Pulmonary Tuberculosis Tuberculosis Infectious disease caused by bacteria Genus Mycobacterium Most common species Mycobacterium tuberculosis Commonly

affect the Lungs Can also involve almost any organ of the body Causal organisms of Tuberculosis Acid Fast Bacilli (AFB) (waxy cell wall c/o mycolic acid) Genus Mycobacterium Species y Mycobacterium tuberculosis y Mycobacterium bovis y Mycobacterium avium (avium, hominis, paratuberculosis) y Mycobacterium intracellulare Diagnosis of Tuberculosis History Physical Findings Radiological Pathological Identification of AFB in smear Culture of tubercle bacilli Identification of M. tuberculosis DNA by PCR Pathogenesis Infection by Mycobacterium tuberculosis Bacilli enter into macrophages Antigenic peptide presented to CD4 T cell by macrophages via interaction b/t Class II MHC & CD4 T cell Cytokines production (IFN- & TNF) Delayed hypersensitivity Reaction Granuloma Cell mediated immunity Activated macrophage bactericidal activity Pulmonary TB Mycobacterium tuberculosis Typical tuberculosis

Mycobacterium avium intracellulare complex (MAC) Atypical tuberculosis

Portal of Entry Inhalation of infected aerosols/ droplets Ingestion of infected sputum/ contaminated milk (GI Tuberculosis) Direct penetration through abraded skin (Skin Tuberculosis) 2 Types of Pulmonary TB Primary TB Form of disease that develops in a previously unexposed & unsensitized person

Source of organism y Exogenous

Secondary TB Pattern of disease that arise in a previously sensitized host Reinfection of dormant primary lesions when host resistance is weakened Source of organism y Endogenous y Exogenous

Virulence of organism Introduction of a delayed hypersensitivity reaction (type IV) Development of cell mediated immunity & tissue destruction Virulence of organism Ability to escape killing by macrophages after phagocytosis Glycolipid in bacterial cell wall lipoarabinomannan (LAM) Cord factor, Heat shock protein Sulfatides prevent fusion of phagosomes (comtaining organism) to lysosomes Events occurring Within 3 weeks Lipoaraninomannan (glycolipid in bacterial cell wall) resist endocytosis by macrophages Bacilli enter macrophages (1° cells to be infected) Bacilli proliferate (by blocking fusion of phagosome & lysosome) Bacteremia (most patients asymptomatic or mild flu-like illness) After 3 weeks Macrophages (1° cell infected by organism) present bacterial Ag to TH1 cell with class II MHC IL-12 produced by Ag presenting cells differentiate TH 1 cell TH1 cell IFNIFN- activate macrophages with acid environment Activated macrophages TNF recruits monocytes epitheloid granuloma

Development of resistance to organism is accompanied by +ve tuberculin test

Pulmonary TB Primary Sites of Primary Tuberculosis Lung SI Oropharynx Skin 1° Focus 1° Focus 1° Focus 1° Focus Regional l/n Mesenteric l/n Regional l/n Regional l/n Ghon complex Tabes Collar stud cold Lupus vulgaris mesentrica abscess Gross Morphology At Lower Part of Upper Lobe or Upper Part of Lower Lobe, close to pleura Ghon Focus 1 1.5cm area of gray white inflammatory consolidation Caseous Necrosis (centre of focus) Ghon Complex Combination of peripheral lung lesion & regional l/n enlargement Secondary (Post primary TB, Reinfected TB, Reactivated TB) Phase of TB infection that arise in a previously sensitized individual Source of infection Endogenous (reactivation of asymptomatic previous Primary TB due to host resistance)

Ghon complex Subpleural Ghon focus Hilar l/n granuloma Histologic Morphology Granulomatous inflammatory reaction y Caseating tubercles y Non-caseating tubercles Granuloma/ Tubercles y Enclosed within fibroblastic rim y Punctuated by epitheloid cells, lymphocytes, plasma cells, multinucleated giant cells with Langhan s giant cell No granuloma in immunocompromised patients

Gross Morphology Apex of upper lobes (of 1 or both lungs) ( O2 tension promotes growth of bacteria) Initial lesion small focus of consolidation (< 2cm diameter within 1 2 cm of apical pleura) Firm, Gray-white to Yellow, Central caseation (yellowish cheesy appearance) Histologic Morphology Characteristic coalescent tubercles (granulomas) with central caseation Histology of granuloma (same as Primary TB)

Granuloma

Multiple caseating granuloma

Pulmonary TB Confined to upper lobe (apex) Cheesy caseous necrosis Cavity formation

Pulmonary TB Extensive caseation Granulomas involve a larger bronchus Necrotic center drain out (leave behind a cavity) Cavitation y Typical for large granulomas with TB y More common in Upper Lobes

Langhan s giant cell

Caseation in granuloma

Acid Fast Bacilli y Red color rod shaped y Ziehl-Neelsen stain Outcome Most cases does not progress Ghon Focus shrinkage, fibrosis, dystrophic calcification, fibrous scarring, puckering of adjacent pleura Tracheobronchial node replaced by fibrocalcified scarring Infecting organism not totally eradicated, may remain viable & reactivated If progress erosion of bronchial tree, Miliary TB

Pulmonary TB Granulomas have areas of caseous necrosis (extensive granulomatous disease) Secondary TB multiple caseating granulomas (upper lobes)

Old, Healed Calcified tuberculous lesion in lung

Outcome of Apical Pulmonary Lesion Apical fibrocalcific arrested TB (with adequate treatment) Erosion into y Bronchus (cavitation lined by caseous material) y Blood vessels (hemoptysis) Miliary Tuberculosis y If inadequate treatment y May spread via airways, lymphatic, vascular y Lymphatic Right Heart Lung Small foci of consolidation scattered through lung parenchyma like foci of millet seeds (military pulmonary TB) Systemic military TB y Infected foci from lung systemic arterial circulation y Liver, BM, Spleen, Adrenals, Meninges, Kidneys, Fallopian tubes, Epididymis Pulmonary lesion erode to pleura y Pleural effusion, Tuberculous empyema y Obliterative fibrous pleuritis Pulmonary lesion erode bronchi y Endobronchial, Endotracheal, Laryngeal tuberculosis Infected sputum is swallowed y Organism trapped in mucosal lymphoid tissue y Ulceration of mucosa (particularly ileum) y Intestinal tuberculosis Isolated organ TB y By haematogenous spread (Meninges, Kidneys, Adrenals, Bones, Fallopian tubes) Tuberculous lymphadenitis y Most frequent form of extra-pulmonary TB y Usually in cervical region (scrofula) Systemic secondary amyloidosis Scar cancer Miliary TB

Mycobacterium Avium-Intracellulare Complex MAC y Mycobacterium avium y Mycobacterium intracellulare Uncommon except in y AIDS y Immunocompromised patients Morphology Hallmark abundant AFB within macrophages Granuloma, Lymphocytes, Tissue destructions are rare Widely disseminated throughout mononuclear cellular system (cause enlargement of LN, Liver, Spleen)

Mycobacterium avium intracellulare in macrophages/ histiocytes of l/n

Miliary TB (Lung) Multiple small foci of granuloma Resemble millet seeds (sago seed)

Miliary TB (Spleen) Gray-white granuloma