What pre-analytical factor most commonly causes pseudohyponatremia?

• A. Hyperlipidemia or hyperproteinemia
• B. Hemolysis
• C. Dehydration
• D. Hypoalbuminemia

Answer: (A)

Pseudohyponatremia arises from how some sodium measurements interpret the sample when there is a lot of non-water solids in plasma. In indirect ion-selective electrode methods, the serum is diluted and the assay assumes a constant plasma water fraction. If the serum has an unusually high amount of lipids (hyperlipidemia) or proteins (hyperproteinemia), the fraction of plasma that is water decreases. Since sodium resides in the aqueous phase, the dilution-based calculation ends up reporting a lower sodium concentration per liter of whole plasma than is actually present in the water portion, giving a falsely low value. The sodium in the water component may be normal; it’s the reduced water fraction that creates the artifact, making hyperlipidemia or hyperproteinemia the most common pre-analytical culprits.

If a direct measurement method is used, which analyzes undiluted plasma, this artifact does not occur, because it does not rely on the diluted aqueous fraction. Hemolysis, dehydration, or hypoalbuminemia don’t produce this specific artifact in the same way, and thus don’t explain the pseudohyponatremia phenomenon.