Acidosis, Metabolic, Increased Anion Gap

KEY FEATURES

Essentials of Diagnosis

• Decreased HCO₃^– with acidemia (low blood pH)

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

• General Considerations

• A gap metabolic acidosis is secondary to the addition of acid—either exogenous or endogenous

• The major causes are lactic acidosis, ketoacidosis, kidney failure, and ingestions

• Calculation of the anion gap is useful in determining the cause of the metabolic acidosis

  • Many clinicians use 12 mEq/L as the normal serum anion gap (range 4–12 mEq/L due to differences in analyzer methods

    • Anion Gap = Na⁺ – (HCO₃^– + Cl^–)

  • If serum potassium is included in the formula, the range for the anion gap increases by about 4 mEq/L

    • Anion gap = (Na⁺ + K⁺) – (HCO₃^– + Cl^–)

  • The principal unmeasured anion usually responsible for the anion gap is albumin

    • The expected anion gap must be adjusted for hypoalbuminemia since the anion gap decreases by approximately 2.5 mEq/L for every 1 g/dL reduction in the serum albumin concentration

    • Corrected serum anion gap = (measured serum anion gap) + (2.5 × [4.0 – serum albumin])

    • In metabolic acidosis from a gain of acid, the anion gap will increase because the addition of acid includes the addition of anions

    • In nongap or hyperchloremic metabolic acidosis, the anion gap is normal because the rise in chloride parallels the fall in bicarbonate

Etiology Lactic Acidosis

• Type A lactic acidosis

  • Results from tissue hypoxia, usually from

    • Septic, cardiogenic, or hemorrhagic shock

    • Mesenteric ischemia

    • Respiratory failure

    • Carbon monoxide poisoning

  • These conditions increase peripheral lactic acid production and decrease hepatic metabolism of lactate as liver perfusion declines

• Type B lactic acidosis

  • Secondary to impaired mitochondrial oxygen utilization

  • May be due to

    • Metabolic causes (eg, diabetes mellitus, liver disease, kidney disease, thiamine deficiency, D-lactic acidosis, leukemia, or lymphoma)

    • Toxins (eg, ethanol, methanol, ethylene glycol, cyanide, isoniazid, or metformin)

  • Propylene glycol can cause lactic acidosis from decreased liver metabolism; it is used as a vehicle for intravenous drugs, such as nitroglycerin, etomidate, and diazepam

• D-Lactic acidosis

  • May develop in patients with short bowel syndrome due to carbohydrate malabsorption and subsequent fermentation by colonic bacteria

  • A specific D-lactic acid assay is required as the standard lactic acid assay only detects the L-isomer

Ketoacidosis

• Diabetic ketoacidosis

  • The anion gap is generally large, often > 20 mEq/L, though it can be variable

  • The elevated serum glucose leads to a marked osmotic diuresis with sizeable losses of sodium, water, and potassium

  • Correction of ketoacidosis can be assessed by measurement of serum β-hydroxybutyrate, pH, or by normalization of the anion gap

• Fasting ketoacidosis

  • Hepatic generation of ketones may occur as a normal response to ...