What is the pathophysiology of Diabetic Ketoacidosis (DKA)?

From the Guidelines

Diabetic Ketoacidosis (DKA) is primarily caused by a reduction in the net effective action of circulating insulin coupled with a concomitant elevation of counterregulatory hormones.

Pathophysiology of DKA

The underlying mechanism of DKA involves:

• A reduction in the net effective action of circulating insulin
• A concomitant elevation of counterregulatory hormones, such as glucagon, catecholamines, cortisol, and growth hormone 1 These hormonal alterations lead to:
• Increased hepatic and renal glucose production
• Impaired glucose utilization in peripheral tissues, resulting in hyperglycemia and parallel changes in osmolality of the extracellular space 1 The combination of insulin deficiency and increased counterregulatory hormones in DKA also leads to:
• The release of free fatty acids into the circulation from adipose tissue (lipolysis)
• Unrestrained hepatic fatty acid oxidation to ketone bodies, resulting in ketonemia and metabolic acidosis 1 Key features of DKA include glycosuria, leading to osmotic diuresis, with loss of water, sodium, potassium, and other electrolytes 1

From the Research

Pathophysiology of Diabetic Ketoacidosis (DKA)

The pathophysiology of DKA is attributed to a combination of two hormonal abnormalities:

• A relative insulin insufficiency
• Stress hormone excess (glucagon, catecholamines, cortisol, and growth hormone) 2, 3 Factors leading to relative insulin insufficiency include:
• Withdrawal of exogenous insulin
• Pancreatic beta cell failure
• Insulin resistance Factors leading to stress hormone excess include:
• Fasting
• Stress
• Dehydration 2

Key Features of DKA Pathophysiology

The combination of these two hormonal abnormalities leads to:

• Impaired carbohydrate utilization
• Ketonaemia
• Metabolic acidosis
• Loss of water through acidotic breaths
• Rise in plasma lipids
• Hyperglycaemia and glycosuria leading to osmotic diuresis and further loss of water
• Excretion of partly neutralised ketoacids via the kidney with loss of cations (Na+ and K+) 2
• Net increase in protein catabolism, leading to an increased amino acid flux from muscle and an enhanced load of gluconeogenic precursor to the liver 2

Common Pathophysiological Mechanisms

Basic common pathophysiological mechanisms in DKA and hyperosmolar hyperglycemic state (HHS) are:

• Reduction in the effective insulin action
• Increased counterregulatory hormones (glucagon, catecholamines, cortisol, and growth hormone) 3 These mechanisms differ only in the magnitude of dehydration and degree of ketoacidosis 3