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Full Exam Answers

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MCQs (Questions 9 & 10)

Q9. Which electrolyte abnormality is typically seen in tumor lysis syndrome?

• Hyperkalemia (from intracellular K+ release)
• Hyperphosphatemia (from intracellular phosphate release)
• Hypocalcemia (secondary to hyperphosphatemia)
• Hyperuricemia (from purine metabolism)

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Q10. The most common organism causing native valve infective endocarditis is:

• Staphylococcus aureus is the most common cause of acute native valve endocarditis and is the most common overall cause in IV drug users and nosocomial IE (it has overtaken viridans streptococci in some modern series)
• Enterococcus is the third most common
• Pseudomonas is rare and associated with IV drug use

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Q.2 Clinical-Based Long Question (15 Marks)

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a) Diagnosis (2 marks)

• Risk factors: hypertension, diabetes mellitus
• Typical ischemic chest pain: sudden, severe, radiating to left shoulder
• Diaphoresis (sweating)
• ECG: ST elevation in V1-V4
• Duration: 2 hours (within the reperfusion window)

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b) ECG Interpretation and Infarct Territory (3 marks)

• ST elevation in leads V1, V2, V3, V4 = anterior STEMI
• Criteria for significant ST elevation: ≥2 mm in V1-V4 in men

• V1-V4 = Anterior wall of the left ventricle
• Culprit artery: Left Anterior Descending (LAD) artery (proximal to mid segment)
• V1-V2 involvement suggests possible septal extension
• V3-V4 = anterior territory

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c) Emergency Management in the First Hour (5 marks)

• 12-lead ECG within 10 minutes of arrival
• Establish IV access x2, continuous cardiac monitoring, pulse oximetry
• Airway assessment; oxygen ONLY if SpO2 <90%

• Activate catheterization lab immediately
• Door-to-balloon time target: <90 minutes (primary PCI)
• If PCI unavailable within 120 min: thrombolysis within 30 min of door arrival

• Troponin (I or T), CK-MB, BNP, CBC, LFTs, RFTs, coagulation, glucose, lipids
• Chest X-ray (portable, should not delay reperfusion)

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d) Reperfusion Strategies and Indications (3 marks)

1. Primary Percutaneous Coronary Intervention (Primary PCI) - PREFERRED

• Door-to-balloon time: <90 minutes (if presenting to PCI-capable center)
• Superior to thrombolysis: lower re-infarction rate, better TIMI 3 flow, lower mortality
• Drug-eluting or bare metal stent placement in the culprit artery

2. Thrombolysis (Fibrinolytic Therapy)

• Prior intracranial hemorrhage (absolute)
• Ischemic stroke within 3 months (absolute)
• Active internal bleeding (absolute)
• Severe uncontrolled hypertension (>180/110 at presentation)
• Recent major surgery/trauma (<3 weeks)
• Aortic dissection suspected

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e) Four Important Complications (2 marks)

1. Cardiogenic shock - pump failure due to extensive myocardial damage (>40% LV loss); most common cause of in-hospital death
2. Ventricular arrhythmias - ventricular fibrillation (VF) or ventricular tachycardia (VT); risk highest in first 24-48 hours (early arrhythmias) and later due to scar re-entry
3. Acute mitral regurgitation - papillary muscle rupture or dysfunction (especially posteromedial papillary muscle); presents with acute pulmonary edema
4. Ventricular free wall rupture / Ventricular septal defect (VSD) - occurs 3-5 days post-MI; free wall rupture causes haemopericardium and tamponade; VSD causes sudden biventricular failure

• Left ventricular aneurysm (late)
• Dressler's syndrome (pericarditis 2-10 weeks post-MI)
• Deep vein thrombosis / pulmonary embolism
• Heart failure / pulmonary edema

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Q.3 Long Answer - Chronic Kidney Disease (15 Marks)

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Definition and KDIGO Staging (3 marks)

• Markers of kidney damage: albuminuria (AER ≥30 mg/24h), urine sediment abnormalities, tubular disorders, histologic abnormalities, structural abnormalities on imaging, history of kidney transplant
• Decreased GFR: eGFR <60 mL/min/1.73 m²

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Etiology (2 marks)

1. Diabetic nephropathy - #1 cause worldwide; glomerulosclerosis from chronic hyperglycemia
2. Hypertensive nephrosclerosis - #2 cause; arteriolar sclerosis and ischemic glomerular damage
3. Primary glomerulonephritis - IgA nephropathy (most common worldwide), focal segmental glomerulosclerosis (FSGS), membranous nephropathy
4. Polycystic kidney disease (ADPKD) - most common hereditary cause
5. Chronic pyelonephritis / recurrent UTI - especially with vesicoureteral reflux
6. Obstructive uropathy - BPH, stones, posterior urethral valves
7. Lupus nephritis - autoimmune
8. Renovascular disease - renal artery stenosis, ischemic nephropathy
9. Drug-induced nephropathy - NSAIDs, calcineurin inhibitors, aminoglycosides

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Clinical Features (2 marks)

• Metabolic acidosis (decreased acid excretion)
• Hyperkalemia (decreased K+ excretion)
• CKD-Mineral Bone Disease (CKD-MBD): hyperphosphatemia, hypocalcemia, secondary hyperparathyroidism, renal osteodystrophy

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Investigations (3 marks)

• eGFR (calculated from serum creatinine using CKD-EPI formula)
• Urine albumin:creatinine ratio (ACR) or 24-hour urine protein
• Urine microscopy (RBC casts = glomerulonephritis, oval fat bodies = nephrotic)
• Serial measurements >3 months to confirm chronicity

• Renal ultrasound (small/echogenic kidneys = CKD; asymmetric = renovascular disease; large kidneys = ADPKD, amyloid, diabetic nephropathy)
• Fasting glucose, HbA1c (diabetes)
• ANA, anti-dsDNA, ANCA, anti-GBM, complement levels (autoimmune)
• Serum protein electrophoresis, urine Bence Jones protein (myeloma)
• Renal biopsy (if etiology unclear, proteinuria >1g/day, unexplained rapid decline)

• CBC (anemia)
• Serum electrolytes: K+, Na+, bicarbonate (acidosis), Ca2+, phosphate, PTH
• Lipid profile
• ECG, echocardiogram (LV hypertrophy, pericardial effusion)
• Bone density (osteodystrophy)

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Principles of Management including Renal Replacement Therapy (5 marks)

A. Slowing CKD Progression

B. Managing Complications

• Anemia: Iron supplementation first; then erythropoiesis-stimulating agents (ESAs) (e.g., epoetin alfa, darbepoetin) if Hb <10 g/dL despite iron repletion; target Hb 10-11.5 g/dL
• CKD-MBD: Dietary phosphate restriction, phosphate binders (calcium carbonate, sevelamer, lanthanum carbonate); active Vitamin D (calcitriol/alfacalcidol); calcimimetics (cinacalcet) for secondary hyperparathyroidism
• Metabolic acidosis: Sodium bicarbonate supplementation (target serum bicarbonate ≥22 mEq/L)
• Hyperkalemia: Dietary K+ restriction, diuretics, patiromer or sodium zirconium cyclosilicate
• Dyslipidemia: Statin therapy
• Cardiovascular risk: Antiplatelet therapy where appropriate, smoking cessation
• Volume overload: Loop diuretics (furosemide), sodium restriction

C. Preparation for Renal Replacement Therapy (RRT)

• Hepatitis B vaccination
• AV fistula creation (if hemodialysis planned) - at least 6 months before expected need
• Patient education and modality selection

D. Renal Replacement Therapy (RRT)

• Acidosis - refractory metabolic acidosis
• Electrolytes - refractory hyperkalemia
• Ingestion - drug/toxin overdose
• Overload - refractory fluid overload/pulmonary edema
• Uremia - uremic symptoms (pericarditis, encephalopathy, neuropathy, bleeding)
• GFR <10 mL/min (G5), even if asymptomatic, or GFR <15 with diabetes

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Full Exam Answers - Part B

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Q.4 Short Answer Questions (4 × 2.5 = 10 Marks)

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a) Hyperosmolar Hyperglycaemic State (HHS) (2.5 marks)

• Extreme thirst, polyuria (days to weeks history - slower onset than DKA)
• Profound dehydration (fluid deficit 8-12 L)
• Altered sensorium - confusion, stupor, coma (proportional to osmolality)
• Focal neurological deficits, seizures
• NO Kussmaul breathing, NO fruity odor (absent ketones)

• Blood glucose, serum electrolytes, BUN/creatinine
• Serum osmolality = 2(Na) + glucose/18 + BUN/2.8
• ABG, CBC, urine ketones, ECG, CXR, cultures (to find precipitant)

1. Fluids: 0.9% NaCl 1-2 L in first hour, then 0.45% NaCl at 250-500 mL/hr; switch to D5W when glucose reaches ~250-300 mg/dL
2. Insulin: Regular insulin infusion 0.1 units/kg/hr (start only after fluids begun and K+ >3.5 mEq/L); target glucose reduction 50-75 mg/dL/hour
3. Potassium: Replace aggressively; hypokalemia worsens with insulin
4. Anticoagulation: Consider (high thrombosis risk)
5. Treat precipitant

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b) Hypertensive Emergency (2.5 marks)

• Severe headache, visual disturbances, confusion (encephalopathy)
• Chest pain, dyspnea (cardiac involvement)
• Oliguria, hematuria (renal involvement)
• Focal neurological deficits (stroke)

• General rule: Reduce MAP by no more than 25% in the first hour, then to 160/100-110 mmHg over 2-6 hours
• Exception - Aortic dissection: Reduce systolic to <120 mmHg within minutes (use labetalol + nitroprusside)
• Exception - Ischemic stroke (no thrombolysis): Treat only if BP >220/120 mmHg; reduce by only 15% in first 24 hours
• Eclampsia: Target <160/110 mmHg; IV magnesium for seizure prophylaxis

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c) Acute Severe Asthma (2.5 marks)

• Severe dyspnea, inability to complete sentences
• Wheeze (or silent chest = very severe)
• Tachycardia, tachypnea, use of accessory muscles
• Pulsus paradoxus
• Agitation, confusion (CO2 retention)

1. Oxygen: High-flow O2 to maintain SpO2 94-98%
2. Bronchodilators:

• Salbutamol (albuterol): 2.5-5 mg nebulized every 20 min x3 (first-line); IV salbutamol if nebulization fails
• Ipratropium bromide: 0.5 mg nebulized 4-6 hourly (add to salbutamol in acute severe/life-threatening)

1. Corticosteroids (mandatory and early):

• Prednisolone 40-50 mg oral OR Hydrocortisone 100 mg IV (if unable to swallow)
• Continue for at least 5 days
• Reduces airway inflammation, prevents relapse

1. IV Magnesium sulphate: 2 g IV over 20 minutes (for life-threatening/failure to respond); causes smooth muscle relaxation
2. IV Aminophylline: 5 mg/kg loading dose over 20-30 min, then infusion (rarely used now, reserved for refractory cases)
3. Heliox: Helium-oxygen mixture; reduces airway resistance (experimental use)
4. Non-invasive ventilation / Mechanical ventilation: For near-fatal asthma with respiratory failure; intubation if exhausted, PaCO2 rising, declining consciousness
5. Monitor: ABG, serial PEF, pulse oximetry, ECG (hypokalemia from salbutamol)
6. Identify and treat triggers: Infection (antibiotics if bacterial), allergen avoidance

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d) Falciparum Malaria (2.5 marks)

• Unique feature: cytoadherence - infected RBCs express PfEMP1 (P. falciparum erythrocyte membrane protein 1), causing them to adhere to vascular endothelium
• This leads to microvascular obstruction, tissue hypoxia, and organ dysfunction
• Rosetting (clustering of infected RBCs) and sequestration (parasites concentrate in deep vessels) occur
• Any proportion >2% parasitemia carries severe risk

• Cerebral malaria - unarousable coma, GCS <11 (most feared; 20% mortality even with treatment)
• Severe normochromic normocytic anemia (Hb <5 g/dL)
• Respiratory distress / metabolic acidosis (pH <7.25)
• Renal failure (creatinine >265 µmol/L)
• Hypoglycemia (glucose <2.2 mmol/L - worsened by quinine-induced insulin release)
• Pulmonary edema / ARDS
• Abnormal bleeding / DIC
• Circulatory collapse (algid malaria)
• Hemoglobinuria (blackwater fever)
• Repeated generalized convulsions (>2 per 24 hours)
• Hyperparasitemia (>5% parasitized RBCs)

• Thick and thin blood films (gold standard) - identify species and quantify parasitemia
• Rapid Diagnostic Tests (RDTs): Detect HRP-2 antigen (P. falciparum specific) - rapid, bedside
• PCR (highly sensitive, for research/confirmation)
• CBC: anemia, thrombocytopenia
• LFTs, RFTs, glucose, LDH

• Artemisinin-based combination therapy (ACT) - first-line globally
• Artemether-lumefantrine (most common)
• Artesunate-amodiaquine
• Artesunate-mefloquine

• IV Artesunate - drug of choice (superior to quinine - shown in SEAQUAMAT and AQUAMAT trials)
• Dose: 2.4 mg/kg IV at 0, 12, 24 hours then daily
• If artesunate unavailable: IV quinine (20 mg/kg loading, then 10 mg/kg 8-hourly) + doxycycline
• Switch to oral ACT once patient can tolerate

• Treat hypoglycemia with 50% dextrose
• Antiepileptics for seizures (IV diazepam)
• Renal replacement therapy for AKI
• Mechanical ventilation for pulmonary edema/ARDS
• Blood transfusion for severe anemia

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Q.5 Clinical-Based Long Question (15 Marks)

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a) Most Likely Diagnosis (2 marks)

• Subacute onset (10 days of fever - not acute like bacterial meningitis)
• Young adult female (common age group in endemic regions)
• Meningeal signs (neck stiffness)
• Altered sensorium
• CSF profile: lymphocytic pleocytosis + elevated protein + LOW glucose

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b) Differential Diagnosis (2 marks)

1. Viral (aseptic) meningitis - usually self-limiting, glucose normal/mildly low, milder course; HSV encephalitis can cause altered sensorium
2. Cryptococcal meningitis - especially in immunocompromised (HIV); CSF similar to TBM; diagnose with India ink stain, cryptococcal antigen
3. Partially treated bacterial meningitis - if antibiotics given before LP, CSF may show lymphocytes with low glucose
4. Cerebral abscess - focal signs, imaging essential
5. Neurosarcoidosis / Carcinomatous meningitis - rare; chronic course
6. Leptospirosis - exposure history, uveitis, renal involvement
7. HIV meningitis / Neurosyphilis - history, serology

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c) Interpretation of CSF Findings (3 marks)

• Lymphocytic pleocytosis = chronic/granulomatous inflammation (not acute bacterial)
• Low glucose = active infection consuming glucose AND impaired transport across blood-brain barrier - characteristic of TBM (and fungal/bacterial)
• Elevated protein = disruption of blood-brain barrier + cellular debris + immunoglobulins

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d) Investigations to Confirm Diagnosis (3 marks)

• AFB smear (Ziehl-Neelsen stain): 3 serial CSF samples; sensitivity 20-40% (multiple samples improve yield)
• CSF culture for M. tuberculosis: Gold standard, 80-90% sensitivity but takes 4-8 weeks (Lowenstein-Jensen medium)
• CSF adenosine deaminase (ADA): ADA >10 IU/L supports TBM (high sensitivity)
• CSF NAAT/GeneXpert MTB/RIF: Molecular diagnosis; rapid (hours), detects MTB and rifampicin resistance
• Interferon-gamma (IFN-γ) in CSF: elevated in TBM

• MRI brain with contrast (preferred) or CT brain: Look for:
• Basilar meningeal enhancement (characteristic of TBM)
• Hydrocephalus (communicating > obstructive)
• Tuberculomas / ring-enhancing lesions
• Infarcts (vasculitis)

• Chest X-ray: Look for pulmonary TB (hilar lymphadenopathy, apical infiltrates, miliary pattern)
• CT chest (more sensitive)
• Mantoux/TST: Positive supports TB; negative does NOT exclude (false-negative in severe disease)
• IGRA (QuantiFERON-TB Gold): More specific than Mantoux
• Sputum AFB smear and culture (3 samples)
• HIV ELISA (immunosuppression increases risk of TBM)
• Blood cultures for MTB (especially if miliary TB suspected)

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e) Management including Corticosteroids and ATT (5 marks)

Anti-Tubercular Therapy (ATT)

• Isoniazid (H): 5 mg/kg/day (max 300 mg) + pyridoxine (B6) 25 mg/day (prevents peripheral neuropathy)
• Rifampicin (R): 10 mg/kg/day (max 600 mg) - monitor LFTs
• Pyrazinamide (Z): 25 mg/kg/day (max 2g) - monitor uric acid, LFTs
• Ethambutol (E): 15-20 mg/kg/day - monitor visual acuity (optic neuritis)

Corticosteroids (MANDATORY in TBM)

• Dexamethasone: 0.4 mg/kg/day IV for 2 weeks, then taper over 6 weeks
• Or Prednisolone: 1-2 mg/kg/day, tapered over 6-8 weeks
• Mechanism: Reduces vasculitis, cerebral edema, and exuberant inflammatory response

• ALL patients with confirmed or highly suspected TBM (regardless of severity)
• Grade II/III TBM especially (British Medical Research Council grading)

Supportive Management:

• Raised ICP / Hydrocephalus: Mannitol 20% (0.5-1 g/kg IV); serial LPs to reduce pressure; neurosurgical ventriculoperitoneal shunt if obstructive hydrocephalus
• Seizures: IV diazepam acutely; phenytoin/levetiracetam for maintenance
• Nutrition: Nasogastric feeding if altered sensorium
• DVT prophylaxis
• Pyridoxine with isoniazid (prevent peripheral neuropathy)
• Monitor: LFTs, visual acuity, neurological status
• Drug-induced hepatitis: Suspend ATT if ALT >3x normal + symptoms; re-introduce sequentially

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Q.6 Long Answer Question (15 Marks)

Decompensated Cirrhosis of Liver

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Etiology (2 marks)

1. Alcohol-related liver disease (ARLD) - most common in Western countries; >80 g/day alcohol for >10 years
2. Viral hepatitis:

• Hepatitis B (with or without Hepatitis D co-infection) - most common globally
• Hepatitis C - major cause; now highly treatable with DAAs (direct-acting antivirals)

1. Non-alcoholic fatty liver disease (NAFLD) / NASH - increasingly prevalent; linked to obesity, diabetes, metabolic syndrome
2. Autoimmune hepatitis
3. Primary biliary cholangitis (PBC) / Primary sclerosing cholangitis (PSC)
4. Hereditary/metabolic:

• Wilson's disease (copper accumulation)
• Hereditary hemochromatosis (iron overload)
• Alpha-1-antitrypsin deficiency

1. Cardiac cirrhosis - chronic right heart failure (congestive hepatopathy)
2. Drug-induced (amiodarone, methotrexate)
3. Cryptogenic (~10%)

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Pathophysiology of Portal Hypertension (2 marks)

1. Increased intrahepatic vascular resistance:

• Structural: fibrosis, regenerative nodules distort sinusoids and portal/hepatic veins
• Functional (reversible): activated hepatic stellate cells (myofibroblasts) contract in response to endothelin-1, thromboxane A2 → reduced NO (eNOS dysfunction within liver) → increased tone

1. Increased portal blood flow (hyperdynamic circulation):

• Splanchnic vasodilation mediated by excess nitric oxide (NO), prostacyclin, glucagon
• Leads to increased blood flow into portal system
• Systemic response: decreased SVR → activation of RAAS, SNS, ADH → sodium and water retention → expansion of plasma volume → worsens portal hypertension

• Varices form at portosystemic anastomoses (esophageal, gastric, anorectal, caput medusae)
• Ascites (see below)
• Splenomegaly + hypersplenism (thrombocytopenia, leukopenia)
• Hepatic encephalopathy (portosystemic shunting of ammonia)

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Clinical Features (3 marks)

• Jaundice (deep yellow/green)
• Coagulopathy (easy bruising, prolonged PT/INR)
• Hypoalbuminemia (edema, loss of muscle mass)
• Palmar erythema, spider naevi (>5 = significant), leukonychia, Terry's nails
• Gynecomastia, testicular atrophy, loss of body hair (estrogen excess)
• Parotid enlargement (alcoholic)
• Hepatic fetor (breath smelling of "raw liver")

1. Ascites: Abdominal distension, shifting dullness, fluid thrill; most common decompensation event
2. Peripheral edema: Pitting, bilateral ankle-sacral edema
3. Hepatic Encephalopathy (HE):

• Grade I: Mild confusion, mood change
• Grade II: Drowsiness, asterixis (flapping tremor)
• Grade III: Stupor, responses to stimulation
• Grade IV: Coma
• Asterixis ("liver flap") = characteristic

1. Variceal bleeding: Sudden large hematemesis/melena; can be fatal
2. Spontaneous Bacterial Peritonitis (SBP): Fever, abdominal pain, worsening encephalopathy
3. Hepatorenal Syndrome (HRS): Oliguria, rising creatinine, dilutional hyponatremia

• Hepatomegaly (early) → small shrunken liver (late cirrhosis)
• Splenomegaly
• Caput medusae (dilated periumbilical veins)

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Investigations (2 marks)

• Raised bilirubin, low albumin, raised PT/INR (poor synthesis)
• Raised AST/ALT (inflammation), raised GGT/ALP

• CBC: Thrombocytopenia (hypersplenism + reduced TPO), anemia, leukopenia
• Coagulation: Prolonged PT, INR >1.5

• Cell count: PMN >250/mm³ = SBP
• Culture and sensitivity (SBP organisms: E. coli, Klebsiella, Streptococcus pneumoniae)
• SAAG (Serum-Ascites Albumin Gradient): SAAG ≥1.1 g/dL = portal hypertension (high sensitivity)
• Protein, cytology (if malignancy suspected)

• Ultrasound abdomen (first-line): Nodular liver, splenomegaly, ascites, portal vein diameter >13 mm (portal hypertension)
• Upper GI endoscopy: Assess esophageal varices (grade I-IV), gastric varices, portal hypertensive gastropathy
• CT abdomen: Better anatomical detail, vascular anatomy, HCC surveillance
• Liver biopsy: Definitive for diagnosis; confirms fibrosis stage (Metavir/ISHAK score) - not always needed if clinical + imaging diagnosis clear

• HBsAg, Anti-HCV, HCV RNA, HBeAg
• ANA, anti-SMA, anti-LKM1 (autoimmune hepatitis)
• AMA (PBC)
• Serum ferritin, transferrin saturation, HFE gene (hemochromatosis)
• Serum ceruloplasmin, 24-hr urine copper (Wilson's)
• Alpha-fetoprotein (AFP) + ultrasound 6-monthly for HCC surveillance

• Child-Pugh score (bilirubin, albumin, PT, encephalopathy, ascites): Class A/B/C
• MELD score (bilirubin, creatinine, INR): Predicts 90-day mortality; used for transplant listing

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Management of Ascites, Hepatic Encephalopathy, and Variceal Bleed (6 marks)

1. Management of Ascites

• Spironolactone (aldosterone antagonist): 100 mg/day, increase to max 400 mg/day (first-line diuretic; ratio maintained at K+ balance)
• Furosemide (loop diuretic): Add at 40 mg/day ratio 100:40 with spironolactone; max 160 mg/day
• Fluid restriction only if Na+ <125 mEq/L
• Monitor: weight loss (target 0.5 kg/day), renal function, electrolytes

• Large volume paracentesis (LVP): >5 L per session
• Must give albumin 6-8 g per liter of ascites removed (to prevent post-paracentesis circulatory dysfunction/PPPD)
• Transjugular Intrahepatic Portosystemic Shunt (TIPS): Creates intrahepatic shunt between portal and hepatic veins; reduces portal pressure; used for refractory ascites and prevention of variceal rebleeding
• Liver transplantation - definitive

• Prophylactic norfloxacin 400 mg/day (or ciprofloxacin) after first episode of SBP
• IV cefotaxime or piperacillin-tazobactam for treatment of SBP

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2. Management of Hepatic Encephalopathy (HE)

• Infection (SBP, UTI, pneumonia) → antibiotics
• GI bleeding → treat bleed
• Constipation → lactulose
• Hypokalemia/alkalosis → correct electrolytes
• Sedative drugs/opioids → stop
• Dehydration/renal failure → fluids

• Lactulose (non-absorbable disaccharide): First-line; 30-45 mL 3-4x/day, titrate to 2-3 soft stools/day; mechanism: acidifies colonic pH → traps NH4+, reduces ammonia-producing bacteria
• Rifaximin 550 mg BD: Non-absorbable antibiotic; reduces gut urease-producing bacteria; excellent for prevention of recurrent HE (add to lactulose)
• Low-protein diet: Outdated - current evidence supports normal protein (1.2-1.5 g/kg/day) with BCAA (branched-chain amino acid) supplementation
• Zinc supplementation (zinc deficiency common in cirrhosis, impairs urea cycle)
• Grade III-IV HE: Airway protection, ICU, possible intubation; lactulose via NGT; treat cerebral edema if present

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3. Management of Variceal Bleed (ACUTE)

• IV access x2, blood group and cross-match, aggressive fluid resuscitation
• Transfuse pRBC to Hb >7 g/dL (restrictive strategy - lower transfusion targets reduce portal pressure and rebleeding)
• Correct coagulopathy: FFP, vitamin K, platelets if <50,000
• Avoid over-transfusion (raises portal pressure)

• Terlipressin 2 mg IV 4-hourly (vasopressin analogue; reduces portal pressure; only drug shown to reduce mortality) - drug of choice
• Or Somatostatin/Octreotide 50 mcg bolus then 50 mcg/hr infusion (if terlipressin unavailable)
• Continue for 3-5 days

• Ceftriaxone 1 g IV daily x 7 days (reduces SBP and infection-related mortality; improves outcomes)
• Or norfloxacin 400 mg BD (oral)

• Endoscopic variceal ligation (EVL/banding) - treatment of choice; superior to sclerotherapy
• Endoscopic sclerotherapy (injection of sclerosant) - if banding not possible

• Sengstaken-Blakemore tube or Minnesota tube if endoscopy fails or unavailable
• Inflates balloons in esophagus and stomach to compress varices
• Maximum 24 hours; high risk of re-bleeding and esophageal necrosis/perforation

• Emergency TIPS for uncontrolled variceal bleeding despite endoscopy + vasoactive drugs
• Early TIPS (within 72 hours) improves survival in high-risk patients (Child-Pugh C or B with active bleeding)

• Non-selective beta-blockers (propranolol/carvedilol) + EVL banding (combination reduces rebleeding risk)
• TIPS for refractory/recurrent bleeding
• Liver transplantation - definitive

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Full Exam Answers

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Q.7 Short Notes (remaining) — 2.5 marks each

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b) Delirium Tremens (2.5 marks)

1. Benzodiazepines (cornerstone of treatment):

• Diazepam 10-20 mg IV/oral, repeat every 5-10 min until calm (symptom-triggered protocol)
• Or Lorazepam 2-4 mg IV (preferred in liver disease as no active metabolites)
• Or Chlordiazepoxide (oral, for outpatient mild-moderate)
• Goal: Prevent seizures, reduce autonomic hyperactivity, sedate without respiratory depression

1. IV Fluids (profound dehydration common)
2. Thiamine (Vitamin B1) 100-500 mg IV BEFORE glucose (prevents Wernicke's encephalopathy - must give before dextrose as glucose depletes thiamine)
3. Electrolyte correction: K+, Mg²+, phosphate (hypomagnesemia worsens seizure threshold)
4. Haloperidol - adjunct for severe agitation/hallucinations (do not use alone - doesn't prevent seizures)
5. Phenobarbital or Propofol - for refractory DTs/benzodiazepine-resistant cases (ICU setting)
6. Phenytoin - NOT effective for alcohol withdrawal seizures (only for structural seizures)
7. Supportive: ICU monitoring, nutrition, treat concurrent infections

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c) Pemphigus Vulgaris (2.5 marks)

• IgG antibodies bind to Dsg3 (found in mucosa and deep epidermis) and Dsg1 (skin)
• Disrupts desmosomal adhesion → acantholysis (loss of cell-cell adhesion between keratinocytes) → intra-epidermal blister formation (suprabasal split)

• Oral mucosa first (in >80%): Painful, non-healing erosions; dysphonia, dysphagia
• Skin blisters: Flaccid (easily rupture), leaving large painful erosions; no scarring but post-inflammatory hyperpigmentation
• Nikolsky sign positive: Lateral pressure on normal-appearing skin causes blister to extend/form
• Asboe-Hansen sign (extended Nikolsky): Pressure on blister roof causes it to spread laterally
• Sites: Scalp, face, chest, axillae, groins, oral cavity; can involve conjunctiva, esophagus, genitalia
• Systemic features: Malnutrition (due to oral erosions), secondary infection (Staphylococcus), sepsis (main cause of death)

• Skin biopsy (H&E): Suprabasal acantholysis; "row of tombstones" sign (basal cells remain attached to dermis)
• Direct immunofluorescence (DIF - gold standard): IgG and C3 deposits in intercellular spaces ("fishnet/chicken wire" pattern)
• Indirect immunofluorescence: Circulating anti-Dsg antibodies in serum (titer correlates with disease activity)
• Anti-Dsg ELISA: Quantifies Dsg1 and Dsg3 antibodies

1. Systemic corticosteroids (first-line): Prednisolone 1-1.5 mg/kg/day; taper once remission achieved
2. Rituximab (anti-CD20): Now preferred steroid-sparing agent; superior to azathioprine (PEMPHIX trial); targets B-cells producing autoantibodies
3. Steroid-sparing immunosuppressants: Azathioprine, mycophenolate mofetil, cyclophosphamide
4. Dapsone / gold - for mild cases
5. Wound care: Non-adherent dressings; treat secondary infection
6. Nutritional support

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d) Thrombotic Thrombocytopenic Purpura (TTP) (2.5 marks)

1. Thrombocytopenia (often severe, <20,000/μL)
2. Microangiopathic hemolytic anemia (MAHA) - schistocytes on blood film, elevated LDH, low haptoglobin, elevated indirect bilirubin
3. Neurological symptoms - headache, confusion, focal deficits, seizures, coma (fluctuating)
4. Renal impairment (usually mild in TTP; more severe in HUS)
5. Fever

• Immune-mediated TTP (iTTP): IgG antibodies against ADAMTS13 (most common); idiopathic or triggered by drugs, pregnancy, HIV, SLE
• Hereditary TTP (Upshaw-Schulman syndrome): Inherited ADAMTS13 mutations

• Blood film: Schistocytes (helmet cells, fragmented RBCs)
• CBC: Low platelets, hemolytic anemia
• LDH: Elevated (hemolysis + tissue ischemia)
• Haptoglobin: Low
• Coagulation (PT, APTT, fibrinogen): Normal (distinguishes from DIC)
• Direct Coombs test: Negative (distinguishes from autoimmune hemolytic anemia)
• ADAMTS13 activity level <10% confirms iTTP; inhibitor assay for antibodies
• Creatinine, urinalysis (renal involvement)

1. Plasma exchange (PEX) - IMMEDIATE and lifesaving: Removes anti-ADAMTS13 antibodies AND replenishes functional ADAMTS13; 1-1.5 plasma volumes daily; continue until platelet count >150,000/μL for 2 consecutive days. Do NOT delay.
2. Corticosteroids: Prednisolone 1 mg/kg/day IV/oral (immunosuppression)
3. Rituximab (anti-CD20): Added in relapsed/refractory cases; also used upfront in severe iTTP; dramatically reduces relapse
4. Caplacizumab (anti-vWF nanobody): New agent; blocks platelet-vWF interaction; faster platelet recovery; added to PEX + steroids ± rituximab
5. Avoid platelet transfusion (accelerates thrombosis - "fuel to the fire" unless life-threatening bleed)
6. Folate supplementation (hemolysis depletes folate)

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Q.8 Ultra-Short Answer Questions (10 × 1 = 10 Marks)

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1. Acidosis - refractory metabolic acidosis (pH <7.1)
2. Electrolytes - refractory hyperkalemia (K+ >6.5 mEq/L despite treatment)
3. Ingestion - poisoning/toxin overdose (e.g., methanol, ethylene glycol, lithium, salicylates)
4. Overload - refractory fluid overload/pulmonary edema (diuretic-resistant)
5. (Uremia) - uremic symptoms: pericarditis, encephalopathy, neuropathy, bleeding; or GFR <10 mL/min

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1. Rivaroxaban (Factor Xa inhibitor - Xarelto)
2. Apixaban (Factor Xa inhibitor - Eliquis)

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1. ACE inhibitor (e.g., Enalapril / Ramipril) - RAAS blockade, reduces afterload/preload; reduces mortality in HFrEF
2. Beta-blocker (e.g., Carvedilol / Bisoprolol / Metoprolol succinate) - reduces heart rate and adrenergic excess; reduces mortality
3. Mineralocorticoid receptor antagonist / MRA (e.g., Spironolactone / Eplerenone) - reduces aldosterone effects; reduces mortality and hospitalizations
4. SGLT2 inhibitor (e.g., Dapagliflozin / Empagliflozin) - reduces HF hospitalizations and mortality in HFrEF AND HFpEF

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1. Diabetic ketoacidosis (DKA) - ketoacid accumulation
2. Lactic acidosis - sepsis, shock, metformin, ischemia

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1. Dapagliflozin (Farxiga/Forxiga)
2. Empagliflozin (Jardiance)

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1. Prior intracranial hemorrhage (at any time)
2. Ischemic stroke within 3 months

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• Elderly/frail patients, limited life expectancy, severe hypoglycemia unawareness: <8.0-8.5%
• Newly diagnosed, young, no comorbidities, high motivation: <6.5%

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• Nystagmus (earliest), ataxia, diplopia, dysarthria
• Confusion, encephalopathy (at high levels)

• Gingival hyperplasia (characteristic; treat with good oral hygiene)
• Hirsutism (facial hair, especially in women)
• Coarsening of facial features
• Peripheral neuropathy (long-term use)
• Megaloblastic anemia (folate deficiency - phenytoin inhibits folate absorption)
• Osteomalacia (induces CYP450, accelerates Vitamin D breakdown)
• Teratogenicity - fetal hydantoin syndrome (cleft palate, cardiac defects, digit hypoplasia)
• Stevens-Johnson syndrome / DRESS (rare, severe hypersensitivity)
• Lymphadenopathy / pseudolymphoma

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1. Chronic myeloid leukemia (CML) - most common cause of massive splenomegaly
2. Hairy cell leukemia
3. Infection - visceral leishmaniasis (kala-azar) (Leishmania donovani); malaria (chronic)
4. Non-Hodgkin's lymphoma / myelofibrosis (primary myelofibrosis = most common in adults overall)
5. Autoimmune - Gaucher's disease (lipid storage)

• Myeloproliferative neoplasms: CML, primary myelofibrosis, polycythemia vera
• Lymphomas (both Hodgkin's and NHL)
• Chronic malaria (hyperreactive malarial splenomegaly)
• Visceral leishmaniasis (kala-azar)
• Gaucher's disease (lysosomal storage)
• Thalassemia major (extramedullary hematopoiesis)

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