Plasma osmolality is determined mainly by Sodium (NA), its counter ions, and uncharged species such as Glucose (GLU) and Urea (UN). Knowledge of the plasma concentration of these species allows calculation of the plasma osmolality to a degree that compares quite well to measured osmolality from freezing point depression. The difference between measured osmolality (MO) and calculated osmolality (CO) is known as the osmolality gap (OG). A large positive (>14) osmolality gap can help identify the presence in plasma of substances such as ethanol, methanol, isopropanol, ethylene glycol, propylene glycol, and acetone. The formula given below for CO was developed using the specific plasma assays available at University of Iowa Hospitals and Clinics.
(1). CO = 2 x NA + GLU/20 + UN/3 - 2 : calculated osmolality
(2). OG = MO - CO : osmolality gap
To calculate the osmolality gap, plasma determination of MO, NA, GLU, and UN are necessary. Proper interpretation of the OG also requires knowledge of the anion gap (AG = NA - HCO3 - CL), the blood pH, and qualitative testing of the plasma ketone bodies (KETO). Determinations of MO and for CO should be performed on the same plasma sample.
The OG was calculated in 119 patients at University of Iowa Hospitals and Clinics using formulas (1) and (2). A mean OG of 0.13 was obtained with an observed range of -11 to +13; 61% of the patients were in the interval -3 to +3, and 97% of the patients were in the interval of -10 to +10. An OG value greater than 14 has traditionally been considered a critical value or cutoff.
When the OG is combined with blood pH and AG, poisonings with toxic alcohols can be quickly recognized. The presence of low blood pH, elevated AG, and greatly elevated OG (>14) is a medical emergency that requires prompt treatment. The specific agent(s) responsible can be identified by the gas chromatographic assays for ethanol, methanol, isopropanol, acetone, and ethylene glycol. The following table summarizes results found in intoxications and other clinical situations.
SITUATION
Ethanol only
Methanol (late)
Isopropanol
(also acetone)
Ethylene Glycol
Alcoholic Ketoacidosis
Diabetic Ketoacidosis
(usually < 20-25)
N = normal
*On the left side of the equals sign are substance concentrations, and on the right side of the equals sign equivalent osmolality contributions. By dividing the OG by the right hand factor and then multiplying by the left hand concentration for this factor, an estimated pure substance concentration can be calculated (see case example).
**Osmolar gap may be increased in early methanol poisoning.
Non-toxic examples of an elevated osmolality gap include hyperlipidemia (less plasma water), chronic renal failure, and myeloma (increased plasma proteins).
EXAMPLE CASE:
A sixty-seven year old white male was found pulseless and resuscitated; then brought to the emergency room. He had been reported to be drinking in a bar all afternoon, and had then fallen from a ten foot balcony to snow covered ground. He arrived in the emergency room with a fractured occiput and was unresponsive.
Admission Data:
NA=141 mEq/l
CL=105 mEq/l
HCO3=19 mEq/l
AG = NA - CL- HCO3= 141 - 105- 19 = 17
CO = 2 x NA + GLU/20 + UN/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0G = MO - CO= 353 - 292 =61
If we assume OG is due to ethanol, then ethanol concentration (see table) would be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl. The OG calculated in this case was consistent with the history and indicated ethanol intoxication.
References:
1. Glasser, L., et al. : Serum Osmolality and Its Applicability to Drug overdose. Am. J. Clin. Path. 60:695, 1973
2. Jacobsen, D., et al.: (Series of three articles dealing with methanol and ethylene glycol overdose and use of AG and OG in diagnosis). Acta. Med. Scand. 212:1-20, 1982
Contact the Laboratory Director of Clinical Chemistry (356-1759) with questions.