The pathogenesis of Tuberculosis

What is TB?

Etiology Tuberculosis is caused by Mycobacterium tuberculosis. TB is spread from person to person through the air. When a person with infectious TB disease (TB that can be spread) coughs or sneezes, tiny particles containing M. tuberculosis may be expelled into the air. These particles, called airborne droplet nuclei. These droplets can remain airborne for minutes to hours after expectoration.

Pathophysiology

Once inhaled, the infectious droplets settle throughout the airways Once inhaled, the infectious droplets settle throughout the airways. The majority of the bacilli are trapped in the upper parts of the airways where the mucus-secreting goblet cells exist. The mucus produced catches foreign substances, and the cilia on the surface of the cells constantly beat the mucus and its entrapped particles upward for removal. This system provides the body with an initial physical defense that prevents infection in most persons exposed to tuberculosis.

if Bacteria in droplets bypass the mucociliary system and reach the alveoli  will be quickly surrounded and engulfed by alveolar macrophages. After being ingested by macrophages the mycobacteria continue to multiply  macrophages produce proteolytic enzymes and cytokines by in an attempt to degrade the bacteria  Released cytokines attract T lymphocytes to the site, the cells that constitute cell-mediated immunity  granuloma formation macrophages present mycobacterial antigens on their surface to the T cells initial immune process continues for 2 to 12 weeks  microorganisms continue to grow until they reach sufficient numbers to fully elicit the cell-mediated immune response, leading to delayed hypersensitivity, which can be detected by the tuberculin (Mantoux) test weight loss : due to  lack of appetite and the altered metabolism associated with the inflammatory and immune responses  Hemoptysis : can be due to destruction of a vessel located in the wall of the cavity, the rupture of a dilated vessel in a cavity, or the formation of an aspergilloma in an old cavity. ( aspergilloma, also known as a mycetoma or fungus ball, is a clump of fungus which exists in a body cavity )

granuloma

Granuloma : Granuloma : A central caseation necrosis An inner cellular zone of epithelioid macrophages and Langhans giant cells admixed with lymphocytes An outer cellular zone of lymphocytes, A rim of fibrosis (in healing lesions)   Granuloma : In granulomas, immune system cells collect in order to destroy the invading pathogen. Sometimes the granulomas can become abscesses that lead to lung cavitation.  a lesion seen in the lung that is caused by tuberculosis. The lesions consist of a calcified focus of infection and an associated lymph node

If the bacilli enter the body, The bacilli have 4 potential fates: killed by the immune system multiply and cause primary TB they may become dormant and remain asymptomatic  (latent tuberculosis infection LTBI) proliferate after a latency period (reactivation disease) Patients with LTBI cannot spread TB. Undergo fibrosis and calcification, successfully controlling the infection  . Microorganisms persist in the necrotic material for years if the immune system later becomes compromised,  disease can be reactivated. * If immunosuppressed  Primary Progressive Miliary TB

Types of TB: Primary Latent TB infection Secondary After 1st exposure dormant bacilli in the body After 2nd infection or reactivation Asymptomatic or minor illness asymptomatic symptomatic Can be multi organ involvement - Usually localized in apices of lungs

Sites of TB: Some e.g Intra pulmonary TB Extra pulmonary TB pulmonary system is the most common location . Within alveolar macrophages in subpleural regions of the lung (may serve as a reactivation site; ALSO may coexist with pulmonary reactivation.) Some e.g CNS, tubercular meningitis Lymphatic TB Bloodstream  disseminated or miliary TB  multiorgan involvement

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