Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content + Download Section PDF Listen ++ 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) + Key Features Download Section PDF Listen +++ +++ Essentials of Diagnosis ++ 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 RTA. Urinary anion gap may help distinguish between these causes +++ 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, beta-hydroxybutyrate, and exogenous toxins Other anions such as isocitrate, alpha-ketoglutarate, malate, and D-lactate may contribute to the anion gap of lactic acidosis, diabetic ketoacidosis (DKA), and acidosis of unknown etiology Uremia creates an increased anion gap metabolic acidosis from unexcreted organic acids and anions (Table 21–13) ++Table Graphic Jump LocationTable 21–13.Common causes and therapy for increased anion gap metabolic acidosis.View Table||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. 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. Ketoacidosis Diabetes mellitus Starvation Alcoholic 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. Ingestions Methylene glycol Ethylene glycol Initial treatment requires rapid stabilization of the patient’s airway and circulation as needed. Sodium bicarbonate should be given to address systemic acidosis by bolus and subsequently continuous infusion therapy to maintain a pH > 7.35. Fomepizole (or less commonly ethanol) can be given to inhibit alcohol dehydrogenase. Fomepizole is loaded at 15 mg/kg intravenously, followed by 10 mg/kg every 12 hours. Hemodialysis is the most effective method for removing parent alcohols and their toxic metabolites. Hemodialysis should be initiated early in patients with an elevated anion gap metabolic acidosis or end organ damage in the setting of known ingestion. Salicylic acid Activated charcoal may be administered to awake or intubated patients within 2 hours of ingestion. Sodium bicarbonate should be initiated by bolus followed by continuous infusion to target a urine pH of 7.5 or higher. Supplemental glucose should be administered to all patients with alteration in mental status. Hemodialysis is effective in removing salicylate and generally reserved for severe cases or marked elevations in salicylate concentration. 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. + Clinical Findings Download Section PDF Listen +++ ++ 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 + Diagnosis Download Section PDF Listen +++ ++ See Table 21–11 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 ++Table Graphic Jump LocationTable 21–11.Primary acid-base disorders and expected compensation.View Table||Download (.pdf) Table 21–11. Primary acid-base disorders and expected compensation. Disorder Primary Defect Compensatory Response Magnitude of Compensation Respiratory acidosis Acute ↑ PCO2 ↑ HCO3– ↑ HCO3– 1 mEq/L per 10 mm Hg ↑ PCO2 Chronic ↑ PCO2 ↑ HCO3– ↑ HCO3– 3.5 mEq/L per 10 mm Hg ↑ PCO2 Respiratory alkalosis Acute ↓ PCO2 ↓ HCO3– ↓ HCO3– 2 mEq/L per 10 mm Hg ↓ PCO2 Chronic ↓ PCO2 ↓ HCO3– ↓ HCO3– 5 mEq/L per 10 mm Hg ↓ PCO2 Metabolic acidosis ↓ HCO3– ↓ PCO2 ↓ PCO2 1.3 mm Hg per 1 mEq/L ↓ HCO3– Metabolic alkalosis ↑ HCO3– ↑ PCO2 ↑ PCO2 0.7 mm Hg per 1 mEq/L ↑ HCO3– + Treatment Download Section PDF Listen +++ ++ Treatment is aimed at the underlying disorder, such as insulin and fluid therapy for diabetes and appropriate volume resuscitation to restore tissue perfusion NaHCO3 therapy is controversial in the treatment of increased anion gap metabolic acidoses, and is usually reserved for severe cases (arterial pH < 7.1–7.2) Administration of large amounts of HCO3– may have deleterious effects, including Hypernatremia Hyperosmolality Volume overload Worsening of intracellular acidosis + Outcome Download Section PDF Listen +++ +++ Prognosis ++ The mortality rate of lactic acidosis exceeds 50% +++ 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 + References Download Section PDF Listen +++ + +Fayfman M et al. Management of hyperglycemic crises: diabetic ketoacidosis and hyperglycemic hyperosmolar state. Med Clin North Am. 2017 May;101(3):587–606. [PubMed: 28372715] + +Lalau JD et al. Metformin-associated lactic acidosis (MALA): moving towards a new paradigm. Diabetes Obes Metab. 2017 Nov;19(11):1502–12. [PubMed: 28417525] + +Palmer BF et al. Electrolyte and acid-base disturbances in patients with diabetes mellitus. N Engl J Med. 2015 Aug 6;373(6):548–59. [PubMed: 26244308] + +Seheult J et al. Lactic acidosis: an update. Clin Chem Lab Med. 2017 Mar 1;55(3):322–33. [PubMed: 27522622] + +Sharma S et al. Comprehensive clinical approach to renal tubular acidosis. Clin Exp Nephrol. 2015 Aug;19(4):556–61. [PubMed: 25951806] + +Suetrong B et al. Lactic acidosis in sepsis: it's not all anaerobic: implications for diagnosis and management. Chest. 2016 Jan;149(1):252–61. [PubMed: 26378980]