Pseudohyponatremia is a laboratory artifact related to which measurement method?

• A. Direct ISE
• B. Indirect ISE
• C. In vivo hemolysis
• D. Hyperlipidemia

Answer: (B)

Pseudohyponatremia arises from how indirect ion-selective electrode measurements handle plasma water. Indirect ISE dilutes the serum and then measures sodium in the diluted sample, assuming a constant fraction of plasma that is water. In samples with excess solids—such as high lipids (hyperlipidemia) or high proteins (hyperproteinemia)—the solid phase takes up more of the plasma volume, reducing the actual water fraction. Because the sodium concentration is reported based on the diluted plasma, the result reflects sodium per liter of plasma rather than per liter of water, making it appear falsely low. This artifact does not occur with direct ISE, which analyzes an undiluted sample and measures sodium in the plasma water itself, so changes in the solid fraction don’t bias the result. In vivo hemolysis isn’t a measurement-method artifact for this chloride; it mainly affects other analytes like potassium. Hyperlipidemia contributes to the artifact when indirect ISE is used, but not when direct ISE is used.