Acidosis, Lactic

Key Features

Essentials of Diagnosis

• Severe metabolic acidosis with compensatory hyperventilation

• Blood pH below 7.30

• Serum bicarbonate < 15 mEq/L

• Anion gap > 15 mEq/L

• Absent serum ketones

• Serum lactate > 5 mmol/L

General Considerations

• Characterized by accumulation of excess lactic acid in the blood

• Principal sources of lactic acid

  • Erythrocytes (which lack enzymes for aerobic oxidation)

  • Skeletal muscle

  • Skin

  • Brain

• Causes

  • Tissue hypoxia (global or local)

  • Disorders that increase epinephrine levels (severe asthma with excess beta-adrenergic-agonist use, cardiogenic or hemorrhagic shock, pheochromocytoma)

  • Drugs that impair oxidative phosphorylation (antiretroviral agents and propofol)

  • Inborn errors of metabolism

  • The MELAS syndrome (mitochondrial encephalopathy, lactic acidosis and stroke-like episodes)

• Chief pathways for removal of lactic acidosis

  • Conversion of lactic acid to glucose and its oxidation

    • Principally by the liver

    • Also by the kidneys

• Metformin-associated lactic acidosis

  • Most cases occur when use of metformin is contraindicated, in particular kidney failure

  • Metformin levels are usually > 5 mcg/L when the drug is implicated as the cause of lactic acidosis

• D-lactic acidosis can occur in patients with short bowel syndrome when unabsorbed carbohydrates are presented as substrate for fermentation by colonic bacteria

Clinical Findings

Symptoms and Signs

• Main clinical feature is marked hyperventilation

• When lactic acidosis is secondary to tissue hypoxia or vascular collapse, the clinical presentation is variable, being that of the prevailing catastrophic illness

• In idiopathic, or spontaneous, lactic acidosis

  • Onset is rapid (usually over a few hours)

  • Blood pressure is normal

  • Peripheral circulation is good

  • No cyanosis

Differential Diagnosis

Other causes of metabolic acidosis

• Diabetic ketoacidosis

• Starvation ketoacidosis

• Alcoholic ketoacidosis

• Kidney failure (acute or chronic)

• Ethylene glycol toxicity

• Methanol toxicity

• Salicylate toxicity

• Other: paraldehyde, metformin, isoniazid, iron, rhabdomyolysis

Diagnosis

Laboratory Tests

• High anion gap (serum sodium minus the sum of chloride and bicarbonate anions [in mEq/L] should be no > 15). A higher value indicates the existence of an abnormal compartment of anions

• Plasma bicarbonate and blood pH are quite low, indicating the presence of severe metabolic acidosis

• Ketones are usually absent from plasma and urine, or at least not prominent

• In the absence of azotemia, hyperphosphatemia occurs in lactic acidosis for reasons that are not clear

• The diagnosis is confirmed by a plasma lactic acid concentration of 5 mmol/L or higher (values as high as 30 mmol/L have been reported)

• Normal plasma values average 1 mmol/L, with a normal lactate–pyruvate ratio of 10:1. This ratio is greatly exceeded in lactic acidosis

Treatment

• Empiric antibiotic coverage for sepsis should be given after culture samples are obtained if the cause of lactic acidosis is unknown

• Alkalinization with intravenous ...