Malaria

REVIEW

Peripheral Edema
Shaun Cho, MD, J. Edwin Atwood, MD
Peripheral edema often poses a dilemma for the clinician because it is a nonspecific finding common to a host of diseases ranging from the benign to the potentially life threatening. A rational and systematic approach to the patient with edema allows for prompt and cost-effective diagnosis and treatment. This article reviews thepathophysiologic basis of edema formation as a foundation for understanding the mechanisms of edema formation in specific disease states, as well as the implications for treatment. Specific etiologies are reviewed to compare the diseases that manifest this common physical sign. Finally, we review the clinical approach to diagnosis and treatment strategies. Am J Med. 2002;113:580 –586. ©2002 by ExcerptaMedica, Inc.

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 space (75%) (1). Starling defined the physiologic forces involved in maintaining the balance of water between these twocompartments (2,3), which include the gradient between intravascular and extravascular hydrostatic pressures, differences in oncotic pressures within the interstitial space and plasma, and the hydraulic permeability of the blood vessel wall (4). The lymphatic system collects fluid and filtered proteins from the interstitial space and returns them to the vascular compartment (Figure). Major perturbationsin this delicate homeostasis that favors net filtration out of the vascular space, or impaired return of fluid by lymphatics from the interstitial space, will result in edema.

The major contributors to interstitial oncotic pressure are mucopolysaccharides, filtered proteins such as albumin, capillary wall protein permeability, and the rate of lymphatic clearance (5,6). Changes in capillary wallpermeability are mediated by cytokines such as tumor necrosis factor, interleukin 1, and interleukin 10, as well as by circulating vasodilatory prostaglandins and nitric oxide (7). Increased vascular permeability is central to edema resulting from local inflammation (e.g., insect bites), allergic reactions, and burns.

Renal and Neurohumoral Factors
Because the tissues constituting theinterstitium easily accommodate several liters of fluid, a patient’s weight may increase nearly 10% before pitting edema is evident. The source of this expansion of interstitial fluid is the blood plasma. Because normal blood plasma is only about 3 L, the diffusion of large amounts of water and electrolytes into the interstitial space necessitates the renal retention of sodium and water to maintainhemodynamic stability (6). Hence, blood volume and normal osmolality are maintained despite movement of large amounts of fluid into the extravascular space. “Effective” intravascular volume depletion, which occurs in chronic heart failure and cirrhosis, initiates a neurohumoral cascade that attempts to maintain effective circulating volume. This cascade reduces glomerular filtration rate via renalvasoconstriction, increases sodium reabsorption proximally mediated by angiotensin II and norepinephrine, and increases sodium and water reabsorption in the collecting tubules mediated by aldosterone and antidiuretic hormone. Additionally, endothelium-derived factors such as nitric oxide and prostaglandins are increasingly recognized as being important in regulating homeostasis (8,9). Collectively, theylimit sodium and water excretion, thereby promoting edema development (5). Over time, these responses become mal0002-9343/02/$–see front matter PII S0002-9343(02)01322-0

Starling Forces
Increased venous pressures due to central or regional venous obstruction or to an expansion in plasma volume are transmitted to the capillary bed, thereby increasing hydrostatic pressure and predisposing to edema...