Question
Pathogenesis and laboratory diagnosis of pulmonary tuberculosis.
Answer
Pathogenesis Pulmonary tuberculosis is caused by Mycobacterium tuberculosis, transmitted by inhalation of droplet nuclei. Inhaled bacilli reach the alveoli and are phagocytosed by alveolar macrophages; the organism’s cell-wall lipids (mycolic acid, cord factor) resist intracellular killing, allowing it to survive and multiply within macrophages (a facultative intracellular pathogen). This forms the initial (Ghon) focus, with spread to hilar lymph nodes constituting the primary complex. In most immunocompetent individuals, cell-mediated immunity (a delayed-type hypersensitivity response, detectable by tuberculin conversion in ~4–6 weeks) contains the infection, producing a caseating granuloma with central caseation necrosis surrounded by epithelioid cells, Langhans giant cells, and a lymphocytic cuff — the lesion typically heals by fibrosis/calcification, leaving viable dormant bacilli (latent infection). Reactivation (post-primary/secondary TB) occurs later if immunity wanes (malnutrition, HIV, immunosuppression, old age), typically in the well-aerated apical/posterior segments of the upper lobes, progressing to cavitation, caseous pneumonia, and potential haematogenous/lymphatic dissemination (miliary TB).
Laboratory diagnosis
- Sputum smear microscopy — Ziehl-Neelsen staining for acid-fast bacilli (at least two samples); fluorescence (auramine-rhodamine) microscopy is more sensitive for screening.
- Culture — Lowenstein-Jensen medium (gold standard, slow, 2–8 weeks); liquid culture (BACTEC MGIT) is faster and permits drug-susceptibility testing.
- Molecular tests — CBNAAT/GeneXpert MTB-RIF for rapid detection and rifampicin-resistance screening; line-probe assays.
- Tuberculin skin test (Mantoux) — indicates infection/exposure, not necessarily active disease.
- Interferon-gamma release assays (IGRA) — more specific than TST, unaffected by BCG vaccination status.
- Radiology — chest X-ray (apical infiltrates, cavitation, fibrosis).
- Histopathology — caseating epithelioid granuloma with Langhans giant cells on biopsy, when tissue is available.