Gibbs memorial lecture. Unifying hypothesis of body fluid volume regulation: implications for cardiac failure and cirrhosis.
ABSTRACT 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.
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ABSTRACT: In advanced heart failure, the compensatory responses to reduced cardiac output, in spite of fluid retention, lead to maladaptive consequences. We performed a Medline survey for fluid overload and heart failure as well as reviewing textbook chapters. The increased sympathetic nervous system, renin-angiotensin-aldosterone system, and antidiuretic hormone stimulation and release lead to a vicious cycle--augmenting pre-load, contractility and after-load, as well as increased fluid overload. The elevated work load on an already failed cardio-circulatory system results in further deterioration. Plasma volume is usually increased in untreated patients with increased extracellular fluid. However, it may range from reduced to increased in treated patients. Currently, diuretics remain the initial first line of therapy. In refractory cases, restoring plasma volume and osmolality, by adding albumin or hypertonic saline solutions, neurohormonal antagonists such as vasopressin receptors antagonists, aldosterone antagonists, or administration of nesiritide, may help in overcoming fluid overload. Exact measurement of plasma volume in various forms of heart failure and adjusting the treatment accordingly, establishing favourable and detrimental effects of various therapies, and introducing additional and new therapeutic options require further investigation.Nephrology Dialysis Transplantation 08/2005; 20 Suppl 7:vii24-7. · 3.40 Impact Factor