Chronic wound

Source: Wikipedia, the free encyclopedia.

A chronic wound is a wound that does not heal in an orderly set of stages and in a predictable amount of time the way most wounds do; wounds that do not heal within three months are often considered chronic.[1] Chronic wounds seem to be detained in one or more of the phases of wound healing. For example, chronic wounds often remain in the inflammatory stage for too long.[2][3] To overcome that stage and jump-start the healing process, a number of factors need to be addressed such as bacterial burden, necrotic tissue, and moisture balance of the whole wound.[4] In acute wounds, there is a precise balance between production and degradation of molecules such as collagen; in chronic wounds this balance is lost and degradation plays too large a role.[5][6]

Chronic wounds may never heal or may take years to do so. These wounds can cause patients severe emotional and physical

stress and create a significant financial burden on patients and the whole healthcare system.[7]

Acute and chronic wounds are at opposite ends of a spectrum of wound-healing types that progress toward being healed at different rates.[8]

Signs and symptoms

Chronic wound patients often report pain as dominant in their lives.[9] It is recommended that healthcare providers handle the pain related to chronic wounds as one of the main priorities in chronic wound management (together with addressing the cause). Six out of ten

venous leg ulcer patients experience pain with their ulcer,[10]
and similar trends are observed for other chronic wounds.

Persistent pain (at night, at rest, and with activity) is the main problem for patients with chronic ulcers.

adhere
to were also identified.

Cause

In addition to poor

Emotional stress can also negatively affect the healing of a wound, possibly by raising blood pressure and levels of cortisol, which lowers immunity.[7]

What appears to be a chronic wound may also be a

squamous cell carcinoma, may also form as the result of chronic wounds, probably due to repetitive tissue damage that stimulates rapid cell proliferation.[13]

Another factor that may contribute to chronic wounds is old age.

gene upregulation of stress-related proteins.[14] In older cells, stress response genes are overexpressed when the cell is not stressed, but when it is, the expression of these proteins is not upregulated by as much as in younger cells.[14]

Comorbid factors that can lead to ischemia are especially likely to contribute to chronic wounds. Such factors include chronic fibrosis, edema, sickle cell disease, and peripheral artery disease such as by atherosclerosis.[2]

Repeated

Munchausen syndrome by proxy, a disease in which the abuser may repeatedly inflict harm on the child in order to receive attention.[16]

Periwound skin damage caused by excessive amounts of exudate and other bodily fluids can perpetuate the non-healing status of chronic wounds. Maceration, excoriation, dry (fragile) skin, hyperkeratosis, callus and eczema are frequent problems [17] that interfere with the integrity of periwound skin. They can create a gateway for infection as well as cause wound edge deterioration preventing wound closure.

Pathophysiology

Chronic wounds may affect only the

neoplasias or metabolic disorders.[18] The reason a wound becomes chronic is that the body's ability to deal with the damage is overwhelmed by factors such as repeated trauma, continued pressure, ischemia, or illness.[8][18]

Though much progress has been accomplished in the study of chronic wounds lately, advances in the study of their healing have lagged behind expectations. This is partly because animal studies are difficult because animals do not get chronic wounds, since they usually have loose skin that quickly contracts, and they normally do not get old enough or have contributing diseases such as neuropathy or chronic debilitating illnesses.[14] Nonetheless, current researchers now understand some of the major factors that lead to chronic wounds, among which are ischemia, reperfusion injury, and bacterial colonization.[14]

Ischemia

complement factors.[14]

While they fight pathogens, neutrophils also release inflammatory

Reactive Oxygen Species (ROS) to kill bacteria, for which they use an enzyme called myeloperoxidase.[14] The enzymes and ROS produced by neutrophils and other leukocytes damage cells and prevent cell proliferation and wound closure by damaging DNA, lipids, proteins,[19] the extracellular matrix (ECM), and cytokines that speed healing.[14] Neutrophils remain in chronic wounds for longer than they do in acute wounds, and contribute to the fact that chronic wounds have higher levels of inflammatory cytokines and ROS.[3][6] Since wound fluid from chronic wounds has an excess of proteases and ROS, the fluid itself can inhibit healing by inhibiting cell growth and breaking down growth factors and proteins in the ECM. This impaired healing response is considered uncoordinated.[20] However, soluble mediators of the immune system (growth factors), cell-based therapies and therapeutic chemicals can propagate coordinated healing.[21]

It has been suggested that the three fundamental factors underlying chronic wound pathogenesis are cellular and systemic changes of aging, repeated bouts of ischemia-reperfusion injury, and bacterial colonization with resulting inflammatory host response.[22]

Bacterial colonization

Since more oxygen in the wound environment allows white blood cells to produce ROS to kill bacteria, patients with inadequate tissue oxygenation, for example those who developed hypothermia during surgery, are at higher risk for infection.[14] The host's immune response to the presence of bacteria prolongs inflammation, delays healing, and damages tissue.[14] Infection can lead not only to chronic wounds but also to gangrene, loss of the infected limb, and death of the patient. More recently, an interplay between bacterial colonization and increases in reactive oxygen species leading to formation and production of biofilms has been shown to generate chronic wounds.[23]

Like ischemia, bacterial colonization and infection damage tissue by causing a greater number of neutrophils to enter the wound site.

resistances to antibiotics may have time to develop.[24] In addition, patients that carry drug resistant bacterial strains such as methicillin-resistant Staphylococcus aureus (MRSA) have more chronic wounds.[24]

Growth factors and proteolytic enzymes

Chronic wounds also differ in makeup from acute wounds in that their levels of

Keratinocyte Growth Factor are lower.[6][18]

Since growth factors (GFs) are imperative in timely wound healing, inadequate GF levels may be an important factor in chronic wound formation.[18] In chronic wounds, the formation and release of growth factors may be prevented, the factors may be sequestered and unable to perform their metabolic roles, or degraded in excess by cellular or bacterial proteases.[18]

Chronic wounds such as diabetic and venous ulcers are also caused by a failure of fibroblasts to produce adequate ECM proteins and by keratinocytes to epithelialize the wound.[25] Fibroblast gene expression is different in chronic wounds than in acute wounds.[25]

Though all wounds require a certain level of elastase and proteases for proper healing, too high a concentration is damaging.

proteoglycans, and collagen,[26] and damages growth factors, fibronectin, and factors that inhibit proteases.[5] The activity of elastase is increased by human serum albumin, which is the most abundant protein found in chronic wounds.[5] However, chronic wounds with inadequate albumin are especially unlikely to heal, so regulating the wound's levels of that protein may in the future prove helpful in healing chronic wounds.[5]

Excess matrix metalloproteinases, which are released by leukocytes, may also cause wounds to become chronic. MMPs break down ECM molecules, growth factors, and protease inhibitors, and thus increase degradation while reducing construction, throwing the delicate compromise between production and degradation out of balance.[6][27]

Diagnosis

Infection

If a chronic wound becomes more painful this is a good indication that it is infected.[28] A lack of pain however does not mean that it is not infected.[28] Other methods of determination are less effective.[28]

Classification

The vast majority of chronic wounds can be classified into three categories:

radiation poisoning or ischemia.[14]

Venous and arterial ulcers

valves that exist in the veins to prevent blood from flowing backward. Ischemia results from the dysfunction and, combined with reperfusion injury, causes the tissue
damage that leads to the wounds.

Diabetic ulcers

Main article: Diabetic foot ulcer

Another major cause of chronic wounds,

immune compromise and damage to small blood vessels, preventing adequate oxygenation of tissue, which can cause chronic wounds.[8] Pressure also plays a role in the formation of diabetic ulcers.[14]

Pressure ulcers

Another leading type of chronic wounds is pressure ulcers,

capillaries, and thus restricts blood flow into the area.[30] Muscle tissue, which needs more oxygen and nutrients than skin does, shows the worst effects from prolonged pressure.[32] As in other chronic ulcers, reperfusion injury
damages tissue.

Treatment

Though treatment of the different chronic wound types varies slightly, appropriate treatment seeks to address the problems at the root of chronic wounds, including ischemia, bacterial load, and imbalance of proteases.[14] Periwound skin issues should be assessed and their abatement included in a proposed treatment plan.[17] Various methods exist to ameliorate these problems, including antibiotic and antibacterial use, debridement, irrigation,

vacuum-assisted closure, warming, oxygenation, moist wound healing (the term pioneered by George D. Winter), removing mechanical stress, and adding cells or other materials to secrete or enhance levels of healing factors.[29]

It is uncertain whether intravenous metronidazole is useful in reducing foul smelling from malignant wounds.[33] There is insufficient evidence to use silver-containing dressings or topical agents for the treatment of infected or contaminated chronic wounds.[34]

The challenge of any treatment is to address as many adverse factors as possible simultaneously, so each of them receives equal attention and does not continue to impede healing as the treatment progresses.[35][36]

Preventing and treating infection

To lower the bacterial count in wounds, therapists may use topical antibiotics, which kill bacteria and can also help by keeping the wound environment moist,[37][38] which is important for speeding the healing of chronic wounds.

Disinfectants are contraindicated because they damage tissues and delay wound contraction.[38] Further, they are rendered ineffective by organic matter in wounds like blood and exudate and are thus not useful in open wounds.[38]

A greater amount of exudate and

lavage.[14]

Removing necrotic or devitalized tissue is also the aim of maggot therapy, the intentional introduction by a health care practitioner of live, disinfected maggots into non-healing wounds. Maggots dissolve only necrotic, infected tissue; disinfect the wound by killing bacteria; and stimulate wound healing. Maggot therapy has been shown to accelerate debridement of necrotic wounds and reduce the bacterial load of the wound, leading to earlier healing, reduced wound odor and less pain. The combination and interactions of these actions make maggots an extremely potent tool in chronic wound care.

mRNAs and to proliferate and produce ECM molecules.[2][8]

Recent technological advancements produced novel approaches such as self-adaptive wound dressings[39] that rely on properties of smart polymers sensitive to changes in humidity levels. The dressing delivers absorption or hydration as needed over each independent wound area and aids in the natural process of autolytic debridement. It effectively removes liquefied slough and necrotic tissue, disintegrated bacterial biofilm as well as harmful exudate components, known to slow the healing process.[40] The treatment also reduces bacterial load by effective evacuation and immobilization of microorganisms from the wound bed, and subsequent chemical binding of available water that is necessary for their replication.[41] Self-adaptive dressings protect periwound skin from extrinsic factors and infection while regulating moisture balance over vulnerable skin around the wound.

Treating trauma and painful wounds

Persistent

diabetes mellitus
.

If wound pain is not assessed and documented it may be ignored and/or not addressed properly. It is important to remember that increased wound pain may be an indicator of wound complications that need treatment, and therefore practitioners must constantly reassess the wound as well as the associated pain.

Optimal management of wounds requires holistic assessment. Documentation of the patient's pain experience is critical and may range from the use of a patient diary, (which should be patient driven), to recording pain entirely by the healthcare professional or caregiver.[43] Effective communication between the patient and the healthcare team is fundamental to this holistic approach. The more frequently healthcare professionals measure pain, the greater the likelihood of introducing or changing pain management practices.

At present there are few local options for the treatment of persistent pain, whilst managing the exudate levels present in many chronic wounds. Important properties of such local options are that they provide an optimal wound healing environment, while providing a constant local low dose release of ibuprofen while worn.

If local treatment does not provide adequate pain reduction, it may be necessary for patients with chronic painful wounds to be prescribed additional systemic treatment for the physical component of their pain. Clinicians should consult with their prescribing colleagues referring to the WHO pain relief ladder of systemic treatment options for guidance. For every pharmacological intervention there are possible benefits and adverse events that the prescribing clinician will need to consider in conjunction with the wound care treatment team.

Ischemia and hypoxia

Blood vessels constrict in tissue that becomes cold and dilate in warm tissue, altering blood flow to the area. Thus keeping the tissues warm is probably necessary to fight both infection and ischemia.[31] Some healthcare professionals use 'radiant bandages' to keep the area warm, and care must be taken during surgery to prevent hypothermia, which increases rates of post-surgical infection.[14]

Underlying ischemia may also be treated surgically by

arterial revascularization
, for example in diabetic ulcers, and patients with venous ulcers may undergo surgery to correct vein dysfunction.

Diabetics that are not candidates for surgery (and others) may also have their tissue oxygenation increased by

Hyperbaric Oxygen Therapy, or HBOT, which may provide a short-term improvement in healing by improving the oxygenated blood supply to the wound.[19][44] In addition to killing bacteria, higher oxygen content in tissues speeds growth factor production, fibroblast growth, and angiogenesis.[2][19] However, increased oxygen levels also means increased production of ROS.[19] Antioxidants, molecules that can lose an electron to free radicals without themselves becoming radicals, can lower levels of oxidants in the body and have been used with some success in wound healing.[6]

Low level laser therapy has been repeatedly shown to significantly reduce the size and severity of diabetic ulcers as well as other pressure ulcers.

Pressure wounds are often the result of local ischemia from the increased pressure. Increased pressure also plays a roles in many diabetic foot ulcerations as changes due to the disease causes the foot to have limited joint mobility and creates pressure points on the bottom of the foot. Effective measures to treat this includes a surgical procedure called the gastrocnemius recession in which the calf muscle is lengthened to decrease the fulcrum created by this muscle and resulting in a decrease in plantar forefoot pressure.[45]

Growth factors and hormones

Since chronic wounds underexpress growth factors necessary for healing tissue, chronic wound healing may be speeded by replacing or stimulating those factors and by preventing the excessive formation of proteases like elastase that break them down.[5][6]

One way to increase growth factor concentrations in wounds is to apply the growth factors directly. This generally takes many repetitions and requires large amounts of the factors, although biomaterials are being developed that control the delivery of growth factors over time.

blood platelets, which then secrete growth factors such as vascular endothelial growth factor (VEGF), insulin-like growth factor 1–2 (IGF), PDGF, transforming growth factor-β (TGF-β), and epidermal growth factor (EGF).[18] Other treatments include implanting cultured keratinocytes into the wound to reepithelialize it and culturing and implanting fibroblasts into wounds.[29][37] Some patients are treated with artificial skin
substitutes that have fibroblasts and keratinocytes in a matrix of collagen to replicate skin and release growth factors.

In other cases, skin from

epithelial cells to crawl across.[2] On the most difficult chronic wounds, allografts may not work, requiring skin grafts from elsewhere on the patient, which can cause pain and further stress on the patient's system.[3]

Collagen dressings are another way to provide the matrix for cellular proliferation and migration, while also keeping the wound moist and absorbing exudate.[6] Additionally Collagen has been shown to be chemotactic to human blood monocytes, which can enter the wound site and transform into beneficial wound-healing cells.[47]

Since levels of

Secretory leukocyte protease inhibitor (SLPI), which inhibits not only proteases but also inflammation and microorganisms like viruses, bacteria, and fungi, may prove to be an effective treatment.[27]

Research into

ovaries removed, possibly by preventing excess neutrophils from entering the wound and releasing elastase.[26]
Thus the use of estrogen is a future possibility for treating chronic wounds.

Epidemiology

Chronic wounds mostly affect people over the age of 60.[14] The

prevalence ranges from 0.18 to 0.32%.[18] As the population ages, the number of chronic wounds is expected to rise.[30]
Ulcers that heal within 12 weeks are usually classified as acute, and longer-lasting ones as chronic.

References

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  42. ^ Flanagan M, Vogensen H, and Haase L. 2006. Case series investigating the experience of pain in patients with chronic venous leg ulcers treated with a foam dressing releasing ibuprofen. World Wide Wounds. 2006
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Further reading

External links
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