Pseudohyponatraemia: lipid and protein artefact
Pseudohyponatraemia is a laboratory artefact (a false result produced by the testing method): methods that dilute the sample report a falsely low sodium when lipid or protein is markedly raised.
Remember
In a well patient with very high lipids or protein, a low sodium with a normal measured osmolality (the concentration of dissolved particles in the blood) is probably pseudohyponatraemia. Recheck the sodium with a direct ion-selective electrode (a sensor that responds to sodium ions) before treating anything.
Memory aid
picture a litre of plasma as a jug part-filled with stones
The jug holds less water and less dissolved sodium, but the water itself is just as salty as before, just as the plasma water keeps its normal sodium concentration.
Plasma contains more than water: it also contains lipid and protein. An indirect ion-selective electrode method (a sensor that responds to sodium ions, used after the sample is diluted) reports sodium per litre of whole plasma, fat and protein included.
When the lipid or protein fraction is markedly raised, as in severe hypertriglyceridaemia (very high blood fats) or in multiple myeloma (a cancer of plasma cells) with its abnormal antibody called a paraprotein, these components take up room in the sample. The measured volume then holds less water and therefore fewer sodium ions, so the reported sodium falls. The sodium concentration in the plasma water is unchanged.
Because the plasma water is normal, the plasma osmolality stays normal and the patient is usually well. The clue is a low reported sodium with a normal measured osmolality, no symptoms and no usual cause of hyponatraemia (a true fall in the sodium in the blood).
To settle it, repeat the sodium with a direct ion-selective electrode, which measures undiluted plasma or whole blood, for example on a blood gas analyser (a machine with this kind of electrode built in). That avoids the problem. The sodium itself is not treated; the lipid or protein abnormality is managed separately.
Key facts
- Cause
- A raised lipid or protein fraction takes up room in the sample, so an indirect method sees less plasma water and under-reads the sodium.
- Enlarged fraction
- Severe hypertriglyceridaemia (very high blood fats) or paraproteinaemia (an abnormal protein, such as the antibody produced in myeloma) enlarges the fat or protein fraction.
- Osmolality
- The measured plasma osmolality stays normal, because the sodium concentration in the plasma water is unchanged.
- Patient
- The patient is usually well, with no symptoms and no usual cause for a low sodium.
- Confirm
- Repeat the sodium with a direct ion-selective electrode on undiluted plasma or whole blood, for example on a blood gas analyser.
- Management
- The sodium is not treated; the underlying lipid or protein abnormality is managed separately.
Exam traps
- Water retention from the syndrome of inappropriate antidiuretic hormone secretion (SIADH), where the kidneys keep water they should excrete, does not fit a low sodium with a normal osmolality, because it dilutes the blood and lowers the plasma osmolality.
- Water pulled out of cells by raised glucose (hyperglycaemia) dilutes the sodium, but it raises the osmolality, so it does not fit a low sodium with a normal osmolality.
- A direct ion-selective electrode is not fooled by raised lipid or protein, because it measures undiluted samples; it is the indirect methods, which dilute the sample, that under-read the sodium.
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