38. Diabetic ketoacidosis (DKA) and ketoacidotic coma

Diabetic ketoacidosis (DKA) ?

Complication primarily affecting people w/ 1DM and not type 2

Complications of DKA?

- Vomiting

- Polyuria

- Polydipsia

- Dehydration

- Altered mental state, potentially coma

- Abdominal pain

- Hyperventilation (Kussmaul)

- Metabolic ketoacidosis

It has a rapid onset...

DKA usually develops due to?

Stress:

- Infection

- Surgeries

- Trauma

- AMI

Incorrect administration of insulin

Cortisol therapy

Why can stress cause DKA?

There is increased secretion of insulin-antagonist hormones, like cortisol or adrenaline

They will increase plasma glucose

- As 1DM patients do not have any insulin secretion, nothing is stopping blood Glc levels to reach 20-30mmol/L

Why does polyuria develop in DKA?

Develops due to osmotic diuresis and glucosuria

Polydipsia in DKA?

The polyuria will stimulate thirst

- But: it is not to compensate for the huge fluid loss

= There will be hypovolemia

Increased anion gap metabolic ketoacidosis?

Develops as insulin deficiency leads to increased lipolysis -> release NEFAs -> travel to liver & broken down to acetyl-CoA -> TCA is blocked, as there is no insulin -> Acetyl-CoA enters ketone body synthesis

2/3 ketone bodies are acidic - causing metabolic acidosis

= Kussmaul breathing

Neurological symptoms - DKA?

Hyperventilation -> hypocapnia -> cerebral vasoconstriction

Brain function is further worsened as acidosis suppresses myocardial contractility

- Even coma may develop

Hyperosmolarity - DKA?

Develops due to hyperglycemia

- Also causes non-specific enzyme inhibition - as the tertiary structure of protein is altered

- Glucose rapidly enters brain cells through GLUT3 - preventing them from being hypotonic & start to shrink

How does the CNS protect itself from the hyperosmolarity in DKA?

Cells of CNS produce "idiogenic osmoles"

- Small particles that maintain isotonicity

= Prevents major change in intracellular volume

Polyol pathway - DKA?

Hyperglycemia causes activation of the polyol pathway

- Causes a pseudohypoxic state

= Inhibits cell function just like real hypoxia

K+ deficit - DKA?

Insulin usually promotes entry of K+ into the cells

- In DKA - insulin is deficient -> the K+ will shift from inside cells to the outside = from here they will be lost in urine

Serum K+ may be normal or elevated, but there is a total body deficit of potassium

= As the cells have lost it

What have to be taken into consideration when administrating insulin to DKA patients?

Administering insulin too quickly causes plasma-potassium to enter the cells quickly

= potentially causing hypokalemia

Osmotic gap?

The difference in measured serum osmolarity and calculated serum osmolarity

Calculated serum osmolarity:

2xNa+ + K+ + serum glucose + serum BUN

How can the measured serum osmolarity be higher than the calculated serum osmolarity?

Because there are other osmotically active compounds in the serum than sodium, potassium, glucose and urea

The "other" compounds may be:

- Ketone bodies

- Alcohols

- Proteins

How is the osmotic gap in DKA?

Diabetic ketoacidosis:

- Increased osmotic gap

As the level of osmotically active ketone bodies increases in the serum

Ketoacidotic coma?

Sets in around 30 mmol/L glucose

- May develop due to non-specific enzyme inhibition

- Due to hyperosmolarity and acidosis

- Due to reduced cerebral perfusion due to hypovolemia and cerebral vasoconstriction

These changes inhibit Na+/K+ ATPase - which is essential for the normal function of CNS

- Hyperosmolarity does not cause brain cells to shrink as the synthesize idiogenic osmoles

= However: the cells of the BBB does not produce osmoles & will shrink

= Causes barrier to become more permeable - allowing toxins to travel into the CNS

DKA in diabetes type 2?

DKA usually does NOT develop in 2DM

- As the small insulin response they have is enough to prevent the development of ketosis and acidosis

These patient will develop hyperosmolar hyperglycemic state

Treatment DKA in 1DM?

Insulin, bicarbonate and electrolyte replacement

- Rehydration must be performed slowly with continuous monitoring of electrolytes, especially K+

BP and HR should be monitored to look for brain edema (Cushing reflex)