Studies have shown for over 100 years that malnutrition impairs wound healing [11–14]. The impairment exists with total protein/calorie (marasmus) malnutrition or with protein (kwashiorkor) malnutrition. Simply, if one holds nutritional support at the time of wounding, a marked impairment in tensile strength will result within 1–2 weeks [15]. The clinical significance of malnutrition relates to the risks of complications with surgery such that if a patient has lost weight from a malignancy or from an inability to eat, then there is a much higher risk for dehiscence. The hidden side of this healing impairment is that altered healing could lead to a bowel anastomosis leak which in turn, may lead to an abscess. Since the metabolic reserve is reduced in the elderly, this complication of failing to heal often leads to sepsis, multiple organ dysfunction syndrome, and ultimately death. The clinician can reduce complications by assessing the nutritional status of the elderly and providing supplemental nutrition prior to surgery. In addition, an aggressive approach to perioperative nutrition may make the difference between normal healing without complications and a rocky course and ultimate death.

There are some vitamins and micronutrients that influence tissue repair. Vitamin C is essential for the hydroxylation of proline or lysine in the formation of normal procollagen triple helices [16]. When there is a deficiency, collagen is not properly produced, and people may suffer from scurvy. Since there is a balance between collagen formation and breakdown during the maturation phase of scar formation, recently healed wounds may break down. In addition, vitamin A has been found to augment tissue repair [17, 18]. Several minerals such as zinc [19, 20] and copper [20] are essential for normal healing, and when they are deficient, problems may result. We have noted that patients with subnormal copper levels have impaired healing of their burn wounds [21]. A deficiency in arginine may also lead to altered tissue repair [22].

Diabetes mellitus is a major cause of healing problems in people of all ages [23–25]. Since the disease is seen more commonly in the elderly, it is important to know its impact on tissue repair. Some statistics are important to emphasize its impact on the development of chronic wounds. Twenty percent of hospital admissions in diabetes are related to wound healing problems. Twenty-five percent of diabetic patients will have a foot ulcer during their lifetimes, and 50 % of all nontraumatic amputations are related to diabetes mellitus. A common scenario is that a diabetic patient will not notice a pebble in their shoe due to their impaired sensation. This will create a small wound that goes unnoticed, and eventually a wound is noticed and not properly treated. When the patient finally seeks care, the wound is infected with purulence tracking up the fascial planes of the foot. This patient often presents with cellulitis or invasive infection that leads to an amputation.

Even if a wound is detected early, tissue repair is significantly impaired. As an example, Margolis reviewed several clinical trials that tested treatments for diabetic ulcers [26]. He collected the “controls” which received “standard” treatment. What he found was that only 31 % healed within 20 weeks of aggressive therapy. It is likely that the two-thirds that did not heal stayed open for the remainder of their lives. There are several reasons why tissue repair is impaired in patients with diabetes mellitus [23–25]. First of all, peripheral vascular disease is increased in this population. Diabetics not only suffer from macrovascular disease but also from microvascular disease where there is thickening of the capillary basement membrane. This microvascular disease leads to impaired delivery of oxygen and nutrients from an increase in edema which impairs diffusion. This process also impairs leukocyte migration into the wound. If the patient suffers from renal disease, healing is inhibited further by uremia and its resulting edema [27].

The second factor that contributes to alter healing in diabetes mellitus is its tendency to cause peripheral neuropathy. Loss of sensation progresses from distal to proximal in the extremity so that the feet are usually involved first. As stated earlier, people with neuropathic feet do not sense injury, and thus minor injuries tend to worsen or go unrecognized by the patient. We have recently reviewed our 10-year experience with diabetics who burn their feet [28]. It is common for them to walk outside on hot pavement or try to warm their “cold” feet with hot water or by placing them near space heaters. We admitted 68 patients with thermal injury to their feet during that period, and the incidence is increasing. As for other types of diabetic wounds, the patients admitted for burns to their feet tended to have prolonged hospital stays and frequent graft failure. Another often unrecognized consequence of neuropathy is that the foot loses its normal feedback to maintain the arch. The foot thus tends to flatten which leads to increased pressure on the first or second metatarsal head. The classic diabetic foot ulcer is a wound that is on the plantar surface on the first or second metatarsal head. The final consequence of neuropathy is that with loss of normal sympathetic innervation, the skin loses its ability to sweat and thus tends to dry and crack. These cracks may then be a site for infection.

There is an increased risk for infection for wounds that form in the diabetic patient. It is well known that hyperglycemia leads to an impaired ability to fight local infection. There are also studies that suggest that leukocyte migration and function is impaired. The impaired ability to fight infections predisposes diabetics to a higher risk for amputation. In addition, there are several metabolic factors that may contribute to impair healing that are covered in other reviews [25, 29]. One interesting concept is that hyperglycemia may lead to deposition of glucose by-products known as advanced glycosylation end-products (AGES) in the tissues. There are “receptors for advanced glycosylation end-products” (RAGES) that detect these products of hyperglycemia and stimulate an inflammatory response. One theory is that activation of RAGES may lead to the chronic inflammatory state (“metabolic syndrome”) of diabetes mellitus and obesity [30]. This chronic inflammatory state may also contribute to impaired tissue repair.

Since healing is so impaired in diabetic patients, it is essential that prevention efforts are made to prevent a wound from developing. The Wound Healing Society has published guidelines for the treatment and prevention of diabetic wounds [31, 32]. All clinicians who treat diabetes mellitus should discuss the risks of foot ulcers with their patients. Diabetics should inspect their feet daily and be extremely careful with the care of their nails. Podiatrists are extremely helpful in these matters. Diabetics with neuropathy should always wear well-fitted shoes and be especially vigilant after the first few days of wearing new shoes. Any new wound should be treated aggressively and early. People with diabetes mellitus should always avoid walking outside while barefoot and never warm their insensate feet with any heated agent. Once a wound develops, they should be treated with something that “off-loads” the pressure point on the wound (metatarsal head). “Total contact casts” have been found to be effective [33]. Studies suggest that topical growth factors or skin substitutes may be effective, but they are extremely costly [34–36]. Vascular disease should be treated if present. Unfortunately, our success with treating these wounds is only marginal, so prevention is essential.

Wound healing involves the recruitment and rapid proliferation of many different cell types. It makes sense, then, that any drug that impairs rapid proliferation of cells alters tissue repair. Unfortunately, the strategy for dealing with many diseases includes suppressing the inflammatory response, which also requires rapid proliferation of cells. Steroids have been known for decades to impair tissue repair, and their use should be minimized if possible to allow for better healing [37, 38]. The treatment of cancer also involves the killing of rapidly proliferating malignant cells, so it is also obvious that chemotherapy agents [39, 40] or radiation [41, 42] impairs tissue repair. With the advent of neoadjuvant therapy (chemotherapy and/or radiation) combined with surgery, it is clear that one must be extremely careful with the healing of these patients. One must optimize their nutritional status if they are to undergo these combined treatments. There are very few agents that augment healing in these situations, but vitamin A has been shown to at least partially reverse impairments due to steroids or radiation [17, 18]. Growth factors may also play a role in improving healing, but these are based on animal studies [43–49].

Neurologic diseases do not impair wound healing, but they do predispose the elderly to the risk of developing wounds. Dementia leads to forgetfulness and risky behavior that may lead to injury. The person may forget to turn off stoves or fail to practice safe techniques for self-care. People with dementia have a more difficult time with cleanliness and maintaining a diet and thus may not clean wounds and tend to be more malnourished. Neuropathies have previously been mentioned as a risk for many types of wounds. Any loss of sensation clearly predisposes a person to pressure sores since pain is the main warning sign of chronic pressure. Tremors may predispose the elderly to spills and an inability to quickly react to a dangerous situation. Incontinence may lead to maceration of the skin which in turn increases the risks for abrasions or tears with moving. Seizures are risky in people who cook or are around hot items since during the seizure, they will not react to an injury. People who seize while cooking or bathing frequently sustain very deep burns.

Pressure ulcers may develop at any age, but they are commonly manifested in the elderly as they develop reduced ability to move or after the development of neuropathy [50, 51, 56]. These wounds are found in around 10 % of inpatients. The pathophysiology is simple; any pressure on the skin and underlying tissues of greater than 30 mmHg that persists for a prolonged period of time can lead to enough ischemia to create a pressure ulcer. Normally, pressure produces pain which leads to a shift in the body to redistribute the pressure to another area. When we sleep we are constantly and subconsciously moving. Even intoxicated people will move to prevent these wounds. When people lose sensation, such as after paralysis, or when so ill that they are unable to move (such as in an intensive care unit), they are prone to pressure ulcers. Nurses play a major prevention role by repositioning patients from side to side. Not uncommonly, however, pressure ulcers develop where bony prominences create pressure. The classic sites are in the presacral region, the occiput, and on the heels. There are scoring systems that grade the severity of pressure ulcers that are useful for documentation. Pressure ulcers are staged as 1 when the skin is intact but just reddened for a prolonged period, 2 when the skin has been broken, 3 when the ulcer has become full-thickness, and 4 when the wound involves deeper tissues [56, 57]. The wound management becomes more difficult with increasing severity. The usefulness of this paradigm, however, has been recently challenged [58]. It is unclear of the relevance of a stage 1 ulcer, and the pathophysiology varies between stage 2 and stage 3 or 4 ulcers. Stage 2 ulcers occur because of damage from the “outside in” and higher-staged ulcers produced from the “inside out.” Despite these limitations, the staging system is helpful for documentation and management strategies.