pathogenesis

Last reviewed 01/2018

In diabetic ketoacidosis, insulin deficiency and high counter regulatory hormone concentrations leads to

  • hyperglycaemia – caused by
    • an accelerated catabolic state resulting in an increased glucose production by the liver and kidney through glycogenolysis and gluconeogenesis. 
    • impaired peripheral glucose utilization – this occurs at the same time, which combine to result in hyperglycemia and hyperosmolality
  • increase lipolysis and ketogenesis and cause ketonemia and  subsequent metabolic acidosis
    • excessive breakdown of adipose stores, resulting in increased levels of free fatty acids
    • oxidation of such free fatty acids by the liver through acetyl CoA produces ketone bodies (acetone, 3-beta-hydroxybutyrate - predominant ketone in DKA, and acetoacetate). Glucagon is the hormone that accelerates such fatty acid oxidation (1,2)
    • the rate at which ketone bodies are formed may exceed the rate at which acetoacetic acid and beta-hydroxybutyric acid can be utilised by muscles and other tissues. Ketogenic amino acids aggravate the derangements in lipid metabolism. Ketogenesis thus increases, leading to ketonaemia and ketonuria. If the urinary excretion is compromised by dehydration, the plasma hydrogen ion concentration increases, and systemic metabolic ketoacidosis results.

Hyperglycaemia and nausea/vomiting associated with severe ketosis leads to osmotic diuresis, severe fluid depletion, and life-threatening electrolyte imbalance (1).

  • on average, patients with DKA may have the following deficit of water and key electrolytes per kg of body weight:
    • free water 100 mL/kg
    • sodium 7–10 mEq/kg
    • potassium 3–5 mEq/kg
    • chloride 3–5 mmol/kg
    • phosphorus 1 mmol/kg (3).

These changes will further worsen hyperglycemia and hyperketonemia by stimulating further stress hormone production. Exogenous insulin plus fluid and electrolyte therapy is needed to interrupt this cycle which otherwise will result in fatal dehydration and metabolic acidosis (1)

Reference:

Related pages:

ketogenesis

ketone bodies