Two patients present with alcohol poisoning. Patient A ingested a substance used in antifreeze and windshield wipers; Patient B ingested spirits. Both have metabolic acidosis and CNS depression. Which metabolic feature best distinguishes methanol poisoning (Patient A) from ethanol poisoning (Patient B)?

Explanation

## Metabolic Distinction: Methanol vs. Ethanol Poisoning ### Pathophysiology of Toxic Metabolites | Aspect | Methanol | Ethanol | |--------|----------|--------| | **Primary toxic metabolite** | Formic acid (formate) | Acetaldehyde → Acetic acid | | **Metabolic consequence** | High anion-gap acidosis + formate accumulation | Lactic acidosis (variable) | | **Serum formate level** | Elevated (diagnostic) | Absent | | **Anion gap magnitude** | Severe (often >20 mEq/L) | Mild to moderate | | **Osmolal gap** | Present early, then closes | Present early, then closes | | **Lactate level** | May be elevated (secondary) | Often elevated (primary) | ### Key Point: **Elevated serum formate is the pathognomonic metabolic marker of methanol poisoning.** Formic acid is the toxic metabolite responsible for the severe anion-gap acidosis and optic nerve damage. ### High-Yield: Methanol metabolism: 1. Methanol → Formaldehyde (alcohol dehydrogenase) 2. Formaldehyde → **Formic acid** (aldehyde dehydrogenase) 3. Formic acid → High anion-gap metabolic acidosis 4. Formate accumulation → Optic nerve toxicity Ethanol metabolism produces acetaldehyde and acetic acid, which do not accumulate to toxic levels and do not cause optic nerve damage. ### Clinical Pearl: In the emergency setting, **serum or urine formate measurement** (if available) is diagnostic of methanol poisoning. The combination of high anion-gap acidosis + elevated formate = methanol. ### Mnemonic: **FORMATE = Formaldehyde → Oxidation → Resultant Metabolic Acidosis + Toxic Accumulation + Elevated levels (diagnostic)** [cite:Park 26e Ch 25]