What is edema?

Process and Effects

Edema is not a disease but a condition that may be caused by a number of diseases. It signals a breakdown in the body’s fluid-regulating mechanisms. The body’s water can be envisioned as divided into three compartments: the intracellular compartment, the interstitial compartment, and the vascular compartment. The intracellular compartment consists of the fluid contained within the individual cells. The vascular compartment consists of all the water that is contained within the heart, the arteries, the capillaries, and the veins. The last compartment, and in many ways the most important for a discussion of edema, is called the interstitial compartment. This compartment includes all the water not contained in either the cells or the blood vessels. The interstitial compartment contains all the fluids between the intracellular compartment and the vascular compartment and the fluid in the lymphatic system. The sizes of these compartments are approximately as follows: intracellular fluid at 66 percent, interstitial fluid at 25 percent, and vascular fluid at only 8 percent of the total body water.

When the interstitial compartment becomes overloaded with fluid, edema develops. To understand the physiology of edema formation, it may be helpful to follow a molecule of water as it travels through the various compartments, beginning when the molecule enters the aorta soon after leaving the heart. The blood has just been ejected from the heart under high pressure, and it speedily begins its trip through the body. It passes from the great vessel, the aorta, into smaller and smaller arteries that divide and spread throughout the body. At each branching, the pressure and speed of the water molecule decrease. Finally, the molecule enters a capillary, a vessel so small that red blood cells must flow in a single file. The wall of this vessel is composed only of the membrane of a
single capillary cell. There are small passages between adjacent capillary cells leading to the interstitial compartment, but they are normally closed.

The hydrostatic pressure on the water molecule is much lower than when it was racing through the aorta, but it is still higher than that of the surrounding interstitial compartment. At the arterial end of the capillary, the blood pressure is sufficient to overcome the barrier of the capillary cell’s membrane. A fair number of water and other molecules are pushed through the membrane into the interstitial compartment.

In the interstitial compartment, the water molecule is essentially under no pressure, and it floats amid glucose molecules, oxygen molecules, and many other compounds. Glucose and oxygen molecules enter the cells, and when the water molecule is close to a glucose molecule it is taken inside a cell with that molecule. The water molecule is eventually expelled by the cell, which has produced extra water from the metabolic process.

Back in the interstitial compartment, the molecule floats with a very subtle flow toward the venous end of the capillary. This occurs because, as the arterial end of the capillary pushes out water molecules, it loses hydrostatic pressure, eventually equaling the pressure of the interstitial compartment. Once the pressure equalizes, another phenomenon that has been thus far overshadowed by the hydrostatic pressure takes over—osmotic pressure. Osmotic pressure is the force exercised by a concentrated fluid that is separated by a membrane from a less concentrated fluid. It draws water molecules across the membrane from the less concentrated side. The more concentrated the fluid, the greater the drawing power. The ratio of nonwater molecules to water molecules determines concentration.

The fluid that stays within the capillary remains more concentrated than the interstitial fluid for two reasons. First, the plasma proteins in the vascular compartment are too large to be forced across the capillary membrane; albumin is one such protein. These proteins stay within the vascular compartment and maintain a relatively concentrated state, compared to the interstitial compartment. At the same time, the concentration of the fluid in the interstitial compartment is being lowered constantly by the cellular compartment’s actions. Cells remove molecules of substances such as glucose to metabolize, and afterward they release water—a by-product of the metabolic process. Both processes conspire to lower the total concentration of the interstitial compartment. The net result of this process is that water molecules return to the
capillaries at the venous end because of osmotic pressure.

The water molecule is caught by this force and is returned to the vascular compartment. Back in the capillary, the molecule’s journey is not yet complete. Now in a tiny vein, it moves along with blood. On the venous side of the circulatory system, the process of branching is reversed, and small veins join to form increasingly larger ones. The water molecule rides along in these progressively larger veins. The pressure surrounding the molecule is still low, but it is now higher than the pressure at the venous end of the capillary. One may wonder how this is possible if the venous pressure at the beginning of the venous system is essentially zero, and there is only one pump, the heart, in the body. As the molecule flows through the various veins, it occasionally passes one-way valves that allow blood to flow only toward the heart. The action of these valves, combined with muscular contractions from activities such as walking or tapping the foot, force blood toward the heart. Without these valves, it would be impossible for the venous blood to flow against gravity and return to the heart; the blood would simply sit at the lowest point in the body. Fortunately, these valves and contractions move the
molecule against gravity, returning it to the heart to begin a new cycle.

In certain disease states, there is marked capillary dilation and excessive capillary permeability, and excessive amounts of fluid are allowed to leave the intravascular compartment. The fluid accumulates in the interstitial space. When capillary permeability is increased, plasma proteins also tend to leave the vascular space, reducing the intravascular compartment’s osmotic pressure while increasing the interstitial compartment’s osmotic pressure. As a result, the rate of return of fluid from the interstitial compartment to the vascular compartment is lowered, thus increasing the interstitial fluid levels.

Another route of return of interstitial fluid to the circulation is via the lymphatic system. The lymphatic system is similar to the venous system, but it carries no red blood cells. It runs through the lymph nodes, carrying some of the interstitial fluid that has not been able to return to the vascular compartment at the capillary level. If lymphatic vessels become obstructed, water in the interstitial compartment accumulates, and edema may result.

Causes and Symptoms

Heart failure is a major cause of edema. When the right ventricle of the heart fails, it cannot cope with all the venous blood returning to the heart. As a consequence, the veins become distended, the interstitial compartment is overloaded, and edema occurs. If the patient with heart failure is mostly upright, the edema collects in the legs; if the patient has been lying in bed for some time, the edema tends to accumulate in the lower back. Other clinical signs of right heart failure include distended neck veins, an enlarged and tender liver, and a “galloping” sound on listening to the heart with a stethoscope.

When the left ventricle of the heart fails, the congestion affects the pulmonary veins instead of the neck and leg veins. Fluid accumulates in the same fashion within the interstitial compartment of the lungs; this condition is termed
pulmonary edema. Patients develop shortness of breath with minimal activity, upon lying down, and periodically through the night. They may need to sleep on several pillows to minimize this symptom. This condition can usually be diagnosed by listening to the lungs and heart through a stethoscope and by taking an x-ray of the chest.

Deep vein thrombosis

is another common cause of edema of the lower limbs. When a
thrombus (a blood clot inside a blood vessel) develops in a large vein of the legs, the patient usually complains of pain and tenderness of the affected leg. There is usually redness and edema as well. If the thrombus affects a small vein, it may not be noticed. The diagnosis can be made by several specialized tests, such as ultrasound testing and impedance plethysmography. Other tests may be needed to make the diagnosis, such as injecting radiographic dye in a vein in the foot and then taking x-rays to determine whether the flow in the veins has been obstructed or using radioactive agents that bind to the clot. Risks for developing venous thrombosis include immobility (even for relatively short periods of time such as a long car or plane ride), injury, a personal or family history of venous thrombosis, the use of birth control pills, and certain types of cancer. Elderly patients are at particular risk because of relative immobility and an increased frequency of minor trauma to the legs.

When repeated or large thrombi develop, the veins deep inside the thigh (the deep venous system) become blocked, and blood flow shifts toward the superficial veins. The deep veins are surrounded by muscular tissue, and venous flow is assisted by muscular contractions of the leg (the muscular pump), but the superficial veins are surrounded only by skin and subcutaneous tissue and cannot take advantage of the muscular pump. As a consequence, the superficial veins become distended and visible as
varicose veins.

When vein blockage occurs, the valves inside become damaged. Hydrostatic pressure of the venous system below the blockage then rises. The venous end of the capillary is normally where the osmotic pressure of the vascular compartment pulls water from the interstitial compartment back into the vascular compartment. In a situation of increased hydrostatic pressure, however, this process is slowed or stopped. As a result, fluid accumulates in the interstitial space, leading to the formation of edema.

A dangerous complication of
deep vein thrombosis occurs when part of a thrombus breaks off, enters the circulation, and reaches the lung; this is called a pulmonary embolus. It blocks the flow of blood to the lung, impairing oxygenation. Small emboli may have little or no effect on the patient, while larger emboli may cause severe shortness of breath, chest pain, or even death.

Another potential cause of edema is the presence of a mass in the pelvis or abdomen compressing the large veins passing through the area and interfering with the venous return from the lower limbs to the heart. The resulting venous congestion leads to edema of the lower limbs. The edema may affect either one or both legs, depending on the size and location of the mass. This diagnosis can usually be established by a thorough clinical examination, including rectal and vaginal examinations and x-ray studies.

Postural (or gravitational) edema of the lower limbs is the most common type of edema affecting older people; it is more pronounced toward the end of the day. It can be differentiated from the edema resulting from heart failure by the lack of signs associated with heart failure and by the presence of diseases restricting the patient’s degree of mobility. These diseases include Parkinson’s disease, osteoarthritis, strokes, and muscle weakness. Postural edema of the lower limbs results from a combination of factors, the most important being diminished mobility. If a person stands or sits for prolonged periods of time without moving, the muscular pump becomes ineffective. Venous compression also plays an important role in the development of this type of edema. It will occur when the veins in the thigh are compressed between the weight of the body and the surface on which the patient sits, or when the edge of a reclining chair compresses the veins in the calves. Other factors that aggravate postural edema include varicose veins, venous thrombi, heart failure, some types of medication, and low blood albumin levels.

Albumin is formed in the liver from dietary protein. It is essential to maintaining adequate osmotic pressure inside the blood vessels and ensuring the return of fluid from the interstitial space to the vascular compartment. When edema is caused by inadequate blood levels of albumin, it tends to be quite extensive. The patient’s entire body and even face are often affected. The liver may be unable to produce the necessary amount of albumin for several reasons, including malnutrition, liver impairment, the aging process, and excessive protein loss.

In cases of malnutrition, the liver does not receive a sufficient quantity of raw material from the diet to produce albumin; this occurs when the patient does not ingest enough protein. Healthy adults need at least 0.5 grams of protein for each pound of their body weight. Infants and children of poor families who cannot afford to prepare nutritious meals often suffer from malnutrition. The elderly, especially men living on their own, are also vulnerable, regardless of their income.

A liver damaged by excessive and prolonged consumption of alcohol, diseases, or the intake of some types of medication or other chemical toxins will be unable to manufacture albumin at the rate necessary to maintain a normal concentration in the blood. Clinically, the patient shows other evidence of liver impairment in addition to edema. For example, fluid may also accumulate in the abdominal cavity, a condition known as ascites. The diagnosis of liver damage is made by clinical examination and supporting laboratory investigations. The livers of older people, even in the absence of disease, are often less efficient at producing albumin.

The albumin also can be deficient if an excessive amount of albumin is lost from the body. This condition may occur in certain types of diseases affecting the kidneys or the gastrointestinal tract. An excessive amount of protein also may be lost if a patient has large, oozing pressure ulcers, extensive burns, or chronic lung conditions that produce large amounts of sputum.

Patients with strokes and
paralysis sometimes develop edema of the paralyzed limb. The mechanism of edema formation in these patients is not entirely understood. It probably results from a combination of an impairment of the nerves controlling the dilation and a constriction of the blood vessels in the affected limb, along with postural and gravitational factors.

Severe allergic states, toxic states, or local inflammation are associated with increased capillary permeability that results in edema. The amount of fluid flowing out to the capillaries far exceeds the amount that can be returned to the capillaries at the venous end. A number of medications, including steroids, estrogens, some arthritis medications, a few blood pressure medications, and certain antibiotics, can induce edema by promoting the retention of fluid. Salt intake tends to cause retention of fluid as well. Obstruction of the lymphatic system often leads to accumulation of fluid in the interstitial compartment. Obstruction can occur in certain types of cancer, after radiation treatment, and in certain parasitic infestations.

Treatment and Therapy

The management of edema depends on the specific reason for its presence. To determine the cause of edema, a thorough history, including current medications, dietary habits, and activity level, is of prime importance. Performing a detailed physical examination is also a vital step. It is frequently necessary to obtain laboratory, ultrasound, and x-ray studies before a final diagnosis is made. Once a treatable cause is found, therapy aimed at the cause should be instituted.

If no treatable, specific disease is responsible for the edema, conservative treatment aimed at reducing the edema to manageable levels without inducing side effects should be initiated. Frequent elevation of the feet to the level of the heart, use of support stockings, and avoidance of prolonged standing or sitting are the first steps. If support stockings are ineffective or are too uncomfortable, then custom-made, fitted stockings are available. A low-salt diet is important in the management of edema because a high salt intake worsens the fluid retention. If all these measures fail, then diuretics in small doses may be useful.

Diuretics work by increasing the amount of urine produced. Urine is made of fluids removed from the vascular compartment by the kidneys. The vascular compartment then replenishes itself by drawing water from the interstitial compartment. This reduction in the amount of interstitial fluid improves the edema. There are various types of diuretics, which differ in their potency, duration of action, and side effects. Potential side effects include dizziness, fatigue, sodium and potassium deficiency, excessively low blood pressure, dehydration, sexual dysfunction, the worsening of a diabetic’s blood sugar control, increased uric acid levels, and increased blood cholesterol levels. Although diuretics are a convenient and effective means of treating simple edema, it is important to keep in mind that the cure should not be worse than the disease. When the potential side effects of diuretic therapy are compared to the almost total lack of complications of conservative treatment, one can see that mild edema that is not secondary to significant disease is best managed conservatively. Edema caused by more serious diseases, however, calls for more intensive measures.

Perspective and Prospects

The prevalence of edema could decrease as people become more health conscious and medical progress is made. Nutritious diets, avoidance of excessive salt, and an increased awareness of the dangers of excessive alcohol intake and of the benefits of regular physical exercise all contribute to decreasing the incidence of edema. Improved methods for the early detection, prevention, and management of diseases that may ultimately result in edema could also significantly reduce the scope of the problem. It is also expected that safer and more convenient methods of treating edema will become available.

Bibliography

Andreoli, Thomas E., et al., eds. Andreoli and Carpenter’s Cecil Essentials of Medicine. 8th ed. Philadelphia: Saunders/Elsevier, 2010.

Cleveland Clinic. "Edema." Cleveland Clinic Foundation, April 26, 2012.

Guyton, Arthur C., and John E. Hall. Human Physiology and Mechanisms of Disease. 6th ed. Philadelphia: W. B. Saunders, 1997.

Hosenpud, Jeffrey D., and Barry H. Greenberg, eds. Congestive Heart Failure. 3d ed. Philadelphia: Lippincott Williams & Wilkins, 2007.

Marieb, Elaine N., and Katja Hoehn. Human Anatomy and Physiology. 9th ed. San Francisco: Pearson/Benjamin Cummings, 2010.

Mayo Clinic. "Edema." Mayo Foundation for Medical Education and Research, October 13, 2011.

MedlinePlus. "Edema." MedlinePlus, January 22, 2013.