In the absence of glucose, the brain requires a water-soluble, fat-derived fuel for metabolism and ketoacids serve this function. Unsurprisingly, as a result of this, the main factor controlling the production of ketoacids is the relative lack of insulin. This explains why type 1 diabetics, who certainly do not lack glucose, are prone to DKA when they go without insulin. Ketoacids are produced by the metabolism of acetyl-CoA in the liver. There are 3 main substrates for the generation of acetyl-CoA – fatty acids (in the setting of relative insulin deficiency), ethanol, and occasionally, the product of the metabolism by bacteria of some poorly-absorbed carbohydrates in the colon.
Alcoholic ketoacidosis most often occurs in the setting of a combination of high alcohol intake and poor nutrition. The decreased carbohydrate intake inhibits insulin production and increases ketoacid generation while the alcohol is itself metabolized to ketoacids via acetaldehyde and acetic acid. Commonly, patients present with a high anion gap metabolic acidosis and ketonemia although the picture can be muddied in certain situations:
1. Lactic acidosis induced by hypoperfusion
2. Metabolic alkalosis due to vomiting
3. In the setting of relatively normal renal function, the ketoacids are rapidly excreted in the urine. If these anions are excreted with Na or K, this can lead to a fall in the anion gap making the diagnosis less apparent.
The treatment is relatively simple, glucose and volume replacement. However, there is one important caveat. After successful treatment, ketoacids are no longer available as brain fuel and glucose again becomes the primary fuel. In order for aerobic glycolysis to proceed efficiently, pyruvate dehydrogenase is required. Thiamine (or vitamin B1) is an essential co-factor for this enzyme and in its absence, anaerobic glycolysis increases in areas of the brain with high metabolic rates leading to an accumulation of lactate and intracellular acidosis. Nutritional deficiencies in alcoholics encompass vitamin deficiencies and many of them lack thiamine. The lactate accumulation induced by this deficiency produces the symptoms of Wernicke’s encephalopathy. For this reason, it is vitally important that the thiamine is administered to these patients prior to treating the ketoacidosis.
One problem I see occasionally in my residency program is residents giving too low dose oral thiamine (I.e., chronic but stable thiamine deficiency) in these situations rather than appropriate, Wernicke-treating doses.
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