diuretics Flashcards
1
Q
what happens in the PCT?
A
- Na is taken up and cotransports water
- lots of basal Na/K ATPases to retain Na gradient
- carbonic anhydrase on inside of lumen ensures that bicarbonate is broken down –> allows CO2 and H20 to pass into cell
2
Q
what happens in descending limb?
A
only H20 reabsorption via AQA molecules
3
Q
what happens in the ascending limb?
A
- impermeable to water (for countercurrent flow)
- triple transporter reabsorbs ions
- Na reabsorbed paracellularly
- generated hypertonic interstitium
4
Q
describe the permeability of limbs
A
- asc limb: impermeable to water, permeable to ions
- desc limb: permeable to water and not ions
5
Q
describe the countercurrent effect
A
- loop filled w/ isotonic fluid
- Na pumped out of asc limb into interstitium (fluid in asc limb dec. in osmolarity)
- conc. interstitium pulls water into it from desc limb (fluid in desc limb inc. osmolarity)
- more fluid flows into tubule, shifts desc limb fluid into asc limb
- Na pumped again out of desc limb into interstitium (asc limb fluid dec. in osmolarity)
6
Q
what happens in the early DCT?
A
- mediated by Na/Cl cotransporter
- draws more ions into interstitium
- impermeable to free water reabsorption (mediated by selective AQA2 channels under VP control)
7
Q
what happens in the collecting duct?
A
- aldosterone induces Na-channel production
- VP induces AQA2 synthesis dependant on blood osmolarity
- AQA3/4 constitutively expressed on basal membrane
- impermeable to free water re-uptake
8
Q
describe the osmolarity as you pass deeper into medulla
A
increases
9
Q
how do diuretics work?
A
- inhibit reabsorption of Na and Cl (raises excretion)
- inc. osmolarity of tubular fluid (dec. osmotic gradient)
10
Q
what are the 5 main classes of diuretics and give an example of each?
A
- osmotic diuretic e.g. mannitol
- carbonic anhydrase inhibitors e.g. Acetazolamide
- loop diuretics e.g. furosemide
- thiazides e.g. Bendroflumethiazide
- K-sparing diuretics e.g. spironolactone
11
Q
how do osmotic diuretics work?
A
- reduce water re-uptake at any part of nephron
- pharmacologically inert
- not reabsorbed after being filtered
- actions to dec. osmotic gradient by raising osmolarity of tubular fluid so reduce water reabsorption
12
Q
how do carbonic anhydrase inhibitors work?
A
- act on PCT
- inc. bicarbonate in tubular fluid
- inc. pH of cell as less H ions are made from CO2 and H2O
- less Na is taken back up by Na/K antiporter
- it inc. tubular fluid osmolarity so dec. water reabsorption
13
Q
how do loop diuretics work?
A
- act on asc limb of LoH
- strongest diuretics (15-30%)
- inhibit triple transporter
- results in K, Na, Ca, Mg loss
- Mg and Ca ion loss due to K recycling
14
Q
what causes the reduced +ve luminal pressure?
A
- small leak of K into tubule from cell
- furosemide inhibits this
- causes less +ve luminal pressure
- less paracellular transport of ions
15
Q
how do thiazides work?
A
- act on early DCT
- inhibit Na/Cl cotransporter
- not as strong as loop diuretic (5-10%)
- results in K and Mg loss and Ca reabsorption
