Tuberculosis

Medical Presentation

1. tuberculosis Done by noel christian

2. introduction Most prevalent communicable infectious disease. C hronic specific inflammatory infectious disease caused by Mycobacterium tuberculosis which is a non-motile, slow-growing, rod-shaped bacillus . It is a delayed type hypersensitivity (hypersensitivity 4). Belongs to cell mediated immunity. Usually attacks the lung but can also effect other parts of the body. Tuberculosis can produce atypical signs and symptoms in infants , elderly persons, and immunocompromised people and it can progress rapidly in these patients.

3. etiology Mycobacterium Tuberculosis: 1) Present as latent Tb infection or as progressive active disease. 2) In patients with progressively active disease, Mtb can cause lung destruction and the patient can die without treatment. Other causes : M. avium intracellulare , M. scrofulaceum M . ulcerans , M. fortuitum , etc .

4. Site of infection Pulmonary Tb (85% of all TB cases ) Extra-pulmonary T b ( hematogenously ) : Lymph node Genito -urinary tract Bones & Joints Meninges Intestine Skin

5. How is tb transmitted? Tuberculosis is spread via respiratory droplets that contain the tubercle bacillus. These are expelled from individuals with active TB and subsequently inhaled. M ost droplets will be stopped from entering the body by the physical barriers found in the upper respiratory tract. T hose that are small (1-2 µm) in size are able to bypass these barriers and reach the lower respiratory tract and lungs. Here the bacteria encounter cells of the immune system.

6. Outcome of infection Depends on the : 1) Host’s immune system and 2) The pathogenicity of the bacteria. M ajority of individuals will be able to control infection and contain it within a  granuloma , which is an aggregate of immune cells that walls off the mycobacteria, but does not eradicate them. As bacteria are still present, it’s called latent infection   and the individual is at risk of future  reactivation  of disease if they become immunocompromised.

7. Immune response The first cells encountered by the  mycobacteria   is the alveolar macrophages . Macrophages and other  antigen presenting cells  (APCs) recognize and phagocytose the mycobacteria, engulfing them into a phagosome . Typically upon  phagocytosis , the bacteria-containing phagosome matures and fuses with lysosomes . T he bacteria are then exposed to enzymes which degrade the bacteria. Pathogenic mycobacteria have developed a mechanisms to protect themselves from the host defense by blocking phagosomal maturation in resting macrophages . Instead, the cytokine   interferon- γ   ( IFN γ) activate macrophages promotes bacterial killing by the formation of toxic  1) Reactive oxygen intermediates  (ROI) and  2) Reactive nitrogen intermediates  (RNI). Activated macrophages also release   tumour necrosis factor α   (TNFα), which induces inflammatory response and direct immune cells to the site of infection.

8. D endritic cells , together with activated macrophages, process antigen and present it to MHC class II   molecules. In the lymph nodes, dendritic cells encounter naive T-cells. Naive  CD4+ T cells, they sample antigen/MHC complex on the surface of migrating APCs . After recognizing the antigen/MHC complex specific for the TCR, the CD4+ cells become activate and proliferate in the presence of cytokines IFNγ  and  IL12 , and differentiate into Th-1 cells . Th1 effector cells  migrate back to the lungs (chemokine) where the activated T cells interact with MHC/antigen complexes on the surface of infected macrophages and produce a range of cytokines including IFNγ ; leading to further activation of macrophages. Combination of Innate and Th1-dominant adaptive immune responses culminates the development of  granulomas .

9. D uring the early innate response  primary granuloma is formed with   centrally located macrophages . T his leads to the formation of a larger well- organised solid granuloma when adaptive immunity is initiated with the infiltration of specific T lymphocytes. Macrophages at the center will be infected and be differentiated into epitheloid cells. Some also combine to form giant multinucleated cells . The centre of the granuloma may exhibit caseous necrosis.

10. If the infection continues, the center may liquefy, producing an environment in which the bacteria can grow. Cavitation may occur if the liquefied contents are released into the bronchial tree where they can then be expelled externally and the infection transmitted to others. T he granulomas will undergo fibrosis or calcification and the infection is contained and becomes latent.

11. Clinical findings

12. diagnoses Infection with M. tuberculosis typically leads to the development of delayed hypersensitivity, M. tuberculosis antigens, which can be detected by the tuberculin ( mantoux ) test. A positive tuberculin test result signifies cell-mediated hypersensitivity to tubercular antigens. About 2 to 4 weeks after infection, intra-cutaneous injection of purified protein derivative of M. tuberculosis (PPD) induces a visible and palpable induration that peaks in 48 to 72 hours.

13. Sputum Examination: Are essential to confirm TB. Best collected in morning before any meal. Sputum examination on 3 days, increase chances of detection. Smear should be prepared from thick dirty part of sputum & stained with Ziehl-Neelson technique.

14. treatment Always treat with multiple drugs. Never add a single drug to a failing regimen. Course of drug for 6 months, sometimes 9 months. 4 drugs for two months : Isoniazid, Rifampicin, Ethambutol, Pyrazinamide . 2 drugs for four or seven months : Isoniazid, Rifampicin. Latent TB : Isoniazid is the preferred drug for treating latent TB infection. Generally , isoniazid alone is given for 9 months for latent TB infection (LTBI ) reduces a person’s lifetime risk of active TB.

15. references Charles A. Peloquin . Tuberculosis. In: Pharmacotherapy: A Pathophysiologic Approach , 7th ed. Dipiro JT, Talbert RL, Yee GC, et al., eds. New York: McGraw-Hill; 2008:1839–1856 . 2. Charles A. Peloquin . Tuberculosis. In: Pharmacotherapy: Principle & Practice , 7th ed. Dipiro JT, Talbert RL, Yee GC, et al., eds. New York: McGraw-Hill . 3. Cotran RS, Kumar V, Collins T. Tuberculosis. In: Cotran RS, Kumar V, Collins T, 7th eds. Robbins’ Pathologic Basis of Disease. Philadelphia: WB Saunders, 1999: 260–328 . 4. CDC. Guidelines for preventing the transmission of Mycobacterium tuberculosis in health-care settings, 2005. MMWR 2005; 54 (No. RR-17). www.cdc.gov/mmwr/preview/mmwrhtml/rr5417a1.htm?s_cid=rr5417a1_e World Health Organization Report on the Global Tuberculosis Epidemic. Geneva: WHO, 2008. Pathology and therapeutics for pharmacist: A B for clinical pharmacy practice-Green and Harris, Chapman and hall publication.