Pseudohyponatremia: Mechanism, Diagnosis, Clinical Associations and Management

Abstract

Pseudohyponatremia remains a problem for clinical laboratories. In this study, we analyzed the mechanisms, diagnosis, clinical consequences, and conditions associated with pseudohyponatremia, and future developments for its elimination. The two methods involved assess the serum sodium concentration ([Na]_S) using sodium ion-specific electrodes: (a) a direct ion-specific electrode (ISE), and (b) an indirect ISE. A direct ISE does not require dilution of a sample prior to its measurement, whereas an indirect ISE needs pre-measurement sample dilution. [Na]_S measurements using an indirect ISE are influenced by abnormal concentrations of serum proteins or lipids. Pseudohyponatremia occurs when the [Na]_S is measured with an indirect ISE and the serum solid content concentrations are elevated, resulting in reciprocal depressions in serum water and [Na]_S values. Pseudonormonatremia or pseudohypernatremia are encountered in hypoproteinemic patients who have a decreased plasma solids content. Three mechanisms are responsible for pseudohyponatremia: (a) a reduction in the [Na]_S due to lower serum water and sodium concentrations, the electrolyte exclusion effect; (b) an increase in the measured sample's water concentration post-dilution to a greater extent when compared to normal serum, lowering the [Na] in this sample; (c) when serum hyperviscosity reduces serum delivery to the device that apportions serum and diluent. Patients with pseudohyponatremia and a normal [Na]_S do not develop water movement across cell membranes and clinical manifestations of hypotonic hyponatremia. Pseudohyponatremia does not require treatment to address the [Na]_S, making any inadvertent correction treatment potentially detrimental.

Keywords: dilution effect; electrolyte exclusion effect; hyperviscosity; hyponatremia; pseudohypernatremia; pseudohyponatremia; pseudonormonatremia; serum lipids; serum proteins; serum sodium concentration; serum solids content; serum water sodium concentration.

Figure 1

Diagnosis of pseudohyponatremia and accompanying dysnatremias. Osmol gaps that are calculated using the direct instead of the indirect [Na]_S value and are still enlarged indicate the presence in serum of a solute other than sodium salts, glucose, or urea. [Na]_S values < 135 mmol/L reported by direct ISE result from either hypotonic or hypertonic hyponatremia. Hyperglycemic states by far represent the most frequent cause of hypertonic hyponatremia. * Hypertonic hyponatremia masked by a mechanism causing hypernatremia, e.g., osmotic diuresis caused by hyperglycemia.