Pathophysiology of DKA

Fig 2: Pathophysiology of DKA [25]


Consequence of a deliberate or inadvertent failure to take exogenous insulin (known patient) or as part of the initial presentation of T1DM.

Counter-regulatory hormones

Low levels of insulin stimulate the release of glucagon, ACTH, growth hormone, prolactin and catecholamines.


Amino acids, lactate and glycerol are converted to glucose within the liver and released into the circulation.


Breakdown of glycogen stores within the striated muscle and liver release glucose into the circulation.

Reduced glucose uptake

Despite the presence of high blood glucose, low levels of insulin inhibit uptake by the peripheral tissues, further exacerbating hyperglycaemia.


Triglycerides within adipose tissue are broken down due to release of free fatty acids. These are subsequently oxidised to form ketone bodies (acetoacetate and β-hydroxybutyrate).

Osmotic diuresis

Plasma glucose concentration increases until it exceeds the reabsorptive capacity of the nephron. At this point, glucose is excreted into the urine along with water and solutes (osmotic diuresis). This leads to significant dehydration and electrolyte imbalance.


As ketone bodies accumulate, the bicarbonate buffering system is overcome resulting in a progressive metabolic acidosis.