Monday, December 19, 2011

The high osmolal gap---toxic alcohol poisoning and other disorders

This topic was reviewed as part of the acid-base teaching series of the American Journal of Kidney Diseases.

Concluding points from the article:

• Increased serum osmolal gap with or without high-anion-gap metabolic acidosis can be an important clue to toxic alcohol intoxications
• The presence and magnitude of serum osmolal gap depends on several factors, including molecular weight of the offending alcohol, baseline serum osmolal gap, and state of metabolism of the parent alcohol
• Patients with toxic alcohol intoxications can present with an increase in serum osmolality alone, increased serum osmolality and high-anion-gap acidosis, or increased-anion-gap acidosis alone. Rare cases in which both serum osmolality and anion gap are within reference ranges also might occur
• Kidney failure, lactic acidosis, and diabetic ketoacidosis also can cause high-anion-gap metabolic acidosis associated with a large serum osmolal gap
• Given the potential severity of all these disorders, they should be excluded in all individuals presenting with serum osmolal gap, serum osmolal gap and high-anion-gap metabolic acidosis, or high-anion-gap metabolic acidosis alone

Also remember this:

Osmolality must be measured by the method of freezing point depression. Other methods may not be reliable. Fortunately, freezing point depression is the method of most hospital labs.

In contrast to the other toxic alcohols, isopropyl alcohol is not metabolized to an acid (it is metabolized to acetone resulting in ketosis but not ketoacidosis because acetone cannot be carboxylated to produce a ketoacid). Thus isopropyl alcohol intoxications produce elevations in the osmolal gap but not the anion gap unless they produce sufficiently severe hypotension to cause lactic acidosis.

The other toxic alcohol ingestions start with only an elevated osmolal gap. As the parent compound is metabolized to acid metabolite(s) the osmolal gap goes down as the anion gap goes up. Late in the course only the anion gap is elevated.

The higher the molecular weight of the offending compound the less it will contribute to the osmolal gap.

An interesting situation exists with DKA. Ketoacids dissociate and the hydrogen ion is buffered. Sodium pairs with ketoacids to maintain electroneutrality. Because sodium figures in the calculated osmolality the ketoacids do not directly contribute to the osmolal gap. They contribute indirectly because acetoacetic acid is irreversibly and non-enzymatically converted to acetone, an osmotically active non ionic compound which is slowly excreted in breath and urine. Glycerol and some amino acids also contribute to the osmolal gap.

High school chemistry question: what's the difference between osmolality and osmolarity? We use the terms interchangeably but there is a difference. No fair googling.