MET2

Question 1

State the anion gap seen in DKA [1]

Answer 1

High anion gap
* Due to build-up of ketoacids
* Increase in K+ and Na+

Question 2

Which HLA do most type 1 diabetic patients have? [2]

Answer 2

HLA-DR3-DQ2 or HLA-DR4-DQ8

Question 3

Describe the pathophysiology of type 1 diabetes [2]

Answer 3

Autoimmune destruction by autoantibodies from loss of self-tolerance of T cells of the pancreatic insulin-secreting Beta cells in the Islets of Langerhans

Causes: insulin deficiency

Thus the continued breakdown of liver glycogen (producing glucose and ketones) leading to glycosuria and ketonuria as more glucose is in the blood

Question 4

What are the 3Ps of symptoms of type 1 diabetes? [3]

Answer 4

Polyuria (lots of urine)
o Glucose draws water into the urine by osmosis - not enough glucose can be reabsorbed as kidneys have reached the renal maximum reabsorptive capacity
o Can cause bed wetting

Polydipsia (extreme thirst)
o Due to high water loss due to XS glucose and water loss

Polyphagia (extreme appetite)
o Weight loss due to lipolysis in adipose tissues and break down of muscle protein because glucose is lost

Question 5

What are the random [1] and fasting [1] plasma glucose levels that would indicate type 1 diabetes?

Answer 5

Random plasma glucose:
* > 11.1 mmol/L

Fasting plasma glucose:
* ≥7.0 mmol/L

Question 6

HbA1c target for most people with type 1 diabetes is [] mmol/mol [1]

Answer 6

HbA1c target for most people with type 1 diabetes is 48 mmol/mol

Question 7

Explain the mechanism by which glucose stimualtes insulin secretion from beta cells of the pancreas [4]

TN

Answer 7

Glucose enters cell via GLUT-2
Metabolism of glucose within beta cell generates ATP
ATP closes potassium channels and causes depolarisation
Ca2+ channels open and Ca2+ ions flow in
Insulin released after Ca2+ comes in

Question 8

Describe the effects of insulin on K+ levels [1]

TN

Answer 8

Insulin stimulates uptake of K+ into tissue by increasing activity of Na/K ATPase

Question 9

Explain the consequence of insulin deficiency on glucose levels [3]
Explain the consequence of insulin deficiency on ketone body levels [2]

TN

Answer 9

Glucose
* Glycogen breakdown stimulated
* Gluconeogenesis stimulated
* Decreased removal of glucose by peripheral tissues

Ketone bodies
* Increased activity of acetyl CoA undergoing B-oxidation of fatty acids in liver
* Causes an increase (in acetoacetate; which leads to more) acetone

Question 10

Describe the mechansim of diabetic ketoacidosis [5]

Answer 10

• Uncontrolled breakdown of glycogen & increased GNG due to lack of insulin; causes hyperglycaemia and therefore glycosuria
• Glycosuria causes osmotic diuresis; loss of electolytes and water
• Lipolysis; causing ketone bodies acetoacetate and 3-hydroxybutyrate ionised; results in an accumulation of ketone bodies; increased pH
• Some unionised acetoacetic and 3-hydroxybutyric acids are excrete in urine
• Increased pH can cause enzyme degradation, CNS depression, cerebral oedema and coma

Question 11

What is the name for the characteristic breathing in DKA? [1]
What speficially causes this symptom? [1]

Answer 11

Kussmauls respiration: rapid deep breathing
Stimulation of H+ on the medullary resp. centre

Question 12

Order of treatment for DKA? [3]

Answer 12

Fluids, electrolytes, insulin

Question 13

Why must K+ be included in DKA therapy? [1]

Answer 13

Injections of insulin will cause rapid fall in K+

Question 14

Why is HCO3- low in DKA? [1]

Answer 14

Excess hydrogen ions bind the bicarbonate, resulting in decreased serum bicarbonate levels

Question 15

Acidosis in DKA is due to the overproduction of which two molecules? [2]

Answer 15

Acidosis in DKA is due to the overproduction of β-hydroxybutyric acid and acetoacetic acid
( At physiological pH, these 2 ketoacids dissociate completely)

Question 16

What mmol/L of blood ketones would indicate DKA? [1]

Answer 16

> 3.0mmol/L

Question 17

What levels of HCO3- would indicate DKA? [1]

Answer 17

< 7.3 mmol/L

Question 18

What is a possible consequence of not monitoring K+ levels in DKA management? [1]

How can you avoid this? [1]

Answer 18

o Hypokalaemia is important because when give insulin drives glucose and K into the cell; Large scale: cause cardiac arrythmias

Manage: Supply K at the same time as insulin

Question 19

Calculate the anion gap from these results [1]
What type of anion gap does the Ptx have? [1]

Answer 19

([Na+] + [K+]) − ([Cl-] + [HCO3−]) = (130+4) - (102+10) = 134 – 112 = 22
normal 12-16/ mEQ/L
[Na+] − ([Cl-] + [HCO3−]) = (130) - (102+10) = 130 – 112 = 18
normal 8-12mEq/L [1 mark]

Elevated anion gap metabolic acidosis (low pH, low bicarb). [1 mark]

Question 20

2) Describe the difference in the modes of action between Humalog and Glargine. [2 marks]

Answer 20

Humalog is a fast-acting insulin that begins to work very quickly. After using Humalog, patients should eat a meal within 5 to 10 minutes.

Glargine is a long-acting analogue It consists of microcrystals that slowly release insulin, giving a long duration of action of 18 to 26 hours with a peakless profile.

Question 21

3) There are two main clinical aspects of DKA you need to treat:
(i) Which ones are they?
(ii) Which one will you treat first?
(iii) Using your knowledge of electrolyte balance: explain why DKA in managed this way and which two dangerous pitfalls you will avoid by proceeding this way. [3 marks]

Answer 21

(i) Hyperglycaemia and Dehydration [0.5 mark]
(ii) Dehydration must be treated first to rebalance electrolytes (including Na+) and K+ in particular (Billy has intracellular K+ deficit) [0.5 mark]
(iii) Slow rehydration is necessary to avoid severe hyponatremia, which could cause brain swelling. [1 mark] Insulin injection will trigger intracellular shift of K+, which will drop plasma levels (if not corrected first) leading to possible tachyarrhythmia / cardiac arrest [1 mark]

Question 22

5) Glucagon is released during periods of fasting which inhibits glycolysis in the liver. How is this inhibition of glycolysis beneficial and what does the liver use instead to produce ATP? [2 mark]

Answer 22

Glycogenolysis is activated so that glucose is released by the liver into the blood to be used by cells that need it [1 mark].

Liver uses fatty acids for beta oxidation to produce ATP rather than glycolysis [0.5 marks].

Question 23

Children with DKA are at high risk of developing [] oedema.

Answer 23

Children with DKA are at high risk of developing cerebral oedema.

Question 24

Explain why children with DKA are at high risk of developing cerebral oedema. [3]

Answer 24

Dehydration and high blood sugar concentration cause water to
move from the intracellular space in the brain to the extracellular space. This causes the brain cells to shrink and become dehydrated.

Rapid correction of dehydration and hyperglycaemia (with fluids and insulin) causes a rapid shift in water from the extracellular space to the intracellular space in the brain cells.

This causes the brain to swell and become oedematous, which can lead to brain cell destruction
and death.

Question 25

To diagnose DKA you require [3]

Answer 25

Hyperglycaemia (i.e. blood glucose > 11 mmol/l)
* Ketosis (i.e. blood ketones > 3 mmol/l)
* Acidosis (i.e. pH < 7

Question 26

Treating DKA? [7[

Answer 26

Question 27

The anion gap is calculated by? [1]
What is a nromal anion gap? [1]

Answer 27

(sodium + potassium) - (bicarbonate + chloride)
A normal anion gap is 8-14 mmol/L

Question 28

Causes of a normal anion gap or hyperchloraemic metabolic acidosis? [5]

Causes of a raised anion gap metabolic acidosis? [5]

Answer 28

Question 29

What does c-peptide levels indicate? [1]

Answer 29

C-peptide level is based on blood sugar level. C-peptide is a sign that your body is producing insulin. A low
level (or no C-peptide) indicates that your pancreas is producing little or no insulin. A low level may be
normal if you have not eaten recently