The pathophysiology (see image) of diabetic ketoacidosis must be considered to help understand its presentation and the necessary management.
There are 3 main biochemical features:
Firstly, lack of insulin causes glucose to remain in the blood rather than be transferred into cells for utilisation. The body therefore responds as if it were in starvation and hepatic glucose production becomes increased. Osmotic diuresis occurs as a consequence of this glucose rich blood being filtered by the kidneys. Glucose is normally reabsorbed by the proximal tubule but in DKA the amount of glucose filtered exceeds the renal threshold for reabsorbtion. The presence of glucose in the tubules causes water retention in the lumen, thus increasing urine output and decreasing reabsorption into the body, leading to dehydration and electrolyte depletion.
Secondly, an absence of insulin together with elevated stress hormones such as catecholamines, leads to lipolysis, resulting in numerous free fatty acids available for hepatic ketogenesis. Consequently, there is increased ketone body formation by fatty acid oxidation in the liver, leading to an elevated level in the blood. These ketones give a distinct smell to the urine and breath.
Thirdly, the ketone bodies lower the pH of the blood resulting in metabolic acidosis. This causes nausea and vomiting resulting in further dehydration. The body compensates for the acidosis by hyperventilation (Kussmals respiration) in an attempt to raise blood pH by clearing carbon dioxide.
Kumar and Clark's Clinical Medicine
Davidson's Principles & Practice of Medicine
Oxford Handbook of Clinical Medicine
Waller et al Medical Pharmacology & Therapeutics
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