A theoretical and experimental study of ionic shifts induced by K depletion and replacement

This study of potassium replacement in induced hypokalemia uses a theoretical model of electrolyte distribution, in conjunction with detailed animal laboratory experiments, to clarify electrolyte changes during K depletion and K replacement. A steady-state model of the electrolyte distribution among the rapidly-exchanging body compartments was designed to simulate animal protocols that compare KCl and KHCO 3 repletion. The potassium depleted, nephrectomized animals maintained at constant pH show that KHCO 3, compared to KCl, repletion results in lower extracellular K + concentration both during infusion and at steady-state, and increased steady-state intracellular Na + concentration. The theoretical model is consistent with this finding and, moreover, it predicts that the phosphate anion will yield results intermediate between KCl and KHCO 3, a prediction yet to be experimentally verified. This paper is concerned with the mechanisms involved. It is known that the alkalinizing effect of the bicarbonate ion promotes cellular H +K + exchange and hence K + uptake. In addition to this exchange, the theoretical work shows the detailed difference due to buffering of HCO 3 − as compared to Cl − and a consequent considerable difference in anion (and therefore cation) distribution among compartments, a difference referred to as a “specific anion effect”. Finally, the best simulation of K depletion and subsequent repletion states were obtained by a 5·5% reduction of electrochemical Na gradient and its restoration to normal levels by KCl but not by KHCO 3 administration. These adjustments which are supported by data in the literature and by our own experimental findings show the potential usefulness of mathematical models in the elucidation of physiological mechanisms involved in disease states.