# Question 20.4

The following biochemical profile is from a 65-year-old male who has been admitted to your Intensive Care Unit with a diagnosis of pancreatitis of unknown aetiology.

 Parameter Patient Value Normal Adult Range Sodium 124 mmol/L* 135 – 145 Potassium 4.3 mmol/L 3.2 – 4.5 Chloride 106 mmol/L 100 – 110 Bicarbonate 23 mmol/L 22 – 27 Urea 15.0 mmol/L* 3.0 – 8.0 Creatinine 340 μmol/L* 70 – 120 Glucose 5.8 mmol/L 3.0 – 7.0 Lipase 562 IU/L* < 220 Total Calcium 2.3 mmol/L 2.15 – 2.6 Phosphate 1.25 mmol/L 0.70 – 1.40 Albumin 26 g/L* 33 – 47 Globulins 35 g/L 25 – 45 Total Protein 61 g/L 60 – 83 Total Bilirubin 20 μmol/L 4 – 20 Conjugated Bilirubin 4 μmol/L 1 – 4 g-Glutamyl transferase (GGT) 6 U/L 0 – 50 Alkaline phosphatase (ALP) 100 U/L 40 – 110 Lactate dehydrogenase (LDH) 380 U/L* 110 – 250 Aspartate aminotransferase (AST) 210 U/L* < 40 Alanine aminotransferase (ALT) 100 U/L* < 40 Measured Osmolarity 290 mOsm/kg 280 – 300

What blood test would you now order?

Lipid profile.

The patient has low serum sodium but a normal measured osmolarity and hence has pseudohyponatraemia. His glucose and protein levels are not elevated. He therefore is likely to have hypertriglyceridemia, which may be the underlying cause of his pancreatitis.

20.4 was the least well answered section with many candidates failing to recognise pseudohyponatraemia.

## Discussion

20.4 was the "least well answered section" because it was poorly worded, not because the candidates could not recognise hyponatremia. To ask" what test would you now order" is like asking "guess what the examiner is thinking".

However, the savvy candidate would have noticed a measured osmolality being offered.

They never give you a measured osmolality unless they expect you to do something with it.

The combination of a normal-ish osmolality and hyponatremia immediately rings alarm bells. Under virtually no conditions is hyponatremia iso-osmolar; the usual pattern is for the osmolality to drop as well as the sodium. An isoosmolar hyponatremia can only be one of two things, high triglycerides or high protein. Of these, the protein is available, and is normal - ergo, triglycerides are to blame.

It might seem that the historical tidbit about pancreatitis is virtually without purpose in this context.  However, a specific literature reference for the importance of recognising pseudohyponatremia is offered in the 1985 article by Howard et al. Six cases of hyperlipaemic pancreatitis are presented. Of the six patients, one was mistakenly resuscitated with hypertonic saline, with intracerebrally disastrous consequences.

So, what is the actual sodium level? You can calculate that. Fortgens and Pillay offer the following equation to correct sodium:

$$"Correct" Na^+ = {"incorrect" Na^+ \times 0.93 \over [99.1 - (0.001 \times [lipid, mg/dL) - (0.7 \times protein, g/dL)] \div 100 }$$

If one plays with this equation, one finds that the effect of lipids on serum sodium measurement is actually rather trivial. For every 10g/L of triglycerides, the sodium level decreases only by  0.84 mmol/L. Thus, in order to be hiding a truly lifethreatening hypernatremia (eg. 150mmol/L), the patient in the college's case study would have to have a serum triglyceride level of 190g/L.

In other words, each litre of blood would have to be be 20% fat by weight. According to the Guiness Book of Records, the highest serum trigluceride level recorded belonged to Terry Culton (USA), who had a triglyceride reading of 3165 mg/dl, or 31.65g/L. This is clearly not much of a record, as the commenters on that page report their own horrific lipid levels as high as 9000 mg/dL, or 90g/L - which is not quite 20% w/v, but still enough to cause a significant sodium drop.

Interestingly, it is important to note that even though the old flame photometry method was the main source of this "pseudohyponatremia" in the pre-1990s literature, m modern analysers are not completely spared.  Modern high-volume pathology labs use various variants of ion-selective electrodes in automated analysers which should theoretically be immune to this error. The “direct” method, anyway, is immune (that is where the ISE membrane comes into direct contact with whole blood, like in an ABG analyser). However, those automated machines typically use the “indirect” method (because it prolongs ISE membrane life). This involves taking the patient’s blood, centrifuging out the red cells, and then diluting the plasma (usually by a factor of 10). This is the step which introduces a dilution error. Because the sodium is confined to the water volume in the sample, any dilution by a fixed amount will decrease the measured sodium concentration.

## References

LADENSON, JACK H., FRED S. APPLE, and DAVID D. KOCH. "Misleading hyponatremia due to hyperlipemia: a method-dependent error." Annals of internal medicine 95.6 (1981): 707-708.

Howard, John M., and Jordan Reed. "Pseudohyponatremia in Acute Hyperlipemic Pancreatitis: A Potential Pitfall in Therapy." Archives of Surgery 120.9 (1985): 1053-1055.

Fortgens, Philip, and Tahir S. Pillay. "Pseudohyponatremia revisited: a modern-day pitfall." Archives of pathology & laboratory medicine 135.4 (2011): 516-519.