Can Changes in the Plasma Sodium Concentration Be Predicted Based on the Mass Balance of Sodium, Potassium, and Water in the Face of Osmotically Inactive Sodium Storage?

<b><i>Context:</i></b> Alterations in the plasma sodium concentration ([Na⁺]_p) is predicted based on changes in the mass balance of Na⁺, K⁺, and H₂O. However, it is well appreciated that Na⁺ retention results in both osmotically active and osmotically inactive Na⁺ storage and that only osmotically active Na⁺ contributes to the modulation of the [Na⁺]_p^. <b><i>Subject of Review:</i></b> Recent clinical studies suggested that prediction of changes in the [Na⁺]_p based on the mass balance of Na⁺, K⁺, and H₂O is inaccurate since the osmotically inactive Na⁺ storage pool is dynamically regulated. In contrast, animal studies demonstrated that changes in the [Na⁺]_p can be predicted if the total body Na⁺, K⁺, and H₂O were to be accurately accounted for. <b><i>Second Opinion:</i></b> Our analysis demonstrated that alterations in the [Na⁺]_p are predictable at the total body level if all sources of input and output of Na⁺, K⁺, and H₂O can be accurately accounted for despite the paradoxical finding that there are changes in the osmotically inactive Na⁺ storage pool at the tissue level. However, future prospective clinical studies are needed to corroborate the findings in the animal studies. We proposed that the fundamental question as to whether changes in the [Na⁺]_p can be predicted in the face of osmotically inactive sodium storage is best addressed by serial measurements of total body exchangeable Na⁺ and K⁺ and total body water by isotope dilution at different time intervals.