Diseases

Diuretics have several other uses in addition treating edema.

• A diuretic may be used as part of the treatment program for patients with hypertension. (High blood pressure may be caused by salt retention, or caused by some antihypertensive medications). Most medications that dilate the blood vessels and reduce blood pressure, except for ACE inhibitors and angiotensin receptor blockers, lead to secondary salt retention by the kidneys.
• Thiazide diuretics also have been used to prevent the formation of kidney stones. These drugs reduce the urinary excretion of calcium, which is a component of the kidney stone.
• Acetazolamide (Diamox) taken a few days before going to high altitudes, appears to reduce the tendency for people to develop altitude sickness.

Some diuretics frequently cause an excessive loss of potassium in the urine, leading to the depletion of body potassium. These drugs include the loop diuretics, the thiazide diuretics, and metolazone. Patients on these diuretics are commonly advised to take potassium supplements and/or to eat foods high in potassium. High potassium foods include certain fruits such as:

• Bananas
• Orange juice
• Tomatoes
• Potatoes

Patients with impaired kidney function often do not require potassium supplements with diuretics because their damaged kidneys tend to retain potassium. In certain instances, the volume of urine induced by the diuretic can be improved by adding a potassium-sparing diuretic, one that does not cause depletion of potassium. These diuretics include spironolactone (Aldactone), triamterene (Dyrenium, a component of Dyazide), and amiloride (Midamor). Adding one of these diuretics to the patient's diuretic regimen may preclude the need for potassium supplements. Another diuretic that can be used is acetazolamide (Diamox), which counteracts the development of an increased concentration of bicarbonate (too much alkali) in the blood. Increased bicarbonate sometimes occurs in patients receiving other diuretics.

The body's balance of salt is usually well-regulated. Most people can consume salt in the diet without concern for developing salt depletion or retention. The intake of salt is determined by dietary patterns and the removal of salt from the body is accomplished by the kidneys. The kidneys have a great capacity to control the amount of salt in the body by changing the amount of salt eliminated (excreted) in the urine. The amount of salt excreted by the kidneys is regulated by hormonal and physical factors that signal whether retention or removal of salt by the kidneys is necessary.If blood flow to the kidneys is decreased by an underlying condition such as heart failure, the kidneys react by retaining salt. This salt retention occurs because the kidneys perceive the body needs more fluid to compensate for the decreased blood flow. If the patient has a kidney disease that impairs the function of the kidneys, the ability to excrete salt in the urine is limited. In both conditions, the amount of salt in the body increases, which causes the patient to retain water and develop edema.People with edema experiencing a disturbance in their ability to normally excrete salt may need to either be placed on a diet limited in salt and/or given diuretic medications (water pills). In the past, patients with diseases associated with edema were placed on diets very restricted in salt intake. With the development of new and very potent diuretics, this marked restriction in dietary salt intake is generally less strict. These diuretics work by blocking the reabsorption and retention of salt by the kidneys, thereby increasing the amount of salt and water eliminated in the urine.

The veins in the legs are responsible for transporting blood up to the veins of the torso, where it is then returned to the heart. The veins of the legs have valves that prevent the backward flow of blood within them. Venous insufficiency is incompetence of the veins that occurs because of dilation, or enlargement, of the veins and dysfunction of their valves. This happens, for example, in people with varicose veins. Venous insufficiency leads to a backup of blood and increased pressure in the veins, thereby resulting in edema of the legs and feet. Edema of the legs also can occur with an episode of deep vein thrombophlebitis (DVT), which is a blood clot within an inflamed vein. In this situation, the clot in the deep vein blocks the return of blood, and consequently causes increased back-pressure in the leg veins.Venous insufficiency is a problem localized to the legs, ankles, and feet. One leg may be more affected than the other (asymmetrical edema). In contrast, systemic diseases that are associated with fluid retention generally cause the same amount of edema in both legs, and can also cause edema and swelling elsewhere in the body. The response to therapy with diuretic drugs in patients with venous insufficiency tends to be unsatisfactory. This is because the continued pooling of fluid in the lower extremities makes it difficult for the diuretics to mobilize the edema fluid. Elevation of the legs periodically during the day and the use of compression stockings may alleviate the edema. Some patients require surgical treatment to relieve chronic edema that is caused by venous insufficiency.

When a woman is pregnant, her body produces 50% more blood and other body fluids than usual to help support the developing fetus. This causes edema of the hands, face, legs, ankles and feet, and is a normal part of pregnancy Swelling can also be pronounced in the legs and feet because of the enlarged womb (uterus) taking up space in the abdomen and inhibiting return of fluids from the legs.Edema during pregnancy can happen any time through gestation, but most women start to experience it around the fifth month, and edema may be worst in the third trimester.Mild swelling is common, but sudden swelling of the hands or face can be a sign of preeclampsia, a complication of pregnancy. See your obstetrician of you experience facial edema, leg edema, or any sudden or severe swelling while pregnant.Edema may continue even after you have given birth. Postpartum edema usually gradually resolves within a week or so after giving birth and is generally not a serious condition. If the postpartum swelling does not resolve within about a week or you experience headaches or pain in your legs, this may be a sign of high blood pressure and preeclampsia. Tell your doctor if this occurs.

In this situation, the people have a problem with kidney function due to a filtration problem involving proteins. Proteins spills through the kidney and into the urine. The heavy loss of protein in the urine (over 3.0 grams per day) with its accompanying edema is termed the nephrotic syndrome. Nephrotic syndrome results in a reduction in the concentration of albumin in the blood (hypoalbuminemia). Since albumin helps to maintain blood volume in the blood vessels, a reduction of fluid in the blood vessels occurs. The kidneys then register that there is depletion of blood volume and attempt to retain salt. Consequently, fluid moves into the interstitial spaces causing pitting edema.

In this situation, people who have kidney diseases that impair renal function develop edema because of a limitation in the kidneys' ability to excrete sodium into the urine. Thus, people with kidney failure from whatever cause will develop edema if their intake of sodium exceeds the ability of their kidneys to excrete the sodium. The more advanced the kidney failure, the greater the problem of salt retention is likely to become. The most severe situation is the patient with end-stage kidney failure who requires dialysis therapy. This patient's salt balance is totally regulated by dialysis, which can remove salt during the treatment. Dialysis is a method of cleansing the body of the impurities that accumulate when the kidneys fail. Dialysis is accomplished by circulating the patient's blood over an artificial membrane (hemodialysis) or by using the patient's own abdominal cavity (peritoneal membrane) as the cleansing surface. Individuals whose kidney function declines to less than 5% to 10% of normal may require dialysis.

Edema is caused by either systemic diseases, that is, diseases that affect the various organ systems of the body, or by local conditions involving just the affected extremities. The most common systemic diseases associated with edema involve the heart, liver, and kidneys. In these diseases, edema occurs primarily because of the body's retention of too much salt (sodium chloride). The excess salt causes the body to retain water, which then leaks into the interstitial tissue spaces, where it appears as edema. Medications also can cause pitting edema.The most common local conditions that cause edema are varicose veins and thrombophlebitis (inflammation of the veins) of the deep veins of the legs. These conditions can cause inadequate pumping of the blood by the veins (venous insufficiency). The resulting increased back-pressure in the veins forces fluid stay in the extremities (especially the ankles and feet). The excess fluid then leaks into the interstitial tissue spaces, causing edema.

Picture of Pitting Edema

Some doctors may use a scale to determine the severity of the pitting edema. These scales are subjective based on either how deep the pitting is, or how long the pitting persists.Following are two examples of edema measurement using 4-point scales, with 1 point being minor edema, to 4 points being severe edema.Pitting Edema Measurement ScalesS.B. O'Sullivan and T.J. SchmitzPhysical rehabilitation: assessment and treatmentM. HoganMedical-Surgical Nursing1+Barely detectable impression when finger is pressed into skin.2mm depression, barely detectable. Immediate rebound.2+Slight indentation. 15 seconds to rebound4mm deep pit. A few seconds to rebound.3+Deeper indentation. 30 seconds to rebound.6mm deep pit. 10-12 seconds to rebound.4+> 30 seconds to rebound.8mm: very deep pit. > 20 seconds to rebound.In non-pitting edema, which usually affects the legs or arms, pressure applied to the skin does not result in a persistent indentation. Non-pitting edema can occur in certain disorders of the lymphatic system such as lymphedema, which is a disturbance of the lymphatic circulation that may occur after a mastectomy, lymph node surgery, radiation therapy, morbid obesity, venous insufficiency, or be present from birth (congenitally).Another cause of non-pitting let edema is called pretibial myxedema, which is a swelling over the shin that occurs in some people with hypothyroidism. Non-pitting leg edema is difficult to treat. Diuretic medications are generally not effective, although elevation of the legs periodically during the day and compressive devices may reduce the swelling.The focus of the rest of this article is on pitting edema, as it is the most common form of edema.

The definition of edema is observable swelling from fluid accumulation in body tissues. When parts of the body are affected with edema, they are considered edematous. Edema most commonly occurs in the feet, ankles, legs, and/or hands where it is referred to as peripheral edema. Edema of the foot is sometimes called pedal edema. The swelling is the result of the accumulation of excess fluid under the skin in the spaces within the tissues.All tissues of the body are made up of cells, blood vessels, and connective tissues that hold the cells together called the interstitium. Most of the body's fluids that are found outside of the cells are normally stored in two spaces; the blood vessels (as the "liquid" or serum portion of your blood) and the interstitial spaces (not within the cells). In various diseases, excess fluid can accumulate in either one or both of these compartments.The body's organs have interstitial spaces where fluid can accumulate, and there are a number of different types of edema. An accumulation of fluid in the interstitial tissue around the air spaces (alveoli) in the lungs occurs in a disorder called pulmonary edema. In addition, excess fluid sometimes collects in what is called the third space, which includes cavities in the abdomen (abdominal or peritoneal cavity - called "ascites") or in the chest (lung or pleural cavity - called "pleural effusion").Anasarca, also known as extreme generalized edema is severe, widespread accumulation of fluid in the all of the tissues and cavities of the body at the same time.This article focuses mainly on leg and feet edema (peripheral edema), but these are other forms of edema that are typically named depending on the parts of the body affected:

• Cerebral edema is an accumulation of excess fluid in the brain.
• Angioedema is swelling underneath the skin. Unlike hives, which affect the surface of the skin, angioedema affects the deeper layers of the skin and often occurs on the face.
• Hereditary angioedema is a rare genetic condition that causes the capillaries to release fluids into surrounding tissue, which results in edema.
• Papilledema is swelling of the optic nerve of the eye that is a result of pressure inside the skull and around the brain (intracranial pressure).
• Macular edema is a swelling of the portion of the eye that perceives central, detailed vision (the macula).
• Dependent edema usually is edema of the legs and lower body, which is affected by gravity and is dependent on a person's position. This edema usually occurs in the legs when a person is standing, and in the buttocks and hands if a person is lying down.
• Scrotal lymphedema is an enlargement of the scrotum due to fluid accumulation around the testes.
• Lipedema is a disorder of the fatty (adipose) tissue that causes swelling of the legs and hips, and can lead to lymphedema.

Idiopathic edema is a pitting edema of unknown cause that occurs primarily in pre-menopausal women who do not have evidence of heart, liver, or kidney disease. In this condition, the fluid retention at first may be seen primarily pre-menstrually (just prior to menstruation), which is why it sometimes is called "cyclical" edema. However, it can become a more constant and severe problem.

Pitting edema can be demonstrated by applying pressure to the swollen area by depressing the skin with a finger. If the pressing causes an indentation that persists for some time after the release of the pressure, the edema is referred to as pitting edema. Any form of pressure, such as from the elastic in socks, can induce pitting with this type of edema. This type of edema may be normal depending on the severity. Almost everyone who wears socks all day will have mild pitting edema by the end of the day.

Patients with idiopathic edema often take diuretics to decrease the edema in order to lessen the discomfort of bloating and swelling. Paradoxically, the edema in this condition can become more of a problem after the use of diuretics. The people can develop fluid retention as a rebound phenomenon each time they discontinue diuretics. Talk to your doctor before using any diuretics.Patients with idiopathic edema appear to have a leak in the capillaries (tiny peripheral blood vessels that connect the arteries with the veins) so that fluid passes from the blood vessels into the surrounding interstitial space. Thus, a patient with idiopathic edema has a decreased blood volume, which leads to the typical reaction of salt retention by the kidneys.

• The leg edema in these people is exaggerated in the standing position, since edema tends to accumulate in those parts of the body that are close to the ground at the time.
• These people often have edema around the eyes (periorbital edema) in the morning because the edema fluid accumulates during the night around their eyes as they lay sleeping flat.

In contrast, edema around the eyes does not tend to develop in cardiac people who keep their heads elevated at night because of shortness of breath when they lie flat. These people characteristically experience varying amounts of edema in different parts of the body at different times of the day.

Patients with idiopathic edema often become dependent on diuretics, and this dependence may be difficult to interrupt. A period as long as three weeks off diuretics may be required to break the dependency cycle. The withdrawal from diuretics may lead to fluid retention that produces major discomfort and swelling. Moreover, there are definite risks associated with the prolonged use of diuretics in these individuals, which are compounded by the tendency to increase the doses of the diuretics.As a result of chronic diuretic use and abuse, people may develop:

• A deficiency of potassium
• Depletion of blood volume in the blood vessels
• Kidney insufficiency or failure

Other side effects of diuretics include:

• High blood sugar (diabetes)
• High uric acid (gout)
• Muscle cramps
• Tender and enlarged breasts (gynecomastia)
• Pancreatitis (inflammation of the pancreas)

Although withdrawal from diuretics is the most important factor in treating these patients, other medications have been used to try to minimize the fluid retention. These medications include ACE inhibitors, low-dose amphetamines, ephedrine, bromocriptine (Parlodel), or levodopa-carbidopa (Sinemet) in combination. However, their effectiveness is uncertain and side effects of these drugs may occur. For example, hypotension (low blood pressure) may be seen with the use of ACE inhibitors, especially if the patient is also taking diuretics.

The type of doctor who treats edema depends on the type and cause of the edema. Because edema is multifactorial (many possible causes), several doctors will likely be involved in your care. This includes your primary care physician (PCP) or internist, a nephrologist (kidney specialist), cardiologist (heart specialist), or gastroenterologist (digestive tract or liver specialist).Some of the complications of edema are managed by other specialists, such as wound care specialists for edema that leads to leg ulcers, or obstetrician/gynecologists for edema during pregnancy.

The treatment of fluid retention in these people is to reduce the loss of protein into the urine and to restrict salt in the diet. The loss of protein in the urine may be reduced by the use of ACE inhibitors (angiotensin-converting enzyme inhibitors) and angiotensin receptor blockers (ARB's). Both categories of drugs, which ordinarily are used to lower blood pressure, prompt the kidneys to reduce the loss of protein into the urine.ACE inhibitor drugs include:

• enalapril (Vasotec)
• quinapril (Accupril)
• captopril (Capoten)
• benazepril (Lotensin)
• trandolapril (Mavik)
• lisinopril (Zestril or Prinivil)
• ramipril (Altace)

Angiotensin receptor blockers include:

• losartan (Cozaar)
• valsartan (Diovan)
• candesartan (Atacand)
• irbesartan (Avapro)

Certain kidney diseases may contribute to the loss of protein in the urine and the development of edema. A biopsy of the kidney may be needed to make a diagnosis of the type of kidney disease, so that treatment may be given.

Edema can become a problem in systemic diseases of the heart, liver or kidneys. Diuretic therapy can be initiated, often alleviating the edema. The most potent diuretics are loop diuretics, so-called because they work in the portion of the kidney tubules referred to as the loop of Henle. The kidney tubules are small ducts that regulate salt and water balance, while transporting the forming urine. Clinical loop diuretics available are:

• furosemide (Lasix),
• torsemide (Demadex),
• butethamine (Bumex),
• ethacrynate (Edecrin)

The doses of these diuretics vary depending upon the patient's clinical circumstances. These drugs can be given orally, although seriously ill patients in the hospital may receive them intravenously for more prompt or effective response. If one of the loop diuretics is not effective alone, it may be combined with an agent that works further down (more distally) in the tubule. These agents include the thiazide type diuretics, such as hydrochlorothiazide (HydroDIURIL), or a similar but more potent type of diuretic called metolazone (Zaroxolyn). Other thiazide diuretics include chlorthalidone (Thalitone) methyclothiazide (enduron), chlorthalidone (Hygroton), indapamide (Lozol), and metolazone (Zaroxolyn, Diulo, Mykrox). When diuretics that work at different sites in the kidney are used together, the response often is greater than the combined responses to the individual diuretics (synergistic response).

Edema forms in people with kidney disease for two reasons:

1. A heavy loss of protein in the urine
2. Impaired kidney (renal) function

In people with chronic diseases of the liver, fibrosis (scarring) of the liver often occurs. When the scarring becomes advanced, the condition is called cirrhosis of the liver. Ascites is excessive fluid that accumulates in the abdominal (peritoneal) cavity. It is a complication of cirrhosis and appears as an abdominal bulge. The peritoneum is the inner lining of the abdominal cavity, which also folds over to cover the organs inside the abdomen such as the liver, gallbladder, spleen, pancreas, and intestines. Ascites develops because of a combination of two factors:

1. Increased pressure in the vein system that carries blood from the stomach, intestines, and spleen to the liver (portal hypertension)
2. A low level of the protein albumin in the blood (hypoalbuminemia). Albumin, which is the predominant protein in the blood and which helps maintain blood volume, is reduced in cirrhosis primarily because the damaged liver is not able to produce enough of it.

Other consequences of portal hypertension include dilated veins in the esophagus (varices), prominent veins on the abdomen, and an enlarged spleen. Each of these conditions is due primarily to the increased pressure and accumulation of blood and excess fluid in the abdominal blood vessels. The fluid of ascites can be removed from the abdominal cavity by using a syringe and a long needle, a procedure called paracentesis. Analysis of the fluid can help differentiate ascites that is caused by cirrhosis from other causes of ascites, such as cancer, tuberculosis, congestive heart failure, and nephrosis. Sometimes, when ascites does not respond to treatment with diuretics, paracentesis can be used to remove large amounts of the ascitic fluid.Peripheral edema, which is usually seen as pitting edema of the legs and feet, also occurs in cirrhosis. The edema is a consequence of the hypoalbuminemia and the kidneys retaining salt and water.The presence or absence of edema in patients with cirrhosis and ascites is an important consideration in the treatment of the ascites. In patients with ascites without edema, diuretics must be given with extra caution. Diuresis (induced increased volume of urine by use of diuretics) that is too aggressive or rapid in these patients can lead to a low blood volume (hypovolemia), which can cause kidney and liver failure. In contrast, when patients who have both edema and ascites undergo diuresis, the edema fluid in the interstitial space serves as somewhat of a buffer against the development of low blood volume. The excess interstitial fluid moves into the blood vessel spaces to rapidly replenish the depleted blood volume.

Heart failure is the result of poor cardiac function and is reflected by a decreased volume of blood pumped out by the heart, called cardiac output. Heart failure can be caused by weakness of the heart muscle, which pumps blood out through the arteries to the entire body, or by dysfunction of the heart valves, which regulate the flow of blood between the chambers of the heart. The diminished volume of blood pumped out by the heart (decreased cardiac output) is responsible for a decreased flow of blood to the kidneys. As a result, the kidneys sense there is a reduction of the blood volume in the body. To counter the seeming loss of fluid, the kidneys retain salt and water. In this instance, the kidneys are fooled into thinking the body needs to retain more fluid volume when, in fact, the body already is holding too much fluid.This fluid increase ultimately results in the buildup of fluid within the lungs, which causes shortness of breath (cardiogenic pulmonary edema or CPE). Because of the decreased volume of blood pumped out by the heart, the volume of blood in the arteries is also decreased, despite the actual increase in the body's total fluid volume. An associated increase in the amount of fluid in the blood vessels of the lungs causes shortness of breath because the excess fluid from the lungs' blood vessels leaks into the airspaces (alveoli) and interstitium in the lungs. This accumulation of fluid in the lung is called pulmonary edema. At the same time, accumulation of fluid in the legs causes pitting edema. This edema occurs because the build-up of blood in the veins of the legs causes leakage of fluid from the legs' capillaries (tiny blood vessels) into the interstitial spaces.An understanding of how the heart and lungs interact will help you better comprehend how fluid retention works in heart failure. The heart has four chambers; an atrium and a ventricle on the left side of the heart and an atrium and ventricle on the right. The left atrium receives oxygenated blood from the lungs and transfers it to the left ventricle, which then pumps it through the arteries to the entire body. The blood then is transported back to the heart by veins into the right ventricle and transferred to the right ventricle, which then pumps it to the lungs for re-oxygenation.Left-sided heart failure, which is due primarily to a weak left ventricle, usually is caused by coronary artery disease, hypertension (high blood pressure), or disease of the heart valves. Typically, when these people initially come to the doctor, they are troubled by shortness of breath with exertion and when lying down at night (orthopnea). These symptoms are due to pulmonary edema that is caused by pooling of the blood in the vessels of the lungs.In contrast, right-sided heart failure, which often is due to obstructive sleep apnea or chronic lung diseases such as emphysema, initially causes salt retention and peripheral edema. Persistent salt retention in these patients, however, may lead to an expanded blood volume in the blood vessels, thereby causing fluid accumulation in the lungs (pulmonary congestion) and shortness of breath.In people with heart failure due to weak heart muscle (cardiomyopathy), both the right and left ventricles of the heart are usually affected. These people initially can suffer from swelling both in the lungs (pulmonary edema) and in the legs and feet (peripheral edema). The physician examining a patient who has congestive heart failure with fluid retention looks for certain signs, including:

• Pitting edema of the legs and feet
• Rales in the lungs (moist crackle sounds from the excess fluid that can be heard with a stethoscope)
• A gallop rhythm (three heart sounds instead of the normal two due to muscle weakness)
• Distended neck veins (The distended neck veins reflect the accumulation of blood in the veins that are returning blood to the heart.)