Much Ado about N…atrium: modelling tissue sodium as a highly sensitive marker of subclinical and localized oedema

Hypertonic Na⁺ accumulation in peripheral tissues is a recently described phenomenon: it has been associated with ageing, hypertension, diabetes, chronic kidney disease and heart failure, but its clinical meaning has yet to be determined. This concept conflicts with the classic physiological paradigm of constant balance between salt intake and excretion, and its water-independent nature is still a matter of debate.We developed a theoretical model explaining changes in the chemical composition of tissues as a function of extracellular volume fraction and excess extracellular fluid, i.e. oedema. The model suggests that the proportional increase in absolute Na⁺ content and concentration due to different degrees of oedema is higher than the parallel increase in water content, thus making Na⁺ a more sensitive index to detect this oedema.Our model would explain some of the recent findings of high tissue Na⁺ content in pathological conditions. More importantly, it prompts the reappraisal of tissue Na⁺ analysis from being a topic of niche interest to a potential diagnostic tool with broad applicability in the investigation of subclinical systemic and localized oedema.