2 ACUTE AND CHRONIC INFLAMMATiiiiION.pptx

2 ACUTE AND CHRONIC INFLAMMATION.pptx

1. ACUTE AND CHRONIC INFLAMMATION Dr. Onyekachi Aniume Consultant, Morbid Anatomy department

2. OVERVIEW Offending agent ------ vascular and cellular response ----- elimination of offending agent ----- termination of reaction ------- repair of damaged tissue.

3. DEFINITION Inflammation is simply defined as a response of living vascularized tissues to offending agents or damage causing the body to mount a host defense with the aim of eliminating the offending agent.

4. HISTORY Celsus , a Roman writer in the first century AD first described cardinal signs of inflammation Tumour Rubor Calor Dolor Rudolf Virchow, in 19 th century added – Functio laesa

5. HISTORY cont’d Other important contributors to the study of inflammation include John Hunter – reported that inflammation was the body’s response to disease Elie Metchnikoff – Father of innate immunity. Recognised phagocytes as the first line of defense Sir Thomas Lewis -

6. ACUTE INFLAMMATION This is the immediate response to injury. The following occur in acute inflammation: Vascular events Cellular events

7. Vascular Events….. Vascular events involve increase in permeability of post-capillary venules and changes in blood flow from the normal lamina flow to turbulent flow. The following occurs Vasodilation of the arteriole and smaller capillary bed leading to increase blood flow Endothelial cell damage and contraction leading to increase in vascular permeability. Stasis in the smaller blood vessels due to loss of fluid Margination and adherence of the leucocytes to the endothelium

8. Cellular Events…….. The cellular events in inflammation is mediated by adhesion molecules and cytokines. It is divided into Margination Rolling Adhesion Transmigration Migration toward a chemotactic stimulus Chemotaxis

9. Cellular Events…….. Margination – due to displacement of white cells to a more peripheral position Rolling – mediated by selectins. Tissue macrophages and mast cells secrete cytokines like TNF-1 And IL-1 in response to offending agents. These cytokines stimulate the expression of these selectins on the leucocytes, endothelium and mast cells. Leucocytes express L-selectins and ligands for P- and E-selectins, endothelial cells express E-selectins and platelets express P-selectins. The ligands for these selectins are the Sialyl -Lewis X facctor

10. Cellular Events…….. Adhesion – TNF and IL-1 induced expression of adhesion molecules VCAM-1 and ICAM-1 on the endothelial cells. The also convert low affinity intergrins on leucocytes to high affinity intergrins VLA-4 and LFA-1 . Transmigration – chemokines act on the cytokines and endothelial cells to express adhesion molecule PECAM-1 which is involved in the migration of leucocytes across the wall of the post-capillary venule.

11. Cellular Events…….. Chemotaxis – movement of leucocytes towards the stimulus of injury. This is mediated by cytokines, components of the complement system and arachidonic acid metabolites. Phagocytosis and clearance – this is mediated by macrophage mannose receptors, macrophage scavenger receptors and some macrophage integrins which bond to molecules on microbial cell walls. These microbial products can also be bound by opsonin to enhance binding to leucocytes.

12. Cellular Events…….. These offending agents are then engulfed into the cytoplasm and eliminated by reactive oxygen species (ROS) or other free radicals. ROS: Oxygen--------------------- Superoxide + Hydrogen peroxide (NOX) Hydrogen peroxide + chloride+ myeloperoxidase ------------ Hypochlorous acid Hypochlorous acid is a potent bactericidal agent.

13. Cellular Events…….. Other free radicals include reactive nitrogen species e.g peroxynitrate (ONOO-), lysosomal enzymes and proteins like proteases, cathelicidins major basic proteins. Inflammation is terminated by lipoxins, TGF- beta and IL-10.

14. MEDIATORS OF INFLAMMATION These are the substances thatninitiate , sustain and regulate inflammatory reactions. They are divided into Cell-derived mediators: these include the vasoactive amines, prostaglandins, leukotrienes, cytokines 2. Plasma-derived mediators: Thes are the complement proteins

15. MORPHOLOGIC PATTERNS OF INFLAMMATION 1. Serous inflammation : this type of inflammation induces exudation of cell-poor fluid into cavities. Examples include pleural effusion, skin blisters from burns. 2. Fibrinous inflammation: there is exudation of protein-rich fluid to the extracellular compartment with deposition of fibrin, giving a dull surface. E.g. meningitis, pericarditis 3. Purulent inflammation: involves exudation of cell-rich and protein-rich fluids (pus) with debris of necrotic tissue. 4. Ulcer: local defect or excavation of the surface of an organ or tissue. E.g. peptic ulcer

16. SEROUS INFLAMMATION

17. FIBRINOUS INFLAMMATION

18. PURULENT INFLAMMATION

19. ULCER

20. Acute inflammation may do either of the following: Resolve Heal by fibrosis Progress to chronic inflammation

21. CHRONIC INFLAMMATION This is a prolonged response to agents of cell injury where inflammation, tissue injury and attempts at healing occur simultaneously in varying proportions. The causes include Chronic infections e.g. tuberculosis Persistent allergic reactions Autoimmune diseases Prolonged steady exposure to toxic agents e.g. asbestos Atherosclerosis

22. CHRONIC INFLAMMATION…… The two mononuclear cells involved in chronic inflammation are Macrophages Lymphocytes Macrophages are the dominant cell population at the site of cell injury within 48hrs of injury. They are activated by two different pathways: Classical pathway Alternative pathway

23. CHRONIC INFLAMMATION…… Activated macrophages secrete cytokines that recruit CD4+ T-lymphocytes that have been exposed to antigens migrate to the site of inflammation. Subset of CD4+ lymphocytes include TH1 cells – secrete IFN gamma and activate macrophages by the classical p.w TH2 cells – secrete IL-13, IL-4 and activate macrophages by the alternative p.w TH17 cells - induce secretion of cytokines for leukocyte recruitment

24. CHRONIC INFLAMMATION…… Other cells involved in chronic inflammation include activated B lymphocytes, eosinophils, mast cells, neutrophils.

25. GRANULOMATOUS INFLAMMATION This is a type of chronic inflammation characterized by a collection of activated epitheloid macrophages with variable numbers of lymphocytes and plasma cells. These epitheloid macrophages may then fuse to form multinucleated giant cells. Types of granuloma include: Foreign body-type granuloma Caseating granuloma Non-caseating granuloma

26. Foreign body-type granuloma

27. Caseating granuloma

28. Non-caseating granuloma

29. Conditions with granulomatous inflammation Tuberculosis Sarcoidosis Fungal infections Crohn’s disease Leprosy Rheumatic fever

30. SYSTEMIC EFFECTS OF INFLAMMATION Fever Myalgia Headache Tachypnoea Anorexia Anaemia Rise in acute phase proteins (CRP, Fibrinogen, SAA, Hepcidin) Leucocytosis