Inflammation DR SINDHURA.pptx

Inflammation

1. inflammation -Dr SINDHURA DEPARTMENT OF PERIODONTICS

2. CONTENT DEFINITION AND CAUSES OF INFLAMMATION AGENTS CAUSING INFLAMMATION SIGNS OF INFLAMMATION TYPES OF INFLAMMATION ACUTE INFLAMMATION CHRONIC INFLAMMATION REGULATION OF INFLAMMATION THE INFLAMMATORY CELLS PERIODONTAL INFLAMMATION REFERENCES

3. DEFINITIONS HARSH MOHAN: Inflammation is the local response of living mammalian tissues to injury due to any agent. It is a body defense reaction in order to eliminate or limit the spread of injurious agent. KIETH L KIRKWOOD (CARRANZA) Inflammation is an observable alteration in tissues associated with changes in vascular permeability and dilation, often with infiltration of leukocytes into affected tissues . N.C.DEY & T.K.DEY: Inflammation is a series of pathological changes associated with Local vascular reaction and cellular response of the living tissue to an injury, insufficient to kill the tissue.

4. AGENTS CAUSING INFLAMMATION INFECTIVE AGENTS : Bacteria , viruses & toxins PHYSICAL AGENTS : Heat, cold ,radiation & mechanical trauma CHEMICAL AGENTS : Organic and inorganic poisons IMMUNOLOGICAL AGENTS : Cell mediated antigen antibody reaction INERT MATERIAL : Foreign bodies

5. 5 CARDINAL SIGNS OF INFLAMMATION

6. Depending upon the defence capacity of the host & duration of response ACUTE CHRONIC Short duration > 2 weeks Early body reaction Resloves quickly Longer duration Occurs after causative agent of acute inflammation persist for long time/chronic inflammation from begining

7. Acute Inflammation Vascular events Cellular events Haemodynamic changes Altered Vascular permeability Exudation of leucocytes phygocytosis

8. The main features of acute inflammation are: 1. accumulation of fluid and plasma at the affected site 2. intravascular activation of platelets and 3. polymorphonuclear neutrophils as inflammatory cells. ACUTE INFLAMMATION

9. I.Vascular events Haemodynamic changes Altered vascular permeability

10. HAEMODYNAMIC CHANGES

11. Lewis Experiment Also known as TRIPLE RESPONSE or RED LINE RESPONSE

12. B. Altered vascular permeability

13. Inflammed tissue -accumulation of oedema fluid in interstitial compartment Starling’s hypothesis

14. MECHANISMS OF INCREASED VASCULAR PERMEABILITY

15. II . CELLULAR EVENTS The cellular phase of inflammation consists of 2 processes: exudation of leucocytes; and phagocytosis

16. Exudation of leucocytes PMNs Monocytes & Macrophages

17. The changes leading to migration of leucocytes are as follows : 1.CHANGES IN THE FORMED ELEMENTS OF BLOOD 2. ROLLING AND ADHESION. 3. EMIGRATION 4. CHEMOTAXIS

18. selectins Selectins are expressed on the surface of activated endothelial cells which recognise specific carbohydrate groups found on the surface of neutrophils, the most important of which is s-Lewis X molecule.

19. INTEGRINS

20. Immunoglobulin gene superfamily adhesion molecule Tighter adhesion & stabilise the interaction between leucocyte & endothelial cells. Intercellular adhesion molecule-1(ICAM-1) Vascular cell adhesion molecule-1 (VCAM-1) Platelet-endothelial cell adhesion molecule-1(PECAM-1) CD31 activated by TNF& IL-1 Involved in margination

21. Emigration

22. Diapedesis simultaneous to emigration of leukocytes- diapedesis of red cells between endothelial cells takes place Passive phenomenon Forced out – increased hydrostatic pressure or escape after emigration gives haemorrhagic appearance to exudate

23. Chemotaxis The chemotactic factor-mediated transmigration of leucocytes after crossing several barriers to reach the interstitial tissues is called chemotaxis.

24. Leukotriens B4 Components of complement system C3a C5a Cytokines ( lnterleukins IL-8 ) Soluble bacterial products (formulated peptids ) Chemotactic factors :

25. Phagocytosis Phagocytosis is defined as the process of engulfment of solid particulate material by the cells (cell-eating). The cells performing this function are called phagocytes

26. There are 2 main types of phagocytic cells: i ) Polymorphonuclear neutrophils (PMNs) ii) Circulating monocytes and fixed tissue mononuclear phagocytes, commonly called as macrophages

27. Stages of phagocytosis

28. 1.Recognition & Attachment stage ( Opsonisation ) receptors on macrophages-(mannose receptor & scavenger receptor) Opsonins coat target(IgG & C3b)

29. 2.Engulfment stage:- Binding of opsonised particle -engulfment with cytoplasmic pseudopods-Phagocytic vacuole- phagolysosome formation.

30. Preformed granules-stored products of PMNs are discharged or secreted into phagosome/ECM Synthesis of certain enzymes (IL2 , IL6, TNF)AA metabolites and Oxygen metabolites. 3.Killing & degradation :

31. killing of microorganism Intracellular mechanisms: Oxidative bactericidal mechanism by oxygen free radical. MPO-dependent MPO-independent Oxidative bactericidal mechanism by lysosomal granules. Non-oxidative bactericidal mechanism Granules Nitric oxide dependent

32. Extracellular mechanisms : Granules Immune mechanism

33. Chemical mediators of inflammation They are broadly classified into 2 groups: mediators released by cells; and ii) mediators originating from plasma

34. 1)Vasoactive Amines Histamine 5-hydroxytryptamin Neuropeptides

35. Histamine physical injury- trauma or heat Anaphylatoxins ; C3a and C5a Neutrophils , monocytes &platelets cytokines (e.g., IL-1 and IL-8) Derived from- Mast cells, basophils and platelets

36. 5-HT or Serotonin- Derived from- cromaffin cells of GIT , spleen, nervous tiss52ue, mast cells and platelets. Actions of 5-HT are similar to histamine but it is a less potent mediator of increased vascular permeability and vasodilatation than histamine. It may be mentioned here that carcinoid tumour is a serotonin-secreting tumour .

37. 2)Arachidonic acid metabolites (Eicosanoids) i . Metabolites via cyclo -oxygenase pathway ii. Metabolites via lipo -oxygenase pathway

38. Metabolites via cyclo -oxygenase pathway

39. Metabolites via lipo -oxygenase pathway

40. 3 . Lysosomal components Neutrophils and monocytes, contain lysosomal granules which on release elaborate a variety of mediators of inflammation. Granules of neutrophils Granules of monocytes and tissue macrophages

41. 4) Platelet Activating Factor(PAF) It is released from: IgE -sensitised basophils or mast cells, other leucocytes, endothelium and platelets .

42. Actions of PAF vascular permeability; bronchoconstriction ; Vasodilatation (low conc.) Vasoconstriction(high conc ) Leukocyte adhesion

43. 5. CYTOKINES Cytokines are polypeptide products of activated lymphocytes ( lymphokines ) and monocytes ( monokines ) that modulate the function of other cell types. Many cell types produce multiple cytokines pleiotropic-different cells are affected differently by the same cytokines redundant in that the same activity may be induced by many different cytokines

44. Cytokines may be roughly grouped into five classes based on their actions or target cells. Regulate lymphocyte function e.g., IL-2, and TGF  . Involved in innate immunity, like TNF and IL-1. Activate inflammatory cells like IFN-  and IL-2. Chemotactic activity for various leukocytes. Stimulate hematopoiesis, like granulocyte-monocyte colony-stimulating factor (GM-CSF) and IL-3.

45. 6) Free Radical :Oxygen Metabolites and Nitric Oxide

46. Inflammation Part 2

47. Many of the effects of inflammation are mediated by 4 interrelated plasma-derived factors: The Kinin system The Clotting system The Fibrinolytic system The Complement system – all 4 systems are linked by the initial activation of Hageman factor II. Plasma-derived Mediators (Plasma Proteases)

48. The Kinin System

49. The Clotting System

50. The Fibrinolytic System

51. The Complement System

52. Activation of Complement System alternate pathway classic pathway

53. Inter-relationship among clotting, fibrinolytic, kinin and complement systems .

54. Outcomes of Inflammation

55. Complete resolution

56. Fate of inflammation

57. Chronic Inflammation Chronic inflammation is of prolonged duration in which active inflammation, tissue injury, and healing proceed simultaneously. Characterized by : Infiltration with mononuclear cells, including macrophages, lymphocytes, and plasma cells. Tissue destruction, largely directed by the inflammatory cells. Repair, involving angiogenesis and fibrosis.

58. Follows acute inflammation Chronic inflammation starting de novo Recurrent attacks of acute inflammation Causes of chronic inflammation

59. T ype Chronic nonspecific inflammation osteomyelitis Chronic granulomatous inflammation-TB, leprosy , syphilis

60. Periodontal inflammation Inflammatory response of periodontium can be divided into 2 main groups Subgingival microflora (i.e. microbial virulence factor) Host immune-inflammatory response

61. Periodontal Inflammation … Gingivitis Periodontitis

62. Histopathology of Gingivitis & Periodontitis

63. MMPs Prostaglandins Cytokines- IL-1,TNF Inflammatory Mediators

64. EVASION OF HOST DEFENSE

65. (Tsai et al 1979) (Slots & Genco 1984) (Jansen et al 1995) ( Aduse -Opoku et al 1995)

66. Inflammation is a major & first event which takes place during any alteration in the body tissue, indicating a need of the treatment for the altered condition. Indeed the survival of the individual depends upon the ability of his or her normal cells to respond to altered condition. Without it none of us would be alive. Conclusion

67. References Harshmohan Textbook of Pathology 6th Ed Robins: Basic pathology 10th edition. CARRANZA’s Clinical periodontology 11 th edition Adriana d.b . ,Isabella G. ,Silvia C. , Maria g.Periodontal disease :linking the primary inflammation to bone loss. Clin Dev Immunol 2013. Thomas E. Van Dike Inflammation and periodontal diseases : a reappraisal. J Periodntol 2008 Thomas E. Van Dike The management of inflammation in periodontal disease .J Periodntol 2008