Anatomical-physiological-chemical mechanisms by which post-primary TB is more common in the upper lobes of the lungs. Based on differences in the physiological-chemical properties between the upper lobes and lower lobes, primary Mtb lesions located in the upper lobes, while fewer than that in the lower lobes, are more likely to reactivate. (A) Diagram showing that primary TB is located mostly in the lower lung zone (green circular structure that represents a calcified granuloma – Ghon complex). This distribution of primary TB is due to greater (3.4X) ventilation in the lower lobes than the upper lobes of an upright human. (B) In the upright human, there is decreased lung perfusion pressure due to lower pulmonary artery pressure in the upper lobes. This decreased perfusion will result in decreased influx of immune cells and soluble mediators to the upper lobes in the upright position. (C) Lymph formation and flow are also significantly decreased in the upper lobes, resulting in increased accumulation of mycobacteria and antigens in the upper lobes and contributing to increased hypersensitivity reactions and lung damage. pH in the upper lobes is more alkalotic which induces glycolysis and, in turn, increases autophagic clearance of Mtb by the macrophages. (D) The PAO2 is also significantly greater in the upper lobes than the lower lobes, which favors Mtb growth. The mechanical stress and alveolar size of the upper lobes are also greater (by 40X and 4X, respectively) than the lower lobes, predisposing this area to the development of cavities, especially with large inspiratory efforts. Mtb, Mycobacterium tuberculosis; PAO2, partial pressure of alveolar oxygen; TB, tuberculosis.
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