ESSENTIALS OF DIAGNOSIS
Severe metabolic acidosis with compensatory hyperventilation.
Blood pH < 7.30.
Serum bicarbonate < 15 mEq/L.
Anion gap > 15 mEq/L.
Absent serum ketones.
Serum lactate > 5 mmol/L.
Lactic acidosis is characterized by accumulation of excess lactic acid in the blood. Normally, the principal sources of this acid are the erythrocytes (which lack enzymes for aerobic oxidation), skeletal muscle, skin, and brain. Conversion of lactic acid to glucose and its oxidation principally by the liver but also by the kidneys represent the chief pathways for its removal. Hyperlactatemia and acidosis occur when lactate production exceeds lactate consumption. Causes include tissue hypoxia (global or local), disorders that increase epinephrine levels (severe asthma with excess beta-adrenergic agonist use, cardiogenic or hemorrhagic shock, pheochromocytoma), and drugs that impair oxidative phosphorylation (antiretroviral agents and propofol). Most cases of metformin-associated lactic acidosis occur in patients in whom there were contraindications to the use of metformin, in particular kidney failure. Metformin levels are usually greater than 5 mcg/L when metformin is implicated as the cause of lactic acidosis. Other causes of lactic acidosis include several inborn errors of metabolism and the MELAS syndrome (mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes). D-lactic acidosis can occur in patients with short bowel syndrome when unabsorbed carbohydrates are presented as substrate for fermentation by colonic bacteria.
The main clinical feature of lactic acidosis 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. However, in the idiopathic, or spontaneous, variety, the onset is rapid (usually over a few hours), blood pressure is normal, peripheral circulation is good, and there is no cyanosis.
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. The first clue may be a high anion gap (serum sodium minus the sum of chloride and bicarbonate anions [in mEq/L] should be no greater than 15). A higher value indicates the existence of an abnormal compartment of anions. If this cannot be clinically explained by an excess of keto acids (diabetes), inorganic acids (uremia), or anions from medication overdosage (salicylates, methyl alcohol, ethylene glycol), then lactic acidosis is probably the correct diagnosis. (See also Chapter 21.) In the absence of azotemia, hyperphosphatemia may be a clue to the presence of 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.1