Paradoxes of body fluid volume regulation in health and disease. A unifying hypothesis.

The body's normal homeostasis is maintained by the integrity of the excretory capacity of the kidneys. In advanced cardiac failure, however, the avidity of the renal sodium and water retention contributes to the occurrence of pulmonary congestion and peripheral edema. In patients with advanced cirrhosis, the kidneys again fail to excrete the amounts of sodium and water ingested, thus leading to ascites and peripheral edema. The signals for this renal retention of sodium and water in a patient with cirrhosis must be extrarenal because when the same kidneys are transplanted into persons with normal liver function, renal sodium and water retention no longer occurs; rather, the kidneys maintain normal fluid and electrolyte balance. Excessive sodium and water retention by the kidneys also occurs during pregnancy despite a 30% to 50% increase in plasma volume, cardiac output, and glomerular filtration rate. What are the afferent and efferent signals whereby normal kidneys retain sodium and water so that total extracellular, interstitial, and intravascular volumes expand far beyond those limits observed in normal subjects? These dilemmas are the subject of this review, in which a "unifying hypothesis of body fluid volume regulation" is presented.