Case 29: Diagnosis & Conclusions

Case 29 Index

Diagnosis: Pseudohyponatremia

Case Summary: This patient’s low serum sodium concentration is actually pseudohyponatremia, most likely due to hypergammaglobulinemia in the setting of multiple myeloma.

Pseudohyponatremia is a laboratory phenomenon in which the serum sodium concentration is artifactually low due to an increase in the nonaqueous component of a serum or plasma sample. More about this laboratory artifact in a bit…but how did we come to the conclusion that this patient’s labs reveal pseudohyponatremia ?

The key is tonicity (a measure of only “effective osmoles” – more on this below)! Our cells, particularly the cells of our central nervous system, care about the movement of water between the extracellular and intracellular space. The majority of patients with true hyponatremia are hypotonic. Due to cerebral edema that occurs as a consequence of water shifting into cells, hypotonic hyponatremia can be symptomatic and life threatening. 

Hypotonicity can be usually assessed by measuring serum osmolality, which is characteristically low (less than 275 mOsm/kg) in true hyponatremia

Let’s take a moment to talk about tonicity and osmolality. They are NOT the same thing! Tonicity accounts for the total concentration of “non-freely penetrating solutes” or those that cannot cross a semi-permeable membrane – these solutes are also referred to as effective osmoles. Osmolality tells us about the total concentration of those solutes that can freely cross this membrane (“ineffective osmoles”)  AND effective osmoles. So, osmolality may be normal or high and co-exist with hypotonicity if there are high levels of ineffective osmoles such as high urea concentrations or alcohol ingestions.

While a quick trick to estimating serum osmolality is “serum sodium x 2,”  it is crucial in certain clinical scenarios to calculate the serum osmolality.

Calculated serum osmolality (click!) =
(2 x [Serum Na meq/L]) + (Glucose mg/dL ÷ 18) + (BUN  mg/dL÷ 2.8) + (Ethanol mg/dL ÷ 3.7)

Iso-osmolality or hyperosmolality does not always mean pseudohyponatremia, as there may be an additional solute (effective or ineffective osmoles) in the extracellular compartment. In a patient such as ours, however, the serum osmolality is normal in the absence of additional solutes such as very high urea, glucose, alcohol, or mannitol – suggesting hyponatremia without hypotonicity.

In the absence of hypotonicity, we should go on the hunt for other effective osmoles.
Here are a few etiologies of hypertonic or isotonic hyponatremia:
Hyperglycemia (elevated glucose, which can be accounted for by manipulating the above equation)
Hypertonic solutions (mannitol, sorbitol, glycine, IV contrast)

Hmm, our patient is not hyperglycemic, and he has not received any hypertonic solutions (but be on the lookout for substances like IV immune globulin therapy, which is usually constituted in hypertonic solution).

Now it’s time to look back at a possible laboratory artifact. Significant hyperlipidemia or paraproteinemia can impact chemistry analyzers that are affected by dilution. High levels of lipids or proteins decrease the percentage of water in a given volume of plasma. If the sodium concentration is measured per volume of plasma (as done with an indirect ion selective electrode), the result will be a lower serum sodium concentration.

In the graphic below, note the increase in the plasma volume on the right and thus decrease in the overall concentration of sodium. 


So, what’s the next step? Time to discuss with your trusty colleagues in the chemistry laboratory! If the patient’s serum sodium can be assessed using a direct ion-selective electrode test (not affected by dilution), we can obtain an accurate result. Often a point of care blood gas analyzer does the trick, but it is important to confirm your institution’s specific laboratory equipment.

This patient’s pseudohyponatremia is most likely a result of paraproteinemia from hypergammaglobulinemia in the setting of his multiple myeloma. Albeit rare, pseudohyponatremia is an important entity to recognize, especially before reaching for the hypertonic saline!

Check out our summary infographic below:

Case 29 Index
Case 29 Introduction
Case 29 Physical Exam
Case 29 Diagnostic Testing