Question 7.2

List three causes for the following combination of findings observed on a serum sample:

Parameter	Patient Value	Normal Adult Range
Measured osmolality	340 mOsm/kg*	280 – 290
Sodium	138 mmol/L	135 – 145
Potassium	4.0 mmol/L	3.5 – 5.0
Chloride	98 mmol/L	95 – 105
Bicarbonate	15 mmol/L*	22 – 32
Glucose	6.0 mmol/L	4.0 – 6.0
Urea	8.0 mmol/L	6.0 – 8.0

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College Answer

Raised osmolar gap with raised AG
Methanol
Ethylene glycol
Ethanol
(Lactic acidosis can lead to a raised OG and AG; however, the osmolar gap does not reach the levels seen here.)

Discussion

Let us dissect these results systematically.

The A-a gradient cannot be calculated.
There is no pH measurement; one assumes that there must be an acidaemia because the bicarbonate value is low.
The PaCO₂ is not available, and it is therefore impossible to assess respiratory compensation
The SBE is not reported.
The respiratory compensation is irrelevant (see point 3).
The anion gap is raised:
(138) - (98 + 15) = 25, or 29 when calculated with potassium
The delta ratio, assuming a normal anion gap is 12 and a normal bicarbonate is 24, would therefore be (25 - 12) / (24 - 15) = 1.44
This suggests a pure high anion gap metabolic acisosis:
The osmolar gap is raised:
Calculated osmolality is (2×138) + (8 + 6) = 290 mOsm/L;
whereas the measured osmolality is 340 mOsm/L, giving us a gap of 50mOsm.

So, what could account for this? Where did the extra osmoles come from?

Fortunately, Jeffrey Kraut comes to the rescue once again with an article which seems tailored to answering this question. In brief, there are a few situations which could cause the simultaneous increase of both the anion gap and the osmolar gap. Kraut lists the following as well-recognised causes:

Toxicological causes

Methanol intoxication
Ethylene glycol intoxication
Diethylene glycol intoxication
Propylene glycol intoxication
Isopropanol intoxication
Salicylate intoxication

Endocrine and metabolic disturbances

Lactic acidosis
Alcoholic or diabetic ketoacidosis
Acute kidney injury

Kraut also cautions us to respect the timeframe of toxic exposure. When one quaffs a facefull of methanol, one imbibes a substance which is not dissociated at physiological pH: methanol has a pKa of 15.5. There will be a raised osmolar gap, but the anion gap will not increase until the intoxicated patient has had some time to process all that methanol into its acidic metabolites. Then, for a period of time the biochemistry results will reveal the classical picture with an increase in both anion and osmolar gaps. Finally, at some hypothetical point (where the patient is blind and comatose but not yet completely dead) the osmolar gap may decrease to a virtually normal level, leaving only a high anion gap.

References

Kraut, Jeffrey A., and Shelly Xiaolei Xing. "Approach to the evaluation of a patient with an increased serum osmolal gap and high-anion-gap metabolic acidosis." American Journal of Kidney Diseases 58.3 (2011): 480-484.

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