DKA, Hypo/Hyperglycaemia

Question 1

What is DKA?

Answer 1

Hyperglycaemia and lack of insulin in patients with type 1 diabetes. Results in uncontrolled catabolism as cells try find other energy sources.

Metabolic acidosis (pH<7.3, Bicarbonate <15mmol/L).
Hyperglycaemia (>13.9mmol/L)
Ketosis (++).

Question 2

Outline the normal response to hyperglycaemia.

Answer 2

High glucose causes an increase in insulin, which leads to glucose uptake by fat, muscle and hepatocytes.
Insulin also causes a decrease in glucagon production and decreased glycogenolysis and gluconeogenesis.

Question 3

How is the normal response to hyperglycaemia altered in DKA?

Answer 3

High glucose but no insulin - so no glucose uptake by fat, muscle or hepatocytes.
Also no glucagon production so no glycogenolysis or gluconeogenesis.

Question 4

Describe the effects DKA has on the kidney?

Answer 4

1. Osmotic Diuresis
   - Glucose (and ketones) are freely filtered at the glomerulus, the maximal reabsorption threshold of glucose is exceeded, so solute conc in the lumen causes an osmotic gradient.
   - This causes water (and glucose and ketones) to be lost in urine.
2. Potassium loss
   - Due to hyperaldosteronism.
   - Lack of insulin prevents K+ from moving into cells.
   - Plasma K+ levels may be elevated but total body K+ is depleted.

Question 5

Describe catabolism in insulin deficiency?

Answer 5

Insulin deficiency causes;

1. Promotes lipolysis , which creates triglycerides and FFa. FFA produces ketone bodies so Ketones are raised and pH is decreased.
2. Promotes proteolysis, creating amino acids for gluconeogenesis. This results in raised plasma glucose.
3. Blocks glucose uptake in peripheral tissues. This causes raised plasma glucose.

Question 6

How is DKA metabolic acidosis compensated for?

Answer 6

Initial H+ renal excretion.
Loss of bicarbonate ions (to buffer H+).
Increased respiratory rate (Kussmal breathing).
Impaired renal compensation with worsening acidosis and renal hypo-perfusion.

Question 7

Describe H+, pH, HCO3 and CO2 in metabolic acidosis?

Answer 7

H+ - high
pH - low
HCO3 - low
CO2 - low

Question 8

What is adrenaline’s role in counter regulation of DKA?

Answer 8

Promotes glycogenolysis, gluconeogenesis and lipolysis.

Question 9

What is cortisols’s role in counter regulating DKA?

Answer 9

Promotes gluconeogenesis, lipolysis and inhibits peripheral glucose uptake.

Question 10

What is growth hormone’s role in counter regulating DKA?

Answer 10

Promotes gluconeogenesis, lipolysis and inhibits peripheral glucose uptake.

Question 11

Describe DKA treatment?

Answer 11

Hypovolaemia: Treated with IV fluid.
Insulin deficiency: IV insulin.
Hypokalaemia: IV Potassium.
Supportive treatmen: NG tube, antiemetics, precipitating causes.

Question 12

Why is IV insulin essential in DKA treatment?

Answer 12

To switch off ketogenesis and uncontrolled catabolism.
Blood sugar will return to normal quickly with IV insulin, but regulation of acidosis requires insulin for longer. If low blood glucose: IV dextrose and continue insulin at a reduced rate.

Question 13

Describe the response to hyperglycaemia in HHS?

Answer 13

High glucose, but not enough insulin, so decrease in Glut4 tranporters and decreased glucose uptake by fat and muscle.
Proteolysis promoted to make amino acides for gluconeogenesis resulting in increase blood glucose.

Question 14

What is HHS?

Answer 14

Hyperosmolar hyperglycaemic state. A complication of DM where high blood glucose results in high osmolarity with no significant acidosis.

Question 15

What differs in the processes of DKA and HHS?

Answer 15

No lipolysis - no ketones - so no acidosis.

Question 16

Describe osmotic diuresis in HHS?

Answer 16

Chronic renal impairment is common, as there is a reduced capacity to excrete glucose.
Longer, insidious onset, with more profound hypovoleamia.
Impaired thirst leads to a lack of water replacement.

Question 17

How is HHS treated?

Answer 17

Hypovolaemia: IV fluid
Insulin deficiency: IV insulin
Hypokalaemia: IV potassium
Supportive treatment: Hypercoagulable (as venous thrombosis is common), foot ulceration treatment (also common).

Question 18

How is IV insulin administered in HHS treatment?

Answer 18

Plasma glucose falls with fluid alone, so insulin started when plasma glucose stable.

Question 19

Is potassium treatment more aggressive in DKA or HHS?

Answer 19

DKA.

Question 20

Outline the normal response to hypoglycaemia?

Answer 20

Decrease in blood glucose = decrease in insulin (so decreased glucose uptake by fat and muscle).
Decrease in blood glucose and decreased insulin = increased glucagon and increased glycogenolysis and gluconeogenesis.

Question 21

List the normal counter regulatory mechanisms to hypoglycaemia?

Answer 21

Increased glucagon, adrenoline, noradrenaline, ACh, cortisol and growth hormone.

Question 22

Why is ACh and Noradrenaline in cresed in hypoglycaemia?

Answer 22

As there is increased smapthetic adrenal outflow to cause hunger.

Question 23

Why is there increased adrenaline in hypoglycaemia?

Answer 23

As there is increased sympathetic outflow to give gluconeogenic precursors (also gives tremor and sweating).

Question 24

List symptoms of hypoglycaemia?

Answer 24

Initial symptoms: Sweating, tremor, palpitations, hunger, anxiety.

Late symptoms (Neuroglycopaenic): Confusion, impaired conscious level.

NB: frequent hypoglycaemic levels is associated with unawareness of hypoglycaemia (due to autonomic dysfunction and altered CNS sensing?).

Question 25

How is mild hypoglycaemia treated?

Answer 25

15-20g fast acting carbohydrate.

BM <4

Question 26

How is severe (requiring help from someone else) hypoglycaemia treated)?

Answer 26

15-20g fast acting carbohydrate.
If reduced consciousness - Intramuscular glucagon or IV dextrose (if access).

Retest glucose after 15-20 mins.
Have a longer acting carbohydrate to prevent further drop in blood sugar.