Clinical Review

Disorders of sodium balance

BMJ 2006; 332 doi: http://dx.doi.org/10.1136/bmj.332.7543.702 (Published 23 March 2006) Cite this as: BMJ 2006;332:702
  1. Rebecca M Reynolds, senior lecturer in endocrinology and diabetes1,
  2. Paul L Padfield, consultant physician2,
  3. Jonathan R Seckl, Moncrieff-Arnott professor of molecular medicine (j.seckl@ed.ac.uk)1
  1. 1 Endocrinology Unit, Centre for Cardiovascular Sciences, University of Edinburgh, Queen's Medical Research Institute, Edinburgh EH16 4TJ
  2. 2 Metabolic Unit, Western General Hospital, Edinburgh EH4 2XU
  1. Correspondence to: J R Seckl
  • Accepted 20 February 2006

Introduction

Disorders of plasma sodium are the most common electrolyte disturbances in clinical medicine, yet they remain poorly understood. Severe hyponatraemia and hypernatraemia are associated with considerable morbidity and mortality,13 however, and even mild hyponatraemia is associated with worse outcomes when it complicates conditions such as heart failure,4 although which is cause and which effect is often uncertain. Distinguishing the cause(s) of hyponatraemia may be challenging in clinical practice, and controversies surrounding its management remain. Here, we describe the common causes of disorders of plasma sodium, offer guides to their investigation and management, and highlight areas of recent advance and of uncertainty.

Sources and selection criteria

We incorporated the latest consensus from systematic reviews and publications identified by a literature search through Medline and Web of Science with the search strategy terms “hyponatraemia,” “hypernatraemia,” and “sodium.” We found fewer than a dozen randomised controlled trials of treatment of any description. Despite their frequency, plasma sodium disorders have not been reviewed by the Cochrane Library, Clinical Evidence, or Best Evidence.

Control of sodium balance

Under normal conditions, plasma sodium concentrations are finely maintained within the narrow range of 135-145 mmol/l despite great variations in water and salt intake. Sodium and its accompanying anions, principally chloride and bicarbonate, account for 86% of the extracellular fluid osmolality, which is normally 285-295 mosm/kg and calculated as (2× [Na]mmol/l + [urea]mmol.l + [glucose]mmol/l. The main determinant of the plasma sodium concentration is the plasma water content, itself determined by water intake (thirst or habit), “insensible” losses (such as metabolic water, sweat), and urinary dilution. The last of these is under most circumstances the most important and is predominantly determined by arginine vasopressin, which is synthesised in the hypothalamus and then stored in and released from the posterior pituitary. In response to arginine vasopressin, concentrated urine is produced by water reabsorption …

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