Chronic wound
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.
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.
In acute wounds, there is a precise balance between production and degradation of molecule
s such as collagen
; in chronic wounds this balance is lost and degradation plays too large a role.
Chronic wounds may never heal or may take years to do so. These wounds cause patients severe emotional and physical stress
and create a significant financial burden on patients and the whole healthcare system.
Acute and chronic wounds are at opposite ends of a spectrum of wound healing types that progress toward being healed at different rates.
s, diabetic, and pressure ulcers. A small number of wounds that do not fall into these categories may be due to causes such as radiation poisoning
or ischemia
.
s, which usually occur in the legs, account for about 70% to 90% of chronic wounds and mostly affect the elderly. They are thought to be due to venous hypertension caused by improper function of valves that exist in the vein
s 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.
than the general population due to chronic ulcers. Diabetes causes neuropathy
, which inhibits nociception
and the perception
of pain
. Thus patients may not initially notice small wounds to legs and feet, and may therefore fail to prevent infection
or repeated injury
. Further, diabetes causes immune compromise and damage to small blood vessels, preventing adequate oxygenation of tissue, which can cause chronic wounds. Pressure also plays a role in the formation of diabetic ulcers.
that inhibit movement of body parts that are commonly subjected to pressure such as the heels, shoulder blades, and sacrum
. Pressure ulcers are caused by ischemia that occurs when pressure on the tissue is greater than the pressure in capillaries, and thus restricts blood flow into the area. Muscle tissue, which needs more oxygen and nutrient
s than skin
does, shows the worst effects from prolonged pressure. As in other chronic ulcers, reperfusion injury
damages tissue.
as dominant in their lives.
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, 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. Frustrations regarding ineffective analgesic
s and plans of care that they were unable to adhere
to were also identified.
. Comorbid
ailments that may contribute to the formation of chronic wounds include vasculitis
(an inflammation of blood vessels), immune suppression, pyoderma gangrenosum
, and diseases that cause ischemia
. Immune suppression can be caused by illnesses or medical drug
s used over a long period, for example steroid
s. Emotional stress can also negatively affect the healing of a wound, possibly by raising blood pressure
and levels of cortisol
, which lowers immunity.
What appears to be a chronic wound may also be a malignancy; for example, cancer
ous tissue can grow until blood cannot reach the cells and the tissue becomes an ulcer. Cancer, especially squamous cell carcinoma
, may also form as the result of chronic wounds, probably due to repetitive tissue damage that stimulates rapid cell proliferation.
Another factor that may contribute to chronic wounds is old age. The skin of older people is more easily damaged, and older cells do not proliferate as fast and may not have an adequate response to stress in terms of gene upregulation of stress-related protein
s. In older cells, stress response gene
s 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.
Comorbid factors that can lead to ischemia are especially likely to contribute to chronic wounds. Such factors include chronic fibrosis
, atherosclerosis
, edema
, sickle cell disease, and arterial insufficiency
-related illnesses.
Repeated physical trauma
plays a role in chronic wound formation by continually initiating the inflammatory cascade. The trauma may occur by accident, for example when a leg is repeatedly bumped against a wheelchair
rest, or it may be due to intentional acts. Heroin users who lose venous access may resort to 'skin popping
', or injecting the drug subcutaneously, which is highly damaging to tissue and frequently leads to chronic ulcers. Children who are repeatedly seen for a wound that does not heal are sometimes found to be victims of a parent with Munchausen syndrome by proxy
, a disease in which the abuser may repeatedly inflict harm on the child in order to receive attention.
, or they may affect tissues all the way to the fascia
. They may be formed originally by the same things that cause acute ones, such as surgery
or accidental trauma, or they may form as the result of systemic infection, vascular, immune, or nerve insufficiency, or comorbidities such as neoplasia
s or metabolic disorders. 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.
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. Nonetheless, current researchers now understand some of the major factors that lead to chronic wounds, among which are ischemia, reperfusion injury
, and bacteria
l colonization.
s, chemokine
s, leukotriene
s, and complement factors.
While they fight pathogens, neutrophils also release inflammatory cytokine
s and enzymes that damage cells. One of their important jobs is to produce Reactive Oxygen Species (ROS)
to kill bacteria, for which they use an enzyme called myeloperoxidase
. The enzymes and ROS produced by neutrophils and other leukocytes damage cells and prevent cell proliferation and wound closure by damaging DNA
, lipid
s, proteins, the extracellular matrix
(ECM), and cytokines that speed healing. 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. 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.
, loss of the infected limb, and death
of the patient.
Like ischemia, bacterial colonization and infection damage tissue by causing a greater number of neutrophils to enter the wound site. In patients with chronic wounds, bacteria with resistances
to antibiotics may have time to develop. In addition, patients that carry drug resistant bacterial strains such as methicillin-resistant Staphylococcus aureus
(MRSA) have more chronic wounds.
. and matrix metalloproteinase
s (MMPs) are higher, while their concentrations of growth factors such as Platelet-derived growth factor
and Keratinocyte Growth Factor
are lower.
Since growth factors (GFs) are imperative in timely wound healing, inadequate GF levels may be an important factor in chronic wound formation. 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.
Chronic wounds such as diabetic and venous ulcers are also caused by a failure of fibroblast
s to produce adequate ECM proteins and by keratinocyte
s to epithelialize the wound. Fibroblast gene expression is different in chronic wounds than in acute wounds.
Though all wounds require a certain level of elastase and proteases for proper healing, too high a concentration is damaging. Leukocytes in the wound area release elastase, which increases inflammation, destroys tissue, proteoglycans, and collagen
, and damages growth factors, fibronectin, and factors that inhibit proteases. The activity of elastase is increased by human serum albumin
, which is the most abundant protein found in chronic wounds. 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.
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.
s, which kill bacteria and can also help by keeping the wound environment moist,
which is important for speeding the healing of chronic wounds. Some researchers have experimented with the use of tea tree oil
, an antibacterial agent which also has anti-inflammatory effects. Disinfectants are contraindicated because they damage tissues and delay wound contraction. Further, they are rendered ineffective by organic matter in wounds like blood and exudate
and are thus not useful in open wounds.
A greater amount of exudate and necrotic tissue in a wound increases likelihood of infection by serving as a medium for bacterial growth away from the host’s defenses. Since bacteria thrive on dead tissue, wounds are often surgically debrided
to remove the devitalized tissue. Debridement and drainage of wound fluid are an especially important part of the treatment for diabetic ulcers, which may create the need for amputation if infection gets out of control. Mechanical removal of bacteria and devitalized tissue is also the idea behind wound irrigation, which is accomplished using pulsed lavage
.
Removing necrotic or devitalzed tissue is also the aim of maggot therapy
, the intentional introduction by a health care practitioner of live, disinfected maggot
s 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.
Negative pressure wound therapy
(NPWT) is a treatment that improves ischemic tissues and removes wound fluid used by bacteria. This therapy, also known as vacuum-assisted closure, reduces swelling in tissues, which brings more blood and nutrients to the area, as does the negative pressure itself. The treatment also decompresses tissues and alters the shape of cells, causes them to express different mRNAs and to proliferate and produce ECM molecules.
associated with non-healing wounds is caused by tissue (nociceptive) or nerve (neuropathic) damage and is influenced by dressing changes and chronic inflammation
. Chronic wounds take a long time to heal and patients can suffer from chronic wounds for many years. Chronic wound healing may be compromised by coexisting underlying conditions, such as venous valve backflow
, peripheral vascular disease, uncontrolled edema and 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. 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 during weartime.
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.
, which increases rates of post-surgical infection.
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 can compensate for limitations of blood supply and correct hypoxia
. In addition to killing bacteria, higher oxygen content in tissues speeds growth factor production, fibroblast growth, and angiogenesis
. However, increased oxygen levels also means increased production of ROS. Antioxidant
s, 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.
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 suffer 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.
One way to increase growth factor concentrations in wounds is to apply the growth factors directly, though this takes many repetitions and requires large amounts of the factors. Another way is to spread onto the wound a gel of the patient’s own 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). Other treatments include implanting cultured keratinocytes into the wound to reepithelialize it and culturing and implanting fibroblasts into wounds. 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 cadaver
s is grafted onto wounds, providing a cover to keep out bacteria and preventing the buildup of too much granulation tissue
, which can lead to excessive scar
ring. Though the allograft (skin transplanted from a member of the same species
) is replaced by granulation tissue and is not actually incorporated into the healing wound, it encourages cellular proliferation and provides a structure for epithelial cells to crawl across. 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.
Collagen dressings are another way to provide the matrix for cellular proliferation and migration, while also keeping the wound moist and absorbing exudate.
Since levels of protease inhibitor
s are lowered in chronic wounds, some researchers are seeking ways to heal tissues by replacing these inhibitors in them. Secretory leukocyte protease inhibitor
(SLPI), which inhibits not only proteases but also inflammation and microorganisms like virus
es, bacteria, and fungi
, may prove to be an effective treatment.
Research into hormone
s and wound healing has shown estrogen
to speed wound healing in elderly humans and in animals that have had their ovaries removed, possibly by preventing excess neutrophils from entering the wound and releasing elastase. Thus the use of estrogen is a future possibility for treating chronic wounds.
The incidence
is 0.78% of the population and the prevalence ranges from 0.18 to 0.32%. As the population ages
, the number of chronic wounds is expected to rise.
Wound
A wound is a type of injury in which skin is torn, cut or punctured , or where blunt force trauma causes a contusion . In pathology, it specifically refers to a sharp injury which damages the dermis of the skin.-Open:...
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.
Chronic wounds seem to be detained in one or more of the phases of wound healing
Wound healing
Wound healing, or cicatrisation, is an intricate process in which the skin repairs itself after injury. In normal skin, the epidermis and dermis exists in a steady-state equilibrium, forming a protective barrier against the external environment...
. For example, chronic wounds often remain in the inflammatory
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
stage for too long.
In acute wounds, there is a precise balance between production and degradation of molecule
Molecule
A molecule is an electrically neutral group of at least two atoms held together by covalent chemical bonds. Molecules are distinguished from ions by their electrical charge...
s such as collagen
Collagen
Collagen is a group of naturally occurring proteins found in animals, especially in the flesh and connective tissues of mammals. It is the main component of connective tissue, and is the most abundant protein in mammals, making up about 25% to 35% of the whole-body protein content...
; in chronic wounds this balance is lost and degradation plays too large a role.
Chronic wounds may never heal or may take years to do so. These wounds cause patients severe emotional and physical stress
Stress (medicine)
Stress is a term in psychology and biology, borrowed from physics and engineering and first used in the biological context in the 1930s, which has in more recent decades become commonly used in popular parlance...
and create a significant financial burden on patients and the whole healthcare system.
Acute and chronic wounds are at opposite ends of a spectrum of wound healing types that progress toward being healed at different rates.
Classification
The vast majority of chronic wounds can be classified into three categories: venous ulcerVenous ulcer
Venous ulcers are wounds that are thought to occur due to improper functioning of venous valves, usually of the legs. They are the major cause of chronic wounds, occurring in 70% to 90% of chronic wound cases...
s, diabetic, and pressure ulcers. A small number of wounds that do not fall into these categories may be due to causes such as radiation poisoning
Radiation poisoning
Acute radiation syndrome also known as radiation poisoning, radiation sickness or radiation toxicity, is a constellation of health effects which occur within several months of exposure to high amounts of ionizing radiation...
or ischemia
Ischemia
In medicine, ischemia is a restriction in blood supply, generally due to factors in the blood vessels, with resultant damage or dysfunction of tissue. It may also be spelled ischaemia or ischæmia...
.
Venous and arterial ulcers
Venous ulcerVenous ulcer
Venous ulcers are wounds that are thought to occur due to improper functioning of venous valves, usually of the legs. They are the major cause of chronic wounds, occurring in 70% to 90% of chronic wound cases...
s, which usually occur in the legs, account for about 70% to 90% of chronic wounds and mostly affect the elderly. They are thought to be due to venous hypertension caused by improper function of valves that exist in the vein
Vein
In the circulatory system, veins are blood vessels that carry blood towards the heart. Most veins carry deoxygenated blood from the tissues back to the heart; exceptions are the pulmonary and umbilical veins, both of which carry oxygenated blood to the heart...
s to prevent blood from flowing backward. Ischemia
Ischemia
In medicine, ischemia is a restriction in blood supply, generally due to factors in the blood vessels, with resultant damage or dysfunction of tissue. It may also be spelled ischaemia or ischæmia...
results from the dysfunction and, combined with reperfusion injury
Reperfusion injury
Reperfusion injury is the tissue damage caused when blood supply returns to the tissue after a period of ischemia or lack of oxygen. The absence of oxygen and nutrients from blood during the ischemic period creates a condition in which the restoration of circulation results in inflammation and...
, causes the tissue
Tissue (biology)
Tissue is a cellular organizational level intermediate between cells and a complete organism. A tissue is an ensemble of cells, not necessarily identical, but from the same origin, that together carry out a specific function. These are called tissues because of their identical functioning...
damage that leads to the wounds.
Diabetic ulcers
Another major cause of chronic wounds, diabetes, is increasing in prevalence. Diabetics have a 15% higher risk for amputationAmputation
Amputation is the removal of a body extremity by trauma, prolonged constriction, or surgery. As a surgical measure, it is used to control pain or a disease process in the affected limb, such as malignancy or gangrene. In some cases, it is carried out on individuals as a preventative surgery for...
than the general population due to chronic ulcers. Diabetes causes neuropathy
Diabetic neuropathy
Diabetic neuropathies are neuropathic disorders that are associated with diabetes mellitus. These conditions are thought to result from diabetic microvascular injury involving small blood vessels that supply nerves in addition to macrovascular conditions that can culminate in diabetic neuropathy...
, which inhibits nociception
Nociception
Nociception is defined as "the neural processes of encoding and processing noxious stimuli." It is the afferent activity produced in the peripheral and central nervous system by stimuli that have the potential to damage tissue...
and the perception
Perception
Perception is the process of attaining awareness or understanding of the environment by organizing and interpreting sensory information. All perception involves signals in the nervous system, which in turn result from physical stimulation of the sense organs...
of pain
Pain
Pain is an unpleasant sensation often caused by intense or damaging stimuli such as stubbing a toe, burning a finger, putting iodine on a cut, and bumping the "funny bone."...
. Thus patients may not initially notice small wounds to legs and feet, and may therefore fail to prevent infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
or repeated injury
Injury
-By cause:*Traumatic injury, a body wound or shock produced by sudden physical injury, as from violence or accident*Other injuries from external physical causes, such as radiation injury, burn injury or frostbite*Injury from infection...
. Further, diabetes causes immune compromise and damage to small blood vessels, preventing adequate oxygenation of tissue, which can cause chronic wounds. Pressure also plays a role in the formation of diabetic ulcers.
Pressure ulcers
Another leading type of chronic wounds is pressure ulcers, which usually occur in people with conditions such as paralysisParalysis
Paralysis is loss of muscle function for one or more muscles. Paralysis can be accompanied by a loss of feeling in the affected area if there is sensory damage as well as motor. A study conducted by the Christopher & Dana Reeve Foundation, suggests that about 1 in 50 people have been diagnosed...
that inhibit movement of body parts that are commonly subjected to pressure such as the heels, shoulder blades, and sacrum
Sacrum
In vertebrate anatomy the sacrum is a large, triangular bone at the base of the spine and at the upper and back part of the pelvic cavity, where it is inserted like a wedge between the two hip bones. Its upper part connects with the last lumbar vertebra, and bottom part with the coccyx...
. Pressure ulcers are caused by ischemia that occurs when pressure on the tissue is greater than the pressure in capillaries, and thus restricts blood flow into the area. Muscle tissue, which needs more oxygen and nutrient
Nutrient
A nutrient is a chemical that an organism needs to live and grow or a substance used in an organism's metabolism which must be taken in from its environment. They are used to build and repair tissues, regulate body processes and are converted to and used as energy...
s than skin
Skin
-Dermis:The dermis is the layer of skin beneath the epidermis that consists of connective tissue and cushions the body from stress and strain. The dermis is tightly connected to the epidermis by a basement membrane. It also harbors many Mechanoreceptors that provide the sense of touch and heat...
does, shows the worst effects from prolonged pressure. As in other chronic ulcers, reperfusion injury
Reperfusion injury
Reperfusion injury is the tissue damage caused when blood supply returns to the tissue after a period of ischemia or lack of oxygen. The absence of oxygen and nutrients from blood during the ischemic period creates a condition in which the restoration of circulation results in inflammation and...
damages tissue.
Signs and symptoms
Chronic wound patients often report painPain
Pain is an unpleasant sensation often caused by intense or damaging stimuli such as stubbing a toe, burning a finger, putting iodine on a cut, and bumping the "funny bone."...
as dominant in their lives.
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, 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. Frustrations regarding ineffective analgesic
Analgesic
An analgesic is any member of the group of drugs used to relieve pain . The word analgesic derives from Greek an- and algos ....
s and plans of care that they were unable to adhere
Compliance (medicine)
In medicine, compliance describes the degree to which a patient correctly follows medical advice...
to were also identified.
Cause
In addition to poor circulation, neuropathy, and difficulty moving, factors that contribute to chronic wounds include systemic illnesses, age, and repeated traumaPhysical trauma
Trauma refers to "a body wound or shock produced by sudden physical injury, as from violence or accident." It can also be described as "a physical wound or injury, such as a fracture or blow." Major trauma can result in secondary complications such as circulatory shock, respiratory failure and death...
. Comorbid
Comorbidity
In medicine, comorbidity is either the presence of one or more disorders in addition to a primary disease or disorder, or the effect of such additional disorders or diseases.- In medicine :...
ailments that may contribute to the formation of chronic wounds include vasculitis
Vasculitis
Vasculitis refers to a heterogeneous group of disorders that are characterized by inflammatory destruction of blood vessels. Both arteries and veins are affected. Lymphangitis is sometimes considered a type of vasculitis...
(an inflammation of blood vessels), immune suppression, pyoderma gangrenosum
Pyoderma gangrenosum
Pyoderma gangrenosum is a disease that causes tissue to become necrotic, causing deep ulcers that usually occur on the legs. When they occur, they can lead to chronic wounds. Ulcers usually initially look like small bug bites or papules, and they progress to larger ulcers. Though the wounds...
, and diseases that cause ischemia
Ischemia
In medicine, ischemia is a restriction in blood supply, generally due to factors in the blood vessels, with resultant damage or dysfunction of tissue. It may also be spelled ischaemia or ischæmia...
. Immune suppression can be caused by illnesses or medical drug
Medication
A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
s used over a long period, for example steroid
Steroid
A steroid is a type of organic compound that contains a characteristic arrangement of four cycloalkane rings that are joined to each other. Examples of steroids include the dietary fat cholesterol, the sex hormones estradiol and testosterone, and the anti-inflammatory drug dexamethasone.The core...
s. Emotional stress can also negatively affect the healing of a wound, possibly by raising blood pressure
Blood pressure
Blood pressure is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. When used without further specification, "blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, BP varies...
and levels of cortisol
Cortisol
Cortisol is a steroid hormone, more specifically a glucocorticoid, produced by the adrenal gland. It is released in response to stress and a low level of blood glucocorticoids. Its primary functions are to increase blood sugar through gluconeogenesis; suppress the immune system; and aid in fat,...
, which lowers immunity.
What appears to be a chronic wound may also be a malignancy; for example, cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
ous tissue can grow until blood cannot reach the cells and the tissue becomes an ulcer. Cancer, especially squamous cell carcinoma
Squamous cell carcinoma
Squamous cell carcinoma , occasionally rendered as "squamous-cell carcinoma", is a histologically distinct form of cancer. It arises from the uncontrolled multiplication of malignant cells deriving from epithelium, or showing particular cytological or tissue architectural characteristics of...
, may also form as the result of chronic wounds, probably due to repetitive tissue damage that stimulates rapid cell proliferation.
Another factor that may contribute to chronic wounds is old age. The skin of older people is more easily damaged, and older cells do not proliferate as fast and may not have an adequate response to stress in terms of gene upregulation of stress-related protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s. In older cells, stress response gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
s 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.
Comorbid factors that can lead to ischemia are especially likely to contribute to chronic wounds. Such factors include chronic fibrosis
Fibrosis
Fibrosis is the formation of excess fibrous connective tissue in an organ or tissue in a reparative or reactive process. This is as opposed to formation of fibrous tissue as a normal constituent of an organ or tissue...
, atherosclerosis
Atherosclerosis
Atherosclerosis is a condition in which an artery wall thickens as a result of the accumulation of fatty materials such as cholesterol...
, edema
Edema
Edema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces swelling...
, sickle cell disease, and arterial insufficiency
Arterial insufficiency
Arterial Insufficiency is a lack of enough blood flow through the arteries typically caused by atherosclerosis. Arterial insufficiency can affect many different parts of the body. The specific symptoms may indicate which artery is involved. If heart arteries are involved, it can cause symptoms of...
-related illnesses.
Repeated physical trauma
Physical trauma
Trauma refers to "a body wound or shock produced by sudden physical injury, as from violence or accident." It can also be described as "a physical wound or injury, such as a fracture or blow." Major trauma can result in secondary complications such as circulatory shock, respiratory failure and death...
plays a role in chronic wound formation by continually initiating the inflammatory cascade. The trauma may occur by accident, for example when a leg is repeatedly bumped against a wheelchair
Wheelchair
A wheelchair is a chair with wheels, designed to be a replacement for walking. The device comes in variations where it is propelled by motors or by the seated occupant turning the rear wheels by hand. Often there are handles behind the seat for someone else to do the pushing...
rest, or it may be due to intentional acts. Heroin users who lose venous access may resort to 'skin popping
Skin popping
Skin popping is a method of administration for the use of drugs by injecting or placing the substance or drug under the skin. It can include subcutaneous placement or intradermal placement though is also rarely used to mean intramuscular injection. It is however as a term distinct from the meaning...
', or injecting the drug subcutaneously, which is highly damaging to tissue and frequently leads to chronic ulcers. Children who are repeatedly seen for a wound that does not heal are sometimes found to be victims of a parent with Munchausen syndrome by proxy
Munchausen syndrome by proxy
Münchausen syndrome by proxy is a label for a pattern of behavior in which care-givers deliberately exaggerate, fabricate, and/or induce physical, psychological, behavioral, and/or mental health problems in others. Other experts classified MSbP as a mental illness...
, a disease in which the abuser may repeatedly inflict harm on the child in order to receive attention.
Pathophysiology
Chronic wounds may affect only the epidermis and dermisDermis
The dermis is a layer of skin between the epidermis and subcutaneous tissues, and is composed of two layers, the papillary and reticular dermis...
, or they may affect tissues all the way to the fascia
Fascia
A fascia is a layer of fibrous tissue that permeates the human body. A fascia is a connective tissue that surrounds muscles, groups of muscles, blood vessels, and nerves, binding those structures together in much the same manner as plastic wrap can be used to hold the contents of sandwiches...
. They may be formed originally by the same things that cause acute ones, such as surgery
Surgery
Surgery is an ancient medical specialty that uses operative manual and instrumental techniques on a patient to investigate and/or treat a pathological condition such as disease or injury, or to help improve bodily function or appearance.An act of performing surgery may be called a surgical...
or accidental trauma, or they may form as the result of systemic infection, vascular, immune, or nerve insufficiency, or comorbidities such as neoplasia
Neoplasia
Neoplasm is an abnormal mass of tissue as a result of neoplasia. Neoplasia is the abnormal proliferation of cells. The growth of neoplastic cells exceeds and is not coordinated with that of the normal tissues around it. The growth persists in the same excessive manner even after cessation of the...
s or metabolic disorders. 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.
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
Animal testing
Animal testing, also known as animal experimentation, animal research, and in vivo testing, is the use of non-human animals in experiments. Worldwide it is estimated that the number of vertebrate animals—from zebrafish to non-human primates—ranges from the tens of millions to more than 100 million...
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. Nonetheless, current researchers now understand some of the major factors that lead to chronic wounds, among which are ischemia, reperfusion injury
Reperfusion injury
Reperfusion injury is the tissue damage caused when blood supply returns to the tissue after a period of ischemia or lack of oxygen. The absence of oxygen and nutrients from blood during the ischemic period creates a condition in which the restoration of circulation results in inflammation and...
, and bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
l colonization.
Ischemia
Ischemia is an important factor in the formation and persistence of wounds, especially when it occurs repetitively (as it usually does) or when combined with a patient’s old age. Ischemia causes tissue to become inflamed and cells to release factors that attract neutrophils such as interleukinInterleukin
Interleukins are a group of cytokines that were first seen to be expressed by white blood cells . The term interleukin derives from "as a means of communication", and "deriving from the fact that many of these proteins are produced by leukocytes and act on leukocytes"...
s, chemokine
Chemokine
Chemokines are a family of small cytokines, or proteins secreted by cells. Their name is derived from their ability to induce directed chemotaxis in nearby responsive cells; they are chemotactic cytokines...
s, leukotriene
Leukotriene
Leukotrienes are fatty signaling molecules. They were first found in leukocytes . One of their roles is to trigger contractions in the smooth muscles lining the trachea; their overproduction is a major cause of inflammation in asthma and allergic rhinitis...
s, and complement factors.
While they fight pathogens, neutrophils also release inflammatory cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
s and enzymes that damage cells. One of their important jobs is to produce Reactive Oxygen Species (ROS)
Reactive oxygen species
Reactive oxygen species are chemically reactive molecules containing oxygen. Examples include oxygen ions and peroxides. Reactive oxygen species are highly reactive due to the presence of unpaired valence shell electrons....
to kill bacteria, for which they use an enzyme called myeloperoxidase
Myeloperoxidase
Myeloperoxidase is a peroxidase enzyme that in humans is encoded by the MPO gene. Myeloperoxidase is most abundantly expressed in neutrophil granulocytes . It is a lysosomal protein stored in azurophilic granules of the neutrophil...
. The enzymes and ROS produced by neutrophils and other leukocytes damage cells and prevent cell proliferation and wound closure by damaging DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
, lipid
Lipid
Lipids constitute a broad group of naturally occurring molecules that include fats, waxes, sterols, fat-soluble vitamins , monoglycerides, diglycerides, triglycerides, phospholipids, and others...
s, proteins, the extracellular matrix
Extracellular matrix
In biology, the extracellular matrix is the extracellular part of animal tissue that usually provides structural support to the animal cells in addition to performing various other important functions. The extracellular matrix is the defining feature of connective tissue in animals.Extracellular...
(ECM), and cytokines that speed healing. 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. 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.
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 suffered hypothermia during surgery, are at higher risk for infection. The host’s immune response to the presence of bacteria prolongs inflammation, delays healing, and damages tissue. Infection can lead not only to chronic wounds but also to gangreneGangrene
Gangrene is a serious and potentially life-threatening condition that arises when a considerable mass of body tissue dies . This may occur after an injury or infection, or in people suffering from any chronic health problem affecting blood circulation. The primary cause of gangrene is reduced blood...
, loss of the infected limb, and death
Death
Death is the permanent termination of the biological functions that sustain a living organism. Phenomena which commonly bring about death include old age, predation, malnutrition, disease, and accidents or trauma resulting in terminal injury....
of the patient.
Like ischemia, bacterial colonization and infection damage tissue by causing a greater number of neutrophils to enter the wound site. In patients with chronic wounds, bacteria with resistances
Antibiotic resistance
Antibiotic resistance is a type of drug resistance where a microorganism is able to survive exposure to an antibiotic. While a spontaneous or induced genetic mutation in bacteria may confer resistance to antimicrobial drugs, genes that confer resistance can be transferred between bacteria in a...
to antibiotics may have time to develop. In addition, patients that carry drug resistant bacterial strains such as methicillin-resistant Staphylococcus aureus
Methicillin-resistant Staphylococcus aureus
Methicillin-resistant Staphylococcus aureus is a bacterium responsible for several difficult-to-treat infections in humans. It is also called multidrug-resistant Staphylococcus aureus and oxacillin-resistant Staphylococcus aureus...
(MRSA) have more chronic wounds.
Growth factors and proteolytic enzymes
Chronic wounds also differ in makeup from acute wounds in that their levels of proteolytic enzymes such as elastaseElastase
In molecular biology, elastase is an enzyme from the class of proteases that break down proteins.- Forms and classification:There exist eight human genes for elastase:Bacterial forms: Organisms such as P...
. and matrix metalloproteinase
Matrix metalloproteinase
Matrix metalloproteinases are zinc-dependent endopeptidases; other family members are adamalysins, serralysins, and astacins. The MMPs belong to a larger family of proteases known as the metzincin superfamily....
s (MMPs) are higher, while their concentrations of growth factors such as Platelet-derived growth factor
Platelet-derived growth factor
In molecular biology, platelet-derived growth factor is one of the numerous growth factors, or proteins that regulate cell growth and division. In particular, it plays a significant role in blood vessel formation , the growth of blood vessels from already-existing blood vessel tissue. Uncontrolled...
and Keratinocyte Growth Factor
Keratinocyte Growth Factor
The Keratinocyte Growth Factor , also known as FGF7, is a growth factor present in the epithelialization-phase of wound healing. In this phase, keratinocytes are covering the wound, forming the epithelium....
are lower.
Since growth factors (GFs) are imperative in timely wound healing, inadequate GF levels may be an important factor in chronic wound formation. 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.
Chronic wounds such as diabetic and venous ulcers are also caused by a failure of fibroblast
Fibroblast
A fibroblast is a type of cell that synthesizes the extracellular matrix and collagen, the structural framework for animal tissues, and plays a critical role in wound healing...
s to produce adequate ECM proteins and by keratinocyte
Keratinocyte
Keratinocytes are the predominant cell type in the epidermis, the outermost layer of the human skin, constituting 95% of the cells found there. Those keratinocytes found in the basal layer of the skin are sometimes referred to as "basal cells" or "basal keratinocytes"...
s to epithelialize the wound. Fibroblast gene expression is different in chronic wounds than in acute wounds.
Though all wounds require a certain level of elastase and proteases for proper healing, too high a concentration is damaging. Leukocytes in the wound area release elastase, which increases inflammation, destroys tissue, proteoglycans, and collagen
Collagen
Collagen is a group of naturally occurring proteins found in animals, especially in the flesh and connective tissues of mammals. It is the main component of connective tissue, and is the most abundant protein in mammals, making up about 25% to 35% of the whole-body protein content...
, and damages growth factors, fibronectin, and factors that inhibit proteases. The activity of elastase is increased by human serum albumin
Human serum albumin
Human serum albumin is the most abundant protein in human blood plasma. It is produced in the liver. Albumin constitutes about half of the blood serum protein...
, which is the most abundant protein found in chronic wounds. 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.
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.
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. Various methods exist to ameliorate these problems, including antibiotic and antibacterial use, debridement, irrigation, vacuum-assisted closure, warming, oxygenation, moist wound healing, removing mechanical stress, and adding cells or other materials to secrete or enhance levels of healing factors.Preventing and treating infection
To lower the bacterial count in wounds, therapists may use topical antibioticAntibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...
s, which kill bacteria and can also help by keeping the wound environment moist,
which is important for speeding the healing of chronic wounds. Some researchers have experimented with the use of tea tree oil
Tea tree oil
Tea tree oil, or melaleuca oil, is a pale yellow colour to nearly clear essential oil with a fresh camphoraceous odor. It is taken from the leaves of the Melaleuca alternifolia, which is native to the northeast coast of New South Wales, Australia...
, an antibacterial agent which also has anti-inflammatory effects. Disinfectants are contraindicated because they damage tissues and delay wound contraction. Further, they are rendered ineffective by organic matter in wounds like blood and exudate
Exudate
An exudate is any fluid that filters from the circulatory system into lesions or areas of inflammation. It can apply to plants as well as animals. Its composition varies but generally includes water and the dissolved solutes of the main circulatory fluid such as sap or blood...
and are thus not useful in open wounds.
A greater amount of exudate and necrotic tissue in a wound increases likelihood of infection by serving as a medium for bacterial growth away from the host’s defenses. Since bacteria thrive on dead tissue, wounds are often surgically debrided
Debridement
Debridement is the medical removal of a patient's dead, damaged, or infected tissue to improve the healing potential of the remaining healthy tissue...
to remove the devitalized tissue. Debridement and drainage of wound fluid are an especially important part of the treatment for diabetic ulcers, which may create the need for amputation if infection gets out of control. Mechanical removal of bacteria and devitalized tissue is also the idea behind wound irrigation, which is accomplished using pulsed lavage
Lavage
In medicine, therapeutic irrigation or lavage is a general term referring to cleaning or rinsing.Specific types include:* Antiseptic lavage* Bronchoalveolar lavage* Gastric lavage* Peritoneal lavage* Arthroscopic lavage* Ductal lavage...
.
Removing necrotic or devitalzed tissue is also the aim of maggot therapy
Maggot therapy
Maggot therapy is a type of biotherapy involving the intentional introduction of live, disinfected maggots into the non-healing skin and soft tissue wound of a human or animal for the purpose of cleaning out the...
, the intentional introduction by a health care practitioner of live, disinfected maggot
Maggot
In everyday speech the word maggot means the larva of a fly ; it is applied in particular to the larvae of Brachyceran flies, such as houseflies, cheese flies, and blowflies, rather than larvae of the Nematocera, such as mosquitoes and Crane flies...
s 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.
Negative pressure wound therapy
Negative Pressure Wound Therapy
Negative-pressure wound therapy is a therapeutic technique using a vacuum dressing to promote healing in acute or chronic wounds and enhance healing of first and second degree burns. The therapy involves the controlled application of sub-atmospheric pressure to the local wound environment, using a...
(NPWT) is a treatment that improves ischemic tissues and removes wound fluid used by bacteria. This therapy, also known as vacuum-assisted closure, reduces swelling in tissues, which brings more blood and nutrients to the area, as does the negative pressure itself. The treatment also decompresses tissues and alters the shape of cells, causes them to express different mRNAs and to proliferate and produce ECM molecules.
Treating trauma and painful wounds
Persistent chronic painChronic pain
Chronic pain has several different meanings in medicine. Traditionally, the distinction between acute and chronic pain has relied upon an arbitrary interval of time from onset; the two most commonly used markers being 3 months and 6 months since the initiation of pain, though some theorists and...
associated with non-healing wounds is caused by tissue (nociceptive) or nerve (neuropathic) damage and is influenced by dressing changes and chronic inflammation
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
. Chronic wounds take a long time to heal and patients can suffer from chronic wounds for many years. Chronic wound healing may be compromised by coexisting underlying conditions, such as venous valve backflow
Venous ulcer
Venous ulcers are wounds that are thought to occur due to improper functioning of venous valves, usually of the legs. They are the major cause of chronic wounds, occurring in 70% to 90% of chronic wound cases...
, peripheral vascular disease, uncontrolled edema and diabetes mellitus
Diabetes mellitus
Diabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced...
.
If wound pain
Pain
Pain is an unpleasant sensation often caused by intense or damaging stimuli such as stubbing a toe, burning a finger, putting iodine on a cut, and bumping the "funny bone."...
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. 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 during weartime.
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.
Treating 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. Some healthcare professionals use ‘radiant bandages’ to keep the area warm, and care must be taken during surgery to prevent hypothermiaHypothermia
Hypothermia is a condition in which core temperature drops below the required temperature for normal metabolism and body functions which is defined as . Body temperature is usually maintained near a constant level of through biologic homeostasis or thermoregulation...
, which increases rates of post-surgical infection.
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
Hyperbaric oxygen therapy
Hyperbaric medicine, also known as hyperbaric oxygen therapy , is the medical use of oxygen at a level higher than atmospheric pressure. The equipment required consists of a pressure chamber, which may be of rigid or flexible construction, and a means of delivering 100% oxygen...
, or HBOT, which can compensate for limitations of blood supply and correct hypoxia
Hypoxia (medical)
Hypoxia, or hypoxiation, is a pathological condition in which the body as a whole or a region of the body is deprived of adequate oxygen supply. Variations in arterial oxygen concentrations can be part of the normal physiology, for example, during strenuous physical exercise...
. In addition to killing bacteria, higher oxygen content in tissues speeds growth factor production, fibroblast growth, and angiogenesis
Angiogenesis
Angiogenesis is the physiological process involving the growth of new blood vessels from pre-existing vessels. Though there has been some debate over terminology, vasculogenesis is the term used for spontaneous blood-vessel formation, and intussusception is the term for the formation of new blood...
. However, increased oxygen levels also means increased production of ROS. Antioxidant
Antioxidant
An antioxidant is a molecule capable of inhibiting the oxidation of other molecules. Oxidation is a chemical reaction that transfers electrons or hydrogen from a substance to an oxidizing agent. Oxidation reactions can produce free radicals. In turn, these radicals can start chain reactions. When...
s, 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.
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 suffer 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.
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.One way to increase growth factor concentrations in wounds is to apply the growth factors directly, though this takes many repetitions and requires large amounts of the factors. Another way is to spread onto the wound a gel of the patient’s own blood platelets, which then secrete growth factors such as vascular endothelial growth factor
Vascular endothelial growth factor
Vascular endothelial growth factor is a signal protein produced by cells that stimulates vasculogenesis and angiogenesis. It is part of the system that restores the oxygen supply to tissues when blood circulation is inadequate....
(VEGF), insulin-like growth factor
Insulin-like growth factor
The insulin-like growth factors are proteins with high sequence similarity to insulin. IGFs are part of a complex system that cells use to communicate with their physiologic environment...
1–2 (IGF), PDGF, transforming growth factor
Transforming growth factor
Transforming growth factor is used to describe two classes of polypeptide growth factors, TGFα and TGFβ....
-β (TGF-β), and epidermal growth factor
Epidermal growth factor
Epidermal growth factor or EGF is a growth factor that plays an important role in the regulation of cell growth, proliferation, and differentiation by binding to its receptor EGFR...
(EGF). Other treatments include implanting cultured keratinocytes into the wound to reepithelialize it and culturing and implanting fibroblasts into wounds. Some patients are treated with artificial skin
Artificial skin
Artificial skin can refer to skin grown in a laboratory that can be used as skin replacement for people who have suffered skin trauma such as severe burns or skin diseases.Alternatively, it can also refer to skin synthetically produced for other purposes....
substitutes that have fibroblasts and keratinocytes in a matrix of collagen to replicate skin and release growth factors.
In other cases, skin from cadaver
Cadaver
A cadaver is a dead human body.Cadaver may also refer to:* Cadaver tomb, tomb featuring an effigy in the form of a decomposing body* Cadaver , a video game* cadaver A command-line WebDAV client for Unix....
s is grafted onto wounds, providing a cover to keep out bacteria and preventing the buildup of too much granulation tissue
Granulation tissue
Granulation tissue is the perfused, fibrous connective tissue that replaces a fibrin clot in healing wounds. Granulation tissue typically grows from the base of a wound and is able to fill wounds of almost any size it heals...
, which can lead to excessive scar
Scar
Scars are areas of fibrous tissue that replace normal skin after injury. A scar results from the biological process of wound repair in the skin and other tissues of the body. Thus, scarring is a natural part of the healing process. With the exception of very minor lesions, every wound results in...
ring. Though the allograft (skin transplanted from a member of the same species
Species
In biology, a species is one of the basic units of biological classification and a taxonomic rank. A species is often defined as a group of organisms capable of interbreeding and producing fertile offspring. While in many cases this definition is adequate, more precise or differing measures are...
) is replaced by granulation tissue and is not actually incorporated into the healing wound, it encourages cellular proliferation and provides a structure for epithelial cells to crawl across. 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.
Collagen dressings are another way to provide the matrix for cellular proliferation and migration, while also keeping the wound moist and absorbing exudate.
Since levels of protease inhibitor
Protease inhibitor
Protease inhibitor can refer to:* Protease inhibitor : a class of medication that inhibits viral protease* Protease inhibitor : molecules that inhibit proteases...
s are lowered in chronic wounds, some researchers are seeking ways to heal tissues by replacing these inhibitors in them. Secretory leukocyte protease inhibitor
Secretory leukocyte protease inhibitor
Secretory leukocyte protease inhibitor is a highly cationic single-chain protein with eight intramolecular disulfide bonds. It is found in large quantities in bronchial, cervical, and nasal mucosa, saliva, and seminal fluids. SLPI inhibits human leukocyte elastase, human cathepsin G, human...
(SLPI), which inhibits not only proteases but also inflammation and microorganisms like virus
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
es, bacteria, and fungi
Fungus
A fungus is a member of a large group of eukaryotic organisms that includes microorganisms such as yeasts and molds , as well as the more familiar mushrooms. These organisms are classified as a kingdom, Fungi, which is separate from plants, animals, and bacteria...
, may prove to be an effective treatment.
Research into hormone
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...
s and wound healing has shown estrogen
Estrogen
Estrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...
to speed wound healing in elderly humans and in animals that have had their ovaries removed, possibly by preventing excess neutrophils from entering the wound and releasing elastase. Thus the use of estrogen is a future possibility for treating chronic wounds.
Epidemiology
Chronic wounds mostly affect people over the age of 60.The incidence
Incidence (epidemiology)
Incidence is a measure of the risk of developing some new condition within a specified period of time. Although sometimes loosely expressed simply as the number of new cases during some time period, it is better expressed as a proportion or a rate with a denominator.Incidence proportion is the...
is 0.78% of the population and the prevalence ranges from 0.18 to 0.32%. As the population ages
Old age
Old age consists of ages nearing or surpassing the average life span of human beings, and thus the end of the human life cycle...
, the number of chronic wounds is expected to rise.
External links
- Maggot Therapy Project web site at the University of California, Irvine, list of maggot therapy practitioners
- http://www.monarchlabs.com/ suppliers of Medical Maggots (disinfected Phaenicia sericata larvae), picture of Medical Maggots vial
- BioTherapeutics Education and Research Foundation
- http://www.thewoundinstitute.com Accredited, interactive wound care education offered at no cost
- http://www.elephantintheroom.com.au Awareness campaign website by the Australian Wound Management Association