The osmolal gap (also referred to as osmotic gap) is the difference between a patient's measured serum osmolality and that estimated from knowledge of the patient's sodium, glucose and SUN levels. An increased osmolal gap may be an indication of unmeasured osmotically active compounds, pseudohyponatremia or laboratory error.
osmolal gap in mOsm/kg H2O =
= (measured osmolality) - (calculated osmolality)
Equation 1
calculated osmolality in mOsm/kg H2O =
= (2 * (sodium in mEq/L)) + ((glucose in mg/dL) / 18) + ((urea nitrogen in mg/dL) / 2.8)
where:
• The molecular mass of glucose is 180 daltons; dividing by 18 converts mg/dL to mmol/L.
• The molecular mass of 2 nitrogen atoms in urea is 28 daltons; dividing by 2.8 converts mg/dL to mmol/L.
• The factor 2 for sodium reflects the matching anions (chloride, bicarbonate, etc.)
Interpretation:
• normal osmolal gap: < 10
• significant osmolal gap: > 10
Equation 2
calculated osmolality in mOsm/kg H2O =
= (1.86 * (sodium in mEq/L)) + ((glucose in mg/dL) / 18) + ((urea nitrogen in mg/dL) / 2.8) + 9
where:
• Each sodium ion in solution is balanced by one anion (2 * 0.93 = 1.86)
• Molecular mass of glucose is 180 daltons; dividing by 18 converts mg/dL to mmol/L
• Molecular mass of 2 nitrogen atoms in urea is 28 daltons; dividing by 2.8 converts mg/dL to mmol/L
• 9 is an empirically derived constant for other electrolytes and osmotically active compounds.
Interpretation:
• normal osmolal gap: 0
• significant osmolal gap: > 0
Equation 3
calculated osmolality in mOsm/kg H2O =
= (2 * (sodium in mEq/L)) + (2 * (potassium in mEq/L)) + ((glucose in mg/dL) / 18) + ((urea nitrogen in mg/dL) / 2.8)
Interpretation:
• normal osmolal gap: 0
• significant osmolal gap: > 0
Equation of Fligner et al
predicted osmolal gap in mOsm per Kg H2O =
= (1.86 * (serum sodium concentration in mEq/L)) + ((serum glucose in mg/dL) / 18) + ((serum BUN in mg/dL) / 2.8)
osmolal gap =
= (measured osmolal gap) – ((predicted osmolal gap) / 0.93)
where:
• The factor 0.93 may reflect that approximately 93% of plasma is water.
Assessment
If the measured osmolality is normal, and if there is a significant osmolal gap present, then either
(1) A low serum sodium present is probably is due to artifact caused by severe hyperlipidemia or hyperproteinemia ("pseudohyponatremia" due to decreased serum water content), or
(2) An unusual osmotically active substance is present (ethanol, methanol, mannitol, ethylene glycol, ethyl ether, isopropyl alcohol, acetone, paraldehyde), or
(3) Laboratory error.
