b. Second line : Rituximab.
Nephrotic syndrome in adults :

Causes : Presentation :
1. MCD. • Occurs over 3-4 weeks.
2. FSGS : M/c worldwide. • Frothy urine.
3. Membranous Nephropathy (M/c in >60y) • Pedal edema.
4. MPGN. • Normal RFT.
5. IgA nephropathy. • No hematuria.
6. Amyloidosis.
Secondary causes of nephrotic syndrome :

MCD FSGS MN MPGN
1. Hodgkin’s 1. Viruses : 1. Colorectal 1. Infective
disease. • HIV adenocarcinoma. endocarditis.
2. NSAIDs. • EBV 2. Hepatitis B 2. Plasma cell
3. Allergy. • CMV virus. disorders.
4. Immunisation. • Parvovirus B19 3. SLE. 3. Hepatitis C
2. Heroin. 4. d-Penicillamine. virus.
3. Obesity.
4. Sickle cell anemia.
5. Hyperfiltration
injury.
6. IFN-a.
7. Pamidronate.
8. Reflux
nephropathy.

188 27 Nephrology

Biopsy findings & management :
Biopsy : Mandatory in adults with nephrotic syndrome.
Uses :
1. To confirm diagnosis and delineate the cause.
2. To r/o secondary casues.
1° MCD 1° FSGS MN MPGN
Thickening of Thickening of BM.
Light Focal, segmental
Normal basement Mesangial proliferation.
microscopy sclerosis
membrane (BM) Lobular architecture.
Granular deposits of
Granular IgG ± C3
IgG + IgM ± C3 along
IF Focal IgM ± C3 deposition on
Normal capillary wall & GBM :
microscopy deposition capillary wall :
Double contour/Tram
Spike pattern
track pattern
Steroids, but Ponticelli regimen :
Steroids
Rx most cases are Steroid + Treat underlying cause
(1 mg/kg)
resistant. Cyclophosphamide
Prognosis Good 2/3 → CKD. 1/3 → CKD Poor
Acute Kidney Injury (AKI) 00:28:04
Causes :
1. Pre-renal (M/C) :
• Due to volume depletion.
• True volume depletion : Loss of fluid.
• Third space losses. Eg. : Burns.
• Hypoalbuminemia.
Leads to ischemic ATN.
2. Renal :
a. ATN :
• Ischemic ATN (D/t sepsis or pre-renal AKI).
• Drugs : “ACES”.
Aminoglycosides, Amphotericin B.
Cisplatin, Cyclophosphamide.
Ethylene glycol.
Salicylates.
Vancomycin.
• Contrast.
• Tumour lysis syndrome : Uric acid nephropathy.
• Rhabdomyolysis.
• Myeloma cast nephropathy.
b. AIN : ----- Active space -----

• Drugs : “BRAND”.
Beta lactams.
Rifampicin.
Anticonvulsants, Allopurinol.
NSAIDs.
Diuretics.
Type 4 hypersensitivity reaction.
Presentation : Asymptomatic (or) rash with eosinophilia.
• Infections.
• Infiltration injury.
3. Post-renal : Usually urological causes.
Pre-renal AKI V/s ATN :
Pre-renal AKI ATN
Normal Albumin present (1+)
Urine examination
Muddy brown epithelial cast
U. Na+ ↓ ↑
U. Creatinine ↑ ↓
FeNa < 1% > 2%
Urine osmolality 300 mOsm/L
Urine pH Normal Alkaline
Urine specific gravity 1.010
BUN : Creatinine 20 : 1 -
FeNa : Fractional excretion of Na+.
FeNa = U. Na+ × Plasma Na+ .

U. Creatinine Plasma Creatinine
Normal FeNa = 1-2%.
Hypokalemia 00:37:22
90% of K+ excreted through kidney.

Causes :
1. Non-renal K+ loss :
• K+ value : 2.5-3.5.
• D/t movement of K+ into the cells.
• Causes : Insulin, b agonists, a antagonists.
2. Renal K+ loss : D/t acidosis (or) alkalosis.

190 27 Nephrology

Acidosis : With NAGMA → RTA 1/2 (Renal Tubular Acidosis).
RTA 1 RTA 2
a Intercalated cells of CD affected PCT dysfunction
Urine pH >5.5 Urine pH <5.5
Hypercalcuria & stone formation Not seen
Moderate to severe acidosis Mild acidosis
Rickets + Rickets ++
Acquired cause : Sjogren’s syndrome Acquired causes :
• Wilson’s disease (In young).
• Myeloma (In elderly).
• Fanconi’s syndrome : Cystinosis (In children).
Alkalosis :
Causes :
1. With HTN :
a. Conn’s syndrome.
b. Liddle syndrome.
c. Cushing’s syndrome.
d. Syndrome of Apparent Mineralocorticoid Excess (AME).
e. Glucocorticoid Remediable Aldosteronism (GRA).
2. Normal/low BP :
a. Bartter syndrome : Thick ascending limb is affected.
b. Gitelman syndrome : DCT is affected.
Bartter syndrome V/s Gitelman syndrome :
Bartter syndrome Gitelman syndrome
Hypercalciuria & stone formation Hypocalciuria
20% cases : Hypomagnesemia 100% cases : Hypomagnesemia
Only in children Survive till adulthood
Hyperkalemia 00:43:38
M/C cause : Renal failure.

If hyperkalemia is disproportionate to degree and duration of renal failure
↓
Hypoaldosteronism
True Pseudo
↓
Hyporeninism Hyper-reninism Seen in chronic tubulo-
↓ ↓ intersiticial disease (CTID)
DM, NSAIDs & b blockers Addison’s disease ↓
RTA 4
Www.Medicalstudyzone.com GIT Revision 28 191
GIT REVISION ----- Active space -----
Malabsorption 00:00:28
Fat malabsorption occurs first as it is the most sensitive nutrient to

malabsorption.
Hallmark of malabsorption : Steatorrhea → Pale, fatty, voluminous, bulky,

greasy, malodorous stools.
Presents as diarrhea → most consistent symptom.
It is osmotic diarrhea.
Diagnosis :
Gold standard : 72 hr fecal fat estimation test.
• If any day shows > 7 g/day → Steatorrhea.
• If patient has ongoing stools, > 14 g/day → Steatorrhea.
• If stool fat is >7% of dietary intake → Steatorrhea.
Qualitative test : Sudan III/Sudan black.
Diarrhea : 00:05:09
Osmotic diarrhea Secretory diarrhea

• Toxin mediated : ETEC, Vibrio cholera.
Unabsorbed content
• Tumor : VIPoma/watery diarrhea
Mechanism in colon draws water
achlorhydria syndrome/pancreatic
from epithelial cells.
diarrhea.
Fasting Improves with fasting -
Stool
osmotic > 100 mOsmol/kg 25-50 mOsmol/kg
gap
Stool osmotic gap :
• Measured osmolality - Calculated osmolality.
• Measured osmolality is measured using osmometer.
• Calculated osmolality : 2 x stool (Na+ + K+).
• Normal stool osmotic gap : 50-100 mOsmol/kg.

192 28 Medicine
----- Active space ----- Note : In factitious diarrhea, stool osmotic gap is < 25 mOsmol/kg. When sample
is collected under supervision, the stool osmotic gap is normal.
Small intestinal diarrhea Large intestinal diarrhea

• Large volume, watery stools. • Small volume, frequent stools.
• No blood, pus, mucus. • Blood, pus, mucus present.
• No frequency, urgency, tenesmus. • Frequency can be seen.
• Abdominal pain seen in ileal • Infection : Invasive organisms
pathologies (Crohn’s disease, TB). (Shigella, Salmonella, Campylobacter,
• Osmotic/secretory diarrhea (ETEC, Yersinia).
Vibrio cholerae). • Inflammatory : Ulcerative colitis.
(Sensitive marker of UC : Fecal
calprotectin).
Note :
Acute diarrhea : < 14 days.
Chronic diarrhea : > 30 days.
Persistent : > 14 days.
Presentation of malabsorption :
GI :
• Diarrhea (Small intestinal).
• Gaseous abdominal distension : Gas produced by fermentation of
unabsorbed carbohydrates in the colon by bacteria.
• Ascites (Mild) : D/t hypoproteinemia.
• Foul smelling malodorous stool.
Musculoskeletal : Bone pain, osteopenia, fracture (D/t vitamin D deficiency).
Cutaneous :
• Hyperpigmentation in B12 deficiency.
• Perifollicular hemorrhage in vitamin C deficiency.
• Acrodermatitis enteropathica in Zn deficiency.
Miscellaneous :
• Anemia : Iron deficiency anemia (Celiac disease), B12 deficiency (Distal ileal
pathologies).
• Ataxia : Vitamin B12, E & Cu deficiency (Posterolateral cord syndrome).
• Neuropathy : Vitamin B12, E & Cu deficiency.
• Renal stones : Oxalate stones.
• Weight loss (Occult malabsorption) : Seen in short intestinal bacterial
overgrowth.
Celiac disease : 00:18:35 ----- Active space -----

Celiac disease
Classical celiac Atypical celiac disease Silent celiac Latent celiac

disease Have features which disease disease
GI malabsorption. are not classical of Only serology Serology -ve.
celiac disease. positive. HLA +ve (HLA DQ2
or DQ8).
Affects any age.

Male = female.
Atypical celiac disease : Associations of celiac disease
• Anemia : Iron deficieny (Proximal small • Dermatitis herpetiformis.
intestinal involvement). • Type 1 DM.
• Ataxia (Vitamins A, D, E, K deficiency). • Thyroid disorders.
• ALT/AST ↑↑ : Cryptogenic cirrhosis. • IgA deficiency.
• Bone fracture. • IgA nephropathy.
• Short stature & failure to thrive.
Diagnosis :
1. Serology :
• Anti TTG antibody (IgA) : M/C done by ELISA.
• Anti endomyseal antibody (IgA) : Specific.
• Anti deaminated glutaminase dipeptide (IgG) : Used in patients with IgA
deficiency.
2. Biopsy (Non specific findings) :

• Total villous atrophy.
Total mucosal thickness remains same.
• Crypt hyperplasia.
• Lymphocytes in lamina propria.
Biopsy & serology -ve : Not celiac disease.

Biopsy +ve, serology -ve : Not celiac disease.
Serology +ve, biopsy -ve : High chance of celiac disease → Repeat biopsy.
Rx : Avoid barley, rye, oats and wheat (BROW).

If no response to gluten restrictions after 6 months → Refractory celiac
disease → Start steroids.
194 28 Medicine

It has risk of :
• Enteropathy associated T cell lymphoma.
• Small intestinal adenocarcinoma.
• Esophageal SCC.
Whipple’s disease : Conditions which can be

• Causative organism : Tropheryma whipplei. diagnosed with biopsy
• It is gram +ve and PAS +ve. alone :
• Seen inside macrophages within lamina propria. • Whipple’s disease.
• 50-60 years. • Abetalipoproteinemia.
• Male > female. • Agammaglobulinemia.
• Involves proximal small intestine > distal
small intestine.
• Diagnosis : Biopsy.
Symptoms :
GIT CVS Joint CNS
• Lymphadenopathy. Culture -ve Seronegative • Seen in 40%.
• Abdominal pain endocarditis. arthritis : Large, • A/w relapse.
(Ileitis). migratory, • Indicates poor prognosis.
intermittent, • Rapidly progressive
oligoarthritis. dementia :
Progressive supranuclear
palsy with oculomasticatory
nystagmus.
Rx :
Ceftriaxone/Meropenem x 14 days.
To prevent relapse : Cotrimoxazole.
Tropical sprue :
M/c cause of malabsorption in India.
Triggered by GI infection (Fermented products of coliform → E. coli, Klebsiella).
Pan intestinal involvement : Predilection for ileum.
Biopsy : Very similar to celiac disease (Has partial villous atrophy).
Rx : Folate + Tetracycline.

Inflammatory Bowel Diseases 00:32:28 ----- Active space -----
2 peaks : 15-30 years & 70-90 years.

Crohn’s disease (CD) Ulcerative colitis (UC)
Gender Female > Male. Male > Female.
OCPs. Smoking & appendicectomy
Associations
Smoking is causative. are protective.
Familial inheritance CD > UC
Abnormal use of
antibiotics in 1st year Risk
of life.
Race More common in Jews.
Syndromes • Turner’s syndrome. • Turner’s syndrome.
associated : • Hermansky Pudlak • IPEX (Immune
Note : IL-10 (Or) IL-10 syndrome. polyendocrinopathy X
receptor defect → • Von Gierke’s disease. linked syndrome) : D/t
Childhood IBD FOXP3 mutation.
(Refractory/drug • Wiskott Aldrich
resistant). syndrome.
• NOD2/CARD 15 gene.
• Defective innate
immunity
Etiopathogenesis Th2 cell mediated.
(M.paratuberculosis).
• Defective autophagy.
• Th1/Th17 mediated.
• Transmural,
segmental Superficial, continuous
Pathology
involvement. involvement.
• Granulomas.
Can occur anywhere • Proctitis.
Parts affected from mouth to anus. • Proctosigmoiditis.
M/C : Ileocolitis > Ileitis. • Backwash ileitis.
Systemic involvement + -
Response to
+ -
antibiotics
Recurrence after Sx + -

196 28 Medicine
----- Active space ----- Crohn’s disease Ulcerative colitis

• Strictures.
• Fissure.
Complications Toxic megacolon.
• Fistula.
• Fibrosis.
• Systemic features. • Fresh bleeding P/R.
• Abdominal pain (Ileal). • Blood streak on surface of hard stool.
Presentation • Malabsorption (Jejunal). • Large intestinal diarrhea.
• Per abdomen :
Inflammatory mass.
• Asymmetric, segmental, • Symmetrical, superficial,
transmural involvement. continuous involvement.
• Granuloma. • Erythematous mucosal surface →
Endoscopy
• Aphthous ulcer → rose thorn ↓ vascularity → friable (superficial
ulcer → cobble stoning → ulcers) →
String sign. Pseudopolyp.
Marker Fecal Calprotectin
• Colonic thickening. • Fine mucosal granularity
• Creeping mesenteric fat. (Earliest) → serrations →
Radiology • Fat halo sign. superficial ulcers → Deep collar
button ulcers.
• Leadpipe appearance.
Extraintestinal manifestations of IBD :

UC : Primary sclerosing cholangitis.
Crohn’s Disease :
• Erythema nodosum. • Episcleritis.
• Peripheral arthritis. • Cholelithiasis.
• Ankylosing spondylitis. • Nephrolithiasis.
String sign Toxic megacolon
• Uveitis. • Thromboembolism.
Pyoderma gangrenosum seen in both.

Manifestations which correlate with relapse :
• Episcleritis.
• Erythema nodosum.
• Large migratory pauciarticular arthritis (Knee). Lead pipe colon
Fat stranding seen in CD CECT : Target appearance. Fat halo sign Collar button ulcers

Serology : ----- Active space -----

CD → Antibodies :
1. ASCA (Anti saccharomyces cerevisiae antibody)
→ Relates to complications.
2. OMPC (Outer membrane protein citrullinated).
3. APB (Anti-pancreatic antibody). Cobble stoning in CD
4. Anti flagellin.
5. Anti 12 → risk of Sx in CD.
UC :
Anti goblet cell antibody.
P-ANCA : Seen when a/w primary sclerosing
cholangitis → ↑ risk for cholangiocarcinoma. Pseudopolyps
Irritable bowel syndrome 00:47:14
Functional disorder.
< 45 years.
Female > male.
Presents with recurrent episodes of lower GI cramping pain which is related to :
1. Defecation.
2. Frequency of stools.
3. Appearance of stools.
Upper gastrointestinal symptoms can be seen.
Mucus in stool can be seen.
Exclude IBS if :
• > 45 years. • Steatorrhea.
• Anemia. • Features of small intestinal pathology
• Fever. • Nocturnal diarrhea.
• Weight loss. • Blood in stools.
• ↑ ESR.
Mx : Low FODMAP diet.
IBS-C IBS-D
(Conspitation predominant) (Diarrhea predominant)
• Chloride channel activator : Lubiprostone. • Loperamide.
• Guanylyl cyclase agonist : Linaclotide. • μ receptor agonist :
• Na-H exchanger : Tenapanor. Eluxadoline.

198 29 Medicine
----- Active space ----- HEPATOLOGY REVISION
Acute hepatitis 00:00:27
Salient features :
Incubation period → Viral prodrome (1-2 days, C/F : Malaise, vomiting,
hypoglycemia) → Jaundice, liver enzymes ↑ (ALT, AST > 1000 U/L, ALT > AST).
Treatment :
Supportive management.
Glucose supplementation : 150g (10ml of 10% dextrose in 100ml NS) → Patient
usually recovers.
Causes :
1. Virus : HAV (M/C in children), HEV (M/C worldwide), HBV.
2. Drug induced liver injury (DILI) :
a. Dose dependent : Paracetamol.
b. Dose independent : Idiosyncratic (Rifampicin), hypersensitivity
(Carbamazepine, phenytoin, azathioprine, PTU, valproate, INH).
3. Toxin : Alcohol, rat poison (ZnO).
4. Ischemic hepatitis.
5. Wilson’s disease/autoimmune disease/Budd-Chiari syndrome.
6. Acute fatty liver of pregnancy.
Paracetamol poisoning :
Potentially toxic : >4 g.
Toxic dose : >7.5 g.
Clinical features :
Time since
Clinical features Treatment
poisoning
24 hrs Nausea and vomiting.
• PT↑.
24-72 hrs • Liver enzymes↑. ≤ 4 hrs : Charcoal hemoperfusion.
• Abdominal pain. ≤ 16 hrs : N-acetyl cysteine (100mg/kg).
Fulminant hepatic
72-96 hrs
failure.

Www.Medicalstudyzone.comHepatology Revision 29 199
Acute viral hepatitis : ----- Active space -----
HAV HEV
Incubation period 30 days 40 days
• Feco-oral route. • Feco-oral route.
Route of transmission • Never vertically • Never parenterally/sexually
transmitted. transmitted.
Immune virus
Type Cytotoxic virus
(Cholestatic phase +ve).
Other important Pregnancy : Risk of fulminant
-
points hepatic failure.
Treatment Supportive management (No risk of chronicity).
Complications :
Time of
occur-
rence Clinical features Treatment Risk of complication
since
jaundice
Fulminant • HAV : 1 in 2 lakh.
• Coagulopathy
hepatic <7 days • HEV :
(INR ≥ 1.5).
failure Liver a. 0.5-2%.
• Acute ↑ ammonia
Acute transplant b. 20% in
levels → ↑ ICT →
hepatic 7-21 days pregnancy.
Encephalopathy.
failure • HBV + HDV : 5-20%.
Other clinical features d/t acute ↑ ammonia :

• CNS issues.
• Lactic acidosis.
• Sepsis/MODS.
• ATN.
• Hypoglycemia & hyponatremia.

200 29 Medicine

Chronic hepatitis 00:09:22
Causes : Complications :
1. NASH. Development of liver cirrhosis leading to :
2. Chronic viral hepatitis (HBV, HCV). 1. Portal HTN.
3. Autoimmune. 2. Liver failure.
4. Hemochromatosis. 3. HCC.
5. Wilson’s disease.
Clinical features : Investigations :

• Asymptomatic. Liver enzymes :
• Fatigue. • ↑sed but < 150 U/L.
• Wasting of muscles. • In chronic hepatitis : ALT > AST.
• ↓sed libido. • In cirrhosis : AST > ALT.
• Altered sleep patterns. Fibroscan (Transient elastography).
Best : MR elastography.
Portal HTN :
Pathophysiology :
Portal pressure = Flow X Resistance.
1. Increased Resistance :
• In liver cirrhosis, the lobules are replaced by nodules.
• Nodules are interconnected by fibrous septations.
• Intra sinusoidal NO levels ↓ses → Sinusoidal vasoconstriction with defenes-
tration of sinusoids.
• Sinusoidal pressure ↑ses → Portal venous pressure ↑ses.
• Compensatory mechanisms :
Compensation Diagnosis
Porto-venous collaterals to
Endoscopy → Variceal bleed.
decompress varices.
Splenic vein pressure ↑ses. Splenomegaly → Earliest clinical finding
Hypersplenism Thrombocytopenia → Earliest lab finding

2. Increased flow : Splanchnic vasodilation (↑NO)
↓sed peripheral resistance. Effective circulatory volume ↓ses.

↑RAAS activation.
Hyperdynamic circulation. Salt and water retention.
Ascites.
Hepatitis B and C 00:22:20 ----- Active space -----
HBV :
Acute hepatitis Chronic hepatitis Complications
Vertical transmission (100 %)
Route Sexual/parenteral
Sexual/parenteral (1-5 %)
Anti Hbc IgG +ve
HbsAg +ve.
Immune tolerance phase :
• 10-30 yrs. • HCC, portal HTN,
• HBV DNA ↑ liver failure.
• HbsAg +ve • HBeAg +ve • HbxAg : Can lead
• HbeAg ± (Degree of • Live enzymes normal, to HCC directly
infectivity/replica- no inflammation after chronic
Infection ↓ hepatitis.
tion).
• Anti Hbc IgM (Single Immune clearance phase : • Acute on
best test) • ALT, AST ↑. chronic hep B :
• Jaundice +ve. Reactivation in
• HBV DNA ↓↓↓. inactive carrier
↓ phase leads to
Inactive carrier phase : cirrhosis.
• HBV DNA < 2000.
• HbsAg +ve, HbeAg -ve
• HbsAg -ve
Recov- • HbeAg -ve
ery • Anti Hbc IgM
• Anti Hbs +ve
Acute Vs Acute on chronic hepatitis B :

Acute hepatitis B Acute on chronic hepatitis B
HbsAg +ve. HbsAg +ve.
HbeAg ±. HbeAg +ve.
HBV DNA < 2000. HBV DNA ↑↑↑.
Anti Hbc IgM +ve. Quantitative HbsAg +ve.
Anti Hbc IgM +ve.
Severe symptoms.
Cirrhosis can be +ve.
Treatment :
Indications :
• Acute hep B with INR ≥ 1.5/Jaundice (Total bilirubin ≥ 3 mg/dL) for 4 weeks.

202 29 Medicine

• Chronic hepatitis + cirrhosis.
• Chronic hep B without cirrhosis : HbeAg +ve, HBV DNA > 20,000 IU, enzymes ↑
(>2 times upper limit of normal).
• Pre core mutant : HbeAg -ve, HBV DNA > 2000 (For effective Rx : ALT > 2
times upper limit of normal).
Rx : Tenofovir alafenamide.
Serological patterns of Hepatitis B infection :

HBsAg Anti-HBs Anti-HBc HBeAg Anti-HBe Interpretation
+ - IgM + - Acute hep B, high infectivity
+ - IgG + - Chronic hep B, high infectivity
Late acute or chronic hep B
+ - IgM - - with low infectivity, Pre-core
mutant (HBeAg -ve hep B)
- - IgM ± ± Acute hepatitis B
- - IgG - ± Remote infection
- + IgG - ± Recovered from acute hep B
- + - - - Vaccinated
HCV :
Acute hepatitis Chronic hepatitis Cirrhosis
• HCC, portal HTN,
liver failure.
85% chance of devel-
Progression - • No direct conver-
oping chronicity
sion from chronic
hepatitis.
Extrahepatic manifestations :
• Sjogren’s syndrome.
Clinical Anicteric, asymptom- • Cryoglobulinemia.
-
features atic • Porphyria cutanea tarda.
• MPGN.
• Lichen planus.
Anti-HCV +ve
Anti-HCV & HCV RNA +ve
Serology HCV RNA +ve → dis- -
appears later
• 99.7 % cure rate.
• NS5A inhibitor (Velpatasvir) + NS5B inhibitor (So-
Treatment - fosbuvir) for 12 weeks.
• In cirrhosis : Ribavirin additionally given for 12
weeks.

Immune disorders of liver 00:35:45 ----- Active space -----
Autoimmune hepatitis (AIH)

AIH type 1 :
AKA Lupoid hepatitis.
Seen in females in 2nd and 3rd decade.
Findings
• Lympho-plasmocytic infiltrate.
Pathological
• Interphase hepatitis : Between portal tract and hepatocyte.
findings
• HPE : Emperipolesis and rosette formation.
• Acute hepatitis with waxing & waning of jaundice and
Presentation polyclonal hypergammaglobulinemia.
• Chronic hepatitis with Fatigue and hepatomegaly.
• ANA.
• SMA (Smooth muscle antibody).
Serology • AAA (Anti-actin antibody) : Poor prognosis.
• Anti-SLA (Anti Soluble liver antigen) : Most specific.
• Atypical p-ANCA.
AIH type 2 :
Seen in children, poor prognosis.
Serology : LKM-1 (Also seen in hepatitis C) + ALC-1.
Primary biliary cholangitis (PBC) vs Primary sclerosing cholangitis (PSC) :

Criteria PBC PSC
Age group Middle aged females Young males
• Autoimmune inflammatory • Fibrosing destruction of
destruction of intra-hepatic intra & extra hepatic
Pathology
bile duct. bile ducts.
• Intrahepatic cholestasis. • Intrahepatic cholestasis.
Sjogren’s syndrome, distal RTA,
Associations Ulcerative colitis (90/5)
xanthomas.
Anti mitochondrial antibody
Serology Atypical p-ANCA
(AMA)
Clinical features Fatigue and pruritis
Investigations ↑ ALP MRCP (IOC)
Treatment Ursodeoxycholic acid Transplant
204 29 Medicine

Metabolic liver disease 00:41:23
Wilson’s disease :
Genetic defect : ATP 7b gene (Wilson’s ATPase) on chromosome 13q.
Age group : 3-20 years.
Pathology :
• Cu2+ is not incorporated into ceruloplasmin → ↑degradation of ceruloplasmin.
• Defective biliary excretion of copper.
Lab findings :
• ↓ Ceruloplasmin bound copper (< 10mg/dl).
• ↓ Total serum copper (Non-ceruloplasmin bound copper (10%) +
ceruloplasmin bound copper (90%)).
• ↑ Free Cu2+ → ↑ Urinary Cu2+ + ↑Accumulation in liver and brain.
• Gold standard : Liver biopsy and quantitative Cu2 estimation.
Presentation :
• Young male (<20 years) with acute hepatitis, ↓ ALP.
• Coomb’s -ve hemolytic anemia.
• Chronic hepatitis, fatty liver, ALT/AST ↑.
• Cirrhosis.
• Decompensated liver disease.
• Jaundice.
Clinical symptoms :
Neurological symptoms Endocrine disorders Other systems
• Dysarthria (M/C). • Hypoparathyroidism. • Hemolysis.
• KF ring : Cu2+ deposition in • Amenorrhea & testicular • Type 2 RTA.
descemet’s membrane (95- problems. • Large joint arthritis.
99 %), also seen in cholestasis • Infertility or repeated spon- • Cardiomyopathy.
syndromes. taneous abortions.
• Psychiatric symptoms. • Pancreatitis.
• Parkinson’s symptoms.
• Risus sardonicus : Dystonia &
posturing.
• Tremor : Classical wing
beating tremor.
Management :
DOC : D-pencillamine.
S/E :
• Myasthenia.
• Membranous nephropathy.
• Drug induced lupus erythematosus.
• Aplastic crisis.
Add on drug : Zinc.

Hemochromatosis : ----- Active space -----

Age group : > 40 years.
No acute phase.
Genetic defect : HFE gene on chromosome 6p → Unregulated iron absorption.
Clinical presentation :
• Cirrhosis, hepatomegaly (Alcohol ↑ses risk).
• Skin : Bronze grey pigmentation.
• Type 3c DM.
• Dilated cardiomyopathy.
• Hypogonadotrophic hypogonadism.
• Non inflammatory arthritis of 2nd and 3rd MCP (Hook like osteophytes +ve).
Management :
Investigation :
• Ferritin + transferrin saturation ratio : ↑
• Gold standard : C282Y mutation.
Treatment : Phlebotomy.
Decompensated liver disease 00:54:35
Complications of portal hypertension :

Complication Symptoms
• Jaundice, Variceal bleed, ascites (Earliest sign),
Decompensated liver hepatic encephalopathy.
disease • Prognosis : <2 years without liver transplant.
• Is treatable in hepatitis C & autoimmune liver disease.
• Jaundice.
• Alopecia, Dupuytren’s contracture, parotid swelling.
• Hyperdynamic circulation → Palmar erythema,
Liver failure
hyperpigmentation, caput medusa.
• ↓ estrogen & defective 5-α reductase type 2 → ↓
DHT → Gynecomastia, testicular atrophy.
• Thrombocytopenia, splenomegaly.
Liver cirrhosis • High SAAG > 1.1, low protein ascites.
• HPE : Nodules + fibrous septations.

206 29 Medicine

Ascites :
Management :
Grade Treatment
Grade 1 Salt restriction < 2 g/day.
Diuretics : Spironolactone + Furosemide.
Grade 2 • Spironolactone 100 mg/day, (max : 400 mg/day).
• Furosemide 40 mg/day, (max : 160 mg/day).
Grade 2 : Diuretic resistant No significant effect even after maximum dose of
ascites diuretics → TIPSS.
Grade 2 :Diuretic Intractable Not able to give full dose of diuretic d/t S/E.
ascites
Grade 3 Large volume paracentesis and TIPSS.
Complications of ascites :
• Hepatorenal syndrome.
• Hepatopulmonary syndrome.
• Spontaneous bacterial peritonitis.
Spontaneous bacterial peritonitis :
Presentation Abdominal pain, fever and chills, sepsis.
• MNNA (Monobacterial non-neutrocytic ascites)
d/t gram +ve organisms.
Milder forms
• CNNA (Culture negative non-neutrocytic
ascites).
• Ascitic fluid total WBC count : >500 cell/microL.
• PMN count : >250 cells/microL, in the absence
Investigations of surgically treatable source of infection.
• Culture +ve : Gram -ve organisms (E. coli).
Treatment Inj. Ceftriaxone 2g IV TDS X 5 days.
Prophylaxis Norfloxacin 400 mg.
Hepato-renal syndrome :
Physiological impairment of kidney :
Portal HTN with ascites → ↑NO → Splanchnic vasodilatation → Intravascular
volume depleted → RAAS ↑↑ → Intrarenal vasoconstriction (Pre-renal failure
unresponsive to fluids).
No structural evidence of kidney disease, diagnosis of exclusion.
Treatment :
• Liver transplant.
• Vasoconstrictors : Terlipressin, norepinephrine, subcutaneous octreotide + oral
Midodrine.
Hepato-pulmonary syndrome : ----- Active space -----
Cirrhosis with portal HTN with unexplained hypoxia and dyspnea

Presentation
and normal EF.
Clinical features Hypoxia, clubbing, platypnea and orthodeoxia.
IOC Bubble echocardiography.
Treatment Liver transplant.
Hepatic/portosystemic encephalopathy :
Reversible condition.
Precipitating factors :
↑ Ammonia Alkalosis
Hypovolemia.
Vomiting.
Sepsis.
Dehydration.
Upper GI bleed.
Diuretics.
↑ protein intake.
Hypokalemia.
Constipation.
Renal failure.
Benzodiazepines.
Toxins responsible :
1. Ammonia :
• Produced from : Dietary protein, bacteria in colon, glutaminase.
• Detoxified in : liver.
2. Other toxins : Mercaptans, phenols, aromatic amino acids, manganese.
Pathology in brain :
• Ammonia + glutamate = Glutamine accumulates in astrocytes.
• ↑ Glutamate in CSF → Stimulates NMDA receptors.
• Secondary neuronal injury.
West haven criteria :
Type of HE Clinical features
Grade 0 Minimal hepatic encephalopathy Psychometric test +ve.
Covert hepatic Short attention span .
Grade 1
encephalopathy Sleep disturbances.
Personality and behavior changes,
Grade 2
asterixis.
Disorientation, clonus, rigidity &
Overt hepatic
Grade 3 hyperreflexia
encephalopathy
Responsive to pain.
Comatose pt.
Grade 4
Triphasic waves on EEG.

208 29 Medicine

Management :
• Bowel wash with lactulose : Non-absorbable disaccharide which reduces pH
of lumen.
• Rifaximin
• LOLA (L-Ornithine-L-aspartate).
• Identifying precipitating factor & its treatment.
Hepatic venous pressure gradient (HPVG) : Wedge hepatic venous pressure

(WHVP) - free hepatic venous pressure (FHVP).
Causes WHVP FHVP HVPG
Prehepatic Normal Normal Normal
Intrahepatic High (Sinusoidal pressure > 6 mm Hg) Normal High
Post-hepatic High High Normal

High HPVG is a risk factor for variceal bleed.
Important formulas :
Serum anion gap.
• Na+ - (Cl- + HCO3-).
• Normal anion gap metabolic acidosis : RTA/VIPoma.
• High anion gap metabolic acidosis : Keto acidosis, lactic acidosis, uremic aci-
dosis, alcoholic ketoacidosis.
Urine anion gap.

• Unmeasured anions - unmeasured cations.
• +ve anion gap : Seen in RTA d/t decreased ↓NH4+.
• -ve anion gap : Physiological (Also seen in VIPoma).
Stool osmotic gap.

• Measured osmolarity of stool - (2 x stool (Na+ + K+)).
• If >100 → Osmotic diarrhea.
SAAG : S. Albumin - Ascitic fluid albumin.

Types :
Low SAAG ascitis (< 1.1) High SAAG ascitis (> 1.1)
Low protein Nephrotic syndrome. Portal HTN
High protein Peritoneal carcinomatosis. Budd-Chiari syndrome.

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Www.Medicalstudyzone.

com CVS Revision 1 01 1

CVS REVISION 1 ----- Active space -----

Aortic Valve Disorder 00:02:49

• Lesser the no. of leaflets → chances of stenosis (Unicuspid > Bicuspid).

Aortic Stenosis (AS) : 00:04:43

Bicuspid aortic valve (M>F) Tricuspid aortic valve (M>F)

Medicine Revision • v1.0 • Marrow 6.5 • 2023

Furthermore You can also request a specific

----- Active space -----

ASD 5/3/2 rule : Chances of survival if surgery not done,

Note : Aortic stenosis → Pressure overload condition (Palpitation not

Medicine Revision • v1.0 • Marrow 6.5 • 2023

Clinical findings : ----- Active space -----

Note : Production of heart sounds.

Medicine Revision • v1.0 • Marrow 6.5 • 2023

----- Active space -----

Acute aortic regurgitation :

Chronic aortic Regurgitation :

Valve Leaflet issues Root issues

Heart sound • Soft S1 : Premature closure.

Medicine Revision • v1.0 • Marrow 6.5 • 2023

----- Active space -----

Mitral Stenosis (MS) :

Classification of Mitral Stenosis : On basis of Valve Surface area.

Medicine Revision • v1.0 • Marrow 6.5 • 2023

Clinical Findings : ----- Active space -----

Mitral Regurgitation (MR) : 01:10:35

Acute Mitral Regurgitation :

----- Active space -----

Factors improving and worsening MR :

Mild to Moderate MR Severe/Decompensated MR

Medicine Revision • v1.0 • Marrow 6.5 • 2023

Clinical Findings : ----- Active space -----

Medicine Revision • v1.0 • Marrow 6.5 • 2023

----- Active space ----- CVS REVISION-2

Physiology of Pulse 00:00:11

Wave Coincides with

Abnormalities in Pulse 00:04:30

Medicine Revision • v1.0 • Marrow 6.5 • 2023

Contour abnormalities : ----- Active space -----

1. Pulsus bisferiens 2. Pulsus dicroticus

HCM d/t SAM. Severe AR ± Mild AS

Jugular venous pulse 00:13:53

Normal JVP waveform :

Medicine Revision • v1.0 • Marrow 6.5 • 2023

----- Active space -----

Heart sounds 00:34:36

Mixed murmur Low pitched murmurs Low pitched heart sounds

Split S2 : ----- Active space -----

Wide variable split Wide fixed split Paradoxical split

S4 : Seen only in AS.

Added systolic sounds :

Medicine Revision • v1.0 • Marrow 6.5 • 2023

----- Active space ----- CVS REVISION 3

Heart Failure 00:00:27

1. Dyspnea : ----- Active space -----

Medicine Revision • v1.0 • Marrow 6.5 • 2023

----- Active space -----

Dysfunction of ventricles 00:29:29

Systolic dysfunction Diastolic dysfunction

Diastolic dysfunction with normal systole.

Constrictive Restrictive (more severe)