1. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Chapter 14 Inflammation, Tissue Repair, and Wound Healing

2. 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)

3. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Factors Involved in Protective Responses and Bodily Repair Inflammatory reaction Immune response Tissue repair and wound healing

4. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Causes of Inflammation Immune response to infectious microorganisms Trauma Surgery Caustic chemicals Extremes of heat and cold Ischemic damage to body tissues

5. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Granulomatous Inflammation Associated with foreign bodies such as –Splinters –Sutures –Silica, asbestos Associated with microorganisms that cause –Tuberculosis –Syphilis, sarcoidosis –Deep fungal infections –Brucellosis

6. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins 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

7. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins 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)

8. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins 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

9. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Inflammatory Mediators Histamine Cytokines Arachidonic acid metabolites –Eicosanoids Prostaglandins Leukotrienes Omega-3 polyunsaturated fatty acids Platelet-activating factor Plasma proteins

10. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins 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

11. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Question Which of the following molecules will induce endothelial cell retraction? −A. Omega-3 fatty acids −B. Leukotrienes −C. Histamine −D. VCAM

12. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Answer C. Histamine Rationale: Histamine is the primary activator of endothelial retraction and increased permeability of the vessels.

13. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins 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

14. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins 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

15. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins 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

16. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins 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

17. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Most Prominent Systemic Manifestations of Inflammation Acute-phase response Alterations in white blood cell count (leukocytosis or leukopenia) Fever Sepsis and septic shock (severe)

18. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Question Is the following statement true or false? Permanent cells, once damaged, can easily be regenerated and their functions recovered.

19. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Answer False Rationale: Many cells in the body cannot be replaced once they die. Neurons and cardiac cells are such examples.

20. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins 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

21. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins 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

22. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins 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

23. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins 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

24. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins 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

25. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Stages of Wound Healing Inflammatory phase Proliferative phase Maturational or remodeling phase

26. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins 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)

27. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Question Which of the following will promote wound healing? −A. Malnutrition −B. Increased blood flow and oxygen delivery −C. Infection −D. Foreign bodies

28. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins 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.

29. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Factors Regulating the Healing Process Action of chemical mediators and growth factors that mediate the healing process Interactions between the extracellular and cell matrix

30. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Two Phases of Scar Formation Emigration and proliferation of fibroblasts into the site of injury Deposition of the ECM by these cells

31. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Causes of Impaired Wound Healing Malnutrition Impaired blood flow and oxygen delivery Impaired inflammatory and immune responses Infection Wound separation Foreign bodies Age effects