Pathology of tuberculosis 2009

(Tuberculosis (TB

Dr: Mie Ali Ali Mohamed

Epidemiology

Tuberculosis

1.7 billion individuals are infected worldwide, 8-10 million new cases develop each year and 1.7 million deaths per year. TB is the leading cause of death worldwide after HIV. Infection with HIV makes people susceptible to rapidly progressive tuberculosis

Epidemiology

Tuberculosis

Tuberculosis flourishes wherever there is poverty, crowding, and chronic debilitating illness. In the United States, tuberculosis is mainly a disease of the elderly, the urban poor, and people with AIDS Incidence increases with DM, Hodgkins disease, renal failure, malnutrition, chronic alcoholism and immune suppression.

TuberculosisT.B bacilli are Aerobic Acid fast Non motile Do not produce toxins

MycobacteriumMode of infection Human typeby droplet infection from an open, active pulmonary disease. Oropharyngeal and intestinal lesions are acquired by drinking raw contaminated milk by bovine type of bacilli.

Organism is phagocytosed by macrophage which is not able to destroy virulent microorganism. In the early phase of primary tuberculosis, (in the non immunized person), there's uncontrolled proliferation of bacilli within pulmonary alveolar macrophages with resulting bacteremia and seeding of multiple sites.

Pathogenesis of tuberculosis


Pathogenesis of tuberculosis After 3 weeks of infection, cell mediated immunity develops. Macrophages process mycobacterial antigen and present it to unstimulated CD4+T0 cells. Under effect of IL-12 secreted by macrophages, CD4+T0 cells mature into CD4+T1 cells which secrete IFN- . IFN- activates macrophages to secrete a group of mediators including:-

Pathogenesis of tuberculosis1- TNF causing recruitment of monocytes, their activation, differentiation to epithelioid cells. It also causes a. Increased NO production which generate free radicals able to destroy the microorganism. b. Secretion of IL-8 which is chemotactic for lymphocytes and monocytes.

Pathogenesis of tuberculosis2- IFN- . which helps in a. Macrophage activation for more phagocytosis, antigen presentation and microbial killing. b. Secretion of TGF- which stimulate fibroblastic proliferation


Pathogenesis of tuberculosis The development of immunity (protection) to TB bacilli is accompanied by hypersensitivity (tissue destruction). Re-exposure to TB bacilli in a previously sensitized host results in rapid mobilization of defensive mechanism and also increased tissue necrosis.


TNF1- Increased NO production which generate free radicals. 2- Secretion of IL-8 which is chemotactic for lymphocytes and monocytes

IFN-1- Macrophage activation 2- Secretion of TGF- which stimulate fibroblastic proliferation


The reaction ends by the formation of epithelioid granulomas with giant cells , central caseation and peripheral fibrosis.

Types of tuberculous reaction

Primary TuberculosisSites 1- Lungs 2- Intestine 3- Tonsils 4- Skin 5- Nose

Primary pulmonary complex It is the form of disease that develops in a previously unexposed, and therefore unsensitized persons. It is more common in children. Source of infection is exogenous. About 5% of infected persons develop significant disease.

Primary pulmonary complexConsists of:1-Gohns focus 2- Lymphangitis 3- Hilar lymphadenitis

Gohns Focus

Primary pulmonary complexGhons focus:-1-1.5 cm in diameter,grey-white. - Found in the lower part of upper lobe or upper part of lower lobe usually close to the pleura. - Central part undergoes caseation.

Primary pulmonary complex

M/E: -Caseating and noncaseating granulomas formed of epithelioid cells,Langhans giant cells, Lymphocytes and peripheral fibroblasts. - Hilar lymph nodes show the same granulomatous reaction

1- Primary infection induces both immunity and hypersensitivity. 2- Healing by fibrous tissue , dystrophic calcification. These foci can harbor viable organism for years (latent tuberculosis) to be activated later if the immunity of the patient is lowered.

Fate of the primary complex

Fate of the primary complex3- Uncommonly, the disease may pass without interruption into progressive primary tuberculosis. -This occurs in immune suppressed patients (HIV infected, malnourished children and elderly patients).

Fate of the primary complex4- Spread a. Local..pleura & adjacent lung tissue. b. Bloodmore in primary TB it leads to miliary tuberculosis c. Lymphatic ++leading to tuberculous lymphadenitis. d. Natural passages....less common than secondaryit leads to the development of tuberculous bronchopneumonia and pneumonia.

Fate of the primary complex ( blood (Spread If an enlarging caseating lymph node erodes a vessel wall, TB bacilli are carried in the blood stream to many parts of the body including the remainder of the lung causing miliary tuberculosis. If drainage occur through the pulmonary vein there is systemic dissemination of the organism (kidneys, liver, spleen). If drainage occur through pulmonary artery, dissemination occurs within the lungs

Miliary T.BIn miliary TB, the affected organ will be studied with multiple, uniform, tiny yellow-white dots in relation to small blood vessels. The dots are not surrounded by hyperemic zones like pyemic abscesses. M/E:Early tubercles with giant cells and little caseation.

TB bronchopneumonia Bronchial spread of organisms produce tuberculous bronchopneumonia. In primary tuberculosis, if an infected lymph node erodes into a bronchus, tuberculous caseous material containing living TB bacilli passes down bronchi and bronchioles under influence of gravity to lower lung tissue causing confluent caseating granulomatous lesions. This lesion is usually rapidly fatal and is called (galloping consumption)

Secondary tuberculosis In secondary TB the organism may be acquired exogenously or from reactivation of a healed primary complex. It usually occurs in adults. Hypersensitivity reaction leads to excessive tissue destruction and extensive caseation. No nodal affection as the organism is destroyed in the necrotic tissue.

Secondary pulmonary tuberculosis An apical lesion (Assmann focus) begins as a small caseating tuberculous granuloma. In most cases, destruction of the lung leads to cavitations. Theres little involvement of lymph nodes as spread of the organism to regional nodes is prevented by massive tissuebased hypersensitivity response.

Secondary pulmonary tuberculosis

M/E:As in Ghons focus, theres a central area of caseation that is surrounded by granulomatous inflammatory reaction.

Fate of Secondary pulmonary tuberculosis

The outcome of the infection depends on the balance between dose and virulence of the organism with the body immunity.

Fate of Secondary pulmonary tuberculosis1- With good immunity, healing of the apical lesion occurs and a dense fibrous capsule surrounds a central area of caseation (Fibrocaseous tuberculosis). - Calcification often supervenes, and a (latent tuberculosis) develops which can be reactivated if the patients immunity is lowered.

Fate of Secondary pulmonary tuberculosis ((bronchial spread

2- In adults with poor immune response, secondary TB progresses locally with massive tissue destruction and poor fibrosis. The release of TB bacilli into the main bronchi leads to:a. Open tuberculous lesion in which TB bacilli are coughed into the atmosphere and droplet infection can occur to other people, or infected sputum is swallowed leading to TB laryngitis or enteritis.

Tuberculous bronchopneumonia

b. TB bronchopneumonia in which spread of infection occurs to the lower lobes of the lungs.

Apical lesion + TB bronchopneumonia

Yellowish patches represent inflammation of bronchioles and surrounding lung tissue (bronchopneum onia(

Apical lesion + TB pneumoniaSpread of infection from the apical lesion to the surrounding lung parenchyma leads to tuberculous pneumonia.

Hemorrhage into a T.B cavityErosion of blood vessels by tuberculous reaction can lead to hemorrhage into the cavity with coughing of blood (hemoptysis)

Fate of Secondary pulmonary tuberculosis ((Blood spread

3- In adults with poor immune response blood spread of the organism can occur, the final outcome of blood spread depends upon dose and virulence of the organism and body immunity. *Low dose organism with low virulence + good body immunitymost of the organism will die.


Moderate dose organism with Moderate virulence + Moderate body immunity.. The organism usually settle in one organ leading to (isolated organ tuberculosis).


Organs most commonly affected are - Kidney -Suprarenal gland - Fallopian tube - Epididymis. - Brain and meninges. - Bone and joints.


High dose organism with high virulence + low body immunity..Spread of the organism to all body organs leading to miliary tuberculosis

Miliary tuberculosis lungGrossly .. Affected organ shows a large number of - Small -Uniform - Grayish yellow dots - Near small blood vessels. - Not surrounded by a zone of hyperemia.

Milliary tuberculosis spleen

Miliary TuberculosisM/E.. The affected organ shows large number of -Small uniform epithelioid granulomas with giant cell but with little caseation and little or no surrounding fibrosis.

Tuberculo ma It is a localized mass of caseating tuberculous reaction surrounded by fibrous tissue. It may reach a large size (to be mistaken for a tumor) It can occur at any organ (lung, kidney, brain)

Complications of pulmonary tuberculosis1- Local tissue destruction. - Blood vesselshemorrhage & hemoptysis - Bronchi..open to the pleura leading to pneumothorax and pyopneumothorax. - Reactive systemic amyloidosis. 2- Pulmonary fibrosispulmonary hypertension ..right sided heart failure (cor pulmonale). 3- Spread..*Local to the pleura (pleurisy) *BronchialTB pneumonia and bronchopneumonia *Blood..isolated organ TB or miliary TB

Thank you

Documents

Pathology of tuberculosis 2009