Edema is defined as a clinically apparent increase in the interstitial fluid volume, which may expand by several liters before

the abnormality is evident. Therefore, a weight gain of several kilograms usually precedes overt manifestations of edema, and a similar weight loss from diuresis can be induced in a slightly edematous patient before "dry weight" is achieved. Anasarca refers to gross, generalized edema. Ascites (Chap. 44) and hydrothorax refer to accumulation of excess fluid in the peritoneal and pleural cavities, respectively, and are considered to be special forms of edema.
Approach to the Patient: Edema An important first question is whether the edema is localized or generalized. If it is localized, those local phenomena that may be responsible should be considered. If the edema is generalized, it should be determined, first, if there is serious hypoalbuminemia, e.g., serum albumin <25 g/L. If so, the history, physical examination, urinalysis, and other laboratory data will help evaluate the question of cirrhosis, severe malnutrition, or the nephrotic syndrome as the underlying disorder. If hypoalbuminemia is not present, it should be determined if there is evidence of congestive heart failure of a severity to promote generalized edema. Finally, it should be determined whether the patient has an adequate urine output, or if there is significant oliguria or anuria. These abnormalities are discussed in Chaps. 45, 273, and 274.

(See also Chap. 243) Edema originating from inflammation or hypersensitivity is usually readily identified. Localized edema due to venous or lymphatic obstruction may be caused by thrombophlebitis, chronic lymphangitis, resection of regional lymph nodes, filariasis, etc. Lymphedema is particularly intractable because restriction of lymphatic flow results in increased protein concentration in the interstitial fluid, a circumstance that aggravates retention of fluid. Generalized Edema The differences among the three major causes of generalized edema are shown in Table 36-2.

Organ History System Cardiac Dyspnea with exertion prominentoften associated with orthopneaor paroxysmal nocturnal dyspnea

Physical Examination Elevated jugular venous pressure, ventricular (S3) gallop; occasionally with displaced or dyskinetic apical pulse; peripheral cyanosis, cool extremities, small pulse pressure when severe

Laboratory Findings Elevated urea nitrogen-tocreatinine ratio common; elevated uric acid; serum sodium often diminished; liver enzymes occasionally elevated with hepatic congestion If severe, reductions in serum albumin, cholesterol, other

Hepatic Dyspnea infrequent, Frequently associated with except if associated with ascites; jugular venous

Organ History System significant degree of ascites; most often a history of ethanol abuse

Physical Examination pressure normal or low; blood pressure lower than in renal or cardiac disease; one or more additional signs of chronic liver disease (jaundice, palmar erythema, Dupuytren's contracture, spider angiomata, male gynecomastia; asterixis and other signs of encephalopathy) may be present Blood pressure may be elevated; hypertensive or diabetic retinopathy in selected cases; nitrogenous fetor; periorbital edema may predominate; pericardial friction rub in advanced cases with uremia

Laboratory Findings hepatic proteins (transferrin, fibrinogen); liver enzymes elevated, depending on the cause and acuity of liver injury; tendency toward hypokalemia, respiratory alkalosis; macrocytosis from folate deficiency

Renal

Usually chronic: may be associated with uremic signs and symptoms, including decreased appetite, altered (metallic or fishy) taste, altered sleep pattern, difficulty concentrating, restless legs or myoclonus; dyspnea can be present, but generally less prominent than in heart failure

Albuminuria, hypoalbuminemia; sometimes, elevation of serum creatinine and urea nitrogen; hyperkalemia, metabolic acidosis, hyperphosphatemia, hypocalcemia, anemia (usually normocytic)

The great majority of patients with generalized edema suffer from advanced cardiac, renal, hepatic, or nutritional disorders. Consequently, the differential diagnosis of generalized edema should be directed toward identifying or excluding these several conditions. Edema of Heart Failure (See also Chap. 227) The presence of heart disease, as manifested by cardiac enlargement and a gallop rhythm, together with evidence of cardiac failure, such as dyspnea, basilar rales, venous distention, and hepatomegaly, usually indicate that edema results from heart failure. Noninvasive tests, such as echocardiography, may be helpful in establishing the diagnosis of heart disease. The edema of heart failure typically occurs in the dependent portions of the body. Edema of the Nephrotic Syndrome

(See also Chap. 277) Marked proteinuria (>3.5 g/d), hypoalbuminemia (<35 g/L), and, in some instances, hypercholesterolemia are present. This syndrome may occur during the course of a variety of kidney diseases, which include glomerulonephritis, diabetic glomerulosclerosis, and hypersensitivity reactions. A history of previous renal disease may or may not be elicited. Edema of Acute Glomerulonephritis and Other Forms of Renal Failure (See also Chap. 277) The edema occurring during the acute phases of glomerulonephritis is characteristically associated with hematuria, proteinuria, and hypertension. Although some evidence supports the view that the fluid retention is due to increased capillary permeability, in most instances the edema results from primary retention of NaCl and H2O by the kidneys owing to renal insufficiency. This state differs from congestive heart failure in that it is characterized by a normal (or sometimes even increased) cardiac output and a normal arterialmixed venous oxygen difference. Patients with edema due to renal failure commonly have evidence of arterial hypertension as well as pulmonary congestion on chest roentgenograms even without cardiac enlargement, but they may not develop orthopnea. Patients with chronic renal failure may also develop edema due to primary renal retention of NaCl and H2O. Edema of Cirrhosis (See also Chap. 302) Ascites and biochemical and clinical evidence of hepatic disease (collateral venous channels, jaundice, and spider angiomas) characterize edema of hepatic origin. The ascites (Chap. 44) is frequently refractory to treatment because it collects as a result of a combination of obstruction of hepatic lymphatic drainage, portal hypertension, and hypoalbuminemia. A sizable accumulation of ascitic fluid may increase intraabdominal pressure and impede venous return from the lower extremities; hence, it tends to promote accumulation of edema in this region as well. Edema of Nutritional Origin A diet grossly deficient in protein over a prolonged period may produce hypoproteinemia and edema. The latter may be intensified by the development of beriberi heart disease, also of nutritional origin, in which multiple peripheral arteriovenous fistulae result in reduced effective systemic perfusion and effective arterial blood volume, thereby enhancing edema formation (Chap. 71). Edema may actually become intensified when famished subjects are first provided with an adequate diet. The ingestion of more food may increase the quantity of NaCl ingested, which is then retained along with H2O. So-called refeeding edema may also be linked to increased release of insulin, which directly increases tubular Na+ reabsorption. In addition to hypoalbuminemia, hypokalemia and caloric deficits may be involved in the edema of starvation. Other Causes of Edema These include hypothyroidism, in which the edema (myxedema) is located typically in the pretibial region and which may also be associated with periorbital puffiness; exogenous hyperadrenocortism; pregnancy; and administration of estrogens and vasodilators, particularly dihydropyridines such as nifedipine.

The distribution of edema is an important guide to its cause. Thus, edema limited to one leg or to one or both arms is usually the result of venous and/or lymphatic obstruction. Edema resulting from hypoproteinemia characteristically is generalized, but it is especially evident in the very soft tissues of the eyelids and face and tends to be most pronounced in the morning because of the recumbent posture assumed during the night. Less common causes of facial edema include trichinosis, allergic reactions, and myxedema. Edema associated with heart failure, by contrast, tends to be more extensive in the legs and to be accentuated in the evening, a feature also determined largely by posture. When patients with heart failure have been confined to bed, edema may be most prominent in the presacral region. Paralysis reduces lymphatic and venous drainage on the affected side and may be responsible for unilateral edema.

Additional Factors in Diagnosis The color, thickness, and sensitivity of the skin are significant. Local tenderness and warmth suggest inflammation. Local cyanosis may signify venous obstruction. In individuals who have had repeated episodes of prolonged edema, the skin over the involved areas may be thickened, indurated, and often red. Estimation of the venous pressure is of importance in evaluating edema. Ordinarily, a significant generalized increase in venous pressure can be recognized by the level at which cervical veins collapse (Chap. 220). In patients with obstruction of the superior vena cava, edema is confined to the face, neck, and upper extremities, in which the venous pressure is elevated compared with that in the lower extremities. Severe heart failure may cause ascites that may be distinguished from the ascites caused by hepatic cirrhosis by the jugular venous pressure, which is usually elevated in heart failure and normal in cirrhosis. Determination of the concentration of serum albumin aids importantly in identifying those patients in whom edema is due, at least in part, to diminished intravascular colloid oncotic pressure. The presence of proteinuria also affords useful clues. The absence of proteinuria excludes nephrotic syndrome but cannot exclude nonproteinuric causes of renal failure. Slight to moderate proteinuria is the rule in patients with heart failure. Distribution of Edema The distribution of edema is an important guide to its cause. Thus, edema limited to one leg or to one or both arms is usually the result of venous and/or lymphatic obstruction. Edema resulting from hypoproteinemia characteristically is generalized, but it is especially evident in the very soft tissues of the eyelids and face and tends to be most pronounced in the morning because of the recumbent posture assumed during the night. Less common causes of facial edema include trichinosis, allergic reactions, and myxedema. Edema associated with heart failure, by contrast, tends to be more extensive in the legs and to be accentuated in the evening, a feature also determined largely by posture. When patients with heart failure have been confined to bed, edema may be most prominent in the presacral region. Paralysis reduces lymphatic and venous

drainage on the affected side and may be responsible for unilateral edema. Additional Factors in Diagnosis The color, thickness, and sensitivity of the skin are significant. Local tenderness and warmth suggest inflammation. Local cyanosis may signify venous obstruction. In individuals who have had repeated episodes of prolonged edema, the skin over the involved areas may be thickened, indurated, and often red. Estimation of the venous pressure is of importance in evaluating edema. Ordinarily, a significant generalized increase in venous pressure can be recognized by the level at which cervical veins collapse (Chap. 220). In patients with obstruction of the superior vena cava, edema is confined to the face, neck, and upper extremities, in which the venous pressure is elevated compared with that in the lower extremities. Severe heart failure may cause ascites that may be distinguished from the ascites caused by hepatic cirrhosis by the jugular venous pressure, which is usually elevated in heart failure and normal in cirrhosis. Determination of the concentration of serum albumin aids importantly in identifying those patients in whom edema is due, at least in part, to diminished intravascular colloid oncotic pressure. The presence of proteinuria also affords useful clues. The absence of proteinuria excludes nephrotic syndrome but cannot exclude nonproteinuric causes of renal failure. Slight to moderate proteinuria is the rule in patients with heart failure.
Glomerulonefritis dan Gagal ginjal hematuria, proteinuria, and hypertension. GFR turun, Ureum creatinin meningkat, Although some evidence supports the view that the fluid retention is due to increased capillary permeability, in most instances the edema results from primary retention of NaCl and H2O by the kidneys owing to renal insufficiency. This state differs from congestive heart failure in that it is characterized by a normal (or sometimes even increased) x foto BGA, EKG, ureum kreatinin cardiac output and a normal arterialmixed venous oxygen difference. Patients with edema due to renal failure commonly have evidence of arterial hypertension as well as pulmonary congestion on chest roentgenograms even without cardiac enlargement, but they may not develop orthopnea. Patients with chronic renal failure may also develop edema due to primary renal retention of NaCl and H2O

(See also Chap. 277) Marked proteinuria (>3.5 g/d), hypoalbuminemia (<35 g/L), and, in some instances, hypercholesterolemia are present. This syndrome may occur during the course of a variety of kidney diseases, which include glomerulonephritis, diabetic glomerulosclerosis, and hypersensitivity reactions. A history of previous renal disease may or may not be elicited.