The plasma osmolal gap is the difference between the measured and calculated plasma osmolality. The calculated plasma osmolality is determined as follows:
$$ Osmolality = 2\times sodium + \frac{glucose}{18} + \frac{urea}{2.8} + \frac{EtOH}{4.6} $$
Plasma Osmolality (mOsm/kg H2O) = (2 × Serum Sodium [mEq/L]) + Plasma Glucose (mg/dL)/18 + Blood Urea Nitrogen (mg/dL)/2.8 + EtOH/4.6
A high osmolal gap (>10 mOsm/kg H2O) indicates the presence of unmeasured osmoles such as methanol or ethylene glycol, which are metabolized to organic acids, thereby increasing the anion gap. A high osmolal gap is also seen in pseudohyponatremia, in which plasma osmolality is normal while calculated osmolality is low. The patient's history should guide further testing for unmeasured anions.
