Chapter 3 – “Pseudohyponatremia”
Welcome to the third installment of “Inconceivable: medical terms that don’t mean what you think they mean.” For an introduction to this series, check out Chapter 1.
You have a patient with IDDM managed with an insulin pump that malfunctioned overnight. She presents with signs and symptoms of DKA. You’ve already started IV hydration when her labs result with a chemistry reported as:
Na 131, K 4.9, Cl 97, Bicarb 10, BUN 70, Cr 1.7, Glc 515
You call the ICU and in your report you mention that the patient has a “pseudohyponatremia.” In fact, your patient has a true hyponatremia.
The markedly decreased plasma sodium in severe hyperglycemia is a result of the osmotic effects of the excess glucose. The increased glucose causes increased plasma water thus diluting the plasma sodium, resulting in a dilutional but true hyponatremia. Fortunately, this is clinically insignificant because it does not cause a severely HYPOosmolar state as other causes of true hyponatremia do (e.g SIADH, beer podomania, etc.) In fact, most patients with elevated glucose are HYPERosmolar, and a similar phenomenon happens iatrogenically in patients receiving mannitol or IVIG.
Pseudohyponatremia, refers to a lab abnormality caused by decreased water content of the serum – most commonly because of elevated lipids (e.g. familial hypertriglyceridemia) or proteins (e.g. multiple myeloma). Why does this error happen? To answer that, we need to understand how the lab measures electrolytes. While this isn’t as exciting as reducing a nursemaid’s or shocking V-tach, it’s actually kind of cool. Hey, even Drake gets fired up about electrolytes!
The vast majority of hospital and outpatient labs use indirect ion-specific electrodes (ISE). Indirect ISE’s require a diluted serum sample and also assume that the diluted serum being run is 100% water. In reality, normal serum is about 93% water and 7% solid – primarily lipids and proteins. Keep in mind we are talking serum here, not whole blood, the cells have already been spun out. When the patient’s sample has an increased percentage of the solid component, there is less water for the sodium ions. Therefore for any given sodium concentration, there will be fewer total sodium ions in the sample, and the machine will give a falsely low serum sodium level. To make matters worse, this effect is magnified because of the pre-test sample dilution. Interestingly, ABG/VBG machines and many of the point of care chemistry machines (e.g. i-STAT) use direct ion-specific electrodes and are not prone to this type of error.1
Now, while the true hyponatremia associated with hyperglycemia is typically not clinically significant and will resolve once the glucose normalizes, the astute clinician should still perform a correction to determine if there is an underlying sodium problem present. Classically, the correction used to estimate the degree of osmotic shift is as follows: 2
Na = (Glucose – 100) x 0.016 + measured Na
Or in other words, add 1.6 mEq/L to the reported sodium for every 100 mg/dl of glucose over 100.
This was based on a study from 1973, but a more recent paper reported a correction of 2.4 mEq/L more accurately corrects the sodium.3 They also found that the glucose-sodium relationship probably isn’t linear. In real life, for the vast majority of patients either 2.4 or 1.6 is adequate for your estimation.
- Fortgens P, Pillay TS. Pseudohyponatremia revisited: a modern-day pitfall. Arch Pathol Lab Med. 2011 Apr;135(4):516-9.
- Katz MA. Hyperglycemia-induced hyponatremia–calculation of expected serum sodium depression. N Engl J Med. 1973 Oct 18;289(16):843-4.
- Hillier TA, Abbott RD, Barrett EJ. Hyponatremia: evaluating the correction factor for hyperglycemia. Am J Med. 1999 Apr;106(4):399-403.