Diabetic Ketoacidosis ll: Pathophysiology

Diabetic ketoacidosis, or DKA, begins with insulin deficiency. In type 1 diabetes, this deficiency is typically absolute. In type 2 diabetes, it happens when there is a severe relative insulin deficiency during physiological stressors, such as infection.

Lack of insulin blocks glucose uptake and raises counterregulatory hormones that drive gluconeogenesis and glycogenolysis, worsening hyperglycemia.

In the liver, increased fatty acid beta-oxidation generates acetyl-CoA, which is then converted into ketone bodies such as acetoacetate, β-hydroxybutyrate, and acetone.

Excess ketones accumulate and cause metabolic acidosis.

Meanwhile, rising blood glucose levels exceed the renal threshold, leading to glucose excretion in the urine. Hyperglycemia leads to osmotic diuresis, which depletes water, sodium, potassium, and phosphate.

Together, hyperglycemia, acidosis, and fluid and electrolyte loss define diabetic ketoacidosis.