Venous ulcer
Encyclopedia
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 wound
s, occurring in 70% to 90% of chronic wound cases. Venous ulcers develop mostly along the medial distal leg, and can be very painful.
of venous ulcers is not certain, but they are thought to arise when venous valves that exist to prevent backflow of blood
do not function properly, causing the pressure
in veins to increase. The body needs the pressure gradient
between arteries and vein
s in order for the heart
to pump blood forward through arteries and into veins. When venous hypertension exists, arteries no longer have significantly higher pressure than veins, blood is not pumped as effectively into or out of the area, and it pools.
Venous hypertension
may also stretch veins and allow blood proteins to leak into the extravascular space, isolating extracellular matrix
(ECM) molecules and growth factor
s, preventing them from helping to heal the wound. Leakage of fibrinogen
from veins as well as deficiencies in fibrinolysis
may also cause fibrin
to build up around the vessels, preventing oxygen
and nutrient
s from reaching cells
. Venous insufficiency may also cause white blood cell
s (leukocytes) to accumulate in small blood vessel
s, releasing inflammatory factors and reactive oxygen species
(ROS, free radicals) and further contributing to chronic wound formation. Buildup of white blood cells in small blood vessels may also plug the vessels, further contributing to ischemia
. This blockage of blood vessels by leukocytes may be responsible for the "no reflow phenomenon
," in which ischemic tissue is never fully reperfused. Allowing blood to flow back into the limb, for example by elevating it, is necessary but also contributes to reperfusion injury
. Other comorbidities
may also be the root cause of venous ulcers.
It is in the crus that the classic venous stasis ulcer occurs. Venous stasis results from damage to the vein valvular system in the lower extremity and in extreme cases allows the pressure in the veins to be higher than the pressure in the arteries. This pressure results in transudation of inflammatory mediators into the subcutaneous tissues of the lower extremity and subsequent breakdown of the tissue including the skin.
Wounds of the distal lower extremities arising from causes not directly related to venous insufficiency (e.g., scratch, bite, burn, or surgical incision) may ultimately fail to heal if underlying (often undiagnosed) venous disease is not properly addressed.
; one study found that up to 48% of venous ulcers had recurred by the fifth year after healing.
A review by Clinical Evidence concluded that several beneficial treatments exist.
is used for venous leg ulcers and can decrease blood vessel diameter and pressure, which increases their effectiveness, preventing blood from flowing backwards. Compression is also used to decrease release of inflammatory cytokine
s, lower the amount of fluid leaking from capillaries
and therefore prevent swelling
, and prevent clotting by decreasing activation of thrombin
and increasing that of plasmin
.
Compression is applied using elastic bandages or boots specifically designed for the purpose. It is not clear whether non-elastic systems are better than a multilayer elastic system. Patients should wear as much compression as is comfortable. The type of dressing applied beneath the compression does not seem to matter, and hydrocolloid is not better than simple low adherent dressings.
of randomized controlled trials by the Cochrane Collaboration
found that "Pentoxifylline is an effective adjunct to compression bandaging for treating venous ulcers and may be effective in the absence of compression".
, made of collagen and cultured
skin cells, is also used to cover venous ulcers and excrete growth factor
s to help them heal. A meta-analysis
of randomized controlled trials by the Cochrane Collaboration
concluded "Bilayer artificial skin, used in conjunction with compression bandaging, increases the chance of healing a venous ulcer compared with compression and a simple dressing".
found that surgery "reduces the recurrence of ulcers at four years and results in a greater proportion of ulcer free time".
Chronic wound
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....
s, occurring in 70% to 90% of chronic wound cases. Venous ulcers develop mostly along the medial distal leg, and can be very painful.
Pathophysiology
The exact etiologyEtiology
Etiology is the study of causation, or origination. The word is derived from the Greek , aitiologia, "giving a reason for" ....
of venous ulcers is not certain, but they are thought to arise when venous valves that exist to prevent backflow of blood
Blood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....
do not function properly, causing the pressure
Pressure
Pressure is the force per unit area applied in a direction perpendicular to the surface of an object. Gauge pressure is the pressure relative to the local atmospheric or ambient pressure.- Definition :...
in veins to increase. The body needs the pressure gradient
Gradient
In vector calculus, the gradient of a scalar field is a vector field that points in the direction of the greatest rate of increase of the scalar field, and whose magnitude is the greatest rate of change....
between arteries and 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 in order for the heart
Heart
The heart is a myogenic muscular organ found in all animals with a circulatory system , that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...
to pump blood forward through arteries and into veins. When venous hypertension exists, arteries no longer have significantly higher pressure than veins, blood is not pumped as effectively into or out of the area, and it pools.
Venous hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
may also stretch veins and allow blood proteins to leak into the extravascular space, isolating 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) molecules and growth factor
Growth factor
A growth factor is a naturally occurring substance capable of stimulating cellular growth, proliferation and cellular differentiation. Usually it is a protein or a steroid hormone. Growth factors are important for regulating a variety of cellular processes....
s, preventing them from helping to heal the wound. Leakage of fibrinogen
Fibrinogen
Fibrinogen is a soluble plasma glycoprotein, synthesised by the liver, that is converted by thrombin into fibrin during blood coagulation. This is achieved through processes in the coagulation cascade that activate the zymogen prothrombin to the serine protease thrombin, which is responsible for...
from veins as well as deficiencies in fibrinolysis
Fibrinolysis
Fibrinolysis is a process that prevents blood clots from growing and becoming problematic. This process has two types: primary fibrinolysis and secondary fibrinolysis...
may also cause fibrin
Fibrin
Fibrin is a fibrous, non-globular protein involved in the clotting of blood. It is a fibrillar protein that is polymerised to form a "mesh" that forms a hemostatic plug or clot over a wound site....
to build up around the vessels, preventing oxygen
Oxygen
Oxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...
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 from reaching cells
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
. Venous insufficiency may also cause white blood cell
White blood cell
White blood cells, or leukocytes , are cells of the immune system involved in defending the body against both infectious disease and foreign materials. Five different and diverse types of leukocytes exist, but they are all produced and derived from a multipotent cell in the bone marrow known as a...
s (leukocytes) to accumulate in small blood vessel
Blood vessel
The blood vessels are the part of the circulatory system that transports blood throughout the body. There are three major types of blood vessels: the arteries, which carry the blood away from the heart; the capillaries, which enable the actual exchange of water and chemicals between the blood and...
s, releasing inflammatory factors and reactive oxygen species
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....
(ROS, free radicals) and further contributing to chronic wound formation. Buildup of white blood cells in small blood vessels may also plug the vessels, further contributing to 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...
. This blockage of blood vessels by leukocytes may be responsible for the "no reflow phenomenon
No reflow phenomenon
No reflow phenomenon is the failure of blood to reperfuse an ischemic area after the physical obstruction has been removed or bypassed.It may be associated with microvascular damage....
," in which ischemic tissue is never fully reperfused. Allowing blood to flow back into the limb, for example by elevating it, is necessary but also contributes to 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...
. Other comorbidities
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 :...
may also be the root cause of venous ulcers.
It is in the crus that the classic venous stasis ulcer occurs. Venous stasis results from damage to the vein valvular system in the lower extremity and in extreme cases allows the pressure in the veins to be higher than the pressure in the arteries. This pressure results in transudation of inflammatory mediators into the subcutaneous tissues of the lower extremity and subsequent breakdown of the tissue including the skin.
Wounds of the distal lower extremities arising from causes not directly related to venous insufficiency (e.g., scratch, bite, burn, or surgical incision) may ultimately fail to heal if underlying (often undiagnosed) venous disease is not properly addressed.
Classification
A clinical severity score has been developed to assess chronic venous ulcers. It is based on the CEAP (clinical, etiology, anatomy, and pathophysiology) classification system developed by an expert panel. A high score gives a poor prognosis.Treatment
Venous ulcers are costly to treat, and there is a significant chance that they will recur after healingHealing
Physiological healing is the restoration of damaged living tissue, organs and biological system to normal function. It is the process by which the cells in the body regenerate and repair to reduce the size of a damaged or necrotic area....
; one study found that up to 48% of venous ulcers had recurred by the fifth year after healing.
A review by Clinical Evidence concluded that several beneficial treatments exist.
Bisgaard regimen
Most venous ulcers respond to a regimen called Bisgaard regimen for treating ulcers. Best remembered as a mnemonic 4E's - education, elevation, elastic compression and evaluation.Compression therapy
Non-elastic, ambulatory, below knee (BK) compression aggressively counters the impact of reflux on venous pump failure. Compression therapyCompression therapy
Compression therapy may refer to:*Attachment therapy, a loosely identified category of mental health interventions*Cold compression therapy, to reduce pain and swelling from a sports or activity injury...
is used for venous leg ulcers and can decrease blood vessel diameter and pressure, which increases their effectiveness, preventing blood from flowing backwards. Compression is also used to decrease release of 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, lower the amount of fluid leaking from capillaries
Capillary
Capillaries are the smallest of a body's blood vessels and are parts of the microcirculation. They are only 1 cell thick. These microvessels, measuring 5-10 μm in diameter, connect arterioles and venules, and enable the exchange of water, oxygen, carbon dioxide, and many other nutrient and waste...
and therefore prevent swelling
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...
, and prevent clotting by decreasing activation of thrombin
Thrombin
Thrombin is a "trypsin-like" serine protease protein that in humans is encoded by the F2 gene. Prothrombin is proteolytically cleaved to form thrombin in the first step of the coagulation cascade, which ultimately results in the stemming of blood loss...
and increasing that of plasmin
Plasmin
Plasmin is an important enzyme present in blood that degrades many blood plasma proteins, most notably, fibrin clots. The degradation of fibrin is termed fibrinolysis. In humans, the plasmin protein is encoded by the PLG gene.- Function :...
.
Compression is applied using elastic bandages or boots specifically designed for the purpose. It is not clear whether non-elastic systems are better than a multilayer elastic system. Patients should wear as much compression as is comfortable. The type of dressing applied beneath the compression does not seem to matter, and hydrocolloid is not better than simple low adherent dressings.
Pentoxifylline
A meta-analysisMeta-analysis
In statistics, a meta-analysis combines the results of several studies that address a set of related research hypotheses. In its simplest form, this is normally by identification of a common measure of effect size, for which a weighted average might be the output of a meta-analyses. Here the...
of randomized controlled trials by the Cochrane Collaboration
Cochrane Collaboration
The Cochrane Collaboration is a group of over 28,000 volunteers in more than 100 countries who review the effects of health care interventions tested in biomedical randomized controlled trials. A few more recent reviews have also studied the results of non-randomized, observational studies...
found that "Pentoxifylline is an effective adjunct to compression bandaging for treating venous ulcers and may be effective in the absence of compression".
Artificial skin
Artificial skinArtificial 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....
, made of collagen and cultured
Cell culture
Cell culture is the complex process by which cells are grown under controlled conditions. In practice, the term "cell culture" has come to refer to the culturing of cells derived from singlecellular eukaryotes, especially animal cells. However, there are also cultures of plants, fungi and microbes,...
skin cells, is also used to cover venous ulcers and excrete growth factor
Growth factor
A growth factor is a naturally occurring substance capable of stimulating cellular growth, proliferation and cellular differentiation. Usually it is a protein or a steroid hormone. Growth factors are important for regulating a variety of cellular processes....
s to help them heal. A meta-analysis
Meta-analysis
In statistics, a meta-analysis combines the results of several studies that address a set of related research hypotheses. In its simplest form, this is normally by identification of a common measure of effect size, for which a weighted average might be the output of a meta-analyses. Here the...
of randomized controlled trials by the Cochrane Collaboration
Cochrane Collaboration
The Cochrane Collaboration is a group of over 28,000 volunteers in more than 100 countries who review the effects of health care interventions tested in biomedical randomized controlled trials. A few more recent reviews have also studied the results of non-randomized, observational studies...
concluded "Bilayer artificial skin, used in conjunction with compression bandaging, increases the chance of healing a venous ulcer compared with compression and a simple dressing".
Surgical correction of superficial venous reflux
A randomized controlled trialRandomized controlled trial
A randomized controlled trial is a type of scientific experiment - a form of clinical trial - most commonly used in testing the safety and efficacy or effectiveness of healthcare services or health technologies A randomized controlled trial (RCT) is a type of scientific experiment - a form of...
found that surgery "reduces the recurrence of ulcers at four years and results in a greater proportion of ulcer free time".