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Inflammation

Inflammation

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Published by: Abutaleb Modaresi on Jan 13, 2011
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NS 521 - Inflammation

‡ Overview of Cellular Mechanisms Involved in Acute Inflammation ‡ Chemical Mediators of Acute Inflammation ‡ Examples of Acute Inflammatory Responses ‡ Differences Between Acute and Chronic Inflammation ‡ Examples of Chronic Inflammation ‡ Discussion of Potential Roles of Nutrition in Inflammation

Acute Inflammation
Acute inflammation is a rapid response to an injurious agent that serves to deliver mediators of host defense²leukocytes and plasma proteins²to the site of injury. Acute inflammation has three major components: (1) alterations in vascular caliber that lead to an increase in blood flow; (2) structural changes in the microvasculature that permit plasma proteins and leukocytes to leave the circulation; and (3) emigration of the leukocytes from the microcirculation, their accumulation in the focus of injury, and their activation to eliminate the offending agent

Acute inflammatory reactions are triggered by a variety of stimuli: ‡ Infections (bacterial, viral, parasitic) and microbial toxins ‡ Trauma (blunt and penetrating) ‡ Physical and chemical agents (thermal injury, e.g., burns or frostbite; irradiation; some environmental chemicals) ‡ Tissue necrosis (from any cause) ‡ Foreign bodies (splinters, dirt, sutures) ‡ Immune reactions (also called hypersensitivity reactions)

phagocytes and other host cells react to the presence of the foreign or abnormal substance by liberating cytokines. .Acute Inflammation When a host encounters an injurious agent. lipid messengers. At the same time. phagocytes that reside in all tissues try to get rid of these agents. and the various other mediators of inflammation. Some of these mediators act on endothelial cells in the vicinity and promote the efflux of plasma and the recruitment of circulating leukocytes to the site where the offending agent is located. such as an infectious microbe or dead cells.

the result may be chronic inflammation. the process subsides and the host returns to a normal state of health. and the activated leukocytes try to remove the offending agent by phagocytosis.Acute Inflammation . If the injurious agent cannot be quickly eliminated. The recruited leukocytes are activated by the injurious agent and by locally produced mediators. .continued As the injurious agent is eliminated and antiinflammatory mechanisms become active.

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Lymphocyte and Neutrophil Monocyte .

and swelling (tumor) of acute inflammation are caused by the increased blood flow and edema. warmth (calor). . The redness (rubor). Increased vascular permeability results in the accumulation of protein-rich extravascular fluid.The vascular phenomena of acute inflammation are characterized by increased blood flow to the injured area. resulting mainly from arteriolar dilation and opening of capillary beds induced by mediators such as histamine. most commonly through widened interendothelial cell junctions of the venules. which forms the exudate. Plasma proteins leave the vessels.

causing tissue damage. . initially predominantly neutrophils. and cytokines. transmigrate across the endothelium. Leukocytes that are activated by the offending agent and by endogenous mediators may release toxic metabolites and proteases extracellularly.Circulating leukocytes. neuropeptides. one of the local symptoms is pain (dolor). and migrate to the site of injury under the influence of chemotactic agents. adhere to the endothelium via adhesion molecules. During the damage. and in part as a result of the liberation of prostaglandins.

notably histamine and nitric oxide on smooth muscle. The loss of fluid results in concentration of red cells in small vessels and increased viscosity of the blood. .Changes in vascular flow and caliber begin early after injury and develop at varying rates depending on the severity of the injury. Vasodilation is induced by the action of several mediators. Increased blood flow is the cause of the heat and the redness. The changes occur in the following order: ‡ Vasodilation. ‡ Stasis. ‡ Increased permeability of the microvasculature.

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The loss of protein from the plasma reduces the intravascular osmotic pressure and increases the osmotic pressure of the interstitial fluid. The net increase of extravascular fluid results in edema. . Together with the increased hydrostatic pressure owing to increased blood flow through the dilated vessels. this leads to a marked outflow of fluid and its accumulation in the interstitial tissue.A hallmark of acute inflammation is increased vascular permeability leading to the escape of a protein-rich fluid (exudate) into the extravascular tissue.

Vascular Permeability ± Leakage of Carbon Particles .

mediated mainly by the actions of histamine and leukotrienes on endothelium. and (3) a prolonged response that is most noticeable after direct endothelial injury. after burns. (2) a delayed response starting at about 2 hours and lasting for about 8 hours. fluid loss from vessels with increased permeability occurs in distinct phases: (1) an immediate transient response lasting for 30 minutes or less.EDEMA In acute inflammation. and other factors. for example. . mediated by kinins. complement products.

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as a prelude to their exit from the blood vessels.The sequence of events in the journey of leukocytes from the vessel lumen to the interstitial tissue. the endothelium has to be activated to permit it to bind leukocytes. Vascular endothelium normally does not bind circulating cells or impede their passage. rolling. Migration in interstitial tissues toward a chemotactic stimulus . called extravasation. and adhesion to endothelium. 2. Transmigration across the endothelium (also called diapedesis) 3. In inflammation. can be divided into the following steps: 1. In the lumen: margination.

Leukocytes Rolling Within a Venule

Neutrophil Pavementing (lining the venule)

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Leukocyte Margination and Diapedesis .

Neutrophil Transendothelial Migration (Diapedesis) .

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Mediator Histamine Serotonin (5±HT) Bradykinin Complement 3a Complement 3b Complement 5a Prostaglandins Leukotrienes Lysosomal proteases Oxygen radicals Vasodilation + + + ± ± ± +++ ± ± ± Immediate +++ + + + ± + + +++ ± ± Sustained ± ± ± ± ± ± +? +? ++1 ++1 Chemotaxis ± ± ± ± ± +++ ± +++ ± ± Opsonin ± ± ± ± +++ ± ± ± ± ± Pain ± ± ++ ± ± ± ± ± ± .Table 3±2. Mediators of Acute Inflammation.

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Resolution of Acute Inflammation .

eosinophilia in blood. The necrotic mucosa and inflammatory exudate form an adherent membrane on the mucosal surface.Table 3±4. allergy (eg. diphtheria bacillus (Corynebacterium diphtheriae) and Clostridium difficile. Common Causes Bacterial infections. viral. Marked neutrophil leukocytosis in blood. anaerobes. lymphocytes and plasma cells predominant. eg. herpes simplex encephalitis. Suppurative (purulent) inflammation Pyogenic bacteria. Toxigenic bacteria. neutrophil leukocytosis in blood. Infections. anthrax (Bacillus anthracis). Paucity of neutrophils in exudate. fungal). Excess fibrin formation. Exaggerated neutrophil response and liquefactive necrosis of parenchymal cells. hemorrhagic inflammation Membranous (pseudomembranou s) inflammation Burns. plague (Yersinia pestis). mucormycosis. Types of Acute Inflammation. Marked fluid exudation. eg. lymphocytosis in blood. Marked edema and numerous eosinophils. Certain hypersensitivity immune reactions Acute inflammation without neutrophils Allergic acute inflammation Serous inflammation (inflammation in body cavities) Catarrhal inflammation (inflammation of mucous membranes) Fibrinous inflammation Necrotizing inflammation. Marked tissue necrosis and hemorrhage. hay fever). pus formation. eg. common cold (rhinovirus). neutropenia. Marked secretion of mucus. many bacterial infections. eg. Highly virulent organisms (bacterial. Type Classic type Features Hyperemia. . staphylococci. streptococci. response to cell necrosis of any cause. Many virulent bacterial infections. gram±negative bacilli. Necrotizing inflammation involving mucous membranes. Viral and rickettsial infections (immune response contributes). exudation with fibrin and neutrophils.

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Inflammed Lung .

necrotic cells.Suppurative or purulent inflammation is characterized by the production of large amounts of pus or purulent exudate consisting of neutrophils. . and edema fluid.

. is derived from either the plasma or the secretions of mesothelial cells lining the peritoneal. and pericardial cavities (called effusion). depending on the size of injury. pleural.Serous inflammation is marked by the outpouring of a thin fluid that.

and fibrin is formed and deposited in the extracellular space . larger molecules such as fibrinogen pass the vascular barrier.FIBRINOUS INFLAMMATION With more severe injuries and the resulting greater vascular permeability.

or excavation.An ulcer is a local defect. of the surface of an organ or tissue that is produced by the sloughing (shedding) of inflammatory necrotic tissue .

Viral Hepatitis .

chronic inflammation is considered to be inflammation of prolonged duration (weeks or months) in which active inflammation. and attempts at repair are proceeding simultaneously.Chronic Inflammation Although difficult to define precisely. tissue destruction. and chronic lung diseases. such as rheumatoid arthritis. tuberculosis. atherosclerosis. This latter type of chronic inflammation is the cause of tissue damage in some of the most common and disabling human diseases. . often asymptomatic response. Although it may follow acute inflammation. chronic inflammation frequently begins insidiously. smoldering. as a low-grade.

either exogenous or endogenous ‡ Autoimmunity .Chronic inflammation arises in the following settings: ‡ Persistent infections ‡ Prolonged exposure to potentially toxic agents.

lymphocytes. edema.In contrast to acute inflammation. chronic inflammation is characterized by: ‡ Infiltration with mononuclear cells. which include macrophages. and predominantly neutrophilic infiltration. ‡ Tissue destruction. ‡ Attempts at healing by connective tissue replacement of damaged tissue. fibrosis . which is manifested by vascular changes. and plasma cells. in particular. accomplished by proliferation of small blood vessels (angiogenesis) and. induced by the persistent offending agent or by the inflammatory cells.

increased plasma immunoglobulin . increased permeability + + Chronic Long (weeks to months) Insidious Specific (where immune response is activated) Lymphocytes. neutrophils. pain) Tissue necrosis ± (Usually) + (Suppurative and necrotizing inflammation) Short (days) Acute Nonspecific Neutrophils. often high Neutrophil leukocytosis. Differences between Acute and Chronic Inflammation. lymphocytosis (in viral infections) + Immune response. nonimmune phagocytosis Fever. macrophages Active vasodilation. properdin. weight loss. fibroblasts New vessel formation (granulation tissue) ± ± + (ongoing) Fibrosis (collagen deposition) Operative host responses ± Plasma factors: complement. swelling. plasma cells. anemia Frequently none.Table 5±1. Acute Duration Onset Specificity Inflammatory cells Vascular changes Fluid exudation and edema Cardinal clinical signs (redness. variable leukocyte changes. phagocytosis. immunoglobulins. heat. etc. macrophages. repair Systemic manifestations Changes in peripheral blood Low±grade fever.

and are responsible for much of the tissue injury in chronic inflammation. . Tissue destruction is one of the hallmarks of chronic inflammation.The products of activated macrophages serve to eliminate injurious agents such as microbes and to initiate the process of repair.

macrophage accumulation persists. macrophages eventually disappear (either dying off or making their way into the lymphatics and lymph nodes). and is mediated by different mechanisms . if the irritant is eliminated. In chronic inflammation.In short-lived inflammation.

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.A granuloma is a focus of chronic inflammation consisting of a microscopic aggregation of macrophages that are transformed into epithelium-like cells surrounded by a collar of mononuclear leukocytes. principally lymphocytes and occasionally plasma cells.

in intravenous drug abuse) Talc.Table 5±2. Common Causes of Epithelioid Cell Granulomas. Disease Antigen Caseous Necrosis Immunologic response Tuberculosis Leprosy (tuberculoid type) Histoplasmosis Coccidioidomycosis Q fever Mycobacterium tuberculosis Mycobacterium leprae Histoplasma capsulatum Coccidioides immitis Coxiella burnetii (rickettsial organism) ++ ± ++ ++ ± Brucellosis Syphilis Brucella species Treponema pallidum ± ++1 Sarcoidosis2 Unknown ± Crohn's disease2 Unknown ± Berylliosis3 Beryllium (? +protein) ± Nonimmunologic response Foreign body (eg. fibers (? +protein) ± .

Lung Granuloma From Tuberculosis (Tubercle) .

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Vacuolated Macrophages in Leprosy .

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Foreign Body Granuloma .

Scar Formation From a Granuloma .

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Potential Roles of Nutrition in Inflammation and Immunity Under-nutrition Deficencies Protein/Calorie Essential Fatty Acids Zinc. Copper. and Iron Vitamin A Antioxidants Other Micronutrients Over-nutrition Obesity Adipokines Omega-6 Fatty Acids Eicosinoids .

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Dietary restriction impairs neutrophil exudation by reducing CD11b/CD18 expression and chemokine production..136(3):297304 . et al. Arch Surg. 2001 Mar. S. Ikeda.

.136:297-304. S. et al.Circulating polymorphonuclear neutrophil (PMN) kinetics Ikeda. Arch Surg 2001. Copyright restrictions may apply.

Arch Surg 2001. Copyright restrictions may apply. et al. S. .Exudative polymorphonuclear neutrophil (PMN) kinetics Ikeda.136:297-304.

et al.Correlation between CD18 expression on circulating polymorphonuclear neutrophils (PMNs) and number of exudative PMNs Ikeda. Arch Surg 2001. Copyright restrictions may apply.136:297-304. . S.

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