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Alcoholic Ketoacidosis
Updated: Jul 2, 2007
Introduction
Background
Alcoholic ketoacidosis (AKA) is an acute metabolic acidosis that typically occurs in people who chronically abuse alcohol and have a recent history of binge drinking, little or no food intake, and persistent vomiting. AKA is characterized by elevated serum ketone levels and a high anion gap. A concomitant metabolic alkalosis is common, secondary to vomiting and volume depletion. Although AKA most commonly occurs in adults with alcoholism, AKA has been reported in less-experienced drinkers of all ages.
Pathophysiology
AKA is a result of starvation with glycogen depletion and counter-regulatory hormone production, a raised nicotinamide adenine dinucleotide (NADH) to nicotinamide adenine dinucleotide (NAD+) ratio related to the metabolism of ethanol, and volume depletion, resulting in ketogenesis.
When the dietary intake of carbohydrates is insufficient to supply glucose for the body's needs and hepatic glycogen stores are depleted by fasting, ketones are produced in the liver as an alternative source of energy. Two steps are required for ketogenesis: (1) enhanced lipolysis with an increased delivery of free fatty acids to the liver and (2) an alteration in hepatic metabolism by which these free fatty acids are converted preferentially into ketones instead of into triglycerides. Decreased insulin activity, increased counter-regulatory hormone levels (primarily glucagon, but also cortisol, catecholamines, and growth hormone), and volume depletion all play a role in ketogenesis.
The body's response to starvation is a decrease in insulin activity and an increase in the production of counter-regulatory hormones. These counter-regulatory hormones cause the release of free fatty acids from peripheral adipose tissue. However, excess fatty acids alone are insufficient to cause ketoacidosis since, normally, the liver metabolizes free fatty acids into triglycerides. The key difference in the starvation state is in mitochondrial enzyme activity; specifically, the rate at which carnitine acyltransferase (CAT) transports free fatty acids into the mitochondria for oxidation. CAT activity is low in the fed state and accelerated in the fasting state. Glucagon excess is believed to have the major role in this hepatic response.
Prolonged vomiting leads to dehydration, which decreases renal perfusion, thereby limiting urinary excretion of ketoacids. Moreover, volume depletion increases the concentration of counter-regulatory hormones, further stimulating lipolysis and ketogenesis.
Ethanol is oxidized to acetaldehyde, which is itself oxidized to acetate. Both steps require the reduction of nicotinamide adenine dinucleotide (NAD+) to reduced nicotinamide adenine dinucleotide (NADH). The increased ratio of NADH to NAD+ has several implications: (1) impaired conversion of lactate to pyruvate with an increase in serum lactic acid levels, (2) impaired gluconeogenesis because pyruvate is not available as a substrate for glucose production, and (3) a shift in the beta-hydroxybutyrate (β-OH) to acetyl acetate (AcAc) equilibrium toward β-OH. β-OH is the predominate ketone in AKA. Understanding this is essential because routine clinical assays for ketonemia test for AcAc and acetone but not for β-OH. Clinicians underestimate the degree of ketonemia if they rely solely on the results of laboratory testing.
Frequency
United States
The prevalence of AKA in the United States correlates with the incidence and distribution of alcohol abuse within a given community.
Mortality/Morbidity
Mortality is rare. Morbidity more often results from associated complications, such as liver dysfunction, acute pancreatitis, seizures, rhabdomyolysis, hypoglycemia, lactic acidosis, heart failure, or systemic infection.
Race
No specific distribution of this disorder has been identified based on race or ethnicity.
Sex
Males and females are affected equally.
Age
AKA usually occurs in persons aged 20-60 years who are chronic abusers of alcohol. AKA occurs only rarely after a binge in persons who are not chronic drinkers.
Clinical
History
Example case of alcoholic ketoacidosis: A man who chronically drinks alcohol and has poor baseline nutritional status engages in a drinking binge. He develops nausea and vomiting and so he stops drinking and eating altogether. He presents to the emergency department 24-48 hours later. The typical symptoms may include the following:
- Nausea, vomiting, abdominal pain, and/or hematemesis (each found in 60-75% of patients
- Dyspnea, tremulousness, and/or dizziness (10-20% each)
- Muscle pain, fever, diarrhea, syncope, seizure, and/or melena (1-8% each)
Physical
Generally, the physical findings relate to volume depletion and chronic alcohol abuse. The fruity odor of ketones may be present on the patient's breath. The patient's mental status may be impaired. Physical findings may include the following:
- Tachycardia, tachypnea, and/or abdominal tenderness (30-40% each)
- Hypotension, hypothermia, fever, abdominal distention, rebound tenderness, hepatomegaly, ascites, and/or heme-positive stools (These are less common, with each found in 1-15% of patients.)
Causes
Most cases of AKA are related to poor nutritional status due to long-standing alcohol abuse.
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| References |
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References
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Further Reading
Keywords
alcoholic ketoacidosis, AKA, alcoholic acidotic coma, alcohol withdrawal, acute metabolic acidosis, metabolic alkalosis, alcohol abuse, glycogen depletion, lipolysis, ketogenesis, ethanol consumption, ketonemia, alcoholism, chronic alcoholism, chronic alcohol abuse, ketones, substance abuse, ketosis, binge drinking, Wernicke encephalopathy, Wernicke's encephalopathy
