Gibbs memorial lecture. Unifying hypothesis of body fluid volume regulation: implications for cardiac failure and cirrhosis.

Body fluid volume regulation is critically important in maintaining life. In this paper, we review our unifying hypothesis of body fluid volume regulation, 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 renal sodium and water retention. Arterial circulatory integrity can be disturbed 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 states such as high-output cardiac failure and cirrhosis. The resulting arterial underfilling is sensed by baroreceptors that are located in the left ventricle, the aortic arch, the carotid sinus and the renal afferent arterioles. Decreased activation of these receptors during arterial underfilling leads to neurohumoral compensatory responses, which include the stimulation of the sympathetic nervous system, activation of the renin-angiotensin-aldosterone system (RAAS) and the non-osmotic release of vasopressin. These compensatory responses maintain arterial circulatory integrity by increasing peripheral and renal arterial vascular resistance together with renal sodium and water retention. However, over the long term, these adaptive responses may have detrimental effects, such as pulmonary congestion, increased myocardial demand, increased cardiac afterload, ascites and hyponatremia. The intensity of the neurohumoral responses correlates with the progression and severity of both cardiac failure and cirrhosis. The understanding of the pathogenesis of sodium and water retention in cardiac failure and cirrhosis has led to therapies that favorably affect the morbidity and mortality of these patients.