Clinical meaning
Methanol and ethylene glycol are toxic alcohols that are relatively harmless in their parent form but are metabolized by alcohol dehydrogenase (ADH) into highly toxic metabolites that cause severe end-organ damage and death if untreated. Methanol is oxidized by ADH to formaldehyde, then rapidly converted by aldehyde dehydrogenase to formic acid (formate). Formic acid inhibits cytochrome c oxidase (complex IV) in the mitochondrial electron transport chain, blocking aerobic metabolism and causing cellular energy failure. The retina and optic nerve are uniquely vulnerable due to their high metabolic demand and limited buffering capacity — formate accumulation produces retinal edema, optic disc hyperemia, and irreversible optic nerve demyelination, manifesting as blurred vision, central scotomata, and permanent blindness. Formic acid also causes severe high anion gap metabolic acidosis (HAGMA) with compensatory Kussmaul respirations. Ethylene glycol follows a parallel but distinct toxic pathway: ADH converts it to glycoaldehyde, then to glycolic acid (the primary cause of early HAGMA), and finally to oxalic acid. Oxalate chelates serum calcium to form insoluble calcium oxalate crystals that precipitate in the renal tubules, causing acute tubular necrosis (ATN), oliguric renal failure, and the pathognomonic finding of calcium oxalate crystals (envelope-shaped) on urinalysis. Hypocalcemia from calcium chelation can cause QT prolongation and cardiac dysrhythmias. Both poisonings present with an early phase of apparent intoxication (CNS depression, similar to ethanol) followed by a latent period (12-24 hours for methanol, 4-12 hours for ethylene glycol) before toxic metabolite accumulation produces HAGMA with an elevated osmolar gap (the osmolar gap is highest early when parent compound is present; the anion gap rises as metabolism proceeds). Treatment centers on blocking toxic metabolite formation: fomepizole (4-methylpyrazole) is the preferred antidote — it competitively inhibits ADH with high affinity, preventing conversion of the parent alcohol to toxic metabolites; ethanol is an alternative ADH inhibitor if fomepizole is unavailable but has a narrow therapeutic window and significant side effects. Hemodialysis is indicated for severe acidosis (pH less than 7.25), renal failure, visual symptoms (methanol), very high serum levels (greater than 50 mg/dL), or clinical deterioration despite antidotal therapy — it removes both the parent compound and toxic metabolites. Adjunctive folinic acid (leucovorin) enhances formate metabolism in methanol poisoning; pyridoxine and thiamine promote oxalate shunting to non-toxic metabolites in ethylene glycol poisoning.