Pathology: Tuberculosis - lectures-.pptx

Pathology of Tuberclosis:
Lecture for preclinical year 2 students

1. Tuberculosis

2. Epidemiology 1.7 million deaths each year 9 million new cases in 2010 , 25 % co infection with HIV 1/3 world pop carriers of latent infection 80 % of cases Africa, Asia & eastern Europe

3. Tuberculosis remains primarily a disease of poverty , crowding , malnutrition , and lack of health care Immunosuppression from any cause & chronic debilitating illnesses predispose to TB Co infection with HIV MDR – TB & XDR - TB

4. Ethiopia 7 th of 22 high burden countries 237/ 100000 pop => prevalence Co infection with HIV 17 % 1.6 % MDR-TB Vs 20 % in eastern Europe

5. The etiologic agents Rod shaped , facultative intracelular > 100 spp , majority non pathogenic Mycobacterium tuberculosis ("M. tuberculosis") => s preads through the air when a person with active TB coughs & Bacilli infect alveoli macropahges Mycobacterium bovis ("M. tuberculosis bovis ")=> spread through cow's milk & usually start in the tonsils or Peyer's patches

6. They are waxy mycobacteria that are hard to kill with disinfectants and survive drying Both bacilli are acid-fast positive by the Ziehl-Neelsen technique Grow slowly doubling time 12 – 24 hrs => culture takes some weeks ( 4 – 8 wks) delaying diagnosis Blacks are much more susceptible than whites

7. Acid-fast positive tubercle bacilli

8. Tuberculosis (TB) Many, if not most, people have met the TB bacillus, but most never become sick Infection Vs disease Tuberculin ("Mantoux") skin test turns positive in any normal person whose T-cells have met the tubercle bacillus i.e., delayed hypersensitivity reaction

9. Many TB bacilli are killed by cell mediated immunity , but there are usually survivors. The bacterium can live indefinitely in the fibrocalcific nodule (inside the healed tiny granulomas that result from primary infection with the organism) There is a risk for developing the active disease when the person’s immune defense is lowered => secondary TB

10. TB skin test With in 48 - 72 hours , a positive skin test is marked by an area of reddish induration greater than 10mm.

11. Pathogenesis of TB Primary tuberculosis Previously unexposed, immuno competent person M. Tb enters macrophages by endocytosis => block fusion of phagosome & lysosome => proliferation of bacteria => bacteremia in < 3wks => seeding of multiple sites

12. About 3wks after infection (IL-12)=> T H 1 response (IFN- γ )=> activates macrophages (TNF) => formation of granuloma & caseous necrosis TB granulomas are called tubercles, and if they are caseating in the center, soft tubercles . Both Langhans ("classic TB") and foreign-body giant cells are common

13. Pathogenesis of TB Secondary tuberculosis Reactivation of the latent infection or re-exposure to the bacilli in a previously sensitized person Rapid defensive reaction & increased tissue necrosis

14. Clinical features of TB- PTB Vs EPTB Primary Tb Source of the organism is exogenous 1. Most have latent disease : host immune response controls infection in latent phase(not suff to eradicate) 2. rarely clearance of infection 3. 5% develop active disease : failure of immune response Primary Progressive tb : Pneumonia, hilar adenopathy, & pleural effusion Primary Lymphohematogenous dissemination => Tb meningitis or miliary Tb

15. Clinical features of TB Secondary Tb In previously exposed sensitized host Reactivation of dormant primary lesions or exogenous re-infection Apical part of lungs => TB bacilli prefer to grow where O 2 is most abundant Preexistence of hypersensitivity => wallS off the focus of infection => regional l. nodes less involved Cavitation & spread through airways

16. Clinical features of TB Slow onset of fatiguability, malaise, fever, weight loss, and night sweats. When the larger airways are involved, cough and hemoptysis occur. TB in other organs can be confused with many other diseases. Miliary TB is often subtle. Death results from pulmonary TB from exsanguinating hemoptysis or asphyxiation

17. Morphology of TB Primary Tb Ghon focus : subpleural graywhite (1.5cm) inflammatory consolidation & caseation => M. Tb drain to the regional l. nodes & caseate i.e., Ghon complex Ghon complex heals by fibrosis & calcification Lymphohematogenous dissemination to other parts of the body

18. Ghon complex, primary TB Ghon focus

19. Ghon complex, primary TB

20. Primary Tb

21. Primary Tb

22. Morphology of Secondary Tb Initially apical consolidation <2cm Progressive secondary pulmonary tuberculosis expansion of apical caseation => erosion into a bronchus => cavity erosion of blood vessels => hemoptysis Miliary pulmonary TB (yellow-white consolidation <2mm): organisms drain through lymphatics => pulmonary artery Miliary TB most heavily involves the liver, bone marrow, spleen, adrenals, epididymis, fallopian tubes, meninges, prostate & kidneys

23. Morphology of Secondary Tb Pleural effusion, empyema or fibrosis Bronchial, tracheal or laryngeal Tb Systemic miliary tuberculosis (organisms enter into pulmonary venous system =>to any organ) Isolated-organ Tb: meninges, kidneys, adrenals, bones, f. tubes & epididymis Lymhadenitis: most frequent form of extrapulmonary Tb

24. Morphology of Secondary Tb Vertebral marrow ( Pott's disease ): collapses the spine; Paraspinal “cold” abscesses or "psoas abscesses" that drain through groin , some times involving anterior abdominal wall.

25. Clinical manifestation OF POTT’S DISEASE Pain on motion, localized tenderness, low grade fever, chills , weight loss. Fluctuant Inguinal mass ( cold abscess ) and Psoas abscess . Severe destruction of vertebre => permanent compression fracture => kyphotic/scoliotic deformities ( gibbus ) and neurologic deficits ( paraparesis or paraplegia)

26. POTT’s DISEASE

27. Pott’s Disease

28. Secondary Tb

29. Cavitary tuberculosis in lung

30. 3 cm cavitary lesion in the right upper lung lobe

31. cavitary lesion in the right upper lung lobe

32. Tb

33. Tb

34. Miliary Tb: lung

35. Miliary Tb: lung

36. Miliary Tb: lung

37. Miliary Tb: lung

38. Miliary Tb: lung

39. Miliary Tb: lung

40. Tb: lung

41. Healed granuloma Fibrosis & calcification

42. Intestinal Tb By drinking of contaminated milk or swallowing coughed up infective material Ulceration of the mucosa of the ileum

43. Jejunum TB

44. Diagnosis of TB History & physical finding X-ray Acid fast smears & culture of the sputum PCR FNAC of LAP BIOPSY

45. Non-tuberculous mycobacterial infection Mycobacterium Avium-intracelluare complex ( MAC ) MAC is common in soil, dust, & water Causes infection in GIT & lung or other organs in AIDS

46. MAC pneumonia in AIDS

47. MAC in AIDS--acid fast stain