L20 - drug effects on the kidney (diuretics)

Question 1

how does a diuretic work generally

Answer 1

they decrease Na reabsorption in the nephron, which in turn decreases water reabsorption - more water & Na lost in urine

Question 2

explain the two main uses of diuretics

Answer 2

1. oedematous conditions (accumulation of fluid in interstitial space)
2. hypertension (high blood pressure)

Question 3

what can cause oedema?

Answer 3

1. heart failure - increased venous pressure due to decreased cardiac function, higher hydrostatic pressure, keeps fluid in interstitial space
2. renal disease - protein being lost from blood into urine lowers the plasma [protein] , less osmotic gradient so water stays in tissues

Question 4

how do diuretics treat hypertension generally

Answer 4

they reduce blood vol (as more water lost from blood into urine)
decrease CO

Question 5

How do diuretics treat oedema generally

Answer 5

1. reduce Na reabsorption and so reduce water reabsorption
2. this decreases blood vol (less water in blood)
3. this increases [protein] in blood (less water but same amount of protein means more concentrated)
4. therefore higher osmotic gradient so water leaves tissues into capillaries

Question 6

how is Na reabsorbed in PCT

Answer 6

mainly Na/H exchanger

Question 7

how is Na reabsorbed in Loop Of Henle

Answer 7

Na/K/2CL cotransporter mainly (NKCC2)

Question 8

how is Na reabsorbed in DCT

Answer 8

Na/Cl cotransporter mainly (NCCT)

Question 9

how is Na reabsorbed in CT

Answer 9

Na channel (anti) coupled with K+ channel mainly (ENaC)

Question 10

what Na pump is on the basolateral membrane

Answer 10

Na/K ATPase

Question 11

what transporter do Loop diuretics block

Answer 11

NKCC2 in thick ascending loop of henle

Question 12

example of loop diuretic drug

Answer 12

furosemide

Question 13

explain mechanism of loop diuretics

Answer 13

1. blocks Na/K/2Cl co transporter (NKCC2) in thick ascending LOH
2. therefore inhibits Na reabsorption ( in the place it is usually mostly absorbed)
3. results in no Na gradient which decreases the osmolality of the interstitium so water doesn’t leave tubule

Question 14

use of loop diuretics

Answer 14

1. treatment of oedema ( heart failure, hepatic cirrhosis)

Question 15

possible side effects of loop diuretics?

Answer 15

1. hypokalemia (low plasma K+) - because more Na reaches CT, meaning there is more Na / K exchange so K+ secretion increases (leaves blood)
2. 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

Question 16

where do thiazide - type diuretics act

Answer 16

the NCCT Na/Cl cotransporter in the DCT

Question 17

example of thiazide - type diuretic

Answer 17

bendroflumethiazide

Question 18

why are loop diuretics more effective than thiazide type diuretics

Answer 18

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.

Question 19

explain thiazide type diuretics mechanism of action (hypertension)

Answer 19

1. block Na/Cl cotransporter in the DCT (NCCT)
2. less Na reabsorption means less water reabsorption
3. plasma vol decreases, which decreases venous return and therefore decreases CO and TPR

Question 20

main treatment of thiazide type diuretics

Answer 20

hypertension (high blood pressure)

Question 21

possible adverse effects of TTD’s

Answer 21

hypokaleamia
metabolic alkalosis
hypergycaemia (less vol = more concentrated)
hyperuriacaemia - TTD competes with urea for excretion

Question 22

How do TTD and Loop Diuretics cause hypokaleamia

Answer 22

1. increase the Na and fluid reaching the CT
2. increased Na reabsorption here , which is coupled to the secretion of K+ and H+
3. K+ and H+ secreted from blood into tubule causing hypokaleamia and metabollic alkalosis

Question 23

what can hypokalemia lead to and how can it be prevented

Answer 23

cardiac arrhythmias

k sparing diuretics

Question 24

explain K+ secretion in CT

Answer 24

1. high [Na] in lumen enters cells via ENaC channel which makes the lumen relatively -ve
2. K+ will flow into lumen following -ve charge
3. high vol of water flow due to diuretic will wash away the K+ before it can backflow into cell

Question 25

example of k sparing diuretic drugs

Answer 25

Aldosterone antagonists (spironolactone) and Amiloride

Question 26

explain how aldosterone antagonists are k sparing diuretics and give a drug example

Answer 26

1. aldosterone upregulates Na pumps and increases Na reabsorption which in turn increases K+ and H+ secretion
2. aldosterone antagonists block this Na reabsorption

spironolactone

Question 27

explain how Amiloride is a k sparing diuretic

Answer 27

1. blocks ENac channel decreasing absorption of Na into cell in CT
2. therefore decreases K+ secretion

Question 28

possible adverse effect of amiloride

Answer 28

may cause hyperkalemia (high plasma [k+] )