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of CO2 generated Once metabolic acidosis is diagnosed, assessment of respiratory compensation can be performed The arterial partial pressure of CO2 (pCO2 ) normally falls at an average of 1.2 mm Hg for every mEq/L reduction in the serum HCO3 − to a minimum pCO2 of 10 to 15 mm Hg The Winters formula can also approximate the expected arterial pCO2 : Arterial pCO2 = (1.5 × measured HCO3 − ) + ± If the fall in pCO is significantly different than the expected value, a mixed acid–base disorder is likely present Patients with metabolic acidosis can be classified in two groups based on the serum AG, and this determination may facilitate the diagnosis of the underlying cause Serum electrolytes should be obtained to calculate the AG using the following formula: AG (mEq/L) = Na+ − (Cl− + HCO3 − ) The normal AG typically ranges between and 13 mEq/L and an AG greater than 14 to 16 mEq/L is elevated In normal subjects, the AG is primarily due to negative charges from plasma proteins, particularly albumin An elevated AG is most often due to an unmeasured anion, though can also result from a low concentration of serum cations (K+ , Ca2+ , Mg2+ ) A low AG can result from an increase in serum cations or low serum albumin For every g/dL reduction in serum albumin level, the AG would be expected to be reduced by approximately 2.5 mEq/L The causes of metabolic acidosis based on elevated or normal AG are outlined in Table 100.11 Potentially life-threatening conditions including septic shock, severe hypovolemia, and certain inborn errors of metabolism are important considerations in the evaluation of children with significant elevated AG metabolic acidosis DKA is associated with an elevated AG due to the accumulation of acetoacetic acid and β-hydroxybutyric acid Lactic acidosis has been observed in patients with severe asthma being treated with highdose β-adrenergic agents and steroids Some toxic ingestions, including ethanol, methanol, ethylene glycol, other alcohols, and salicylates, are associated with unmeasured serum osmoles This leads to an elevated