Trauma and Wound Healing
Factors that Compromise Wound Healing
Infection. Infection caused by normal bacteria of the body or those from the external environment can trigger significant inflammation and impair the wound healing process (Guo 2010; Demidova-Rice 2012). Poor oxygenation or immune compromise can inhibit the natural antibacterial defenses of the healing wound and increase infection risk (Daley 2017). Infection is a significant cause of delayed healing in chronic wounds (Leaper 2015). Local wound infection has the potential to extend into deeper soft tissue and bone, or progress to potentially life-threatening systemic infection called sepsis (Healy 2006; Leaper 2015; Daley 2017).
Low oxygenation. Oxygen is critical for virtually all phases of the healing process. It is necessary for the prevention of infection in early stages of healing, efficient cellular energy production, and to support the increased metabolic needs of healing tissues. While temporary hypoxia (low oxygenation) stimulates the initial stages of healing, prolonged oxygen deprivation impairs healing and is a hallmark of chronic wounds. Hypoxia becomes more common with poor circulation, which can occur during aging or with medical conditions such as diabetes and cardiovascular disease (Sen 2009; Guo 2010).
Foreign body. Foreign debris in the wound can interfere with the restoration of tissue structure, promote inflammation, and serve as a reservoir for infection-causing bacteria (Daley 2017; Leaper 2015).
Venous insufficiency. Increased pressure and permeability in the venous system, as seen in chronic venous insufficiency, may lead to accumulation of fibrin around the small blood vessels. It is thought that deposits of fibrin, a protein normally involved in blood clotting, create a barrier to movement of nutrients and oxygen across the blood vessel wall and disrupt wound healing (Demidova-Rice 2012; Vasudevan 2014).
Age and gender. In older individuals, increased platelet adherence to the inner lining of blood vessels and higher levels of inflammatory chemicals from platelets can compromise wound healing. Reduced or altered immune cell movement and function, growth factor production, collagen synthesis, remodeling, and wound strength are also seen with advancing age (Gosain 2004). Women may have slightly faster wound healing capability than men because estrogens promote healing by modulating tissue regeneration, inflammation, matrix production, and skin function (Guo 2010).
Stress. Mental and physical stress can lead to increased production of the hormone cortisol, which reduces inflammatory and cell-activating cytokines necessary for the initial phases of wound healing. Cortisol also impairs healing by reducing immune cell development, connective tissue formation, and collagen synthesis (Tiganescu 2013; Saito 1997; Godbout 2006). Stressed individuals may also suffer from poor sleep, inadequate nutrition and exercise, and alcohol or drug abuse, which can further contribute to poor wound healing (Gouin 2011).
Diabetes. Diabetes poses several challenges to wound healing. Poor circulation, which is common in those with diabetes, leads to poor tissue oxygenation (Guo 2010). Diabetic wounds also have impaired blood vessel growth following injury (Brem 2007) and contain higher levels of compounds that negatively affect new tissue formation (Muller 2008; Ayuk 2016; Sibbald 2008). Persistently elevated blood glucose levels and a pro-oxidative state favor glycation, the bonding of glucose to proteins and fats, interfering with their function. Molecules damaged through glycation, known as advanced glycation end products (AGEs), have been shown to slow healing in animal models (Huijberts 2008).
Other disorders. Conditions associated with poor wound healing include previous scarring, hereditary healing disorders, liver and kidney diseases, hypertension, peripheral vascular disease, cardiovascular disease, pulmonary disease, and gastrointestinal diseases that cause malnutrition (Guo 2010; Ahmed 2011; Young 1988; Sorensen 2005). Wound healing is also impaired in immunocompromised individuals, such as those with HIV or cancer (Aird 2011; Burns 2000; Payne 2008; Pyter 2016). Sleep disorders trigger a stress response, and obstructive sleep apnea may lead to intermittently low oxygen levels, which can impair healing of chronic wounds. In a report on three cases of obstructive sleep apnea in patients with non-healing diabetic ulcers, correction of the apnea with continuous positive airway pressure (CPAP) therapy led to significant improvements in wound healing in two of the patients (Vas 2016).
Obesity. Obesity has many negative effects on wound healing. Adipose (fat) tissue has relatively low blood and oxygen supply, and pressure from the weight of excess adipose tissue can reduce oxygen levels around sites of injury. Tension on surgical wounds due to excess adipose tissue can lead to reduced tissue oxygenation or failure of wound closure (Wilson 2004; Anaya 2006; Fantuzzi 2005). Skin folds in overweight individuals can harbor moisture or bacteria that increase risk of infection. Fat tissue secretes inflammatory chemicals that can hamper healing. Finally, obesity is associated with conditions such as cardiovascular disease, hypertension, and type II diabetes that have recognized negative effects on wound healing (Hellmann 2012; Klein 2014; Ahmed 2011).
Medications. Systemic glucocorticoid steroids can have a negative effect on healing via a mechanism similar to that of cortisol (Guo 2010). Studies suggest use of non-steroidal anti-inflammatory drugs (NSAIDs) might impair wound and ulcer healing (Jones 1999). Also, a meta-analysis of data from 17 studies comprising over 20,000 participants found that use of non-selective NSAIDs after colorectal surgery led to increased risk of leakage at the interface of conjoined tissue (anastomotic dehiscence) compared with non-NSAID treatment and selective NSAID treatment (Huang 2017). Some chemotherapy drugs interfere with wound healing by inhibiting cell division and blood vessel formation (Erinjeri 2011).
Alcohol and smoking. Alcohol increases risk of wound infection. Acute alcohol consumption suppresses inflammatory cytokine release, reducing the inflammatory phase of healing and preventing immune cell movement to the wound. It also reduces tissue regrowth in animal models of wound healing (Guo 2010). Smoking, in addition to its negative vascular effects and reduction of tissue oxygenation, can increase risk of infection, wound rupture, and tissue death (Guo 2010; Sorensen 2012).
Poor nutrition. The higher metabolic needs of healing tissues require increased energy and nutrient availability. Inadequate protein intake is especially detrimental during wound healing (Wolfe 2008). Moreover, deficiencies in total energy and several nutrients have been associated with impaired healing; these deficiencies including (Shepherd 2003; Arnold 2006; Campos 2008; Burgess 2008):
- Vitamin C
- Vitamin A
- Vitamin E