Tuberculosis

pathology inflammation

1. TUBERCULOSIS Presented by: Dr. D. VAMSHIKRISHNA, M.D (H)

2. Learning Objectives Introduction Etiology Risk Factors Transmission Sites Pathogenesis of Tuberculosis. Types of Tuberculosis Clinical Diagnosis

3. Introduction: It is a Chronic Granulomatous inflammatory infectious disease caused by Mycobacterium tuberculosis in humans.

4. Etiology: CAUSATIVE ORGANISM Tubercle bacillus or Koch’s bacillus called Mycobacterium tuberculosis causes tuberculosis in the lungs and other tissues of the human body. The organism is a strict aerobe and thrives best in tissues with high oxygen tension such as in the apex of the lung. Out of various pathogenic strains for human disease included in Mycobacterium tuberculosis complex, currently the most common is M. tuberculosis hominis (human strain).

5. M. tuberculosis bovis (bovine strain ) used to be common pathogen to human beings during the era of consumption of unpasteurised milk but presently constitutes a small number of human cases Infection with M. avium-intracellulare (avian or bird strain) is common in patients with HIV/AIDS

6. Risk Factors: More common in developing countries of Asia, Africa and Latin America. Malnutrition. Inadequate medical care. Poverty. Crowding. Chronic debilitating conditions like uncontrolled diabetes. Alcoholism and immunocompromised states. In the western countries, there has been a resurgence of tuberculosis due to HIV-AIDS.

7. Mode of Transmission: Human beings acquire infection with tubercle bacilli by one of the following routes: Inhalation of organisms present in fresh cough droplets or in dried sputum from an open case of pulmonary tuberculosis.

8. 2. Ingestion of the organisms leads to development of tonsillar or intestinal tuberculosis.

9. 3. Inoculation of the organisms into the skin may rarely occur from infected postmortem tissue.

10. 4. Transplacental route results in development of congenital tuberculosis in foetus from infected mother and is a rare mode of transmission.

11. Sites: PULMONARY REGION – 85 % EXTRA-PULMONARY SITES- 15 % Lymph Nodes (most common) G.U.T Bones & Joints Intestine Meninges Skin

12. Pathogenesis of Tuberculosis: EVOLUTION OF TUBERCLE The sequence of events which take place when tubercle bacilli enters body: TUBERCLE BACILLI ENTRY If bacilli enters through blood Neutrophils are evoked initially which are rapidly destroyed by the organisms . Later by macrophages and T cells . If the tubercle bacilli are inhaled into the lung alveoli Macrophages predominate the picture from the beginning.

13. Tubercle Bacilli engulfment by Macrophages Macrophages try to kill the bacteria or die away themselves. Macrophages present bacilli to CD4+T lymphocytes Activated lymphocytes release lymphokines. IL-1, IL-2, Interferon- γ TNF- α PROLIFERATION OF MORE T CELLS ACTIVATES MACROPHAGES FIBROBLAST PROLIFERATION If Poorly degradable bacilli are present

14. ACTIVATED MACROPHAGES TRANSFORM TO EPITHELIOID CELLS AFTER 2-3 DAYS SOME MACROPHAGES, UNABLE TO DESTROY TUBERCLE BACILLI, FUSE TOGETHER AND FORM MULTINUCLEATED GIANT CELLS.- LANGHAN TYPE Around the mass or cluster of epithelioid cells and a few giant cells, a zone of lymphocytes and plasma cells is formed which is further surrounded by fibroblasts. The lesion at this stage is called HARD TUBERCLE due to absence of central necrosis.

15. Within 10-14 days, the centre of the cellular mass begins to undergo caseation necrosis , characterized by cheesy appearance and high lipid content. This stage is called SOFT TUBERCLE which is the hallmark of Tuberculous lesions Caseation Necrosis

16. *** The soft tubercle which is a fully-developed granuloma with caseous centre does not favour rapid proliferation of tubercle bacilli. Acid-fast bacilli are difficult to find in these lesions and may be demonstrated at the margins of recent necrotic foci and in the walls of the cavities.

17. Fate of Tubercles: The fate of a granuloma is variable: COLD ABSCESS: The caseous material may undergo liquefaction and extend into surrounding soft tissues, discharging the contents on the surface. This is called cold abscess although there are no pus cells in it.

18. 2. SINUS TRACTS: - In tuberculosis of tissues like bones, joints, lymph nodes and epididymis , sinuses are formed and the sinus tracts are lined by Tuberculous granulation tissue.

19. 3. SIZE INCREASE: The adjacent granulomas may coalesce together enlarging the lesion which is surrounded by progressive fibrosis.

20. 4. CALCIFICATION & OSSIFICATION: - In the granuloma enclosed by fibrous tissue, calcium salts may get deposited in the caseous material (dystrophic calcification) and sometimes the lesion may even get ossified over the years. dystrophic calcification

21. Types of Tuberculosis: Infection with tubercle bacilli is of 2 main types: Primary Tuberculosis. Secondary Tuberculosis.

22. Primary Tuberculosis: The infection of an individual who has not been previously infected or immunised is called Primary Tuberculosis or Ghon’s complex or Childhood Tuberculosis.

23. Sites: The most commonly involved tissues for primary complex are: Lungs and Hilar lymph nodes . Other tissues which may show primary complex are Tonsils and Cervical lymph nodes Small intestine and mesenteric lymph nodes.

24. Primary complex or Ghon’s complex Primary complex or Ghon’s complex is the lesion produced in the tissue of portal of entry with foci in the draining lymphatic vessels and lymph nodes.

25. Ghon's Complex in Lungs: It consists of 3 components: Pulmonary component It is 1-2 cm solitary area of primary Tuberculous foci. Subpleural focus in the upper part of Lower lobe. Lymphatic vessel component - Lymphatics draining the lung lesion contain phagocytes containing bacilli. Lymph node component Enlarged hilar and tracheo -bronchial lymph nodes in the area drained. The affected lymph nodes are matted and show caseation necrosis.

26. Fate Of Primary Tuberculosis Primary complex may have one of the following sequelae: Fibrosis, Calcification and Ossification.

27. 2. Progressive primary tuberculosis : Caseous material is disseminated through bronchi to the other parts of the same lung or the opposite lung.

28. 3. Primary Miliary Tuberculosis: Bacilli may enter the circulation through erosion in a blood vessel and spread by haematogenous route to other tissues and organs. The lesions may be seen in organs like the liver, spleen, kidney, brain and bone marrow.

29. 3. Progressive Secondary Tuberculosis: Lowered resistance (AIDS) and increased hypersensitivity of the host, the healed lesions of Primary tuberculosis may get reactivated. The bacilli lying dormant in acellular caseous material or healed lesion are activated and can cause secondary TB.

30. Secondary Tuberculosis The infection of an individual who has been previously infected or sensitized is called Secondary TB, or Post-Primary or Reinfection or Chronic Tuberculosis.

31. The infection may occur from : Endogenous source such as reactivation of dormant primary complex; or Exogenous source such as fresh dose of Reinfection by the tubercle bacilli. Secondary tuberculosis occurs most commonly in lungs. Other sites and tissues which can be involved are lymph nodes, tonsils, pharynx, larynx, small intestine and skin.

32. Infection with M. avium-intracellulare occurs more frequently in cases of AIDS. Patients with HIV infection previously exposed to tuberculous infection have particularly high incidence of reactivation of primary tuberculosis.

33. Morphological Features of Secondary TB The lesions in secondary pulmonary tuberculosis usually begin as 1-2 cm apical pleura. It occurs by lymphohaematogenous spread of infection from primary complex to the apex of the affected lung where the oxygen tension is high and favourable for growth of aerobic tubercle bacilli. The pattern of lesions in such cases is similar to that of primary tuberculosis.

34. FATE OF SECONDARY PULMONARY TUBERCULOSIS 1. The lesions may heal with fibrous scarring and calcification.

35. 2. The lesions may produce progressive secondary pulmonary tuberculosis with the following pulmonary and extrapulmonary involvements: i ) Fibrocaseous tuberculosis ii) Tuberculous caseous pneumonia iii) Miliary tuberculosis iv) Tuberculous empyema

36. FIBROCASEOUS TUBERCULOSIS: The original area of tuberculous undergoes peripheral healing and massive central caseation necrosis which may: SOFT CASEOUS LESION WITHOUT DRAINAGE INTO A BRONCHUS OR BRONCHIOLE TO PRODUCE A NON-CAVITARY LESION (CHRONIC FIBROCASEOUS TUBERCULOSIS). BREAK INTO A BRONCHUS FROM A CAVITY (CAVITARY OR OPEN FIBROCASEOUS TUBERCULOSIS)

37. CAVITARY OR OPEN FIBROCASEOUS TUBERCULOSIS CHRONIC FIBROCASEOUS TUBERCULOSIS

38. PROGNOSIS OF CAVITARY OR OPEN FIBROCASEOUS TUBERCULOSIS The cavity may communicate with bronchial tree and becomes the source of spread of infection (‘OPEN TUBERCULOSIS’). May implant tuberculous lesion on the mucosal lining of air passages producing ENDOBRONCHIAL AND ENDOTRACHEAL TUBERCULOSIS . Ingestion of sputum containing tubercle bacilli from endogenous pulmonary lesions may produce LARYNGEAL AND INTESTINAL TUBERCULOSIS.

39. ENDOTRACHEAL TUBERCULOSIS INTESTINAL TUBERCULOSIS LARYNGEAL TUBERCULOSIS

40. TUBERCULOUS CASEOUS PNEUMONIA The caseous material from a case of secondary tuberculosis in an individual with high degree of hypersensitivity may spread to rest of the lung producing caseous pneumonia

41. MILIARY TUBERCULOSIS This is lymphohaematogenous spread of tuberculous infection from primary focus or later stages of tuberculosis. The spread may occur to systemic organs or isolated organ. The spread is either by entry of infection into pulmonary vein producing disseminated or isolated organ lesion in different extra-pulmonary sites (e.g. liver, spleen, kidney, brain, meninges , genitourinary tract and bone marrow).

42. TUBERCULOUS EMPYEMA The caseating pulmonary lesions of tuberculosis may be associated with empyema. Empyema may heal by fibrosis and obliterate the pleural space (thickened pleura by chronic pleuritis). Occasionally, pleural cavity may contain caseous material and develop into tuberculous empyema.

43. TUBERCULOUS EMPYEMA The caseating pulmonary lesions of tuberculosis may be associated with empyema. Empyema may heal by fibrosis and obliterate the pleural space (thickened pleura by chronic pleuritis). Occasionally, pleural cavity may contain caseous material and develop into tuberculous empyema.

44. EMPYEMA

45. Clinical Features: SYSTEMIC FEATURES: FEVER, NIGHT SWEATS, FATIGUE, LOSS OF WEIGHT AND APPETITE. REFERABLE TO LUNGS: PRODUCTIVE COUGH HAEMOPTYSIS, PLEURAL EFFUSION, DYSPNOEA, ORTHOPNOEA etc.

46. Diagnosis of Tuberculosis The diagnosis is made by the following tests: i ) AFB microscopy of diagnostic specimen such as sputum, aspirated material .

47. ii) Mycobacterial culture: T raditional method on LJ medium for 4-8 weeks .

48. iii) Molecular methods- PCR . iv) Complete Haemogram- Lymphocytosis and raised ESR. v) Radiographic procedures e.g. chest X-ray showing characteristic hilar nodules and other parenchymal changes).

49. vi ) Mantoux skin test: This test is done by intradermal injection of 0.1 ml of tuberculoprotein , purified protein derivative (PPD).

50. Delayed type of hypersensitivity develops in individuals who are having or have been previously infected with tuberculous infection which is identified as an indurated area of more than 15 mm in 72 hours .

51. The test may be FALSE POSITIVE: in atypical mycobacterial infection and previous BCG vaccination, FALSE NEGATIVE: in weakened immune system. sarcoidosis , some viral infections, Hodgkin’s disease , Recent tuberculous (8-10 weeks of exposure) infection

52. CAUSES OF DEATH IN PULMONARY TUBERCULOSIS P ulmonary insufficiency, P ulmonary haemorrhage, Sepsis due to disseminated miliary tuberculosis , Cor Pulmonale Secondary Amyloidosis.