3. INFLAMMATION.pptxschoolofclinicalscie

This slide give complete explanation about inflammation.

1. Acute and Chronic Inflammation By Dr. Abu Bakarr Kanu

2. Learning Objectives Understand the features of acute and chronic inflammation Know the cardinal signs of inflammation Know the causes of inflammation K now the major components of acute inflammation Know the outcomes of acute inflammation To understand Chronic inflammation

3. Definition Inflammation is a response of vascularized tissues with infections, and tissue damage that brings cells and molecules of host defense from the circulation to the sites where they are needed, to eliminate the offending agents .

4. Inflammation Inflammation is induced by chemical mediators that are produced by host cells in response to injurious stimuli. The external manifestations of inflammation, often called its cardinal signs are: Heat ( calor in Latin), redness ( rubor ), swelling (tumor), pain (dolor), and loss of function ( functio laesa )

5. Inflammation Although normally protective, in some situations , the inflammatory reaction becomes the cause of disease, and the damage it produces is its dominant feature.

6. CAUSES OF INFLAMMATION Infections (bacterial, viral, fungal, parasitic) & microbial Toxins Tissue necrosis Foreign bodies (splinters, dirt, sutures) may elicit inflammation by themselves or because they cause traumatic tissue injury or carry microbes.

7. CAUSES OF INFLAMMATION Immune reactions (also called hypersensitivity) are reactions in which the normally protective immune system damages the individual’s own tissues. The injurious immune responses may be directed against self antigens, causing autoimmune diseases, or May be inappropriate reactions against environmental substances, as in allergies, or against microbes. Inflammation is a major cause of tissue injury in these diseases.

8. Acute inflammation Acute inflammation has three major components: Dilation of small vessels leading to an increase in blood flow Increased permeability of the microvasculature enabling plasma proteins and leukocytes to leave the circulation , and Emigration of the leukocytes from the microcirculation , their accumulation in the focus of injury , and their activation to eliminate the offending agent .

9. A. Changes in Vascular Flow and Caliber Vasodilation is induced by the action of several mediators, notably histamine , on vascular smooth muscle . The result is increased blood flow , which is the cause of heat and redness (erythema) at the site of inflammation.

10. A. Changes in Vascular Flow and Caliber Vasodilation is quickly followed by increased permeability of the microvasculature , with the outpouring of protein-rich fluid (an exudate) into the extravascular tissues. The loss of fluid and increased vessel diameter lead to slower blood flow, concentration of red cells in small vessels, and increased viscosity of the blood.

11. A. Changes in Vascular Flow and Caliber These changes result in: stasis of blood flow, engorgement of small vessels jammed with slowly moving red cells, Seen histologically as vascular congestion and externally as localized redness ( erythema) of the involved tissue .

12. B . Increased Vascular Permeability (Vascular Leakage) Several mechanisms are responsible for increased vascular permeability in acute inflammation which include: Retraction of endothelial cells resulting in opening of interendothelial spaces is the most common mechanism of vascular leakage. It is elicited by histamine, bradykinin, leukotrienes, and other chemical mediators . Endothelial injury , resulting in endothelial cell necrosis and detachment.

13. B . Increased Vascular Permeability (Vascular Leakage) Increased transport of fluids and proteins, called transcytosis, through the endothelial cell . As stasis develops, blood leukocytes, principally neutrophils, accumulate along the vascular endothelium. At the same time endothelial cells are activated by mediators produced at sites of infection and tissue damage, and express increased levels of adhesion molecules.

14. C. Leukocyte Recruitment to Sites of Inflammation Leukocytes that are recruited to sites of inflammation perform the key function of eliminating the offending agents. The most important leukocytes in typical inflammatory reactions are the ones capable of phagocytosis, namely, neutrophils and macrophages

15. C. Leukocyte Recruitment to Sites of Inflammation The journey of leukocytes from the vessel lumen to the tissue is a multistep process that is mediated and controlled by adhesion molecules and cytokines Leukocytes normally flow rapidly in the blood, and in inflammation, they have to be stopped and then brought to the offending agent or the site of tissue damage, outside the vessels.

16. C. Leukocyte Recruitment to Sites of Inflammation This process can be divided into phases, consisting first of: adhesion of leukocytes to endothelium at the site of inflammation, then transmigration of the leukocytes through the vessel wall , and movement of the cells toward the offending agent.

17. C. Leukocyte Recruitment to Sites of Inflammation Selectins mediate the initial weak interactions between leukocytes and endothelium . Firm adhesion of leukocytes to endothelium is mediated by a family of leukocyte surface proteins called integrins.

18. C. Leukocyte Recruitment to Sites of Inflammation After being arrested on the endothelial surface, leukocytes migrate through the vessel wall primarily by squeezing between cells at intercellular junctions. This extravasation of leukocytes, called transmigration, occurs mainly in postcapillary venules, the site at which there is maximal retraction of endothelial cells.

19. C. Leukocyte Recruitment to Sites of Inflammation Further movement of leukocytes is driven by chemokines produced in extravascular tissues, which stimulate leukocytes to travel along a chemical gradient.

20. Chemotaxis of Leukocytes After exiting the circulation, leukocytes move in the tissues toward the site of injury by a process called chemotaxis, which is defined as locomotion along a chemical gradient

21. SUMMARY LEUKOCYTE RECRUITMENT TO SITES OF INFLAMMATION • Leukocytes are recruited from the blood into the extravascular tissue where infectious pathogens or damaged tissues may be located, migrate to the site of infection or tissue injury, and are activated to perform their functions. • Leukocyte recruitment is a multistep process consisting of loose attachment to and rolling on endothelium (mediated by selectins); firm attachment to endothelium (mediated by integrins); and migration through inter-endothelial gaps.

22. SUMMARY LEUKOCYTE RECRUITMENT TO SITES OF INFLAMMATION Various cytokines promote the expression of selectins and integrin ligands on endothelium (TNF, IL-1), increase the avidity of integrins for their ligands (chemokines), and promote directional migration of leukocytes (also chemokines).

23. SUMMARY LEUKOCYTE RECRUITMENT TO SITES OF INFLAMMATION Tissue macrophages and other cells responding to the pathogens or damaged tissues produce many of these cytokines. • Neutrophils predominate in the early inflammatory infiltrate and are later replaced by monocytes and macrophages.

24. Phagocytosis and Clearance of the Offending Agent Recognition of microbes or dead cells induces several responses in leukocytes that are collectively called leukocyte activation After leukocytes (particularly neutrophils and monocytes) have been recruited to a site of infection or tissue injury they must be activated to perform their functions.

25. Phagocytosis and Clearance of the Offending Agent This makes perfect sense because, while we want our defenders to patrol our body constantly, it would be wasteful to keep them at a high level of alert and expending energy before they are required . The functional responses that are most important for destruction of microbes and other offenders are phagocytosis and intracellular killing.

26. fr

27. Leukocyte-Mediated Tissue Injury Leukocytes are important mediators of injury to normal cells and tissues under several circumstances: • As part of a normal defense reaction against infectious microbes, when tissues at or near the site of infection suffer collateral damage. In some infections that are difficult to eradicate, such as tuberculosis and certain viral diseases such as hepatitis, the prolonged host response contributes more to the pathology than does the microbe itself.

28. Leukocyte-Mediated Tissue Injury When the inflammatory response is inappropriately directed against host tissues, as in certain autoimmune diseases. When the host “hyper-reacts” against usually harmless environmental substances, as in allergic diseases, including asthma, and some drug reactions.

29. Termination of the Acute Inflammatory Response Such a powerful system of host defense, with its inherent capacity to cause tissue injury, needs tight controls to minimize damage. In part, inflammation declines after the offending agents are removed simply because the mediators of inflammation are produced in rapid bursts, only as long as the stimulus persists, have short half-lives, and are degraded after their release.

30. Termination of the Acute Inflammatory Response Neutrophils also have short half-lives in tissues and die by apoptosis within hours to a day or two after leaving the blood. In addition, as inflammation develops, the process itself triggers a variety of stop signals that actively terminate the reaction.

31. Termination of the Acute Inflammatory Response These active termination mechanisms include a switch in the type of arachidonic acid metabolite produced, from proinflammatory leukotrienes to anti-inflammatory lipoxins and the liberation of anti-inflammatory cytokines, including transforming growth factor-β (TGF-β) and IL-10, from macrophages and other cells. Other control mechanisms that have been demonstrated experimentally include neural impulses (cholinergic discharge), which inhibit the production of TNF in macrophages.

32. OUTCOMES OF ACUTE INFLAMMATION Complete resolution . Healing by connective tissue replacement (scarring, or fibrosis ). Progression of the response to chronic inflammation.

33. CHRONIC INFLAMMATION Chronic inflammation is a response of prolonged duration (weeks or months) in which inflammation, tissue injury, and attempts at repair coexist, in varying combinations . It may follow acute inflammation, as described earlier, or may begin insidiously, as a smoldering, sometimes progressive, process without any signs of a preceding acute reaction.

34. Causes of Chronic Inflammation Persistent infections by microorganisms that are difficult to eradicate, such as mycobacteria and certain viruses, fungi, and parasites . Hypersensitivity diseases. Chronic inflammation plays an important role in a group of diseases that are caused by excessive and inappropriate activation of the immune system

35. Causes of Chronic Inflammation Prolonged exposure to potentially toxic agents, either exogenous or endogenous. An example of an exogenous agent is particulate silica, a non-degradable inanimate material that, when inhaled for prolonged periods, results in an inflammatory lung disease called silicosis.

36. Morphologic Features Infiltration with mononuclear cells, which include macrophages, lymphocytes, and plasma cells . Tissue destruction, induced by the persistent offending agent or by the inflammatory cells Attempts at healing by connective tissue replacement of damaged tissue, accomplished by angiogenesis (proliferation of small blood vessels) and, in particular, fibrosis

37. Any Question (s)?

38. Summary Inflammation can be acute or chronic The cardinal signs of inflammation are: Heat, redness, swelling, pain , and loss of function Increased blood flow is the cause of heat and redness at the site of inflammation .

39. Summary Increased vascular permeability is the cause of edema Outcomes of acute inflammation includes Complete resolution, healing by connective tissue replacement (scarring, or fibrosis) or progression of the response to chronic inflammation

40. THE END