161 - Alcoholic Ketoacidosis

in severity: ketoacidosis, lactic acidosis, acetic acidosis, and loss of bicarbonate in urine. AKA arises from a complicated interplay of the metabolic effects of alcohol in fasted, dehydrated alcoholics who abruptly stop their intake of ethanol. β-Hydroxybutyrate is the predominant ketoacid. Metabolism of ethanol to acetaldehyde is catalyzed by alcohol dehydrogenase in the liver and results in accumulation of the reduced form of nicotinamide adenine dinucleotide (NADH) relative to the oxidized form of nicotinamide adenine dinucleotide (NAD+). The altered ratio of NADH/NAD+ is the rate-limiting step in alcohol metabolism and favors the conversion of acetoacetate to β-hydroxybutyrate, as illustrated in Figure 161.1. Impaired insulin effects, dehydration, and hormonal responses propagate the accumulation of ketoacid. Ethanol consumption, acute starvation, and catecholamine release cause a relative insulin insufficiency that acts to favor lipolysis and limit glycogen storage. The formation of ketone bodies is further promoted by a dehydration-induced stress response– related release of cortisol, growth hormone, glucagons, and catecholamines. It is unclear whether the elevated levels of cortisol and growth hormone observed in patients with AKA initiate or sustain this process. Ketone bodies in the form of β-hydroxybutyrate are produced as a result of the NADH/ NAD+ ratio induced by ethanol metabolism, as well as the lipolytic effect of counterregulatory hormones. Renal excretion of ketone bodies becomes impaired because of dehydration, volume contraction, and diminished renal clearance. Accumulation of ketoacid ensues. Lactic acidosis is a common, concurrent acid-base disorder, in addition to ketoacidosis. Although lactic acidosis may result from another cause such as sepsis or seizures, alcohol consumption can cause mild accumulation of lactic acid by two distinct mechanisms. First, the elevated NADH/NAD+ ratio can shift the pyruvate–lactic acid equilibrium in favor of lactic acidosis. Second, the thiamine deficiency common in chronic alcoholics prohibits the alternative oxidation of pyruvate to acetyl coenzyme A because thiamine is a coenzyme in this reaction.