Acute inflammation- vascular & cellular events

Acute inflammation- vascular & cellular events

1. ACUTE INFLAMMATION Dr. P. Shiny latha M.B.B.S., M.D.(Path).,

2. ACUTE INFLAMMATION Protective response of vascularised tissue Neutralise / eliminate agents

3. TYPES OF INFLAMMATION ACUTE CHRONIC ONSET Rapid, min to hrs Slow, days CELLS neutrophils Lymphocytes, monocytes / macrophages TISSUE INJURY Mild, self limited Severe& progressive SIGNS: local & systemic prominent Less prominent

4. STEPS OF INFLAMMATORY RESPONSE- 5 ‘R’s

5. STEPS OF INFLAMMATORY RESPONSE- 5 ‘R’s of injurious agents

6. STEPS OF INFLAMMATORY RESPONSE- 5 ‘R’s of inflammatory cells

7. STEPS OF INFLAMMATORY RESPONSE- 5 ‘R’s repair

8. STEPS OF INFLAMMATORY RESPONSE- 5 ‘R’s Control of inflammatory response

9. STEPS OF INFLAMMATORY RESPONSE- 5 ‘R’s of injurious agents

10. CAUSES OF A/C INFLAMMATION Heat, cold, radiation Poisons, toxins

11. EVENTS OF A/C INFLAMMATION

12. SIGNS OF INFLAMMATION RUBOR- redness CALOR- increased temperature DOLOR- Pain TUMOR- swelling FUNCTIO LAESA- functional impairment

13. ACUTE INFLAMMTION

14. VASCULAR EVENTS Increased vasodilatation - Increased blood flow Increased vascular permeability – enabling plasma proteins & leucocytes to leave circulation to the site of infection /injury. Emigration of leucocytes from microcirculation to focus of injury and their activation to eliminate offending agents.

15. Slow blood flow, concentration of RBCs, increased viscosity Engorgement of small vessels STASIS

16. VASODILATION Histamine  acts on smooth muscle of the vessels Earliest manifestation of inflammation Arteriolar and capillary dilation increased blood flow Erythema ( heat & redness)

17. INCREASED VASCULAR PERMEABILITY = Vascular leakage Outpouring of fluid consisting of plasma proteins and leucocytes from blood vessels into the extravascular tissue HALLMARK – increased vascular permeability of postcapillary venules

18. MECHANISMS OF INCREASED VASCULAR PERMEABILITY Formation of endothelial gaps Direct endothelial injury Retraction of endothelial cells Transcytosis Leucocyte mediated endothelial injury

19. MECHANISMS OF INCREASED VASCULAR PERMEABILITY Formation of endothelial gaps Direct endothelial injury Retraction of endothelial cells Transcytosis Leucocyte mediated endothelial injury HISTAMINE

20. MECHANISMS OF INCREASED VASCULAR PERMEABILITY Formation of endothelial gaps Direct endothelial injury Retraction of endothelial cells Transcytosis Leucocyte mediated endothelial injury NEUTROPHILS- Venules , Capillaries , Arterioles

21. MECHANISMS OF INCREASED VASCULAR PERMEABILITY Formation of endothelial gaps Direct endothelial injury Retraction of endothelial cells Transcytosis Leucocyte mediated endothelial injury Due to cytoxines & hypoxia

22. MECHANISMS OF INCREASED VASCULAR PERMEABILITY Formation of endothelial gaps Direct endothelial injury Retraction of endothelial cells Transcytosis Leucocyte mediated endothelial injury Vascular leak- proteins & fluids- VEGF

23. MECHANISMS OF INCREASED VASCULAR PERMEABILITY Formation of endothelial gaps Direct endothelial injury Retraction of endothelial cells Transcytosis Leucocyte mediated endothelial injury Venules , glomerular /pulmonary capillaries

24. CELLULAR EVENTS Journey Of Leukocytes From The Vascular Compartment To The Tissues Recruitment of leukocytes - In the lumen  margination , rolling, adhesion - across the vessel wall - Outside the vessel wall

25. CELLULAR EVENTS The influx of leucocytes ( neutrophils & monocytes ) to the site of injury Phagocytosis Secretes growth factors needed for repair

26. CELLULAR EVENTS

27. MARGINATION

28. ROLLING Leukocytes adhere transiently to the endothelial cells , detach and bind again SELECTINS – P,E,L Cytokines regulate the expression of SELECTINS and their ligands Histamine / thrombin cause redistribution of P selectin from endothelial granules (WEIBEL PALADE BODIES) to their cell surface

29. ROLLING

30. ADHESION TNF ,IL- 1 (tissue macrophages, mast) act on the endothelial cells  induce expression of ligands for INTEGRIN INTEGRINS – promote cell-cell and cell-matrix adhesion They interact with VCAM and ICAM on the endothelial cell.

31. ADHESION

32. TRANSMIGRATION/ DIAPEDESIS

33. CHEMOTAXIS

34. CHEMOTAXIS

35. Why neutrophils predominates early?

36. EXCEPTIONS

37. NEUTROPHILS & MACROPHAGES Recognition & attachment of the particle to be ingested by the leukocyte. Engulfment and formation of a phagocytic vacuole Killing of the microbe and degradation of indigested material. PHAGOCYTOSIS

38. Defensin - toxic to the microbe Lysozyme - hydrolyses muramic acid Nacetyl glucosamine bond found in the glycopeptide coat of bacteria Cathelicidin - toxic to the bacteria MBP - produced by eosinophil is toxic to the microbe Lactoferrin LYSOSOMAL ENZYMES

39. Neutral protease ( elastase , cathepsin G, nonspecific collagenase , proteinase 3) Degrade ECMs causing tissue destruction Cleave C3 and C5  Release of kinin from kininogen ( inf. mediators) Neutrophil elastase - degrade virulence factors of bacteria Harmful proteases are controlled by antiproteases in the serum( ά 1 antitrypsin, ά 2 Macroglobulin) ά 1 antitrypsin inhibitor of neutrophil elastase

40. PHAGOCYTOSIS Occurs in neutrophils & macrophages  reactive oxygen species  reactive nitrogen species  lysosomal enzymes The killing occur in phagolysosomes  avoiding damage to cell’s cytoplasm & nucleus

41. REACTIVE OXYGEN SPECIES Hypochlorite A potent antimicrobial

42. CLINICAL SIGNIFICANCE- ROS

43. REACTIVE NITROGEN SPECIES

44. OTHER MECHANISMS OF KILLING

45. NEUTROPHIL EXTRACELLULAR TRAPS (NETs)

46. MORPHOLOGICAL PATTERNS of Acute Inflammation

47. SEROUS INFLAMMATION Exudation of cell poor fluid Into spaces created by cell injury or into body cavities Does not contain microbes/ large no. of leukocytes Non-inflammatory conditions- heart failure, kidney & liver disease Skin blisters

48. FIBRINOUS INFLAMMATION Greater increase in vascular permeability Large molecules of fibrinogen pass out of the blood  fibrin is formed  deposited in the extravascular spaces Local procoagulant stimulus

49. Fibrin- eosinophilic meshwork of threads/ amorphous coagulum Fibrin exudates – dissolved by fibrinolysis If not: ingrowth of fibroblasts & blood vessels  scarring

50. BREAD & BUTTER appearance FIBRINOUS PERICARDITIS

51. PURULENT INFLAMMATION Production of pus, an exudate consists of neutrophils liquified debris of necrotic cells edema fluid SUPPURATIVE INFLAMMATION

52. Cause of purulent inflammation Infection with bacteria that cause liquefactive tissue necrosis- staphylococci Eg . Acute appendicitis ABSCESS = localised collection of pus Suppuration buried in a tissue Seeding of pyogenic bacteria into a tissue

53. Central liquefied region- necrotic leukocytes & tissue cells Zone of preserved neutrophils around this necrotic focus Outside – vascular dilation, fibroblastic proliferation Chronic inflammation & repair

54. ULCERS Local defect or excavation of the surface of an organ or tissue Produced by the sloughing (shedding) of inflamed necrotic tissue Mucosa of mouth, stomach or genito -urinary The skin & subcutanoeus tissue

55. OUTCOMES OF ACUTE INFLAMMATION