What is the pathogenesis of methanol toxicity?

Updated: Nov 05, 2018
  • Author: Kalyani Korabathina, MD; Chief Editor: Tarakad S Ramachandran, MBBS, MBA, MPH, FAAN, FACP, FAHA, FRCP, FRCPC, FRS, LRCP, MRCP, MRCS  more...
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Answer

Methanol has a relatively low toxicity. The adverse effects are thought to be from the accumulation of formic acid, a metabolite of methanol metabolism.

Upon ingestion, methanol is quickly absorbed in the gastrointestinal tract and metabolized in the liver. In the first step of degradation, methanol is transformed into formaldehyde via the enzyme alcohol dehydrogenase (ADH). This reaction is slower than the next step, the transformation of formaldehyde into formic acid via the enzyme aldehyde dehydrogenase. This may explain the reason for the latency of symptoms between ingestion and effect. The half-life of formaldehyde is estimated to be 1-2 minutes. [10]

Formic acid is further oxidized to carbon dioxide and water in the presence of tetrahydrofolate. The metabolism of formic acid is very slow; thus, formic acid often accumulates in the body, which results in metabolic acidosis. [10]

The eye damage caused by methanol has been well described; however, the mechanism behind this phenomenon is not well understood. Vision loss is thought to be caused by interruption of mitochondrial function in the optic nerve, resulting in hyperemia, edema, and optic nerve atrophy.

Optic nerve demyelination has been reported to be due to formic acid destruction of myelin. The major damage occurs at the retrolaminar optic nerve, with intra-axonal swelling and organelle destruction. Little to no change is seen in the retina. [11]

Methanol also affects the basal ganglia. Hemorrhagic and nonhemorrhagic damage to the putamen are common problems in cases of severe intoxication. As a result of this damage, patients can develop parkinsonism or other dystonic/hypokinetic clinical pictures. [12]

The predilection for and mechanism of toxicity to the putamen is not understood. Some postulate that striatal neurons have a varying sensitivity to toxic metabolites of methanol. However, this remains to be proven. [6]


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