45. Diabetic ketoacidosis (DKA) and ketoacidotic coma

Last updated on May 17, 2019 at 19:18

Diabetic ketoacidosis

Also called DKA, this complication primarily affects people with type 1 diabetes and not type 2. It’s a potentially life-threatening complication that involves:

  • Vomiting
  • Polyuria
  • Polydipsia
  • Dehydration
  • Altered mental state, potentially coma.
  • Abdominal pain
  • Hyperventilation (Kussmaul breathing)
  • Metabolic ketoacidosis

It has a rapid onset (within hours).

DKA is caused by absolute or relative insulin deficiency. It usually develops due to:

  • Stress
    • Infection
    • Surgeries
    • Trauma
    • Myocardial infarction
  • Incorrect administration of insulin
  • Cortisol therapy

The first three causes cause increased secretion of insulin-antagonist hormones, like cortisol or adrenaline. These hormones increase the plasma glucose level by increasing gluconeogenesis and glycogenolysis. As 1DM patients don’t have any insulin secretion there is nothing stopping the blood glucose level from reaching even 20 – 30 mmol/L in response to the insulin-antagonist hormones.

Polyuria develops due to osmotic diuresis and glucosuria. There is also polydipsia, but this doesn’t cause enough fluid intake to compensate for the massive fluid loss, causing hypovolaemia. Fluid loss up to 3L is common.

Increased anion gap metabolic ketoacidosis develops as insulin deficiency leads to increased lipolysis, which releases non-esterified fatty acids (NEFAs). These travel to the liver and are broken down into acetyl-CoA by β-oxidation, however the TCA cycle is insulin-dependent. Acetyl-CoA is therefore redirected into ketone body synthesis. Two of the three ketone bodies are acidic, causing increased anion gap metabolic acidosis with ketosis. Severe acidosis causes hyperventilation with Kussmaul breathing. Patients’ breath has a fruity odour due to the ketone bodies.

Neurological symptoms: Hyperventilation causes hypocapnia, which causes brain vasoconstriction. Brain function is further worsened as acidosis suppresses myocardial contractility and non-specifically inhibits enzymes. Even coma may develop.

Hyperosmolarity develops due to the hyperglycaemia. This also causes non-specific enzyme inhibition as the tertiary structure of proteins is altered. Glucose rapidly enters brain cells through GLUT3 which prevents them from being hypotonic and starting to shrink.

The cells of the CNS produce “idiogenic osmoles”, small particles that maintain isotonicity between the intracellular and extracellular compartments. This prevents any major change in intracellular volume.

These idiogenic osmoles must be kept in mind during the treatment of DKA. If the extracellular osmolarity is reduced too quickly will the intracellular compartment have much higher osmolarity than the extracellular, because the brain cells need time to get rid of these idiogenic osmoles.

Polyol pathway: Hyperglycaemia causes activation of the polyol pathway, which causes a pseudohypoxic state as described in topic 41. This inhibits cell functions just like real hypoxia does.

K+ deficit: Insulin usually promotes entry of K+ into cells. In DKA, where insulin is deficient, will K+ shift from inside cells to the outside, from which they’re lost through the urine. Serum potassium may be normal or even elevated, but there is total body deficit of potassium as the cells have lost a lot of it. This must be kept in mind as insulin is administered; administering insulin too quickly causes plasma potassium to enter the cells quickly, potentially causing hypokalaemia.

We need to introduce a term called “osmotic gap”. It’s kinda similar to anion gap. The “gap” is equal to the difference in measured serum osmolarity (measured with a blood test) and the calculated serum osmolarity. The calculated serum osmolarity is calculated like this:

Calculated serum osmolarity = 2 x serum Na+ + serum K++ serum glucose + serum BUN/urea

The reason that the measured serum osmolarity is higher than the calculated serum osmolarity is because there are other osmotically active compounds in the serum than sodium, potassium, glucose and urea. These “other” osmotically active compounds may be ketone bodies, alcohols or proteins.

Increased osmotic gap: In diabetic ketoacidosis there is an increased osmotic gap as the level of osmotically active ketone bodies increases in the serum.

Ketoacidotic coma: Coma usually sets in around 30 mmol/L glucose. Coma may develop due to non-specific enzyme inhibition due to hyperosmolarity and acidosis, and due to reduced cerebral perfusion due to hypovolaemia and hypocapnia. These changes inhibit the Na+/K+ ATPase, which is essential for the normal function of the CNS. Hyperosmolarity doesn’t cause brain cells to shrink as they synthesize idiogenic osmoles, however the cells of the blood-brain barrier doesn’t produce these osmoles and will shrink. This causes the barrier to become more permeable, allowing toxins to traverse into the CNS.

Diabetes type 2: DKA usually doesn’t develop in people with 2DM as the small insulin response they have is enough to prevent the development of ketosis and acidosis. These patients instead develop hyperosmolar hyperglycaemic state (HHS).


Insulin, bicarbonate, electrolyte replacement and rehydration must be performed slowly with continuous monitoring of electrolytes, especially K+. Blood pressure and heart rate should be monitored to look for brain oedema (Cushing reflex).

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44. Etiology and pathogenesis of 2DM

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46. Diabetic hyperosmolar syndrome (HHS) and coma

2 thoughts on “45. Diabetic ketoacidosis (DKA) and ketoacidotic coma”

  1. Szia, Nik, and happy 17th of May!

    You write that: “Glucose rapidly enters brain cells through GLUT3 which prevents them from being hypotonic and starting to swell.” This is wrong, as the glucose prevent the cells from shrinking.

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