Chapter 14 Inflammation, Tissue Repair, and Fever Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Inflammation • Inflammation is an automatic response to cell injury that: – Neutralizes harmful agents – Removes dead tissue Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Inflammation • Damaged cells release inflammatory mediators Corticosteroids • These compounds stimulate inflammation Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins NSAIDs damaged cells release inflammatory mediators local responses vascular cellular stage stage systemic (wholebody) responses white blood cell response acute-phase response Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Acute Inflammation • Vascular stage – Prostaglandins and leukotrienes affect blood vessels – Arterioles and venules dilate º Increasing blood flow to injured area º Redness and warmth result – Capillaries become more permeable º Allowing exudate to escape into the tissues º Swelling and pain result Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Vascular Stage Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Question What mechanism causes the redness (erythema) associated with the inflammatory process? a. Prostaglandins b. Leukotrienes c. Arachidonic acid d. All of the above e. a and b Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Answer e. a and b Rationale: Prostaglandins and leukotrienes cause vasodilation, which brings more blood to the injured/affected area. The symptoms caused by this vasodilation are redness/erythema and warmth. Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Kinds of Exudate • Serous • Hemorrhagic • Fibrinous • Membranous • Purulent Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Scenario A woman has peritonitis. • She has a distended abdomen, low blood pressure, and fluid in her abdominal cavity • After surgery, she is told to report any GI distress as it may indicate fibrous adhesions Question: • What kinds of exudate are involved? What useful purposes do they serve? What complications may they cause? Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Cellular Stage • White blood cells enter the injured tissue: – Destroying infective organisms – Removing damaged cells – Releasing more inflammatory mediators to control further inflammation and healing Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins White Blood Cells Involved in Inflammation • Granulocytes – Neutrophils – Eosinophils – Basophils – Mast cells • Monocytes – Monocytes macrophages Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Leukocytes • Leukocytes enter the injured area • Leukocytes express adhesive proteins Pavementing • Attach to the blood vessel lining • Squeeze between the cells • Follow the inflammatory mediators to the injured area Emigration Chemotaxis Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Leukocytes (cont.) Leukocytes release many inflammatory mediators at the injured area: • Histamine and serotonin • Platelet-activating factor • Cytokines – Colony-stimulating factors – Interleukins – Interferons – Tumor necrosis factor • Nitric oxide Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Question Which leukocytes participate in the acute inflammatory response? a. Eosinophils b. Monocytes c. Neutrophils d. All of the above e. a and c Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Answer d. All of the above Rationale: Granulocytes and monocytes play a role in the acute phase of the immune response. Eosinophils and neutrophils are granulocytes, so all of the leukocytes listed participate. Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Other Inflammatory Mediators Other inflammatory mediators travel in the plasma • Kinins • Coagulation and fibrinolysis proteins • Complement system • C-reactive protein Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins damaged cells release inflammatory mediators local responses vascular cellular stage stage systemic (wholebody) responses white blood cell response acute-phase response Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Acute-phase Response • Leukocytes release interleukins and tumor necrosis factor – Affect thermoregulatory center fever – Affect central nervous system lethargy – Skeletal muscle breakdown • Liver makes fibrinogen and C-reactive protein – Facilitate clotting – Bind to pathogens – Moderate inflammatory responses Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Fever Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Question Tell whether the following statement is true or false. Body temperature is controlled through negative feedback loops. Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Answer True Rationale: When the body senses a change out of the norm (as illustrated in the previous slides), it activates mechanisms that oppose that change (vasodilation and sweating with increased temperatures; vasocontriction and shivering with decreased temperatures). This is known as negative feedback. Positive feedback, on the other hand, senses a change, but activates a mechanism that exaggerates the change. Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Scenario Mr. X says he has “chills and fever.” • His daughter wants you to explain how he could have both at the same time and from the same disease Question: • Should she be keeping him warmer or helping him cool off? Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins White Blood Cell Response • Inflammatory mediators cause WBC production • WBC count rises • Immature neutrophils (bands) released into blood Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Chronic Inflammation • Macrophages accumulate in the damaged area and keep releasing inflammatory mediators • Nonspecific chronic inflammation – Fibroblasts proliferate – Scar tissue forms • Granulomatous inflammation – Macrophages mass together around foreign bodies – Connective tissue surrounds and isolates the mass Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Scenario • A man had tuberculosis long ago and when he first had the disease, he had a fever, productive cough, and bloody sputum • Later, he had trouble breathing and the doctor said his lungs were “consolidated” with fibrous proteins • He recovered and his fever went down; he thought he was cured • Three years later, an x-ray showed nodules in his lungs and he was told they contained the TB bacteria Question: • Identify inflammatory events in his case Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Tissue Repair • Growth factors stimulate local cells to divide • Tissue organization is controlled by the extracellular matrix • New cells are laid down on the extracellular matrix – Tissue regeneration: injured tissue is replaced by the same kind of cells – Fibrous tissue repair: injured tissue is replaced by connective tissue º Granulation tissue scar tissue Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Question Tell whether the following statement is true or false. If you get a paper cut, epithelial tissue will be replaced with connective tissue. Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Answer False Rationale: The surface epithelial cells of the skin are most likely to be damaged in this instance. Surface epithelial tissue has the ability to regenerate, replacing the damaged tissue with the same type (epithelial). Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Wound Healing • Inflammatory phase • Proliferative phase • Remodeling phase Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins