- Ethylene glycol (EG) is a widely used industrial chemical, most commonly recognised as the primary component of automotive antifreeze. Although the parent compound itself has relatively low inherent toxicity, its metabolic breakdown in the liver produces highly toxic intermediates responsible for severe metabolic disturbances and organ damage. Understanding this metabolic pathway is essential for recognising and treating ethylene glycol poisoning effectively.
- Once ingested, ethylene glycol is rapidly absorbed and transported to the liver, where it undergoes enzymatic metabolism. The first and most critical step is catalysed by alcohol dehydrogenase (ADH), converting ethylene glycol into glycoaldehyde. This intermediate is then further oxidised by aldehyde dehydrogenase (ALDH) to form glycolic acid, the metabolite most responsible for the profound high anion‑gap metabolic acidosis seen in poisoning. Glycolic acid accumulates in the bloodstream, overwhelming the body’s buffering systems and leading to tachypnoea, cardiovascular stress, and neurological symptoms.
- As metabolism continues, glycolic acid is converted into glyoxylic acid, which can follow several pathways. The most harmful route produces oxalic acid, a compound that readily binds to calcium to form calcium oxalate crystals. These crystals precipitate in tissues throughout the body, but the kidneys are particularly vulnerable. Crystal deposition within renal tubules causes obstruction, inflammation, and acute tubular necrosis, ultimately resulting in acute kidney injury. Patients may also develop hypocalcaemia, as circulating calcium is consumed during crystal formation, leading to muscle spasms, tetany, and cardiac arrhythmias.
- Clinically, ethylene glycol poisoning progresses through three recognisable stages. The first resembles alcohol intoxication, with central nervous system depression. The second stage is dominated by metabolic acidosis as glycolic acid accumulates. The third stage involves renal failure due to calcium oxalate deposition. Diagnosis relies on identifying metabolic acidosis, an elevated osmolar gap, hypocalcaemia, and the presence of calcium oxalate crystals in urine.
- Treatment focuses on preventing further metabolism of ethylene glycol and correcting metabolic disturbances. Fomepizole, an inhibitor of alcohol dehydrogenase, is the preferred antidote, while ethanol may be used as an alternative competitive inhibitor. Severe cases require haemodialysis to remove both ethylene glycol and its toxic metabolites. Supportive therapy includes bicarbonate for acidosis, calcium supplementation when needed, and cofactors such as thiamine and pyridoxine to promote non‑toxic metabolic pathways.
- Ethylene glycol toxicity is a clear example of how a relatively benign parent compound can become dangerous through metabolic transformation. The production of glycolic acid and oxalic acid explains the characteristic acidosis, renal injury, and systemic complications. Early recognition and prompt inhibition of alcohol dehydrogenase are critical to preventing the formation of these harmful metabolites and improving patient outcomes.
