tuberculosis B S K KANTH INTRODUCTION Mycobacterium 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: open case of tuberculosis In INDIA , an average open case of tuberculosis infect an average of 25 contacts before death (or)cure.

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.

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PRIMARY TUBERCULOSIS

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 “PHAGOSOMELYSOSOME”

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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.

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.

Contd… Mature TH-1 cells Interferon-gamma • Critical mediator which drives macrophages to become competent to contain tuberculous infection

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.

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

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

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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”

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

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

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”

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”

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.

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

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.

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.

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.

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.

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

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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

Picture of miliary tb in lung

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

Contd… In progressive pulmonary tb: -hilar adenopathy -plueral effusion

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

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

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)

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

“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”