Porth's Essentials of Pathophysiology, 4e

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Cell and Tissue Function

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the plasma. Hyperbaric oxygen is currently reserved for the treatment of problem wounds in which hypoxia and infection interfere with healing. Impaired Inflammatory and Immune Responses Inflammatory and immune mechanisms function in wound healing. Inflammation is essential to the first phase of wound healing, and immune mechanisms prevent infections that impair wound healing. Among the condi- tions that impair inflammation and immune function are disorders of phagocytic function, diabetes mellitus, and therapeutic administration of corticosteroid drugs. Phagocytic disorders may be divided into extrinsic and intrinsic defects. Extrinsic disorders are those that impair attraction of phagocytic cells to the wound site, prevent engulfment of bacteria and foreign agents by the phagocytic cells (i.e., opsonization), or cause sup- pression of the total number of phagocytic cells (e.g., immunosuppressive agents). Intrinsic phagocytic dis- orders are the result of enzymatic deficiencies in the metabolic pathway for destroying the ingested bac- teria by the phagocytic cell. The intrinsic phagocytic disorders include chronic granulomatous disease, an X-linked inherited disease in which there is a deficiency of myeloperoxidase and nicotinamide adenine dinucleo- tide peroxidase (NADPH)–dependent oxidase enzyme. Deficiencies of these compounds prevent generation of hydrogen superoxide and hydrogen peroxide needed for killing bacteria. Wound healing is a problem in persons with dia- betes mellitus, particularly those who have poorly controlled blood glucose levels. 27 Studies have shown delayed wound healing, poor collagen formation, and poor tensile strength in diabetic animals. Of particular importance is the effect of hyperglycemia on phagocytic function. Neutrophils, for example, have diminished chemotactic and phagocytic function, including engulf- ment and intracellular killing of bacteria, when exposed to altered glucose levels. Small blood vessel disease is also common among persons with diabetes, impairing the delivery of inflammatory cells, oxygen, and nutrients to the wound site. The therapeutic administration of corticosteroid drugs decreases the inflammatory process and may delay the healing process. These hormones decrease capillary permeability during the early stages of inflammation, impair the phagocytic property of the leukocytes, and inhibit fibroblast proliferation and function.

contaminated at the time of injury. Although body defenses can handle the invasion of microorganisms at the time of wounding, badly contaminated wounds can overwhelm host defenses. Trauma and existing impair- ment of host defenses also can contribute to the devel- opment of wound infections. Approximation of the wound edges (i.e., suturing of an incision type of wound) greatly enhances healing and prevents infection. Epithelialization of a wound with closely approximated edges occurs within 1 to 2 days. Large, gaping wounds tend to heal more slowly because it is often impossible to effect wound closure with this type of wound. Mechanical factors such as increased local pressure or torsion can cause wounds to pull apart, or dehisce . Foreign bodies tend to invite bacterial contami- nation and delay healing. Fragments of wood, steel, glass, and other compounds may have entered the wound at the site of injury and can be difficult to locate when the wound is treated. Sutures are also for- eign bodies, and although needed for the closure of surgical wounds, they are an impediment to healing. This is why sutures are removed as soon as possible after surgery. Wound infections are of special concern in persons with implantation of foreign bodies such as orthopedic devices (e.g., pins, stabilization devices), cardiac pacemakers, and shunt catheters. These infec- tions are difficult to treat and may require removal of the device.  Wound Healing in the Elderly A number of structural and functional changes have been reported to occur in aging skin, including a decrease in dermal thickness, a decline in collagen con- tent, and a loss of elasticity. 29,30 The observed changes in skin that occur with aging are complicated by the effects of sun exposure. Since the effects of sun expo- sure are cumulative, older persons show more changes in skin structure. Wound healing is thought to be progressively impaired with aging. The elderly have alterations in wound-healing phases including hemostasis and inflammation, cell proliferation, and resolution. 30 Keratinocytes, fibroblasts, and vascular endothelial cells display a reduced rate of proliferation. There is also a reported decrease in angiogenesis and collagen synthesis, impaired wound contraction, and slower reepithelialization of open wounds. Although wound healing may be delayed, most wounds heal, even in the debilitated elderly patient undergoing major surgical procedures. The elderly are more vulnerable to chronic wounds, chiefly pressure, diabetic, and ischemic ulcers, than younger persons, and these wounds heal more slowly. However, these wounds are more likely due to other dis- orders such as immobility, diabetes mellitus, or vascular disease, rather than aging.

Infection,Wound Separation, and Foreign Bodies

Wound contamination, wound separation, and for- eign bodies delay wound healing. Infection impairs all dimensions of wound healing. 28 It prolongs the inflammatory phase, impairs the formation of granu- lation tissue, and inhibits proliferation of fibroblasts and deposition of collagen fibers. All wounds are