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Sri Aurobindo Medical College - MBBS 3rd Prof Part II

Model Answers

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Q.1 (20 Marks) — 74-year-old male, chest pain on climbing stairs, sweating, palpitation, ST elevation in inferior leads

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1. Most Likely Diagnosis

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2. Clinical Features of STEMI

• Severe, crushing/squeezing chest pain - central or retrosternal, radiating to left arm, jaw, or epigastrium
• Onset at rest or with exertion (as in this case - climbing stairs)
• Duration >20-30 minutes (unlike angina, not relieved by rest or nitrates)
• Profuse sweating (diaphoresis) - as in this patient
• Palpitations, nausea, vomiting
• Breathlessness, feeling of impending doom

• Patient appears anxious, pale, and diaphoretic
• Tachycardia (though inferior STEMI may cause bradycardia due to vagal activation)
• Hypotension may occur
• Fourth heart sound (S4) - due to reduced LV compliance
• Signs of heart failure (S3, basal crepitations) in extensive infarcts
• In RV involvement (common in inferior STEMI): raised JVP, hypotension, clear lungs

• ST elevation in leads II, III, aVF
• Reciprocal ST depression in I, aVL
• Subsequent Q wave formation in II, III, aVF
• Check right-sided leads (V3R, V4R) for RV infarction

• ECG (serial)
• Cardiac biomarkers: Troponin I/T (rises 3-4h, peaks 24h, persists 7-10 days), CK-MB (rises 4-6h, peaks 18-24h)
• CBC, RFT, LFT, coagulation profile
• Echocardiogram - wall motion abnormalities
• Chest X-ray
• Coronary angiography (for PCI)

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3. Management of Inferior STEMI

• MONA protocol:
  • Morphine - 4-8 mg IV for pain (with caution)
  • Oxygen - only if SpO2 <94%
  • Nitrates - sublingual GTN (avoid if hypotension or RV infarction suspected)
  • Aspirin - 300 mg loading dose (chew)
• Clopidogrel 300-600 mg loading (or Ticagrelor 180 mg, or Prasugrel 60 mg)
• Anticoagulation: Heparin (UFH or LMWH - enoxaparin)
• 12-lead ECG, cardiac monitor, IV access, blood samples

• Primary PCI - preferred if available within 90 min of first medical contact (door-to-balloon time <90 min)
• Thrombolysis (Fibrinolysis) - if PCI not available within 120 min; use Streptokinase or Alteplase (tPA) within 12h of symptom onset. Contraindicated in active bleeding, recent stroke, BP >180/110

• Beta-blockers (Metoprolol, Carvedilol) - reduce mortality
• ACE inhibitors (Ramipril, Lisinopril) - especially if EF <40%, hypertension, diabetes
• Statins (Atorvastatin 40-80 mg) - high intensity, regardless of baseline LDL
• Dual antiplatelet therapy (aspirin + clopidogrel/ticagrelor) for 12 months
• Aldosterone antagonist (Eplerenone) if EF <40% + heart failure/diabetes

• Caution with nitrates (may worsen hypotension in RV involvement)
• IV fluids may be needed if RV infarction (fluids are the treatment for RV infarction-related hypotension)
• Watch for heart block (AVN supplied by RCA)

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4. Complications of Inferior STEMI

• Sinus bradycardia and heart blocks (1st, 2nd - Mobitz I / complete heart block) - due to AV node ischemia (RCA supplies AV node)
• Ventricular fibrillation / tachycardia (in first 24-48 hrs)

• Papillary muscle rupture - acute mitral regurgitation (posteromedial papillary muscle supplied by RCA)
• Free wall rupture - hemopericardium and tamponade (day 3-7)
• Ventricular septal defect (VSD)
• LV aneurysm (late)

• Acute pulmonary edema
• Cardiogenic shock (mortality ~80% without revascularization)
• Right ventricular infarction (15-20% of inferior MIs) - presents as hypotension + elevated JVP + clear lungs (Beck's triad minus the muffled sounds)

• Pericarditis (Dressler's syndrome - 2-10 weeks later)
• Mural thrombus and systemic embolism
• Post-MI angina
• Sudden cardiac death

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Q.2 (20 Marks) — Rheumatoid Arthritis: Etiopathogenesis, Clinical Features, Diagnosis, Complications, Management

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Etiopathogenesis

• HLA-DR4 and HLA-DR1 association (shared epitope hypothesis)
• PTPN22 polymorphism

1. Antigen presentation - APCs present citrullinated peptides to CD4+ T helper cells via MHC class II
2. T-cell activation - Th1 and Th17 cells activated; Th17 produces IL-17
3. B-cell activation - produce antibodies: Rheumatoid Factor (RF) (IgM anti-IgG) and Anti-CCP antibodies (Anti-citrullinated protein antibodies - more specific)
4. Synovial inflammation - cytokines (TNF-α, IL-1, IL-6) recruit neutrophils, macrophages; synovial fibroblasts proliferate
5. Pannus formation - hyperplastic synovium (pannus) invades and destroys cartilage and bone
6. Bone erosion - activated osteoclasts (by RANKL) cause juxta-articular osteoporosis and erosions

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Clinical Features

• Insidious onset of symmetrical, small joint polyarthritis
• Joints involved: MCPs, PIPs, wrists (characteristic), shoulders, knees, ankles, MTPs
• Spares DIP joints (unlike OA and psoriatic arthritis)
• Morning stiffness >1 hour (hallmark) - improves with activity
• Deformities (late):
  • Boutonniere deformity (flexion at PIP, hyperextension at DIP)
  • Swan-neck deformity (hyperextension at PIP, flexion at DIP)
  • Z-deformity of thumb
  • Ulnar deviation of fingers at MCPs
  • Hammer toes, Subluxation of MTP joints
  • Atlanto-axial subluxation (C1-C2 - can compress spinal cord)

• Skin: Rheumatoid nodules (20-35%) - over extensor surfaces; subcutaneous, firm, non-tender
• Eyes: Keratoconjunctivitis sicca (secondary Sjogren's), scleritis, episcleritis, corneal melting
• Lungs: Pleural effusion, ILD (fibrosis), Caplan's syndrome, nodules
• Heart: Pericarditis, myocarditis, accelerated atherosclerosis
• Vasculitis: Digital infarcts, leg ulcers
• Hematologic: Anemia of chronic disease (most common), Felty's syndrome (RA + splenomegaly + neutropenia)
• Neuropathy: Carpal tunnel syndrome, peripheral neuropathy
• Amyloidosis: Secondary (AA) amyloidosis - renal failure

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Diagnosis

• RF (IgM): positive in 75-85% (not specific - also +ve in SLE, infections, elderly)
• Anti-CCP antibodies: 95% specific, 70% sensitive - best diagnostic test
• ESR, CRP elevated
• CBC: Anemia (normocytic normochromic), thrombocytosis (active disease)
• X-ray hands/feet: periarticular osteoporosis, joint space narrowing, marginal erosions (juxta-articular), deformities
• Synovial fluid: Inflammatory pattern (WBC 5,000-50,000, predominantly neutrophils)
• ANA: weakly positive in 30%

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Complications

• Joint destruction and deformities
• Atlanto-axial subluxation (neurological emergency)
• Cervical myelopathy
• Felty's syndrome
• Amyloidosis (AA)
• Increased cardiovascular risk (accelerated atherosclerosis)
• Lymphoma (2-fold increased risk)
• Side effects of medications (GI bleeds from NSAIDs, osteoporosis from steroids, infections from biologics)

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Management

• Patient education, physiotherapy, occupational therapy
• Splints, assistive devices
• Smoking cessation
• Aerobic exercise - improves function without worsening disease

• NSAIDs (Naproxen, Celecoxib) - for pain and stiffness; do not modify disease course
• Short-term low-dose Corticosteroids (Prednisolone 5-10 mg/day) as bridge therapy

• Start early (within 3-6 months of symptom onset)
• Methotrexate (MTX) - ANCHOR drug; 7.5-25 mg/week oral; supplement folic acid; monitor LFT
• Hydroxychloroquine (HCQ) - milder disease; annual eye check (retinopathy)
• Sulfasalazine - moderate disease
• Leflunomide - alternative to MTX
• Combination DMARDs ("triple therapy": MTX + HCQ + SSZ) for active disease

• Anti-TNF agents: Etanercept, Infliximab, Adalimumab
• Anti-IL-6: Tocilizumab
• Anti-CD20 (B cell depletion): Rituximab
• T-cell co-stimulation blocker: Abatacept
• JAK inhibitors (targeted synthetic DMARDs): Tofacitinib, Baricitinib

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Q.3 (10 Marks) — Management of Osteoarthritis

Definition

Management

• Patient education and self-management programs
• Weight loss (most effective intervention - 1 kg loss = 4 kg off knee force)
• Exercise - aerobic (swimming, cycling) and muscle strengthening (quadriceps for knee OA)
• Physiotherapy - TENS, heat/cold application, ultrasound
• Assistive devices - walking stick (contralateral hand), orthotics, braces
• Reduction of joint loading activities

• Topical NSAIDs (Diclofenac gel) - less systemic side effects
• Topical Capsaicin - depletes substance P; burning sensation initially

• Paracetamol (Acetaminophen) - first-line oral; 500-1000 mg TDS (though recent evidence shows modest benefit)
• NSAIDs (Ibuprofen, Naproxen, Celecoxib) - more effective than paracetamol; use lowest dose for shortest time; add PPI; caution in elderly/cardiovascular/renal disease
• Duloxetine (SNRI) - for moderate-severe OA with central sensitization
• Opioids (Tramadol, Codeine) - short-term for severe pain not responding to other agents; significant side effects

• Corticosteroids (Triamcinolone, Methylprednisolone) - short-term relief 4-8 weeks; no more than 3-4 per year
• Hyaluronic acid (Viscosupplementation) - moderate evidence; series of injections; slower onset but longer duration

• Glucosamine and Chondroitin sulfate - controversial; may have modest benefit; safe

• Total joint replacement (arthroplasty) - gold standard for severe disabling OA of hip/knee; dramatically improves pain and function
• Unicompartmental knee replacement (medial compartment OA)
• Osteotomy (tibial/femoral) - younger patients with malalignment; to shift load from affected compartment
• Arthroscopy - NOT recommended for OA (lavage/debridement no better than placebo - NEJM 2002)

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Q.4 (10 Marks) — Diagnostic Criteria for SLE

ACR/EULAR 2019 Classification Criteria for SLE

Older ACR 1997 Criteria (still widely used in exams - 4 of 11 criteria):

1. Malar (butterfly) rash
2. Discoid rash
3. Photosensitivity
4. Oral ulcers (painless)
5. Arthritis - non-erosive, 2+ joints
6. Serositis - pleuritis or pericarditis
7. Renal disorder - proteinuria >0.5g/day or cellular casts
8. Neurological - seizures or psychosis
9. Hematologic - hemolytic anemia, leukopenia, lymphopenia, thrombocytopenia
10. Immunologic - anti-dsDNA, anti-Sm, antiphospholipid antibodies
11. ANA positive

• ANA - most sensitive (95%) but not specific; best screening test
• Anti-dsDNA - 70% sensitive, 95% specific; correlates with disease activity and nephritis
• Anti-Smith (Anti-Sm) - 25-30% sensitive, >99% specific; pathognomonic
• Anti-Ro (SSA) and Anti-La (SSB) - neonatal lupus, subacute cutaneous lupus
• Antiphospholipid antibodies - lupus anticoagulant, anti-cardiolipin, anti-β2GP1

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Q.5 (10 Marks) — Megaloblastic Anemia

Definition

Causes

• Decreased intake: strict veganism
• Impaired absorption: Pernicious anemia (autoimmune - anti-intrinsic factor antibodies), gastrectomy, terminal ileal resection, Crohn's disease, bacterial overgrowth, fish tapeworm (D. latum)
• Drugs: Metformin (reduces absorption)

• Decreased intake: alcoholism, poor diet
• Increased demand: pregnancy, hemolytic anemia, malignancy
• Malabsorption: celiac disease
• Drugs: Methotrexate, phenytoin, trimethoprim (folate antagonists)

Pathogenesis

Clinical Features

• Subacute combined degeneration of spinal cord (SACD): demyelination of dorsal columns (loss of vibration + proprioception) and lateral columns (upper motor neuron signs) - paresthesias, ataxia, spasticity
• Glossitis - beefy red tongue (Hunter's glossitis)
• Dementia, psychiatric disturbances
• Mild jaundice (hemolysis)

• Similar to B12 but NO neurological features
• Prominent in pregnancy (neural tube defects in fetus)

Investigations

• CBC: Macrocytic anemia (MCV >100 fL), oval macrocytes, hypersegmented neutrophils (≥5 lobes in >5% of PMNs - hallmark)
• Pancytopenia in severe cases
• Bone marrow: Megaloblasts, giant metamyelocytes
• Serum B12 levels (<200 pg/mL = deficient)
• Serum folate (<4 ng/mL), RBC folate (more reliable)
• Methylmalonic acid (MMA): elevated in B12 deficiency (NOT folate)
• Homocysteine: elevated in BOTH B12 and folate deficiency
• LDH and indirect bilirubin: elevated (ineffective erythropoiesis)
• Anti-intrinsic factor antibodies (specific for pernicious anemia)
• Schilling test (now largely replaced by antibody testing)

Treatment

• Vitamin B12 deficiency:
  • Cyanocobalamin/Hydroxocobalamin 1000 µg IM daily x 7 days, then weekly x 4, then monthly for life (if PA or malabsorption)
  • Oral high-dose B12 (1000-2000 µg/day) - effective even without IF (passive absorption)
  • Response: reticulocytosis in 5-7 days, Hb normalizes in 4-8 weeks
• Folate deficiency:
  • Folic acid 5 mg/day orally x 4 months (or life-long if malabsorption)
  • IMPORTANT: Always rule out B12 deficiency before giving folate alone - folate can correct anemia but worsen neurological damage of B12 deficiency

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Q.6 (10 Marks) — Autoimmune Hemolytic Anemia (AIHA)

Definition

Classification

• Antibody type: IgG (rarely IgA)
• Reacts optimally at 37°C
• Causes: Idiopathic (50%), SLE, CLL, drugs (alpha-methyldopa, penicillin, cephalosporins), lymphomas

• Antibody type: IgM
• Reacts optimally at 4°C
• Agglutinates RBCs in cold peripheries
• Causes: Mycoplasma pneumoniae (acute), EBV (infectious mononucleosis), CLL, lymphoma
• Features: acrocyanosis, Raynaud's phenomenon in cold

• Antibody: IgG (Donath-Landsteiner antibody) - binds in cold, lyses in warm
• Rare; associated with viral infections, syphilis
• Features: cold-induced hemolysis + hemoglobinuria

Clinical Features

• Anemia symptoms: fatigue, pallor, dizziness
• Jaundice (indirect/unconjugated hyperbilirubinemia)
• Splenomegaly (extravascular hemolysis site)
• Dark urine (hemoglobinuria in severe/intravascular hemolysis)
• May be acute or chronic and relapsing

Investigations

• CBC: Normocytic (sometimes macrocytic due to reticulocytosis) anemia
• Peripheral smear: Polychromasia (reticulocytes), spherocytes, microspherocytes
• Direct Antiglobulin Test (DAT / Coombs test): POSITIVE - cornerstone of diagnosis
  • IgG only - warm AIHA
  • IgG + complement (C3d) - warm AIHA + SLE
  • C3d only - cold AIHA or PCH
• Reticulocyte count: Elevated
• LDH: Elevated
• Indirect bilirubin: Elevated
• Serum haptoglobin: Decreased (binds free Hb)
• Peripheral film for spherocytes
• Cold agglutinin titer (if cold AIHA suspected)

Treatment

• 1st line: Oral corticosteroids (Prednisolone 1 mg/kg/day) - initial response ~70-80%
• 2nd line: Splenectomy (removes main site of destruction + IgG-coated RBC clearance)
• 3rd line: Immunosuppressants - Azathioprine, Mycophenolate, Cyclophosphamide
• Rituximab (anti-CD20): Increasingly used as 2nd line for refractory/severe cases
• Folic acid supplementation (to support increased erythropoiesis)
• Blood transfusion: only for life-threatening anemia (compatible blood difficult to cross-match; use least incompatible blood)

• Keep patient warm (most important)
• Avoid cold exposure
• Treat underlying cause (Mycoplasma → azithromycin)
• Rituximab - effective
• Steroids and splenectomy are NOT effective in cold AIHA
• Plasmapheresis (short-term, removes IgM)

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Q.7 (10 Marks) — Blood Components Therapy: Indications and Adverse Reactions of Blood Transfusion

Blood Components and Their Indications

Adverse Reactions of Blood Transfusion

1. Acute Hemolytic Transfusion Reaction (AHTR) - Most dangerous
   • Cause: ABO incompatibility (clerical error most common cause)
   • Onset: Within minutes to hours
   • Features: Fever, rigors, back/loin pain, hypotension, hemoglobinuria (red/brown urine), DIC, renal failure
   • Management: STOP transfusion immediately; IV fluids; furosemide; treat DIC; notify blood bank
2. Delayed Hemolytic Transfusion Reaction (DHTR)
   • Onset: 2-14 days later
   • Cause: Anamnestic response to minor RBC antigens (Kidd, Duffy, Kell)
   • Features: Gradual fall in Hb, jaundice, positive DAT
3. Febrile Non-Hemolytic Transfusion Reaction (FNHTR)
   • Most common reaction (1-2%)
   • Cause: Recipient antibodies against donor HLA antigens/leukocytes
   • Features: Fever + rigors within 1-6 hours; no hemolysis
   • Management: Slow/stop transfusion; antipyretics; leukocyte-depleted blood in future
4. Allergic Reactions:
   • Urticaria (common) - antihistamines; continue transfusion slowly
   • Anaphylaxis (rare) - in IgA-deficient patients with anti-IgA antibodies; epinephrine + stop transfusion
5. Transfusion-Related Acute Lung Injury (TRALI)
   • Acute hypoxemic respiratory failure within 6 hours of transfusion
   • Cause: Donor HLA or neutrophil antibodies activate recipient neutrophils in lungs
   • Features: Bilateral infiltrates on CXR, hypoxia, non-cardiogenic pulmonary edema
   • Management: Supportive (O2, mechanical ventilation if needed); usually resolves in 48-96h

1. Transfusion-Associated Circulatory Overload (TACO)
   • Pulmonary edema from fluid overload, especially in elderly/cardiac patients
   • Management: Diuretics, slow infusion rate, packed cells preferred
2. Infections:
   • Bacterial contamination (most risk with platelets - room temperature storage)
   • Viral: HIV, HCV, HBV (risk now extremely low with modern screening)
   • Parasites: Malaria, Chagas disease (geographical)
3. Metabolic:
   • Hypocalcemia - citrate (preservative) chelates calcium; treat with IV calcium
   • Hyperkalemia - from stored blood
   • Hypothermia - from rapid large-volume infusion; use blood warmers
   • Iron overload - in chronically transfused patients (thalassemia); treat with Desferrioxamine
4. Post-Transfusion Purpura (PTP)
   • Thrombocytopenia 5-10 days post-transfusion; anti-HPA-1a antibodies
   • Treat with IVIG
5. Graft-vs-Host Disease (TA-GvHD)
   • Rare; donor T-cells attack immunocompromised recipient
   • Fatal in most cases; prevent by irradiating blood products in immunocompromised patients

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Q.8 (10 Marks) — Treatment of Acute Myeloid Leukemia (AML)

Overview

Treatment Phases

1. Induction Therapy

• Cytarabine (Ara-C): 100-200 mg/m² continuous IV infusion x 7 days
• Anthracycline (Daunorubicin or Idarubicin): IV x 3 days (day 1, 2, 3)
• CR achieved in ~60-80% of patients
• Assess bone marrow at day 14-21

• Low-intensity therapy: Azacitidine (hypomethylating agent) or Decitabine
• Glasdegib + low-dose Ara-C
• Venetoclax (BCL-2 inhibitor) + Azacitidine - current standard for unfit/elderly

2. Special Case: Acute Promyelocytic Leukemia (APL / AML-M3)

• t(15;17) translocation → PML-RARα fusion protein
• MUST NOT use standard 7+3 first - risk of fatal DIC
• Treatment: ATRA (All-Trans Retinoic Acid) + ATO (Arsenic Trioxide) - highly curative (~90% cure rate); or ATRA + anthracycline
• ATRA induces differentiation of promyelocytes
• APL Differentiation Syndrome: Fever, respiratory distress, weight gain, pleuropericardial effusions - treat with dexamethasone
• DIC - treat aggressively with FFP, cryoprecipitate, platelets

3. Post-Remission (Consolidation) Therapy

4. Targeted Therapies (Modern/Current)

• FLT3 inhibitors: Midostaurin (FLT3-mutated AML, added to 7+3); Gilteritinib (relapsed/refractory)
• IDH1 inhibitor: Ivosidenib
• IDH2 inhibitor: Enasidenib
• BCL-2 inhibitor: Venetoclax (+ Azacitidine) - now standard for older/unfit patients
• CD33 antibody-drug conjugate: Gemtuzumab ozogamicin (Mylotarg) - favorable risk AML

5. Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

• Considered for intermediate/adverse risk patients in CR1
• Provides both high-dose chemotherapy conditioning AND graft-vs-leukemia (GVL) effect
• Donor: HLA-matched sibling (preferred) or matched unrelated donor
• Complications: GvHD, infections, organ toxicity

6. Supportive Care

• G-CSF - reduce neutropenia duration
• Blood transfusions (PRBC, platelets) during induction aplasia
• Antibiotics, antifungals, antivirals (broad-spectrum empiric coverage in febrile neutropenia)
• Tumor lysis syndrome prophylaxis: IV fluids + Allopurinol or Rasburicase
• DIC management (especially in APL)
• CNS prophylaxis (less common in AML than ALL; LP + intrathecal chemotherapy if CNS involvement)

7. Relapsed/Refractory AML

• FLAG-IDA regimen (Fludarabine + Ara-C + G-CSF + Idarubicin)
• Targeted agents (Gilteritinib, Enasidenib, Ivosidenib)
• Clinical trials
• Allogeneic HSCT after achieving CR2

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