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Section A - Complete Answers

Q.1 Fill in the Blanks (6×1=6)

a) Hereditary haemochromatosis is a genetic disorder characterized by the presence of excessive levels of iron in the body.

It is an autosomal recessive condition (HFE gene mutation, most commonly C282Y) causing excessive intestinal iron absorption and iron deposition in organs (liver, heart, pancreas, skin, joints).

b) All viral hepatitis are caused by RNA viruses except Hepatitis B (and D).

Hepatitis B is a DNA virus (Hepadnaviridae). Hepatitis A, C, D, and E are all RNA viruses.

c) Tall tented T waves are classically seen on ECG in patients with raised serum levels of potassium (hyperkalemia).

Hyperkalemia causes progressive ECG changes: peaked/tented T waves → widened QRS → sine wave pattern → ventricular fibrillation.

d) The four pillars of heart failure management are beta blockers, RAAS inhibitors, mineralocorticoid receptor antagonists and SGLT2 inhibitors (Sodium-Glucose Cotransporter-2 inhibitors, e.g., dapagliflozin/empagliflozin).

These four classes form the current evidence-based cornerstone of HFrEF management.

e) The valvular heart disease that can cause water hammer pulse is aortic regurgitation (AR).

Also called Corrigan's pulse - a rapidly rising and collapsing bounding pulse due to wide pulse pressure from diastolic backflow. (Fuster and Hurst's The Heart, 15th Ed.)

f) Argyll Robertson pupil is classically seen in infection of the central nervous system by Treponema pallidum (syphilis / neurosyphilis).

The pupil accommodates but does not react to light ("prostitute's pupil" - accommodates but does not react). (Localization in Clinical Neurology, 8th Ed.)

Q.2 MCQs (4×1=4)

i. Weil's disease is caused by: d) Leptospirosis

Weil's disease is the severe icteric form of leptospirosis, caused by Leptospira interrogans, characterised by jaundice, acute kidney injury, and bleeding tendencies.

ii. The international criteria for diagnosis and management of COPD is known as: a) GOLD

GOLD = Global Initiative for Chronic Obstructive Lung Disease. It provides staging (GOLD 1-4 based on FEV1%) and treatment recommendations.

iii. All of the following cause microcytic anemia EXCEPT: c) Folate deficiency

Folate deficiency causes macrocytic (megaloblastic) anemia, not microcytic.
Iron deficiency, sideroblastic anemia, and lead poisoning all cause microcytic hypochromic anemia.

iv. All of the following are used in the management of thyroid storm EXCEPT: c) Levothyroxine

Levothyroxine is a thyroid hormone replacement - it would worsen thyroid storm, not treat it.
Treatment of thyroid storm includes: PTU or carbimazole (block synthesis), beta blockers (propranolol - control sympathetic symptoms), glucocorticoids (reduce T4→T3 conversion, treat relative adrenal insufficiency), iodine (Lugol's), and supportive care.

Q.3 Clinical Case - Pulmonary Embolism (4+4+7=15)

Clinical scenario: 30-year-old male, bedridden 2 weeks (femur shaft fracture) → sudden onset breathlessness + palpitations → HR 130 bpm, BP 70/50 mmHg (hypotensive/shock). ACS ruled out.

a) Probable Diagnosis:

Massive Pulmonary Embolism (PE)

Reasoning:

Prolonged immobilization (fracture + bedridden) = major risk factor for DVT → PE (Virchow's triad: stasis)
Sudden onset dyspnea and palpitations
Hemodynamic instability: HR 130 (tachycardia), BP 70/50 (cardiogenic shock)
ACS excluded

This is massive/high-risk PE with hemodynamic compromise.

b) Classical ECG Findings in PE:

The most classic ECG pattern is the S1Q3T3 pattern:

S wave in lead I (deep)
Q wave in lead III
T wave inversion in lead III

Other ECG findings in PE:

Sinus tachycardia (most common ECG finding overall)
Right axis deviation
Right bundle branch block (RBBB) - complete or incomplete
T wave inversions in V1-V4 (right heart strain)
P pulmonale (peaked P waves)
Atrial fibrillation/flutter

c) Further Management of Massive PE:

Immediate resuscitation:

IV access, oxygen (high flow), continuous monitoring
Fluid resuscitation (cautious - 500 mL IV crystalloid)
Vasopressors (norepinephrine) for refractory hypotension

Confirm diagnosis:

CT Pulmonary Angiography (CTPA) - gold standard (if patient stable enough)
Bedside echocardiography - shows right heart strain, RV dilation, McConnell's sign
D-dimer (elevated but non-specific; not needed if high clinical probability + hemodynamic instability)
ABG: hypoxemia, hypocapnia, respiratory alkalosis

Definitive treatment - Reperfusion (PRIORITY in massive PE):

Systemic thrombolysis - First choice for massive PE with hemodynamic collapse
- Alteplase (tPA) 100 mg IV over 2 hours (or 0.6 mg/kg over 15 min if cardiac arrest)
- Contraindicated if recent surgery/active bleeding - consider surgical embolectomy instead
Surgical embolectomy - If thrombolysis contraindicated or fails
Catheter-directed thrombolysis/thrombectomy - Interventional option

Anticoagulation:

Unfractionated heparin (UFH) IV infusion - start immediately (before/alongside thrombolysis)
Transition to LMWH/NOAC (e.g., rivaroxaban) after stabilization
Duration: minimum 3-6 months (provoked PE from immobilization)

Other:

IVC filter if anticoagulation absolutely contraindicated
Monitor for reperfusion complications (bleeding)
ICU admission

Q.4 Short Notes (any 5, 5×2=10)

a) Causes of Acute Kidney Injury (AKI)

Classified as Pre-renal, Intrinsic renal, and Post-renal:

Pre-renal (most common, ~60%): Hypovolemia (hemorrhage, diarrhea, burns), reduced cardiac output (HF, cardiogenic shock), renal artery stenosis, sepsis (distributive shock)
Intrinsic renal:
- Glomerular: glomerulonephritis, vasculitis
- Tubular: Acute Tubular Necrosis (ATN) - ischemic (most common intrinsic) or nephrotoxic (aminoglycosides, contrast, cisplatin, myoglobin in rhabdomyolysis)
- Interstitial: Acute Interstitial Nephritis (AIN) - NSAIDs, antibiotics (penicillins)
- Vascular: renal vein thrombosis, HUS/TTP
Post-renal (obstructive): BPH, ureteral stones, pelvic malignancy, retroperitoneal fibrosis

b) Blood Pressure Management in Acute Ischemic Stroke

Thrombolysis eligible: Lower BP to <185/110 mmHg before tPA; maintain <180/105 mmHg for 24h after
Thrombolysis NOT eligible: Allow permissive hypertension up to 220/120 mmHg (auto-regulation maintains penumbra)
- Only treat if BP >220/120 mmHg, or if hypertensive emergency with end-organ damage
Target reduction: No more than 15-25% in first 24 hours
Agents: IV labetalol, nicardipine, clevidipine preferred (avoid sublingual nifedipine - rapid drop dangerous)
Hypotension: Treat aggressively with IV fluids/vasopressors (worsens ischemia)

c) Treatment of Chronic Hepatitis C

Direct Acting Antivirals (DAAs) - Highly effective (>95% SVR):
- Sofosbuvir + Ledipasvir (NS5B + NS5A inhibitors) - 8-12 weeks
- Sofosbuvir + Velpatasvir (pan-genotypic) - 12 weeks
- Glecaprevir + Pibrentasvir - 8 weeks for non-cirrhotic, treatment-naive
Goal: Sustained Virologic Response (SVR) = undetectable HCV RNA at 12 weeks post-treatment (= cure)
Pre-treatment: genotyping, liver fibrosis assessment, screen for HBV co-infection
Interferon + ribavirin regimens now largely obsolete due to DAA efficacy

d) Jones Criteria for Acute Rheumatic Fever (ARF)

Used to diagnose initial episode of ARF (requires evidence of preceding Group A Streptococcal infection):

Major criteria (JONES):

J - Joints (migratory polyarthritis) - most common
O - carditis (O = Oh the heart!) - pancarditis, most serious
N - Nodules (subcutaneous nodules - painless, over bony prominences)
E - Erythema marginatum (skin rash)
S - Sydenham's chorea (involuntary movements)

Minor criteria:

Fever, raised ESR/CRP, prolonged PR interval on ECG, arthralgia (only if arthritis not used as major)

Diagnosis: 2 Major OR 1 Major + 2 Minor criteria + evidence of preceding streptococcal infection (raised ASO titre, positive throat culture, recent scarlet fever)

e) Procedure of Lumbar Puncture (LP)

Position: Lateral decubitus (fetal position) or sitting forward-flexed - to widen intervertebral spaces

Site: L3-L4 or L4-L5 interspace (below spinal cord termination at L1-L2 in adults)

Steps:

Confirm no raised ICP (papilledema, focal neurology → do CT head first)
Aseptic technique, local anesthesia (lignocaine)
Insert spinal needle (22G) through skin → supraspinous ligament → interspinous ligament → ligamentum flavum → epidural space → dura/arachnoid → subarachnoid space
Feel "give" (pop) as needle enters subarachnoid space; remove stylet
Measure opening CSF pressure (normal: 6-20 cmH2O)
Collect CSF: 4 bottles labeled in order (cell count, protein/glucose, culture, special tests)

Complications: Post-LP headache (most common - treat with bed rest, fluids, caffeine, blood patch), bleeding, infection, transtentorial herniation if raised ICP not excluded

f) CSF Findings in TB Meningitis

Parameter	Finding
Appearance	Clear/turbid, forms cobweb clot on standing
Pressure	Raised (>20 cmH2O)
Cells	100-500 cells/mm³, predominantly lymphocytes
Protein	Markedly elevated (100-500 mg/dL)
Glucose	Low (<45 mg/dL); CSF:serum glucose ratio <0.5
AFB smear	Positive in ~40% (low sensitivity)
Culture	Gold standard (Lowenstein-Jensen medium); takes 4-8 weeks
ADA	Elevated adenosine deaminase (>10 U/L)
PCR	High sensitivity/specificity for M. tuberculosis

Q.5 Short Essays (any 3, 3×5=15)

a) Chronic Myeloid Leukemia (CML)

Definition: A myeloproliferative neoplasm characterized by clonal expansion of a pluripotent stem cell carrying the BCR-ABL1 fusion gene (Philadelphia chromosome).

Genetics/Pathogenesis:

t(9;22)(q34;q11) translocation → Philadelphia chromosome (Ch22)
BCR-ABL1 fusion gene encodes a constitutively active tyrosine kinase → unregulated cell proliferation

Phases:

Chronic phase (CP): Most common at diagnosis; well-differentiated cells; indolent
Accelerated phase (AP): 15-29% blasts
Blast crisis (BC): ≥30% blasts; like acute leukemia (myeloid 70%, lymphoid 30%)

Clinical features:

Often asymptomatic (incidental finding on CBC)
Massive splenomegaly (hallmark)
Weight loss, fatigue, sweating, early satiety
Rarely: leukostasis, gout (hyperuricemia)

Investigations:

CBC: very high WBC (often >100,000/mm³), basophilia, eosinophilia, thrombocytosis
Peripheral smear: all stages of myeloid maturation ("left shift"), basophilia
Bone marrow: hypercellular; myeloid:erythroid ratio increased
Cytogenetics: Philadelphia chromosome (t(9;22))
PCR/FISH: BCR-ABL1 fusion (quantitative PCR for monitoring treatment response)
Low Leukocyte Alkaline Phosphatase (LAP) score (differentiates from leukemoid reaction)

Treatment:

Tyrosine Kinase Inhibitors (TKIs) - first-line, oral, highly effective:
- Imatinib (Gleevec) - 1st generation
- Dasatinib, Nilotinib - 2nd generation
- Bosutinib, Ponatinib - 3rd generation (for resistance/T315I mutation)
Allogeneic stem cell transplantation: potentially curative; reserved for blast crisis or TKI failure
Hydroxyurea: cytoreduction before TKI initiation

Monitoring: BCR-ABL PCR every 3 months; aim for Major Molecular Response (MMR = BCR-ABL <0.1%)

b) Peripheral Blood Film Examination and Its Uses

Procedure: Thin blood smear on glass slide, fixed with methanol, stained with Romanowsky stain (Leishman/Giemsa).

Normal components assessed:

Red cell morphology (size, shape, color, inclusions)
White cell differential count and morphology
Platelet count and morphology

Uses and findings:

Condition	PBF Finding
Iron deficiency anemia	Microcytic hypochromic RBCs, pencil cells, anisopoikilocytosis
Megaloblastic anemia	Macro-ovalocytes, hypersegmented neutrophils (≥5 lobes)
Sickle cell disease	Sickle cells (drepanocytes)
Hereditary spherocytosis	Spherocytes, no central pallor
Microangiopathic hemolytic anemia (TTP/HUS, DIC)	Schistocytes (fragmented RBCs)
Malaria	Intraerythrocytic parasites (ring forms, gametocytes)
CML	All stages of myeloid maturation, basophilia
CLL	Lymphocytosis, smear/smudge cells (Basket cells)
Infectious mononucleosis	Atypical/reactive lymphocytes
ITP	Low platelets, large platelets
Lead poisoning	Basophilic stippling of RBCs
Thalassemia	Target cells, microcytic hypochromic, nucleated RBCs

Clinical utility: Cheap, rapid, widely available; guides further investigations and initial diagnosis.

c) Etiology of Portal Hypertension

Definition: Portal vein pressure >10 mmHg (normal 5-10 mmHg) or portal pressure gradient (HVPG) >5 mmHg. Clinically significant >10 mmHg.

Classified by site of obstruction:

1. Pre-hepatic (pre-sinusoidal, outside liver):

Portal vein thrombosis (most common pre-hepatic cause)
Splenic vein thrombosis
Arteriovenous fistula
Massive splenomegaly

2. Intra-hepatic:

Pre-sinusoidal: Schistosomiasis (most common worldwide), primary biliary cholangitis, hepatic sarcoidosis, congenital hepatic fibrosis
Sinusoidal (most common in developed world): Liver cirrhosis (hepatitis B, C, alcohol, NAFLD, autoimmune hepatitis) - accounts for >90% of portal hypertension
Post-sinusoidal: Veno-occlusive disease (sinusoidal obstruction syndrome - post-chemo/BMT)

3. Post-hepatic (outside liver):

Budd-Chiari syndrome (hepatic vein thrombosis)
Constrictive pericarditis
Right heart failure (cardiac cirrhosis)
IVC obstruction/web

Consequences of Portal Hypertension:

Esophageal/gastric varices (risk of bleeding)
Ascites
Splenomegaly (hypersplenism → cytopenia)
Hepatic encephalopathy
Hepatorenal syndrome
Portosystemic shunts (caput medusae, hemorrhoids)

d) Management of TB with HIV

Principles: Both TB and HIV must be treated; drug interactions (especially rifampicin-ARVs) and immune reconstitution inflammatory syndrome (IRIS) must be managed.

Anti-TB Treatment:

Standard regimen: 2HRZE / 4HR (same as HIV-negative patients)
- Intensive phase: Isoniazid (H) + Rifampicin (R) + Pyrazinamide (Z) + Ethambutol (E) × 2 months
- Continuation phase: Isoniazid + Rifampicin × 4 months
Add Pyridoxine (Vitamin B6) to prevent INH-related peripheral neuropathy (especially important in HIV)

When to start ART:

CD4 <50 cells/μL: Start ART within 2 weeks of TB treatment initiation (survival benefit)
CD4 ≥50 cells/μL: Start ART within 8 weeks (2-8 weeks) of TB treatment
TB Meningitis: Delay ART by 4-8 weeks (IRIS in CNS is dangerous)

ART drug interactions with Rifampicin:

Rifampicin is a potent CYP450 inducer → reduces levels of many ARVs
Preferred ART: Efavirenz-based regimen (EFV is less affected; dose 600mg/day maintained or increase to 800mg if >60kg)
Nevirapine: avoid (subtherapeutic levels)
Protease inhibitors: avoid with rifampicin (use rifabutin instead if PI necessary)
Integrase inhibitors (dolutegravir): double dose of dolutegravir (50mg BD) if used with rifampicin

IRIS (Immune Reconstitution Inflammatory Syndrome):

Paradoxical worsening of TB symptoms after ART initiation (due to immune recovery unmasking occult TB)
Usually mild - continue both ART and TB treatment
Severe IRIS: prednisolone 1 mg/kg/day, taper over 4 weeks

Monitoring:

TB sputum smear/culture at 2 months, end of treatment
CD4 count and viral load every 6 months
LFTs (hepatotoxicity from both INH and ARVs)
Adherence counseling (two complex regimens simultaneously)

Sources: Goldman-Cecil Medicine, Fuster and Hurst's The Heart 15th Ed., Localization in Clinical Neurology 8th Ed., Rosen's Emergency Medicine - all from the medical textbook library.

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