The osmolar gap is a calculated value used in medical settings to assess the concentration of substances dissolved in a person’s blood. It represents the difference between the measured osmolality of the blood and a predicted osmolality based on common blood components. This calculation helps healthcare professionals identify the presence of unusual substances in the bloodstream that are not typically accounted for in routine blood tests, serving as an indicator for potential issues requiring further investigation.
Understanding Osmolality and Predicted Osmolality
Serum osmolality refers to the total concentration of dissolved particles, or solutes, in the liquid portion of the blood. This measurement is obtained directly by laboratory instruments and reflects the overall osmotic activity of the blood.
Predicted osmolality, in contrast, is an estimated value derived from the concentrations of the most abundant and osmotically active substances normally present in the blood. These primary contributors include sodium, glucose, and blood urea nitrogen (BUN). These specific components are used because they are readily measured and typically account for the majority of the blood’s osmotic pressure.
Sodium is a major electrolyte that significantly influences osmolality, and its concentration often dictates much of the predicted value. Glucose, a sugar, and BUN, a waste product from protein metabolism, also contribute to the total solute concentration. While other substances exist, these three are considered the main drivers for the estimated osmolality.
The Formula for Osmolar Gap
Calculating the osmolar gap involves a straightforward subtraction: the measured serum osmolality minus the predicted serum osmolality. This difference highlights whether there are additional osmotically active substances present that are not captured by the standard prediction.
The most commonly used formula for predicted osmolality is:
Predicted Osmolality = (2 \ Sodium) + (Glucose / 18) + (BUN / 2.8).
In this formula, sodium is measured in milliequivalents per liter (mEq/L), while glucose and BUN are typically measured in milligrams per deciliter (mg/dL). The divisors 18 and 2.8 convert glucose and BUN from mg/dL into units compatible with osmolality, which is expressed in milliosmoles per kilogram of water (mOsm/kg H2O).
For example, if a blood sample has a measured osmolality of 310 mOsm/kg H2O, a sodium level of 140 mEq/L, glucose of 90 mg/dL, and BUN of 14 mg/dL, the calculation would proceed as follows:
Predicted Osmolality = (2 \ 140) + (90 / 18) + (14 / 2.8) = 280 + 5 + 5 = 290 mOsm/kg H2O.
Then, the osmolar gap would be: 310 (Measured) – 290 (Predicted) = 20 mOsm/kg H2O.
What Your Osmolar Gap Result Means
A normal osmolar gap typically falls below 10 mOsm/kg H2O, though some sources suggest a normal range between -10 and +10 mOsm/kg H2O. This small difference indicates that the measured osmolality is closely aligned with what is predicted from the main blood components.
An elevated osmolar gap signals the presence of unmeasured substances that are osmotically active in the blood. These are compounds not included in the standard predicted osmolality formula, such as certain alcohols or other toxins. The larger the gap, the greater the concentration of these unmeasured solutes.
A low or negative osmolar gap is uncommon and usually suggests laboratory error or, in rare cases, extremely low sodium levels. The primary focus of the osmolar gap calculation is to detect elevations. This calculation serves as a valuable diagnostic tool, particularly when there is suspicion of exposure to certain substances.
Common Causes of an Elevated Osmolar Gap
An elevated osmolar gap can be caused by various substances that contribute to the measured osmolality but are not part of the predicted formula. Toxic alcohols are frequent culprits, including methanol, found in windshield washer fluid and some industrial solvents, and ethylene glycol, a component of antifreeze. Isopropyl alcohol, and propylene glycol, can also elevate the gap.
These substances increase the measured osmolality because they are dissolved in the blood, yet they are not sodium, glucose, or BUN. As a result, the difference between the measured and predicted values increases. For example, in the early stages of toxic alcohol ingestion, the osmolar gap can be significantly elevated before the body metabolizes these substances into acidic byproducts.
Beyond toxic ingestions, other medical conditions can also contribute to an elevated osmolar gap. These include severe kidney failure, where waste products accumulate, and certain metabolic conditions like diabetic ketoacidosis or lactic acidosis. Additionally, the use of certain therapeutic agents, such as mannitol, can also lead to an increased osmolar gap. The timely identification of an elevated osmolar gap is important for appropriate medical intervention.