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MYCOBACTERIUM TUBERCULOSIS. Introduction. Chronic granulomatous inflammation. Granuloma -granule like lesion Epithelioid cells,giant cells,necrosis & fibrosis. Factors favouring -poorly digestible irritant -cell mediated immunity. Causative organism.
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Introduction • Chronic granulomatous inflammation. • Granuloma-granule like lesion • Epithelioidcells,giantcells,necrosis & fibrosis. • Factors favouring-poorly digestible irritant -cell mediated immunity.
Causative organism • Koch’s bacillus • Pathogenic strains -tuberculosis -bovis -avium -murine
Atypical mycobacteria-photochromogens -scotochromogens -nonphotochromogens -rapid growers. • Lesions caused-pulmonary -abscesses -lymphadenitis -bacteremia -ulcers -longer,thicker, more coarsely beaded,bent.
Mycobacterium TB • Slender, strictly aerobic rods • Waxy cell wall of mycolic acid • Methods of demonstration- -Ziehl-Neelsen method -fluorescent dye -culture-LJ medium -guinea pig inoculation
Epidemiology • 8 to 10 million cases/year • Leading infectious cause of death after HIV • Incidence increased after emergence of HIV • Flourishes-poverty,crowding,chronic debilitating illnesses,immunosuppression.
Modes of spread • Inhalation-airborne droplets • Ingestion-bovine TB • Inoculation - • Trans-placental- ?
Pathogenesis • Inhalation of tubercle bacilli • Mannose receptor of macrophage binds lipoarabinomannan on bacteria • Unchecked proliferation-?reasons • TH1 response-bactericidal macrophages • IFN gamma induces NO formation • TH1 response orchestrates formation of granuloma & caseous necrosis.
IFN gamma activates macrophages producing TNF • TNF recruits monocytes –epithelioid & giant cells • In summary- central role of TH1 -confers immunity -hypersensitivity- granuloma -caseation.
No infection 78% Exposure (close contact) Primary active TB 5% Continued latent TB Infection 22% Secondary TB 10%/lifetime Latent TB 95% HIV infection 10%/year Outcome of Exposure to M. tuberculosis
Primary tuberculosis: initial infection, usually in children - Ghon complex - subpleuralgranuloma + granulomatous hilar lymph node infection • Secondary tuberculosis: mostly in adults as a reactivation of previous infection (or reinfection)- granulomatous inflammation is much more florid and widespread - Typically, the upper lung lobes are most affected • Miliary tuberculosis- small millet seed (1-3 mm) sized granulomas
Tubercle • Caseous/non-caseous focus of inflammation consisting of: • Epitheloid cells • Langhan’s giant cells • Surrounded by lymphocytes and fibroblasts. • Fate of the tubercles– cold abscess, sinuses, coalesce to form large tubercles, dystrophic calcification.
Tubercle bacilli Lymphocyte Giant cells Fully activated macrophage Partially activated macrophage
Types PRIMARY TB: -previously unexposed, unsensitized -exogenous source of infection -primary or Ghon complex a)primary Ghon focus b)lymphatic c)lymph node
2.PROGRESSIVE PRIMARY TB -resemble acute bacterial pneumonia -lower & middle lobe consolidation -hilaradenopathy -pleural effusion -cavitation rare 3.PRIMARY MILIARY TB -TB meningitis,miliary TB.
Fate of primary TB In 95% of cases healing by fibrosis -calcification -Ranke complex (X-ray)
SECONDARY TB: • Previously sensitized. • Re-activation of dormant bacilli • Re-infection TB A)high dose of virulent bacilli B)primary immunity wanes off.
Morphology • Initial lesion: -small focus(<2cm) of consolidation within 1-2 cms of apical pleura. -sharply circumscribed,firm ,grey-white to yellow areas with central caseation & peripheral fibrosis. -Because of good hypersensitivity ,walling off occurs.-FIBROCASEOUS SCARS.
PROGRESSIVE PULMONARY TB: -Elderly,Immunosuppression -apical lesion enlarges -erosion into a bronchus -ragged irregular cavity,poorly walled off • Cavities may remain or collapse • spread-airways,lymphatic,hematogenous
Miliary TB MILIARY PULMONARY DISEASE • Through lymphatics to rt.side of heart and pulmonary arteries. • Small(2mm) yellow white consolidation scattered throughout lung. -Pleural spread -effusion -empyema -obliterative fibrous pleuritis.
SYSTEMIC MILIARY DISEASE Hematogenous dissemination Organs affected: liver, spleen, kidneys, adrenals, bone marrow. Multiple tiny tubercles –grey white to yellow,
Endobronchial, endotracheal and laryngeal TB: • Infective material spread through lymphatics • Expectorated infectious material. • Mucosa studded with minute granulomas • Isolated organ TB & lymhadenitis are other forms of TB.
TB & HIV • Increased incidence in HIV • CD4 count >300 -secondary TB • CD4 count <200 -progressive primary • Sputum smear –ve,TUBERCULIN test –ve & rare formation of granulomas. • Sheets of foamy histiocytes packed with bacilli.
In AIDS ,MAC causes widely disseminated infections • Proliferation in lungs & GIT • Fever, drenching night sweats & weight loss. • Enlargement of lymph nodes, liver & spleen • Granulomas, lymphocytes & tissue destruction are rare.
Diagnosis History Clinical examination X-ray examination Smear for AFB Culture PCR-
Laboratory diagnosis of tuberculosis Proper collection of samples • Sputum – the commonest SPOT-EARLY MORNING-SPOT • Well-coughed-up mucoid- collected into a wide mouthed waxed carton / plastic container with a lid • Examined as quickly as possible
MYCOBACTERIUM • Aerobic bacilli –non spore forming -non motile • Cell wall –rich in lipids • Acid-fast bacilli • Chains of cells in smears made from in vitro-grown colonies often form distinctive serpentine cords
Digestion & decontamination • Samples that are contaminated with normal flora- sputum,gastric aspirates, urine • Treated with acid alkali or detergent • Kill normal flora & allow mycobacteria to survive • Mucolytic • Weak- NaOH , N-acetylcysteine, oxalic acid • Modified Petroffs – all samples Oxalic acid for – Bronchoalveolar lavage.
Newer Techniques in the identification of M tbc • PCR Polymerase chain reaction • Quantiferon Assay • HPLC- Fatty acid profile