Pathology of GenitourinaryTuberculosis

Pathology of GenitourinaryTuberculosis

• Caused by Mycobacterium Tuberculosis• Aerobic bacteria• Intracellular Pathogen• Predilection for organs with O2 supply• Primary infection in Lung, upper

Respiratory tract, Gastrointestinal tract,• Extrapulmonary TB in the Genitourinary

tract is secondary Tuberculosis in the formof caseating granulomas.

• Caused by Mycobacterium Tuberculosis• Aerobic bacteria• Intracellular Pathogen• Predilection for organs with O2 supply• Primary infection in Lung, upper

Respiratory tract, Gastrointestinal tract,• Extrapulmonary TB in the Genitourinary

tract is secondary Tuberculosis in the formof caseating granulomas.

Zeil-Neilson stain for Acid fastbacillus

Pathogenesis of Tuberculosisstep 1

1. Binding of M.Tuberculosis to Macrophages• Role played by Cell surface receptors, mannose

receptors and Complement receptors in binding• Function upregulated by Prostaglandin E2, IL4 and

some cytokines2. Phagolysosome fusion• The bacteria is dehydrated in the lysosome of a

macropahage …. A very significant antimicrobialmechanism of phagocytosis.

3. Presentation of antigen to CD4 helper cell4. Activation of CD8, Bcell, NK cell, Macrophage for

attacking the bacteria. Th1 and Th2 response for

1. Binding of M.Tuberculosis to Macrophages• Role played by Cell surface receptors, mannose

receptors and Complement receptors in binding• Function upregulated by Prostaglandin E2, IL4 and

some cytokines2. Phagolysosome fusion• The bacteria is dehydrated in the lysosome of a

macropahage …. A very significant antimicrobialmechanism of phagocytosis.

3. Presentation of antigen to CD4 helper cell4. Activation of CD8, Bcell, NK cell, Macrophage for

attacking the bacteria. Th1 and Th2 response for

So how does Macrophage handlethe engulfed Bacteria?

1. Produce reactive oxygen in the form of H2O2.… Pleural tap and ascitic tap in TB patients havehigher levels of H2O2. Not an effectivemechanism for TB

2. Interferon and Tumor necrosis factor act onmacrophages to generate nitric oxide. This doeshelp partially in controlling the Bacteria.

3.Programmed cell death or Apoptosis by downregulating Bcl2 gene. Apoptosis results inreduced viability of TB bacteria.

1. Produce reactive oxygen in the form of H2O2.… Pleural tap and ascitic tap in TB patients havehigher levels of H2O2. Not an effectivemechanism for TB

2. Interferon and Tumor necrosis factor act onmacrophages to generate nitric oxide. This doeshelp partially in controlling the Bacteria.

3.Programmed cell death or Apoptosis by downregulating Bcl2 gene. Apoptosis results inreduced viability of TB bacteria.

Human Immune mechanism in TB

Minor mechanisms• Innate Immune response like neutrophils, NK cell

activation• Humoral response with Serum antibodies and

circulating Immune complex bound antibodies

Major Cellular ResponseCell mediated immunity

Minor mechanisms• Innate Immune response like neutrophils, NK cell

activation• Humoral response with Serum antibodies and

circulating Immune complex bound antibodies

Major Cellular ResponseCell mediated immunity

Cell mediated immunityCells involved :

CD4+(stimulate CD 8),CD8+ (kill target cells - A.perforin-granzyme dependant B. fas-fas ligand inducedapoptosis ), Macrophage (secrete TGF, PDGF )

Chemical Mediators involved in CMI:Cytokines like Interferon y(activates macrophages),

Interleukin12 (helps Th1 cell activation),IL-1(can causefever cachexia), IL-2(causes proliferation of T cells), IL-4,IL-6, IL-10, Tumour Necrosis factor , Transforminggrowth factor, PDGF

Cells involved :CD4+(stimulate CD 8),CD8+ (kill target cells - A.perforin-

granzyme dependant B. fas-fas ligand inducedapoptosis ), Macrophage (secrete TGF, PDGF )

Chemical Mediators involved in CMI:Cytokines like Interferon y(activates macrophages),

Interleukin12 (helps Th1 cell activation),IL-1(can causefever cachexia), IL-2(causes proliferation of T cells), IL-4,IL-6, IL-10, Tumour Necrosis factor , Transforminggrowth factor, PDGF

Evasion strategies of Host Immune responseby M. Tuberculosis

1. Mycobacterial sulphatides inhibit lysosomalfusion

2. Mycobacterium releases Ammonia to inhibitdehydration

3. Antagonize Nitic Oxide4. Neutralize O2 radicals and act as scavenger of

oxygen radicals5. Modulation of antigen presentation to avoid T

cell elimination6. Reduce the ability of macrophage to present the

antigen to CD4 helper cell by stimulating IL10,IL6, TGF release

7. By increasing its virulence(genetic modification)so that they escape from macrophage andmigrate for survival

1. Mycobacterial sulphatides inhibit lysosomalfusion

2. Mycobacterium releases Ammonia to inhibitdehydration

3. Antagonize Nitic Oxide4. Neutralize O2 radicals and act as scavenger of

oxygen radicals5. Modulation of antigen presentation to avoid T

cell elimination6. Reduce the ability of macrophage to present the

antigen to CD4 helper cell by stimulating IL10,IL6, TGF release

7. By increasing its virulence(genetic modification)so that they escape from macrophage andmigrate for survival

Role of Human Genetics in increased susceptibilityto Tuberculosis due to alteration of immune

response• HLA – DR2• Mannose binding lectin gene• Vitamin D receptor• IL -1 Receptor antagonist

Other factors causing increased susceptibilityHIV infection

Drug induced immunosupressionAny malignancy

• HLA – DR2• Mannose binding lectin gene• Vitamin D receptor• IL -1 Receptor antagonist

Other factors causing increased susceptibilityHIV infection

Drug induced immunosupressionAny malignancy

Cytology of aspirate from alesion in Kidney

Cytology of aspirate from alesion in Kidney

Histology of Tuberculosis

Classical picture of Tuberculosis

Histology of Kidney . Architecture is altered anddestroyed by the presence of multiple granulomas

Renal Tuberculosis

Tuberculous orchitis

Tuberculous cystitis

Tuberculous cystitis

Tuberculous cystitis