Osmolal Gap


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Subject: Osmolal Gap

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  • The osmolal gap is a mathematical concept similar to the AG that is used to detect concentration changes in osmotically active solutes rather than ion changes. The osmolal gap is calculated by subtracting the calculated osmolality from the measured osmolality.

  • Normal range: <10 mOsm/kg.


  • Osmolal gap has been used to estimate the blood alcohol. Serum osmolality increases 22 mOsm/kg for every 100 mg/dL of ethanol; therefore, estimated blood alcohol (mg/dL) = osmolal gap × 100 ÷ 22.


Increased In

  • Decreased serum water content:

    • Hyperlipidemia (serum will appear lipemic)

    • Hyperproteinemia (total protein >10 g/dL)

  • Additional low molecular weight substances in the serum (measured osmolality is >300 mOsm/kg water).

  • Ethanol; an especially large osmolal gap with a low or only moderately elevated ethanol level should raise the possibility of another low molecular weight toxin (e.g., methanol).

    • Methanol

    • Isopropyl alcohol

    • Mannitol (osmolal gap can be used to detect accumulation of infused mannitol in serum)

    • Ethylene glycol, acetone, ketoacidosis, and paraldehyde result in relatively small osmolal gaps, even at lethal levels

  • Severely ill patients, especially those in shock, acidosis (lactic, diabetic, alcoholic), renal failure.


  • Laboratory analytic error

    • Random error from all measurements could add or subtract ≤15 mOsm/kg

    • Use of incorrect blood collection tubes