Focus on Inflammation Relates to Chapter 13 Inflammation

Focus on Inflammation (Relates to Chapter 13, “Inflammation and Wound Healing, ” in the textbook) Copyright © 2007, 2004, 2000, Mosby, Inc. , an affiliate of Elsevier Inc. All Rights Reserved.

Inflammatory Response n Sequential response to cell injury Neutralizes and dilutes inflammatory agent n Removes necrotic materials n Establishes an environment suitable for healing and repair n Copyright © 2007, 2004, 2000, Mosby, Inc. , an affiliate of Elsevier Inc. All Rights Reserved.

Inflammatory Response Mechanism of inflammation basically same regardless of injuring agent n Inflammation is always present with infection n Infection is not always present with inflammation n Copyright © 2007, 2004, 2000, Mosby, Inc. , an affiliate of Elsevier Inc. All Rights Reserved.

Inflammatory Response n Causes Heat n Radiation n Trauma n Allergens n Infection n Copyright © 2007, 2004, 2000, Mosby, Inc. , an affiliate of Elsevier Inc. All Rights Reserved.

Inflammatory Response n Intensity of the response depends on Extent and severity of injury n Reactive capacity of injured person n Copyright © 2007, 2004, 2000, Mosby, Inc. , an affiliate of Elsevier Inc. All Rights Reserved.

Inflammatory Response n Inflammatory response can be divided into Vascular response n Cellular response n Formation of exudate n Healing n Copyright © 2007, 2004, 2000, Mosby, Inc. , an affiliate of Elsevier Inc. All Rights Reserved.

Inflammatory Response Vascular Response After cell injury, arterioles in area briefly undergo transient vasoconstriction n After release of histamine and other chemicals by the injured cells, vessels dilate resulting in hyperemia n Copyright © 2007, 2004, 2000, Mosby, Inc. , an affiliate of Elsevier Inc. All Rights Reserved.

Vascular Response Cell injury Cell death Release of kinins, histamine, prostaglandins Momentary local vasoconstriction Local vasodilation Hyperemia FIG. 13 -1 Capillary permeability Fluid exudate Copyright © 2007, 2004, 2000, Mosby, Inc. , an affiliate of Elsevier Inc. All Rights Reserved.

Inflammatory Response Vascular Response n Vasodilation Results in hyperemia n Increased blood flow in the area n Raises filtration pressure n Copyright © 2007, 2004, 2000, Mosby, Inc. , an affiliate of Elsevier Inc. All Rights Reserved.

Inflammatory Response Vascular & Chemical Response n Vasodilation chemical mediators Endothelial cell retraction n Increased capillary permeability n Movement of fluid from capillaries into tissue spaces n Copyright © 2007, 2004, 2000, Mosby, Inc. , an affiliate of Elsevier Inc. All Rights Reserved.

Inflammatory Response Vascular Response n Fluid in tissue spaces Initially composed of serous fluid n Later contains plasma proteins, primarily albumin n Proteins exert oncotic pressure that further draws fluid from blood vessels n Tissue becomes edematous n Copyright © 2007, 2004, 2000, Mosby, Inc. , an affiliate of Elsevier Inc. All Rights Reserved.

Inflammatory Response Vascular Response As plasma protein fibrinogen leaves blood, it is activated to fibrin by products of the injured cells n Fibrin strengthens a blood clot formed by platelets n In tissue, clots trap bacteria to prevent spread n Copyright © 2007, 2004, 2000, Mosby, Inc. , an affiliate of Elsevier Inc. All Rights Reserved.

Inflammatory Response Cellular Response Blood flow through capillaries in the area of inflammation slows as fluid is lost and viscosity increases n Neutrophils and monocytes move to the inner surface of the capillaries and then migrate through the capillary wall to the site of the injury n Copyright © 2007, 2004, 2000, Mosby, Inc. , an affiliate of Elsevier Inc. All Rights Reserved.

Inflammatory Response Cellular Response n Chemotaxis Directional migration of WBCs along concentration gradient of chemotactic factors n Mechanism for accumulating neutrophils and monocytes at site of injury n Copyright © 2007, 2004, 2000, Mosby, Inc. , an affiliate of Elsevier Inc. All Rights Reserved.

Margination, Diapedesis, and Chemotaxis FIG. 13 - 3 Copyright © 2007, 2004, 2000, Mosby, Inc. , an affiliate of Elsevier Inc. All Rights Reserved.

Inflammatory Response Cellular Response n Chemotactic factors Bacterial-derived n Complement-derived (C 5 a, C 3 a) n Lipid-derived n Platelet-derived n Coagulation-related n Chemokines n Copyright © 2007, 2004, 2000, Mosby, Inc. , an affiliate of Elsevier Inc. All Rights Reserved.

Inflammatory Response Cellular Response n Neutrophils First leukocytes to arrive at site of injury (6 to 12 hours) n Phagocytize bacteria, other foreign material, and damaged cells n Short life span (24 to 48 hours) n Copyright © 2007, 2004, 2000, Mosby, Inc. , an affiliate of Elsevier Inc. All Rights Reserved.

Inflammatory Response Cellular Response n Neutrophils n Pus is composed of Dead neutrophils accumulated at the site of injury n Digested bacteria n Other cell debris n Copyright © 2007, 2004, 2000, Mosby, Inc. , an affiliate of Elsevier Inc. All Rights Reserved.

Inflammatory Response Cellular Response n Neutrophils n Bone marrow releases more neutrophils in response to infection resulting in elevated WBC Copyright © 2007, 2004, 2000, Mosby, Inc. , an affiliate of Elsevier Inc. All Rights Reserved.

Inflammatory Response Cellular Response n Monocytes Second type of phagocytic cells to migrate to site of injury from circulating blood n Attracted to the site by chemotactic factors n Arrive within 3 to 7 days after the onset of inflammation n Copyright © 2007, 2004, 2000, Mosby, Inc. , an affiliate of Elsevier Inc. All Rights Reserved.

Inflammatory Response Cellular Response n Monocytes On entering tissue spaces, monocytes transform into macrophages n Assist in phagocytosis of inflammatory debris n Macrophages have a long life span and can multiply n Copyright © 2007, 2004, 2000, Mosby, Inc. , an affiliate of Elsevier Inc. All Rights Reserved.

Inflammatory Response Cellular Response n Macrophage Important in cleaning the area before healing can occur n May stay in damaged tissues for weeks n Cells may fuse to form a multinucleated giant cell n Copyright © 2007, 2004, 2000, Mosby, Inc. , an affiliate of Elsevier Inc. All Rights Reserved.

Inflammatory Response Cellular Response n Lymphocytes Arrive later at the site of injury n Primary role of lymphocytes involve n Cell-mediated immunity n Humoral immunity n Copyright © 2007, 2004, 2000, Mosby, Inc. , an affiliate of Elsevier Inc. All Rights Reserved.

Cellular Response in Inflammation FIG. 13 - 2 Copyright © 2007, 2004, 2000, Mosby, Inc. , an affiliate of Elsevier Inc. All Rights Reserved.

Inflammatory Response Cellular Response n Eosinophils Released in large quantities during an allergic reaction n Release chemicals that act to control the effects of histamine and serotonin n Involved in phagocytosis of allergen– antibody complex n Copyright © 2007, 2004, 2000, Mosby, Inc. , an affiliate of Elsevier Inc. All Rights Reserved.

Inflammatory Response Cellular Response n Basophils Carry histamine and heparin in their granules that are released during inflammation n Have limited phagocytic capabilities n Copyright © 2007, 2004, 2000, Mosby, Inc. , an affiliate of Elsevier Inc. All Rights Reserved.

Inflammatory Response Cellular Response n Chemical mediators Histamine n Serotonin n Kinins (e. g. , bradykinin) n Copyright © 2007, 2004, 2000, Mosby, Inc. , an affiliate of Elsevier Inc. All Rights Reserved.

Inflammatory Response Cellular Response n Chemical mediators Complement components (C 3 a, C 4 a, C 5 a) n Prostaglandins and leukotrienes n Cytokines n Copyright © 2007, 2004, 2000, Mosby, Inc. , an affiliate of Elsevier Inc. All Rights Reserved.

Inflammatory Response Cellular Response n Complement system Major mediator of the inflammatory response n When activated, the components occur in sequential order involving two pathways n Each activated complex can act on the next component n Copyright © 2007, 2004, 2000, Mosby, Inc. , an affiliate of Elsevier Inc. All Rights Reserved.

Inflammatory Response Complement System FIG. 13 - 4 Copyright © 2007, 2004, 2000, Mosby, Inc. , an affiliate of Elsevier Inc. All Rights Reserved.

Inflammatory Response Cellular Response n Major functions of the complement system Enhanced phagocytosis n Increased vascular permeability n Chemotaxis n Cellular lysis n Copyright © 2007, 2004, 2000, Mosby, Inc. , an affiliate of Elsevier Inc. All Rights Reserved.

Inflammatory Response Cellular Response n Major functions of the complement system Enhanced phagocytosis n Increased vascular permeability n Chemotaxis n Cellular lysis n Copyright © 2007, 2004, 2000, Mosby, Inc. , an affiliate of Elsevier Inc. All Rights Reserved.

Inflammatory Response Cellular Response n Complement system Activation increases phagocytosis through opsonization and chemotaxis n The entire complement sequence of C 1 to C 9 must be activated for cell lysis to occur n Copyright © 2007, 2004, 2000, Mosby, Inc. , an affiliate of Elsevier Inc. All Rights Reserved.

Inflammatory Response Cellular Response n Complement system (cont’d) n C 8 and C 9, the final components of the complement system, pierce the cell surface, causing rupture of the cell membrane and lysis Copyright © 2007, 2004, 2000, Mosby, Inc. , an affiliate of Elsevier Inc. All Rights Reserved.

Inflammatory Response Cellular Response n Prostaglandins Synthesized from the phospholipids of cell membranes of most body tissues, including blood cells n Phospholipids are converted to arachidonic acid, which is then oxidized by two different pathways n Copyright © 2007, 2004, 2000, Mosby, Inc. , an affiliate of Elsevier Inc. All Rights Reserved.

Inflammatory Response Cellular Response n Prostaglandins Series E and I prostaglandins are potent vasodilators and inhibit platelet and neutrophil aggregation n Prostaglandins are generally considered proinflammatory, contributing to increased blood flow, edema, and pain n Copyright © 2007, 2004, 2000, Mosby, Inc. , an affiliate of Elsevier Inc. All Rights Reserved.

Inflammatory Response Cellular Response n Prostaglandins n Drugs that inhibit prostaglandin synthesis Nonsteroidal anti-inflammatory drugs n Aspirin n Corticosteroids n Copyright © 2007, 2004, 2000, Mosby, Inc. , an affiliate of Elsevier Inc. All Rights Reserved.

Pathway of Arachidonic Acid Oxygenation FIG. 13 - 5 Copyright © 2007, 2004, 2000, Mosby, Inc. , an affiliate of Elsevier Inc. All Rights Reserved.

Inflammatory Response Cellular Response n Exudate Consists of fluid and leukocytes that move from the circulation to the site of injury n Nature and quantity depend on the type and severity of the injury and the tissues involved n Copyright © 2007, 2004, 2000, Mosby, Inc. , an affiliate of Elsevier Inc. All Rights Reserved.

Inflammatory Response Clinical Manifestations n Local response to inflammation Redness n Heat n Pain n Swelling n Loss of function n Copyright © 2007, 2004, 2000, Mosby, Inc. , an affiliate of Elsevier Inc. All Rights Reserved.

Inflammatory Response Clinical Manifestations n Systemic response to inflammation Increased WBC count with a shift to the left n Malaise n Nausea and anorexia n Increased pulse and respiratory rate n Fever n Copyright © 2007, 2004, 2000, Mosby, Inc. , an affiliate of Elsevier Inc. All Rights Reserved.

Inflammatory Response Clinical Manifestations n Systemic response to inflammation The causes of the systemic response are poorly understood, but it is probably due to complement activation and the release of cytokines n Some of the cytokines are IL-1, IL-6, and tumor necrosis factor n Copyright © 2007, 2004, 2000, Mosby, Inc. , an affiliate of Elsevier Inc. All Rights Reserved.

Inflammatory Response Clinical Manifestations n Systemic response to inflammation n Fever Onset is triggered by release of cytokines n Cytokines cause fever by initiating metabolic changes in the temperatureregulating center n Epinephrine released from the adrenal medulla increases metabolic rate n Copyright © 2007, 2004, 2000, Mosby, Inc. , an affiliate of Elsevier Inc. All Rights Reserved.

Inflammatory Response Clinical Manifestations n Systemic response to inflammation n Fever Patient then experiences chills and shivering n Body is hot yet person seeks warmth until the circulating temperature reaches core body temperature n Copyright © 2007, 2004, 2000, Mosby, Inc. , an affiliate of Elsevier Inc. All Rights Reserved.

Inflammatory Response Clinical Manifestations n Systemic response to inflammation n Fever n Beneficial aspects of fever include increased killing of microorganisms, increased phagocytosis, and increased proliferation of T lymphocytes Copyright © 2007, 2004, 2000, Mosby, Inc. , an affiliate of Elsevier Inc. All Rights Reserved.

Production of fever Fig. 10 -6 Copyright © 2007, 2004, 2000, Mosby, Inc. , an affiliate of Elsevier Inc. All Rights Reserved.

Inflammatory Response Types of Inflammation n Acute Healing occurs in 2 to 3 weeks, usually leaving no residual damage n Neutrophils are the predominant cell type at the site of inflammation n Copyright © 2007, 2004, 2000, Mosby, Inc. , an affiliate of Elsevier Inc. All Rights Reserved.

Inflammatory Response Types of Inflammation n Subacute n Has same features as acute inflammation but persists longer Copyright © 2007, 2004, 2000, Mosby, Inc. , an affiliate of Elsevier Inc. All Rights Reserved.

Inflammatory Response Types of Inflammation n Chronic May last for years n Injurious agent persists or repeats injury to site n Predominant cell types involved are lymphocytes and macrophages n May result from changes in immune system (e. g. , autoimmune disease) n Copyright © 2007, 2004, 2000, Mosby, Inc. , an affiliate of Elsevier Inc. All Rights Reserved.

Inflammatory Response Healing Process n Regeneration n Replacement of lost cells and tissues with cells of the same type Copyright © 2007, 2004, 2000, Mosby, Inc. , an affiliate of Elsevier Inc. All Rights Reserved.

Inflammatory Response Healing Process n Regeneration Ability to regenerate depends on cell type n Constantly dividing cells that rapidly regenerate n n Skin, bone marrow, lymphoid organs, as well as mucous membrane cells of the urinary, reproductive, and GI tracts Copyright © 2007, 2004, 2000, Mosby, Inc. , an affiliate of Elsevier Inc. All Rights Reserved.

Inflammatory Response Healing Process n Regeneration n Replacement of lost cells and tissues with cells of the same type n Stable cells such as liver, bone, kidney, and pancreas regenerate in response to injury Copyright © 2007, 2004, 2000, Mosby, Inc. , an affiliate of Elsevier Inc. All Rights Reserved.

Inflammatory Response Healing Process n Regeneration Permanent cells such as neurons, skeletal and cardiac muscle do not divide n Neurons are replaced by glial cells, and new neurons may be produced by stem cells n Skeletal and cardiac muscle will be repaired with scar tissue n Copyright © 2007, 2004, 2000, Mosby, Inc. , an affiliate of Elsevier Inc. All Rights Reserved.

Inflammatory Response Healing Process n Repair Healing as a result of lost cells being replaced with connective tissue n Repair is more complex than regeneration n Copyright © 2007, 2004, 2000, Mosby, Inc. , an affiliate of Elsevier Inc. All Rights Reserved.

Inflammatory Response Healing Process n Repair is the most common type of healing and usually results in scar formation Initial phase–lasts 3 to 5 days n Granulation phase–lasts from 5 days to 3 weeks n Maturation phase and scar contraction– from 7 days to several months or years n Copyright © 2007, 2004, 2000, Mosby, Inc. , an affiliate of Elsevier Inc. All Rights Reserved.