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  • Decreased HCO3 with acidemia.

  • Classified into increased anion gap acidosis and normal anion gap acidosis.

  • Lactic acidosis, ketoacidosis, and toxins produce metabolic acidoses with the largest anion gaps.

  • Normal anion gap acidosis is mainly caused by gastrointestinal HCO3 loss or renal tubular acidosis (RTA). Urinary anion gap may help distinguish between these causes.


The hallmark of metabolic acidosis is decreased HCO3. Metabolic acidoses are classified by the anion gap, usually normal or increased (Table 21–12). The anion gap is the difference between readily measured anions and cations.

In plasma,


Major unmeasured cations are calcium (2.5 mEq/L), magnesium (2 mEq/L), gamma-globulins, and potassium (4 mEq/L). Major unmeasured anions are albumin (2 mEq/L per g/dL), phosphate (2 mEq/L), sulfate (1 mEq/L), lactate (1–2 mEq/L), and other organic anions (3–4 mEq/L). Traditionally, the normal anion gap has been 12 ± 4 mEq/L. With current auto-analyzers, the reference range may be lower (6 ± 1 mEq/L), primarily from an increase in Cl values. Despite its usefulness, the anion gap can be misleading. Non–acid-base disorders may cause errors in anion gap interpretation; these disorders include hypoalbuminemia, hypernatremia, or hyponatremia. Antibiotics (eg, carbenicillin is an unmeasured anion; polymyxin is an unmeasured cation) may also cause errors in anion gap interpretation. Although not usually associated with metabolic acidosis, a decreased anion gap can occur because of a reduction in unmeasured anions or an increase in unmeasured cations. In hypoalbuminemia, a 2–3 mEq/L decrease in anion gap will occur for every 1 g/dL decline in serum albumin.

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