Ketoacidosis

Ketoacidosis is a metabolic state associated with pathologically high serum and urine concentrations of ketone bodies, namely acetone, acetoacetate, and beta-hydroxybutyrate. During catabolic states, fatty acids are metabolized to ketone bodies, which can be readily utilized for fuel by individual cells in the body. Of the three major ketone bodies, acetoacetic acid is the only true ketoacid chemically, while beta-hydroxybutyric acid is a hydroxy acid, and acetone is a true ketone. Figure 1 shows the schematic of ketogenesis where the fatty acids generated after lipolysis in the adipose tissues enter the hepatocytes via the bloodstream and undergo beta-oxidation to form the various ketone bodies. This biochemical cascade is stimulated by the combination of low insulin levels and high glucagon levels (i.e., a low insulin/glucagon ratio). Low insulin levels, most often secondary to absolute or relative hypoglycemia as with fasting, activate hormone-sensitive lipase, which is responsible for the breakdown of triglycerides to free fatty acid and glycerol.

The clinically relevant ketoacidoses to be discussed include diabetic ketoacidosis (DKA), alcoholic ketoacidosis (AKA), and starvation ketoacidosis. DKA is a potentially life-threatening complication of uncontrolled diabetes mellitus if not recognized and treated early. It typically occurs in the setting of hyperglycemia with relative or absolute insulin deficiency. The paucity of insulin causes unopposed lipolysis and oxidation of free fatty acids, resulting in ketone body production and subsequent increased anion gap metabolic acidosis. Alcoholic ketoacidosis occurs in patients with chronic alcohol abuse, liver disease, and acute alcohol ingestion. Starvation ketoacidosis occurs after the body is deprived of glucose as the primary source of energy for a prolonged time, and fatty acids replace glucose as the major metabolic fuel.