Chapter 18 Inflammation, Tissue Repair, and Wound Healing Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Cardinal Signs of Inflammation • Rubor (redness) • Tumor (swelling) • Calor (heat) • Dolor (pain) • Functio laesa (loss of function) Copyright © 2017 Wolters Kluwer • All Rights Reserved Factors Involved in Protective Responses and Bodily Repair • Inflammatory reaction • Immune response • Tissue repair and wound healing Copyright © 2017 Wolters Kluwer • All Rights Reserved Causes of Inflammation • Immune response to infectious microorganisms • Trauma • Surgery • Caustic chemicals • Extremes of heat and cold • Ischemic damage to body tissues Copyright © 2017 Wolters Kluwer • All Rights Reserved Granulomatous Inflammation • Associated with foreign bodies such as – Splinters – Sutures – Silica, asbestos • Associated with microorganisms that cause – Tuberculosis – Syphilis, sarcoidosis – Deep fungal infections – Brucellosis Copyright © 2017 Wolters Kluwer • All Rights Reserved Vascular Changes that May Occur with Inflammation • An immediate transient response – Occurs with minor injury • An immediate sustained response – Occurs with more serious injury and continues for several days and damages the vessels in the area • A delayed hemodynamic response – Involves an increase in capillary permeability that occurs 4 to 24 hours after injury Copyright © 2017 Wolters Kluwer • All Rights Reserved Cellular Stage of Acute Inflammation • Marked by movement of phagocytic white blood cells (leukocytes) into the area of injury • Two types of leukocytes participate in the acute inflammatory response: – Granulocytes (neutrophils, eosinophils, and basophils) – Monocytes (the largest of the white blood cells) Copyright © 2017 Wolters Kluwer • All Rights Reserved Direction of Cellular Response • Margination, adhesion, transmigration – Cytokines • Adhesion molecules • Selectins, integrins, and immunoglobulin • Initiation of adhesion • Aggregation of inflammatory cells • Movement into underlying tissue Copyright © 2017 Wolters Kluwer • All Rights Reserved Inflammatory Mediators • Histamine • Cytokines • Arachidonic acid metabolites – Eicosanoids • Prostaglandins • Leukotrienes • Omega-3 polyunsaturated fatty acids • Platelet-activating factor • Plasma proteins Copyright © 2017 Wolters Kluwer • All Rights Reserved Classification of Inflammatory Mediators by Function • Those with vasoactive and smooth muscle–constricting properties • Chemotactic factors such as complement fragments and cytokines • Plasma proteases that can activate complement and components of the clotting system • Reactive molecules and cytokines liberated from leukocytes, which when released into the extracellular environment can damage the surrounding tissue Copyright © 2017 Wolters Kluwer • All Rights Reserved Question • Which of the following molecules will induce endothelial cell retraction? − A. Omega-3 fatty acids − B. Leukotrienes − C. Histamine − D. VCAM Copyright © 2017 Wolters Kluwer • All Rights Reserved Answer • C. Histamine • Rationale: Histamine is the primary activator of endothelial retraction and increased permeability of the vessels. Copyright © 2017 Wolters Kluwer • All Rights Reserved Types of Inflammatory Exudates • Serous Exudates – Watery fluids low in protein content – Result from plasma entering the inflammatory site • Hemorrhagic Exudates – Occur when there is severe tissue injury that causes damage to blood vessels or when there is significant leakage of red cells from the capillaries Copyright © 2017 Wolters Kluwer • All Rights Reserved Types of Inflammatory Exudates (cont.) • Membranous or Pseudomembranous Exudates – Develop on mucous membrane surfaces – Are composed of necrotic cells enmeshed in a fibropurulent exudate • Purulent or Suppurative Exudates – Contain pus; composed of degraded white blood cells, proteins, and tissue debris • Fibrinous Exudates – Contain large amounts of fibrinogen and form a thick and sticky meshwork Copyright © 2017 Wolters Kluwer • All Rights Reserved Basic Patterns of Inflammation • Acute inflammation – Of relatively short duration; nonspecific early response to injury – Aimed primarily at removing the injurious agent and limiting tissue damage • Chronic inflammation – Longer duration lasting for days to years – A recurrent or progressive acute inflammatory process or a low-grade smoldering response that fails to evoke an acute response Copyright © 2017 Wolters Kluwer • All Rights Reserved Chronic Versus Acute Inflammation • Acute inflammation—self-limited and of short duration – Infiltration of neutrophils – Exudate • Chronic inflammation—self-perpetuating and may last for weeks, months, or even years – Infiltration by mononuclear cells (macrophages) and lymphocytes – Proliferation of fibroblasts Copyright © 2017 Wolters Kluwer • All Rights Reserved Most Prominent Systemic Manifestations of Inflammation • Acute-phase response • Alterations in white blood cell count (leukocytosis or leukopenia) • Fever • Sepsis and septic shock (severe) Copyright © 2017 Wolters Kluwer • All Rights Reserved Question • Is the following statement true or false? • Permanent cells, once damaged, can easily be regenerated and their functions recovered. Copyright © 2017 Wolters Kluwer • All Rights Reserved Answer • False • Rationale: Many cells in the body cannot be replaced once they die. Neurons and cardiac cells are such examples. Copyright © 2017 Wolters Kluwer • All Rights Reserved Types of Structures of Body Organs and Tissues • Parenchymal – Tissues contain the functioning cells of an organ or body part (e.g., hepatocytes, renal tubular cells) • The Stromal Tissues – Consist of the supporting connective tissues, blood vessels, extracellular matrix, and nerve fibers Copyright © 2017 Wolters Kluwer • All Rights Reserved Types of Body Cells • Labile – Continue to divide and replicate throughout life, replacing cells that are continually being destroyed • Stable – Normally stop dividing when growth ceases • Permanent Cells – Cannot undergo mitotic division Copyright © 2017 Wolters Kluwer • All Rights Reserved Healing by Primary or Secondary Intention • The objective of the healing process is to fill the gap created by tissue destruction and to restore the structural continuity. • Primary healing—small, clean wound • Secondary healing—great loss of tissue with contamination Copyright © 2017 Wolters Kluwer • All Rights Reserved Basic Components of the Extracellular Matrix (ECM) • Fibrous structural proteins – Collagen and elastin fibers • Water-hydrated gels that permit resilience and lubrication – Proteoglycans and hyaluronic acid • Adhesive glycoproteins that connect the matrix elements to each other and to cells – Fibronectin and laminin Copyright © 2017 Wolters Kluwer • All Rights Reserved Basic Forms of the ECM • Basement Membrane – Surrounds epithelial, endothelial, and smooth muscle cells • Interstitial Matrix – Present in the spaces between cells the connective tissue and between the epithelium and supporting cells of blood vessels Copyright © 2017 Wolters Kluwer • All Rights Reserved Stages of Wound Healing • Inflammatory phase • Proliferative phase • Maturational or remodeling phase Copyright © 2017 Wolters Kluwer • All Rights Reserved Steps in Development of a New Capillary Vessel • Proteolytic degradation of the parent vessel basement membrane, allowing for formation of a capillary sprout • Migration of endothelial cells from the original capillary toward an angiogenic stimuli • Proliferation of the endothelial cells behind the leading edge of the migrating cells • Maturation of the endothelial cells and proliferation of pericytes (for capillaries) and smooth muscle cells (for larger vessels) Copyright © 2017 Wolters Kluwer • All Rights Reserved Question • Which of the following will promote wound healing? − A. Malnutrition − B. Increased blood flow and oxygen delivery − C. Infection − D. Foreign bodies Copyright © 2017 Wolters Kluwer • All Rights Reserved Answer • B. Increased blood flow and oxygen delivery • Rationale: Increasing blood flow and oxygen delivery is one of the main objectives of the inflammatory response. This will allow for greater energy production and faster removal of dead material. Copyright © 2017 Wolters Kluwer • All Rights Reserved Factors Regulating the Healing Process • Action of chemical mediators and growth factors that mediate the healing process • Interactions between the extracellular and cell matrix Copyright © 2017 Wolters Kluwer • All Rights Reserved Two Phases of Scar Formation • Emigration and proliferation of fibroblasts into the site of injury • Deposition of the ECM by these cells Copyright © 2017 Wolters Kluwer • All Rights Reserved Causes of Impaired Wound Healing • Malnutrition • Impaired blood flow and oxygen delivery • Impaired inflammatory and immune responses • Infection • Wound separation • Foreign bodies • Age effects Copyright © 2017 Wolters Kluwer • All Rights Reserved
