The paradox of sodium's volume of distribution. Why an extracellular solute appears to distribute over total body water

When treating hyponatremia, one must know how sodium distributes in the body in order to calculate how much sodium is needed to raise the serum sodium concentration by a desired amount. Most clinicians recognize that while sodium is primarily restricted to the extracellular space it appears to distribute over total body water.1However, the reason for this seeming paradox is not self-evident. The standard explanation is that the osmotic effect of added sodium draws water out of cells into the extracellular space.2-5But is this the whole story? If so, one would predict that other solutes restricted to the extracellular space (eg, mannitol) would also appear to distribute over total body water. However, such is not the case. Therefore, it is our purpose to review why sodium appears to distribute over a different volume than the anatomic space in which it resides. We further show why solutes restricted