Worth one's salt: the master dysnatremia equation.

Fish, birds, amphibians, reptiles, and mammal share the interesting physiological fact that their plasma salt concentration ([Na ϩ ] pw) is virtually identical, amounting to ϳ9 g/l. This is the equivalent of a 0.9% salt solution. In humans, the [Na ϩ ] pw is maintained within a very narrow range, where its value varies by only 1% (11). Diseases that perturb the [Na ϩ ] pw are collectively known by clinicians as the " dysnatremias. " Understanding the physiological basis for changes in the [Na ϩ ] pw has remained a major challenge for physiologists and clinicians alike; for unlike the concentration of the majority of substances in plasma, it has been known since the 1950s that the mass balance of Na ϩ per se cannot account quantitatively for changes in the [Na ϩ ] pw. In addition to the mass balance of Na ϩ , the mass balance of K ϩ and H 2 O play an important role in determining the [Na ϩ ] pw. In a landmark paper, Edelman et al. (1) reported for the first time an equation relating the [Na ϩ ] pw to the exchangeable Na ϩ , exchangeable K ϩ , total body water (TBW) where [Na ϩ ] pw ϭ 1.11(Na ϩ ϩ K ϩ)/ TBW Ϫ 25.6. Changes in the mass balance of Na ϩ , K ϩ , and H 2 O affected the terms in this equation and therefore the [Na ϩ ] pw. In most texts, the equation was simplified to [Na ϩ ] pw ϭ (Na ϩ ϩ K ϩ)/TBW and the slope and y-intercept were ignored. Until the landmark studies of Nguyen and Kurtz (3, 5– 8, 10), the validity of the simplified equation had remained unquestioned despite the fact that it could not account for several clinical and physiological factors that affect [Na ϩ ] pw. These factors included: hyperglymia-induced hyponatremia, the effect of Gibbs-Donnan equilibrium in altering the distribution of Na ϩ ions between the plasma and interstitial fluid (ISF), the fact that not all Na ϩ-containing salts are completely dissociated in an aqueous solution, the fact that not all ex-changeable Na ϩ and K ϩ is osmotically active, and the effect of osmotically active non-Na ϩ and non K ϩ osmoles in inducing intercompartmental water shifts (2, 4, 12). One of the important key insights of the recent elegant studies by Nguyen and …