A variety of toxic ingestions cause a metabolic acidosis. Acute salicylate intoxication occurs after a large overdose.Chronic salicylate intoxication is possible because of the gradualbuildup of the drug. In addition to a metabolic acidosis, somepatients may have a respiratory alkalosis. Other symptoms ofsalicylate intoxication include fever, seizures, lethargy, andcoma. Hyperventilation may be particularly marked. Tinnitus,vertigo, and hearing impairment are more likely with chronicsalicylate intoxication. Ethylene glycol, a component of antifreeze, is converted in the liver to glyoxylic and oxalic acids,causing a severe metabolic acidosis. Excessive oxalate excretion causes calcium oxalate crystals to appear in the urine, andcalcium oxalate precipitation in the kidney tubules can cause renal failure. The toxicity of methanol ingestion also depends on liver metabolism; formic acid is the toxic end product thatcauses the metabolic acidosis and other sequelae, which includedamage to the optic nerve and central nervous system.
There are many inborn errors of metabolism that maycause a metabolic acidosis (see Section 10). The metabolic acidosis may be due to excessive production of ketoacids, lactic acid, or other organic anions. Some patients have accompanying hyperammonemia. In most patients, acidosis occurs only episodically during acute decompensations, which may be precipitated by ingestion of specific dietary substrates (proteins), the stress of a mild illness (fasting, catabolism), or poor compliance with dietary or medical therapy.
The underlying disorder usually produces most of the signs andsymptoms in children with a mild or moderate metabolic acidosis. The clinical manifestations of the acidosis are related to the degree of acidemia; patients with appropriate respiratory compensation and less severe acidemia have fewer manifestations than patients with a concomitant respiratory acidosis. At a serumpH less than 7.20, there is impaired cardiac contractility andan increased risk of arrhythmias, especially if underlying heartdisease or other predisposing electrolyte disorders are present.With acidemia, there is a decrease in the cardiovascular responseto catecholamines, potentially exacerbating hypotension in children with volume depletion or shock. Acidemia causes vasoconstriction of the pulmonary vasculature, which is especiallyproblematic in neonates with primary pulmonary hypertension of the newborn (see Chapter 61). The normal respiratory response to metabolic acidosis—compensatory hyperventilation—may be subtle with mild metabolic acidosis, but it causesdiscernible increased respiratory effort with worsening acidemia. Chronic metabolic acidosis causes failure to thrive.
The plasma anion gap is useful for evaluating patients with a metabolic acidosis. It divides patients into two diagnostic groups: normal anion gap and increased anion gap. The following formula determines the anion gap: