Metabolic acidosis develops when there is an accumulation of hydrogen ions in or an excessive loss of bicarbonate from the bloodstream. There are numerous causes of metabolic acidosis, and determination of the anion gap can narrow the differential diagnosis considerably. The anion gap refers to the unmeasured anions in the bloodstream which, in conjunction with chloride and bicarbonate, counteract the main cation sodium (Table 140.1).

An increase in the anion gap occurs with increased production of endogenous acids, as in diabetic or starvation ketoacidosis; decreased excretion of fixed acids, as in uremia or chronic renal insufficiency; or ingestion of exogenous acids, such as salicylates. Toxic alcohol ingestion with methanol and ethylene glycol can also result in increased exogenous acids as the parent alcohol gets broken down into its metabolites.

Toxic alcohol ingestion from methanol or ethylene glycol results in predictable clinical toxidromes. Both toxidromes are characterized by extensive central nervous system, cardiopulmonary, and gastrointestinal involvement (Table 140.2). Ethylene glycol intoxication also involves the kidneys, while methanol intoxication has extensive ophthalmologic involvement. However, clinical manifestations of intoxication by either substance are often delayed until significant metabolism of the parent alcohol has occurred. This makes the initial diagnosis more difficult, especially in the absence of an ingestion history. The presence of an anion gap metabolic acidosis without alternative explanation can provide a clue to the diagnosis of toxic alcohol ingestion.

Furthermore, both methanol and ethylene glycol intoxication can result in an elevation of the osmolal gap. Other causes of anion gap metabolic acidosis do not. Serum osmolality refers to the total amount of osmotically active particles in the blood stream. It is influenced primarily by small molecules that are present in high concentrations such as sodium, potassium, chloride, bicarbonate, urea, and glucose. Several formulas exist for the calculation of the serum osmolality, and a common formula is listed in Table 140.1. The osmolal gap represents the difference between the measured and the calculated serum osmolality. Both methanol and ethylene glycol are osmotically

active substances that increase the serum osmolality and subsequently the osmolal gap.