Tissue Damage and Inflammation

Chapter 6 This chapter outlines the concepts of innate immunity, inflammation, and wound healing. Innate immunity refers to the body's initial defense mechanisms against invasion and injury. Inflammation is the body's response to injury and infection, aimed at protecting and healing the body. Wound healing involves several phases, including hemostasis, inflammation, tissue formation, and remodeling. Bullet points Tissue Damage and Inflammation  Dying phagocytes release enzymes that can cause inflammation and tissue destruction at the site  Natural inhibitors in blood minimize the destructive effects of these enzymes Quick Check Questions 1. PRRs are pattern recognition receptors 2. Cytokines are signaling molecules that promote inflammation by recruiting immune cells and mediating immune responses 3. Mast cells release chemical mediators such as histamine, prostaglandins, and leukotrienes, which increase vascular permeability and cause vasodilation and pain 4. Phagocytic cell types involved in acute inflammation include neutrophils and monocytes/macrophages; neutrophils are first responders and macrophages play a role in clearance and tissue repair 5. Opsonins function as "glue" to enhance adherence between phagocytes and targets, making phagocytosis more effective 6. The four steps in phagocytosis are opsonization, engulfment, fusion with lysosomes, and destruction of the target Acute and Chronic Inflammation  Inflammation can be divided into acute and chronic phases  Acute inflammation is self-limiting and lasts until the threat is eliminated  Chronic inflammation may develop if the acute response is inadequate and may persist for weeks or months  If healing hasn't occurred, inflammation may progress to a granulomatous response  Both acute and chronic phases involve different mediators and cells but can lead to healing Inflammatory Phases and Healing  Cellular injury leads to acute inflammation  Acute inflammation may result in resolution and healing of the injured site or progress into chronic inflammation  Chronic inflammation may result in healing or development of a granuloma  The final step of the inflammatory process is usually healing and reconstruction of the damaged tissue Local Manifestations of Acute Inflammation  Characteristic signs include swelling, pain, heat, redness, and, in some injuries, loss of function  Inflammatory exudates result from increased vascular permeability and leakage of fluid into tissues  Exudates vary in composition, from serous (watery) to fibrinous (thick and clotted) to purulent (pus) to hemorrhagic (filled with erythrocytes) Systemic Manifestations of Acute Inflammation  Fever is induced by cytokines released from neutrophils and macrophages  Fever can be beneficial to fight microorganisms, but may have harmful side effects  Leukocytosis is an increase in the number of circulating white blood cells  Inflammation stimulates the proliferation and release of granulocyte and monocyte precursors in bone marrow, resulting in increased numbers of immature cell forms Blood cell types and infection  Monitoring the ratio of blood cell types can indicate an ongoing infection  An increase in white blood cells alongside an abnormal differential count suggests infection Plasma protein synthesis and inflammation  Inflammation leads to increased synthesis of plasma proteins, produced primarily by the liver  These proteins, known as acute-phase reactants, can be proinflammatory or antiinflammatory  Levels of acute-phase reactants, such as fibrinogen, reach a peak within 10 to 40 hours after inflammation onset  Tests measuring acute-phase reactants can be used to assess inflammation Measuring inflammation in the laboratory  Elevation in erythrocyte sedimentation rate (ESR) indicates increased blood levels of acute-phase reactants, often caused by inflammation  Cross-reactive protein (CRP), another acute-phase reactant, is also used to measure inflammation Chronic inflammation  Chronic inflammation lasts for 2 weeks or longer  It can result from a prolonged acute inflammatory response or occur as a distinct process  Conditions associated with chronic inflammation include cardiac and neurologic disorders, malignancy, autoimmune disorders, and chronic infection Granuloma formation  Granulomas form when the body attempts to wall off and isolate an infected area  Infections caused by certain bacteria, fungi, parasites, or retained foreign objects commonly result in granuloma formation  Many autoimmune conditions are also associated with granulomatous tissue changes  TNF-a and other proinflammatory cytokines mediate granuloma formation Anatomy of a granuloma  Granulomas consist of a central area of necrosis surrounded by lymphocytes and enlarged epithelioid macrophage cells  Activated macrophages can fuse into multinucleated giant cells  Fibrous deposits of collagen encapsulate the granuloma, which may become cartilaginous or calcified Tuberculosis-associated granuloma  Tuberculosis granuloma is characterized by a wall of lymphocytes and epithelioid cells surrounding the mycobacteria  Cell death within the granuloma leads to the release of acids and enzymatic lysosomal contents, resulting in caseous necrosis  The granuloma undergoes liquefaction necrosis, forming a hollow structure that replaces normal tissue Healing and repair  Resolution is the most favorable outcome, with complete healing and restoration of function  Regeneration can occur in some tissues, while repair involves the replacement of destroyed tissue with scar tissue composed mostly of collagen  Scar tissue lacks the physiologic functions of the original tissue Stages of Healing by Primary Intention  Healing primarily occurs through primary intention in clean incisions with minimal tissue loss and close apposition of wound edges  Healing is quick Stages of Healing by Secondary Intention  Occurs in open wounds with significant tissue replacement  Healing occurs at a slower rate compared to primary intention Rate of Healing and Tissue Regeneration  Epidermal wounds and unsutured internal lesions do not completely restore to their original state  Only epithelial, hepatic, and bone marrow cells can fully regenerate the tissue  Fibrous connective tissue, such as joints and ligaments, are replaced with new tissue that may not replicate the original structure and function  Some tissues heal with fibrous scar tissue and do not regain full function