Ethylene Glycol Toxicity

<p>As with ethyl alcohol and methanol, ethylene glycol is metabolized by the enzyme alcohol dehydrogenase. In this step it forms glycoaldehyde. Through interaction with aldehyde dehydrogenase, ethylene glycol is then metabolized to glycolic acid (GA). A profound <a href="http://emedicine.medscape.com/article/768268-overview" target="_self">acidosis</a> often ensues with this intoxication which is attributable to the glycolic acid in circulation. This glycolate is then transformed into glyoxylic acid. At this point, the molecule may be transformed into the highly toxic oxalate or the safer glutamate or α -ketoadipic acid metabolites.

With the formation of <a href="http://emedicine.medscape.com/article/817016-overview" target="self">oxalate crystals</a> in the urine, calcium oxalate crystals 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. Calcium is consumed in circulation, and <a href="http://emedicine.medscape.com/article/767260-overview" target="self">hypocalcemia</a> may occur.

The rate-limiting step of ethylene glycol metabolism is the alcohol dehydrogenase–catalyzed step. Common ethyl alcohol (ethanol) binds much more easily to alcohol dehydrogenase than ethylene glycol or methanol does. Because ethanol is the preferred substrate for alcohol dehydrogenase, 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 <a href="http://emedicine.medscape.com/article/814701-treatment#TreatmentEmergencyDepartmentCare" target="_self">Emergency Department Care</a>). This is the basis of one therapy used in the United States.

Upon oral ingestion the peak-serum levels of ethylene glycol are achieved within 1-4 hours. The elimination half-life (assuming preserved renal function) is 3 hours.</p>