Low Sodium in a Grossly Lipemic Sample
A 62-year-old man has routine fasting blood work. The serum is grossly lactescent. Results: sodium 119 mmol/L (indirect ion-selective electrode), potassium 4.2 mmol/L, chloride 90 mmol/L, bicarbonate 25 mmol/L, glucose 95 mg/dL, BUN 14 mg/dL, creatinine 0.9 mg/dL, total protein 7.2 g/dL, cholesterol 380 mg/dL, triglycerides 2600 mg/dL. Measured serum osmolality is 289 mOsm/kg. The patient is asymptomatic, with no edema, normal mental status, and no history of diuretic use. The clinician calls asking whether to start hypertonic saline.
1. Is this true hyponatremia? Show the reasoning and calculations.
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Probably not. The calculated osmolality is:
2(119) + 95/18 + 14/2.8 = 238 + 5.3 + 5.0 ≈ 248 mOsm/kg
Measured osmolality is 289 mOsm/kg, so measured minus calculated is about 41. In true hypo-osmolar hyponatremia, measured and calculated osmolality should agree. Here the measured osmolality is normal, which is the signature of pseudohyponatremia.
The mechanism: the indirect ion-selective electrode dilutes the sample before measurement. In severe hypertriglyceridemia, lipid occupies a large fraction of plasma volume, so the aqueous fraction per unit volume is reduced and sodium is falsely low. Total protein is normal, making hyperproteinemia a less likely cause. The normal measured osmolality and asymptomatic patient argue strongly against true hyponatremia.
2. What test confirms the diagnosis, and how should the result be reported?
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Direct ion-selective electrode (undiluted sample, as on a blood gas analyzer) measures sodium in the aqueous phase and will give the true value. Alternatively, the laboratory can clarify the sample (ultracentrifugation or lipid extraction) and reanalyze, or check for a discrepancy between indirect and direct methods.
Reporting:
- Report the direct ISE sodium as the clinically valid value, or report the indirect result with a clear comment that it is falsely low due to lipemia.
- Do not start hypertonic saline for a pseudohyponatremia; treating a normal serum sodium with 3% saline risks hypernatremia.
- Note that the calculated osmolal gap is artifactual here and should not be interpreted as an osmolar gap from toxins.
- Recommend fasting lipid evaluation and follow-up of the hypertriglyceridemia.
3. Suppose the measured osmolality had been 250 mOsm/kg instead of 289. How would your interpretation change?
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With measured osmolality 250 and calculated ~248, the values agree and there is no osmolal gap. That pattern indicates true hypo-osmolar hyponatremia, not pseudohyponatremia.
The evaluation would then focus on volume status and urine studies:
- Assess for hypovolemia, euvolemia (SIADH), or hypervolemia.
- Check urine osmolality and urine sodium; in SIADH, urine osmolality is inappropriately high and urine sodium is typically >30 mmol/L with euvolemia.
- Review medications (thiazides, SSRIs, carbamazepine) and thyroid/adrenal status.
- Treat according to symptoms and chronicity, with cautious correction to avoid osmotic demyelination.
The key lesson: always compare measured and calculated osmolality before treating a low sodium.