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INTERNAL DISEASES — 4th Year Medical Faculty

Complete Detailed Answers

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PULMONOLOGY (Questions 1–52)

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Q1. Modern Classification of Acute Pneumonia

• Community-Acquired Pneumonia (CAP) — occurs outside hospital or within 48 h of admission
• Hospital-Acquired (Nosocomial) Pneumonia (HAP) — develops ≥48 h after hospital admission
• Ventilator-Associated Pneumonia (VAP) — ≥48–72 h after endotracheal intubation
• Healthcare-Associated Pneumonia (HCAP) — in patients with recent hospitalization, dialysis, nursing home residence

• Bacterial (typical and atypical), viral, fungal, parasitic, mixed

• Lobar (croupous) — entire lobe
• Focal (bronchopneumonia) — lobules/segments
• Interstitial — connective tissue/alveolar walls

• Mild, moderate, severe (using scoring: CURB-65, PSI/PORT)

• Confusion, Urea >7 mmol/L, RR ≥30/min, BP <90/60 mmHg, Age ≥65
• Score 0–1: outpatient; 2: inpatient; ≥3: ICU

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Q2. Etiological Factors Determining Course of Acute Pneumonia

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Q3. Diagnostic Criteria for Community-Acquired Pneumonia (CAP)

• Acute onset of fever (>38°C), cough (productive or dry), chest pain (pleuritic)
• Dyspnea, tachypnea, fatigue, myalgia

• Dullness on percussion over affected area
• Increased vocal fremitus/bronchophony
• Bronchial breath sounds or crepitations (crepitatio indux/redux)
• Pleural friction rub (if pleural involvement)

• Leukocytosis (>10×10⁹/L) with left shift (neutrophilia), elevated CRP, elevated ESR
• Elevated procalcitonin (distinguishes bacterial from viral)

• Chest X-ray: new lobar, segmental, or diffuse infiltrate/consolidation not present before
• CT chest (gold standard) for equivocal cases

• Sputum Gram stain and culture
• Blood cultures (in severe CAP)
• Urinary antigen for Legionella and Pneumococcus

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Q4. Diagnostic Criteria for Hospital-Acquired (Nosocomial) Pneumonia

• New or progressive pulmonary infiltrate on CXR or CT
• Plus ≥2 of: fever >38°C or hypothermia <36°C; leukocytosis >12×10⁹ or leukopenia <4×10⁹; purulent tracheobronchial secretions

• Early HAP (<5 days): S. pneumoniae, H. influenzae, MSSA
• Late HAP (≥5 days): Pseudomonas aeruginosa, MRSA, Acinetobacter, Klebsiella, E. coli (MDR organisms)

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Q5. Diagnostic Criteria for Atypical Pneumonia

• Gradual onset (days–weeks)
• Dry, nonproductive cough (prominent)
• Headache, myalgia, malaise ("walking pneumonia")
• Low-grade or absent fever (except Legionella — high fever)
• Minimal or no pleuritic chest pain
• Extrapulmonary: rash, hemolytic anemia (cold agglutinins in Mycoplasma), diarrhea, hepatitis, hyponatremia (Legionella)

• Bilateral, patchy, interstitial or peribronchial infiltrates (not lobar consolidation)
• "Ground-glass" appearance on CT

• Normal or mildly elevated WBC
• Cold agglutinin titer ≥1:64 (Mycoplasma)
• Serological tests (IgM/IgG rise 4× in paired sera)
• Urinary Legionella antigen (best for L. pneumophila serogroup 1)
• PCR of respiratory secretions

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Q6. Diagnostic Criteria for Viral Pneumonia

• Acute onset with prodromal viral symptoms: fever, myalgia, malaise, sore throat, rhinorrhea
• Dry cough progressing to dyspnea
• CXR: bilateral, diffuse interstitial/alveolar infiltrates ("ground-glass" on CT), often bilateral
• Leukopenia or normal WBC (lymphocytopenia in COVID-19)
• No response to antibiotics
• Virological confirmation: PCR (nasopharyngeal/BAL), rapid antigen tests, viral culture
• Serological: 4× rise in specific antibody titer

• Influenza: rapid antigen test or RT-PCR; bilateral peribronchial infiltrates
• COVID-19: bilateral peripheral ground-glass opacities on CT, elevated CRP/D-dimer/ferritin/IL-6
• CMV (immunocompromised): CMV antigenemia (pp65), PCR, characteristic "owl eye" inclusions on biopsy

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Q7. Diagnostic Criteria for Fungal Pneumonia

• Criteria (EORTC/MSG): host factors + CT findings (halo sign, air-crescent sign, nodule with cavitation) + mycological evidence
• Serum galactomannan ≥0.5 or β-D-glucan ≥80 pg/mL
• BAL culture or PCR positive for Aspergillus

• HIV+ with CD4 <200/μL
• Bilateral diffuse interstitial/ground-glass opacities (perihilar, "bat wing")
• LDH markedly elevated
• Silver stain (GMS) or immunofluorescence of BAL/induced sputum
• PCR from BAL

• Cryptococcal antigen in serum/CSF
• India ink prep, culture

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Q8. Pneumonia in Individuals with Immunodeficiencies

• Atypical presentation: absent fever, minimal cough due to blunted inflammatory response
• Rapid progression to ARDS
• Multiple simultaneous pathogens (co-infections)
• Poor response to standard therapy

• BAL mandatory (multiple stains and cultures)
• Galactomannan, β-glucan, CMV PCR, Cryptococcal antigen
• Lung biopsy if BAL non-diagnostic
• CXR may be normal even with severe disease (neutropenia)

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Q9. Pneumonia in Elderly People

• Fever may be absent (hypothermia is a bad sign)
• No or minimal cough; confusion/delirium may be the ONLY presenting sign
• Falls, functional decline, anorexia, tachycardia
• Pleuritic chest pain less common

• Reduced cough reflex → aspiration risk
• Decreased mucociliary clearance
• Impaired humoral and cellular immunity (immunosenescence)
• Multiple comorbidities (DM, CHF, COPD, renal failure)

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Q10. Aspiration Pneumonia

• Chemical (acid) pneumonitis (Mendelson syndrome) — immediate reaction to gastric acid
• Bacterial infection — anaerobes from oropharynx predominate (Bacteroides, Fusobacterium, Peptostreptococcus) + gram-negatives in hospitalised patients

• Foul-smelling (putrid) sputum — strongly suggests anaerobic infection
• Necrotizing pneumonia, lung abscess formation
• Slow insidious onset; fever, weight loss

• Clindamycin (drug of choice for aspiration with anaerobes)
• Amoxicillin-clavulanate, piperacillin-tazobactam for hospital settings
• Duration: 4–6 weeks if abscess present

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Q11. Principles of Antibacterial Therapy of Pneumonia

1. Start empirically before culture results; modify on receipt of sensitivities
2. Choose antibiotic based on: setting (CAP/HAP/VAP), severity, local resistance patterns, comorbidities, prior antibiotics
3. Adequate dosing and route (IV for severe; oral for mild–moderate)
4. Duration: CAP = 5–7 days (mild), 7–14 days (severe); HAP/VAP = 7–8 days (unless MDR)

• Outpatient mild (no comorbidities): Amoxicillin 1g TID OR Doxycycline 100mg BD
• Outpatient with comorbidities: Amoxicillin-clavulanate + Macrolide OR Respiratory fluoroquinolone (Levofloxacin/Moxifloxacin)
• Inpatient non-ICU: Beta-lactam + Macrolide OR Respiratory fluoroquinolone alone
• ICU: Beta-lactam (ceftriaxone/cefotaxime) + Azithromycin OR Anti-pneumococcal fluoroquinolone ± anti-MRSA (if risk)

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Q12. Pathogenetic Therapy of Acute Pneumonia

1. Anti-inflammatory: Corticosteroids (severe CAP with CRP >150, refractory septic shock, autoimmune causes) — e.g., methylprednisolone 0.5–1 mg/kg/day × 5–7 days. Reduce cytokine storm.
2. Mucolytic agents: N-acetylcysteine, ambroxol, bromhexine — improve mucus clearance
3. Immunomodulation: IgG infusions for hypogammaglobulinemia
4. Anticoagulation: Low-molecular-weight heparin (LMWH) in severe pneumonia (prevents microthrombosis, DVT prophylaxis)
5. Maintaining perfusion: IV fluids guided by hemodynamic monitoring; vasopressors in septic shock
6. Nutritional support: Early enteral nutrition in ICU patients

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Q13. Symptomatic Therapy and Oxygen Therapy for Pneumonia

• Antipyretics: Paracetamol, ibuprofen (fever >38.5°C)
• Analgesics: NSAIDs for pleuritic chest pain
• Antitussives: Only if dry distressing cough; avoid in productive cough
• Mucolytics/expectorants: Ambroxol, ACC, bromhexine to facilitate expectoration
• Bronchodilators: Salbutamol/ipratropium if bronchospasm present

• Target SpO₂ ≥94% (≥90% in COPD)
• Delivery methods: Nasal cannula (1–6 L/min), simple face mask (6–10 L/min), non-rebreather mask (10–15 L/min, FiO₂ up to 0.8)
• High-Flow Nasal Cannula (HFNC): up to 60 L/min, heated humidified — reduces intubation rate
• Non-Invasive Ventilation (NIV/BiPAP): for hypercapnic respiratory failure
• Mechanical ventilation: if SpO₂ <90% on maximal O₂, PaO₂/FiO₂ <200 (ARDS criteria)

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Q14. Pulmonary Complications of Acute Pneumonia

1. Pleural Effusion (parapneumonic): Exudative; if purulent → empyema (requires drainage)
2. Empyema Thoracis: Pus in pleural space; pH <7.2, glucose <2.2 mmol/L, LDH >1000; requires chest tube drainage ± decortication
3. Lung Abscess: Necrotizing infection with cavitation; air-fluid level on CXR; prolonged antibiotics 4–8 weeks; drainage if large
4. Pneumothorax: Rare, usually from barotrauma or necrotizing pneumonia
5. ARDS (Acute Respiratory Distress Syndrome): Bilateral infiltrates, PaO₂/FiO₂ <300, non-cardiogenic pulmonary edema; requires mechanical ventilation with lung-protective strategy
6. Respiratory Failure: Type I (hypoxemia) or Type II (hypercapnia)
7. Organizing Pneumonia: Failure to resolve; COP (cryptogenic organizing pneumonia) pattern

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Q15. Extrapulmonary Complications of Acute Pneumonia

1. Sepsis/Septic Shock: Most dangerous; criteria: infection + organ dysfunction (SOFA score ≥2); vasopressors required
2. Infective Endocarditis: Hematogenous seeding of valves (especially S. aureus, S. pneumoniae)
3. Meningitis/Brain Abscess: Bacteremic spread
4. Pericarditis/Myocarditis: Especially Legionella, viral pneumonia
5. Acute Kidney Injury (AKI): From sepsis, hypovolemia, nephrotoxic antibiotics
6. DIC (Disseminated Intravascular Coagulation): Severe septic pneumonia
7. Hepatitis: Elevated transaminases (Legionella, Q fever)
8. Hemolytic Anemia: Mycoplasma (cold agglutinins)
9. Reactive Arthritis, Stevens-Johnson syndrome: Post-mycoplasma
10. Venous Thromboembolism (DVT/PE): Immobility, inflammation, hypercoagulability

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Q16. Combating Complications and Intoxication in Pneumonia

• IV crystalloid infusion (saline, Ringer's lactate) 1500–2000 mL/day to dilute toxins and maintain perfusion
• Forced diuresis (with furosemide if fluid overloaded)
• Enterosorption: activated charcoal (in mild cases)
• Detoxification: hemodialysis in severe AKI

• Empyema: Chest tube drainage; fibrinolytics (streptokinase) if loculated; VATS
• Lung abscess: Prolonged antibiotics (clindamycin/metronidazole); postural drainage; bronchoscopic drainage; resection if refractory
• Septic shock: "Surviving Sepsis Campaign" — vasopressors (norepinephrine first-line), corticosteroids (hydrocortisone 200 mg/day in refractory shock), early antibiotics within 1 hour
• ARDS: Prone positioning, low tidal volume ventilation (6 mL/kg IBW), PEEP optimization
• Fever: Antipyretics; cooling measures
• DIC: FFP, platelet concentrates, cryoprecipitate

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Q17. Causes Underlying Infiltrative Syndrome in the Lungs

• Bacterial pneumonia (most common)
• Tuberculosis (infiltrative TB)
• Fungal pneumonia
• Viral pneumonia

• Peripheral lung cancer
• Bronchoalveolar carcinoma (lepidic adenocarcinoma)
• Lymphoma
• Metastases

• Sarcoidosis (bilateral hilar lymphadenopathy + infiltrates)
• Extrinsic allergic alveolitis (hypersensitivity pneumonitis)
• Wegener's granulomatosis (GPA)

• Pulmonary infarction (PE)
• Pulmonary hemorrhage (Goodpasture, SLE)

• Cryptogenic Organizing Pneumonia (COP)
• Eosinophilic pneumonia
• Drug-induced pneumonitis
• Pulmonary edema (cardiogenic/non-cardiogenic)
• Alveolar proteinosis

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Q18. Clinical and Radiological Signs of Pulmonary Infiltrate

• Fever, cough, dyspnea
• Dullness on percussion
• Increased vocal fremitus over consolidation
• Bronchial breath sounds, crepitations
• If large: mediastinal shift away (if pleural effusion), toward (if atelectasis)

• Homogeneous opacity — lobar consolidation (bacterial pneumonia)
• Air bronchogram — air-filled bronchi visible within opacity (alveolar process)
• Fluffy, ill-defined margins — acute inflammatory/edema
• Sharp margins — tumor, infarct
• Cavity within infiltrate — abscess, TB, cancer, Wegener's
• Bilateral butterfly/bat-wing pattern — pulmonary edema
• Upper lobe — TB, sarcoidosis
• Lower lobe — CAP, aspiration

• Ground-glass opacity (partial alveolar filling)
• Consolidation (complete alveolar filling)
• Halo sign (ring of ground-glass around nodule) — Aspergillus
• Air-crescent sign (crescent of air around necrotic nodule) — late IPA
• Peribronchovascular distribution — sarcoidosis, lymphangitis

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Q19. Differential Diagnosis of Tumor vs. Inflammatory Infiltrate

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Q20. Differential Criteria: Pneumonia vs. Infiltrative Tuberculosis

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Q21. Differential Criteria: Pneumonia vs. Pulmonary Infarction (PE)

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Q22. Differential Diagnostic Criteria for Sarcoidosis

• Bilateral hilar lymphadenopathy (BHL) — "potato nodes"
• Skin: erythema nodosum (acute), lupus pernio (chronic)
• Eyes: uveitis (blurred vision, photophobia)
• Fatigue, fever, weight loss, night sweats
• Respiratory: dry cough, dyspnea, chest tightness
• Hypercalcemia (macrophages produce 1,25-OH-D)
• Neurosarcoidosis: cranial nerve palsies, meningitis
• Cardiac: arrhythmias, conduction defects

• Stage 0: Normal CXR
• Stage I: BHL only
• Stage II: BHL + pulmonary infiltrates
• Stage III: Pulmonary infiltrates without BHL
• Stage IV: Pulmonary fibrosis

• Serum ACE elevated (60–80%)
• Elevated serum calcium and 24h urine calcium
• IGRA/TST negative (helps differentiate from TB)
• Bronchoalveolar lavage: CD4:CD8 ratio >3.5
• Biopsy (transbronchial, skin, lymph node): non-caseating granulomas
• PET-CT shows active inflammation

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Q23. Differential Diagnostic Criteria for Peripheral Lung Cancer

• May be asymptomatic (incidental finding on CXR/CT)
• Insidious cough, hemoptysis, dyspnea
• Weight loss, fatigue, anorexia ("B-symptoms")
• Pancoast tumor (apex): shoulder pain, Horner's syndrome (ptosis, miosis, anhidrosis), ulnar nerve pain

• Spiculated or lobulated margins
• Size >3 cm
• Pleural "tethering" or tail sign
• Associated lymphadenopathy (mediastinal)
• Pleural effusion (exudate, often bloody)
• Cavitation with thick irregular inner walls

• Calcification: benign if central/laminar; suspicious if eccentric/absent
• Growth: doubling time 30–400 days (malignant); <30 days (infection); >400 days (benign)

• CT-guided biopsy; bronchoscopy (endobronchial) + BAL; PET-CT (SUV >2.5)
• EBUS-guided TBNA for lymph nodes
• Sputum cytology (low sensitivity)
• Tumor markers: CEA, NSE, CYFRA 21-1 (not diagnostic alone)
• Staging: TNM + CT/PET/MRI brain/bone scan

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Q24. Role of Serological and Immunological Methods in Infiltrative Syndrome

• Mycoplasma: IgM/IgG, cold agglutinins (≥1:64)
• Legionella: Urinary antigen (rapid, sensitive for SG1)
• Chlamydia: Complement fixation, microimmunofluorescence
• Coxiella burnetii (Q fever): Phase I/II IgG/IgM
• Aspergillus: Galactomannan (ELISA); precipitins (allergic bronchopulmonary aspergillosis); β-D-glucan
• Cryptococcal antigen
• HIV: ELISA + Western blot (for PCP risk assessment)

• ANA, anti-dsDNA, anti-Sm (SLE)
• ANCA (c-ANCA/PR3 in GPA, p-ANCA/MPO in MPA)
• Anti-GBM (Goodpasture syndrome)
• Serum ACE (sarcoidosis)
• Rheumatoid factor + anti-CCP (RA-associated ILD)
• Serum IgG4 (IgG4-related pulmonary disease)

• Serum IgE (total and specific): ABPA, eosinophilic pneumonia
• Specific IgG precipitins against inhaled antigens (hypersensitivity pneumonitis)

• CEA, CYFRA 21-1, NSE, SCC-Ag (not diagnostic but support clinical picture)

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Q25. Laboratory and Instrumental Methods for Diagnosing Infiltrative Syndrome

• CBC, differential — infection (leukocytosis), malignancy (anemia), eosinophilia
• CRP, ESR, procalcitonin — infectious vs. non-infectious
• Biochemistry: LDH (elevated in PCP, ARDS, lymphoma), calcium (sarcoidosis), ACE
• Sputum: Gram stain, culture, AFB, cytology
• Blood cultures, urinary Legionella/pneumococcal antigen
• Serological panel (as above)
• Coagulation (DIC in sepsis)
• ABG (respiratory failure assessment)

• CXR: first-line, orientation
• HRCT chest: high-resolution CT — best for characterizing infiltrate pattern (ground-glass, consolidation, nodule, fibrosis, honeycombing)
• Bronchoscopy + BAL: cytology, culture, differential cell count
• Transbronchial lung biopsy (TBLB): tissue diagnosis
• CT-guided percutaneous biopsy: peripheral lesions
• EBUS-TBNA: mediastinal/hilar lymph node sampling
• Video-Assisted Thoracoscopic Surgery (VATS): definitive tissue when less invasive fails
• PET-CT: metabolic activity (malignancy vs. infection/inflammation)
• Spirometry + DLCO: functional assessment; DLCO reduced in interstitial disease

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Q26. Role of Computed Tomography in Differential Diagnosis of Infiltrative Syndrome

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Q27. Interpretation of PET-CT in Suspected Tumor Infiltration

• SUV >2.5 (or significantly higher than mediastinal blood pool): suggestive of malignancy
• SUV <2.5: likely benign (but not definitive — inflammatory lesions can show high SUV)

• Characterize solitary pulmonary nodule (high sensitivity ~96% for malignancy)
• Staging: mediastinal nodes (N staging), distant metastases (M staging)
• Monitor treatment response (decrease in SUV = response)
• Distinguish recurrence from fibrosis after treatment

• Tuberculosis, aspergillosis, sarcoidosis, histoplasmosis, rheumatoid nodules, organizing pneumonia

• Bronchoalveolar (lepidic) carcinoma (low metabolic activity), small lesions <8mm, well-differentiated carcinoid, mucinous adenocarcinoma

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Q28. Role of Bronchoscopy in Differential Diagnosis of Infiltrative Syndrome

1. Bronchoalveolar Lavage (BAL): Instill 100–300 mL saline → retrieve for microbiology (bacteria, mycobacteria, fungi, viruses), cytology, differential cell count (eosinophilia → eosinophilic PNA; lymphocytosis → HP/sarcoidosis; CD4:CD8>3.5 → sarcoidosis; hemosiderin-laden macrophages → alveolar hemorrhage)
2. Transbronchial Lung Biopsy (TBLB): Tissue from peripheral areas; good for sarcoidosis, infection
3. Endobronchial Biopsy: Visible endobronchial lesions
4. Endobronchial Ultrasound (EBUS)-TBNA: Real-time needle aspiration of mediastinal/hilar lymph nodes
5. Protected Specimen Brush (PSB): Quantitative culture (≥10³ CFU/mL) for HAP/VAP

• Sarcoidosis: TBLB ≥80%
• Pneumocystis: BAL immunofluorescence >90%
• Central carcinoma: endobronchial biopsy >90%
• Peripheral lesion <2cm: guided bronchoscopy 20–30%; EBUS/fluoroscopy improves this

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Q29. Diagnostic Role of Microbiological Methods (Sputum Culture, PCR)

• Must be a valid specimen: >25 PMN and <10 epithelial cells per LPF
• Gram stain: rapid presumptive identification (positive in 60% of CAP)
• Culture: specific organism + sensitivity
• AFB smear (Ziehl-Neelsen) + mycobacterial culture (Lowenstein-Jensen medium, 6–8 weeks; liquid MGIT: 2–3 weeks)
• Fungal stains: GMS (silver), PAS; fungal culture

• Legionella pneumophila SG1: sensitivity 70–90%, specificity >99%
• S. pneumoniae: sensitivity 60–70%, specificity >90%; remains positive after antibiotics

• Respiratory virus panel (influenza, RSV, rhinovirus, coronavirus, SARS-CoV-2)
• Mycoplasma, Chlamydophila, Bordetella pertussis PCR from nasopharyngeal swab or BAL
• M. tuberculosis: GeneXpert MTB/RIF (detects MTB + rifampicin resistance in 2 hours); high sensitivity
• Aspergillus, PCP PCR from BAL
• Advantage: rapid turnaround (hours vs. days for culture), detects non-cultivable organisms
• Disadvantage: detects DNA (dead or alive organisms); contamination risk; expensive

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Q30. Pathogenetic Therapy for Diseases with Infiltrative Syndrome

• Bacterial: Antibiotics targeting specific pathogen
• TB: 4-drug regimen (HRZE for 2 months + HR for 4 months)
• Fungal: Antifungals (Voriconazole, Amphotericin B)
• PCP: TMP-SMX + corticosteroids (if PaO₂ <70 mmHg)
• Sarcoidosis: Oral prednisolone 0.5 mg/kg/day × 6–24 months for progressive disease
• COP: Prednisolone 0.75–1 mg/kg/day; very responsive
• IPF: Nintedanib or Pirfenidone (anti-fibrotic agents); no steroids (harmful)
• Hypersensitivity pneumonitis: Remove antigen + corticosteroids
• Vasculitis (GPA): Cyclophosphamide + prednisolone (induction); azathioprine/MTX (maintenance)
• Goodpasture: Plasmapheresis + immunosuppression
• Pulmonary edema: Diuretics (furosemide), ACE inhibitors, CPAP/BiPAP
• Cancer: Chemotherapy, targeted therapy (EGFR inhibitors, ALK inhibitors), immunotherapy (PD-L1 inhibitors), radiotherapy

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Q31. Use of Antibacterial Drugs in Treatment of Infiltrative Syndrome

• Amoxicillin 1g TID × 5–7 days (oral, outpatient)
• Ceftriaxone 1–2g IV od (inpatient)
• Penicillin G (sensitive strains)

• Azithromycin 500mg day 1, then 250mg days 2–5
• Doxycycline 100mg BD × 14 days
• Levofloxacin 500mg od

• Azithromycin IV/oral × 10–14 days OR Levofloxacin 750mg od

• Clindamycin 600mg TID or Amoxicillin-clavulanate
• Metronidazole 500mg TID + beta-lactam

• Piperacillin-tazobactam 4.5g TID IV
• Meropenem 1–2g TID IV (carbapenem-resistant organisms → Polymyxin B/E, Ceftazidime-avibactam)
• MRSA → Vancomycin (15–20 mg/kg IV BD) or Linezolid 600mg BD

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Q32. Role of Glucocorticosteroids in Treatment of Sarcoidosis

1. Pulmonary disease: progressive symptoms, worsening PFTs, radiological Stage II–III with symptoms
2. Hypercalcemia/hypercalciuria
3. Cardiac involvement (arrhythmia, heart block)
4. Neurosarcoidosis
5. Uveitis not responding to topical steroids
6. Severe constitutional symptoms

• Induction: Prednisolone 0.5–1 mg/kg/day (30–40 mg/day) × 4–6 weeks, then taper
• Maintenance: 10–15 mg/day × 12–24 months minimum
• Relapse on tapering → increase dose

• Methotrexate 10–15 mg/week (most evidence)
• Azathioprine 50–200 mg/day
• Hydroxychloroquine (skin/hypercalcemia)
• Infliximab (refractory pulmonary/cardiac/neuro)

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Q33. Management of a Patient with Infiltrative Syndrome: Regimen, Nutrition, Care

• Inpatient hospitalization for severe disease; semi-bed rest during acute phase
• Early mobilization reduces complications (DVT, atelectasis)
• Isolation precautions: respiratory isolation for TB/MRSA; droplet precautions for viral pneumonia
• Nurse in high Fowler's position (30–45°) to improve oxygenation
• Chest physiotherapy (percussion, vibration, postural drainage) to mobilize secretions

• High-calorie, protein-rich diet (1.5–2 g/kg/day protein) — fever increases catabolism
• Oral rehydration for mild cases; IV fluids for severe cases (1.5–2 L/day)
• Enteral nutrition via NG tube if oral intake inadequate (mechanically ventilated patients)
• Avoid NGT if risk of aspiration
• Vitamin supplementation (C, D, zinc) for immune support

• Monitor SpO₂, RR, HR, BP every 4–8 hours
• Sequential chest auscultation and percussion
• Spirometry/DLCO follow-up
• Thromboprophylaxis (LMWH) in bedridden patients
• Smoking cessation counseling
• Pneumococcal and influenza vaccination on discharge

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Q34. Predicting Diseases with Pulmonary Tissue Infiltration

1. CURB-65 / PSI (for pneumonia severity and prediction of complications)
2. Immunosuppression status: Predict opportunistic infections before they occur (PCP prophylaxis with TMP-SMX if CD4 <200)
3. Occupational/environmental exposure history: Predicts hypersensitivity pneumonitis, pneumoconioses
4. CT features predictive of malignancy:
   • Spiculated nodule + age >50 + smoking + size >15mm → high-probability cancer
   • Fleischner Society guidelines for nodule follow-up
5. DLCO decline as early predictor of ILD progression
6. Serum KL-6 / SP-D (surfactant proteins): elevated in ILD, predict fibrotic progression
7. Genetic testing: TERT/TERC mutations in familial ILD
8. FDG-PET: High baseline SUV predicts aggressive malignancy

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Q35. Etiological Factors Contributing to Asthmatic Syndrome

• Bronchial asthma (allergic, non-allergic)
• COPD with bronchospasm
• Bronchiectasis
• Endobronchial tumor obstructing airway
• Foreign body aspiration
• Vocal cord dysfunction

• Cardiac asthma (acute left heart failure with bronchospasm)

• Allergens: Pollen, house dust mite (Dermatophagoides), pet dander, mold (Alternaria, Aspergillus)
• Infections: Viral URTIs (rhinovirus most common trigger); bacterial sinusitis
• Occupational: Isocyanates, latex, flour dust, laboratory animals, chemical fumes
• Drugs: Aspirin/NSAIDs (aspirin-exacerbated respiratory disease — AERD); beta-blockers; ACE inhibitors (cough → triggers attacks)
• Physical: Exercise (exercise-induced bronchoconstriction — EIB); cold air
• Emotional: Stress, anxiety
• Environmental: Pollution (SO₂, NO₂, ozone), tobacco smoke, indoor allergens
• Endocrine: Menstrual cycle variations (perimenstrual asthma); thyroid disease

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Q36. Classification of Bronchial Asthma

• Well-controlled: Daytime symptoms ≤2×/week, no limitation, no nocturnal symptoms, SABA use ≤2×/week, normal lung function
• Partially controlled: 1–2 features above but not meeting all
• Uncontrolled: ≥3 features of poorly controlled asthma

• Allergic (atopic) — early onset, eosinophilic, responds to ICS
• Non-allergic — adult onset, may be neutrophilic
• Late-onset
• Exercise-induced
• Aspirin-exacerbated (AERD) — nasal polyps, aspirin sensitivity
• Occupational asthma
• Severe refractory asthma (>2 GINA Step 4–5 medications)

• Step 1: Low-dose ICS-formoterol as needed (or SABA as needed + low-dose ICS)
• Step 2: Low-dose ICS daily + SABA as needed
• Step 3: Low-dose ICS-LABA
• Step 4: Medium-dose ICS-LABA
• Step 5: High-dose ICS-LABA ± add-on (LAMA, anti-IgE [Omalizumab], anti-IL5 [Mepolizumab])

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Q37. Role of Allergic Factors in Bronchial Asthma

• Type I (IgE-mediated) hypersensitivity reaction
• First exposure: sensitization — allergen-specific IgE produced by B cells, binds to mast cells and basophils in airway mucosa
• Re-exposure: Early Phase Reaction (0–30 min): allergen crosslinks IgE → degranulation → histamine, PGD₂, LTC₄/D₄/E₄ → bronchoconstriction, edema, mucus secretion
• Late Phase Reaction (3–12 h): Eosinophils, T-helper 2 (Th2) lymphocytes recruited → sustained inflammation, airway hyperresponsiveness
• Key cytokines: IL-4 (IgE switching), IL-5 (eosinophil differentiation), IL-13 (mucus/IgE)

• Perennial: house dust mites (Dermatophagoides pteronyssinus/farinae) — most important indoor allergen; cockroach; pet dander; mold
• Seasonal: tree/grass/weed pollen
• Occupational: isocyanates (#1 cause occupational asthma), latex, flour, animal proteins

• Skin prick tests (SPT): wheal ≥3 mm vs. negative control
• Serum specific IgE (RAST/ImmunoCAP): levels correlate with sensitivity
• Total serum IgE: often elevated (but non-specific)
• Oral challenge (aspirin), bronchial provocation with specific allergen

• Allergen avoidance (mattress covers, air purifiers, pet removal)
• Anti-IgE: Omalizumab (Xolair) — monoclonal antibody binds free IgE; for severe allergic asthma
• Allergen immunotherapy (AIT/SIT): desensitization; subcutaneous or sublingual

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Q38. Influence of Occupational Hazards on Bronchial Asthma

1. Sensitizer-induced (most common): IgE-mediated or T-cell mediated; latency period of months to years before first symptoms; worsens with re-exposure even at low concentrations
2. Irritant-induced (RADS — Reactive Airways Dysfunction Syndrome): Single high-dose exposure; no latency; persistent non-specific bronchial hyperreactivity

• Serial peak flow monitoring at work vs. away from work (Oasys analysis)
• Specific bronchial provocation with suspected agent
• Specific IgE to occupational agents
• Positive serial methacholine challenge (worsens on workdays)

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Q39. Hereditary Predisposition to Bronchial Asthma

• Heritability estimated at ~60–80% (polygenic)
• Concordance in monozygotic twins: 60–75%; dizygotic: 25–30%
• If one parent has asthma: child risk ~25%; if both parents: ~50%

• 17q21 locus (ORMDL3/GSDMB): Most replicated; associated with childhood asthma
• IL-4/IL-13 pathway genes: IL4RA (IL-4 receptor alpha), IL13 — increased IgE production
• IL-5 / TSLP / IL-33: Th2 pathway activation; eosinophilic inflammation
• ADAM33: Airway remodeling
• Filaggrin (FLG) gene mutations: Impaired skin barrier → atopic march (eczema → food allergy → rhinitis → asthma)
• HLA-DRB1: Associated with occupational asthma and aspirin-exacerbated disease
• Beta-2 adrenergic receptor (ADRB2): Arg16Gly polymorphism affects bronchodilator response

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Q40. Diagnostic Criteria for Infectious-Allergic Bronchial Asthma

• Adult onset (typically >30 years)
• No personal/family history of atopy (eczema, rhinitis)
• Triggered by respiratory infections (viral: rhinovirus; bacterial: Chlamydia pneumoniae, Haemophilus)
• Negative skin prick tests and normal/low specific serum IgE
• Normal total IgE
• Eosinophilia may be present (non-IgE eosinophilic asthma)
• Perennial symptoms; not seasonal

• Viral infections activate innate immunity → airway epithelial damage → increased permeability → nonspecific bronchial hyperreactivity
• Th2 activation via non-IgE pathways; IL-5-driven eosinophilia
• Chlamydia pneumoniae chronic low-grade infection → persistent airway inflammation

• Symptoms of asthma (wheeze, cough, dyspnea, chest tightness)
• Reversible airflow obstruction: FEV₁ improvement ≥12% and 200 mL after salbutamol
• Positive bronchial provocation test (methacholine or histamine) — PC₂₀ <8 mg/mL
• Negative IgE-mediated allergy tests
• Correlation between infection episodes and asthma exacerbations
• Exclude cardiac, COPD, vocal cord dysfunction

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Q41. Diagnostic Criteria for Atopic (Allergic) Bronchial Asthma

• Onset: childhood or young adult
• Personal/family history of atopy (eczema, allergic rhinitis, food allergy)
• Episodic symptoms: wheeze, dyspnea, chest tightness, cough (especially nocturnal or early morning)
• Symptoms triggered by allergen exposure, exercise, cold air, viral URTI
• Improvement with inhaled bronchodilators

• Spirometry: FEV₁/FVC <0.7 (obstructive pattern)
• Significant reversibility: ↑FEV₁ ≥12% and ≥200 mL after 400 mcg salbutamol
• PEF variability >10% (daily variation on diary)
• Positive bronchial challenge (methacholine PC₂₀ <8 mg/mL) if spirometry normal

• Positive skin prick tests (≥3 mm wheal)
• Elevated specific serum IgE (RAST/ImmunoCAP) to relevant allergens
• Elevated total serum IgE (often >100 IU/mL)
• Blood eosinophilia (>300/μL typical)
• Elevated exhaled NO (FeNO >25 ppb) — marker of eosinophilic/Th2 airway inflammation

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Q42. Diagnostic Criteria for Status Asthmaticus

• Early: Respiratory alkalosis (↓PaCO₂, ↑pH, normal PaO₂)
• Moderate: Normal PaCO₂ with hypoxemia (PaCO₂ normalizing = patient tiring)
• Late: Respiratory acidosis (↑PaCO₂, ↓pH) = impending respiratory arrest

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Q43. Signs and Symptoms of Cardiac Asthma as a Polyetiological Syndrome

• Acute myocardial infarction (most common)
• Hypertensive crisis
• Acute mitral regurgitation (papillary muscle rupture)
• Acute aortic regurgitation
• Hypertrophic cardiomyopathy (HOCM)
• Tachy-/bradyarrhythmias
• Acute myocarditis
• Flash pulmonary edema (renal artery stenosis)

• Left heart failure → ↑pulmonary venous pressure → pulmonary congestion and interstitial edema → reflex bronchospasm (peribronchial edema compresses airways)

• Sudden onset at night (orthopnea/PND) — patient sits bolt upright
• Dyspnea: severe, inspiratory AND expiratory
• Cough with frothy/pink sputum (distinguishes from bronchial asthma)
• Wheezing (bronchospasm — may sound identical to asthma)
• Cyanosis (central)
• Cold, diaphoretic, clammy skin (sympathetic activation — absent in bronchial asthma)
• Tachycardia and hypertension (or hypotension in cardiogenic shock)
• Auscultation: bilateral basal crepitations (moist rales); may have S3/S4 gallop; cardiac murmur if valvular cause
• JVP elevated (signs of right heart failure if chronic)
• CXR: cardiomegaly, Kerley B lines, butterfly/bat-wing pulmonary edema, bilateral perihilar haziness, pleural effusion

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Q44. Differential Diagnosis of Bronchial Asthma vs. Cardiac Asthma

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Q45. Differential Diagnosis of Bronchial Asthma vs. COPD

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Q46. Laboratory and Instrumental Diagnostics of Bronchial Asthma

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Q47. Relief of Asthmatic Status: Tactics and Drugs

• Salbutamol (Albuterol) 2.5–5 mg via nebulizer every 20 min × 3 doses in first hour OR MDI 4–8 puffs via spacer
• Ipratropium bromide 0.5 mg nebulized every 20 min × 3 doses (adds to SABA effect)
• O₂: Target SpO₂ 93–95%
• Systemic corticosteroids: Prednisolone 40–50 mg oral or methylprednisolone 80–125 mg IV (give within 1 hour)
• Reassess after 1 hour → if PEF >70%, discharge on oral prednisolone + ICS

• Continuous nebulized salbutamol 10–15 mg/h
• IV magnesium sulfate 2g over 20 min (bronchodilator; reduces need for ICU)
• IV aminophylline (0.9 mg/kg/h) if not on theophylline — narrow therapeutic window (monitor levels)
• IV corticosteroids: methylprednisolone 125 mg IV every 6h
• IV fluids (avoid over-hydration)
• Heliox (70/30 helium:oxygen) — reduces work of breathing

• ICU admission
• Non-invasive ventilation (NIV/BiPAP) — trial before intubation
• Intubation + mechanical ventilation: low tidal volumes, long expiratory time (I:E ratio 1:4), permissive hypercapnia
• Ketamine IV sedation (bronchodilator properties)
• Epinephrine 0.3 mg SC/IM (for near-fatal)
• Heliox
• Continue IV bronchodilators and corticosteroids

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Q48. Use of Bronchodilators in Bronchial Asthma

• Salbutamol (Albuterol), Terbutaline, Fenoterol
• Onset: 3–5 min; Duration: 4–6h
• Mechanism: Activate β₂ receptors → ↑cAMP → smooth muscle relaxation
• Use: acute relief; pre-exercise; as needed for intermittent asthma
• GINA 2023: prefer low-dose ICS-formoterol as reliever over SABA alone (reduces exacerbations even in Step 1)

• Formoterol (fast onset), Salmeterol (slow onset)
• Duration: 12h
• NEVER use LABA without ICS in asthma (increases asthma-related deaths when used alone)
• First-line add-on at Step 3 (combined with ICS in single inhaler)

• Ipratropium bromide — additional bronchodilation in acute attacks; added to SABA in ED
• Onset: 15–20 min; Duration: 4–6h

• Tiotropium — add-on therapy at Step 4–5 in adults with frequent exacerbations
• Reduces exacerbations; may be less effective than LABA

• Aminophylline, Theophylline — IV aminophylline in status asthmaticus; narrow therapeutic window (5–15 mcg/mL); multiple drug interactions; less used now
• Mechanism: Inhibits phosphodiesterase → ↑cAMP; also anti-inflammatory

• MDI (metered-dose inhaler) + spacer (most efficient, reduces oropharyngeal deposition)
• DPI (dry powder inhaler) — requires adequate inspiratory flow
• Nebulizer (for acute attacks, unable to use MDI)

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Q49. Basic Drugs and Principles of Intensive Therapy for Bronchial Asthma

1. Inhaled Corticosteroids (ICS) — mainstay of asthma control:
   • Beclomethasone, Budesonide, Fluticasone, Mometasone, Ciclesonide
   • Reduce eosinophilic inflammation, airway hyperresponsiveness, exacerbations
   • Low dose: 200–400 mcg BDP equivalent; High dose: >800 mcg
   • Side effects: oral candidiasis (rinse mouth), dysphonia; at high doses: adrenal suppression, osteoporosis
2. ICS + LABA combinations (preferred for Step 3+):
   • Fluticasone/Salmeterol (Seretide), Budesonide/Formoterol (Symbicort), Fluticasone/Formoterol (Flutiform)
   • Budesonide/Formoterol — unique: can be used for both maintenance AND relief (MART regimen)
3. Leukotriene Receptor Antagonists (LTRA):
   • Montelukast 10 mg od — add-on; especially in AERD, exercise-induced, rhinitis comorbidity; less potent than ICS
4. Biologics (severe Step 5):
   • Omalizumab (anti-IgE): for high IgE, sensitized patients; reduces exacerbations by ~50%
   • Mepolizumab, Reslizumab (anti-IL-5): eosinophilic asthma
   • Benralizumab (anti-IL-5Rα): depletes eosinophils completely; q8-weekly SC injection
   • Dupilumab (anti-IL-4Rα): blocks IL-4 and IL-13; for eosinophilic asthma + atopic dermatitis
   • Tezepelumab (anti-TSLP): for severe asthma regardless of phenotype
5. Systemic corticosteroids: Reserved for severe exacerbations or very severe persistent asthma; minimize long-term use.

• Step-up if uncontrolled; step-down when stable ≥3 months
• Check inhaler technique and adherence before stepping up
• Address comorbidities (GERD, rhinitis, obesity, OSA)

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Q50. Principles of Treatment of Cardiac Asthma and Acute Pulmonary Edema

1. Position: Sitting upright (legs dependent → reduces preload)
2. Oxygen: High-flow O₂; target SpO₂ >95%
3. Non-invasive ventilation (CPAP/BiPAP): First-line in cardiogenic pulmonary edema:
   • CPAP 5–10 cmH₂O improves oxygenation, reduces preload/afterload, prevents intubation
   • Reduces mortality
4. Diuretics — cornerstone:
   • Furosemide 40–80 mg IV bolus (onset 15–30 min) → venodilation (within minutes) then diuresis
   • Bumetanide, torasemide alternatives
5. Nitrates — vasodilation:
   • Nitroglycerin (GTN) IV infusion 10–200 mcg/min (or SL 0.4 mg) — primarily venodilation at low doses; reduces preload dramatically; excellent in hypertensive pulmonary edema
6. Morphine 2–4 mg IV (controversial — reduces anxiety, venodilates; may worsen hypotension; use cautiously)
7. Treat underlying cause:
   • Arrhythmia → cardioversion/rate control
   • Hypertension → IV nitrates/nitroprusside
   • ACS → revascularization (PCI)
   • Valvular emergency → surgery
8. Inotropes (if cardiogenic shock + pulmonary edema):
   • Dobutamine 2–20 mcg/kg/min IV
   • Dopamine (if hypotension)
   • Avoid beta-blockers acutely
9. Intubation + mechanical ventilation: If no improvement with NIV or altered consciousness

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Q51. Algorithm for Emergency Care During Cardiac Asthma Attack

• ABC: Airway, Breathing, Circulation
• Vital signs: HR, BP, RR, SpO₂
• ECG (12-lead) — rule out ACS, arrhythmia
• IV access × 2; blood: BNP, troponin, ABG, U&E, CBC

• Sit patient upright, legs down
• O₂ via face mask 10–15 L/min → SpO₂ >95%
• Initiate CPAP if SpO₂ <90% on O₂ (CPAP 5 cmH₂O, titrate to 10)

• Furosemide 40–80 mg IV (if BP >90 systolic)
• Nitroglycerin SL 0.4 mg (if SBP >110 mmHg), then IV 10–20 mcg/min, titrate
• Morphine 2–5 mg IV slow (if not contraindicated)

• If BP falls <90: stop nitrates, consider dobutamine
• If bronchospasm dominant: IV aminophylline 240 mg over 15 min
• Reassess SpO₂, RR, BP every 5–15 min

• ACS: aspirin 300 mg + heparin + emergency PCI
• Hypertensive crisis: IV labetalol or nicardipine
• AF with rapid rate: IV digoxin or amiodarone

• BiPAP (IPAP 12–20, EPAP 4–8 cmH₂O)
• Intubation if coma/exhaustion/RR >35 or SpO₂ <85%
• ICU transfer

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Q52. Principles of Treatment of COPD

• Smoking cessation — single most effective intervention; slows FEV₁ decline
• Pulmonary rehabilitation: exercise + education → reduces dyspnea, hospitalizations
• Long-term oxygen therapy (LTOT): if PaO₂ ≤55 mmHg or ≤60 mmHg + polycythemia/cor pulmonale; ≥15 h/day; only intervention that improves survival
• Nutritional support
• Annual influenza vaccination; pneumococcal vaccination
• Avoidance of occupational/environmental irritants

• LAMA (Long-Acting Muscarinic Antagonist): Tiotropium (Spiriva), Umeclidinium, Aclidinium — superior to LABA in reducing exacerbations in COPD
• LABA: Salmeterol, Formoterol, Indacaterol, Olodaterol
• LAMA + LABA combination (preferred for symptomatic patients): e.g., Tiotropium/Olodaterol (Spiolto), Umeclidinium/Vilanterol (Anoro)
• SABA/SAMA for rescue: Salbutamol, Ipratropium

• ADD to LAMA+LABA if eosinophils ≥300/μL OR frequent exacerbations (≥2/year) despite dual bronchodilation
• Not first-line in COPD; can worsen pneumonia risk

• Roflumilast (PDE4 inhibitor): chronic bronchitis phenotype with frequent exacerbations; oral; reduces exacerbations; GI side effects
• Azithromycin 250 mg daily × 1 year: reduces exacerbations (especially in ex-smokers); monitor for hearing loss, QTc
• N-acetylcysteine (mucolytic): modest benefit in chronic bronchitis

• SABA + SAMA nebulized; oral prednisolone 40 mg × 5 days; antibiotics (amoxicillin-clavulanate, doxycycline, macrolide) if purulent sputum/elevated CRP; NIV for type II respiratory failure (PaCO₂ >45 + pH <7.35)

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HEMATOLOGY (Questions 53–82)

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Q53. Modern Classification of Anemia

1. Blood loss (hemorrhagic): Acute or chronic
2. Impaired RBC production:
   • Iron deficiency anemia (IDA)
   • B12 and folate deficiency (megaloblastic)
   • Aplastic / hypoplastic (bone marrow failure)
   • Anemia of chronic disease (ACD)
   • Sideroblastic anemia
   • Pure red cell aplasia
3. Increased RBC destruction (hemolytic):
   • Intravascular vs. extravascular
   • Congenital vs. acquired

• Mild: Hb 90–120 g/L (women), 90–130 g/L (men)
• Moderate: Hb 70–89 g/L
• Severe: Hb <70 g/L
• Life-threatening: Hb <40–50 g/L

• Regenerative: hemolytic, acute blood loss
• Aregenerative: aplastic, B12/folate, IDA (early), infiltrative marrow disease

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Q54. Etiological Factors Contributing to Anemic Syndrome

• Iron deficiency: Blood loss (GI, menstrual), malabsorption (celiac, post-gastrectomy), increased demand (pregnancy, infancy), inadequate intake
• B12 deficiency: Pernicious anemia (autoimmune — anti-IF antibodies), gastrectomy, ileal disease/resection, strict vegan diet, Diphyllobothrium latum (fish tapeworm)
• Folate deficiency: Poor diet (elderly, alcoholics), pregnancy (increased demand), malabsorption, drugs (methotrexate, phenytoin, trimethoprim)
• Bone marrow failure: Aplastic anemia (idiopathic autoimmune, drugs — chloramphenicol, benzene, radiation, viral — parvovirus, EBV, hepatitis)
• Bone marrow infiltration: Leukemia, lymphoma, metastatic cancer, myeloma, myelofibrosis
• Anemia of chronic disease/inflammation: Cytokines (IL-6 → ↑hepcidin → ↓iron release), shortened RBC survival

• Intrinsic (corpuscular): hereditary spherocytosis, G6PD deficiency, sickle cell disease, thalassemia, PNH
• Extrinsic (extracorpuscular): autoimmune (AIHA), microangiopathic (TTP, HUS, DIC), malaria, hypersplenism, mechanical (prosthetic valves)

• Acute: trauma, surgery, GI bleeding, obstetric hemorrhage
• Chronic: peptic ulcer, GI malignancy, NSAIDs, menorrhagia, hookworm

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Q55. Classification of Hemolytic Anemias: Congenital and Acquired Forms

Congenital (Hereditary) — Intrinsic RBC Defects:

• Hereditary spherocytosis (HS): Ankyrin/spectrin mutations; AD; spherocytes on smear; positive osmotic fragility; responds to splenectomy
• Hereditary elliptocytosis: Spectrin mutations; usually mild
• Hereditary stomatocytosis

• G6PD deficiency: X-linked; episodic hemolysis triggered by oxidant stress (drugs — primaquine, dapsone, nitrofurantoin; fava beans; infection); Heinz bodies; bite cells; normal between episodes
• Pyruvate kinase deficiency: AR; chronic normocytic hemolysis; splenomegaly

• Sickle cell disease (HbSS): AR; Glu→Val substitution in β-globin; crisis (pain, ACS, stroke); target cells, sickle cells; Hb electrophoresis diagnostic
• Thalassemia:
  • α-thalassemia: deletion of α-globin genes (1–4 gene deletions)
  • β-thalassemia: minor (trait, mild), intermedia, major (Cooley's — transfusion dependent); hypochromic microcytic; target cells; elevated HbA2 (>3.5%) and HbF
• Other: Unstable hemoglobins, HbC, HbE

Acquired (Extrinsic) — Extracorpuscular Defects:

• Autoimmune hemolytic anemia (AIHA): Warm (IgG — splenic; drug-induced, lymphoma, SLE, idiopathic) and Cold (IgM + complement — cold agglutinin disease, Mycoplasma, lymphoma, paroxysmal cold hemoglobinuria)
• Alloimmune: Hemolytic transfusion reactions; HDN (hemolytic disease of newborn)

• Microangiopathic hemolytic anemia (MAHA): Schistocytes (fragmentation) — TTP, HUS, DIC, malignant hypertension, HELLP
• Cardiac mechanical hemolysis (prosthetic valves)
• March hemoglobinuria (foot-strike)

• Paroxysmal Nocturnal Hemoglobinuria (PNH): Clonal PIG-A mutation → absent GPI-anchored complement regulatory proteins (CD55, CD59) → complement-mediated intravascular hemolysis; thrombosis; cytopenias; dark morning urine; diagnosed by flow cytometry (CD55/CD59 absent)
• Hypersplenism
• Infectious: Malaria (Plasmodium falciparum), Clostridium, Bartonella
• Liver disease (spur cell anemia — acanthocytes)

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Q56. Diagnostic Criteria for Iron Deficiency Anemia (IDA)

• Anemic syndrome: fatigue, pallor, dyspnea on exertion, palpitations, headache
• Sideropenic syndrome (iron-deficient tissue):
  • Angular cheilitis (perlèche), glossitis (smooth tongue), dysphagia (Plummer-Vinson/Patterson-Kelly syndrome)
  • Koilonychia (spoon nails), brittle nails, hair loss
  • Pica (craving for ice — pagophagia, clay, chalk)
  • Restless legs syndrome
  • Blue sclerae

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Q57. Diagnostic Criteria for B12 and Folate Deficiency Anemia

Vitamin B12 Deficiency:

• Macrocytic megaloblastic anemia
• Neurological (B12 only, NOT folate): Subacute combined degeneration of spinal cord — posterior column (vibration/proprioception loss) + lateral corticospinal (pyramidal signs); peripheral neuropathy; cognitive impairment; optic neuropathy
• Glossitis (beefy red tongue), angular cheilitis
• Fatigue, jaundice (ineffective erythropoiesis)

Folate Deficiency:

• Clinical: identical macrocytic anemia; NO neurological features
• Serum folate <7 nmol/L (<3 ng/mL)
• RBC folate <340 nmol/L (reflects body stores better)
• Homocysteine elevated; MMA normal (differentiates from B12 deficiency)

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Q58. Diagnostic Criteria for Hypo- and Aplastic Anemia

• Idiopathic (autoimmune T-cell destruction — 70%)
• Acquired: Drugs (chloramphenicol, phenytoin, sulfonamides), chemicals (benzene), radiation, viral (EBV, CMV, hepatitis non-A/B/C, parvovirus B19), PNH (related)
• Inherited (Fanconi's anemia, dyskeratosis congenita)

• Anemic syndrome: fatigue, pallor, dyspnea
• Hemorrhagic syndrome: petechiae, ecchymoses, mucosal bleeding (thrombocytopenia)
• Infectious syndrome: recurrent/severe infections (neutropenia)

• Neutrophils <0.5 × 10⁹/L (very severe: <0.2)
• Platelets <20 × 10⁹/L
• Reticulocytes <20 × 10⁹/L (or <1% corrected)
• Bone marrow cellularity <25% (or 25–50% with <30% residual hematopoietic cells)

• Normocytic/macrocytic normochromic anemia
• Pancytopenia (all three cell lines reduced)
• Reticulocytes markedly reduced (aregenerative)
• Normal/elevated MCV
• Elevated HbF (in Fanconi's, may be elevated in acquired AA)

• Hypocellular (<25%); fatty replacement; absent megakaryocytes, erythroid, and myeloid precursors
• May see residual lymphocytes and plasma cells

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Q59. Diagnostic Criteria for Hemolytic Anemia

• Reticulocytosis (>2–3%; reticulocyte count >100 × 10⁹/L)
• Polychromasia (young RBCs appear bluish/grey on smear)
• Bone marrow: erythroid hyperplasia (M:E ratio reversal — normal 3:1; hemolysis 1:3)
• Elevated MCV (from reticulocytes)

• Spherocytes → HS, warm AIHA
• Schistocytes → MAHA (TTP, DIC, HUS), microangiopathy
• Sickle cells → sickle cell disease
• Target cells → thalassemia, HbC, liver disease
• Bite cells / blister cells → G6PD deficiency
• Elliptocytes → hereditary elliptocytosis
• Agglutinated RBCs → cold agglutinin disease

• Positive → Immune hemolysis (AIHA, drug-induced, alloimmune)
• Negative → Non-immune hemolysis (hereditary, MAHA, mechanical)

• Intravascular: Hemoglobinemia, hemoglobinuria, ↓↓haptoglobin, hemosiderinuria; causes: PNH, ABO incompatibility, G6PD, mechanical, complement-mediated
• Extravascular (splenic/hepatic): Jaundice, splenomegaly, no hemoglobinuria; causes: HS, warm AIHA, sickle cell

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Q60. Differential Diagnosis of Hypo-Aplastic Anemia vs. Leukemia

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Q61. Laboratory Indicators for Hypo- and Aplastic Anemia

• Hemoglobin: markedly reduced (often <70 g/L in severe)
• MCV: normal to mildly elevated
• MCH, MCHC: normal
• WBC: reduced (neutropenia <0.5 × 10⁹/L in severe AA)
• Platelets: markedly reduced (<20 × 10⁹/L severe; <50 × 10⁹/L moderate)
• Reticulocytes: markedly reduced (<20 × 10⁹/L or <0.5%)
• Blood smear: normochromic, normocytic; no abnormal cells; no blasts

• Serum iron: elevated (no utilization by absent erythroid precursors)
• Ferritin: elevated (iron accumulation)
• TIBC: reduced
• EPO: markedly elevated (appropriate response to severe anemia)
• LDH: mildly elevated (minor cell destruction)

• HLA typing (for stem cell transplantation planning)
• PNH clone: CD55/CD59 by flow cytometry (present in ~30–50% AA)
• Fanconi anemia: chromosomal fragility test (diepoxybutane/DEB)

• Cellularity <25% (or <50% with <30% residual hematopoiesis)
• Fatty marrow replacement
• Absent or rare erythroid, myeloid, megakaryocytic precursors
• Lymphocytes and plasma cells relatively preserved (reactive)

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Q62. Methods of Bone Marrow Examination

• Site: Posterior superior iliac spine (PSIS) preferred (safer); sternum (easier access; no biopsy)
• Technique: Local anesthesia; needle to cortex; aspirate 1–2 mL
• Smear and stain: May-Grünwald-Giemsa (MGG), Prussian blue (iron stain), PAS, MPO, Sudan Black B
• Provides: Cell morphology, differential count of precursors, blast percentage, iron stores
• Indications: Diagnosis of hematologic malignancies, aplastic anemia, megaloblastic anemia, storage diseases

• Site: PSIS only (sternal trephine too dangerous)
• Technique: 8–11G trephine needle → core 2 cm × 2 mm; fixed in formalin → decalcified → paraffin section → stained (H&E, reticulin)
• Provides: Architecture, cellularity, fibrosis, infiltration, vascularity
• Essential for: Aplastic anemia (cellularity assessment), myelofibrosis (reticulin grade 0–3/MF-0–3), lymphoma infiltration, metastatic cancer

• Flow cytometry: Immunophenotyping (CD markers) — leukemia classification, MRD monitoring, lymphoma
• Cytogenetics (karyotype): Chromosome analysis — t(9;22) BCR-ABL (CML), t(15;17) PML-RARα (APL), del(5q), monosomy 7
• FISH (Fluorescence In Situ Hybridization): Rapid specific chromosomal abnormalities
• Molecular studies: PCR for BCR-ABL, JAK2 V617F (MPN), NPM1, FLT3 mutations
• Microbiological culture: In febrile patients with suspected disseminated infection (TB, fungal)

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Q63. Diagnosis and Principles of Treatment of Iron Deficiency Anemia

• Establish: low ferritin + low serum iron + elevated TIBC + microcytic hypochromic anemia
• Identify cause: GI endoscopy, gynecology review, malabsorption workup (anti-endomysial/tTG for celiac)

• Ferrous sulfate 325 mg (65 mg elemental iron) TID — most evidence, cheapest
• Ferrous fumarate (33% elemental iron), ferrous gluconate (12%)
• Take on empty stomach (absorption ↑ with vitamin C; ↓ by tea, calcium, antacids)
• Duration: Continue 3–6 months after Hb normalizes (to replenish stores; ferritin >50 μg/L)
• Side effects: Nausea, constipation, dark stools; take with food if intolerant

• Indications: Malabsorption (celiac, IBD), intolerance of oral iron, ongoing losses exceeding replacement, pre-operative optimization, CKD on ESA
• Preparations: Iron sucrose (Venofer), ferric carboxymaltose (Ferinject — single large dose), iron dextran
• Risk: Anaphylaxis (low with newer preparations); infusion reactions

• Reticulocytosis peak at 7–10 days (first response)
• Hb rises ~10–20 g/L per week
• Ferritin reaches target (>50 μg/L) at 3–6 months

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Q64. Iron-Containing Drugs: Indications and Contraindications

• Confirmed IDA (ferritin <12 μg/L + low Hb)
• Iron-deficiency without anemia but symptomatic (fatigue, restless legs, pica) with ferritin <30 μg/L
• Prophylaxis: pregnancy (especially 2nd/3rd trimester), preterm neonates, vegetarians/vegans, blood donors
• Preoperative optimization (elective surgery with anemia)
• CKD + erythropoiesis-stimulating agent (ESA) therapy

• Hemochromatosis, hemosiderosis — absolute contraindication (iron overload)
• Hemolytic anemia without iron deficiency — can worsen iron accumulation
• Aplastic anemia without iron deficiency
• Anemia not due to iron deficiency — first exclude B12/folate deficiency and other causes
• Oral iron contraindicated if: inflammatory bowel disease (active flare) → use IV instead
• Parenteral iron contraindicated: active infection (risk of bacterial proliferation in iron-rich environment), first trimester pregnancy, known hypersensitivity

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Q65. Diagnosis and Principles of Treatment of B12 and Folate Deficiency Anemia

• Distinguish B12 from folate: Elevated MMA (B12 deficiency only); neurological features (B12 only)
• Pernicious anemia: Anti-IF antibody positive; gastroscopy shows atrophic gastritis

B12 Deficiency:

• Intramuscular (IM) — for pernicious anemia/malabsorption (cannot absorb oral B12):
  • Hydroxocobalamin 1000 μg IM daily × 5 days (loading), then 1000 μg every 3 months lifelong
  • Cyanocobalamin 1000 μg IM (equivalent but hydroxocobalamin preferred — longer-lasting)
• Oral — for dietary deficiency only: Cyanocobalamin 1000–2000 μg/day orally (high-dose oral can compensate IF-independent absorption)
• Intranasal B12 — option for dietary deficiency

Folate Deficiency:

• Folic acid 5 mg orally once daily × 4 months (until deficiency corrected and underlying cause treated)
• Prophylaxis in pregnancy: 400 μg/day (or 5 mg/day if high risk — prior neural tube defect, anticonvulsants, malabsorption) — start periconceptionally
• Do NOT give folate alone if B12 status unknown — will correct anemia but accelerate neurological damage of B12 deficiency

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Q66. Diagnosis and Principles of Treatment of Hemolytic Anemia

Hereditary Spherocytosis:

• Folic acid 5 mg/day supplementation (high cell turnover)
• Splenectomy (curative for moderate-severe): Laparoscopic preferred; vaccinate 2 weeks before (pneumococcal, meningococcal, Hib); lifelong penicillin prophylaxis post-splenectomy
• Cholecystectomy if pigment gallstones

G6PD Deficiency:

• Avoid triggers (primaquine, dapsone, fava beans, naphthalene)
• Supportive during acute crisis: fluids, transfusion if severe
• No specific drug treatment

Sickle Cell Disease:

• Hydroxyurea (hydroxycarbamide): ↑HbF → ↓sickling; reduces crisis frequency by 50%; standard of care
• Folic acid 5 mg/day
• Pain crises: Opioids (morphine), IV fluids, NSAIDs, oxygen
• Prophylactic penicillin V (functional asplenia) + vaccinations
• Curative: Allogeneic HSCT (in severe cases with matched sibling donor); gene therapy (Betibeglogene — FDA approved 2023)
• Exchange transfusion: stroke prevention, ACS

Autoimmune Hemolytic Anemia (AIHA):

• Warm AIHA: Prednisolone 1–1.5 mg/kg/day (first-line); splenectomy (second-line); Rituximab (anti-CD20); Azathioprine; Danazol; avoid transfusion unless life-threatening (compatible blood hard to find)
• Cold AIHA: Avoid cold; Rituximab; Bendamustine + Rituximab; treat underlying lymphoma; complement inhibitors (Sutimlimab — FDA approved)

TTP:

• Emergency: Plasma exchange (PLEX/TPE) — removes ADAMTS13 antibody + supplies ADAMTS13
• Corticosteroids; Rituximab (anti-ADAMTS13 antibody); Caplacizumab (anti-vWF)

PNH:

• Eculizumab (anti-C5 complement inhibitor) — prevents intravascular hemolysis; reduces thrombosis risk; lifelong
• Ravulizumab (longer-acting anti-C5)
• HSCT for aplastic PNH

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Q67. Modern Classification of Hemorrhagic Diathesis

• Hereditary: Hereditary hemorrhagic telangiectasia (HHT/Osler-Weber-Rendu)
• Acquired: Henoch-Schönlein purpura (HSP/IgAV), scurvy (vitamin C deficiency — vascular fragility), steroid purpura, senile purpura, amyloidosis, infections (meningococcemia — Waterhouse-Friderichsen)

• Thrombocytopenia (reduced number):
  • Decreased production: Aplastic anemia, leukemia, drugs, B12/folate
  • Increased destruction: ITP (Werlhof's disease), TTP, HUS, DIC, HIT
  • Sequestration: Hypersplenism
• Thrombocytopathy (dysfunction despite normal count):
  • Hereditary: Glanzmann's thrombasthenia (GP IIb/IIIa absent), Bernard-Soulier (GP Ib absent), storage pool disease
  • Acquired: Uremia, drugs (aspirin, clopidogrel, NSAIDs), myeloproliferative disorders

• Hereditary: Hemophilia A (F.VIII), Hemophilia B (F.IX), von Willebrand disease (vWD), rare factor deficiencies
• Acquired: Liver disease (↓factors II, V, VII, IX, X, fibrinogen), Vitamin K deficiency (↓II, VII, IX, X), anticoagulant therapy (warfarin, heparin), DIC (consumption of all factors), acquired inhibitors (factor VIII inhibitor — acquired hemophilia)

• DIC: Thrombocytopenia + consumption of coagulation factors + fibrinolysis
• Liver failure: Multiple factor deficiencies + thrombocytopenia

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Q68. Etiological Factors Underlying Hemorrhagic Diathesis

• Autoimmune: IgA vasculitis (HSP), SLE, cryoglobulinemia
• Infectious: Viral (dengue, viral hemorrhagic fevers), meningococcemia
• Metabolic: Scurvy (↓vitamin C → defective collagen → weak vessel walls)
• Hereditary: HHT (ACVRL1, ENG mutations)
• Toxic/drug: Corticosteroids (skin atrophy), prolonged glucocorticoid use

• Thrombocytopenia by decreased production: Cytotoxic drugs, radiation, alcohol, viral infections (EBV, CMV, HIV, parvovirus, hepatitis), infiltration of marrow
• Increased platelet destruction (immune): Primary ITP; secondary ITP (SLE, CLL, HIV, drugs — heparin, quinine, sulfonamides)
• Platelet consumption: DIC, TTP, HUS, HELLP
• Platelet dysfunction: Aspirin (irreversible COX inhibition → ↓TXA₂), clopidogrel (P2Y12 inhibition), uremia (↓vWF function), liver disease

• Hereditary: Hemophilia A (F.VIII gene mutation on X chromosome), Hemophilia B (F.IX mutation), vWD
• Acquired: Liver disease (hepatocytes synthesize all clotting factors except vWF and F.VIII); Vitamin K deficiency (malabsorption, warfarin, broad-spectrum antibiotics eliminating gut flora); DIC (consumption + fibrinolysis)

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Q69. Types of Bleeding According to Z.S. Barkagan

• Small pinpoint petechiae (<3 mm), ecchymoses (bruises), not palpable
• Location: Skin, mucous membranes; symmetric distribution
• Associated with: Thrombocytopenia, thrombocytopathies, vascular defects
• Characteristic of: ITP, aplastic anemia, scurvy, drug-induced thrombocytopenia

• Large, deep, tense, painful hematomas in muscles, joints (hemarthroses), retroperitoneal spaces
• Spontaneous or after minor trauma
• Severe hemorrhage after dental extraction, surgery
• Associated with: Coagulation factor deficiencies
• Characteristic of: Hemophilia A and B, severe factor deficiencies

• Features of both petechiae AND hematomas
• Associated with: Combined platelet and coagulation defects
• Characteristic of: DIC, severe von Willebrand disease, acquired hemophilia, liver failure

• Palpable purpura (raised, symmetric, lower extremities), urticaria
• May be associated with arthralgia, abdominal pain, nephritis
• Associated with: Immune complex vasculitis
• Characteristic of: IgA vasculitis (Henoch-Schönlein purpura), cryoglobulinemia

• Recurring bleeding from the same site (telangiectasia)
• No generalized bleeding tendency
• Characteristic of: Hereditary hemorrhagic telangiectasia (HHT/Osler-Weber-Rendu disease)
• Sites: Nasal (epistaxis), GI, pulmonary arteriovenous malformations

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Q70. Clinical Features of Platelet Hemorrhages

• Petechiae: Pinpoint red/purple non-blanching spots <3 mm; flat (not palpable); result from capillary microhemorrhage
• Ecchymoses/bruises: Variable size, painless, flat, appear with minimal trauma
• Purpura: Confluent petechiae forming larger areas of discoloration
• Mucosal bleeding: Epistaxis (nosebleed), gingival bleeding, oral blood blisters (wet purpura — sign of severe thrombocytopenia <10×10⁹/L)
• Menorrhagia: Heavy/prolonged menstrual bleeding
• GI bleeding: Hematochezia; risk of intracranial hemorrhage (most feared if platelets <10×10⁹/L)

• Superficial (skin, mucous membranes) — no deep hematomas
• Immediate bleeding after injury (primary hemostasis defect)
• Bleeding stops temporarily then restarts (poor platelet plug, compensated by clot)
• No hemarthroses (no deep muscle bleeds)

• Platelets >50×10⁹/L: Bleeding only with trauma/surgery
• 20–50×10⁹/L: Spontaneous purpura/mucosal bleeding
• <20×10⁹/L: Spontaneous petechiae, mucosal bleeding; at 10×10⁹/L: risk of intracranial hemorrhage

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Q71. Clinical Features of Vascular Hemorrhages (Vasopathy)

• Palpable purpura — raised (unlike thrombocytopenic purpura), non-blanching, lower extremities and buttocks
• Arthralgia/arthritis (knees, ankles — migratory)
• Abdominal pain (colicky — GI vasculitis; risk of intussusception)
• Nephritis — IgA nephropathy (hematuria, proteinuria); risk of chronic renal failure

• Telangiectasias: Spider-like, on lips, tongue, nasal mucosa, fingertips
• Epistaxis: Recurrent, often severe; may be disabling
• GI bleeding (angiodysplasia of gut)
• Pulmonary/cerebral AVMs: Risk of paradoxical emboli, stroke, brain abscess

• Perifollicular hemorrhage — pathognomonic (corkscrew hairs with surrounding hemorrhage)
• Gingival bleeding (spongy, swollen gums)
• Subperiosteal hemorrhage (painful, in children)
• Poor wound healing; joint effusions

• Easy bruising, skin atrophy, purpura on dorsum of hands and forearms
• No petechiae, no mucosal bleeding
• Platelets and coagulation normal

• Superficial bleeding (skin, mucous membranes)
• Normal platelet count and coagulation studies
• Positive Rumpel-Leede (tourniquet/capillary fragility) test

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Q72. Clinical Features of Coagulation Hemorrhages

• Hemarthroses (pathognomonic of severe hemophilia): Bleeding into large joints (knee, elbow, ankle); swollen, warm, painful; recurrent → hemophilic arthropathy (destruction of cartilage, joint deformity)
• Deep muscle hematomas: Iliopsoas (inguinal pain, hip flexion deformity), calf, forearm, tongue (dangerous — airway obstruction)
• Retroperitoneal hematomas: Mimics acute abdomen; compress femoral nerve (femoral neuropathy — anterior thigh weakness)
• Post-surgical/dental hemorrhage: Delayed bleeding (30 min to hours after initial hemostasis — primary platelet plug normal, clot formation defective)
• Prolonged bleeding after minor cuts
• CNS hemorrhage: Intracranial, subdural, epidural hemorrhage; most dangerous

• Deep tissue locations (joints, muscles)
• Delayed onset after injury (primary hemostasis intact)
• Prolonged bleeding not corrected by local pressure
• No petechiae or mucosal bleeding (unless severe)

• Prolonged APTT (intrinsic pathway defects — FVIII, FIX, FXI, FXII)
• Prolonged PT (extrinsic — FVII deficiency, warfarin, vitamin K deficiency)
• Both prolonged: common pathway (FX, FV, FII, fibrinogen) or combined defect (DIC, liver disease, supratherapeutic anticoagulation)
• Normal platelet count (unless combined defect)
• Normal bleeding time (platelet function intact)

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Q73. Types of Hemophilia

• Factor VIII deficiency
• Most common: 1 in 5,000–10,000 male births; 80% of all hemophilia
• Gene: F8 on Xq28; inversions at intron 22 most common (45% of severe HA)

• Factor IX deficiency
• 1 in 30,000 male births; 15–20% of hemophilia
• Gene: F9 on Xq27

• Factor XI deficiency (Rosenthal syndrome)
• Autosomal recessive; common in Ashkenazi Jews
• Milder, unpredictable bleeding; no hemarthroses typically

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Q74. Diagnostic Criteria for Hemophilia

• Male patient with bleeding history (or female manifesting carrier)
• Family history (X-linked — maternal uncles affected; 30% are de novo mutations)
• Hemarthroses, muscle hematomas, prolonged bleeding after minor trauma/surgery/dental procedures

• If poor response to factor replacement → measure inhibitor titer (Bethesda units)
• Inhibitor ≥5 BU/mL = high-responding inhibitor (recombinant FVIIa or APCC required)

• DNA analysis: Identify specific mutation (F8/F9); guides carrier testing and prenatal diagnosis
• Carrier females: Factor level often 50% (may overlap with low-normal)

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Q75. Clinical Features of Hemophilia

• Knee (most common), elbow, ankle, shoulder, hip, wrist
• Acute: Warm, swollen, painful, restricted ROM; tense joint
• Chronic recurrent → hemophilic arthropathy: synovial hypertrophy → iron deposition → chondrolysis → bone destruction → chronic pain, deformity, muscle wasting
• End-stage: Joint ankylosis, severe deformity ("target joint")

• Any muscle; iliopsoas hematoma → pseudo-appendicitis, femoral nerve compression
• Compartment syndrome risk (forearm, calf)
• Voluminous; may take weeks to resolve

• Intracranial hemorrhage (ICH): Spontaneous or after minor head trauma; most common cause of death; headache, vomiting, focal neurology → EMERGENCY
• Pharyngeal/laryngeal: Airway obstruction
• GI: Hematemesis, melena
• Retroperitoneal: Mimics acute abdomen

• Viral transmission (HIV, HCV) from plasma-derived concentrates (1980s)
• Inhibitor development (25–30% severe HA, 3–5% severe HB)

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Q76. Vasopathies: Causes and Clinical Manifestations

1. Hereditary Hemorrhagic Telangiectasia (HHT/Osler-Weber-Rendu):
   • AD; mutations in ENG (Endoglin) or ACVRL1 genes (TGF-β pathway)
   • Multiple telangiectasias on skin and mucous membranes
   • Recurrent severe epistaxis (often presenting symptom)
   • GI bleeding (occult or overt)
   • Pulmonary and cerebral AVMs → paradoxical emboli, stroke, brain abscess
   • Diagnosis: Curaçao criteria (≥3 of: epistaxis, telangiectasias, visceral AVMs, positive family history)
2. Ehlers-Danlos syndrome (EDS): Connective tissue disorder; hypermobile joints, hyperextensible skin; easy bruising; vascular type (EDS IV): risk of arterial rupture
3. Marfan syndrome: Fibrillin-1 mutations; aortic aneurysm; less prominent bleeding tendency

1. IgA vasculitis (HSP/Henoch-Schönlein): See Q79
2. Hypersensitivity vasculitis: Drug-induced, infections, cryoglobulinemia
3. Scurvy (Vitamin C deficiency): Perifollicular hemorrhage, gingival bleeding, poor wound healing
4. Corticosteroid/senile purpura: Atrophic skin; purpura on sun-exposed areas; no mucosal bleeding; normal platelets and coagulation
5. Infectious vasculopathy: Meningococcemia (purpura fulminans — widespread skin necrosis from DIC + vasculopathy), rickettsial disease, viral hemorrhagic fevers
6. Amyloidosis: Amyloid deposits in vessel walls → "pinch purpura," periorbital purpura (raccoon eyes)
7. Waldenström macroglobulinemia: Hyperviscosity + vasopathy → mucosal/retinal bleeding

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Q77. Clinical Features and Diagnosis of Werlhof's Disease (ITP)

• Autoantibodies (anti-GPIIb/IIIa, anti-GPIb/IX) bind platelets → opsonization → macrophage-mediated destruction in spleen
• T-cell mediated direct platelet destruction also contributes
• Impaired megakaryocyte function (antibodies also inhibit thrombopoiesis)

• Newly diagnosed (<3 months), Persistent (3–12 months), Chronic (>12 months)
• Primary (no underlying cause) vs. Secondary (SLE, HIV, HCV, CLL, H. pylori, drugs)

• Children: Acute onset; follows viral URTI (2 weeks prior); petechiae; self-limiting in 80%
• Adults: Insidious onset; chronic course; predominantly women 20–40 years
• Petechiae (especially lower extremities, dependent areas)
• Ecchymoses (spontaneous bruising)
• Mucosal bleeding: epistaxis, gingival, oral blood blisters, menorrhagia
• GI bleeding, hematuria (less common)
• No splenomegaly (distinguishes from hypersplenism)
• No lymphadenopathy, no fever (distinguishes from lymphoproliferative disease)
• Life-threatening: Intracranial hemorrhage (1–5%; risk at platelets <10×10⁹/L)

• Platelet count <100×10⁹/L (typically <50×10⁹/L at presentation)
• Normal Hb and WBC (unless severe mucosal bleeding causing anemia)
• Normal PT, APTT, fibrinogen
• Blood smear: reduced platelets; large platelets (megathrombocytes/young platelets); no RBC fragmentation
• Bone marrow: Normal/increased megakaryocytes (normal morphology); performed only to exclude other causes (>60 years, atypical presentation, before splenectomy)
• Anti-platelet antibody testing: low sensitivity; not recommended routinely
• Screen for secondary causes: ANA, anti-dsDNA, HIV, HCV, H. pylori antibodies/antigen, TSH

• No treatment: Platelets >30×10⁹/L without significant bleeding
• First-line: Prednisolone 1 mg/kg/day × 3–4 weeks, then taper; or IV methylprednisolone pulse (1g/day × 3 days)
• IVIG: 1 g/kg × 2 days; rapid response; use in severe bleeding or pre-procedure
• Anti-D (WinRho): Only Rh+ non-splenectomized; hemolytic mechanism raises platelets
• Second-line: Rituximab (anti-CD20); Thrombopoietin receptor agonists (Romiplostim SC weekly, Eltrombopag oral); Splenectomy (highest cure rate 60–70% but last resort)
• Emergency (intracranial hemorrhage): IVIG + steroids + platelet transfusion + emergency splenectomy

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Q78. Diagnosis of Hemorrhagic Vasculitis and Its Clinical Forms

1. Palpable purpura (100%): Mandatory; non-blanching, palpable (raised), symmetric, lower extremities and buttocks; may become confluent, necrotic, bullous
2. Arthralgia/Arthritis (75%): Periarticular swelling, painful; knees and ankles most common; non-destructive
3. Abdominal pain (50–65%): Colicky; GI vasculitis; hematochezia; risk of intussusception (children); can mimic acute abdomen
4. Nephritis (40–60%): Hematuria (microscopic or macroscopic), proteinuria; IgA nephropathy pattern on biopsy; risk of chronic renal failure (especially in adults)

• Mandatory: Palpable purpura (or petechiae) with lower limb predominance
• Plus ≥1 of:
  • Diffuse abdominal pain
  • IgA deposits (biopsy of skin or kidney by IF)
  • Arthritis/arthralgia
  • Renal involvement (hematuria/proteinuria)
• Elevated serum IgA
• Normal platelet count (distinguishes from thrombocytopenic purpura)
• Positive skin biopsy: IgA deposits in vessel walls by immunofluorescence

• ANCA-associated vasculitis (GPA, MPA): Pulmonary hemorrhage + renal failure; ANCA positive; lung biopsy
• Cryoglobulinemic vasculitis (HCV-associated): Palpable purpura, arthralgia, glomerulonephritis; cryoglobulins in serum; low C4

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Q79. Clinical Features and Diagnosis of Henoch-Schönlein Disease

• Begins as urticarial wheals or maculopapules → purpuric, non-blanching
• Crops of lesions; new crops with activity/position
• Predominantly buttocks, lower extremities (gravity/pressure-dependent)
• May involve scalp, ears; rarely truncal

• Typically knees and ankles; periarticular swelling (not true arthritis)
• Resolves without deformity

• Colicky periumbilical or diffuse pain
• Bloody stools (hematochezia)
• Vomiting; risk of intussusception, intestinal perforation (rare)

• Appears 4–6 weeks after skin involvement
• Hematuria (macro or micro), proteinuria
• Hypertension in severe cases
• Renal biopsy: Mesangial IgA deposits (identical to primary IgAN)
• Adults: worse renal prognosis than children

• Clinical (see Q78 criteria)
• Elevated serum IgA (50%)
• UA: Hematuria, casts, proteinuria
• Skin biopsy (if diagnosis uncertain): IgA + C3 deposits in dermal capillary walls
• Renal biopsy (for significant nephritis): Mesangial IgA deposits

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Q80. DIC Syndrome — Clinical Presentation

• Trigger → tissue factor (TF) release → massive thrombin generation → fibrin everywhere → consumption of F.V, F.VIII, fibrinogen, AT-III, protein C → clotting factor depletion → bleeding
• Secondary fibrinolysis: plasminogen → plasmin → FDPs/D-dimers → further impair hemostasis

• Sepsis (most common — gram-negative endotoxin, gram-positive exotoxins)
• Trauma (especially head injury — brain TF release)
• Obstetric emergencies: amniotic fluid embolism, placental abruption, retained dead fetus, eclampsia
• Malignancy (especially APL — M3 AML and mucin-secreting adenocarcinomas)
• Transfusion reactions, transplant rejection
• Burns, snake envenomation

• Purpura fulminans (skin necrosis): Symmetric, progressive; starts as petechiae → confluent skin necrosis → gangrene; especially extremities/nose/ears
• Multi-organ failure: Renal (oliguria/anuria), hepatic, pulmonary (ARDS), CNS (confusion, coma)
• Peripheral ischemia, acrocyanosis

• Diffuse bleeding: Venipuncture sites, surgical wounds, GI, genitourinary, mucous membranes
• Petechiae, ecchymoses
• Deep hematomas (in decompensated DIC)

• Prolonged PT, APTT, TT
• ↓ Fibrinogen (<1.5 g/L)
• ↑ D-dimers (markedly; >4 μg/mL)
• ↑ FDPs
• ↓ Antithrombin III
• Schistocytes on blood smear (microangiopathic hemolysis from fibrin strands)

• Treat underlying cause (most critical — stop the trigger)
• Fresh Frozen Plasma (FFP): 10–15 mL/kg for active bleeding/coagulation factor replacement
• Platelet concentrate: Maintain >50×10⁹/L (bleeding) or >20×10⁹/L (prophylaxis)
• Cryoprecipitate: Fibrinogen replacement if <1.5 g/L (contains fibrinogen, vWF, F.VIII, F.XIII)
• Heparin: Controversial; may be used in thrombosis-dominant DIC (purpura fulminans) or APL-DIC at low doses
• Antithrombin III concentrate (if levels <70%)
• Avoid fibrinolytic inhibitors (ε-aminocaproic acid) unless primary fibrinolysis

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Q81. Principles of Treatment of Hemorrhagic Vasculitis (IgAV/HSP)

1. Identify and treat trigger: Infections (antibiotics for bacterial trigger), discontinue offending drugs, eliminate food allergens
2. Supportive care: Rest (reduces purpuric crops), hydration, analgesia
3. Most cases self-limiting (especially children): Resolve in 4–6 weeks with supportive care

• Mild disease: NSAIDs for arthralgia (but monitor GI side effects and renal function carefully)
• Corticosteroids (prednisolone 1 mg/kg/day) NOT recommended for isolated skin/joint involvement (no benefit; may mask deterioration)

• Corticosteroids (prednisolone 1–2 mg/kg/day × 2–4 weeks, then taper): Reduces severity and duration of abdominal pain; useful in severe GI involvement; reduces risk of intussusception if given early
• Surgical intervention if perforation or intractable intussusception

• Isolated microscopic hematuria: Observe; monitor BP and urine; ACE inhibitor/ARB for proteinuria
• Nephrotic range proteinuria or nephritic syndrome: Prednisolone ± azathioprine/cyclophosphamide
• Crescentic GN (rapidly progressive): IV methylprednisolone pulse + cyclophosphamide or azathioprine; plasma exchange in severe cases
• RAAS blockade (ACEi/ARB) — long-term renoprotection

• Monitor BP, urinalysis, serum creatinine monthly × 6 months, then annually for adults with nephritis
• Adults have worse renal prognosis — require longer follow-up

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Q82. Methods of Hemostasis Research

• Tourniquet test (Rumpel-Leede): BP cuff at 100 mmHg × 5 min → positive if >10 petechiae in 5×5 cm area; indicates capillary fragility (thrombocytopenia, scurvy, vasculitis)
• Capillaroscopy: Microscopic examination of nailfold capillaries; abnormal in SSc, vasculitis

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CARDIOLOGY (Questions 83–85)

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Q83. Classification of Cardialgia Depending on Their Origin

I. Cardiac (Cardiogenic) Pain

1. Stable angina pectoris: Predictable, exertional; relieved by rest/nitrates in <5 min; atherosclerotic stenosis (fixed)
2. Unstable angina: Rest or new-onset or crescendo angina; ACS spectrum
3. NSTEMI: Troponin elevation + ischemic symptoms; no ST elevation; partial occlusion
4. STEMI: Complete occlusion; ST elevation + troponin rise; transmural infarction
5. Prinzmetal (vasospastic) angina: At rest, typically nocturnal/early morning; ST elevation during attacks; coronary spasm; responds to nitrates/calcium antagonists
6. Cardiac syndrome X / microvascular angina: Anginal symptoms + positive stress test but normal coronary arteries (microvascular dysfunction)
7. Silent ischemia: No pain; common in diabetics, elderly

1. Pericarditis: Sharp, pleuritic; worse lying flat, relieved leaning forward; pericardial friction rub; ST elevation (diffuse saddle-shaped) on ECG
2. Myocarditis: Chest pain + signs of heart failure; elevated troponin; young patients after viral illness
3. Aortic stenosis: Effort-related angina (supply-demand mismatch)
4. Hypertrophic cardiomyopathy (HOCM): Exertional chest pain; dynamic outflow obstruction
5. Mitral valve prolapse: Non-specific atypical chest pain; mid-systolic click

II. Aortic/Vascular Pain

1. Aortic dissection: Sudden tearing/ripping pain; maximal at onset; radiates to back/interscapular; BP asymmetry between arms; widened mediastinum on CXR; type A (ascending) = surgical emergency; type B (descending) = medical
2. Aortic aneurysm rupture/expansion: Acute severe pain; hemodynamic instability
3. Pulmonary embolism (PE): Pleuritic or pressure-like; sudden onset; dyspnea; right heart strain; elevated D-dimer; CTPA confirms

III. Pleuropulmonary Pain

1. Pleuritis/Pleurisy: Sharp, worse with breathing and coughing; unilateral; pleural friction rub; reduced breath sounds
2. Pneumothorax: Sudden sharp; dyspnea; hyperresonance; absent breath sounds; tracheal deviation (tension)
3. Pneumonia with pleuropneumonic involvement
4. Pulmonary infarction (PE with infarct): Pleuritic + hemoptysis

IV. Gastrointestinal Pain (referred to chest)

1. Gastroesophageal reflux (GERD): Burning, substernal; after meals, lying down; relieved by antacids; responds to PPI trial; may mimic angina
2. Esophageal spasm: Severe, squeezing; may radiate to jaw/arm; triggered by swallowing; relieved by nitrates (confounds with cardiac); "corkscrew esophagus" on barium swallow
3. Esophageal rupture (Boerhaave syndrome): Excruciating pain after forceful vomiting; surgical emergency; mediastinal air on CXR
4. Peptic ulcer/gastritis: Epigastric + lower sternal; related to meals; Helicobacter pylori
5. Pancreatitis: Upper abdominal + chest; elevated amylase/lipase
6. Cholecystitis: Right upper quadrant + referred to right shoulder/scapula

V. Musculoskeletal Pain

1. Costochondritis/Tietze syndrome: Reproducible tenderness at costochondral junctions; worse with palpation/breathing; no cardiac abnormality
2. Rib fracture: Trauma history; point tenderness; X-ray
3. Cervical/thoracic radiculopathy: Dermatomal distribution; worse with neck movement; paresthesias
4. Fibromyalgia: Multiple tender points; no local tenderness over costochondral junctions

VI. Psychogenic/Functional Pain

1. Panic disorder/anxiety: Atypical; associated with palpitations, hyperventilation, tingling of extremities; young patients; normal workup
2. Depression: Persistent atypical chest pain; somatic complaints
3. Somatoform disorder
4. Hyperventilation syndrome: Tingling of lips/fingers; carpopedal spasm; reduced PaCO₂

VII. Referred/Other

1. Herpes zoster (Shingles): Burning, unilateral, dermatomal; precedes rash; vesicular eruption after 2–5 days
2. Breast disorders: Mastodynia, breast abscess; anterior chest wall; palpable abnormality
3. Mediastinal tumors/masses: Thymoma, lymphoma; constant aching; other mediastinal compression signs

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Q84. Differential Diagnosis of Cardiogenic vs. Non-Cardiogenic Chest Pain

Cardiogenic Chest Pain

• Character: Pressure, tightness, squeezing, heaviness — "like a weight on the chest"; rarely described as sharp
• Location: Substernal/retrosternal; diffuse; difficult to localize with one finger (positive "palm sign")
• Radiation: Left arm (ulnar surface), jaw, neck, epigastrium, right arm; interscapular (aortic dissection/posterior MI)
• Duration: Stable angina: 2–10 min with rest/nitrates; NSTEMI: 20–30 min at rest; STEMI: >30 min; unrelieved by rest
• Precipitants: Exertion, emotional stress, cold, eating (stable angina); at rest (unstable, vasospastic)
• Relief: Sublingual nitroglycerin (within 3–5 min); rest; NOT relieved by antacids, position change, or analgesics
• Associated symptoms: Dyspnea (LV dysfunction), diaphoresis (sympathetic activation — suggests severe ischemia or infarction), nausea/vomiting, palpitations, syncope, radiation to arm/jaw
• Skin: Pale, cold, diaphoretic
• ECG changes: ST depression (ischemia), ST elevation (infarction/vasospasm), T-wave inversions, LBBB
• Biomarkers: Elevated troponin (I or T) — NSTEMI/STEMI; elevated CK-MB

Non-Cardiogenic Chest Pain

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Q85. Differences in the Clinical Picture of Cardiogenic vs. Non-Cardiogenic Chest Pain

Practical "Red Flags" Indicating Cardiogenic/Dangerous Etiology:

1. Pain with exertion that relieves with rest
2. Diaphoresis + nausea with chest pain
3. ST elevation or depression on ECG
4. Positive troponin
5. BP asymmetry between arms (dissection)
6. Sudden severe tearing pain + hemodynamic instability (dissection/aortic rupture)
7. Shock + raised JVP + muffled heart sounds (cardiac tamponade — Beck's triad)
8. New onset chest pain with tachycardia + hypoxia (PE)

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Summary Index