17-Diuretics Flashcards
Name the 5 classes of diuretics and where they act
1) Osmotic diuretics (work everywhere)
2) Carbonic anhydrase inhibitors: PCT
3) Loop diuretics: Ascending limb of Loop of Henle
4) Thiazides: DCT
5) K+ sparing: DCT
Describe what happens at the Proximal convoluted tubule
Apical:
Na+/H2O reabsorption
Na/H+ antiporter reabsorbs Na+ in exchange for H+
Glucose/AA/Na+ symporter
CO2 (from HCO3- + H+) diffuses into cell, combines with water to form HCO3- and H+. The H+ is used in the Na/H+ antiporter and the bicarb is reabsorbed via Na/HCO3- symporter
Basal:
Na/K ATPase absorbs Na+ in exchange for pumping K+ into cell
Na/HCO3- symporter pumps them into the capillary
Describe what happens in the descending limb of the Loop of Henle
Water permeable, salt impermeable
Fluid in lumen is isotonic, hypertonic in the interstitium
Describe what happens in the Ascending Limb of the Loop of Henle
Water impermeable, salt permeable
Apical:
Na/Cl/K reabsorption
Basal:
Na/K ATPase
K/Cl symporter for reabsorption
Describe the countercurrent effect in the loop of Henle
Na+ leaves the ascending limb and enters medullary interstitium, making lumen less concentrated (decreases osmolarity, closer to 0)
The now more concentrated interstitium draws water from the descending limb, making lumen more concentrated (increases osmolarity, further from 0)
More fluid enters, forcing fluid from descending to ascending limb, replacing the dilute fluid in the ascending limb with concentrated fluid
Second round of pumping
third round of pumping
Describe what happens in the DCT
Apical
Na/Cl symport
Basal
Na/K ATPase
K/Cl symproter
Normally impermeable to water (both apical + basal) unless ADH/vasopressin present, which acts via V2 receptors to insert aquaporin-2 on both surfaces for H2O reabsorption
Describe what happens in the collecting duct
Apical:
Na+ reabsorption ONLY IF ALDOSTERONE IS PRESENT (inserts ENaCs)
Cl- reabsorption
K+ secretion
Basal
Na/K ATPase
Normally impermeable to water (both apical + basal) unless ADH/vasopressin present, which acts via V2 receptors to insert aquaporin-2 on both surfaces for H2O reabsorption
How do osmotic diuretics work?
Filtered by not reabsorbed anywhere, therefore increase the osmolarity of the luminal fluid
Decreased H2O reabsorption where permeable (PCT, descending limb, collecting duct)
Can cause increased ECF volume -> hyponatraemia
How do carbonic anhydrase inhibitors work?
Blocks carbonic anhydrase on both sides
Can’t reabsorb bicarb (basally) and reduces production of bicarb and H+ inside the cell, so less H+ available to exchange apically with Na+, Na+ stays in lumen
How do loop diuretics work?
Inhibit the Na/Cl/K symporter - inhibit Na and Cl reabsorption in ascending limb
Increase Na+ delivery to distal tubule = increased K+ excretion (basolateral Na/KATPase) - hypokalaemia
Powerful diuretics - can cause hypovolaemia and hypotension, causing RAAS activation, further increasing K+ loss
Hypokalaemia -> metabolic alkalosis (K+ loss means H+ moves into cells to maintain neutrality, so decrease in H+ increases pH -> alkalosis)
How do thiazides work?
Inhibit Na/Cl symporter in the DCT
Increased delivery of Na+ to DCT = K+ loss via basolateral Na/K ATPase
Can cause hypokalaemia/metabolic alkalosis
How do potassium-sparing diuretics work
Aldosterone antagonists inhibit aldosterone receptor, so no insertion of ENaCs, so no Na/K exchange apically
Increased Na+ delivery to DCT causes H+ retention -> acidosis
Increased K+ retention = hyperkalaemia
May cause hyperaldosteronism
