A  45  year old  man  is  admitted unconscious  to  the  Emergency  Department.                      

   His electrolytes are as follows:



132-144 mmol/L



3.1-4.8 mmol/L



93-108 mmol/L



20-30 mmol/L



3.0-8.0 mmol/L



60-120 micromol/L



3.0-5.5 mmol/L



<2 mmol/L

Measured osmolality


275-295 mOsm/kg

Urine ketones


Please interpret these results.  Outline a differential diagnosis based on the biochemical findings and indicate how you will exclude each.

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College Answer

Results demonstrate an increased anion gap metabolic acidosis with mild hyperglycaemia and hyperosmolar hyponatraemia. The marked anion gap (39.5) is not solely explained by the lactate level, and ketones or renal failure are not present. There is also a large osmolar gap (calculated osmolality = 340 –261=81), which suggests an additional agent/toxin is causing acidosis and having osmotic effect.
Differential diagnosis includes:
•    Methanol: History (“hootch” consumption); measurement of methanol and formate levels often takes time, but negative ethanol may be useful. The lack of renal dysfunction does not exclude methanol.
•    Ethylene glycol: History (?suicidal intent), plasma ionised calcium, oxalate crystalluria, Woods lamp examination for fluorescence; unlikely given normal renal function
•    Alcoholic ketoacidosis: measure ethanol and plasma beta- hydroxybutyrate. Negative urinary ketones (acetoacetate) might reflect a low redox state, with most of the keto-anion being in the form of beta-hydroxybutyrate, and with a huge amount of acetone and glycerol (plus some ethyl alcohol) causing the osmolar gap. The enormous anion gap would then be a mixture of lactate, beta-hydroxybutyrate and some acetate from ethanol metabolism.
•    Pyroglutamic acidosis: History of paracetamol ingestion in the face of liver dysfunction.
Measure pyrogluamic acid levels. Less likely as large osmolar gap.
•    Salicylic acid: History (?suicidal intent), measure salicylate levels, may have respiratory alkalosis. Less likely as large osmolar gap.
Hypoadrenalism could be considered (hyponatraemia, hyperkalaemia, metabolic acidosis), but on its own does not explain the osmolar gap and the non-lactate component of the anion gap.
DKA is on the differential, but the osmolar gap (acetone, glycerol) is higher than it usually gets, unconsciousness is not normally a feature and needs to be explained separately, and the lactate is unusually high.
Factitious causes of hyponatraemia (hyperlipidaemia etc) might have been mentioned. However, although they will artefactually raise the osmolar gap, they do not increase the anion gap, and they don’t cause acidosis or unconsciousness.


Let us dissect these results systematically.

  1. The A-a gradient cannot be calculated
  2. There is no pH reported
  3. The PaCO2 is not reported
  4. The SBE is not reported, but the bicabonate is less than 5mmol/L, suggesting a severe metabolic acidosis
  5. The respiratory compensation cannot be assessed
  6. The anion gap is (119) - (80 + 5) = 34, or 39.5 when calculated with potassium
    The delta ratio, assuming a normal anion gap is 12 and a normal bicarbonate is 24, would therefore be (34 - 12) / (24 - 5) = 1.15. This delta ratio suggests that there is a pure high anion gap metabolic acidosis here.
  7. The osmolar gap is raised:
    340 - [ (2 × 119) + 13 + 10] = 79

The lactate cannot account for this increase in anion gap, much less the increase in osmolar gap.

Differential diagnoses of a raised osmolar gap in metabolic acidosis include the following:



Kraut, Jeffrey A., and Ira Kurtz. "Toxic alcohol ingestions: clinical features, diagnosis, and management." Clinical Journal of the American Society of Nephrology 3.1 (2008): 208-225.