A chronic wound is a
wound
A wound is a rapid onset of injury that involves laceration, lacerated or puncture wound, punctured skin (an ''open'' wound), or a bruise, contusion (a ''closed'' wound) from blunt force physical trauma, trauma or compression. In pathology, a '' ...
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.
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.
In acute wounds, there is a precise balance between production and degradation of
molecule
A molecule is a group of two or more atoms held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions which satisfy this criterion. In quantum physics, organic chemistry, and bioch ...
s such as
collagen
Collagen () is the main structural protein in the extracellular matrix found in the body's various connective tissues. As the main component of connective tissue, it is the most abundant protein in mammals, making up from 25% to 35% of the whole ...
; 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 may refer to:
Science and medicine
* Stress (biology), an organism's response to a stressor such as an environmental condition
* Stress (linguistics), relative emphasis or prominence given to a syllable in a word, or to a word in a phrase ...
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.
Signs and symptoms
Chronic wound patients often report
pain
Pain is a distressing feeling often caused by intense or damaging stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sensory and emotional experience associated with, or resembling that associated with, ...
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
Venous ulcer is defined by the American Venous Forum as "a full-thickness defect of skin, most frequently in the ankle region, that fails to heal spontaneously and is sustained by chronic venous disease, based on venous duplex ultrasound testing." ...
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
An analgesic drug, also called simply an analgesic (American English), analgaesic (British English), pain reliever, or painkiller, is any member of the group of drugs used to achieve relief from pain (that is, analgesia or pain management). It ...
s and plans of care that they were unable to
adhere 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
trauma
Trauma most often refers to:
*Major trauma, in physical medicine, severe physical injury caused by an external source
*Psychological trauma, a type of damage to the psyche that occurs as a result of a severely distressing event
*Traumatic inju ...
. The genetic skin disorders collectively known as epidermolysis bullosa display skin fragility and a tendency to develop chronic, non-healing wounds.
Comorbid
In medicine, comorbidity - from Latin morbus ("sickness"), co ("together"), -ity (as if - several sicknesses together) - is the presence of one or more additional conditions often co-occurring (that is, concomitant or concurrent) with a primary c ...
ailments that may contribute to the formation of chronic wounds include
vasculitis
Vasculitis is a group of disorders that destroy blood vessels by inflammation. Both arteries and veins are affected. Lymphangitis (inflammation of lymphatic vessels) is sometimes considered a type of vasculitis. Vasculitis is primarily caused b ...
(an inflammation of blood vessels),
immune suppression
Immunosuppression is a reduction of the activation or efficacy of the immune system. Some portions of the immune system itself have immunosuppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse react ...
,
pyoderma gangrenosum
Pyoderma gangrenosum is a rare, inflammatory skin disease where painful pustules or nodules become ulcers that progressively grow. Pyoderma gangrenosum is not infectious.
Treatments may include corticosteroids, ciclosporin, infliximab, or cana ...
, and diseases that cause
ischemia
Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism (to keep tissue alive). Ischemia is generally caused by problems wi ...
.
[ Immune suppression can be caused by illnesses or medical ]drug
A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via insuffla ...
s used over a long period, for example steroid
A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and a ...
s.[ ]Emotional stress
In psychology, stress is a feeling of emotional strain and pressure. Stress is a type of psychological pain. Small amounts of stress may be beneficial, as it can improve athletic performance, motivation and reaction to the environment. Excess ...
can also negatively affect the healing of a wound, possibly by raising blood pressure
Blood pressure (BP) is the pressure of circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term "blood pressure" r ...
and levels of cortisol
Cortisol is a steroid hormone, in the glucocorticoid class of hormones. When used as a medication, it is known as hydrocortisone.
It is produced in many animals, mainly by the ''zona fasciculata'' of the adrenal cortex in the adrenal gland ...
, which lowers immunity.[
What appears to be a chronic wound may also be a ]malignancy
Malignancy () is the tendency of a medical condition to become progressively worse.
Malignancy is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous ''benign'' tumor in that a malignancy is not s ...
; for example, cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
ous tissue can grow until blood cannot reach the cells and the tissue becomes an ulcer.[Trent, JT. 2003.]
Wounds and malignancy.
''Advances in Skin & Wound Care''. Accessed January 1, 2007. Cancer, especially squamous cell carcinoma
Squamous-cell carcinomas (SCCs), also known as epidermoid carcinomas, comprise a number of different types of cancer that begin in squamous cells. These cells form on the surface of the skin, on the lining of hollow organs in the body, and on the ...
, may also form as the result of chronic wounds, probably due to repetitive tissue damage that stimulates rapid cell proliferation
Cell proliferation is the process by which ''a cell grows and divides to produce two daughter cells''. Cell proliferation leads to an exponential increase in cell number and is therefore a rapid mechanism of tissue growth. Cell proliferation re ...
.[
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
In the biological context of organisms' production of gene products, downregulation is the process by which a cell decreases the quantity of a cellular component, such as RNA or protein, in response to an external stimulus. The complementary proce ...
of stress-related protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
s.[ In older cells, stress response ]gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
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, also known as fibrotic scarring, is a pathological wound healing in which connective tissue replaces normal parenchymal tissue to the extent that it goes unchecked, leading to considerable tissue remodelling and the formation of perma ...
, edema
Edema, also spelled oedema, and also known as fluid retention, dropsy, hydropsy and swelling, is the build-up of fluid in the body's Tissue (biology), tissue. Most commonly, the legs or arms are affected. Symptoms may include skin which feels t ...
, sickle cell disease
Sickle cell disease (SCD) is a group of blood disorders typically inherited from a person's parents. The most common type is known as sickle cell anaemia. It results in an abnormality in the oxygen-carrying protein haemoglobin found in red blo ...
, and peripheral artery disease
Peripheral artery disease (PAD) is an abnormal narrowing of arteries other than those that supply the heart or brain. When narrowing occurs in the heart, it is called coronary artery disease, and in the brain, it is called cerebrovascular diseas ...
such as by atherosclerosis
Atherosclerosis is a pattern of the disease arteriosclerosis in which the wall of the artery develops abnormalities, called lesions. These lesions may lead to narrowing due to the buildup of atheroma, atheromatous plaque. At onset there are usu ...
.[
Repeated ]physical trauma
An injury is any physiological damage to living tissue caused by immediate physical stress. An injury can occur intentionally or unintentionally and may be caused by blunt trauma, penetrating trauma, burning, toxic exposure, asphyxiation, ...
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
A wheelchair is a chair with wheels, used when walking is difficult or impossible due to illness, injury, problems related to old age, or disability. These can include spinal cord injuries ( paraplegia, hemiplegia, and quadriplegia), cerebr ...
rest, or it may be due to intentional acts. Heroin
Heroin, also known as diacetylmorphine and diamorphine among other names, is a potent opioid mainly used as a recreational drug for its euphoric effects. Medical grade diamorphine is used as a pure hydrochloride salt. Various white and brow ...
users who lose venous access may resort to 'skin popping
Skin popping is a route of administration of street drugs where they are injected or deposited under the skin. It is usually a depot injection, either subcutaneous or intradermal, and not an intramuscular injection. After deposition, the drug the ...
', 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
Factitious disorder imposed on another (FDIA), also known as fabricated or induced illness by carers (FII), and first named as Munchausen syndrome by proxy (MSbP), is a condition in which a caregiver creates the appearance of health problems in a ...
, a disease in which the abuser may repeatedly inflict harm on the child in order to receive attention.
Periwound skin damage caused by excessive amounts of exudate
An exudate is a fluid emitted by an organism through pores or a wound, a process known as exuding or exudation.
''Exudate'' is derived from ''exude'' 'to ooze' from Latin ''exsūdāre'' 'to (ooze out) sweat' (''ex-'' 'out' and ''sūdāre'' 'to ...
and other bodily fluids
Body fluids, bodily fluids, or biofluids, sometimes body liquids, are liquids within the human body. In lean healthy adult men, the total body water is about 60% (60–67%) of the total body weight; it is usually slightly lower in women (52-55%) ...
can perpetuate the non-healing status of chronic wounds. Maceration, excoriation, dry (fragile) skin, hyperkeratosis, callus and eczema are frequent problems 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 epidermis
The epidermis is the outermost of the three layers that comprise the skin, the inner layers being the dermis and hypodermis. The epidermis layer provides a barrier to infection from environmental pathogens and regulates the amount of water rele ...
and dermis
The dermis or corium is a layer of skin between the epidermis (with which it makes up the cutis) and subcutaneous tissues, that primarily consists of dense irregular connective tissue and cushions the body from stress and strain. It is divided i ...
, or they may affect tissues all the way to the fascia
A fascia (; plural fasciae or fascias; adjective fascial; from Latin: "band") is a band or sheet of connective tissue, primarily collagen, beneath the skin that attaches to, stabilizes, encloses, and separates muscles and other internal organs. ...
.[ They may be formed originally by the same things that cause acute ones, such as ]surgery
Surgery ''cheirourgikē'' (composed of χείρ, "hand", and ἔργον, "work"), via la, chirurgiae, meaning "hand work". is a medical specialty that uses operative manual and instrumental techniques on a person to investigate or treat a pat ...
or accidental trauma, or they may form as the result of systemic infection, vascular, immune, or nerve insufficiency, or comorbidities such as neoplasia
A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
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 studies is a recently recognised field in which animals are studied in a variety of cross-disciplinary ways. Scholars who engage in animal studies may be formally trained in a number of diverse fields, including geography, art history, ant ...
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, sometimes called ischemia-reperfusion injury (IRI) or reoxygenation injury, is the tissue damage caused when blood supply returns to tissue ('' re-'' + '' perfusion'') after a period of ischemia or lack of oxygen (anoxia or h ...
, and bacteria
Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...
l colonization.[
]
Ischemia
Ischemia
Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism (to keep tissue alive). Ischemia is generally caused by problems wi ...
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 ]neutrophil
Neutrophils (also known as neutrocytes or heterophils) are the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. They form an essential part of the innate immune system, with their functions varying in ...
s such as interleukin
Interleukins (ILs) are a group of cytokines (secreted proteins and signal molecules) that are expressed and secreted by white blood cells (leukocytes) as well as some other body cells. The human genome encodes more than 50 interleukins and related ...
s, chemokine
Chemokines (), or chemotactic cytokines, are a family of small cytokines or signaling proteins secreted by cells that induce directional movement of leukocytes, as well as other cell types, including endothelial and epithelial cells. In additio ...
s, leukotriene
Leukotrienes are a family of eicosanoid inflammatory mediators produced in leukocytes by the oxidation of arachidonic acid (AA) and the essential fatty acid eicosapentaenoic acid (EPA) by the enzyme arachidonate 5-lipoxygenase.
Leukotrienes ...
s, and complement factor
The complement system, also known as complement cascade, is a part of the immune system that enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promote inflammation, and ...
s.[
While they fight pathogens, neutrophils also release inflammatory ]cytokine
Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...
s and enzymes that damage cells.[ One of their important jobs is to produce ]Reactive Oxygen Species (ROS)
In chemistry, reactive oxygen species (ROS) are highly reactive chemicals formed from diatomic oxygen (). Examples of ROS include peroxides, superoxide, hydroxyl radical, singlet oxygen, and alpha-oxygen.
The reduction of molecular oxygen () pr ...
to kill bacteria, for which they use an enzyme called myeloperoxidase
Myeloperoxidase (MPO) is a peroxidase enzyme that in humans is encoded by the ''MPO'' gene on chromosome 17. MPO is most abundantly expressed in neutrophil granulocytes (a subtype of white blood cells), and produces hypohalous acids to carry ou ...
.[ The enzymes and ROS produced by neutrophils and other leukocytes damage cells and prevent cell proliferation and wound closure by damaging DNA, ]lipid
Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include ...
s, proteins, the extracellular matrix
In biology, the extracellular matrix (ECM), also called intercellular matrix, is a three-dimensional network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide stru ...
(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. This impaired healing response is considered uncoordinated. However, soluble mediators of the immune system (growth factors), cell-based therapies and therapeutic chemicals can propagate coordinated healing.
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.]
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.[ The host's ]immune response
An immune response is a reaction which occurs within an organism for the purpose of defending against foreign invaders. These invaders include a wide variety of different microorganisms including viruses, bacteria, parasites, and fungi which could ...
to the presence of bacteria prolongs inflammation, delays healing, and damages tissue.[ Infection can lead not only to chronic wounds but also to ]gangrene
Gangrene is a type of tissue death caused by a lack of blood supply. Symptoms may include a change in skin color to red or black, numbness, swelling, pain, skin breakdown, and coolness. The feet and hands are most commonly affected. If the ga ...
, loss of the infected limb, and death
Death is the irreversible cessation of all biological functions that sustain an organism. For organisms with a brain, death can also be defined as the irreversible cessation of functioning of the whole brain, including brainstem, and brain ...
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 the generate chronic wounds.
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.
Growth factors and proteolytic enzymes
Chronic wounds also differ in makeup from acute wounds in that their levels of proteolytic enzyme
A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes (increases reaction rate or "speeds up") proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the for ...
s such as elastase
In molecular biology, elastase is an enzyme from the class of ''proteases (peptidases)'' that break down proteins. In particular, it is a serine protease.
Forms and classification
Eight human genes exist for elastase:
Some bacteria (includin ...
.[ and ]matrix metalloproteinase
Matrix metalloproteinases (MMPs), also known as matrix metallopeptidases or matrixins, are metalloproteinases that are calcium-dependent zinc-containing endopeptidases; other family members are adamalysins, serralysins, and astacins. The MMPs b ...
s (MMPs) are higher, while their concentrations of growth factors such as Platelet-derived growth factor
Platelet-derived growth factor (PDGF) is one among numerous growth factors that regulate cell growth and division. In particular, PDGF plays a significant role in blood vessel formation, the growth of blood vessels from already-existing blood v ...
and Keratinocyte Growth Factor
The keratinocyte growth factor (KGF), 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.
KGF is a small signaling molecule t ...
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
A fibroblast is a type of cell (biology), biological cell that synthesizes the extracellular matrix and collagen, produces the structural framework (Stroma (tissue), stroma) for animal Tissue (biology), tissues, and plays a critical role in wound ...
s to produce adequate ECM proteins and by keratinocyte
Keratinocytes are the primary type of Cell (biology), cell found in the epidermis (skin), epidermis, the outermost layer of the skin. In humans, they constitute 90% of epidermal skin cells.
Basal cells in the stratum basale, basal layer (''str ...
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
Proteoglycans are proteins that are heavily glycosylated. The basic proteoglycan unit consists of a "core protein" with one or more covalently attached glycosaminoglycan (GAG) chain(s). The point of attachment is a serine (Ser) residue to whic ...
, and collagen
Collagen () is the main structural protein in the extracellular matrix found in the body's various connective tissues. As the main component of connective tissue, it is the most abundant protein in mammals, making up from 25% to 35% of the whole ...
, and damages growth factors, fibronectin, and factors that inhibit proteases.[ The activity of elastase is increased by ]human serum albumin
Human serum albumin is the serum albumin found in human blood. It is the most abundant protein in human blood plasma; it constitutes about half of serum protein. It is produced in the liver. It is soluble in water, and it is monomeric.
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.]
Diagnosis
Infection
If a chronic wound becomes more painful this is a good indication that it is infected. A lack of pain however does not mean that it is not infected.[ Other methods of determination are less effective.][
]
Classification
The vast majority of chronic wounds can be classified into three categories: venous ulcer
Venous ulcer is defined by the American Venous Forum as "a full-thickness defect of skin, most frequently in the ankle region, that fails to heal spontaneously and is sustained by chronic venous disease, based on venous duplex ultrasound testing." ...
s, diabetic
Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level (hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased app ...
, and pressure ulcer
Pressure ulcers, also known as pressure sores, bed sores or pressure injuries, are localised damage to the skin and/or underlying tissue that usually occur over a bony prominence as a result of usually long-term pressure, or pressure in combi ...
s.[ A small number of wounds that do not fall into these categories may be due to causes such as radiation poisoning or ]ischemia
Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism (to keep tissue alive). Ischemia is generally caused by problems wi ...
.[
]
Venous and arterial ulcers
Venous ulcer
Venous ulcer is defined by the American Venous Forum as "a full-thickness defect of skin, most frequently in the ankle region, that fails to heal spontaneously and is sustained by chronic venous disease, based on venous duplex ultrasound testing." ...
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
Chronic venous insufficiency (CVI) is a medical condition in which blood pools in the veins, straining the walls of the vein. The most common cause of CVI is superficial venous reflux which is a treatable condition. As functional venous valves are ...
caused by improper function of valves
A valve is a device or natural object that regulates, directs or controls the flow of a fluid (gases, liquids, fluidized solids, or slurries) by opening, closing, or partially obstructing various passageways. Valves are technically fittings ...
that exist in the vein
Veins are blood vessels in humans and most other animals 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 b ...
s to prevent blood from flowing backward. Ischemia
Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism (to keep tissue alive). Ischemia is generally caused by problems wi ...
results from the dysfunction and, combined with reperfusion injury
Reperfusion injury, sometimes called ischemia-reperfusion injury (IRI) or reoxygenation injury, is the tissue damage caused when blood supply returns to tissue ('' re-'' + '' perfusion'') after a period of ischemia or lack of oxygen (anoxia or h ...
, causes the tissue damage that leads to the wounds.
Diabetic ulcers
Another major cause of chronic wounds, diabetes
Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...
, is increasing in prevalence. Diabetics have a 15% higher risk for amputation
Amputation is the removal of a limb by trauma, medical illness, 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 indi ...
than the general population[ due to chronic ulcers. Diabetes causes ]neuropathy
Peripheral neuropathy, often shortened to neuropathy, is a general term describing disease affecting the peripheral nerves, meaning nerves beyond the brain and spinal cord. Damage to peripheral nerves may impair sensation, movement, gland, or o ...
, which inhibits nociception
Nociception (also nocioception, from Latin ''nocere'' 'to harm or hurt') is the sensory nervous system's process of encoding noxious stimuli. It deals with a series of events and processes required for an organism to receive a painful stimulus, co ...
and the perception
Perception () is the organization, identification, and interpretation of sensory information in order to represent and understand the presented information or environment. All perception involves signals that go through the nervous system ...
of pain
Pain is a distressing feeling often caused by intense or damaging stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sensory and emotional experience associated with, or resembling that associated with, ...
.[ Thus patients may not initially notice small wounds to legs and feet, and may therefore fail to prevent ]infection
An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable dise ...
or repeated injury
An injury is any physiological damage to living tissue caused by immediate physical stress. An injury can occur intentionally or unintentionally and may be caused by blunt trauma, penetrating trauma, burning, toxic exposure, asphyxiation, o ...
.[ 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 ]paralysis
Paralysis (also known as plegia) is a loss of motor function in one or more muscles. Paralysis can also be accompanied by a loss of feeling (sensory loss) in the affected area if there is sensory damage. In the United States, roughly 1 in 50 ...
that inhibit movement of body parts that are commonly subjected to pressure such as the heels, shoulder blades, and sacrum
The sacrum (plural: ''sacra'' or ''sacrums''), in human anatomy, is a large, triangular bone at the base of the spine that forms by the fusing of the sacral vertebrae (S1S5) between ages 18 and 30.
The sacrum situates at the upper, back part ...
. Pressure ulcers are caused by ischemia that occurs when pressure on the tissue is greater than the pressure in capillaries
A capillary is a small blood vessel from 5 to 10 micrometres (μm) in diameter. Capillaries are composed of only the tunica intima, consisting of a thin wall of simple squamous endothelial cells. They are the smallest blood vessels in the body: ...
, and thus restricts blood flow into the area.[ Muscle tissue, which needs more oxygen and ]nutrient
A nutrient is a substance used by an organism to survive, grow, and reproduce. The requirement for dietary nutrient intake applies to animals, plants, fungi, and protists. Nutrients can be incorporated into cells for metabolic purposes or excret ...
s than skin
Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation.
Other cuticle, animal coverings, such as the arthropod exoskeleton, have diffe ...
does, shows the worst effects from prolonged pressure.[ As in other chronic ulcers, ]reperfusion injury
Reperfusion injury, sometimes called ischemia-reperfusion injury (IRI) or reoxygenation injury, is the tissue damage caused when blood supply returns to tissue ('' re-'' + '' perfusion'') after a period of ischemia or lack of oxygen (anoxia or h ...
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.[ Periwound skin issues should be assessed and their abatement included in a proposed treatment plan.]
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.[
It is uncertain whether intravenous metronidazole is useful in reducing foul smelling from malignant wounds. There is insufficient evidence to use silver-containing dressings or topical agents for the treatment of infected or contaminated chronic wounds.
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.
]
Preventing and treating infection
To lower the bacterial count in wounds, therapists may use topical antibiotic
An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention 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, also known as melaleuca oil, is an essential oil with a fresh camphoraceous odor and a colour that ranges from pale yellow to nearly colourless and clear. It is derived from the leaves of the tea tree, ''Melaleuca alternifolia'', ...
, an antibacterial agent which also has anti-inflammatory effects. Disinfectants
A disinfectant is a chemical substance or compound used to inactivate or destroy microorganisms on inert surfaces. Disinfection does not necessarily kill all microorganisms, especially resistant bacterial spores; it is less effective than st ...
are contraindicated because they damage tissues and delay wound contraction.[ Further, they are rendered ineffective by organic matter in wounds like blood and ]exudate
An exudate is a fluid emitted by an organism through pores or a wound, a process known as exuding or exudation.
''Exudate'' is derived from ''exude'' 'to ooze' from Latin ''exsūdāre'' 'to (ooze out) sweat' (''ex-'' 'out' and ''sūdāre'' 'to ...
and are thus not useful in open wounds.[
A greater amount of exudate and ]necrotic tissue
Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. Necrosis is caused by factors external to the cell or tissue, such as infection, or trauma which result in the unregulated dige ...
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
In medicine, therapeutic irrigation or lavage ( or ) is cleaning or rinsing. Types
Specific types include:
* Antiseptic lavage
* Bronchoalveolar lavage
* Gastric lavage
* Peritoneal lavage
* Arthroscopic lavage
* Ductal lavage
* Nasal irrigati ...
.[
Removing necrotic or devitalized tissue is also the aim of ]maggot therapy
Maggot therapy (also known as larval therapy) is a type of biotherapy involving the introduction of live, disinfected maggots (fly larvae) into non-healing skin and soft-tissue wounds of a human or other animal for the purpose of cleaning out the ...
, the intentional introduction by a health care practitioner of live, disinfected maggot
A maggot is the larva of a fly (order Diptera); it is applied in particular to the larvae of Brachycera 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 (NPWT), also known as a vacuum assisted closure (VAC), is a therapeutic technique using a suction pump, tubing and a dressing to remove excess exudate and promote healing in acute or chronic wounds and second- 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 ]mRNA
In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein.
mRNA is ...
s and to proliferate and produce ECM molecules.[
Recent technological advancements produced novel approaches such as self-adaptive wound dressings that rely on properties of ]smart polymer
Smart polymers, stimuli-responsive polymers or functional polymers are high-performance polymers that change according to the environment they are in. Such materials can be sensitive to a number of factors, such as temperature, humidity, pH, chem ...
s 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
A biofilm comprises any syntrophic consortium of microorganisms in which cells stick to each other and often also to a surface. These adherent cells become embedded within a slimy extracellular matrix that is composed of extracellular ...
as well as harmful exudate components, known to slow the healing process. 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. 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 chronic pain
Chronic pain is classified as pain that lasts longer than three to six months. In medicine, the distinction between Acute (medicine), acute and Chronic condition, chronic pain is sometimes determined by the amount of time since onset. Two commonly ...
associated with non-healing wounds is caused by tissue (nociceptive
Nociception (also nocioception, from Latin ''nocere'' 'to harm or hurt') is the Somatosensory system, sensory nervous system's process of encoding Noxious stimulus, noxious stimuli. It deals with a series of events and processes required for an org ...
) or nerve (neuropathic
Peripheral neuropathy, often shortened to neuropathy, is a general term describing disease affecting the peripheral nerves, meaning nerves beyond the brain and spinal cord. Damage to peripheral nerves may impair sensation, movement, gland, or or ...
) damage and is influenced by dressing changes and chronic inflammation
Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...
. Chronic wounds take a long time to heal and patients can experience chronic wounds for many years.[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 Chronic wound healing may be compromised by coexisting underlying conditions, such as venous valve backflow, peripheral vascular disease
Peripheral artery disease (PAD) is an abnormal narrowing of arteries other than those that supply the heart or brain. When narrowing occurs in the heart, it is called coronary artery disease, and in the brain, it is called cerebrovascular diseas ...
, uncontrolled edema and diabetes mellitus
Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...
.
If wound pain
Pain is a distressing feeling often caused by intense or damaging stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sensory and emotional experience associated with, or resembling that associated with, ...
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 th
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.[ Some healthcare professionals use ' radiant bandages' to keep the area warm, and care must be taken during surgery to prevent ]hypothermia
Hypothermia is defined as a body core temperature below in humans. Symptoms depend on the temperature. In mild hypothermia, there is shivering and mental confusion. In moderate hypothermia, shivering stops and confusion increases. In severe h ...
, 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 medicine is medical treatment in which an ambient pressure greater than sea level atmospheric pressure is a necessary component. The treatment comprises hyperbaric oxygen therapy (HBOT), the medical use of oxygen at an ambient pressure ...
, or HBOT, which may provide a short-term improvement in healing by improving the oxygenated blood supply to the wound.[ In addition to killing bacteria, higher oxygen content in tissues speeds growth factor production, fibroblast growth, and ]angiogenesis
Angiogenesis is the physiological process through which new blood vessels form from pre-existing vessels, formed in the earlier stage of vasculogenesis. Angiogenesis continues the growth of the vasculature by processes of sprouting and splitting ...
.[ However, increased oxygen levels also means increased production of ROS.][ ]Antioxidant
Antioxidants are compounds that inhibit oxidation, a chemical reaction that can produce free radicals. This can lead to polymerization and other chain reactions. They are frequently added to industrial products, such as fuels and lubricant ...
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 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.
]
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. 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.] Another way is to spread onto the wound a gel of the patient's own blood platelet
Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby ini ...
s, which then secrete growth factors such as vascular endothelial growth factor
Vascular endothelial growth factor (VEGF, ), originally known as vascular permeability factor (VPF), is a signal protein produced by many cells that stimulates the formation of blood vessels. To be specific, VEGF is a sub-family of growth factors, ...
(VEGF), insulin-like growth factor
The insulin-like growth factors (IGFs) are proteins with high sequence similarity to insulin. IGFs are part of a complex system that cells use to communicate with their physiologic environment. This complex system (often referred to as the IGF "a ...
1–2 (IGF), PDGF, transforming growth factor Transforming growth factor (, or TGF) is used to describe two classes of polypeptide growth factors, TGFα and TGFβ.
The name "Transforming Growth Factor" is somewhat arbitrary, since the two classes of TGFs are not structurally or genetically rel ...
-β (TGF-β), and epidermal growth factor
Epidermal growth factor (EGF) is a protein that stimulates cell growth and differentiation by binding to its receptor, EGFR. Human EGF is 6-k Da and has 53 amino acid residues and three intramolecular disulfide bonds.
EGF was originally descr ...
(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 is a collagen scaffold that induces regeneration of skin in mammals such as humans. The term was used in the late 1970s and early 1980s to describe a new treatment for massive burns. It was later discovered that treatment of deep ski ...
substitutes that have fibroblasts and keratinocytes in a matrix of collagen to replicate skin and release growth factors.
In other cases, skin from cadaver
A cadaver or corpse is a dead human body that is used by medical students, physicians and other scientists to study anatomy, identify disease sites, determine causes of death, and provide tissue to repair a defect in a living human being. Stud ...
s is grafted
Grafting or graftage is a horticultural technique whereby tissues of plants are joined so as to continue their growth together. The upper part of the combined plant is called the scion () while the lower part is called the rootstock. The succ ...
onto wounds, providing a cover to keep out bacteria and preventing the buildup of too much granulation tissue
Granulation tissue is new connective tissue and microscopic blood vessels that form on the surfaces of a wound during the healing process. Granulation tissue typically grows from the base of a wound and is able to fill wounds of almost any size ...
, which can lead to excessive scar
A scar (or scar tissue) is an area of fibrous tissue that replaces normal skin after an injury. Scars result from the biological process of wound repair in the skin, as well as in other organs, and tissues of the body. Thus, scarring is a na ...
ring. Though the allograft
Allotransplant (''allo-'' meaning "other" in Greek) is the transplantation of cells, tissues, or organs to a recipient from a genetically non-identical donor of the same species. The transplant is called an allograft, allogeneic transplant, o ...
(skin transplanted from a member of the same species
In biology, a species is the basic unit of classification and a taxonomic rank of an organism, as well as a unit of biodiversity. A species is often defined as the largest group of organisms in which any two individuals of the appropriate s ...
) is replaced by granulation tissue and is not actually incorporated into the healing wound, it encourages cellular proliferation and provides a structure for epithelial cell
Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellula ...
s 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.][ 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.]
Since levels of protease inhibitors are lowered in chronic wounds, some researchers are seeking ways to heal tissues by replacing these inhibitors in them.[ ]Secretory leukocyte protease inhibitor
Antileukoproteinase, also known as secretory leukocyte protease inhibitor (SLPI), is an enzyme that in humans is encoded by the ''SLPI'' gene. SLPI is a highly cationic single-chain protein with eight intramolecular disulfide bonds. It is found in ...
(SLPI), which inhibits not only proteases but also inflammation and microorganisms like virus
A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea.
Since Dmitri Ivanovsky's 1 ...
es, bacteria, and fungi
A fungus ( : fungi or funguses) is any member of the 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, separately from ...
, may prove to be an effective treatment.[
Research into ]hormone
A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are required ...
s and wound healing has shown estrogen
Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal acti ...
to speed wound healing in elderly humans and in animals that have had their ovaries
The ovary is an organ in the female reproductive system that produces an ovum. When released, this travels down the fallopian tube into the uterus, where it may become fertilized by a sperm. There is an ovary () found on each side of the body. T ...
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 is 0.78% of the population and the prevalence
In epidemiology, prevalence is the proportion of a particular population found to be affected by a medical condition (typically a disease or a risk factor such as smoking or seatbelt use) at a specific time. It is derived by comparing the number o ...
ranges from 0.18 to 0.32%. As the population ages Ages may refer to:
*Advanced glycation end-products, known as AGEs
*Ages, Kentucky, census-designated place, United States
* ''Ages'' (album) by German electronic musician Edgar Froese
*The geologic time scale, a system of chronological measuremen ...
, the number of chronic wounds is expected to rise. Ulcers that heal within 12 weeks are usually classified as acute, and longer-lasting ones as chronic.
References
Further reading
*
*
External links
Maggot Therapy Project
web site at the University of California, Irvine, list of maggot therapy practitioners
BioTherapeutics Education and Research Foundation
Accredited, interactive wound care education offered at no cost
Awareness campaign website by the Australian Wound Management Association
Website of the European Wound Management Association (EWMA)
{{DEFAULTSORT:Chronic Wound
Skin conditions resulting from physical factors
Necrosis