Water and Sodium Retention in Edematous Disorders: Role of Vasopressin and Aldosterone
Section snippets
Arterial underfilling as a unifying hypothesis for edematous disorders
In recent years, a hypothesis explaining many of these contradictions with respect to water and sodium retention in edematous disorders has emerged in several reports.1, 2, 3, 4, 10, 11 Total blood volume consists of approximately 85% of blood on the venous side of the circulation, with the remaining 15% on the arterial side of the circulation. Although there are low-pressure receptors on the venous side of the circulation, the unifying hypothesis of body fluid volume regulation focused on the
Nonosmotic stimulation of atrial vasopressin secretion
The first demonstration of a role of nonosmotic vasopressin release in congestive heart failure was published in 1981 in The New England Journal of Medicine.6 Some 30 of 37 patients with cardiac failure who had hyponatremia and hypo-osmolality, of a degree that would have suppressed plasma AVP to undetectable levels in normal subjects, revealed “nonosmotic” plasma AVP concentrations measured by radioimmunoassay. In earlier studies, a bioassay for measuring plasma AVP was used, but the
Contribution from the renin-angiotensin-aldosterone system
Figure 4 illustrates the pathophysiologic events occurring during heart failure that lead not only to sodium and water retention but also are associated with deleterious effects of angiotensin and aldosterone on cardiac remodeling.15 Taken together, the enhanced understanding of the pathophysiology of heart failure has been accompanied by several prospective, randomized clinical trials that have reported increased survival in patients with cardiac conditions treated with β-blocker therapy,
Pathophysiologic role of primary arterial vasodilation
The critical pathophysiologic question in cirrhosis relates to the potential mediators of the splanchnic arterial vasodilation that initiate the arterial underfilling with resultant water and sodium retention.32 The portal hypertension of cirrhosis is associated with splanchnic dilatation and increased splanchnic blood flow. The increased splanchnic blood flow is associated with an upregulation of endothelial nitric oxide synthase (eNOS) and increased nitric oxide levels.33 Nitric oxide is a
Summary
Absolute arterial underfilling due to a decrease in cardiac output (e.g., low-output cardiac failure), and relative arterial underfilling due to systemic arterial vasodilation (e.g., cirrhosis and/or pregnancy), activate the neurohumoral axis including AVP, RAAS, and the sympathetic nervous system. Although these events initially maintain arterial perfusion in edematous patients, in patients with advanced edematous disorders the resultant sodium and water retention leads to deleterious
Acknowledgment
The author thanks Jan Darling for her excellent support in the preparation of the manuscript.
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This work was supported by Grant No. P01 DK19928 from the National Institute of Diabetes, Digestive, and Kidney Diseases.