Flashcards in Week 7 - Diuretics Deck (46)
Explain tubular reabsorption of Na and H2O in PCT
-NaKATPase on basolateral membrane sets up an Na gradient
-Na symporter on apical membrane allows Na to enter the cell down its concentration gradient
-Water follows by osmosis
Name the Na transporters of the PCT
Name the Na transporters of the loop of henle
Name the Na transporters of the DCT
Name the Na transporters of the late DCT and CD
Describe Na resorption and K secretion in Late DCT and CD
-Occurs in principle cells
-NaKATPase on basolateral membrane sets up a Na Gradient
-Na enters the cell via a channel called ENaC
-Influx of Na+ produces a lumen negative potential which favours K+ secretion through K channels
What are the effects of aldosterone at a molecular level?
-Increases expression of NaKATPase, ENaC and K channel
What is meant by a potassium sparing diuretic?
-A diuretic which also decreases potassium secretion in its mechanism of action eg spironolactone
Which diuretics work by direct action? What is meant by this?
-K sparing diuretics
-> The diuretics work by directly acting on Na transporters to block them and prevent resorption and this water resorption
Which channels do loop diuretics work on?
-NKCC2 in LoH
Which channels do thiazide diuretics work on?
-NCCT in early DCT
Which channels do K sparing diuretics work on?
-ENaC in late DCT and CD
How do direct action diuretics reach their target site?
-They are secreted into the lumen in the PCT
Explain how a diuretic would work by antagonising the action of aldosterone? Name an example
-Aldosterone increases the expression of NaKATPase, ENaC and K channels in late DCT and CD, thus it works to increase Na and water resorption
-Competitive inhibition of aldosterone would decrease expression of these channels and thus increase renal excretion of Na and water
Explain how some diuretics work by modification of filtrate. Give an example
-These diuretics are small molecules which are free filtered at the glomerulus but are not reabsorbed
-They increase the osmolarity of the filtrate and thus decrease water resorption
Explain how inhibiting the activity of carbonic anhydrase would ace as a diuretic
-Inhibition of CA -> decreased CO2 and H20 entering the cell
-Decreased activity of NHE
-Decreased Na and H2O resorption
Give an example of a loop diuretic
Give an example of a diuretic which inhbits ENaC
Which diuretics work in PCT?
What is essential to ensure the continual action of NKCC2 in the loop?
-Diffusion of K back into the lumen so it can be used again
Which diuretic also helps to drive reabsorption of Ca and Mg?
Why does decreasing resorption in the loop increase renal excretion?
-Segments downstream have limited capacity for reabsorption and thus cannot reabsorp the flodding of Na and water
Why are loop diuretics used in HF?
-Vaso and venodilation reduce after/pre load
When are loop diuretics used?
To treat fluid retention and oedema in
To treat hypercalcaemia as impairs Ca resorption in the loop
When are thiazide diuretics used?
Which diuretics are the least potent at Na resorption?
In what situations are K sparing diuretics contraindicated and why?
-When pt on ACE inhibitor, K supplements or patients with renal impairment
-Can lead to life threatening hyperkalaemia
Explain why ACE inhibitor and K sparing diuretics can cause hyperkalaemia when used together
-ACE inhibitor blocs angiotensin I to angiotensin II
-Decrease angiotensin II results in decreased aldosterone
-Decreased aldosterone increases k retention as K secretion is decreased
-K aring diuretics also cause K retention
-Together can lead to hyperkalaemia
When is spironolactone used?
-Hypertension due to primary hyperaldosteronism (conn's syndrome)
-Ascites and oedema in cirrhosis
-In addition to loop diuretics in HF