Body fluid volume regulation in health and disease

The unifying hypothesis of body fluid volume regulation explains the renal handling of sodium and water in health and in various disease states associated with edema formation and no intrinsic renal parenchymal disease. According to this hypothesis, underfilling of the arterial vascular compartment, resulting from either a decrease in cardiac output or peripheral arterial vasodilation, initiates a sequence of events that results in activation of the sympathetic nervous and renin-angiotensin-aldosterone systems and the nonosmotic release of AVP. Activation of these neurohormonal vasoconstrictor systems causes diminished renal hemodynamics and renal sodium and water retention that persist despite an increase in total extracellular and blood volume. In edematous patients, a vasoconstrictor-mediated increase in proximal tubular sodium reabsorption results in diminished sodium delivery to the distal tubular sites of action of aldosterone and ANP; this explains the failure of such patients to escape from the sodium-retaining effects of aldosterone and the resistance to the natriuretic and diuretic effects of ANP. In pregnancy, an early decrease in systemic vascular resistance associated with activation of the neurohormonal vasoconstrictor systems precedes the normal expansion of blood and plasma volumes and is consistent with the arterial underfilling hypothesis. The loss of this peripheral vasodilatory response in some pregnancies may contribute to the development of preeclampsia and eclampsia.