Pseudohyponatremia: does it matter in current clinical practice?

Abstract

Serum consists of water (93% of serum volume) and nonaqueous components, mainly lipids and proteins (7% of serum volume). Sodium is restricted to serum water. In states of hyperproteinemia or hyperlipidemia, there is an increased mass of the nonaqueous components of serum and a concomitant decrease in the proportion of serum composed of water. Thus, pseudohyponatremia results because the flame photometry method measures sodium concentration in whole plasma. A sodium-selective electrode gives the true, physiologically pertinent sodium concentration because it measures sodium activity in serum water. Whereas the serum sample is diluted in indirect potentiometry, the sample is not diluted in direct potentiometry. Because only direct reading gives an accurate concentration, we suspect that indirect potentiometry which many hospital laboratories are now using may mislead us to confusion in interpreting the serum sodium data. However, it seems that indirect potentiometry very rarely gives us discernibly low serum sodium levels in cases with hyperproteinemia and hyperlipidemia. As long as small margins of errors are kept in mind of clinicians when serum sodium is measured from the patients with hyperproteinemia or hyperlipidemia, the present methods for measuring sodium concentration in serum by indirect sodium-selective electrode potentiometry could be maintained in the clinical practice.

Keywords: Hyperlipidemia; Hyperproteinemia; Intravenous immunoglobulin; Potentiometry; Pseudohyponatremia; Sodium-selective electrode.

Fig. 1

Serum chemistries and osmolality pre- and post-IVIG infusion. Serum sodium and calculated osmolality significantly decreased and serum protein and viscosity significantly decreased 24 hr after the completion of IVIG therapy. From Reference 10.

Fig. 2

Schematic representation of undiluted and diluted sampling techniques used by direct potentiometry and indirect potentiometry or flame photometry methods. From Reference 19.

Fig. 3

Predicted Influence of water content on sodium measurements for 100 mmol/L NaCI solution. From Reference 19.

Fig. 4

Psesudohyponatremia from non-aqueous plasma volume. The use of ion-selective electrodes that measure Na⁺ activity theoretically rids the entity of pseudohyponatraemia from non-aqueous volumes in the plasma if the plasma is never diluted. However, automated aspirator/dilutors perpetuate this problem. The top panel depicts the situation in normal plasma. A 10×dilution of plasma with water dilutes [Na⁺] to 14 mEq/L and the back-calculation with a factor of 10 recapitulates the original plasma [Na⁺] of 140 mEq/L. The bottom panel depicts plasma with normal [Na⁺] of 140 but an excessive non-aqueous space. The aspirator will take an erroneously smaller amount of aqueous plasma and dilute it 10×with water, yielding a final [Na⁺] of 11.2 mEq/L. Back calculation with the same dilution factor gives a plasma [Na⁺] of 112 mEq/L. From Reference 21.