A gap metabolic acidosis is secondary to the addition of acid, either exogenous or endogenous. The major causes are lactic acidosis, ketoacidosis, kidney disease, and ingestions (Table 21–12). A useful mnemonic for the differential diagnosis of increased anion gap metabolic acidosis is GOLDMARK (glycols [ethylene glycol and propylene glycol], oxoproline, L-lactate, D-lactate, methanol, aspirin, renal failure, and ketoacidosis) (Table 21–13).
++ Table Graphic Jump Location Table 21–13.Common causes and therapy for increased anion gap metabolic acidosis. ||Download (.pdf) Table 21–13. Common causes and therapy for increased anion gap metabolic acidosis.
|Cause ||Treatment |
|Lactic acidosis ||Therapy aimed at correcting the underlying cause. Treatment of type A requires improving perfusion and matching oxygen consumption with fluids, packed red cells, vasopressors, and inotropes as needed. Treatment of type B generally requires removal of the offending agent or supplementing key cofactors of anaerobic metabolism. |
|D-Lactic acidosis ||Sodium bicarbonate may be administered in the setting of severe acidemia. Specific antimicrobial agents (metronidazole, neomycin) can be utilized in patients with short gut syndrome. A low carbohydrate diet can be effective by decreasing substrate delivery to the distal colon. Fecal transplant has been utilized successfully in patients unresponsive to conventional therapies. |
|Therapy involves correction of the state of insulin deficiency and glucagon excess. In diabetic ketoacidosis, this requires administration of exogenous insulin, generally with a continuous infusion. In starvation and alcoholic ketoacidosis, dextrose-containing fluids will stimulate endogenous insulin release. In all groups, correction of volume depletion with isotonic fluids as well as judicious repletion of electrolytes (particularly potassium and phosphorous) are imperative. |
|Kidney failure ||Supplemental alkali therapy (sodium bicarbonate or sodium citrate). Hemodialysis when necessary. |
|See Chapter 38. |
|Salicylic acid ||See Chapter 38. |
|Pyroglutamic acid (5-Oxoproline) ||Therapy is directed at the underlying cause. Generally requires withdrawal of the offending agent (acetaminophen) and sodium bicarbonate therapy for severe acidemia. N-acetylcysteine may be effective in restoring glutathione stores. |
Lactic acidosis is a common cause of metabolic acidosis, producing an elevated anion gap and decreased serum pH when present without other acid-base disturbances. Lactate is formed from pyruvate in anaerobic glycolysis. Normally, lactate levels remain low (1 mEq/L) because of metabolism of lactate principally by the liver through gluconeogenesis or oxidation via the Krebs cycle. In lactic acidosis, lactate levels are at least 4–5 mEq/L but commonly significantly higher. There are three types of lactic acidosis.
Type A (hypoxic) lactic acidosis is most common, resulting from tissue hypoxia, usually from septic, cardiogenic, or hemorrhagic shock; mesenteric ischemia; respiratory failure; and carbon monoxide poisoning. These conditions increase peripheral lactic acid production and decrease hepatic metabolism of lactate as liver perfusion declines.
Type B lactic acidosis is secondary to impaired mitochondrial oxygen utilization and may be due to metabolic causes (eg, diabetes mellitus, liver disease, kidney disease, thiamine deficiency, ...