Severe Hyponatremia in a Lipemic Serum Sample
A 62-year-old man with type 2 diabetes and poorly controlled hypertriglyceridemia has routine chemistry drawn in the morning. The serum is visibly lactescent (lipemia 4+, triglycerides 2,650 mg/dL). Results from the main analyzer (indirect ion-selective electrode, diluted sample): sodium 119 mmol/L, potassium 4.1, chloride 96, bicarbonate 25, glucose 92, BUN 14, creatinine 1.1 mg/dL. Measured osmolality by freezing-point depression is 288 mOsm/kg. The patient is fully alert and oriented, with no seizures, confusion, or focal deficits, and takes no diuretics. The night nurse pages the on-call resident because the sodium is 119 mmol/L, asking whether to start a rapid response and hypertonic saline.
1. Explain the discrepancy between the sodium result and the measured osmolality. What is the diagnosis?
Read the worked answer
This is pseudohyponatremia. The indirect ISE measures sodium in the diluted, protein/lipid-containing sample and reports it per unit of total volume. When the nonaqueous (lipid) fraction of plasma is markedly expanded, the aqueous fraction per unit volume falls, and the reported sodium is falsely low even though the sodium concentration in plasma water is normal.
Key supporting evidence.
- Measured osmolality is 288 mOsm/kg - normal. True hypotonic hyponatremia of 119 mmol/L would produce a measured osmolality near 250–260 mOsm/kg, and this patient would be symptomatic.
- The patient is asymptomatic and has no neurologic findings.
- Triglycerides of 2,650 mg/dL is exactly the magnitude of lipemia required to shift the aqueous fraction meaningfully.
- Calculating an osmolal gap from the reported sodium gives a spuriously positive gap; the gap is an artifact of the falsely low sodium, not evidence of an unmeasured osmole.
Hyperproteinemia (e.g., multiple myeloma, large-volume IVIG) produces the identical artifact, and the same mechanism can cause pseudohypernatremia when the aqueous fraction is contracted.
2. What do you do before any result is acted on, and what do you report?
Read the worked answer
Confirm with a direct (undiluted) ISE. Run the sample on the blood gas analyzer or another direct ISE platform, which measures sodium activity in whole blood/plasma water without dilution. A result near 138–140 mmol/L confirms pseudohyponatremia.
Reporting and communication.
- Report the corrected sodium with a comment stating that the result is affected by marked lipemia and that the indirect ISE value is falsely low; state the method used for the corrected value.
- Telephone the resident immediately - the purpose of the call is to prevent hypertonic saline, which would be harmful here. Document who was notified and when.
- Recommend that future specimens from this patient be analyzed by direct ISE, or after ultracentrifugation, if the local platform permits.
- Remind the clinical team that other analytes measured by dilution-dependent techniques in the same sample may shift modestly; interpret with the lipemic index in mind.
No treatment for hyponatremia is indicated. The real clinical problem is severe hypertriglyceridemia, which should be addressed on its own merits.
3. A second patient with a sodium of 119 mmol/L has a measured osmolality of 254 mOsm/kg and is confused. How does your interpretation differ?
Read the worked answer
This is true hypotonic hyponatremia and is a medical emergency. A measured osmolality of 254 mOsm/kg is consistent with, and confirms, a genuinely low sodium in plasma water; the patient is symptomatic (confusion), which is the indication most predictive of seizures and herniation.
How the reasoning differs from the first case:
- In pseudohyponatremia the measured osmolality is normal and the patient is asymptomatic; the lab's job is to prevent treatment.
- In true hypotonic hyponatremia the measured osmolality is low and symptoms correlate with the degree and rapidity of the fall; the lab's job is to report rapidly and accurately so treatment is not delayed.
- Compare the osmolal gap: a gap that remains positive after correcting the sodium (e.g., with normal sodium but high measured osmolality) points to an unmeasured osmole such as mannitol, ethanol, isopropanol, or ethylene glycol, or to hyperglycemia - a different differential from both cases above.
- Verify that the sample is not contaminated by IV fluid (draw downstream of a saline line) before the result drives hypertonic saline therapy.