chemical mediators of inflammation.pptx 01

chemical mediators of inflammation.pptx

1. Presented by Dr . Harshit Agarwal 1 st year PGT Dept of P rosthodontics CHEMICAL MEDIATORS OF INFLAMMATION Guided by Dr . Rahul Kulkarni Associate Professor Dept of P rosthodontics

2. CONTENTS Introduction Definition Causes Types Microscopic features. Chemical mediators. The inflammatory cells. Morphology. Systemic effects. Fate of acute inflammation. Chronic inflammation. Prosthodontic considerations. Conclusion References

3. INTRODUCTION Inflammation is defined as the local response of living mammalian tissues to injury from any agent. It is a body defense reaction in order to eliminate or limit the spread of injurious agent, followed by removal of the necrosed cells and tissues.

4. Causes of inflammation. Physical Immunological Viruses Bacteria Heat and cold Radiation Trauma Chemicals Acids Infective Organic poisons Parasites Cell-mediated Antigen-antibody

5. SIGNS OF INFLAMMATION Rubor (redness) Tumor (swelling) Calor (heat) Dolor (pain) Functio lasea (loss of function)

6. TYPES: Depending on defense capacity of the host & duration of response, it is classified – 1.Acute inflammation- is of short duration & represents the early body reaction & is usually followed by repair . 2. Chronic inflammation- is of longer duration & occurs after the causative agent of acute inflammation persists for a long time.

7. Acute inflammatory response by the host to any agent is a continuous process but for the purpose of discussion, it can be divided into following two events: I. Vascular events II. Cellular events

8. Acute inflammation. Transient vasoconstriction Persistent progressive vasodilatation Increase in local hydrostatic pressure Slowing or stasis Leucocytic margination Vascular events- alteration in the microvasculature is the earliest response to tissue injury. Includes haemodynamic changes and changes in the vascular permeability.

9. Altered vascular permeability Mechanisms of altered vascular permeability. 1.Contraction of the endothelial cells. 2 . Contraction or mild of the endothelial damage. 3.Direct injury to the endothelial cells. 4.Endothelial injury mediated by leucocytes . 5. Leakiness from neovascularisation

10. Cellular events. The cellular events consists of two processes A. Exudation of leucocytes. B. Phagocytosis . Exudation of leucocytes - The escape of leucocytes from the lumen of microvasculature to the interstitial tissue. 1. Changes in the formed elements of the blood 2.Adhesion or rolling 3.Emigration

11. 4.Chemotaxis . 1.Leukotriene B4 2.Platelet factor 4 3.Components of the complement system(c5a in particular) 4.Cytokines-IL8 5.Soluble bacterial products. 6.Chemotactic factor for CD4 cells.

12. Phagocytosis Phagocytosis is defined as the process of engulfment of a solid particulate matter by the cells. The cells are called phagocytes. There are two main types of phagocytic cells 1. Polymorphonuclear neutrophils which appear in acute inflammatory response and are also called as microphages. 2. Circulating monocytes & fixed mononuclear phagocytes called as macrophages.

13. Phagocytosis involves 4 steps 1.Attachment stage( Opsonisation ) 2.Engulfment stage 3.Secretion or degranulation stage 4.Killing or Degradation stage - A ) Oxygen dependant mechanism B) Oxygen independent mechanism C) Nitric oxide mechanism

14. CHEMICAL MEDIATORS

15. CCHJHJHK

16. Vasodilation Bronchoconstriction

17. KININ SYSTEM Bradykinin acts in the early stage of inflammation and its effects include: i ) smooth muscle contraction; ii) vasodilatation; iii) increased vascular permeability; and iv) pain. This system on activation by factor Xlla generates bradykinin , so named because of the slow contraction of smooth muscle induced by it.

18. CLOTTING SYSTEM THE CLOTTING SYSTEM Factor Xlla initiates the cascade of the clotting system resulting in formation of fibrinogen which is acted upon by thrombin to form fibrin and fibrinopeptides . The actions of fibrinopeptides in inflammation are: i ) increased vascular permeability; ii) chemotaxis for leucocyte ; and iii) anticoagulant activity.

19. FIBRINOLYTIC SYSTEM This system is activated by plasminogen activator, the sources of which include kallikrein of the kinin system, endothelial cells and leucocytes . T he actions of plasmin : Activates factor XII, forming prekallikrein activator . Stimulates kinin system, producing bradykinin . Splits complement C3 to form C3a.C3a acts as permeability factor . Degrades fibrin into split products . Products increase vascular permeability, chemoattract leucocytes.

20. Kininogen Plasminogen activator

21. COMPLEMENT SYSTEM Three pathways: Classical pathway (antibodies) Alternate pathway (microbe LPS) Lectin pathway (sugar on microbes)

22. REGULATION OF INFLAMMATION Damaging effects are kept in check by the host mechanisms so as to resolve inflammation as seen in hypersensitivity reactions. 1.Acute phase proteins- T hese are α1-antitrypsin,protease inibitor , haptoglobin , C-reactive protein, serum amyloid A & P component . 2 . Corticosteroids- The endogenous glucocorticoids act as anti inflammatory agents.

23. 3.Free cytokine receptors- the presence of free receptors for cytokines in the serum correlates directly the disease activity. 4. Suppressor T-Cells- these inhibit the function of T & B cells 5. Anti-inflammatory chemical mediators- these are PGE2 and Prostacyclin which have both pro-inflammatory as well as anti-inflammatory actions.

24. FACTORS DETERMINING VARIATION IN INFLAMMATORY RESPONSE 1.Factors involving the organisms I) Type of injury & infection II) Virulence III) Dose IV) Portal of entry V) Product of the organisms 2.Factors involving the Host I) General health of the host II) Immune state of the host III) Leucopenia IV) Type of tissue involved V) Local host factors 3.Type of exudation I) Serous II) Fibrinous III) Purulent IV) Haemorrhagic V) Catarrhal 4.Necrosis I) Gas Gangrene II) Acute appendicitis

25. MORPHOLOGY OF ACUTE INFLAMMATION 1.Pseudomembranous inflammation- Mucous surface response to toxins . Denudation of epithelium leads to exudation . Plasma coagulates with necrosed epithelium . Forms false membrane ( pseudomembrane ). 2.Ulcer - Local defects on organ surface . Result from inflammatory processes . Common sites: stomach, duodenum, intestines . Seen in typhoid, varicose veins (leg ulcers).

26. 3.Suppuration(Abscess formation) Neutrophilic infiltrate causes tissue necrosis . Forms abscess cavity with purulent exudate . Examples : Boil (furuncle) in hair follicles . 4.Cellulitits- diffuse inflammation of soft tissues resulting from spreading effects of substances like hyaluronidase released by some bacteria. 5.Bacterial infection of the blood- a) Bacteraemia b) Septicemia c) Pyaemia

27. SYSTEMIC EFFECTS OF INFLAMMATION The systemic effects of inflammation are 1. Fever- occurs due to bacteraemia mediated by the release of factors like prostaglandins,interleukin-1 and tumour necrosis factor. 2. Leucocytosis - In bacterial infections there is neutrophilia,in viral infections lymphocytosis & in parasitic infestations eosinophilia .

28. e 3.Lymphagitis-Lymphadenitis- Hyperplasia of lymphoid follicles in lymph . Proliferation of mononuclear phagocytic cells . 4.Shock- Massive cytokine release in severe cases . TNF-a contributes to systemic vasodilatation . Increased vascular permeability and hypotension . Systemic coagulation activation leads to microthrombi .

29. FATE OF ACUTE INFLAMMATION 1.Resolution- 2.Healing by scarring- 3.Progression to suppuration 4.Progression to Chronic inflammation.-

30. CHRONIC INFLAMMATION Chronic inflammation can be defined as a prolonged process in which tissue destruction and inflammation occur at the same time.

31. Causes of Chronic inflammation 1.Chronic inflammation following Acute inflammation- Extensive tissue destruction or persistent bacteria . Examples : Osteomyelitis , lung abscess from pneumonia . 2.Recurrrent attacks of acute inflammation- Repeated acute inflammation episodes . Leads to chronic inflammatory condition . Example : Recurrent UTI causing chronic pyelonephritis . 3.Chronic inflammation starting de novo- Chronic infection from low-pathogenic organisms . Example : Mycobacterium tuberculosis infection.

32. GENERAL FEATURES OF CHRONIC INFLAMMATION 1. MONONUCLEAR CELL INFILTRATION 2 . TISSUE DESTRUCTION OR NECROSIS 3. PROLIFERATIVE CHANGES

33. TYPES OF CHRONIC INFLAMMATION Chronic Non-Specific Inflammation Non-specific reaction to irritant substance. Granulation tissue formation, healing by fibrosis. Examples: Chronic osteomyelitis , chronic ulcers. Chronic Suppurative Inflammation Variant with polymorph infiltration. Abscess formation like acute inflammation. Example: Actinomycosis . Chronic Granulomatous Inflammation Characteristic tissue response forming granulomas . Examples: Tuberculosis, leprosy, syphilis, sarcoidosis .

34. PROSTHODONTIC CONSIDERATIONS

35. Mucosal Response to removable and fixed prosthesis: Complete denture Denture stomatitis Epulis fissuratum Denture irritation hyperplasia Traumatic ulcers Angular cheilitis Oral cancers in denture wearers BMS Allergic reactions

36. Denture stomatitis is a chronic inflammation of the denture-bearing mucosa (basal seat). Area confined to max removable denture h/o sleeping with dentures Causes: 1)Ill-fitting denture. 2) inadequate curing of acrylic 3) contiued denture wearing 4) poor oral hygiene Rx – correction of irregularities of max. denture,rebasing,new dentures, Instruction on oral hygiene,antifungal therapy. Denture stomatitis

37. Allergic reaction Severe blistering of mucosa from residual monomer content

38. Epulis fissuratum Fibrous growth around the border of the denture referred to as epulis fissuratum . Causes: Reaction to chronic ill-fitting denture Hyperplasia of tissue-denture borders Single/multiple folds of hyperplastic tissue.. Mandi >max, F>M Treatment: Surgical excision only after a period of prescribed tissue rest to reduce the edema .

39. Inflammatory papillary hyperplasia Palatal papillomatosis, denture irritation hyperplasia Reactive tissue growth- denture Site of lesion  denture base (relief chamber) Rx – surgical excision, rebasing old dentures(tissue conditioners), New dentures

40. Angular cheilosis , perleche : (inflammation of the angle of the mouth) Commissural cheilitis Cause  reduced vertical dimension of occlusion. due to riboflavin or thiamine deficiency. Secondary to denture stomatitis and usually the result of Candida infection from contaminated saliva. Treatment: Antifungal therapy

41. Burning mouth syndrome Burning sensation in areas contact with dentures. Burning sensation in supporting tissues and tongue. Symptoms appear for first time with placement of new dentures. Dry mouth, insomnia, altered taste sensation.

42. Oral cancer in denture wearers If sore spot does not heal after correction of the denture, malignancy should be suspected. Prognosis is poor for oral carcinomas, especially in the floor of the mouth.

43. Removable partial denture inflammation is demarcated by the outline of the palatal connector The denture has sunk into the tissues, stripping away the gingival tissues on the distal and lingual aspects The pdl attachment is progressively destroyed,

44. FIXED PARTIAL DENTURE Factors of specific influence are 1.Ridge contact- Pressure-free pontic -tissue contact crucial . Blanching indicates pressure points, adjust pontic . Ensure passive contact on keratinized mucosa . Avoid scraping cast to prevent pressure . 2. Oral hygiene considerations - Teach effective oral hygiene techniques.

45. PONTIC MATERIAL Glazed porcelain most biocompatible material . Well-polished gold reduces corrosion, plaque retention . Meticulous oral hygiene vital for pontic inflammation prevention. . OCCLUSAL FORCES Reducing pontic width by 30% reduces occlusal forces . Facilitates plaque control by lingual contour reduction . USE OF SOFT TISSUE MODELS Soft tissue models guide prosthesis fabrication . Ensure accurate soft tissue contour replication.

46. CONCLUSION The mouth represents one of the most complex areas of the body with regard to the broad range of disorders affecting it. By virtue of its partial ectodermal and endodermal origin, the oral mucosa may show manifestations of the systemic diseases. Oral mucosa is extremely sensitive to metabolic disturbances perhaps only paralleled by the bone marrow and thus serves as an excellent marker for such disorders. The modern concept of practicing dentistry is to recognize these basic etiological factors & pathological changes occurring in the oral tissues as it is a significant diagnostic aid representing the patient’s general medical status.

47. REFERENCES Harsh Mohan ; Textbook of pathology;7 th edition. Gen. & systemic Pathology-Underwood 2 nd edition Boucher’s Prosthodontic treatment for edentulous patients; 9 th edition. Contemporary Fixed Prosthodontics-Rosenstiel 3 rd edition Text book of complete dentures – Heartwell 4 th edition. Shafer’s text book of oral pathology – 5 th edn . Orsini et al ;Versatility of the complement system in neuroinflammation , neurodegeneration and brain homeostasis November 2014 | Volume 8 | Article 380.