L20 - drug effects on the kidney (diuretics) Flashcards
how does a diuretic work generally
they decrease Na reabsorption in the nephron, which in turn decreases water reabsorption - more water & Na lost in urine
explain the two main uses of diuretics
- oedematous conditions (accumulation of fluid in interstitial space)
- hypertension (high blood pressure)
what can cause oedema?
- heart failure - increased venous pressure due to decreased cardiac function, higher hydrostatic pressure, keeps fluid in interstitial space
- renal disease - protein being lost from blood into urine lowers the plasma [protein] , less osmotic gradient so water stays in tissues
how do diuretics treat hypertension generally
they reduce blood vol (as more water lost from blood into urine)
decrease CO
How do diuretics treat oedema generally
- reduce Na reabsorption and so reduce water reabsorption
- this decreases blood vol (less water in blood)
- this increases [protein] in blood (less water but same amount of protein means more concentrated)
- therefore higher osmotic gradient so water leaves tissues into capillaries
how is Na reabsorbed in PCT
mainly Na/H exchanger
how is Na reabsorbed in Loop Of Henle
Na/K/2CL cotransporter mainly (NKCC2)
how is Na reabsorbed in DCT
Na/Cl cotransporter mainly (NCCT)
how is Na reabsorbed in CT
Na channel (anti) coupled with K+ channel mainly (ENaC)
what Na pump is on the basolateral membrane
Na/K ATPase
what transporter do Loop diuretics block
NKCC2 in thick ascending loop of henle
example of loop diuretic drug
furosemide
explain mechanism of loop diuretics
- blocks Na/K/2Cl co transporter (NKCC2) in thick ascending LOH
- therefore inhibits Na reabsorption ( in the place it is usually mostly absorbed)
- results in no Na gradient which decreases the osmolality of the interstitium so water doesn’t leave tubule
use of loop diuretics
- treatment of oedema ( heart failure, hepatic cirrhosis)
possible side effects of loop diuretics?
- hypokalemia (low plasma K+) - because more Na reaches CT, meaning there is more Na / K exchange so K+ secretion increases (leaves blood)
- metabolic alkalosis - water retention decreases plasma volume, causing increase in plasma [angiotensin 2] which increases Na/H exchange in PCT and LOH , resulting in increased H+ secretion
where do thiazide - type diuretics act
the NCCT Na/Cl cotransporter in the DCT
example of thiazide - type diuretic
bendroflumethiazide
why are loop diuretics more effective than thiazide type diuretics
because loop diuretics block na absorption in the LOH which is where most na reabsorption occurs. (more than in the DCT where Thiazide-type act.
explain thiazide type diuretics mechanism of action (hypertension)
- block Na/Cl cotransporter in the DCT (NCCT)
- less Na reabsorption means less water reabsorption
- plasma vol decreases, which decreases venous return and therefore decreases CO and TPR
main treatment of thiazide type diuretics
hypertension (high blood pressure)
possible adverse effects of TTD’s
hypokaleamia
metabolic alkalosis
hypergycaemia (less vol = more concentrated)
hyperuriacaemia - TTD competes with urea for excretion
How do TTD and Loop Diuretics cause hypokaleamia
- increase the Na and fluid reaching the CT
- increased Na reabsorption here , which is coupled to the secretion of K+ and H+
- K+ and H+ secreted from blood into tubule causing hypokaleamia and metabollic alkalosis
what can hypokalemia lead to and how can it be prevented
cardiac arrhythmias
k sparing diuretics
explain K+ secretion in CT
- high [Na] in lumen enters cells via ENaC channel which makes the lumen relatively -ve
- K+ will flow into lumen following -ve charge
- high vol of water flow due to diuretic will wash away the K+ before it can backflow into cell
example of k sparing diuretic drugs
Aldosterone antagonists (spironolactone) and Amiloride
explain how aldosterone antagonists are k sparing diuretics and give a drug example
- aldosterone upregulates Na pumps and increases Na reabsorption which in turn increases K+ and H+ secretion
- aldosterone antagonists block this Na reabsorption
spironolactone
explain how Amiloride is a k sparing diuretic
- blocks ENac channel decreasing absorption of Na into cell in CT
- therefore decreases K+ secretion
possible adverse effect of amiloride
may cause hyperkalemia (high plasma [k+] )
