At variance with the classic physiology concept of constant balance between salt intake and excretion, hypertonic Na + accumulation has been shown to occur in peripheral tissues, particularly in the skin. In humans, higher 23 Na MR signal from skin and skeletal muscle has been associated with aging, hypertension, CKD and diabetes.In a rodent model of aging and hypertension, we recently identified an increase in absolute Na + content and concentration in the myocardium, but paralleled by water accrual and an associated decrease in K + , thus pointing to an overall isotonic accumulation. To further investigate the phenomenon, we developed a mathematical model for expected chemical composition of tissues, as a function of extracellular volume fraction (ECV%) and the amount of fluid isotonic to the extracellular space added to the system (i.e. edema; fig, closed circles ).Total Na + concentration is higher in tissues with larger ECV%; the opposite occurs relative to K + ( fig A, open symbols ). The proportional increase in Na + concentration due to different degrees of edema is higher than the increase in water content in tissues where ECV% is < 45% (3-4 times higher for skeletal muscle and myocardium, where ECV% is 18-30%; fig B, black ). When absolute Na + content is assessed, similarly to 23 Na MR signal analysis, the proportionally higher increase occurs across the whole spectrum of ECV% ( fig B, red ).We conclude that Na + is more sensitive than water to detect edema. This could justify some of the recent evidence of high tissue Na + content in multiple conditions, including hypertension, CKD and diabetes, and holds the broad potential for early diagnosis of subclinical congestion and localised edema.