Unifying hypothesis of body fluid volume regulation: Implications for cardiac failure and cirrhosis

Body fluid volume regulation is critically important in maintaining life. I n this paper, we review our unifying hypothesis of body fluid volume regula tion, which maintains arterial circulatory integrity in health and disease. The integrity of the arterial circulation, as determined by cardiac output and peripheral vascular resistance, is the predominant determinant of rena l sodium and water retention. Arterial circulatory integrity can be disturb ed either by a decrease in cardiac output, as in low-output cardiac failure , or by a decrease in peripheral vascular resistance, as in high-output sta tes such as high-output cardiac failure and cirrhosis. The resulting arteri al underfilling is sensed by baroreceptors that are located in the left ven tricle, die aortic arch, die carotid sinus and the renal afferent arteriole s. Decreased activation of these receptors during arterial underfilling lea ds to neurohumoral compensatory responses, which include the stimulation of the sympathetic nervous system, activation of die renin-angiotensin-aldost erone system (RAAS) and the non-osmotic release of vasopressin. These compe nsatory responses maintain arterial circulatory integrity by increasing per ipheral and renal arterial vascular resistance together with renal sodium a nd water retention. However, over the long term, these adaptive responses m ay have detrimental effects, such as pulmonary congestion, increased myocar dial demand, increased cardiac afterload, ascites and hyponatremia. The int ensity of the neurohumoral responses correlates with the progression and se verity of both cardiac failure and cirrhosis. The understanding of the path ogenesis of sodium and water retention in cardiac failure and cirrhosis has led to therapies that favorably affect the morbidity and mortality of thes e patients.