Physiology of extracellular sodium; more complicated than than we have been supposing.

I have long despaired of Experts, many of professorial appellation, who  peddle the obviously oversimplified message that sodium is oedemagenic. In this post I’ll look at the growing body of work on tissue sodium, and we’ll see that plasma sodium concentration does not reflect the overall ECF sodium status. Reports on the distribution of sodium in the tissues go back more than 40 years. Helge Wiig in Bergen is now a leading expert in this field and is presenting us with amazing insights into the role of skin macrophages as regulators of total body water compartmentalisation.

Let’s start with a re-assessment of the basics. When sodium intake is greater than sodium requirement, there are consequences. The first three are obvious and well appreciated, but the realisation that there is a fourth important mechanism to deal with sodium excess needs dissemination.

  1. Sodium is excreted in urine and sweat.
  2. Sodium and water accumulate in the extracellular fluid while body water tonicity remains constant.
  3. Sodium accumulates in excess of water and tonicity increases.
  4. Sodium accumulates in excess of water with no change in body water tonicity – this is the concept of excess sodium storage. It is important to appreciate that the stored sodium is not all rendered osmotically inactive; some is compartmentalised away from the hypothalamically regulated portion of the total body water.

There are several mechanisms for excess sodium storage.

  • negative potassium balance helps to maintain total cation contribution to tonicity
  • negative balance of other cationic osmoles.
  • positive cation balance with excess osmotically-active sodium associating with interstitial glycosaminoglycans
  • positive cation balance with sodium rendered osmotically inactive by association with mineral matrix or perhaps with intracellular proteins.

The skin seems to be an important anatomic location for excess sodium storage, and mononuclear phagocytes are emerging as local on-site sensors of interstitial electrolyte concentration. Together with lymphatics, skin macrophages can be considered systemic regulators of body fluid volume. Let’s end with a quote from Bhave and Neilson (2011);

“… the interstitium plays a larger role in short term blood and interstitial volume adjustments. Short term Na+ storage and interstitial volume homeostasis may be relevant to transient or non-equilibrium phenomena such as blood pressure dipping, flash pulmonary edema, rapid blood loss, burns, and sepsis, to name a few. Future investigation will hopefully unify the molecular and structural biology of interstitial cell-matrix interactions with classic Starling physiology to identify new therapeutic targets for hemodynamic derangements.”

Useful Open Access resources on this topic include

Bhave & Neilson. J Am Soc Nephrol. 2011.

Nikpey, Karlsen, Rakova et al. Hypertension. 2017;69:660-668


By admin

after more than a quarter of a century of intensive care medicine consultancy in one of the UK's largest teaching hospitals Dr Woodcock is on a mission to ensure the steady state Starling principle is known and understood by every student and every practitioner.

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