A 25-year-old with type 1 diabetes presents with Kussmaul breathing, blood glucose 480 mg/dL, pH 7.1, bicarbonate 8 mEq/L. The primary biochemical mechanism generating this metabolic acidosis is:
- A Uncontrolled ketogenesis producing acetoacetic acid and beta-hydroxybutyric acid that dissociate to release H⁺ and consume bicarbonate ✓
- B Increased lactate production from anaerobic glycolysis due to insulin deficiency
- C Renal tubular acidosis from glucosuria-induced tubular injury impairing H⁺ secretion
- D Hyperchloremic acidosis from excessive saline administration during prior treatment
Correct answer: A. Uncontrolled ketogenesis producing acetoacetic acid and beta-hydroxybutyric acid that dissociate to release H⁺ and consume bicarbonate
Explanation
In DKA, absolute insulin deficiency with glucagon excess unleashes lipolysis and hepatic ketogenesis. Acetyl-CoA flux into ketone body synthesis produces acetoacetic acid and beta-hydroxybutyric acid (strong organic acids). These dissociate at physiologic pH, releasing H⁺ that consumes HCO3⁻ via the Henderson-Hasselbalch buffer, producing high anion gap metabolic acidosis. The ratio of beta-HB to acetoacetate is 3:1 in DKA. Lactic acidosis may coexist but is not primary. Hyperchloremic acidosis is a complication of saline resuscitation, not the primary DKA mechanism.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.