Acute inflammation

robbins general path

1. ACUTE INFLAMMATION DR PREETI AGRAWAL

2. INFLAMMATION DEFINITION : It is defined as the local response of living mammalian tissues to injury from any agent . it is body’s defense reaction .

3. CAUSES : Infective agents – baceria , viruses,fungi parasites Immunological agents-cell mediated and antigen antibody reactions. Physical agents- heat, cold, radiation, mechanical trauma Chemical agents-organic and inorganic poisons Inert material – foreign bodies

4. SIGNS OF INFLAMMATION FOUR CARDINAL SIGNS OF INFLAMMATION rubor (redness) tumor ( swelling) calor (heat) dolor (pain) Fifth sign added by virchow Functio laesa

5. TYPES OF INFLAMMATION ACUTE INFLAMMATION- is of short duration , early body reaction , resolves quickly, followed by healing . Features are: Accumulation of fluid and plasma at the affected site Intravascular activation of platelates Neutrophils as inflammatory cells

6. B) CHRONIC INFLAMMATION- It is of longer duration and occurs after delay , char. Feature is presence of lymphocytes , plasma cells , macrophages , granulation tissue formation , and in specific situations as granulomatous inflammation

7. ACUTE INFLAMMATION Rapid onset and short duration Marked vascular changes More abundant fluid exudate Main inflammatory cells: neutrophils and macrophages Absent or mild fibrosis CHRONIC INFLAMMATION Gradual onset and long duration Mild vascular changes, vascular thickening Usually scanty fluid exudate Main inflammatory cells: macrophages, lymphocytes, plasma cells and giant cells. Marked fibrosis

8. Acute inflammatory response can be divided into following two events: vascular events : these alteration includes Haemodynamic changes; Changes in vascular permiability cellular events :consists of two processes exudation of leucocytes; phagocytosis

9. Changes in Vascular Flow and Caliber( Haemodynamic changes) begin early after injury and consist of the following.     •     Vasodilation is one of the earliest manifestations of acute inflammation; sometimes it follows a transient constriction of arterioles, lasting a few seconds.. The result is increased blood flow , which is the cause of heat and redness ( erythema ) at the site of inflammation. Vasodilation is induced by the action of several mediators, notably histamine and nitric oxide (NO), on vascular smooth muscle . •    Vasodilation is quickly followed by increased permeability of the microvasculature , with the outpouring of protein-rich fluid into the extravascular tissues

10. •    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. These changes result in dilation of small vessels that are packed with slowly moving red cells, a condition termed stasis    •    As stasis develops, blood leukocytes, principally neutrophils , accumulate along the vascular endothelium( leukocyte margination ) Leukocytes then adhere to the endothelium, and soon afterward they migrate through the vascular wall into the interstitial tissue( emigration )

11. Increased Vascular Permeability (Vascular Leakage) Several mechanisms are responsible for the increased vascular permeability Contraction of endothelial cells : it is the most common mechanism of vascular leakage and is elicited by histamine, bradykinin , leukotrienes , the neuropeptide substance P, and many other chemical mediators It is called the immediate transient response because it occurs rapidly after exposure to the mediator and is usually short-lived (15–30 minutes)

12. 2)contraction of endothelial cells or mild endothelial damage . In some forms of mild injury (e.g. after burns, x-irradiation or ultraviolet radiation, and exposure to certain bacterial toxins), vascular leakage begins after a delay of 2 to 12 hours, and lasts for several hours or even days; this delayed prolonged leakage . Late-appearing sunburn is a good example of this type of leakage. 3) Endothelial injury, resulting in endothelial cell necrosis and detachment . Direct damage to the endothelium is encountered in severe injuries, for example, in burns In most instances leakage starts immediately after injury and is sustained for several hours until the damaged vessels are thrombosed or repaired.

13. 4) Leukocyte mediated endothelial injury : Neutrophils that adhere to the endothelium during inflammation may also injure the endothelial cells and thus amplify the reaction 5) Transcytosis : VEGF , seem to promote vascular leakage in part by increasing the number and perhaps the size of vesiculovacuolar organelle( channels)

14. CELLULAR EVENTS : The processes involving leukocytes in inflammation consist of: their recruitment from the blood into extravascular tissues, recognition of microbes and necrotic tissues, removal of the offending agent.

15. Recruitment of Leukocytes to Sites of Infection and Injury The journey of leukocytes from the vessel lumen to the interstitial tissue, called extravasation , can be divided into the following steps:    1.    In the lumen: margination , rolling, and adhesion 2.    Migration across the endothelium and vessel wall    3.    Migration in the tissues toward a chemotactic stimulus

16. Leukocyte Adhesion to Endothelium. In normally flowing blood in venules , red cells are confined to a central axial column, and the leukocytes toward the wall of the vessel. Because of stasis a white cells assume a peripheral position along the endothelial surface. This process of leukocyte redistribution is called margination . Subsequently, individual and then rows of leukocytes adhere transiently to the endothelium, detach and bind again, thus rolling on the vessel wall. The cells finally come to rest at some point where they adhere firmly

17. Endothelial Molecule Leukocyte Molecule Major Role P- selectin Sialyl -Lewis X–modified proteins Rolling (neutrophils, monocytes, T lymphocytes) E-selectin Sialyl-Lewis X–modified proteins Rolling and adhesion (neutrophils, monocytes, T lymphocytes) GlyCam-1, CD34 L-selectin [*] Rolling (neutrophils, monocytes) ICAM-1 (immunoglobulin family) CD11/CD18 ( β 2 ) integrins (LFA-1, Mac-1) Adhesion, arrest, transmigration (neutrophils, monocytes, lymphocytes) VCAM-1 (immunoglobulin family) VLA-4 ( β 1 ) integrin Adhesion ( eosinophils , monocytes , lymphocytes)   Endothelial-Leukocyte Adhesion Molecules

18. Leukocyte Migration through Endothelium. The next step in the process of leukocyte recruitment is migration of the leukocytes through the endothelium , called transmigration or diapedesis . occurs mainly in post-capillary venules . Chemokines act on the adherent leukocytes and stimulate the cells to migrate through interendothelial spaces toward the site of injury or infection where the chemokines are being produced. leukocytes pierce the basement membrane, probably by secreting collagenases , and enter the extravascular tissue. The cells then migrate toward the chemotactic gradient created by chemokines and accumulate in the extravascular site.

19. Chemotaxis of Leukocytes After exiting the circulation, leukocytes emigrate in tissues toward the site of injury by a process called chemotaxis , defined as locomotion oriented along a chemical gradient. Both exogenous and endogenous substances can act as chemoattractants . Endogenous chemoattractants include several chemical mediators (described later): (1) cytokines , particularly those of the chemokine family (e.g., IL-8); (2) components of the complement system, particularly C5a ; and (3) arachidonic acid (AA) metabolites, mainly leukotriene B 4 (LTB 4 ) .

20. Recognition of Microbes and Dead Tissues After recruitment at the site of cell death,leukocyte resopnd by two sequential events : (1) recognition of the offending agents (2) leukocytes then ingest and destroy the offending agents and amplify the inflammatory reaction .

21. Leukocytes express several receptors that recognize external stimuli and deliver activating signals Receptors for microbial products: Toll-like receptors (TLRs) recognize components of different types of microbes. G protein–coupled receptors found on neutrophils , macrophages, and most other types of leukocytes recognize short bacterial peptides containing N - formylmethionyl residues.

22. Receptors for opsonins : Leukocytes express receptors for proteins that coat microbes. The process of coating a particle, such as a microbe, to target it for ingestion ( phagocytosis ) is called opsonization , and substances that do this are opsonins . These substances include antibodies, complement proteins, and lectins Receptors for cytokines : Leukocytes express receptors for cytokines that are produced in response to microbes. One of the most important of these cytokines is interferon-γ (IFN-γ),

23. Removal of the Offending Agents Recognition of microbes or dead cells by the receptors described above induces leukocyte activation . The functional responses that are most important for destruction of microbes and other offenders are phagocytosis and intracellular killing.

24. Phagocytosis . Phagocytosis involves three sequential steps : (1) recognition and attachment of the particle to be ingested by the leukocyte; Mannose receptors , scavenger receptors, and receptors for various opsonins all function to bind and ingest microbes. (2) its engulfment , with subsequent formation of a phagocytic vacuole; After a particle is bound to phagocyte receptors, extensions of the cytoplasm ( pseudopods ) flow around it, and the plasma membrane pinches off to form a vesicle ( phagosome ) that encloses the particle

25. The phagosome then fuses with a lysosomal granule, resulting in discharge of the granule's contents into the phagolysosome (see Fig. 2-9 ). During this process the phagocyte may also release granule contents into the extracellular space. (3) killing or degradation of the ingested material Microbial killing is accomplished largely by reactive oxygen species ( ROS , also called reactive oxygen intermediates) and reactive nitrogen species , mainly derived from NO. Microbial killing can also occur through the action of other substances in leukocyte granules.

26. Patterns of acute inflammation Serous is derived from either the plasma or the secretions of mesothelial cells lining the peritoneal, pleural, and pericardial cavities (called effusion). The skin blister resulting from a burn or viral infection represents a large accumulation of serous fluid, either within or immediately beneath the epidermis of the skin

27. Fibrinous With more severe injuries and the resulting greater vascular permeability, larger molecules such as fibrinogen pass the vascular barrier, and fibrin is formed and deposited in the extracellular space. fibrinous exudate is characteristic of inflammation in the lining of body cavities, such as the meninges , pericardium and pleura Either entirely removed or becomes fibrotic

28. Fibrinous pericarditis . A- Deposits of fibrin on the pericardium. B- A pink meshwork of fibrin exudate (F) overlies the pericardial surface (P).

29. Suppurative Suppurative or purulent inflammation is characterized by the production of large amounts of pus ( pyogenic staph spp.) or purulent exudate consisting of neutrophils , necrotic cells, and edema fluid

30. Suppurative inflammation. A- A subcutaneous bacterial abscess with collections of pus. B- The abscess contains neutrophils , edema fluid, and cellular debris.

31. Ulceration An ulcer is a local defect, or excavation, of the surface of an organ or tissue that is produced by the sloughing (shedding) of inflammatory necrotic tissue It is most commonly encountered in: inflammatory necrosis of the mucosa of the mouth, stomach, intestines, or genitourinary tract; and subcutaneous inflammation of the lower extremities in older persons who have circulatory disturbances that predispose to extensive necrosis . Trauma, toxins, vascular insufficiency

32. A- A chronic duodenal ulcer. B- Low-power cross-section of a duodenal ulcer crater with an acute inflammatory exudate in the base.

33. Summary Definition of inflammation Types Acute inflammation Vascular events -change in vessel caliber and change in permiability Cellular events -Recruitment of Leukocytes to Sites of Infection and Injury,( Leukocyte Adhesion to Endothelium, Leukocyte Migration through Endothelium, Chemotaxis of Leukocytes), Recognition of Microbes , Removal of the Offending Agents, Phagocytosis ,