Foundations · Year 1 · from Foundations
Case 1: Diabetic Ketoacidosis (Uncontrolled Ketogenesis)
Clinical Image
Source: Wikipedia - Diabetic ketoacidosis - Public Domain
Case Presentation
A 22-year-old man with type 1 diabetes presents to the emergency department with nausea, vomiting, abdominal pain, and altered mental status. He reports running out of insulin 3 days ago. On examination, he is lethargic but arousable, has dry mucous membranes, deep rapid breathing (Kussmaul respirations), and a fruity odor on his breath. Vital signs show heart rate 120, blood pressure 95/60, respiratory rate 28. Laboratory studies reveal blood glucose 485 mg/dL, pH 7.15, pCO2 18 mmHg, HCO3 8 mEq/L, anion gap 28, serum ketones strongly positive, potassium 5.8 mEq/L (elevated due to acidosis causing cellular shift). Urinalysis shows 3+ ketones and 4+ glucose. He is diagnosed with diabetic ketoacidosis (DKA). The pathophysiology is explained: absolute insulin deficiency combined with elevated glucagon creates a metabolic state mimicking severe starvation. Hormone-sensitive lipase in adipose tissue is maximally activated, flooding the liver with free fatty acids. Hepatic beta-oxidation generates excess acetyl-CoA, but gluconeogenesis diverts oxaloacetate away from the TCA cycle. Unable to enter the cycle, acetyl-CoA is converted to ketone bodies (acetoacetate, beta-hydroxybutyrate, acetone). He is treated with IV insulin, aggressive fluid resuscitation, and potassium replacement.
Key Learning Points
- In insulin deficiency, unrestrained lipolysis releases fatty acids that undergo hepatic beta-oxidation to acetyl-CoA; simultaneously, gluconeogenesis depletes oxaloacetate, preventing acetyl-CoA from entering the TCA cycle
- Excess acetyl-CoA is diverted to ketogenesis; ketone bodies are moderately strong organic acids that cause metabolic acidosis with a high anion gap
- The fruity breath odor results from acetone (formed by spontaneous decarboxylation of acetoacetate), which is volatile and exhaled; Kussmaul respirations represent respiratory compensation for metabolic acidosis