Mechanisms of sodium balance: total body sodium, surrogate variables, and renal sodium excretion

The classical concepts of human sodium balance include 1) a total pool of Na⁺ of ≈4,200 mmol (total body sodium, TBS) distributed primarily in the extracellular fluid (ECV) and bone, 2) intake variations of 0.03 to ≈6 mmol·kg body mass^-1·day^-1, 3) asymptotic transitions between steady states with a halftime (T½) of 21 h, 4) changes in TBS driven by sodium intake measuring ≈1.3 day [ΔTBS/Δ(Na⁺ intake/day)], 5) adjustment of Na⁺ excretion to match any diet thus providing metabolic steady state, and 6) regulation of TBS via controlled excretion (90-95% renal) mediated by surrogate variables. The present focus areas include 1) uneven, nonosmotic distribution of increments in TBS primarily in "skin," 2) long-term instability of TBS during constant Na⁺ intake, and 3) physiological regulation of renal Na⁺ excretion primarily by neurohumoral mechanisms dependent on ECV rather than arterial pressure. Under physiological conditions 1) the nonosmotic distribution of Na⁺ seems conceptually important, but quantitatively ill defined; 2) long-term variations in TBS represent significant deviations from steady state, but the importance is undetermined; and 3) the neurohumoral mechanisms of sodium homeostasis competing with pressure natriuresis are essential for systematic analysis of short-term and long-term regulation of TBS. Sodium homeostasis and blood pressure regulation are intimately related. Real progress is slow and will accelerate only through recognition of the present level of ignorance. Nonosmotic distribution of sodium, pressure natriuresis, and volume-mediated regulation of renal sodium excretion are essential intertwined concepts in need of clear definitions, conscious models, and future attention.