Most of the extracellular fluid is interstitial fluid (ISF) in the tissue spaces, providing the transport medium between capillaries and cells. The sodium concentration in plasma is slightly above that in ISF because plasma contains more proteins, notably albumin, which do not readily escape into ISF across the capillary membranes, and the effect of their negative charges is to hold more positively charged ions, notably sodium, in circulation (Gibbs-Donnan equilibrium).
The main effects of excess ECF volume are seen as expanded ISF, visible clinically as edema (or ascites when fluid accumulates in the abdomen rather than the tissue spaces). Mild edema is merely a cosmetic problem in itself but pulmonary or cerebral edema, or severe ascites, are potentially serious forms. Edema can result from excess ingestion or retention of sodium (overall expansion of ECF) or 'leakage' from plasma to ISF, with plasma volume continuously replenished by renal sodium retention. Such maldistribution of ECF occurs if plasma albumin is very low (renal leakage, hepatic impairment, or severe malnutrition), or with excessive capillary blood pressure (venous blockage, inactivity, heart failure, or arteriolar dilation, e.g., from heat or allergy), capillary damage, or lymphatic blockage. The latter prevents the removal of proteins that have leaked into ISF. Accumulation of protein in ISF undermines the osmotic gradient, normally favors uptake of water at the venous end of the capillary, where the pressure is lower. Since edema involves the expansion of a larger compartment (ISF) from a smaller one (plasma) it is only possible as long as the latter is replenished; hence the kidney, while seldom the primary cause of edema, is always the enabling cause; the use of diuretics is therefore appropriate in the treatment of nonrenal as well as renal causes of edema.
The main effect of inadequate ECF volume is to reduce plasma volume and thus to compromise cardiovascular function, in extreme cases by causing circulatory shock.
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