Understanding chronic wound healing

Nonhealing, or chronic wounds, are complex wounds that do not progress through the usual phases of healing. This can be caused by intrinsic or extrinsic influences and all age groups or patient types from the healthy to those with multiple comorbidities can be affected. It is not uncommon for NPs to evaluate and treat chronic wounds regardless of their practice specialty. Having a basic understanding of the skin, the phases of acute wound healing, and knowing when to refer to a wound-care clinic are all part of comprehensive patient care.

Types of wounds

Wound healing is a complex and dynamic process of restoring cellular structures and tissue layers. There are two types of wounds: acute and chronic. Acute wounds are either traumatic or surgical and move through the healing process at a predictable rate from insult to closure. Chronic wounds do not progress through the predictable stages of wound healing.

The type of wound repair is classified as either primary, secondary, or tertiary intention. In primary intention, the wound edges are approximated and held together with staples, sutures, or some form of adhesive tape. Healing occurs with epithelialization and connective tissue attachments, usually without complications.

Secondary intention is the treatment of choice for dirty surgical wounds, trauma, or wounds resulting from chronic disease. The wound edges are not approximated and healing occurs with granulation tissue, contraction of the wound edges, and epithelialization. In large wounds, granulation tissue is the only tissue reassembled by the body. Muscle, tendons, and ligaments do not regenerate.

In tertiary intention, the wound is left open for an amount of time determined by the surgeon, usually to decontaminate the wound base and restart the granulation process. Granulation is allowed to continue to a given depth, and then the wound edges are approximated.

A chronic wound is a wound that has not resolved over a reasonable period of time no matter the cause.Changes occur within the molecular environment of a chronic wound that are not conducive to healing, such as high levels of inflammatory cytokines, proteases, and low levels of growth factors.These changes terminate the healing process and increase the potential for septic infections. Addressing the issues that might be responsible for the physiological wound changes may restart healing.

All chronic wounds begin as acute wounds The most common chronic wounds are lower extremity ulcers. Chronic venous insufficiency (CVI) accounts for 80% to 90% of lower extremity ulcers and affects 2% to 5% of the population. The cost of treating CVI ulcers alone is estimated at 1 billion dollars/year in the United States. Other types of nonhealing wounds are surgical, diabetic, arterial, burns, dermatitis, vasculitis, and radiation. With the increase in new cases of diabetes, treatment of neuropathic and pressure ulcers are likely to increase proportionately.

Chronic wounds are encountered in every specialty and the occurrence of nonhealing wounds will continue to rise as the population ages, people continue to live longer with chronic diseases, and the nutritional needs of the body are not met. Approximately 2 to 3 million people suffer from chronic wounds in the United States.

Skin

The skin is the largest organ of the body and is continually adapting to meet the needs of an ever-changing external environment. It is a protective barrier from the outside world, and maintains a homeostatic internal environment. The skin consumes about one-third of the body's blood supply and is the first organ to lose that blood supply when the body is in crisis.

Normal skin is elastic, lubricated, and has a pH of approximately 4 to 6.8. The pH of the skin is acidic due to the sebum secreted by sebaceous glands onto the skin surface.Sebum contains antimicrobial properties and, along with the acid pH, inhibits the growth of microorganisms.

Langerhans cells, antigen presenting cells, are part of the immune system of the skin preventing microorganism invasion (see Langerhans cells). Other cells involved in the skin's immune system can be found in the dermal layer. Macrophages ingest bacteria and mast cells are involved in the inflammatory process caused by the injury. Keeping the skin intact is essential to protect the rest of the body from microbial invasion.

As the skin ages, or with chronic disease, some of the protective properties are lost or diminished. There is a reduction in sebum production and the skin becomes dryer and less elastic. Dryness leads to small cracks in the skin, which will support bacterial invasion. Combined with a chronic disease such as vascular disorders or diabetes, reduction in blood flow to the skin will occur, directly impacting wound healing.

Aging skin is more susceptible to damage due to thinning and increased friability. Other issues are a decrease in the inflammatory response, cell senescence, decrease in cytokines and growth factor production, and a reduction in receptor sites

Healing cascade

Understanding the phases of wound healing will assist the practitioner with evaluating where and when the healing stopped and what might have contributed to the wound stalling. The healing cascade starts with the injury or insult and progresses toward complete closure. The phases of acute wound healing are the inflammatory phase, the proliferative phase, and the remodeling phase.

Inflammatory phase

There are two parts to this phase starting from the initial injury and progressing toward the formation of the clot. Clot formation is a crucial step within the inflammatory phase because the clot itself brings cytokines (polypeptide regulators) to the site of injury. Another important chemical released by the clot is platelet-derived growth factor, which influences cellular growth and development.The formation and degradation of the clot are important aspects of the inflammatory phase.

Hemostasis begins when the injury occurs and lasts only a few hours.The injury creates a vascular response to try to control the bleeding. The exposure of the epithelium of the blood vessels triggers platelet aggregation which generates a temporary barrier to bacteria and controls the bleeding. Vasoconstriction, thromboplastin production and clot formation are the major components of hemostasis.

After the bleeding has been controlled the body focuses on cleaning up the debris generated by the healing process. This phase starts with vasodilation causing the leakage of plasma, neutrophils, and other cytokines into the tissue surrounding the injury site. Usually what will be noted clinically is edema, induration and heat in the periwound skin. This is part of the wound-healing process and does not, alone, signify infection. The practitioner should evaluate lab tests such as a white blood cell count and quantitative wound culture to evaluate for infection.

The mediators of this phase are nitric oxide, neutrophils, and macrophages. Macrophages are responsible for the release of growth factors, enzymes that stimulate angiogenesis, fibroblasts, and the process of connective tissue synthesis.This is the phase of healing where most chronic wounds stop progressing.

Proliferative phase

The proliferative phase usually lasts 2 days to 3 weeks and can be broken down into two phases. The first phase is the foundation of the wound base with granulation tissue. Remember muscle, tendon, fascia cannot regenerate. All the body can produce to fill in the wound base is granulation tissue. Granulation will only begin after the dead tissue has been removed from the wound base.

Macrophages release fibroblasts to create the foundation of the wound base after the debris has been removed. Fibroblasts build the foundation or framework to construct the wound base. Angiocytes create the blood supply to stimulate angiogenesis. The macrophage release many physiologic activators and messengers to stimulate connective tissue formation. The end product of this process is the wound base framework to support the granulation tissue. The major mediators for this phase are the macrophage and the vascular endothelial growth factor responsible for angiogenesis.

After the wound base is completely filled with granulation tissue, the wound edges are stimulated to start epithelialization. The process is similar to the freezing of a pond in winter. Epithelialization starts from the outside edges and progresses toward the center. Keratinocytes start the process of migration across the wound base leading to eventual closure of the wound.

Remodeling phase

After the wound is closed, the body continues to heal the wound. The remodeling phase lasts anywhere from 6 months to 2 to 3 years depending on the patient's health. During this time, the body's cytokines change the wound matrix and strengthen the collagen support structure.This process increases the strength of the scar, known as tensile strength. The highest tensile strength that can be restored is 80% of the original strength of the tissue. Before the completion of this phase the wound is vulnerable to reinjury. (See Cellular view of acute wound healing).

Etiology

There are many reasons for a wound to stall during the healing process (see Pathologic process of chronic wounds). Some factors are unusual and related to the individual such as autoimmune diseases. There are a few factors that cross all age barriers and when understood will help the practitioner with the screening process for impaired wound healing. Aging, as mentioned before, has an impact on healing. A few of those changes are; decrease in blood supply to the skin, alteration in collagen formation, flattening of the basement membrane, and a slower inflammatory response. The elderly seem to have a higher percentage of chronic illnesses that may lead to polypharmacy.

Impaired perfusion influences oxygen transport. Decreased oxygen availability will have an impact on collagen formation, angiogenesis and epithelialization. Neutrophil and macrophage microorganism ingestion consumes an increased amount of oxygen. Impaired perfusion and decreased tissue oxygenation increases the patient's risk of infection.

Proper nutrition is key to continued wound healing. Malnutrition leads to decreased collagen production, impaired fibroblast production, and impaired angiogenesis. Poor eating habits lead to decreased available protein needed for wound repair. Bacteria, usually Gram-negative, in higher concentrations compete with granulation tissue for the nutrients available in the wound bed and their byproducts are toxic.

The age of the wound, in other words how long the wound has been open, also affects healing. As mentioned earlier, "old" wounds seem to have "old" cells that lose the ability to proliferate. The problem is not limited to the elderly. Underlying chronic disease, such as diabetes, can affect the wound chemistry.

Stressors have been implicated in the impaired healing process. An increase in the production of cortisol and vasoconstriction can impair wound healing.Early research findings have shown a correlation between decreased wound healing and psychological stressors, pain, and noise.Further research on how stressors influence wound healing is needed.

The bioburden is the number of bacteria, on the wound base. Chronic wounds are contaminated and the degree of contamination will have an effect on the rate of healing. In other words, the higher the quantity of the bioburden the slower the healing rate.