Pathophysiology

Methanol is a colorless, volatile liquid with a distinctive odor. It is well absorbed from the gastrointestinal tract, with peak levels attained 30 to 90 min after ingestion. Most incidents of toxicity occur after oral ingestion, but significant absorption may also occur through the lungs or skin. The serum half-life after mild toxicity is 14 to 20 h. With severe toxicity, this increases to 24 to 30 h. Methanol has a volume of distribution of 0.6 to 0.7 L/kg.

Following ingestion, highest concentrations are found in the kidney, liver, and gastrointestinal tract, but high levels are also found in the vitreous humor and optic nerve. Most methanol—90 to 95 percent—is eliminated by the liver, while renal excretion accounts for 2 to 5 percent; pulmonary excretion is minimal. In overdose situations, elimination follows saturation (zero-order) kinetics.

Toxicity from methanol poisoning results from the metabolism by hepatic alcohol dehydrogenase of methanol to formaldehyde and formic acid ( Fig 160.-2). The accumulation of formic acid is associated with the onset of clinical symptoms. Lactate is produced from formate-induced inhibition of mitochondrial respiration, as a result of tissue hypoxia, and to a lesser extent as a result of a decrease in the intracellular NAD/NADH ratio caused by the oxidation of methanol and thus stimulation of anaerobic glycolysis and lactate production. Formaldehyde production in the retina causes optic papillitis and retinal edema, in severe cases resulting in blindness; hence the term "blind drunk." Since folate is a cofactor in the breakdown of formic acid to carbon dioxide and water, alcoholics who are folate-deficient may be especially susceptible to methanol toxicity.

FIG. 160-2. Metabolism of methanol in the liver.

The amount of methanol required to cause toxicity varies; death has been reported after ingestion of a dose as small as 15 mL of a 40% solution. Although 30 mL of a 40% solution is considered the minimal lethal dose, amounts as large as 500 to 600 mL have been ingested with survival reported.

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