Which physiologic states with low serum sodium levels are not hyponatremic?

Updated: Aug 24, 2020
  • Author: Kartik Shah, MD; Chief Editor: Romesh Khardori, MD, PhD, FACP  more...
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In addition to sampling and analysis errors, several physiologic states exist in which correct laboratory analysis yields low serum sodium levels, but these levels do not reflect a true hyposmolar state.

The most common example is serum hyperglycemia. Accumulation of extracellular glucose induces a shift of free water from the intracellular space to the extracellular space. Serum sodium concentration is diluted by a factor of 1.6 mEq/L for each 100 mg/dL increase above normal serum glucose concentration. Systemic osmolarity is normal or even increased, not decreased, as in true (ie, hyposmolar) hyponatremia. This hypertonic hyponatremia has no physiologic significance, and serum sodium concentration corrects as normoglycemia is reestablished.

A similar phenomenon is observed in patients treated with glycerol or mannitol in an effort to control acute glaucoma or intracranial hypertension. This phenomenon is also seen in patients with advanced renal disease who receive radiocontrast agents for diagnostic testing.

Hyponatremia may be noted in patients whose serum contains unusually large quantities of protein or lipid. In these patients, an expanded plasma protein or lipid fraction leads to a decrease in the plasma water fraction in which sodium is dissolved. Laboratory techniques that measure absolute sodium content per unit of plasma water report low sodium levels despite the fact that the concentration of sodium in serum water remains within the normal range. This phenomenon, known as pseudohyponatremia, occurs when flame emission spectrophotometry or indirect potentiometry is used to assay serum sodium levels rather than direct potentiometry techniques. This occurs in approximately 60% of US laboratories.

Serum osmolarity remains undisturbed, and attempts at correcting serum sodium level are not indicated. Hyperlipidemia that is severe enough to produce pseudohyponatremia almost always is accompanied by a notably lipemic appearance of the serum sample. Hyperproteinemia of sufficient magnitude to induce pseudohyponatremia commonly is due to coexisting multiple myeloma.

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