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tuberculosis

tuberculosis. B.S.K.KANTH. INTRODUCTION. Mycobacterium tuberculosis is responsible for most cases of tuberculosis. Mycobacterium bovis causes oropharyngeal and intestinal tuberculosis . Tuberculosis is second leadind infectious cause of death in world. PATHOGENESIS. Source of Infection:

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tuberculosis

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  1. tuberculosis . B.S.K.KANTH

  2. INTRODUCTION • Mycobacterium tuberculosis is responsible for most cases of tuberculosis. • Mycobacterium bovis causes oropharyngeal and intestinal tuberculosis . • Tuberculosis is second leadind infectious cause of death in world.

  3. PATHOGENESIS • Source of Infection: open case of tuberculosis In INDIA , an average open case of tuberculosis infect an average of 25 contacts before death (or)cure.

  4. Contd… • Mode of Infection: *direct inhalation of aerosolised bacilli contained in droplet nuclei of expectorated sputum. *Infection also occurs infreequently by ingestion for eg; through infected milk.

  5. Contd…

  6. Contd…

  7. PRIMARY TUBERCULOSIS

  8. CONTD… • M.tuberculosis enters macrophages by endocytosis mediated my macrophage mannose receptors which bind to “LIPOARABINOMANNAN”, a glycolipid in bacterial cell wall. • M.tuberculosis replicate inside by blocking fusion of “PHAGOSOME- LYSOSOME”

  9. Contd…

  10. CONTD… • “LYMPHO – HEMATEGENOUS” spread of bacilli is seen because in early stages of primary infection Th -1 response is not seen. • Because of this lympho hemategenous dissemination , bacilli reaches lymphnodes leading to development of Th-1 response , which activates macrophages to become bactericidal.

  11. Contd… • TH-1 cells are stimulated by mycobacterial antigens drained to lymphnodes, which are presented with class II MHC by APC. • Differentiation of TH-1 cells depends on presence of IL-12, which is produced by APC .

  12. Contd…

  13. Contd… • Interferon gamma stimulates phagolysosome formation in infected macrophages, exposing the bacteria to an acidic environment. • It also stimulate expression of inducible nitric oxide synthase,which produces nitric oxide.

  14. Contd… • Nitric oxide generates reactive nitrogen intermediates and free radicals capable of oxidative destruction of several mycobacterial constituents. • Activated marophages stimulated by ifn-gamma, produce TNF, which recruits monocytes.

  15. Contd… • These monocytes differentiate into “epitheloid histiocytes” that characterise formation of granulomas and c.asseous formation.

  16. Contd…

  17. Contd… • In this primary tuberculosis infection , exudative lesion is seen. • Exudative type of lesion consists of acute inflamatory reaction,edema fluid, pmn , later monocytes around bacilli. • This parenchymal lung lesion is called “GHON FOCUS”

  18. CONTD… • This ghon focus is seen mainly in lower part of upper lobe(or)in lower lobe. • This ghon focus along with enlarged hilum lymph nodes constitutes “GHON COMPLEX” • It is also called primary complex

  19. Contd…

  20. Contd… • Ghon complex undergoes progressive fibrosis leading to radiological detectable calcification called RANKE COMPLEX

  21. Contd… • About 5% of newly infected people develops clinical significant disease. • The elderly and profound immunosuppressed persons may lose their immunity to the tubercle bacillus and develops this “PROGRESSIVE PRIMARY TB”

  22. CONTD… • In primary progressive TB, lymphnode involvement may lead endobronchial consequences such as bronchial stenosis. • Progressive primary TB may also lead to massive hematogenous dissemination , causing “MILIARY TB”

  23. CONTD… • Thus primary infection takes one of the following paths: • A)healed lesions • B)latent lesions(organism is dormant) • - they may be pulmonary (or)extrapulmonary • -persons with latent infection cannot spread infection to others.

  24. Contd… • C)it may end as progressive primary TB, which is disseminated hamatogenously leading to miliary TB.

  25. SECONDARY TUBERCULOSIS • It arises because of: • a)reactivation of dormant primary lesions, when host resistance is weekened. • b)exogenous re-infection. • Reactivation of tuberculosis is more common in low prevalence areas,while re-infection plays an important role in high contagious areas.

  26. Contd… • It is clasically localised to apex or upper lobes of lungs. • Bacause of pre existance of hypersensitivity the bacilli elicit a prompt and marked tissue response that tends to wall off the focus of infection. • As a result of this localisation regional lymphnodes are less involved.

  27. Contd… • Cavitation occurs readily in secondary form leading to dissemination of mycobacteria along the air ways. • Now the patient sputum contains active bacilli. • Seconday tuberculous infection is characterised by productive type of lesion.

  28. Contd… • Exudative lesion : • - it is a chronic avascular granuloma. • -3 zones • -central zone:multinucleated giant cells. • -mid zone:radially arranged epitheloid cells. • -peripheral zone of fibroblasts,lymphocytes,monocytes.

  29. Contd… • Such a lesion is called tubercle. • It is the characteristic fauture of tuberculosis. • This secondary TB , also disseminate hematogenously,leading to MILIARY TB.

  30. Contd…

  31. EXTRA PULMONARY TB • SYSTEMIC MILIARY TUBERCULOSIS • -seen in liver, lngs, kidney,adrenals… • ISOLATED ORGAN TUBERCULOSIS • -In kidney:renal TB • -in meninges:tuberculous meningitis • -in bones: osteomyelitis • -in fallopian tubules:salpingitis - in intestine: intestine tuberculosis

  32. Picture of miliary tb in lung

  33. Clinical manifestations • In primary tuberculosis: • -usually asymptomatic • -may have mild flu like symptoms

  34. Contd… • In progressive pulmonary tb: • -hilaradenopathy • -plueral effusion

  35. Contd… • In secondary pulmanarytb: • -FEVER: low grade and remittent(appearing each afternoon and subsiding) &night sweats occur. • -SPUTUM: initially:mucoid • later:purulent • half of cases:hemoptysis is seen

  36. Contd… • In secondary pulmonary tb • -PLUERITIC PAIN • -WEIGHT LOSS • -APPETITE LOSS • -EASY FATIGUABILITY • -ANOREXIA

  37. CONTD… • IN ACUTE MILIARY TB • -HIGH FEVER,DRAMATIC INFECTIOUS ILLNESS. • LOCALISING SYMPTOMS MAY POINT OUT ORGAN INVOLVEMENT • EG:HEADACHE(MENINGITIS), • CHEST PAIN(PLUERITIS), • ABDOMINAL PAIN(PERITONITIS)

  38. CONTD… • IN CHRONIC MILIARY TB: • *fever of unknown origin • hematological dsorders: • -thrombocytopenia, • -leukaemoid reaction, • -POLYCYTHEMIA .

  39. “The greatest killer of all time… The captain of all these men of death… …During this centuary and last, One billion people died of tuberculosis “THE WHITE PLAGUE”

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