Paper I
Question
Primary tuberculosis – morphology and pathogenesis
Answer
Pathogenesis
- Occurs in a previously unexposed (non-sensitized) individual, typically in childhood, following inhalation of Mycobacterium tuberculosis
- Bacilli are phagocytosed by alveolar macrophages, which initially fail to kill the organism due to its resistant cell wall (mycolic acids inhibiting phagolysosome fusion)
- Over 2–4 weeks, a cell-mediated (Th1) immune response develops, with sensitized T cells activating macrophages via IFN-γ, forming granulomas that control (though usually do not completely eliminate) the infection
- Some bacilli may disseminate via lymphatics to regional (hilar) lymph nodes before the immune response is established
Morphology
- Ghon focus: A single, 1–1.5 cm grey-white area of caseous necrosis, typically located in the periphery of the lung, just below the pleura, usually in the lower part of the upper lobe or upper part of the lower lobe (site of highest airflow)
- Ghon complex: The combination of the Ghon focus plus caseous necrosis in the draining hilar/mediastinal lymph nodes
- Microscopically, both the Ghon focus and involved lymph nodes show classic caseating granulomas — epithelioid macrophages, Langhans giant cells, a peripheral lymphocytic cuff, and central caseous necrosis
Outcomes
- In the majority of immunocompetent individuals, the primary complex heals by fibrosis and calcification (visible radiologically), and viable bacilli may persist dormant within the scar for years (latent infection, risk of later reactivation)
- Progressive primary tuberculosis: In malnourished/immunocompromised individuals, the primary lesion may progress directly to active, symptomatic disease
- Miliary tuberculosis: Haematogenous dissemination from the primary complex can produce widespread small granulomas across multiple organs