Acidosis, Metabolic, Increased Anion Gap

For further information, see CMDT Part 21-17: Metabolic Acidosis

For further information, see CMDT Part 21-18: Increased Anion Gap Acidosis (Increased Unmeasured Anions)

Essentials of Diagnosis

• Hallmark of this disorder is that metabolic acidosis (thus low HCO₃^–) is associated with normal serum Cl^–, so that the anion gap increases

• Decreased HCO₃^– is also seen also in respiratory alkalosis, but pH distinguishes between the two disorders

General Considerations

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

• Normochloremic (increased anion gap) metabolic acidosis

  • Generally results from addition to the blood of organic acids such as lactate, acetoacetate, β-hydroxybutyrate, and exogenous toxins

  • Uremia produces an increased anion gap metabolic acidosis via unexcreted organic acids and anions

Etiology

• Lactic acidosis

  • Type A: cardiogenic, septic, or hemorrhagic shock; carbon monoxide or cyanide poisoning

  • Type B: metabolic causes (eg, diabetes mellitus, ketoacidosis, liver disease, kidney disease, infection, leukemia, or lymphoma); toxins (eg, ethanol, methanol, salicylates, isoniazid, or metformin); nucleoside analog reverse transcriptase inhibitors

• Diabetic ketoacidosis

• Alcoholic ketoacidosis

  • Acid-base disorders in alcoholism are frequently mixed (10% have triple acid-base disorder)

  • Three types of metabolic acidoses: ketoacidosis, lactic acidosis, and hyperchloremic acidosis from bicarbonate loss in urine from ketonuria

  • Metabolic alkalosis from volume contraction and vomiting

  • Respiratory alkalosis from alcohol withdrawal, pain, sepsis, or liver disease

• Uremic acidosis (usually at glomerular filtration rate < 15–30 mL/min)

• Ethylene glycol toxicity

• Methanol toxicity

• Salicylate toxicity (mixed metabolic acidosis with respiratory alkalosis)

Symptoms and Signs

• Symptoms are mainly those of the underlying disorder

• Compensatory hyperventilation may be misinterpreted as a primary respiratory disorder

• When severe, Kussmaul respirations (deep, regular, sighing respirations indicating intense stimulation of the respiratory center) occur

Laboratory Tests

• See Table 21–13

• Blood pH, serum HCO₃^–, and PCO₂ are decreased

• Anion gap is increased (normochloremic)

• Hyperkalemia may be seen

• In lactic acidosis, lactate levels are at least 4–5 mEq/L but commonly 10–30 mEq/L

• The diagnosis of alcoholic ketoacidosis is supported by the absence of a diabetic history and no evidence of glucose intolerance after initial therapy

Medications

• Supplemental HCO₃^– is indicated for treatment of hyperkalemia but is controversial for treatment of increased anion gap metabolic acidosis

• Administration of large amounts of HCO₃ ^– may have deleterious effects, including

  • Hypernatremia

  • Hyperosmolality

  • Volume overload

  • Worsening of intracellular acidosis

• In salicylate intoxication, alkali therapy must be started unless blood pH is already alkalinized by respiratory alkalosis, because the increment in pH converts salicylate to more impermeable salicylic acid and thus prevents CNS damage

• The amount of HCO₃ ^– deficit can be calculated as follows:

  • Amount of HCO₃^– deficit = 0.5 × body weight × (24 – HCO₃^–)

• Half of the calculated deficit should be administered within the first 3–4 h to avoid overcorrection and volume overload

• In methanol intoxication, ethanol is administered as a competitive substrate for alcohol dehydrogenase, the enzyme that metabolizes methanol to formaldehyde

• Inhibition of alcohol dehydrogenase by fomepizole is the standard of care

Therapeutic Procedures

• Treatment is aimed at the underlying disorder, such as insulin and volume resuscitation to restore tissue perfusion

• Lactate will later be metabolized to produce HCO₃^– and increase pH

Prognosis

• The mortality rate of lactic acidosis exceeds 50%

Prevention

• Avoid metformin use if there is tissue hypoxia or acute kidney injury

• Acute kidney injury can occur rarely with the use of radiocontrast agents in patients receiving metformin therapy

• Metformin should be temporarily halted on the day of the test and for 2 days after injection of radiocontrast agents to avoid potential lactic acidosis if renal failure occurs

When to Admit

• Because of the high mortality rate, all patients with lactic acidosis should be admitted

• Other patients with significant metabolic acidosis are almost always admitted, particularly those resulting from diabetic ketoacidosis, alcoholic ketoacidosis, uremic acidosis, or ethylene glycol, methanol toxicity or salicylate toxicity