Diuretics (10.02.2020) Flashcards
How do diuretics work?
Inhibit the reabsorption of Na+ and Cl-
i.e.increased excretion
Increase the osmolarity of tubular fliud
i.e. decreased the osmotic gradient across the epithelia
What is the counter current mechanism?
Descending limb of LoH – permeable to water
Ascending limb of LoH – impermeable to water
- Na+ leaves the ascending limb and enters medullary
Interstitium - Fluid in ascending limb decreases in osmolarity
- More concentrated medullary interstitium draws water from the permeable descending limb
- Fluid in descending limb increases in osmolarity
- More fluid enters and forces fluid from descending to ascending limb – this fluid has increased in osmolarity due to increased Na+ concentration in the medulla.
- Na+ leaves the ascending limb and enters medullary Interstitium
- Fluid in ascending limb decreases in osmolarity
How do the different parts of the nephron work?
- Blood is filtered at the glomerulus and passes to the pct
- in the pct about 65-70% of sodium is reabsorbed from the lumen into the blood.
- osmotic pressure draws water across the cell (there is protein in blood but non in the filtrate in the lumen)
- also CO2 taken in the cell, CA makes it to HCO3- and H+, HCO3- enters blood and H+ enters lumen, CA in the lumen can make CO2 + H2O with CA (CA works both ways)
- the descending LoH is only permeable to water -> a lot of the water is reabsorbed into the interstituum from the lumen
- the ascending LoH is not permeable to water; there is uptake of (Na+, 2Cl-, K+) on the apical side and a Na+K+ ATPase on the basolteral side (Na+ into blood, K+ into cell) and K+ and Cl- are transported out of the cell via a transporter. Cl- can also diffuse.
- dct: Na+ and K+ reabsorption. H20 reabsorption. Late dct is aldosterone and ADH sensitive, there is more water permeability because of VP dependant AQP channels.
- collecting duct:
Which part of the nephron is aldosterone and ADH sensitive/
late distal convoluted tubule
What are the main classes of diuretics?
- Osmotic diuretics (e.g. mannitol)
- Carbonic anhydrase inhibitors (e.g. acetazolamide)
- Loop diuretics (e.g. frusemide (furosemide))
- Thiazides (e.g. bendrofluazide (bendroflumethiazide))
- Potassium sparing diuretics (e.g. amiloride, spironolactone)
Where in the nephron do osmotic diuretics act?
pct
LoH
collecting duct
Where in the nephron do carbonic anhydrase inhibitors act?
pct
Where in the nephron fo loop diuretics act?
ascending LoH
Where in the nephron do thiazides act?
dct
Where in the nephron do potassium sparing diuretics act?
late dct and collecting duct
How do loop diuretics work?
- inhibit the triple transporter (Na+, 2Cl, K+) in the ascending limb
- this interferes with the descending limbs ability to concentrate the interstituum which then interferes with water reabsorption in the collecting duct because maximal water reabsorption requires the countercurrent mechanism
- 15-30% water loss => VERY POWERFUL
- increased delivery of Na+ to distal tubule K+ loss ( Na+/K+) exchange) - in common with thiazides
- Ca2+ & Mg2+ - Loss of K+ recycling (because K+ recycling drives the positive lumen potential that drives the paracellular movement of these ions from lumen to interrstituum.
e. g, Furosemide
What is an example of a loop diuretic?
Furosemide
Furosemide (drug class)
= loop diuretic
How do thiazide diuretics work?
- in early dct
- blocks Na+/Cl- reuptake protein (cotransporter)
- does not affect countercurrent mechanism so far less powerful than loop diuretics - 5-10%
- increased tubular fluid osmolarity = decreased H2O reabsorption in the collecting duct.
- increased delivery of Na+ to distal tubule increased K+ loss (increased Na+/K+ exchange) – in common with loops
- increased Mg2+ loss and increased Ca2+ reabsorption (unknown)
What is an example of a thiazide diuretic?
bendroflumethiazide
