Evolving concepts in the quantitative analysis of the determinants of the plasma water sodium concentration and the pathophysiology and treatment of the dysnatremias

Abstract

The physiologic and clinical implications of the empirical formula originally discovered by Edelman et al [J Clin Invest 37:1236-1256, 1958] relating the plasma water sodium concentration ([Na+]pw) to the total exchangeable sodium (Nae), total exchangeable potassium (Ke), and total body water (TBW) have recently been elucidated. It is quite remarkable that the full significance of the Edelman equation discovered almost 50 years ago had remained unrecognized by clinicians and physiologists until recently. Although Edelman and colleagues had shown that the [Na +]pw is proportional to the magnitude of (Nae + Ke)/TBW, the linear equation relating [Na+]pw to (Nae + Ke)/TBW had a slope greater than unity of 1.11, and a non-zero y intercept of -25.6 whose significance was unrecognized and more often than not ignored. It has recently been demonstrated that the slope and y intercept in this equation are quantitatively determined by several additional physiologic parameters, which in addition to (Nae + K e)/TBW, play a role both in modulating the [Na+] pw and in the generation of the dysnatremias. Even more remarkably, based only on the theoretical principles of Gibbs-Donnan and osmotic equilibrium, all the physiologic parameters that determine the magnitude of the [Na+]pw can be incorporated into a simple conceptual and mathematical framework that sheds light on a broad of range of seemingly unrelated topics that have heretofore been treated separately clinically, including (1) effect of changes in the mass balance of Na+, K +, and H2O on the [Na+]pw; (2) modulation of [Na+]pw in hyperglycemic states; (3) definition of an isonatric solution; (4) current formulas used to quantitate electrolyte-free water excretion; (5) complex role of K+ in modulating the [Na+]pw; and (6) quantitative analysis of the generation and treatment of the dysnatremias. Moreover, this analysis has also proven to be an indispensable tool for deriving new formulas to aid the clinician in both interpreting the pathogenesis and treating the dysnatremias. © 2005 by the International Society of Nephrology.