The Osmolar Gap (OG) is a calculation used in clinical settings to assess the concentration of osmotically active particles in the blood. This value represents the difference between a patient’s actual measured osmolality and a predicted concentration derived from routine blood work. It functions as a rapid, indirect screening tool for substances not typically found in the bloodstream, helping healthcare providers determine if an abnormal solute is contributing to a patient’s condition.
Understanding Measured vs. Calculated Osmolality
The foundation of the Osmolar Gap calculation lies in comparing two different values for serum osmolality: one directly determined and one mathematically estimated. Measured osmolality is the true concentration of all solutes present in a sample of blood serum or plasma. This measurement is obtained by a laboratory instrument, such as an osmometer, typically using the principle of freezing point depression. Because this method measures the colligative property of the solution, it captures the effect of every particle, whether known or unknown.
Calculated osmolality is an estimate derived from the concentrations of the major known solutes that contribute most significantly to the total osmolality. These primary contributors are sodium, glucose, and blood urea nitrogen (BUN). Sodium is the largest factor, as it and its associated anions account for nearly all of the serum’s osmolality. Glucose and BUN are the two main uncharged particles that also exert a measurable osmotic force.
The reason these two values often differ slightly is that the calculated formula intentionally excludes minor solutes and any potentially unknown substances. The measured value is typically reported in milliosmoles per kilogram of water (\(\text{mOsm/kg}\)), reflecting a weight-based concentration. The calculated value is technically an osmolarity (\(\text{mOsm/L}\)), a volume-based concentration, but for practical clinical purposes, the two units are used interchangeably. This difference provides the basis for the Osmolar Gap.
Step-by-Step Guide to Calculating the Osmolar Gap
The calculation of the Osmolar Gap begins with determining the estimated osmolality from routine laboratory results. The formula for Calculated Osmolality accounts for the concentration of sodium, glucose, and blood urea nitrogen (BUN). When glucose and BUN concentrations are reported in conventional units of \(\text{mg/dL}\), specific conversion factors must be applied to translate them into millimoles per liter (\(\text{mmol/L}\)).
The widely accepted formula for Calculated Osmolality is:
$\(\text{Calculated Osmolality} = (2 \times \text{Sodium}) + (\text{Glucose} / 18) + (\text{BUN} / 2.8)\)$
Sodium concentration is multiplied by two to account for the accompanying negative ions, such as chloride and bicarbonate, that balance the positive charge. The divisor of 18 for glucose and 2.8 for BUN converts their concentrations from \(\text{mg/dL}\) into \(\text{mmol/L}\) based on their respective molecular weights. The final step is to subtract this predicted value from the laboratory-provided Measured Osmolality.
$\(\text{Osmolar Gap} = \text{Measured Osmolality} – \text{Calculated Osmolality}\)$
For example, consider a patient with a Measured Osmolality of \(315 \text{ mOsm/kg}\), a Sodium concentration of \(140 \text{ mEq/L}\), a Glucose of \(90 \text{ mg/dL}\), and a BUN of \(14 \text{ mg/dL}\). First, the calculated osmolality is determined: \((2 \times 140) + (90 / 18) + (14 / 2.8) = 280 + 5 + 5 = 290 \text{ mOsm/kg}\). The Osmolar Gap is then calculated: \(315 – 290 = 25 \text{ mOsm/kg}\). This result represents the magnitude of the gap.
Clinical Interpretation of an Elevated Gap
The normal range for the Osmolar Gap is generally small, typically less than \(10 \text{ mOsm/kg}\). A result within this range suggests that the major solutes accounted for in the calculation are responsible for most of the total osmotic activity in the blood. A significant elevation above this threshold, such as the \(25 \text{ mOsm/kg}\) in the example, indicates the presence of a substantial concentration of an unknown, osmotically active substance.
This elevated gap indicates the presence of unmeasured solutes that the formula does not include. These substances must have a low molecular weight to be present in high enough concentrations to affect the osmolality significantly. The primary clinical utility of a high Osmolar Gap is as a screening tool in emergency medicine, particularly when toxic ingestion is suspected.
The most common substances that cause a notable elevation in the Osmolar Gap are alcohols and glycols, often involved in accidental or intentional poisonings. These include methanol (windshield washer fluid), ethylene glycol (antifreeze), and isopropyl alcohol (rubbing alcohol). Ethanol (drinking alcohol) is also a frequent cause of an elevated gap, and its concentration is often specifically measured to account for its contribution. An elevated Osmolar Gap, especially when combined with other laboratory findings, alerts clinicians to the possibility of an unmeasured toxin requiring immediate intervention.