بسم الله الرحمن الرحيم

2. بسم الله الرحمن الرحيم

3. INFLAMMATION DR:Gehanmohamed

4. Learning objectives: • understand the definition of Inflammation. • List the classification of inflammation. • Identify the Pathogenesis of Acute Inflammation. • Recognize the difference between acute and chronic inflammation regarding the onset ,causes and microscopic picture. • .

5. Learning objectives: • Outline the mechanism of formation and function of the inflammatory fluid exudate

6. Inflammation • Definition: *Inflammation is the local vascular, lymphatic and cellular reactions of living tissue against an irritant. *Inflammation is a protective mechanism with the purpose of: - localization and removal of the irritant. • To defend against and to eliminate the injurious agent responsible for injury. • Rid the tissue of the consequences of injury (necrotic cells). • To start healing and repair of injured tissue. • *

7. Inflammation is designated by adding the suffix “itis” to the English, Latin or Greek name of the organ affected : Examples: • Appendix  appendicitis • Pancreas  pancreatitis • Meninges  meningitis • Pericardium  pericarditis • Liver  hepatitis • Joints Arthritis

8. CAUSES OF INFLAMMATION(1) Living Irritants: Bacteria and their toxins, viruses, parasites and fungi. (2) Non Living Irritants: include: (a) Physical irritants: e.g. excess heat, excess cold and radiations. (b) Chemical irritants: e.g. concentrated acids, alkalis, organic and inorganic poisons. (c) Mechanical irritants: e.g. trauma, mechanical friction and foreign bodies. (3) Antigens: Cause allergic inflammation.

9. Do not confuse inflammation with infection !!!! • Infection not synonymous with inflammation. • Infection: refers to tissue invasion by an infectious organism and usually results in inflammation.

10. TYPES OF INFLAMMATION • (1) Acute Inflammation: • Caused by an irritant of short duration . • The tissue response is rapid i.e. sudden onset. • lasts for days to weeks. • characterized by the presence of fluid exudates, fibrin threads and polymorphonuclear leucocytes.

11. (2) Chronic Inflammation: • Caused by an irritant of prolonged action. • The tissue response is slow i.e. gradual onset. • Inflammation lasts for months to years. • characterized by the presence of macrophages, plasmacells, lymphocytes and fibrosis. (3) Subacute Inflammation:Grades between the acute and the chronic types.

12. Acute Inflammation

13. Pathogenesis of Acute Inflammation The acute inflammatory reaction consists of: I. Local tissue damage. II. Local vascular reactions. III. Chemical mediators .

14. I. LOCALTISSUEDAMAGE Occurs at the centre of the inflamed area with the maximum concentration of the irritant. Local death of tissue (necrosis) will result. • This local damage of cells together with inflammatory stimulus trigger the release and activation of chemical substances called chemical mediatorsas histamine, serotonin and prostaglandins. These chemical mediators play an important role in promoting the vascular and cellular changes in the inflamed area.

15. II. LOCAL VASCULAR REACTIONS

17. Normal lung: microscopy

18. Lung: acute inflammation Dilated blood vessels = VASODILATON Neutrophils Exudate rich in fibrin

19. II. LOCAL VASCULAR REACTIONS occur in this sequence: (1)Transient vasoconstriction of the small arterioles: Caused by the direct effect of the irritant on the vascular wall. Vasoconstriction is a protective mechanism and lasts for seconds to minutes only.

20. (2)Vasodilatation of the Blood Vessels: Occurs in the arterioles, venules and capillaries due to: (a) Direct action of histamine on the vascular wall. (b) Local axon reflex. The dilatation of the arterioles and capillaries will increase the blood flow & is called hyperaemia. The inflamed area becomes red and hot.

21. (3)Slowingof the Blood Stream (Stasis):Caused by: • Increased viscosity of the blood due to formation inflammatory fluid exudates. This is the main cause of stasis. (b) Histamine causes swelling of the vascular endothelium which become sticky and offer mechanical resistance to the blood.

22. (3) Formation of the Inflammatory Exudates: The intravascular contents (plasma and cells) escape into the interstitial tissue spaces forming the inflammatory exudates which consists of a fluid component and a cellular component. (4) Dilatation of lymphatic vessels: to accelerate the lymph flow and drains the fluid exudates.

23. Terms for abnormal accumulations of fluid • Edema may be : - Exudate (pus, serous,….) - Transudate

24. Edema: excess amount of fluid in the interstitial tissue spaces or body cavities. • Can be exudate or transudate - Exudation: the escape of fluid, proteins & blood cells from the vascular system into the interstitial tissue or body cavities. • Occurs when blood vessels become leaky. - Exudate: an inflammatory extravascular fluid with a high protein concentration, cells/cell debris & an SG (specific gravity) > 1020 • Implies: significant alteration in permeability of small blood vessels in an area of injury.

25. Pus (purulent exudate) is inflammatory exudate rich in neutrophils and debris of dead cells.

26. Exudate : microscopy Neutrophils Exudate rich in fibrin

27. Transudate: an extravascular fluid with a low protein content, few or no cells & SG < 1012 • Results due to imbalance in hydrostatic pressure. • Occurs when there’s organ failure as heart failure leading to systemic congestion and formation of transudate.

28. Pitting Edema Laryngeal edema A B

29. A-The Inflammatory Fluid Exudates Mechanism of formation: • Increased capillary permeability to plasma and its proteins caused by histamine (the main cause). (2) Increased capillary hydrostatic pressure due to dilatation of the arterioles and increased blood flow. This pushes fluids outside the capillaries.

30. (3) Increased osmotic pressure of the interstitial tissue fluid as the large protein molecules split into smaller ones in the process of tissue necrosis. This acts as a suction force from the capillaries.

31. Characters: - High protein content, 4-8 gm% (the normal interstitial tissue fluid contains 1 gm% protein). - High fibrinogen content (turbid & clots on standing). - High specific gravity (above 1018). - High cellular content (polymorphs & macrophages)

32. Functions: (1) It dilutes toxins, chemicals and poisons, so minimizes their effects. (2) Brings antibodies from the blood to the site of inflammation. (3) Supplies nutrition for the cells and carries away waste products.

33. (4) Fibrinogen forms a fibrin network, which acts as a mechanical barrier to the spread of infection and as a bridge for leucocytes to reach the irritant.

34. Sequence of events in the extravasation of leukocytes • Margination • Rolling • Adhesion • Transmigration (also called diapedesis) • Migration toward chemotactic factor = chemotaxis

35. Step 1 : Margination • Accumulation of leukocytes along the endothelial surface: • Partly mechanical (stacks of RBCs push neutrophils to the surface). • Partly mediated by chemical mediators • C5a, leukotriene B4 and bacterial products. • Usually secreted at the site of injury.

37. Neutrophil Margination

38. Rolling, adhesion and transmigration Mediated by binding of complementaryadhesion moleculesonleukocytesand endothelial surfaces

39. Selectins Integrins Adhesion molecules Immunoglobulins

41. Step-2: Rolling • Neutrophils weakly bind to the endothelial selectins and roll along the surface (Rolling).

42. Rolling Sialyl-Lewis X P-Selectin E-Selectin

43. Step 3: Leukocyte activation • Neutrophils are stimulated by chemotactic agents (chemokines and C5a) to express their integrins.

44. Step-4: Transmigration • Leukocytes emigration  pseudopods. • Interaction of platelet endothelial cell adhesion molecule 1 (PECAM-1) on leukocytes and endothelial cells mediates transmigration between cells. • Neutrophils release type IV collagenase that degrades the Basement membrane.

45. Transmigration

46. Chemotaxis • Chemotaxis is the attraction of cells toward a chemical mediator that is released in the area of inflammation. • Important chemotactic factors for neutrophils: Exogenous: • Bacterial products Endogenous: • Leukotriene B4 (LT-B4) • Complement system products C5a • Alpha Chemokines (IL-8)

47. Phagocytosis • Engulfment of particulate material (e.g. tissue debris, living and dead bacteria, other foreign particles) by phagocytic cells. • Neutrophils and macrophages are the most important. Phagocytic cells. • Phagocytosis: Three steps • Recognition and attachment • Engulfment • Killing and degradation of the ingested material

48. Recognition and attachment • Receptors on leukocytes recognize the particle to be ingested. • Opsonization:facilitates phagocytosis • It Is coating of particulate matter by substances referred to as OPSONINS. • Important opsonins • IgG • Complement system product C3b • Plasma protein – Collectins

49. Engulfment • Triggered by binding of opsonised particle to phagocytic receptor. • Neutrophil sends out cytoplasmic processes (pseudopods) that surround the bacteria. • The bacteria are internalized within a phagosome. • The phagosomefuses with lysosome to form phagolysosome. • Release of lysosomal contents (degranulation).

50. Intracellular microbial killing • The final step in Phagocytosis of microbes is killing and degradation. • Mediated within phagocytic cells by: • Oxygen dependent • Oxygen independent mechanisms • Usually mediated by lysosomes of the neutrophils (lysozyme, defensins, basic proteins, etc.)