Pathophysiology
Clinical meaning
Diabetic ketoacidosis results from absolute or relative insulin deficiency combined with counter-regulatory hormone excess (glucagon, cortisol, catecholamines, growth hormone). Insulin deficiency prevents glucose uptake by peripheral tissues and fails to suppress hepatic gluconeogenesis and glycogenolysis, producing severe hyperglycemia (typically > 14 mmol/L). Without insulin, adipose tissue undergoes unrestrained lipolysis, releasing free fatty acids that undergo hepatic beta-oxidation to acetyl-CoA. Excess acetyl-CoA overwhelms the Krebs cycle and is diverted to ketogenesis, producing acetoacetate, beta-hydroxybutyrate, and acetone. These ketoacids dissociate at physiologic pH, releasing hydrogen ions and causing high anion gap metabolic acidosis (pH < 7.3, bicarbonate < 18 mmol/L). Osmotic diuresis from glycosuria causes profound dehydration (average 5-7 L deficit), electrolyte losses (especially potassium, sodium, phosphate), and prerenal azotemia. Total body potassium is severely depleted despite initial serum levels that may be normal or elevated due to acidosis-driven transcellular shift.