Differential diagnoses of hyperlactatemia

Increased lactate production occurs when cellular metabolism is abnormal owing to either a lack of oxygen in the tissues (acute circulatory failure) or, more rarely, a failure of cellular oxygen utilization despite the presence of adequate oxygen delivery ( Table,!). Clinically, the most important causes are those due to hypoxia, but let us briefly consider the other conditions.

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Table 1 Causes of lactic acidosis

Biguanides accelerate the conversion of glucose into lactate; at high levels they inhibit gluconeogenesis and pyruvate oxidation, thus raising lactate levels. This complication has been described primarily with phenformin, which is no longer available, so that this problem has become extremely rare.

In alcohol intoxication ethanol is oxidized to acetoacetic acid, producing large amounts of NADH and an increase in the ratio of NADH to NAD.

Thiamine is involved in the pyruvate dehydrogenase complex and biotin is involved in pyruvate carboxylase. Therefore deficiency of either substance can increase pyruvate and lactate levels.

Tumors are known to have high glycolytic and lactate production rates, probably due to increased lactate production by the tumor. Liver metastases leading to diminished hepatic lactate metabolism may represent a contributory factor.

Fructose infusion causes a rise in phosphofructokinase levels which reduces intracellular phosphate levels and hence ATP. Glycolysis is thus stimulated and gluconeogenesis inhibited, raising lactate levels. Today glucose has become preferable to fructose and sorbitol as an infused nutrient, and so this problem has virtually disappeared.

Diabetic ketoacidosis impairs lactate transport, and diabetic patients also have reduced muscle pyruvate dehydrogenase activity. However, the degree of lactic acidosis is usually fairly mild in such cases, unless associated with severe hypovolemia when some degree of tissue hypoxia may develop.

Inborn errors of metabolism, including glucose-6-phosphate deficiency and pyruvate dehydrogenase deficiency, can also cause lactate levels that are higher than normal owing to interference with the normal metabolic pathways.

All the above are fairly easily recognized and can be distinguished from hyperlactatemia due to cellular hypoxia.

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