pulmmonary tuberculosis
DESCRIPTION
TRANSCRIPT
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Pulmmonary Tuberculosis
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Causative agent (P.T.)
• : Mycobacterium tuberculosis
• Was an important cause of death prior the antibiotic era
• Currently its importance rising again due to - AIDS
• - multidrug resistance
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Etiology and Pathogenesis (PT)
• M. tuberculosis: transmitted by infective droplets
• M. bovis: milk diseased cow
• M. avium : avirulent to normal subjects
• M. intracellulare: disseminated infection in 15-24% AIDS patients
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Pathogenesis
• Mycobacterium - has no known exotoxin, endotoxin, proteolytic enzyme
• Pathogenecity of M. tubeculosa is related to ability to:
1. escape killing by macrophages
2. induce delayed hypersensitivity
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Pathogenesis
• Induction of delayed hypersensitivity by P.T. attributed to several components of M. tubersulosa cell wall:
1. cord factor: surface glycolipid, facilitates cultured mycobacter to grow in cords.Pathogenic mycobacter: cord factor positive, Non-pathogenic: cord factor negative:
Injection purified cord factor in mice granuloma formation
2. Lipoarabimannam (LAM): heteropolysaccharide similar to endotoxin in gram negative bacteria.
a.
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Pathogenesis
LAM a. - inhibits macrophage activation by interferon-– b. induces macrophages to secrete TNF-
(fever, weight loss, tissue damage)
c. induces macrophages to secrete IL-10 suppresses mycobacteria-nduced T-cell proliferation)
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Pathogenesis
• iii. Complement -activated on surface of mycobacteria may opsonise mycobacteria macrophage complement receptor (CR3) (Mac-1 integrin) without triggering the respiratory burst necessary to kill the bacteria.
iv. Highly immunogenic Tuberculous heat-shock protein is similar to human autoimmune reactions induced by mycobacteria.
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Pathogenesis
• Mycobacter resides in phagosomes which are not acidified into lysosomes.
• Inhibition of acidification is associated with urease secreted by mycobacter.
• The development of cell-mediated, type IV, hypersensitivity to the mycobacteria explains the organism’s destructiveness in tissues and also the emergence of resistance the mycroorganism.
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Pathogenesis
• Initial exposure to the M. tuberculosa no-specific inflammatory reaction
• After 2-3 weeks: reaction changes to granulomatous, center caseates
• The patteren of host response depends on whether the infection is a primary exposure (primary) or it is in a sensitized host (secondary).
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Primary Tuberculosis
• Disease acquired from initial exposure to M. tuberculosa
• Inhaled microorganisms multiply in alveoli, alveolar macrophages can not readily kill the bacteria.
• Naïve macrophages can not kill mycobacteria multiply, lyse the cell infect other macrophages, spread by the blood stream.
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Pathogenesis
• After a few weeks (2-3) development T-cell-mediated immunity.
• Mycobacteria-activated T-cells react with macrophages through following ways:
• 1. CD4+ helper T-cells secrete interferon-• interferon- activates macrophages
killing of intracellular mycobacteria2. mycobacter through intermediate nitrogen
species. epithelioid granuloma formation
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Pathogenesis
2. CD8+ suppressor T cells lyse macrophages infected with mycobacter through Fas-independent pathway.
3. CD4-, CD8- (double-negative) T –cells lyse macrophages by Fas-dependent pathway, without killing mycobacteria.
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Pathogenesis primary tuberculosis
• Mycobacteria can not grow in acidic extracellular environment
• infection is controlled.
• Fate of primary tuberculosis: calcification
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The Ghon Complex:
• first lesion of primary tuberculosis• G.C. consists of - peripheral
parenchymal granuloma (often located in lower lobes) (Ghon nodule)
• a prominent infected mediastinal (hilar) lymphnode
• lymphangitis joining nodule to hilar L. node
Grossly: Ghon nodule: 1-2 cm
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Pathogenesis
• Histo: Granuloma, central caseous necrosis.• Clinically: Usualy assymptomatic, localized
lesions healing (`~90% cases).
• In occasional cases, however, primary tb• - spreads to other parts of the
lung (progressive primary TB)common in children, immunocompromised adults
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Pathogenesis
• Gross: primary lesion enlarges to lesions ~6 cm cavities occupying most of lower lobes
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Secondary TB
• This stage results from: • - reactivation of primary pulmonary TB• new infection in a previously sensitized
individual• This stage results from: • - reactivation of primary pulmonary TB• new infection in a previously sensitized
individual
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• new infection in a previously sensitized individual
• Initial response to M. tuberculosa is different in patients with secondary TB.
• Infection latent period cellular immune response formation of many granulomas , extensive tissue necrosis
• Apical and posterior segments upper lobes most commonly affected
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Histology tuberculous granuloma
• Gross: Diffuse fibrotic lesions, with caseative necrosis
• heal and calcify
• erosion of bronchidrainage caseous material and infectious agents tuberculous cavity
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Tuberculous Cavities
• Size: 1- 10 cm
• Location: apices of upper lobes
• Wall of cavity consists fibrotic material with granulation tissue
• Cavity: caseous material with bacilli
• On healing: fibrosis with calcifications
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Complications of secondary tuberculosis
1. milliary TB: presence of multiple, small (size of millet seeds)
• granulomas in many organs.• Spread usually haematogenous,
mostly from primary pulmonary Tb or from other sites
2.Hemopthysis: Bleeding from eroded blood vessel in cavity
Drowning into one’s own blood.
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Complication tuberculous granuloma
3. Bronchopleural fistula: rupture of subpleural cavity pleural
• space tuberculous empyema pneumothorax
4. Intestinal tuberculosis: follows swallowing of tuberculous
• material
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M.tuberculosis and M. avium intracellulare lesions in AIDS
• Mycobacterial infection in AIDS can take three forms depending on degree of immunosuppression
• 1. In developing countries where M. tuberculosis is frequent: HIV infected individuals have primary and secondary M. tuberculosis infection with the usual well formed granulomas, composed of epithelioid cells, Langerhan’s giant cells and lymphocytes. In these granulomas acid-fast bacilli are few and difficult to find.
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tuberculosis in AIDS
2. When HIV patients develop AIDS and are moderately immunocompressed (< 200 CD4+ T helper lymphocytes/ml): infection is mostly from reactivation/re-infection. Because mycobacteria infect T-cells and macrophages, defects in the host immune response to M. tuberculosis may be;
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tuberculosis in AIDS
a. secondary to the failure of CD4 helper T-lymphocytes to secrete lymphokines that activate macrophages to kill bacteria
b. failure of infected helper T-lymphocytes to secrete and mycobacteria infected macrophages to respond to lymphokines.
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tuberculosis in AIDS
• The relative increase in number of CD8+ cytotoxic T-lymphocytes to cause macrophage destruction in the M. tuberculosa lesions.
• histologically: granulomas less well formed, are more frequent necrotic, and contain more abundant acid fast bacilli.
• Though sputum is positive for mycobacteria in 31-83% of AIDS patients , only 33% react with PPD.
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tuberculosis in AIDS
• extrapulmonary TB occurs in 70% cases involving LN, blood, CNS, and GIT.
• 3. Opportunistic infection with M. avium intracellulare (occurs in severely immunocompromised patients: < 60 CD+ T-lymphocytes) Most organisms originate from GIT though some from RT
• Infection usually widely disseminated throughout the reticulo-endothelial system enlargement of lymphnodes
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tuberculosis in AIDS
• There is a large number of mycobacteria in the enlarged nodes.
• Granulomas, lymphocytes and tissue destruction are rare