Pathophysiology
Clinical meaning
M. tuberculosis is an aerobic, slow-growing acid-fast bacillus that establishes infection primarily in the lungs. After inhalation, bacilli are phagocytosed by alveolar macrophages but resist intracellular killing by inhibiting phagosome-lysosome fusion. Cell-mediated immunity (Th1 response) is activated after 2-8 weeks, producing granulomas that contain but do not eliminate infection. The Ghon complex (primary lung focus + draining lymph node) represents contained primary infection. Latent TB infection (LTBI) harbors dormant bacilli within granulomas โ 5-10% lifetime risk of reactivation, increased to 5-15% per year in HIV with CD4 < 200. Active TB occurs when immune surveillance fails. Cavitary disease develops in the upper lobes (highest oxygen tension promotes bacillary growth), producing cough with hemoptysis, weight loss, night sweats, and high bacillary load (infectious). Drug resistance arises from spontaneous chromosomal mutations; combination therapy with RIPE prevents selection of resistant mutants.