Archive for the ‘ L2-Patho TB ’ Category

L2- Pathological of Tuberculosis (TB)

Tuberculosis

It is an infective granuloma caused by myco-bacterium tuberculosis – What is a granuloma – It is a collection of chronic inflammatory cells with predominating histiocytes.

Epidemiology

– 1.7 billion individuals are infected worldwide, 8-10 million new cases develop each year and 3 million deaths per year. – TB is the 6th leading cause to death worldwide. – The incidence increased abruptly after the increase of HIV infection. – TB is the disease of poverty, crowdening,old age,  and debilitating diseases. – Incidence increases with DM, Hodgkin’s disease, renal failure, malnutrition, alcoholism and immune suppression. – The emergence of drug resistant new strains added to the difficulty in controlling the disease. -T.B bacilli are

  1. Aerobic
  2. Acid fast
  3. Non motile
  4. Do not produce toxins

Mycobacterium

Mode of infection

– Human type by droplet infection from an open, active pulmonary disease. – Oropharyngeal and intestinal lesions are acquired by drinking raw contaminated milk by bovine type of bacilli. This type of infection is greatly reduced by pasteurization of milk. Picture5

Pathogenesis of tuberculosis

-Organism is phagocytosed by macrophage which is not able to destroy virulent micro-organism.

In the early phase of primary tuberculosis,

(in the non immunized person) -there’s uncontrolled proliferation of bacilli within pulmonary alveolar macrophages with resulting bactremia and seeding of multiple sites. Picture6

After 3 weeks of infection

-cell mediated immunity develops. Macrophages process mycobacterial antigen and present it to unstimulated CD4+Tн0 cells. – Under effect of IL-12 secreted by macrophages, CD4+Tн0 cells mature into CD4+Tн1 cells which secrete IFN-γ . – IFN-γ activates macrophages to secrete a group of mediators including:-

1- 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 micro-organism. b. Secretion of IL-8 which is chemotactic for lymphocytes and monocytes.

2- IFN-γ

-which helps in a. Macrophage activation for more phagocytosis, antigen presentation and microbial killing. b. Secretion of TGF- β which stimulate fibroblastic  proliferation Picture7 -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. What type of necrosis? Picture8 Picture9 Picture12

The reaction ends by the formation of epithelioid granulomas with giant cells , central caseation and peripheral fibrosis.
Can we find T.B bacilli in the central caseious material? Why?

Picture13

Types of tuberculous reaction

Picture1

Primary Tuberculosis

– Tuberculosis of non-immune patients (usually children)

Sites

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.

Picture2

Consists of:-

1-Gohn’s focus

2- Lymphangitis

3- Hilar lymphadenitis

Ghon’s 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.

Picture3

M/E:

-Caseating and noncaseating granulomas formed of epithelioid cells,Langhan’s giant cells, Lymphocytes and peripheral fibroblasts.

– Hilar lymph nodes show the same granulomatous reaction

Picture4

Picture5

Fate of the primary complex

1-Good Fate

a- 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.

Picture6

2- Bad Fate

– Uncommonly, the disease may pass without interruption into progressive primary tuberculosis.

-This occurs in immune suppressed patients (HIV infected, malnourished children and elderly patients).

3- Spread

a. Local

-pleura & adjacent lung tissue.

b. Blood

-more in primary TB it leads to miliary tuberculosis

c. Lymphatic

-leading to tuberculous lymphadenitis.

d. Natural passages

-less common than secondary

-it leads to the development of tuberculous bronchopneumonia and pneumonia.

Picture7

Miliary T.B

– In miliary TB, the affected organ will be studied with multiple, uniform, tiny yellow-white dots in relation to small blood vessels.

– M/E:-
Early tubercles with giant cells and little caseation.

Picture8

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.

– There’s little involvement of lymph nodes as spread of the organism to regional nodes is prevented by massive tissue-based hypersensitivity response.

Picture9

M/E:-

– As in Ghon’s focus, there’s a central area of caseation that is surrounded by granulomatous inflammatory reaction.

Picture10

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.

1- With good immunity, healing of the apical lesion occurs and a dense fibrous capsule surrounds a central area of caseation (Fibrocaseous tuberculosis) and Calcification often supervenes,

a- (latent tuberculosis) develops which can be reactivated if the patient’s immunity is lowered.

-What is Fibrocaseous tuberculosis ?

Picture11

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.

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

Picture11

Tuberculous bronchopneumonia

Picture12

Yellowish patches represent inflammation of bronchioles and surrounding lung tissue (bronchopneumonia

Apical lesion + TB bronchopneumonia

3-(Blood spread) 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 immunity → most 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

  1. – Kidney
  2. -Suprarenal gland
  3. – Fallopian tube
  4. – Epididymis.
  5. – Brain and meninges.
  6. – Bone and joints.

* Large dose organism with high virulence + low body immunity → The organism usually spreads causing miliary  tuberculosis.

Picture13

Tuberculoma

– 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…)

Picture14