Pseudohyponatremia Definition and Causes
Pseudohyponatremia is not true hyponatremia but a false result of the measurement of blood sodium levels usually caused by 1:
- Hyperlipidemia (hypertriglyceridemia, hypercholesterolemia 7)
- Hyperproteinemia (for example, in multiple myeloma 8 or intravenous infusion of immunoglobulins)
- Radiocontrast used in chronic renal insufficient patients.
- Dextran used in treatment of hypovolemic shock
Pseudohyponatremia is not a medical condition, has no symptoms and requires no treatment.
True hyponatremia means the decrease of sodium levels in the aqueous phase of the blood serum.
Pseudohyponatremia is a false result of certain older tests (flame-emission spectrophotometry and indirect potentiometry I-ISE) that measure sodium levels in the whole serum (aqueous and nonaqueous phase). When the volume of the nonaqueous phase of the serum increases due to severely increased lipid or protein levels or radiocontrast substances or dextran, these tests show hyponatremia, but this is only pseudohyponatremia, because the sodium levels in the aqueous phase of the serum remain unchanged 1,3. Newer tests that use direct potentiometry with ion-specific Na+ electrodes (D-ISE), which measure sodium only in the aqueous part of the serum are not affected by hyperlipidemia or hyperproteinemia 1,3.
Correction Formula for Pseudohyponatremia in Hypertriglyceridemia and Hyperlipidemia
Plasma triglycerides (g/L) x 0.002 = mEq/L decrease in Na+
Plasma proteins – 8 (g/L) x 0.025 = mEq/L decrease in Na+
Other Typical Changes Associated With Pseudohyponatremia
Increased blood lipids or proteins result not only in pseudohyponatremia but also in false low levels of potassium (pseudohypokalemia), uric acid and blood urea nitrogen (BUN).
The proliferation of the blood cells: leukocytosis, thrombocytosis, polycythemia vera is not associated with pseudohyponatremia.
Hyperglycemia, Diabetic Ketoacidosis (DKA) and Hyponatremia
The term pseudohyponatremia is often erroneously used for hyponatremia caused by hyperglycemia, which increases the blood osmolality what results in the movement of water from the cells into the blood and therefore in dilutional hyponatremia, which is true hypertonic hypervolemic hyponatremia.
Hyponatremia Correction Calculation in Hyperglycemia
Hyponatremia due to hyperglycemia usually has no significant effect on an individual because it is not associated with hypoosmolality, so it can be neglected. However, hyponatremia by causes other than hyperglycemia can be present: this is likely if hyponatremia is greater than expected from the extent of hyperglycemia. To calculate the effect of hyperglycemia on hyponatremia the following formula is usually recommended:
- For every increase of blood glucose levels by 100 mg/dL above the normal glucose levels, the measured sodium levels decrease by 1.6 mmol/L 2 or, according to one study, by 2.4 mmol/L.
- However, at glucose levels >400 mg/dL), every further increase of glucose by 100 mg/dL can decrease the measured sodium levels by 4 mmol/L 4.
Example: The actual sodium level in someone who has a measured sodium level 130 mmol/L and glucose level 500 mg/dL (and assuming the normal glucose level is 100 mg/dL) would be:
- 130 + (3 x 1.6) + 4 = 139 mmol/L (Or, use this calculator.)
In untreated diabetes mellitus, hyperglycemia is often associated with ketoacidosis, which can result in glycosuria and ketonuria (loss of glucose and ketones with urine), which can aggravate (true) hyponatremia 6 and with hyperlipidemia, which can cause pseudohyponatremia 5.
Other substances that can cause hyponatremia the same way as glucose:
- Sucrose or maltose (in intravenous IgG preparations)
- Mannitol or glycine in solutions used for irrigation in urologic or gynecologic investigations.
- Reference 1,2
One should suspect pseudohyponatremia, when the blood sodium levels are low in the presence of normal blood osmolality.
- Pseudohyponatremia definition, mechanism (Archivesofpathology.org)
- Hyperlipidemia, hyperproteinemia, hyperglycemia and pseudohyponatremia (Emedicine)
- How different tests affect blood serum sodium levels (ajprenal.physiology.org)
- Correction of hyponatremia in hyperglycemia (PubMed)
- Hyperglycemic hyperosmolar syndrome (Diabetesjournals)
- RW Shrier, Renal and electrolyte disorders, p.30
- Hypercholesterolemia (ResearchGate)
- Vaswani SK et al, 1993, Pseudohyponatremia in multiple myeloma PubMed