A Gunn Flashcards
What antagonises the effects of insulin?
Glucagon, catacholeamines (adrenalin), growth hormone, corticosteroids (cortisol)
What does insulin do in terms of glucose?
It causes the break down of glucose (glycolysis) and the formation of glucagon. It promotes glucose uptake in muscle and adipose tissue.
It also causes protein synthesis and uptake of ions (especially K+ ions).
What does glucagon do in terms of glucose?
Gluconeogenesis, break down of glycogen (glycogenolysis).
It also causes lipolysis, ketogenesis and proteolysis
How does insulin cause the uptake for glucose?
It binds to the insulin receptor causing the upregulation of GLUT4. This allows glucose into the cell.
How are ketones made?
Needs excess glucagon and deficiency of insulin
2 Steps: mobilise fat and stimulate beta-oxidation (glucagon)
Fat cells are filled with triglycerides.
Glucagon, corticosteroids and catecholamines and lack of insulin drive lipolysis via a hormone sensitive lipase.
MOBILISE FAT:
The breakdown of triglycerides creates glycerol and non-esterified free fatty acids.
Stimulate beta oxidation - this occurs in the hepatocytes.
The glycerol is used to make more triglycerides.
The free fatty acids get beta-oxidised into acetylo co-A
Acetyl CoA is converted to acetoacetate, which is converted to acetone or beta-hydroxybutyrate. This conversion requires H+ and so the more H+ the more this favours beta-hydroxybutyrate formation. These are the three ketone bodies.
This process requires a lack of insulin and an excess glucagon.
What do the formation of ketone bodies do?
Ketone bodies circulate as anions. Increase the anion gap.
Beta-hydroxybutyrate and acetoacetic acid dissociate completely.
Excess H+ + HCO3- -> CO2 + H20 = decreaced HCO3-.
Thus, bicarbonate is being replace with beta-hydroxybutyric acid and acetoacitic acid.
The decrease in HCO3- increases the anion gap.
What is the anion gap equation?
Na+ - (Cl- + HCO3-)
What happens to the sodium and chloride balance in ketoacidosis?
If beta-hydroxybutyrate is dissociated and hydrogen is converted to CO2 and H2O.
Then what is left?
Na-beta-hydroxybutyrate and Cl-.
The Na-betahydroxybutyerate is excreted in the urine leaving the Cl-.
After clinical treatment: volume is replaced with 0.9% NaCL -> normal Na but hyperchloraemia
What is the criteria for DKA?
Hyperglycaemia (blood glucose >11 mmol/L), venous pH <7.3 or bicarbonate <15mmol/L, and the presence of hetonemia or ketonuria
Need lack of insulin and STRESS (illness) and fat to break down
What controls K+ after a meal (acute K+ change)?
The main regulation is caused by insulin during a meal that stimulates the uptake of K+ into cells. Insulin stimulates the Na/K ATPase resulting in K+ uptake into a cell.
Aldosterone results in an uptake of K into muscle cells and stimulates renal K+ excretion.
Beta 2 adrenergic stimulation (adrenaline) also increases uptake - beta blockers increase serum potassium.
In muscle contraction, potassium is excreted from the cell. The adrenaline released then promoted the re-uptake of that potassium. Use of a beta blocker in exercise can cause issues.
Acidosis increases K+ loss from cells
Cell lysis (e.g. muscle cells) increases K+ in the ECF.
Increases ECF osmolarity causes eflux of water. This causes the cells to have increased potassium and the outside of the cell which has more water is now decreased in potassium. This causes potassium to leave the cells (occurs in diabetes mellitus). That potassium is then excreted by the kidneys causing a net loss of hypokalaemia.
How is secretion of K+ controlled?
We consume in one meal more K+ than is in our total ECF. Initially after eating, the K+ is taken into cells. It is then slowly released for excretion.
96% of potassium is reabsorbed. The remaining 4% is secreted in the distal tubule, buy it can also be reabsorbed.
About the same amount that we consume is excreted. This happens in the distal tubule and collecting duct where potassium is excreted.
Can excrete large amounts of potassium. > than the GFR rate. Slow to conserve potassium though.
What controls the distal secretion of K+ and how is it reabsorbed?
96% of potassium is reabsorbed. The remaining four % is secreted in the distal tubule, buy it can also be reabsorbed.
4 things cause potassium secretion:
1) high Potassium levels. This stimulates the Na/K ATPase. Can also stimulate aldosterone.
2) Distal tubular flow rate (higher urine rate decreases time for reabsorbtion, increases osmotic diuresis, increases the gradient in urine)
3) aldosterone
4) alkalosis increases secretion
Aldosterone acts on principle cells (Na reabsorption and K+ excretion). It causes the upregulation of existing potassium uniporters and Na/K ATPase channels and the production of more channels.
Acidosis decreases decreased K excretion.
What are some causes of polyurea?
Drinking too much water - habit or psychological issues
Excess loss of water - renal (nephrotic syndrome) - endocrine (decreased ADH or excess naturetic peptides)
Why does a patient get thirsty with diabetic ketoacidosis?
Because they are urinating out excess glucose, causing osmotic diuresis. This water loss causes an increase in the plasma osmolality that is sensed in the hypothalamus.
How do you compensate to reduced volume and water loss?
Aldosterone release -> retain Na
Release ADH -> retain H20
Why is Na low in someone with ketoacidosis?
Pseudohyponatraemia
Because the water is moving out of cells and lots of water is being held by the glucose in the ECF. this dilutes the Na. There is an equation to calculate the effective osmolality:
= (2x measured serum sodium) + serum glucose
How do you calculate the effective osmolality?
Effective osmolality: = (2x measured serum sodium) + serum glucose
Why would someone with DKA have decreased urination?
Because of a reduced BP driving renal artery constriction to reduce GFR, Done by angiotensen II and sympathetic activity.` Rehydration restores the GFR -> osmotic diuresis
