Clinical meaning
Ethylene glycol (EG) is a colorless, odorless, sweet-tasting liquid found in antifreeze, de-icing solutions, brake fluid, and industrial solvents. The lethal dose is approximately 1-1.5 mL/kg (roughly 100 mL in an adult). EG itself is relatively non-toxic; it is the sequential METABOLITES produced by hepatic alcohol dehydrogenase (ADH) that cause organ damage. The metabolic pathway is: ethylene glycol → (ADH) → glycoaldehyde → (aldehyde dehydrogenase) → glycolic acid → glyoxylic acid → oxalic acid. Glycolic acid accumulates as the rate-limiting metabolite and is the PRIMARY cause of the severe anion gap metabolic acidosis characteristic of EG poisoning (pH may fall below 7.0). Oxalic acid combines with serum calcium to form CALCIUM OXALATE CRYSTALS, which precipitate in the renal tubules causing acute tubular necrosis, and in other tissues (brain, heart, lungs) causing direct organ injury. The crystal deposition also causes HYPOCALCEMIA through calcium sequestration, potentially leading to tetany, QT prolongation, and cardiac dysrhythmias. EG toxicity classically progresses through three clinical stages: Stage 1 -- NEUROLOGICAL (30 minutes to 12 hours): CNS depression resembling alcohol intoxication (ataxia, slurred speech, nystagmus) but WITHOUT the odor of alcohol on the breath; nausea, vomiting; seizures may occur. Stage 2 -- CARDIOPULMONARY (12-24 hours): tachycardia, hypertension or hypotension, tachypnea from metabolic acidosis (Kussmaul respirations), pulmonary edema, congestive heart failure, ARDS. Stage 3 -- RENAL (24-72 hours): flank pain, costovertebral angle tenderness, oliguria/anuria, hematuria, proteinuria, calcium oxalate crystalluria on urinalysis; acute oliguric renal failure requiring dialysis. Treatment is TIME-CRITICAL: blocking ADH with fomepizole or ethanol BEFORE significant metabolism prevents toxic metabolite formation.