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Physiology of Wound Healing and Surgical Wound Care

Phillips, Steven J.

Supplement on Infection

Wound healing is a systemic process, which occurs stepwise and involves the stages of hemostasis, inflammation, and repair. Hemostasis with fibrin formation creates a protective wound scab. The scab provides a surface beneath which cell migration and movement of the wound edges can occur. Inflammation brings nutrients to the area of the wound, removes debris and bacteria, and provides chemical stimuli for wound repair. Repair begins immediately after wounding and proceeds rapidly through the processes of epithelialization, fibroplasia, and capillary proliferation into the healing area. Different tissues have their own normal rates of growth during the process of healing. The optimal rate of healing is approached when factors advantageous to healing are present and factors having the ability to disturb or retard the healing processes are controlled or absent. These factors are discussed.

From the National Library of Medicine, National Institutes of Health, Washington, DC.

Reprint requests: Steven J. Phillips, MD, Assistant Director for Research and Education, National Library of Medicine, National Institutes of Health, 8600 Rockville Pike, Bethesda, MD 20894.

Wound healing is a systemic process that begins with an injury and continues with a series of physiologic responses that will ultimately impact the ability of the wound to heal. In humans, repair of tissues and organs after surgery occurs almost entirely by replacement with scar tissue and regeneration. 1–6 Many factors, both intrinsic and extrinsic, that influence healing will be discussed.

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Normal Healing

The normal healing process for a full-thickness surgical injury occurs in a predictable manner and involves the stages of hemostasis, inflammation, and repair.

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Hemostasis

The immediate response to a surgical injury is the vasoconstriction of blood vessels at the point of injury. Vasoconstriction reduces the volume of blood flow, which is part of the blood-clotting mechanism to limit blood loss. Blood flows into the gap created by the cutting instrument, fills the space, and clots, thereby uniting the edges of the wound. Fibrinogen molecules from the blood quickly link up as interconnected strands of fibrin. On the surface, fibrin and other proteins in the serum dehydrate to form a scab. The scab provides limited protection from external contamination, maintains internal homeostasis and provides a surface beneath which cell migration and movement of the wound edges can occur. 1,3,4,7,8

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Inflammatory Process

Wound healing begins with the process of inflammation. The inflammatory process brings nutrients to the area of surgery, removes debris and bacteria, and provides stimuli for wound repair. 9,10 Immediately after injury, vascular fluid and cellular changes occur in the area adjacent to the site of injury. Vasodilation of area vessels allows plasma like fluid to leak into the tissue space. This fluid contains enzymes, proteins, antibodies, and complement. Inflammation creates a migration of nutrients, antibodies, and substances such as histamine, serotonin, proteolytic enzymes, kinins, prostaglandins and cells into the surgical site. 11,12 A chemical reaction is initiated, which stimulates polymorphonuclear leukocytes to synthesize mucopolysaccharides, which are important in the early phases of healing. This inflammatory exudate, which is present in all wounds, contains leukocytes, dead tissue, and cellular debris. 13 Wound debridement occurs when polymorphonuclear leukocytes degenerate, rupture, and release enzyme-containing granules that attack extracellular debris. In a relatively clean and healthy wound, polymorphs are soon superseded by monocytes. Monocytes are important cells in wound healing; they are necessary for both wound debridement and the repair process. Upon entering the wound area, monocytes become phagocytic macrophages. The role of macrophages to removal of debris is their enhancement of lysozomal enzyme activity, secretion of proteases, production of interferon, and synthesis of prostaglandins. Also, there is evidence that macrophages release chemotactic substances that attract mesenchymal cells to the area and influence their differentiation into fibroblasts.

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Repair Process

Repair processes begins immediately after surgery and proceeds rapidly. These processes are epithelialization and fibroplasia, which also involves capillary proliferation into the healing area. 14 Epithelial migration and proliferation are the first clear-cut signs of repair taking place in the wound. In general, the epidermal response to trauma includes mobilization of basal cells from dermal attachments, migration of cells to a place of cell deficit, proliferation by mitosis in pre-existing cells, and differentiation to restore cellular function in new cells. 1,4,15–17 Fibroplasia, the fundamental aspect of this process, is the production of ground substances and collagen fibers by fibroblasts. New capillaries originate as budlike structures on nearby vessels, penetrate the wound, and form into loops that ramify through the wound. The formation of new capillaries, to supply blood and its contained nutrients to a wound, is the first step of fibroplasia. Within 48 hours of surgery, migratory fibroblasts appear in the wound edges. The migrating fibroblasts use the strands of fibrin as a scaffold either to provide orientation or contact guidance, and the fibrin disappears coincidentally with collagen deposition by fibrinolysis.

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Factors Affecting Wound Healing

Different tissues have their own normal rates of growth during the process of healing; the optimal rate is approached when factors advantageous to healing are present and factors having the ability to disturb or retard the healing processes are controlled or absent. 15,16

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Surgical technique

A certain degree of injury is inevitable during surgery. Excess trauma increases the amount of debris that must be removed by phagocytosis and decreases the viability and activity of phagocytic cells. The inflammatory phase of healing is prolonged, the rate of gain of tensile strength is decreased, the possibility of infection is increased, and excessive scar production can occur. 18

To reduce tissue trauma during surgery, incisions should be performed with a scalpel, and scissors reserved for dissection. Healing is delayed by prolonged pressure and tearing action of retractors, massive ligatures with large necrotic portions of tissue distal to the ligature, and plugs of necrotic tissue from electrocoagulation. The removal of the devitalized tissue in wounds by various techniques of debridement is an accepted principle in operative care. Prolonged exposure and dessication of tissue can delay healing. Also, the incidence of wound infection is increased in long operative procedures. 5,19,20

Collections of clotted blood and serum between tissue layers prevent proper apposition of tissues. A large hematoma can exert sufficient pressure to interfere with blood supply to adjacent tissues. Hematomas that are slow to resorb should be evacuated. Left alone, hematomas can become a cavity containing encapsulated fluid. Free fluid in the wound encourages growth of organisms. Epithelial migration and proliferation occur in all wounds in the healing area, including the wounds made by insertion of sutures. If large, irritating sutures are used and left in place for excessive periods, the epithelium in the suture tracts, and particularly the resulting keratin, can cause unsightly suture reactions that have been confused with abscesses caused by infection. Using fine, nonirritating suture material and removing the sutures as early as possible can reduce these suture scars. 1,21

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Nutrition and Medication

Nutrients are essential to wound healing. Critically ill patients are often nutritionally deficient, which can result in impaired healing. Understanding the role of the various nutrients in healing provides the basis for assessment and therapy. Use of a practical and consistent nutritional assessment technique is an important part of care for critically ill patients with wounds. The health care team must provide care based on current knowledge of the effects of nutrition on wound healing and work collaboratively in doing nutritional assessment and providing nutritional support to optimize wound healing outcomes.

Nutrition has a profound effect on wound healing. Deficiency of any nutrient during the healing process may result in impaired or delayed wound healing. Some nutrients are more important than others are, and the deficiencies of these nutrients have specific effects on the healing process. 22–24

Protein is one of the most important nutrients, and its deficiency impairs new capillary formation, fibroblastic proliferation, proteoglycans, and collagen synthesis. Deficiency of protein also affects phagocytosis leading to a higher risk for infection. 14,22,25,26

Deficiency of vitamin A results in a retardation of epithelialization, closure of wounds, the rate of collagen synthesis, and crosslinking. Deficiency of vitamin E in the body adversely affects wound healing, collagen production, and intermolecular collagen cross-linking. 24,27,28

Vitamin C, ascorbic acid, is required when the amino acids proline and lysine are hydroxylated to form hydroxyproline and hydroxylysine, two constituents of collagen. Without vitamin C, the collagen molecules remain incomplete and may not be secreted by the fibroblast when rapid synthesis is required in wound healing. 1,15,19,22 A deficiency of vitamin C increases capillaries fragility and also makes the wound susceptible to infection.

Minerals and other elements also play an important role in wound healing. Deficiency of zinc causes decreased rate of epithelialization, collagen synthesis, and results in decreased tensile strength. Deficiency of magnesium can result decreased collagen synthesis. The deficiency of copper may lead to altered cross-linking, affecting the tensile strength. Although iron is necessary for collagen synthesis, research has not confirmed whether iron deficiency further compromises wound healing by virtue of anemia. Severe anemia has been reported to interfere with wound repair. 1,9,29

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Medications

Patients undergoing surgery frequently take systemic medications. Although medications such as antibiotics do prevent and/or get rid of infection, some systemic medications have an adverse effect on wound healing. Steroids decrease the tensile strength of wounds, rate of epithelialization and neovascularization, and inhibit wound contraction. The inhibition of wound healing by high doses of glucocorticoids can be reversed by administration of high doses of vitamin A. Nonsteroidal anti-inflammatory drugs causes vasoconstriction, thereby suppressing the inflammatory response. These drugs also decrease collagen synthesis and reduce tensile strength and wound contraction, probably based upon their anti-inflammatory properties. Chemotherapeutic agents interfere with cell proliferation and prolong inflammation, inhibit protein synthesis, and decrease collagen synthesis. Immunosuppressive drugs have adverse affect on wound healing and certain antibiotics such as nitrofurazone can significantly retard the rate of healing. 21,25,27,28

Chemotherapy and radiation therapy interferes with cell proliferation and has their greatest effect on dividing cells. Cell proliferation is an essential component of the healing process, and these agents can significantly affect wound healing. In addition, high doses of radiation, especially during the first 3 days of healing, significantly reduce wound tensile strength. 4,30

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Environmental Issues

Temperature.

Wounds have been reported to heal more quickly at a temperature of 30°C than at the normal room temperature of 18 to 20°C. At 12°C, the rate of gain of tensile strength in wounds decreases by about 20%. It is believed that within physiologic limits, the effect of cold upon wound healing is related to reflex vasoconstriction and, therefore, to a decrease in blood supply to the wound. The effect of temperature could have practical considerations in surgery. For example, an external heat source such as a heat lamp could be used to accelerate wound healing. 19,31

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Oxygen tension.

Oxygen is required for cell metabolism and functions such as cell migration, multiplication, and protein synthesis. The synthesis of collagen by fibroblasts involves hydroxylation of proline and lysine and this process requires additional oxygen. A small but significant increase in wound strength occurs with 40% oxygen compared with controls breathing 20% oxygen. 11,32,33

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Uremia.

Uremia occurring during the first 5 days of wound healing causes significant impairment of the healing process. Wound healing is not affected when uremia occurs after 9 days. The adverse effects of uremia are caused by changes in enzyme systems, biochemical pathways, and cellular metabolism. 4,34

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Foreign bodies.

A foreign body is described as a mass that is not normal for the tissues in which it is found. Introduced foreign bodies include the intentional type such as suture material and metals and plastics used in biomedical devices. 20,21 If foreign material becomes infected or causes irritation, the wound rarely heals until the material is extruded or removed.

The physical characteristics of the foreign body affect tissue tolerance. Porous materials are tolerated less well than the solid and impervious ones. A monofilament suture is tolerated better than one made with twisted or braided fibers. Metal such as plates and screws can be inert in the tissues if they are smooth and can be irritants if they have a rough surface.

One of the main problems associated with foreign bodies is their relationship to infection. If they are absorbable, the process of absorption can cause inflammation and free fluid, which encourages bacterial growth. If the foreign bodies are porous, bacteria can persist within the foreign body and survive the effect of antibodies and antibacterial drugs. Antibiotics can control the reaction in the tissues by suppressing infection; however, the infection recurs. 35,36

Some foreign bodies delay wound healing because their presence blocks the migration of healing cells. The presence of cyanoacrylate fragments between tissues delays wound healing by preventing the proliferation of the fibroblasts and capillaries bridging the wounded surfaces.

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Dressings.

The mechanics of wound dressing can affect wound healing. 6,8 The choices of dressing may range from a totally occlusive impermeable, to semiocclusive and semipermeable, to nonocclusive and permeable. 37 Conventional gauze permeable wet-to-dry dressing functions as debridement and helps wounds with large amounts of necrotic tissues. 38 However, when this type of dressing is applied to newly formed granulation tissue, it may damage the granulation tissue when the dressing is removed. Furthermore, the dry gauze dressing may cause dehydration of the wound, resulting in prolonged inflammation. All dressings have some advantages and some disadvantages. It is an important clinical decision to choose the type of dressing for a given wound type during different stages of healing that may not have a detrimental effect on the healing process. Research has established that the use of conventional gauze type dressings may cause reinjury and dessication in wounds, whereas moisture-retentive hydrocolloid dressings will maintain a favorably moist environment while sequestering the natural growth factors and enzymes that are essential to the healing process. 39 Wound care based on the scientific evidence will result in an improved rate of healing. 36

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Summary

A thorough understanding of normal wound healing is of utmost importance for the physicians who are involved in the implantation and care of patients with a biomedical device. Special consideration must be given to our patients preoperatively, because most are in a negative nitrogen balance associated with dysfunctional immune and fluid and electrolyte systems. The surgeon should adhere to the principles of careful handling of tissues, and the obliteration of dead space while performing the procedure. The obliteration of dead space in wounds has been stressed since the time of Kocher. The performance of a successful surgical procedure to implant a ventricular assist device (VAD), total artificial heart (TAH), or any other biomedical device, requires a knowledge of wound physiology. Principles of postoperative wound care include providing a moist wound healing environment through the use of proper dressings, protecting the surgical site from further injury, and providing nutritional substrates are essential to the healing process.

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