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?

Give your reasoning.    (30% marks)

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College Answer

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.

Additional Examiners’ Comments:

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.

References

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.