What is ethanol (etoh) induced ketoacidosis and how does it occur?

Alcoholic Ketoacidosis: Pathophysiology and Clinical Manifestations

Alcoholic ketoacidosis (AKA) is a metabolic disorder characterized by high anion gap metabolic acidosis with ketosis that occurs in chronic alcoholics following a recent binge, typically when they stop drinking and eating due to gastritis or another intercurrent illness. 1

Pathophysiology

• AKA develops due to a combination of insulin deficiency and increased counterregulatory hormones, leading to release of free fatty acids from adipose tissue (lipolysis) and unrestrained hepatic fatty acid oxidation to ketone bodies (β-hydroxybutyrate and acetoacetate), resulting in ketonemia and metabolic acidosis 2

• The underlying mechanism involves:

  • Poor glycogen stores from malnutrition 1
  • Elevated nicotinamide adenine dinucleotide and hydrogen ratio (NADH/NAD+) from alcohol metabolism 1
  • Starvation state leading to decreased insulin and increased counterregulatory hormones 3
  • Predominance of β-hydroxybutyrate over acetoacetate, which may cause false-negative or weakly positive ketone tests 4

Clinical Presentation

• AKA typically develops after a period of increased alcohol intake followed by:

  • Abdominal pain and vomiting 4
  • Marked decrease in caloric intake 4
  • Dehydration 4
  • Nausea and gastrointestinal symptoms 1

• Physical findings may include:

  • Poor skin turgor indicating dehydration 2
  • Tachycardia and hypotension 2
  • Altered mental status (ranging from alert to profound lethargy) 2
  • Kussmaul respirations (deep, rapid breathing) may be present 2

Laboratory Findings

• Blood glucose levels typically range from hypoglycemic to mildly elevated (rarely >250 mg/dL) 2
• High anion gap metabolic acidosis 1
• Serum bicarbonate usually >18 mEq/L in starvation ketosis, but can be lower in AKA 2
• Ketosis with predominance of β-hydroxybutyrate 4
• Variable blood pH findings depending on coexisting metabolic alkalosis (from vomiting) and respiratory alkalosis (from pain or delirium tremens) 5
• Electrolyte abnormalities are common 1

Differential Diagnosis

AKA must be distinguished from other causes of ketoacidosis and high anion gap metabolic acidosis:

• Diabetic ketoacidosis (DKA) - typically has blood glucose >250 mg/dL 2
• Starvation ketosis - usually has serum bicarbonate not lower than 18 mEq/L 2
• Other causes of high anion gap metabolic acidosis:
  • Lactic acidosis 2
  • Ingestion of drugs (salicylate, methanol, ethylene glycol, paraldehyde) 2
  • Chronic renal failure (typically hyperchloremic acidosis) 2

Treatment

• The cornerstone of AKA management includes intravenous fluid resuscitation with isotonic saline and glucose administration to stop ketogenesis. 4, 3

• Specific treatment components:

  • Fluid rehydration with isotonic saline (0.9% NaCl) 2
  • Intravenous glucose administration 4
  • Electrolyte repletion, particularly potassium 5
  • Thiamine supplementation to prevent Wernicke's encephalopathy 5
  • Insulin is usually not necessary unless the patient has diabetes 5

• Careful monitoring and evaluation for concurrent medical conditions is essential, as these often precipitate AKA and may contribute to morbidity and mortality 4

Prognosis and Complications

• The prognosis for the acute metabolic disorder itself is excellent with proper treatment 5
• Major causes of morbidity and mortality are failure to adequately treat concurrent medical or surgical conditions 4
• Patients rarely die from the ketoacidosis or lactic acidosis associated with alcohol abuse, but may succumb to other precipitating or coexisting illnesses 3

Common Pitfalls in Diagnosis and Management

• False-negative or weakly positive ketone tests due to predominance of β-hydroxybutyrate over acetoacetate 4
• Failing to recognize and treat underlying precipitating conditions 4
• Unnecessary insulin administration in non-diabetic patients 5
• Overlooking the need for thiamine supplementation in alcoholic patients 5
• Failure to address the underlying alcohol use disorder 5