Pulmonary Tuberculosis, Integrated teaching Dr Naila.pptx

Airborne droplet containing M.TB enter the lung & travel to small alveoli
Airflow & lung anatomy favors deposition of bacilli into midzone of lung
a)Most bacilli are destroyed by lysosomal enzymes during phagocytosis-->M.TB clear from the body
b)Few bacilli survived intracellularly -->Intracellular multiplication & produce Localized infection. These infected alveolar macrophage will release cytokines leading to Primary lesion.
Infection also spreads to hilar lymph nodes.
During this stage(3weeks after exposure  CMI occurs
In LN, macrophage acts as an APC, they present bacterial Ag to CD4Th (TCR) cell via MHC-II molecule. then activated CD4 cell release IFN gumma that activate macrophage & stimulate the formation of phagolysosome in infected macrophage
So, macrophage become more efficient to kill microbes.When activated macrophage (epithelioid cell) unable to destroy tubercular bacilli. They fuse together to form MNG cell
In turn macrophage release PDGF that stimulate fibroblast to release collagen.
Activated CD 4 also release IL-2 which causes Proliferation & more accumulation of CD4 lymphocyte at the site of infection
and TNF alpha which Acts on endothelial cell of regional blood vessel
endothelial cell secret
a. PGI2 that causes vasodilation, fluid and cells comes out from the vessel.
b. IL-8 that causes chemotaxis at the site of infection.
caseating granuloma heal and calcified , but many of them , bacili may lie as a dormant even for years. Problem occurs when patient become immunocompromised.
Memory T cell  Ck more caseous necrosis-->Cavitation
Extrapulmonary involvement
(Disseminated TB)
Miliary TB :Occurs when micro-organism drains through lymphatics enter the venous blood & circulate back to lung.
It is fatal disease, if left untreated, it would kill the patient in days/ weeks.
Diagnostic approach (pathology)
FNAC- Lymph node or other accessible site
Guided FNAC


Biopsy followed by
Histopathpathological examination
CT guided biopsy –potts disease
Complications of TB
Concomitant Immunosuppressive Illness in Tuberculosis
Impact of Immunosuppressive Illnesses on TB
HIV/AIDS
HIV is a significant risk factor for developing active TB because it weakens the immune system, making it difficult to control TB bacteria.
Co-infection with HIV and TB is particularly challenging.
Diabetes Mellitus:
Diabetic patients are more likely to develop active TB from latent infections
It impairs the immune response, increasing the risk of TB infection and complicating its treatment
Chronic Kidney Disease (CKD):
CKD patients, especially those on dialysis, have a higher risk of TB due to their compromised immune systems.
Additionally, kidney transplant recipients using immunosuppressive drugs are at an even greater risk
Medications:
Cancer patients on chemotherapy and individuals using medications -corticosteroids, TNF-α inhibitors, and biologics for autoimmune disease

1. Integrated Teaching Pulmonary Tuberculosis Department of Pathology Dr Naila Awal Associate Professor

2. Pathogenesis 1 Department of Pathology 2 Complication of TB 2 Concomitant Immunosuppressive Illness in Tuberculosis 3

3. Lung infected Lung becoming infected TB Transmission Pic courtesy: CDC

4. Airflow & lung anatomy favors deposition of bacilli into midzone of lung (Lower part of upper lobe or upper part of lower lobe, close to pleura) 1 st infection Most bacilli are destroyed by lysosomal enzymes during phagocytosis M.TB clear from the body Few bacilli survived intracellularly due to Sulfatide in their cell wall preventing phagosome-lysosome fusion & Catalase resisting host cell activation Intracellular multiplication & produce Localized infection

5. These infected alveolar macrophage will release cytokines leading to Primary lesion. Infection also spreads to hilar lymph nodes. During this stage(< 3 weeks), most people are asymptomatic or have mild flu-like symptom >3weeks after exposure  CMI occurs 1 st infection Pic courtesy: Osmosis

6. IFN Ƴ stimulate the formation of phagolysosome in infected macrophage So, macrophage become more efficient to kill microbes. When activated macrophage (epithelioid cell) unable to destroy tubercular bacilli. They fuse together to form MNG cell PDGF

7. IL-2 Proliferation & more accumulation of CD4 lymphocyte at the site of infection TNF α Acts on endothelial cell of regional blood vessel

8. PGI2 IL-8 Pic courtesy: Lecturio

9. The lesion of this stage is called Hard tubercle (absence of Central necrosis) When lipid-rich macrophages die, their lipids accumulate at the center of a granuloma, giving it a cheesy appearance (caseous necrosis) Soft Tubercle (hallmark of tubercular lesions). Pic courtesy: Muhadhraty , ilovepathology

10. Clearance Dormant Latent TB Caseating Granuloma Sub clinical infection Pic courtesy: Nature

11. M.TB remain viable inside host lung- latent TB Immune system compromise Memory T cell  Ck more caseous necrosis Cavitation Extrapulmonary involvement (Disseminated TB) Reactivation TB

12. 12 Miliary TB Occurs when micro-organism drains through lymphatics enter the venous blood & circulate back to lung. It is fatal disease, if left untreated, it would kill the patient in days/ weeks. Pic courtesy:University of Cape town

13. Diagnostic approach (pathology) FNAC- Lymph node or other accessible site Guided FNAC Biopsy followed by Histopathpathological examination CT guided biopsy – potts disease 13

14. Complications of TB 01 02 03 06 05 04 Bronchopneumonia Fibrosis TB empyema Bronchiectasis Aspergilloma Peritonitis Intestinal Obstruction Pleural effusion Systemic infection Pyelonephritis Obstructive uropathy Hydronephrosis Renal failure. Infertility

15. Concomitant Immunosuppressive Illness in Tuberculosis 15

16. Impact of Immunosuppressive Illnesses on TB HIV/AIDS HIV is a significant risk factor for developing active TB because it weakens the immune system , making it difficult to control TB bacteria. Co-infection with HIV and TB is particularly challenging.

17. Diabetes Mellitus: Diabetic patients are more likely to develop active TB from latent infections It impairs the immune response, increasing the risk of TB infection and complicating its treatment.

18. Chronic Kidney Disease (CKD): CKD patients, especially those on dialysis , have a higher risk of TB due to their compromised immune systems. Additionally, kidney transplant recipients using immunosuppressive drugs are at an even greater risk

19. Medications: Cancer patients on chemotherapy and individuals using medications like corticosteroids, TNF- α inhibitors, and biologics for autoimmune diseases (e.g., rheumatoid arthritis, Crohn’s disease) can increase risk for TB due to suppression of the immune system

20. QUIZ 20 Pic courtesy: Radiopaedia

21. 21 Have a good Day