1. Granulomatous inflammation

2. Granulomatous Inflammation
Granuloma = Nodular collection of epithelioid macrophages surrounded by a rim of lymphocytes
Epitheloid macrophage: squamous cell-like appearance

3. Why is it important?
Granulomas are encountered in certain specific pathologic diseases ; consequently, recognition of the granulomatous pattern is important because of the limited number of conditions (some life-threatening) that cause it

4. Granulomatous Inflammation Causes
Immune granuloma:
Type IV hypersensitvity
Non-immune granuloma
Bacteria
Tuberculosis
Leprosy
Actinomycosis
Cat-scratch disease
Parasites
Schistosomiasis
Leishmaniasis
Fungi
Histoplasmosis
Blastomycosis
Metal/Dust
Berylliosis
Silicosis
Foreign body… non-necrotizing granuloma
Splinter
Suture
unknown
- Sarcoidosis ……. non-necrotizing granuloma

5. Granulomatous Inflammation pathogenesis
Neutrophils ordinarily remove agents that incite an acute inflammatory response. However, there are circumstances in which reactive neutrophils cannot digest the substances that provoke acute inflammation.

6. Granulomatous Inflammation mechanism
What is the initiating event in granuloma formation?
deposition of a indigestible antigenic material
IFN-γ released by the CD4+ T cells of the TH1 subset is crucial in activating macrophages.
Type IV hypersensitvity

7. Epithelioid cell granulomas
When macrophages have successfully phagocytosed the injurious agent but it survives inside them.
When an active T lymphocyte-mediated cellular immune response occurs. Lymphokines produced by activated T lymphocytes inhibit migration of macrophages and cause them to aggregate in the area of injury and form granulomas.

8. Granuloma

9. Leishmaniasis

10. Schistosomiasis

11. A 49-year-old female with shortness of breath is found to have hilar lymphadenopathy on chest x-ray. Biopsy of one of the lymph nodes reveals granulomas. Which of the following histological findings must have been present in the biopsy material to support the diagnosis of granulomatous inflammation?
A. Granulocytes
B. Caseous necrosis
C. Epithelioid histiocytes
D. Fibroblast proliferation
E. Multinucleated giant cells

12. Tuberculosis

13. Etiology Mycobacterum tuberculosis
Mycobacteria – ‘fungus like..
Acid fast bacilli [AFB] (i.e., they have a high content of complex lipids that readily bind the Ziehl-Neelsen stain and subsequently resist decolorization by acid).
Virulence : cord factor
Mycobacterium bovis …..intestinal TB , milk injection
Other types
M. leprae (Hansen bacillus) ………………………..Leprosy
M. kansasii, M. avium, M. intracellulare …………..Atypical mycobacterial infections
M. ulcerans ………………………………………….Buruli ulcer

14. AFB - Ziehl-Nielson stain

15. TB Pathogenesis

16. Pathogenesis of TB:
Infection Immunity

18. If the bacilli enter the body……
(1) They may be killed by the immune system,
(2) They may multiply and cause primary TB,
(3) They may become dormant and remain asymptomatic,
(4) They may proliferate after a latency period (reactivation disease). Reactivation TB may occur following either (2) or (3) above.
(5 ) if immunosuppressed ---- Primary Progressive TB or Miliary TB

19. TB Primary tuberculosis [initial infection]
secondary tuberculosis [ re-activation or re-infetion ]

20. Primary tuberculosis Ghon’s focus and Complex
initial infection
non immunized individual
5-6 days …granuloma
2 to 8 weeks – healing
subpleural zone…. Ghon focus
+ lymph node  Ghon complex
Develop immunity – tuberculin positive [ PPD ]

21. Secondary Tuberculosis:
Reactivation or Reinfection
Lung apex or upper part of lower lobes – O2
Caseous necrosis…….cavity
Pulmonary or extra-pulmonary ( any organ )
Local or systemic spread / Miliary
Vein – ……..left ventricle………….whole body
Artery –…… miliary spread within the lung

22. Miliary TB Millet like – grain. Low immunity blood or bronchial spread
Pulmonary or Systemic types.

23. Adrenal TB - Addison Disease

24. Testes TB Orchitis.

25. TB Peritonitis + liver Miliary TB

26. TB Brain – Caudate n.

28. TB Intestine any part can be affected ileum

29. Prostate TB

30. Spinal TB - Potts Disease

31. Diagnosis of TB Clinical features Depend on organ involved.
Pulmonary tuberculosis (TB):
productive cough, fever, and weight loss, night sweats.

32. Investigations Patients suspected of having tuberculosis (TB)
Tuberculin skin testing (Mantoux test, PPD)
Intradermal injection of purified protein derivative ( PPD).
The response is measured as the amount of induration at hours.
The size of induration, rather than erythema, is diagnostic.
Type IV hypersensitivty
BCG gives + result
Sputum, bronchial wash or biopsy
Acid fast smear ( ZN stain ) …….false negative
cultures require weeks for growth and identification
Newer technologies, ….DNA polymerase chain reaction, allow identification within 24 hours.
Chest radiographs
patchy or nodular infiltrate.
may be found in any part of the lung, but upper-lobe involvement is most common

33. PPD result after – 72 hours

35. AFB - Ziehl-Nielson stain

36. Granuloma

37. What is your action after diagnosis ?
Patients with TB should remain in isolation until sputum becomes smear-negative;

38. Match A and B A B
The most important cell in granulomatous inflammation
A cytokines that is important in activating macrophages and transforming them into epithelioid cells
Multinucleated cell in TB
Antigen presenting cells
pathogenesis of immune type granulomatous inflammation
Tuberculin test
Microscopic finding of TB
Virulence of mycobacterium TB
IFN-γ
Langhans cells
Epitheliod histiocyes
Cord factor
Langerhan’s cells
Type IV hypersensitivity reaction
Caseating granuloma

39. TB investigation PPD Sputum Tissue Biopsy Culture
BCG may give false positive result
Require weeks to be positive
Type IV hypersensitivty
Acid fast smear ( ZN stain )
Patchy or nodular infiltrate of the lung
Intradermal injection of purified protein derivative
HIV may give false negative result
Allow identification within 24 hours.
PPD
Sputum
Tissue Biopsy
Culture
DNA polymerase chain reaction
X-ray

40. A B PRIMARY TB TB in bone SECONDARY TB Low immunity MILIARY TB
Reactivation or re-infection of TB
TB in bone
Low immunity
Subpleural zone of lung
Lung apex
Cavity formation
PRIMARY TB
SECONDARY TB
MILIARY TB
POTTS DISEASE

42. 50 yo M presents with cough productive of bloody sputum accompanied by night sweats, weight loss, and fatigue of three months’ duration.
On examination : Lungs: ↓ breath sounds in upper lobe of Rt lungs

44. After 2 days

45. sputum