Diabetic Ketoacidosis ll: Pathophysiology

Diabetic ketoacidosis (DKA) is a metabolic emergency characterized by hyperglycemia, ketonemia, and metabolic acidosis. It results from severe insulin deficiency and an excess of counterregulatory hormones, leading to uncontrolled lipolysis, ketogenesis, and widespread electrolyte and fluid disturbances.

Pathophysiology 
The central event in DKA is a profound loss of insulin action. Without insulin, glucose uptake in insulin-dependent tissues is impaired, while hepatic glucose production increases due to the unopposed actions of glucagon, cortisol, catecholamines, and growth hormone. This results in marked hyperglycemia.

At the same time, the absence of insulin allows lipolysis to proceed unchecked. Free fatty acids (FFAs) released from adipose tissue undergo beta-oxidation in the liver, producing the ketone bodies—acetoacetate, beta-hydroxybutyrate, and acetone. The accumulation of these organic acids causes high anion gap metabolic acidosis.

Hyperglycemia leads to osmotic diuresis, resulting in polyuria, electrolyte losses, and volume depletion. Continued diuresis and reduced fluid intake worsen hypovolemia and reduce renal perfusion, further impairing the clearance of glucose and ketones.

Despite severe total-body potassium depletion, serum potassium levels may appear normal or elevated due to extracellular shifts driven by acidosis and insulin deficiency. However, with insulin therapy and correction of acidosis, potassium rapidly moves into cells, creating a risk of hypokalemia unless replaced.

Acidosis stimulates the respiratory center, producing Kussmaul respirations that lower CO₂ to compensate. As plasma osmolality rises—often exceeding 330 mOsm/kg—cerebral dehydration may cause confusion, stupor, or coma. In DKA, hyperosmolality, rather than acidosis, is the primary cause of coma.