PBL 3 - Diabetes T1 Flashcards
) (i) What are the main plasma unmeasured anions responsible for the anion gap
in this scenario? (1/2 mark) (ii) What other metabolite could contribute as well?
Ketoacids
ii) Lactic acid (from dancing
Billy is in hyperglycemia. What are the two main hormones involved and how
does their respective levels affect the various pathways of glucose metabolism? [2
marks]
Lack of insulin: inhibits glycolysis, stimulate glycogenolysis and gluconeogenesis
[1]
Excess glucagon (insulin normally restrains glucagon secretion): inhibits
glycolysis. [1]
* Glucagon inhibits formation of fructose2,6biphosphate, an extremely potent
allosteric regulator of phosphofructokinase1: a controlling step in glycolys
3) What is the effect of lack of insulin on lipid metabolism? How does it contribute
to ketogenesis? [2
Lack of insulin: stimulates lipolysis [1] that delivers Free Fatty Acids used for
ketogenesis
What is the effect of alcohol on the NAD/NADH ratio in the liver and how does
this affect glucose metabolism? [
Alcohol is broken down by alcohol dehydrogenase, which also catalyses the
reduction of NAD+ to NADH. NAD/NADH are cofactors used in hepatic
gluconeogenesis. This change the ratio inhibits hepatic gluconeogenesis.
Briefly explain the mechanism that normally prevents appearance of
glucose in the urine and how it is affected in patients with Type 1 diabetes. [3
marks]
Glucose is freely filtered by the glomerulus and normally reabsorbed in the
proximal tubule [1 mark]
In hyperglycemia patients have high plasma concentrations of glucose. [1 mark] so
there is saturation of glucose transporters in the proximal tubule and some glucose
end up in urine.
OR renal threshold for total glucose reabsorption is exceeded. [1 mark]
What is type 1 diabetes
auto-immune T-cell mediated disruption of pancreatic B cells resulting in decreased insulin production within islets of Langerhans
When does T1D develop
5-14 years old
Normal action of insulin
o Stimulates uptake via GLUT 4
o Increased glycolysis
o Increased glycogenesis
o Stimulates adipogenesis
o Stimulates protein synthesis and uptake of a.a. into cells
o Promotes uptake of K+ into cells
o Increase translation of MRNA –> new proteins
Normal function of glucagon
o Increased glycogenolysis
o Increased gluconeogenesis
o Lipolysis via HSL
What usually inhibits glucagon
Insulin
Somatostatin
What occurs in hyperglycaemia
More glycogenolysis, gluconeogenesis than needed due to excess glucagon
Less glycolysis as high glucagon –> Inhibits F2,6,BP –> PFK-1 not activated
How does high blood sugar levels cause osmotic diuresis
Normally all glucose reabsorbed after ultrafiltration, but above 11mmol/L, glucose transporters become saturated and cannot reabsorb glucose
Hyperosmolality of ECF occurs, shift of fluid from inside –> outside –> hyponatremia (diluted) –> excess water excreted in urine
What causes diabetic ketoacidosis
o Lack of insulin and inability to use carbohydrate –> mimics starvation state –>body switches to metabolising lipids.
o Lipolysis occurs –> glycerol + FFA –> FFA–> ketogenesis
FFA also used for Beta oxidation –> acetyl coA
Glycerol –> glucose
What is kussmaul breathing
Deep laboured breathing
Ketones!!
Ketones are acidic and will dissociate to form H+ and anions
Acidosis will pull Na+ and K+ out of the cell via H+/K+ ATPase (cell exchanges H+ for K+ to try and reduce acidity) –> elevated serum K+ when total K+ is lower due to loss through urine.
Acidity –> Kussmaul breathing (deep laboured breathing)- body tries to compensate for acidity by getting rid of CO2. Compensatory respiratory alkalosis
Acidity –> denatures enzymes –> slows down metabolism even more –>more ketones accumulate
What is the anion gap
Difference in measured cations – measured anions = unmeasured (Na+ +K+) – (Cl- +HCO3-)
o Used to find out cause of metabolic acidosis
Normal anion gap
<12
or <16 if include K
Why is there a high anion gap in scenario
- This is because there is an increase in unmeasured anions due to the ketone bodies dissociating. The H+ is removed by the bicarbonate (hence why it’s low).
- Other examples of high anion gap acidosis- methanol, lactate
Effect of alcohol on T1D
- Sweetened wine/beer can cause temporary glucose levels
- Excess alcohol –> hypoglycaemia next morning
- Alcohol –> acetaldehyde using NAD+ –> NADH, increase in NADH:NAD ration inhibit malate dehydrogenase which converts malate –> oxaloacetate used in gluconeogenesis. (inhibits gluconeogenesis)
- Especially true in diabetics as body has less glycogen stores to rely on
- Dancing –>lactate. Lactate –> pyruvate via pyruvate dehydrogenase requires NAD+ which is inhibited lactate acidosis.
Acute tx
Replace fluid and electrolytes lost (Saline infusion)
Bolus of insulin of 0.1 unit per kg
Pottasium supplements as insulin decreases potassium levels in blood –> cardiac complications
Management of T1D
Humalog
Glargine lifestyle factors
What is humalog
Fast acting insulin (lispro)
Taken before and after eating (more flexible)
What is glargine
Long-acting basal insulin analogue given once daily at night
Resembles basal insulin secretion in non-diabetics
Lifestyle factors in T1D
Low carbohydrate diet/GI diet
Avoid sugary drinks/soda
Plenty of fluid to avoid dehydration
Exercise
