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, [1][2][3] 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 criteriaWe 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 balanceUnder 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 across the renal collecting ducts. This is mediated by specialised cellular membrane transport proteins called aquaporins.
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HyponatraemiaDetermining the cause of hyponatraemia may be straightforward if an obvious precipitating cause is present-for example, in the setting of vomiting or diarrhoea, when both sodium and total body water are low, and especially if the patient (typically elderly) is taking diuretics. In hospital practice, diagnosing the cause is often less clear cut. Here, hyponatraemia almost always reflects an excess of water relative to sodium, commonly by dilution of total body sodium secondary to increases in total body water (water overload) and sometimes as a result of depletion of total body sodium in excess of concurrent body water losses. The clinical classification of hyponatraemia according to the patient's extracellular fluid volume status, as hypovola...
