🫁 MBBS Final Year Respiratory System Question Bank

General Respiratory Physiology & Anatomy

EASY (Foundation / 1st-2nd Year Recall)

Key Answer: Normal FEV1/FVC is >0.70 (70%). A reduced ratio indicates obstructive lung disease (e.g., COPD, asthma). In restrictive disease, both FEV1 and FVC fall but the ratio remains normal.

Key Answer: Primary inspiration - diaphragm, external intercostals. Accessory - scalene, sternocleidomastoid. Expiration is usually passive (elastic recoil); active expiration uses internal intercostals and abdominals.

Key Answer: TV ~500 mL (normal resting breath). RV ~1200 mL (cannot be expelled). FRC = ERV + RV = volume in lungs at end of normal expiration.

Key Answer: V/Q is ventilation-perfusion ratio, normally ~0.8. Apex: V/Q >1 (high, well-ventilated, poorly perfused - physiologic dead space). Base: V/Q <1 (low, overperfused relative to ventilation - prone to shunting).

Key Answer: Surfactant layer, alveolar epithelium (type I pneumocytes), basement membrane, interstitial space, capillary basement membrane, capillary endothelium.

MODERATE (Standard MBBS / Clinical Application)

Anatomical dead space = volume of conducting airways (~150 mL) that do not participate in gas exchange. Physiological dead space = anatomical + alveolar dead space (poorly perfused but ventilated alveoli). Normally these are equal; they diverge in disease states like COPD and pulmonary embolism.

PAO₂ = FiO₂ × (Patm - PH₂O) - PaCO₂/R, where R=0.8. Normal A-a gradient: <15 mmHg in young adults, increases with age. Elevated in V/Q mismatch, shunt, and diffusion limitation.

Right shift (reduced O₂ affinity, increased O₂ delivery to tissues): increased CO₂, decreased pH (Bohr effect), increased temperature, increased 2,3-DPG. Left shift (increased O₂ affinity): fetal Hb, CO poisoning, alkalosis, hypothermia.

P = 2T/r. Smaller alveoli have higher pressure and tend to collapse into larger ones. Surfactant (dipalmitoylphosphatidylcholine, produced by type II pneumocytes) reduces surface tension, especially in small alveoli, stabilizing them and preventing atelectasis.

DIFFICULT (Short/Long Answer Exam Level)

In systemic circulation, hypoxia causes vasodilation to increase blood flow. In pulmonary circulation, hypoxia causes vasoconstriction (HPV), redirecting blood away from poorly ventilated alveoli to better-ventilated areas, thereby optimizing V/Q matching. Mechanism involves inhibition of K⁺ channels in pulmonary arterial smooth muscle, leading to membrane depolarization, Ca²⁺ influx, and vasoconstriction. Chronic generalized HPV (as in COPD) leads to pulmonary hypertension and cor pulmonale.

True shunt - blood bypasses ventilated alveoli entirely (consolidated lung, intracardiac shunt). Unlike V/Q mismatch, shunting does NOT respond to supplemental oxygen because the shunted blood is never exposed to the enriched alveolar gas. This is the basis of the 100% O₂ shunt test.

MIGET (developed by Peter Wagner, 1974) measures how 6 inert gases of different solubilities are eliminated from blood, allowing calculation of the distribution of V/Q ratios across nearly 50 compartments (vs. the older 3-compartment Riley model of shunt/ideal/dead space). It can distinguish true shunt from low V/Q units - a distinction the Riley model cannot make - and can identify diffusion limitation as a separate cause of hypoxemia. (Fishman's Pulmonary, 2-Volume Set)

COPD Questions

EASY

COPD is a chronic, progressive obstructive lung disease characterized by functional outflow obstruction due to loss of elastic tissue in alveolar walls. Main subtypes: Emphysema (pink puffer) and Chronic bronchitis (blue bloater). They frequently coexist. (Robbins Pathology)

Persistent productive cough for at least 3 consecutive months in at least 2 consecutive years, without another identifiable cause. (Robbins Pathology)

• Centriacinar (centrilobular): Most common; affects respiratory bronchioles in upper lobes; strongly associated with cigarette smoking
• Panacinar (panlobular): Affects the entire acinus; associated with α1-antitrypsin (AAT) deficiency; lower lobe predominance (Robbins Pathology)

MODERATE

Cigarette smoke recruits neutrophils and macrophages to the lung, which release elastase and other proteases (e.g., MMP-9). These proteases destroy the elastic support structures of alveolar walls. Normally, α1-antitrypsin (AAT) inhibits elastase. Smoking also oxidatively inactivates AAT, tipping the balance toward protease activity. The net result is progressive alveolar wall destruction, enlargement of air spaces distal to terminal bronchioles, and loss of radial traction on airways - causing dynamic air trapping and obstructive physiology. (Robbins Pathology)

Post-bronchodilator FEV1/FVC < 0.70 confirms fixed airflow limitation = COPD. GOLD staging (Global Initiative for Chronic Obstructive Lung Disease) grades severity by FEV1 % predicted: GOLD 1 (mild, ≥80%), GOLD 2 (moderate, 50-79%), GOLD 3 (severe, 30-49%), GOLD 4 (very severe, <30%).

An acute event with worsening of respiratory symptoms beyond normal day-to-day variation requiring a change in treatment. Most common triggers: respiratory tract infections (viral > bacterial - H. influenzae, S. pneumoniae, M. catarrhalis), air pollution, non-compliance with medications.

HARD

In chronic CO₂ retainers, the central chemoreceptors become blunted to hypercapnia. The hypoxic drive via peripheral chemoreceptors (carotid/aortic bodies) becomes the primary stimulus to breathe. Administering high-flow O₂ abolishes this hypoxic drive, causing hypoventilation and worsening CO₂ retention (hypercapnic respiratory failure). Additionally, the Haldane effect - O₂ displacing CO₂ from haemoglobin - raises PaCO₂. Target SpO₂ in COPD: 88-92%, using controlled low-flow O₂ (24-28% Venturi mask).

Chronic hypoxemia stimulates renal production of erythropoietin (EPO), which drives red cell production. Secondary polycythemia increases blood viscosity, raises the risk of thrombosis (DVT, PE, stroke), and contributes to pulmonary hypertension. Hematocrit >55% warrants consideration of phlebotomy.

Chronic hypoxia triggers hypoxic pulmonary vasoconstriction and vascular remodeling (smooth muscle hypertrophy, intimal fibrosis in pulmonary arterioles). This chronically elevated pulmonary vascular resistance imposes a pressure overload on the right ventricle (RV). RV hypertrophies initially (compensation), then dilates and fails. Signs: raised JVP, RV heave, loud P2, tricuspid regurgitation, peripheral edema, hepatomegaly. ECG shows right axis deviation, P pulmonale, RV strain (tall R in V1, deep S in V5/V6).

PNEUMONIA Questions

EASY

Pneumonia acquired outside of hospital (or within 48 hours of admission). Features: fever, productive cough (rusty sputum in pneumococcal), pleuritic chest pain, dyspnea, tachypnea, tachycardia. Examination: dullness to percussion, bronchial breath sounds, increased tactile fremitus, egophony (E→A change).

Streptococcus pneumoniae - the classic lobar pneumonia organism. Other important causes: Haemophilus influenzae (COPD patients), Mycoplasma pneumoniae (atypical, young adults), Legionella pneumophila (atypical, air conditioning), Staphylococcus aureus (post-influenza).

Homogeneous opacification of an entire lobe with an air bronchogram sign (visible air in bronchi against a consolidated background). The air bronchogram sign indicates alveolar filling (consolidation), not collapse.

MODERATE

1. Congestion (Day 1-2): Vascular engorgement, fluid exudate in alveoli, few bacteria
2. Red hepatization (Day 2-4): Alveoli filled with RBCs, fibrin, neutrophils - lung firm, liver-like, red
3. Grey hepatization (Day 4-8): RBCs lyse; fibrin, neutrophils, macrophages persist - grey appearance
4. Resolution (Day 8+): Enzymatic digestion of exudate by macrophages, normal lung architecture restored

HARD

In severe pneumonia, consolidated alveoli are perfused but not ventilated (true intrapulmonary shunt). As severity increases, both shunt fraction and low-V/Q blood flow increase significantly (shunt 22%, low-V/Q 11% in mechanically ventilated severe CAP vs. shunt 7.5%, low-V/Q 4% in mild CAP). Supplemental oxygen helps only the low-V/Q component, not the true shunt. In pleural effusion, hypoxemia is generally mild (shunt ~7%), and removal of 700 mL does not reliably improve PaO₂ - the low-V/Q contribution may actually increase transiently. (Fishman's Pulmonary)

HCAP (now largely subsumed into Hospital-Acquired Pneumonia/VAP categories in newer guidelines) includes pneumonia in patients from nursing homes, on dialysis, or with recent hospitalization. These patients are colonized with gram-negatives (Pseudomonas, Klebsiella, Acinetobacter) and MRSA - organisms rarely responsible for true CAP. Treatment must cover these resistant pathogens.

• Wrong organism (atypical, resistant organism, TB, fungal)
• Wrong diagnosis (pulmonary infarction, organizing pneumonia, lung cancer with post-obstructive pneumonia)
• Parapneumonic effusion or empyema (requires drainage)
• Lung abscess formation
• Immune compromise (HIV, DM, lymphoma)
• Non-infectious mimics: Eosinophilic pneumonia, cryptogenic organizing pneumonia (COP)

TUBERCULOSIS (TB) Questions

EASY

Mycobacterium tuberculosis (human type). Acid-fast bacillus - identified by Ziehl-Neelsen (ZN) stain (carbol fuchsin retains red color despite acid-alcohol decolorization, due to high mycolic acid content in cell wall). Also Auramine-rhodamine fluorescence stain (more sensitive for screening).

HRZE - Isoniazid (H), Rifampicin (R), Pyrazinamide (Z), Ethambutol (E)

• Intensive phase: 2 months HRZE
• Continuation phase: 4 months HR Key mnemonic: "2 HRZE / 4 HR"

Intradermal injection of 0.1 mL purified protein derivative (PPD = 5 TU) into volar forearm. Read at 48-72 hours. Positive if induration (not erythema) is:

• ≥5 mm: HIV+, recent TB contact, radiological evidence
• ≥10 mm: Healthcare workers, recent immigrants, IV drug users, diabetes, silicosis
• ≥15 mm: Low-risk individuals

MODERATE

Ghon focus: Peripheral subpleural caseous granuloma (usually lower lobe, near pleura). Ghon complex: Ghon focus + ipsilateral hilar/paratracheal lymph node caseation + lymphangitis connecting them. Ranke complex: Calcified Ghon focus + calcified hilar lymph nodes = healed primary TB (seen on CXR as calcified lesions).

1. Cavitation - can harbor aspergilloma (fungal ball)
2. Empyema / bronchopleural fistula
3. Haemoptysis (Rasmussen's aneurysm - erosion of pulmonary artery wall by cavity)
4. Miliary TB - haematogenous dissemination (1-2 mm "millet seed" nodules on CXR)
5. TB meningitis, Pott's spine (vertebral TB), TB pericarditis
6. MDR-TB (resistant to at least H + R); XDR-TB (MDR + fluoroquinolone + injectable resistance)

HARDEST

This is anti-TB drug induced hepatitis - a serious complication. Criteria for stopping drugs: Bilirubin >2 × ULN OR transaminases >3 × ULN with symptoms OR >5 × ULN without symptoms. Management: Stop all hepatotoxic drugs (H, R, Z). Provide supportive care. Once LFTs normalize, sequentially reintroduce: E → H → R → Z (most hepatotoxic last). If unable to tolerate, use hepato-safe regimen: S + E + fluoroquinolone. Involve hepatologist if severe.

MDR-TB: Resistant to at least Isoniazid AND Rifampicin (the two most effective drugs). Pre-XDR-TB (old term) = MDR + resistance to any fluoroquinolone. XDR-TB (2022 WHO new definition): MDR/RR-TB + resistance to any fluoroquinolone + at least one of bedaquiline or linezolid (replacing the older injectable-based definition). This reflects new all-oral regimens. Treatment: BPaL (Bedaquiline + Pretomanid + Linezolid) - TB-PRACTECAL and ZeNix trials.

• CD4 > 200: Similar to immunocompetent (upper lobe cavitary disease)
• CD4 < 200: Atypical presentations - lower lobe, pleural effusion, lymphadenopathy, miliary; CXR may be normal
• Smear may be negative (low bacillary load)
• Immune Reconstitution Inflammatory Syndrome (IRIS): Starting ART causes CD4 recovery which mounts an exaggerated inflammatory response to TB antigens, causing clinical worsening despite treatment. Occurs 2-8 weeks after ART initiation.
• Start TB treatment first, then ART 2-8 weeks later (earlier if CD4 <50)
• Rifampicin is a potent CYP3A4 inducer - lowers levels of many ARVs; use rifabutin or adjust ART regimen (efavirenz preferred)

PLEURAL EFFUSION Questions

EASY

Abnormal accumulation of fluid in the pleural space (normal ~5-15 mL). Two categories:

• Transudate: Imbalance of hydrostatic/oncotic pressures; pleura itself is normal (CHF, nephrotic syndrome, cirrhosis)
• Exudate: Increased pleural capillary permeability or impaired lymphatic drainage; pleura is diseased (pneumonia, TB, malignancy, PE)

• Stony dullness to percussion
• Absent/reduced breath sounds
• Reduced tactile vocal fremitus (TVF) and vocal resonance
• Tracheal deviation away from large effusions
• Bronchial breathing at the upper level of effusion (Skodaic resonance)
• Chest movement reduced on the affected side

MODERATE

An effusion is classified as an exudate if ANY ONE of the following is met:

1. Pleural fluid protein / serum protein > 0.5
2. Pleural fluid LDH / serum LDH > 0.6
3. Pleural fluid LDH > 2/3 of upper limit of normal serum LDH

Sensitivity: ~98% for exudates. Specificity: ~75% (25% of transudates are misclassified as exudates, especially in diuretic-treated CHF). If Light's criteria call an effusion an exudate but clinical context suggests transudate: use the serum-to-pleural fluid albumin gradient - if gradient >1.2 g/dL, it is a transudate. (Fishman's Pulmonary; Symptom to Diagnosis 4e)

Complication of advanced liver disease/cirrhosis affecting 5-10% of patients. Caused by small diaphragmatic defects allowing ascitic fluid to pass into the pleural space. Nearly always transudative. Right-sided in 85%. Managed with: sodium restriction + diuretics (first-line). If refractory: TIPS (transjugular intrahepatic portosystemic shunt, response rate 70-80% but risk of hepatic encephalopathy), VATS diaphragmatic repair, indwelling pleural catheters (bridge to transplant). Serial thoracentesis is palliative only. (Fishman's Pulmonary)

HARDEST

TB pleuritis is a delayed hypersensitivity (Type IV) reaction to mycobacterial antigens in the pleural space - it is not bacterial invasion of the pleura. Therefore, bacillary load is low, making smear-positive rare (<5%). Diagnosis confirmation:

• Pleural fluid ADA >40 U/L (high sensitivity ~90%, specificity ~85% in high-prevalence settings)
• Pleural biopsy (Abrams needle or VATS): caseating granulomas on histology; AFB culture yield 40-80%
• IFN-γ in pleural fluid (elevated)
• LDH elevated, lymphocytes >85%, protein >3g/dL
• Pleural culture alone: positive in only ~25%

Two mechanisms:

1. After thoracentesis, previously atelectatic lung re-expands and is now ventilated but transiently has low perfusion due to loss of HPV compensation - temporarily creating low-V/Q units, actually lowering PaO₂.
2. The pleural effusion itself had compressed underlying lung tissue, paradoxically preserving some V/Q matching; removal breaks this compensation. Studies with MIGET have shown that 30 minutes after removing ~700 mL from effusion patients, PaO₂, A-a gradient, and shunt did not change, but the fraction of blood in low-V/Q units actually increased slightly. (Fishman's Pulmonary)

• Simple parapneumonic: Exudate, pH >7.2, glucose >40, no organisms. Treat the pneumonia - no drainage needed.
• Complicated parapneumonic: pH <7.2, glucose <40, LDH >1000, or positive Gram stain/culture. Must drain (intercostal tube) + antibiotics.
• Empyema: Frank pus in pleural space (frank pus visible OR Gram stain/culture positive). Requires tube thoracostomy; if loculated, use intrapleural fibrinolytics (tPA + DNase) or surgical VATS decortication. REMEMBER: pH is the single most reliable indicator for drainage - pH <7.0 = emergency drainage.

INTEGRATIVE / VIVA LEVEL Questions

Loss of mucociliary clearance, impaired cough reflex, enlarged mucus glands with mucus stasis, altered respiratory epithelium, chronic low-grade inflammation impairing neutrophil function, use of inhaled corticosteroids (dose-dependent risk). Common organisms: H. influenzae, M. catarrhalis, S. pneumoniae, Pseudomonas (severe COPD, GOLD 3-4).

Likely malignant pleural effusion (lung cancer, mesothelioma). Investigation: CXR, CT chest with contrast, thoracentesis with cytology (sensitivity 60-70%), CEA/LDH in fluid. If cytology negative: VATS-guided pleural biopsy (gold standard, sensitivity >95%). Hemorrhagic, exudative effusion with markedly elevated LDH suggests malignancy.

Via rupture of a subpleural caseous focus (Ghon focus or peripheral cavity) into the pleural space, releasing mycobacterial antigens. This triggers a cell-mediated (Type IV) hypersensitivity reaction causing protein-rich lymphocytic exudate. The classic hallmarks: ADA >40 U/L, lymphocyte-predominant, low glucose, positive Mantoux, caseating granulomas on biopsy. Usually self-limiting if treated, but can lead to fibrothorax (trapped lung) if untreated.

Sources consulted: Robbins & Kumar Basic Pathology (Robbins Pathology), Fishman's Pulmonary Diseases and Disorders (2-Volume Set), Murray & Nadel's Textbook of Respiratory Medicine, Harrison's Principles of Internal Medicine 22E (2025), Symptom to Diagnosis 4e, Park's Textbook of Preventive and Social Medicine.

Quick Summary: Exam Strategy Tips

• COPD spirometry: Post-BD FEV1/FVC <0.70 is the defining criterion. GOLD staging uses FEV1 % predicted.
• TB drugs: Remember HRZE side effects - H = neuropathy, R = orange urine + inducer, Z = gout, E = eye (optic neuritis).
• Pleural fluid: Light's criteria - memorize all 3 criteria. ADA >40 = TB till proven otherwise in lymphocytic exudate.
• Pneumonia CURB-65: ≥3 = admit. The two most important predictors of ICU need: RR ≥30 and confusion.
• Cor pulmonale: COPD → chronic HPV → pulmonary hypertension → RV failure. Signs are right-sided heart failure signs.
• High-flow O₂ in COPD: Target SpO₂ 88-92%, NOT 95-100%. This is a classic exam trap and a real clinical danger.