A 13-year-old boy with type 1 diabetes presents with polyuria, polydipsia, and blood glucose of 410 mg/dL. C-peptide is undetectable. Anti-GAD65 antibodies are positive. He develops DKA. Which pathophysiological mechanism is responsible for the high anion gap metabolic acidosis in this child?
- A Lactic acid accumulation due to tissue hypoperfusion
- B Excessive beta-oxidation of fatty acids producing ketone bodies (acetoacetate and beta-hydroxybutyrate) ✓
- C Impaired renal bicarbonate reabsorption due to tubular acidosis
- D Hyperchloraemic acidosis from saline infusion
Explanation
In diabetic ketoacidosis, absolute insulin deficiency leads to unopposed glucagon action, which activates hormone-sensitive lipase, releasing free fatty acids from adipose tissue. Hepatic beta-oxidation of these fatty acids generates excess acetyl-CoA, which overwhelms the TCA cycle and is channelled into ketone body synthesis (acetoacetate and beta-hydroxybutyrate). These strong organic acids dissociate completely at physiological pH, consuming bicarbonate buffers and producing a high anion gap metabolic acidosis. Lactic acidosis may complicate severe DKA but is not the primary mechanism. Hyperchloraemic acidosis is a dilutional complication of aggressive saline resuscitation, not the primary cause.
Reference: Ghai Essential Pediatrics, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.