Question 7.3

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


Patient Value

Normal Adult Range

Measured osmolality

310 mOsm/L*

280 – 290


125 mmol/L*

135 – 145


4.0 mmol/L

3.5 – 5.0


98 mmol/L

95 – 105


21 mmol/L*

22 – 32


6.0 mmol/L

4.0 – 6.0


8.0 mmol/L

3.0 – 8.5

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College Answer

Raised osmolar gap with normal AG


Let us dissect these results systematically.

  1. The A-a gradient cannot be calculated.
  2. There is no pH measurement; one assumes that there must be an acidaemia because the bicarbonate value is low.
  3. The PaCO2 is not available, and it is therefore impossible to assess respiratory compensation
  4. The SBE is not reported.
  5. The respiratory compensation is irrelevant (see point 3).
  6. The anion gap is  normal:
    (125) - (98  + 21) = 6, or 10 when calculated with potassium
  7. The osmolar gap is raised:
    Calculated osmolarity is  (2×125) + (8 + 6) = 264 mOsm/L;
    whereas the measured osmolarity is 310 mOsm/L, giving us a gap of 46 mOsm/L.

What could raise the osmolar gap but not  the anion gap? Well, any osmotically active agent which is not anionic, for instance any substance which fails to dissociate at physiologic pH. Counterintuitively, virtually all toxic alcohols fall into this category, as do various soluble sugars. A high anion gap acidosis does not develop until after you have managed t metabolise a large amount of toxic alcohol into some sort of organic acid.

Thus, the list of explanations includes the following:

  • Mannitol therapy
  • Glycine absorption (TURP syndrome)
  • Non-metabolised glycols: propylene glycol or polyethylene glycol (found in IV drug ampoules)
  • Maltose (IV immunoglobulin is suspended in maltose)
  • Ethanol
  • Soon (immediately) after toxic alcohol ingestion.


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.