What is the pathophysiology of ethylene glycol (EG) toxicity?

Updated: Dec 05, 2017
  • Author: Daniel C Keyes, MD, MPH; Chief Editor: Sage W Wiener, MD  more...
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[2] Like the other toxic alcohols mentioned above, ethylene glycol is a parent compound that exerts most of its toxicity by conversion to metabolites. Ethylene glycol itself may cause some alteration of mental status but it is a relatively nontoxic compound before it is metabolized. The metabolites cause the distinctive toxicity associated with this compound.

Knowing the pathway of ethanol metabolism is necessary to understanding ethylene glycol toxicity properly. Ethanol is metabolized by the enzyme alcohol dehydrogenase (ADH), which is located in the liver and gastric mucosa, and by the cytochrome P-450 mixed function oxidase (MFO) system in the liver. The mixed function oxidase component is subject to greater inducibility than alcohol dehydrogenase.

Like ethyl alcohol and methanol, ethylene glycol is metabolized by ADH. In this step it forms glycoaldehyde. Through interaction with aldehyde dehydrogenase, ethylene glycol is then metabolized to glycolic acid (GA), which accumulates and can cause a profound metabolic acidosis. This glycolic acid is eventually converted into glyoxylic acid, and then into the highly toxic oxalate or the safer glutamate or α-ketoadipic acid metabolites.

Calcium oxalate crystals may form and accumulate in blood and other tissues. The precipitation of calcium oxalate in the renal cortex results in decreased glomerular filtration and renal insufficiency. The formation of these crystals consumes circulating calcium, and hypocalcemia may occur, though this is uncommon.

The rate-limiting step of ethylene glycol metabolism is the ADH-catalyzed step. Common ethyl alcohol (ethanol) binds much more easily to ADH than ethylene glycol or methanol does. Because ethanol is the preferred substrate for ADH, the presence of ethanol may essentially block metabolism of ethylene glycol. In addition, this enzyme is blocked by the administration of fomepizole (4-methylpyrazole [4-MP]), which is discussed below (see Emergency Department Care). This is the basis of one therapy used in the United States.

Upon oral ingestion, serum concentrations of ethylene glycol peak within 1-4 hours. The elimination half-life (assuming preserved renal function) is 3 hours. When alcohol dehydrogenase is inhibited by ethanol or fomepizole, the elimination half-life increases to about 16 hours.

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