Diabetic Ketoacidosis

Pathogenesis

• v Insulin
• v glucose uptake in cells
• v glycogen formation
• v FFA esterification and synthesis and TG synthesis
• ^ glucagon secretion (counter-regulatory hormone)

• ^ glycogenolysis
• ^ gluconeogensis (amino acids > glucose)
• ^ lipolysis, ketone body formation (v malonyl CoA > v carnitine palmitoyltransferase I (CPT-1) > ^ acyl CoA)

Net effects ('starvation in a land of plenty')

• Hyperglycaemia
• Ketonaemia (normally only occurs when CHO low as an alternative source of energy)

Hyperglycaemia

• Osmotic diuresis - renal water loss (polyuria) > dehydration > shock (later), potassium loss, magnesium loss, phosphate loss

Ketonaemia

• Metabolic acidosis - v pH (^ serum K+ by various mechanisms), gastritis > epigastric pain & vomiting, urinary phosphate buffer loss

Compensatory mechanisms

• Dehydration > thirst, polydipsia
• Metabolic acidosis > respiratory compensation (Kussmaul breathing)

Serum potassium and DKA

• v - osmotic diuresis, vomiting
• ^ - metabolic acidosis / transcellular shifts / decreased renal excretion, shock > decreased GFR > v renal excretion

Therefore can be elevated, normal or depressed (but usually total body levels are depleted)

Treatment principles

• Rehydrate
• Insulin (aim to reverse ketoacidosis, decreased glucose is a secondary goal)
• Potassium replacement
• Magnesium replacement
• Phosphate replacement

Complications of treatment

• Excessive fluid - diuresis of keto-base > worsening acidosis, cerebral oedema
• Rapid fall in serum osmolality - fluid shifts back into cells > cerebral oedema

malonyl CoA: required for FFA elongation
CPT-1: assists in movement of acyl CoA into mitochondria
Acyl CoA: FFA + CoA. Beta-oxidised to Acetyl CoA.
Ketone bodies: formed from condensation of two acetyl CoA into acetoacetate