Soft tissue swelling due to abnormal expansion of interstitial fluid volume. Edema fluid is a plasma transudate that accumulates when movement of fluid from vascular to interstitial space is favored. Because detectable generalized edema in the adult reflects a gain of ≥3 L, renal retention of salt and water is necessary for edema to occur. Distribution of edema can be an important guide to cause.
Limited to a particular organ or vascular bed; easily distinguished from generalized edema. Unilateral extremity edema is usually due to venous or lymphatic obstruction (e.g., deep venous thrombosis, tumor obstruction, primary lymphedema). Stasis edema of a paralyzed lower extremity also may occur. Allergic reactions (“angioedema”) and superior vena caval obstruction are causes of localized facial edema. Bilateral lower-extremity edema may have localized causes, e.g., inferior vena caval obstruction, compression due to ascites, and abdominal mass. Ascites (fluid in peritoneal cavity) and hydrothorax (in pleural space) also may present as isolated localized edema, due to inflammation or neoplasm.
Soft tissue swelling of most or all regions of the body. Bilateral lower-extremity swelling, more pronounced after standing for several hours, and pulmonary edema are usually cardiac in origin. Periorbital edema noted on awakening often results from renal disease and impaired Na excretion. Ascites and edema of lower extremities and scrotum are frequent in cirrhosis, nephrotic syndrome, or CHF.
In CHF, diminished cardiac output and arterial underfilling result in both decreased renal perfusion and increased venous pressure with resultant renal Na retention due to renal vasoconstriction, intrarenal blood flow redistribution, direct Na-retentive effects of norepinephrine and angiotensin II, and secondary hyperaldosteronism.
In cirrhosis, arteriovenous shunts and peripheral vasodilation lower renal perfusion, resulting in Na retention. Ascites accumulates when increased intrahepatic vascular resistance produces portal hypertension. As in heart failure, the effects of excess intrarenal and circulating norepinephrine, angiotensin II, and aldosterone lead to renal Na retention and worsening edema. Reduced serum albumin and increased abdominal pressure also promote lower-extremity edema.
In acute or chronic renal failure, edema occurs if Na intake exceeds kidneys’ ability to excrete Na secondary to marked reductions in glomerular filtration. Severe hypoalbuminemia (<25 g/L [2.5 g/dL]) of any cause (e.g., nephrotic syndrome, nutritional deficiency, chronic liver disease) may lower plasma oncotic pressure, promoting fluid transudation into interstitium; lowering of effective blood volume stimulates renal Na retention and causes edema.
Less common causes of generalized edema: idiopathic edema, a syndrome of recurrent rapid weight gain and edema in women of reproductive age; hypothyroidism, in which myxedema is typically located in the pretibial region; drugs (Table 36-1).
TABLE 36-1DRUGS ASSOCIATED WITH EDEMA FORMATION ||Download (.pdf) TABLE 36-1DRUGS ASSOCIATED WITH EDEMA FORMATION
|Nonsteroidal anti-inflammatory drugs |
|Antihypertensive agents |
| Direct arterial/arteriolar vasodilators |
| Hydralazine |
| Clonidine |
| Methyldopa |
| Guanethidine |
| Minoxidil |
| Calcium channel antagonists |
| α-Adrenergic antagonists |
| Thiazolidinediones |
|Steroid hormones |
| Glucocorticoids |
| Anabolic steroids |
| Estrogens |
| Progestins |
|Growth hormone |
| Interleukin 2 |
| OKT3 monoclonal antibody |
Primary management is to identify and treat the underlying cause of edema (Fig. 36-1).
Diagnostic approach to edema. CO, cardiac output; JVD, jugular venous distention. (From Chap. 42: HMOM-18.)
Dietary Na restriction (<500 mg/d) may prevent further edema formation. Bed rest enhances response to salt restriction in CHF and cirrhosis. Supportive stockings and elevation of edematous lower extremities help to mobilize interstitial fluid. If severe hyponatremia (<132 mmol/L) is present, water intake also should be reduced (<1500 mL/d). Diuretics (Table 36-2) are indicated for marked peripheral edema, pulmonary edema, CHF, and inadequate dietary salt restriction. Complications are listed in Table 36-3. Weight loss by diuretics should be limited to 1–1.5 kg/d. Distal (“potassium sparing”) diuretics or metolazone may be added to loop diuretics for enhanced effect. Note that intestinal edema may impair absorption of oral diuretics and reduce effectiveness. When desired weight is achieved, diuretic doses should be reduced.
TABLE 36-2DIURETICS FOR EDEMA ||Download (.pdf) TABLE 36-2DIURETICS FOR EDEMA
|Drug ||Usual Dose ||Comments |
|Loop (May be administered PO or IV) |
|Furosemide ||20–120 mg qd or bid ||Short acting; potent; effective with low GFR |
|Bumetanide ||0.5–2 mg qd or bid ||Better oral absorption than furosemide, but shorter duration of action |
|Torsemide ||20–200 mg qd ||Better oral absorption than furosemide, longer duration of action |
|Distal, K-Losing |
|Hydrochlorothiazide ||12.5–25 mg qd ||Causes hypokalemia; need GFR >25 mL/min |
|Chlorthalidone ||12.5–25 mg qd ||Long acting (up to 72 h); hypokalemia |
|Metolazone ||1–5 mg qd ||Long acting; hypokalemia; effective with low GFR, especially when combined with a loop diuretic |
|Distal, K-Sparing |
|Spironolactone ||12.5–100 mg qd ||Hyperkalemia; acidosis; blocks aldosterone; gynecomastia, impotence, amenorrhea; onset takes 2–3 days; avoid use in renal failure or in combination with ACE inhibitors or potassium supplement |
25–50 mg qd
Similar side effects to spironolactone, but more specific for mineralocorticoid receptor; lower incidence of gynecomastia and amenorrhea
5–10 mg qd or bid
Hyperkalemia; once daily; less potent than spironolactone
|Triamterene ||100 mg bid ||Hyperkalemia; less potent than spironolactone; renal stones |
TABLE 36-3COMPLICATIONS OF DIURETICS ||Download (.pdf) TABLE 36-3COMPLICATIONS OF DIURETICS
|Common ||Uncommon |
|Volume depletion ||Interstitial nephritis (thiazides, furosemide) |
|Prerenal azotemia ||Pancreatitis (thiazides) |
|Potassium depletion ||Loss of hearing (loop diuretics) |
|Hyponatremia (thiazides) ||Anemia, leukopenia, thrombocytopenia (thiazides) |
|Metabolic alkalosis || |
|Hypercholesterolemia || |
|Hyperglycemia (thiazides) || |
|Hyperkalemia (K-sparing) || |
|Hypomagnesemia || |
|Hyperuricemia || |
|Hypercalcemia (thiazides) || |
|GI complaints || |
|Rash (thiazides) || |
In CHF (Chap. 124), avoid overdiuresis because it may bring a fall in cardiac output and prerenal azotemia. Avoid diuretic-induced hypokalemia, which predisposes to digitalis toxicity.
In cirrhosis and other hepatic causes of edema, spironolactone is the initial diuretic of choice but may produce acidosis and hyperkalemia. Thiazides or small doses of loop diuretics may also be added. However, renal failure may result from volume depletion. Overdiuresis may result in hyponatremia, hypokalemia, and alkalosis, which may worsen hepatic encephalopathy (Chap. 154).
For a more detailed discussion, see Braunwald E, Loscalzo J: Edema, Chap. 50, p. 250, in HPIM-19.