Discuss the aetiopathogenesis, clinical features, diagnosis and management of pulmonary tuberculosis.

Aetiology

TB is caused by *Mycobacterium tuberculosis*, an aerobic, non-motile, acid-fast bacillus with a waxy mycolic acid cell wall and a slow generation time of 12–24 hours — the reason treatment must be prolonged. India carries the world's largest TB burden; it is a notifiable disease, treated free under the National Tuberculosis Elimination Programme (NTEP).

Transmission: airborne droplet nuclei (1–5 µm) from a person with sputum smear-positive pulmonary disease. Risk depends on infectiousness of the source, proximity, duration of contact and ventilation — which is why crowded, poorly ventilated housing drives transmission.

Risk factors: HIV (the strongest — raising lifetime risk from 10% to 10% per YEAR), diabetes mellitus (triples the risk; highly prevalent in India), malnutrition, smoking, alcohol, silicosis, chronic kidney disease, anti-TNF therapy and corticosteroids, malignancy, transplantation, overcrowding and poverty.

Pathogenesis

Primary infection:

1. Inhaled bacilli reach alveoli, usually mid or lower zones (best ventilated), and are ingested by alveolar macrophages

2. The bacillus blocks phagosome–lysosome fusion, allowing intracellular survival — the central immune evasion mechanism

3. Spread to hilar nodes: the subpleural GHON FOCUS plus draining nodes = the GHON (PRIMARY) COMPLEX

4. At 2–8 weeks, cell-mediated immunity develops: CD4+ Th1 cells release IFN-gamma, activating macrophages to form epithelioid and Langhans giant cells — the CASEATING GRANULOMA

5. Outcomes: ~90% contained, healing with fibrosis and calcification (Ranke complex) leaving LATENT TB INFECTION; ~10% progress — immediately (progressive primary TB, in children and the immunosuppressed) or later

Post-primary (reactivation) TB occurs as immunity wanes, and characteristically affects the APICAL AND POSTERIOR SEGMENTS OF THE UPPER LOBES, where oxygen tension is highest for this obligate aerobe. Liquefaction of caseum discharging into a bronchus produces a CAVITY — the hallmark of post-primary disease, containing enormous bacillary loads and making the patient highly infectious.

Clinical Features

Constitutional: low-grade fever with EVENING RISE and night sweats, weight loss and anorexia, fatigue.

Respiratory:

• COUGH FOR MORE THAN 2 WEEKS — the cardinal symptom and the basis of case-finding
• HAEMOPTYSIS — from ulcerated vessels or a Rasmussen aneurysm; TB remains the commonest cause of haemoptysis in India
• Pleuritic chest pain; breathlessness in extensive disease
• Signs may be minimal despite extensive radiological disease — a classic feature; look for post-tussive apical crackles, bronchial breathing, and signs of effusion or fibrosis

In HIV coinfection the presentation is atypical: less cavitation, more lower zone and miliary disease, more lymphadenopathy and extrapulmonary involvement, and frequently smear-negative — a normal-looking film never excludes TB in an HIV-positive patient.

Complications: massive haemoptysis, pneumothorax, pleural effusion and empyema, bronchiectasis and destroyed lung, aspergilloma in a healed cavity, cor pulmonale, laryngeal TB (highly infectious), amyloidosis, and post-TB obstructive airway disease.

Diagnosis

1. Bacteriological confirmation — the priority

• CBNAAT (Xpert MTB/RIF Ultra) — the recommended FIRST test for all presumptive TB in India: detects *M. tuberculosis* and rifampicin resistance within about 2 hours, far more sensitive than smear
• Sputum smear microscopy (ZN or fluorescence) — requires 5,000–10,000 bacilli/mL; sensitivity only 50–60%
• Culture — the gold standard: liquid (MGIT) 10–14 days, solid LJ 4–8 weeks; provides drug susceptibility testing
• Line probe assay for rapid resistance detection
• UNIVERSAL DRUG SUSCEPTIBILITY TESTING is programme policy — every patient should have rifampicin resistance status determined
• Where sputum is unobtainable: induced sputum, gastric aspirate (children), bronchoalveolar lavage

2. Radiology: chest X-ray — upper lobe infiltrates with CAVITATION, fibrosis, volume loss, calcified nodes; MILIARY TB — uniform 1–2 mm "millet seed" nodules; effusion. CT for early disease, "tree-in-bud" nodularity and complications.

3. Tests of INFECTION, not of disease: Mantoux and IGRA detect immune sensitisation — they indicate latent infection and cannot distinguish latent from active disease. Both may be falsely negative in miliary TB, HIV, severe malnutrition and immunosuppression.

4. Supporting: CBC, raised ESR, HIV testing in every patient, blood glucose (bidirectional TB–diabetes screening is national policy), baseline liver and renal function, and pleural fluid ADA where there is an effusion.

Management

• Multiple drugs, adequate dose, adequate duration, taken regularly — fixed-dose combinations by weight band, free under NTEP
• Intensive phase with four drugs (isoniazid, rifampicin, pyrazinamide, ethambutol), then a continuation phase, with adherence support and follow-up sputum examination
• Pyridoxine with isoniazid; nutritional support (India's programme provides direct benefit transfer)
• Monitor for drug-induced hepatitis — the most important adverse effect
• Drug-resistant TB — managed with all-oral regimens built around bedaquiline, linezolid and fluoroquinolones (see the antitubercular therapy answer in Infectious Diseases)

Public health: NOTIFY every case (mandatory for public and private practitioners); contact screening and TB preventive therapy for eligible contacts and people with HIV; airborne infection control; BCG at birth (protects against disseminated and meningeal TB in children); and action on diabetes, undernutrition, smoking and indoor air pollution.