Recent advancements in technology have led to numerous adjunctive therapies for healing chronic wounds. In many cases, though, we can achieve healing in a short period of time once we identify the underlying factors that inhibit proper healing. With this in mind, let’s take a closer look at some of these common impediments. While wound hypoxia is the most common obstacle we see, it is also the most difficult hurdle in facilitating wound healing. You can measure wound hypoxia with transcutaneous oxygen pressure (TcPO2). A TcPO2 reading of less than 40mmHg has been correlated with poor wound healing. Wound hypoxia impairs all three phases of wound healing. Low oxygen tension predisposes wounds to bacterial invasion by impeding oxygen-depending intracellular bacterial killing. Some antimicrobial agents require adequate amounts of oxygen in their antimicrobial activity. Vancomycin and aminoglycosides, such as gentamicin, tobramycin, amikacin and netilmicin, are examples of the oxygen dependent agents that do not kill microorganisms effectively if there is low oxygen tension. The effect of wound hypoxia on the proliferative phase has been well documented. Low oxygen tension deceases ATP production, which is necessary for every cellular function. Replication of fibroblasts, epidermal and endothelial cells also decrease. Therefore, the whole secondary healing process (i.e. angiogenesis, collagen synthesis and epithelialization) becomes significantly impaired. Tissue perfusion can be decreased by many disorders, including poor cardiac output, focal ischemia, peripheral vascular disease, atherosclerosis, chronic infection or tobacco consumption. You should make very attempt to improve tissue perfusion by identifying the etiology and making an adequate referral as necessary. Reviewing Causal Factors For Infections Wound infection has been shown to impair wound contraction in both acute and chronic wounds by several mechanisms. Some bacteria are believed to release endotoxins that inhibit the migration of keratinocytes and fibroblasts into the wound. Proteases from bacteria can degrade fibrin and growth factor in the wound. Infection causes prolonged elevation of inflammatory mediators and cytokines, resulting in a prolonged inflammatory response to the wound. The presence of bacteria is not the only cause of impairment as the necrotic tissue left in the wound also inhibits the healing process. Foreign debris in the wound will serve as a growth medium for bacteria and increase the probability of infection. It will also promote pro-inflammatory mediators and proteinases that destroy endogenous growth factors, and degrade the glycosaminoglycan matrix needed for wound healing. Therefore, one should not treat an infection with antimicrobials alone. Indeed, good wound debridement is essential as it helps to: • reduce the bacterial load; • decrease inhibitors of growth factors; and • stimulate the production of growth factors from cells involved in healing. When Other Medications Affect Healing There are numerous medications known to inhibit wound healing. Steroids are known to interfere with angiogenesis and fibrogenesis. They also inhibit wounds from contraction. Oral or topical administration of vitamin A has been proposed to reverse the effect of steroids on wounds. Nonsteroidal antiinflammatory drugs (NSAIDs) are also commonly used by patients who have chronic diabetic ulcers. Researchers have shown that NSAIDs decrease collagen production. While the mechanism is unknown, it is believed to be associated with impaired prostaglandin metabolism. It is important to review the patient’s medication list. Doing so can help you identify possible medications that are inhibiting wound healing and allows you to make appropriate substitutions and/or discontinue problematic medications until the wound shows signs of improved healing. Consider The Possibilities Of A Tumor And Hyperglycemia Whenever you evaluate a chronic wound, you should include a tumor as one of the differential diagnoses. Be aware that basal cell carcinoma, squamous cell carcinoma, melanoma or cutaneous manifestations of systemic cancer can mimic ulcers. Chronic ulcerations can develop into squamous cell carcinoma known as Marjolin’s ulcer. You should obtain a tissue biopsy if you are in doubt. Growth factors are absolutely contraindicated for these patients. It’s also critical to ensure adequate blood sugar control for patients who have chronic ulcers. For optimal healing capability, the patient’s blood sugar level should range between 100 and 200 mg/dL. Hyperglycemia causes red blood cells to be less deformable and increases blood viscosity, causing vascular stasis in the microcirculation. Glycosylated hemoglobin also has a higher affinity for oxygen. This impairs the delivery of oxygen to ischemic tissues. As a result, macrophage and granulocytes cannot function effectively against bacteria, and there is interference with collagen synthesis and angiogenesis. This leads to delayed secondary healing. Other Key Factors That Affect Wound Healing Malnutrition is fairly common in chronic ulcer patients. It accounts for up to 50 percent of medical/surgical patients and 60 percent of patients placed in nursing homes. Numerous studies have shown the relationship between specific nutrient deficiency and delayed wound healing, and between nutritional status and length of hospital stay. Protein, fats and carbohydrates are important in cell division as well as fuel sources in the repair process. Vitamins and trace elements work as co-factors in cell differentiation or collagen synthesis. It has been reported that the status of visceral proteins dictates the patient’s ability to heal wounds and mount an immune response. The visceral proteins that should be included in a nutritional assessment are serum albumin, total protein and serum transferrin (see the table above). Nutritional deficiencies can be associated with nausea, depression, poor social circumstance and chronic disease. It’s important to evaluate these patients critically and initiate adequate nutritional intervention. External factors, including pressure, edema and poor patient compliance, can also significantly affect the wound healing process. Shear force can destroy the fragile layer of epithelial cells of an open wound. Gross wound contamination by stool, saliva or urine makes the wound more susceptible for prolonged infection. Self-inflicted chronic wounds or Munchausen’s syndrome may be more common than traditionally thought, and may require psychiatric consultation in order to achieve optimal wound healing. Final Notes There are many factors that prevent wounds from healing. Those factors must be identified and if possible, corrected, for healing to occur. Even before we consider adjunctive therapy, we need to evaluate potential underlying causes of chronic ulcers in order to achieve optimal healing. It takes the simple practice of good history taking, adding simple lab works, preparing the optimal wound base and making adequate referrals for individual patients. Dr. Morita is a first year resident at the University of Texas Health Science Center, Division of Podiatry. Dr. Steinberg (pictured) is an Assistant Professor in the Department of Orthopaedics/Podiatry Service at the University of Texas Health Science Center.
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