Edema is a palpable swelling produced by expansion of the interstitial fluid volume and is often nonspecific. When massive and generalized, the excess fluid accumulation is called anasarca. A variety of clinical conditions, ranging from the benign to the potentially life threatening, is associated with the development of peripheral edema. These include common conditions such as heart failure (HF), cirrhosis, and nephrotic syndrome (NS), but edema may also be idiopathic (see Table 1).1 A systematic approach to the patient with edema allows for prompt and cost-effective diagnosis and treatment.1
Anatomy and pathophysiology
Total body water is divided between the intracellular and extracellular spaces. The extracellular space, which comprises about one third of total body water, is composed of the intravascular plasma volume (25%) and the extravascular interstitial spaces (75%).2 According to Starling's law, the physiologic forces involved in maintaining the balance of water between these two compartments include the gradient between extravascular and intravascular hydrostatic pressures, differences in oncotic pressures within the interstitial space and plasma, and the permeability of the blood vessel wall.3
Fluid and filtered proteins from the interstitial space are collected by the lymphatic system and returned to the 
vascular compartment. Peripheral edema results from a disturbance in this delicate equilibrium with net filtration out of the vascular space or from impaired return of fluid by lymphatics in the interstitial space.4,5
Alteration of Starling forces plays a central role in the pathophysiology of edema. Increased venous pressure due to central or regional venous obstruction or to an expansion in plasma volume is transmitted to the capillary bed, thereby increasing hydrostatic pressure and predisposing to edema. Conversely, local autoregulation by smooth muscle sphincters on the precapillary (or arterial) side protect the capillary bed from increases in systemic arterial pressure, which explains why hypertensive patients do not have edema despite elevated BP.6,7
An increase in capillary permeability due to vascular injury is a key event in edema formation resulting from local inflammation. Capillary permeability is under the control of cytokines, circulating vasodilatory prostaglandins, and nitric oxide.8 Increase in capillary permeability promotes the development of edema both directly and indirectly by permitting albumin to move into the interstitium, thereby diminishing the oncotic pressure gradient.
The lymphatics play an essential role in reabsorption of interstitial fluid and proteins, returning them to the central circulation. Lymphatic obstruction is an unusual cause of edema (called lymphedema) that is most often seen with nodal enlargement due to malignancy and with surgical removal of lymph nodes, such as during radical mastectomy. In certain disease conditions such as myxedema, the lymphatic system is overwhelmed because of the marked increase in interstitial accumulation of albumin and other proteins.9
Multiple renal and neurohumoral factors control fluid and electrolyte homeostasis. In certain disease states, such as chronic HF and cirrhosis, the neurohumoral cascade that attempts to maintain effective circulating volume becomes maladaptive, leading to a cycle of further sodium and water retention. In chronic edematous states, end-organ resistance to natriuretic peptides inevitably occurs, which explains the sodium retention in these conditions despite high circulating levels of these peptides.10,11
History and physical examination
Use a multisystem approach when evaluating a patient with edema. Of particular importance is excluding major organ system dysfunction, especially cardiac, liver, and renal dysfunction. Document the location of the edema, its progression, and whether it occurs intermittently or persistently. Analyze these clinical findings in relation to the patient's medical history of coronary artery disease, renal disease, liver disease, and so forth.
Ask questions such as the following:
• Do the rings on your fingers get tight?
• Have you had to let your belt out?
• Have your clothes or shoes gotten too tight?12
Pay special attention to the patient's medications; several can cause edema, such as NSAIDs, calcium channel blockers, and estrogens.13-16 Assess whether patients who are already taking a diuretic to treat peripheral edema are adhering to their drug regimen. Also, obtain a thorough dietary history, paying careful attention to the patient's dietary sodium intake, total daily fluid intake, and adherence to special dietary restrictions (see www.heartfailure.org and www.kidney.org for special dietary instructions for salt and fluid restriction).
The physical examination In addition to the standard physical examination, chart the patient's weight and note 
general appearance, paying special attention to the edema with respect to location, symmetry, pitting or nonpitting appearance, tenderness, and associated skin changes, such as ulceration and rubor. Look for ascites. Evaluating the peripheral and central venous systems may shed light on the pathogenesis of edema. Lastly, assess the severity of edema with a method such as the four-point scale (+1, slight, to +4, very marked), the presence of sacral edema, and the height in the case of lower extremity edema.12
Diagnostic testing Order simple, safe, and cost-effective tests, including a chemistry panel and urinalysis to evaluate renal and liver function and albumin levels to assess nutritional status. Consider measuring the thyrotropin level to rule out hypothyroidism. In cases where screening for a cardiac etiology is required, an ECG and chest radiograph may be helpful in assessing cardiac function. When considering diagnostic tests in the context of a potentially long list of etiologies, a comprehensive history and physical examination, along with basic metabolic laboratory tests, can yield an accurate diagnosis in the majority of cases; expensive testing is usually unnecessary.