Week 7 - Diuretics

Question 1

Explain tubular reabsorption of Na and H2O in PCT

Answer 1

• 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

Question 2

Name the Na transporters of the PCT

Answer 2

• Na:glucose
• Na:a’a
• NHE

Question 3

Name the Na transporters of the loop of henle

Answer 3

-NaKCC2

Question 4

Name the Na transporters of the DCT

Answer 4

-NCCT

Question 5

Name the Na transporters of the late DCT and CD

Answer 5

-ENaC

Question 6

Describe Na resorption and K secretion in Late DCT and CD

Answer 6

• 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

Question 7

What are the effects of aldosterone at a molecular level?

Answer 7

-Increases expression of NaKATPase, ENaC and K channel

Question 8

What is meant by a potassium sparing diuretic?

Answer 8

-A diuretic which also decreases potassium secretion in its mechanism of action eg spironolactone

Question 9

Which diuretics work by direct action? What is meant by this?

Answer 9

• Loop Diuretics
• Thiazide Diuretics
• K sparing diuretics
• > The diuretics work by directly acting on Na transporters to block them and prevent resorption and this water resorption

Question 10

Which channels do loop diuretics work on?

Answer 10

-NKCC2 in LoH

Question 11

Which channels do thiazide diuretics work on?

Answer 11

-NCCT in early DCT

Question 12

Which channels do K sparing diuretics work on?

Answer 12

-ENaC in late DCT and CD

Question 13

How do direct action diuretics reach their target site?

Answer 13

-They are secreted into the lumen in the PCT

Question 14

Explain how a diuretic would work by antagonising the action of aldosterone? Name an example

Answer 14

-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
eg spironolactone

Question 15

Explain how some diuretics work by modification of filtrate. Give an example

Answer 15

-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
eg mannitol

Question 16

Explain how inhibiting the activity of carbonic anhydrase would ace as a diuretic

Answer 16

• Inhibition of CA -> decreased CO2 and H20 entering the cell
• Decreased activity of NHE
• Decreased Na and H2O resorption

Question 17

Give an example of a loop diuretic

Answer 17

-Furosemide

Question 18

Give an example of a diuretic which inhbits ENaC

Answer 18

-Amiloride

Question 19

Which diuretics work in PCT?

Answer 19

-CA inhibitors

Question 20

What is essential to ensure the continual action of NKCC2 in the loop?

Answer 20

-Diffusion of K back into the lumen so it can be used again

Question 21

Which diuretic also helps to drive reabsorption of Ca and Mg?

Answer 21

-Loop diuretics

Question 22

Why does decreasing resorption in the loop increase renal excretion?

Answer 22

-Segments downstream have limited capacity for reabsorption and thus cannot reabsorp the flodding of Na and water

Question 23

Why are loop diuretics used in HF?

Answer 23

• Diuretic effect

- Vaso and venodilation reduce after/pre load

Question 24

When are loop diuretics used?

Answer 24

To treat fluid retention and oedema in
-HF
-Nephrotic syndrome
-renal failure
To treat hypercalcaemia as impairs Ca resorption in the loop

Question 25

When are thiazide diuretics used?

Answer 25

-Hypertension

Question 26

Which diuretics are the least potent at Na resorption?

Answer 26

-K sparing

Question 27

In what situations are K sparing diuretics contraindicated and why?

Answer 27

- When pt on ACE inhibitor, K supplements or patients with renal impairment - Can lead to life threatening hyperkalaemia

Question 28

Explain why ACE inhibitor and K sparing diuretics can cause hyperkalaemia when used together

Answer 28

- 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

Question 29

When is spironolactone used?

Answer 29

- Hypertension due to primary hyperaldosteronism (conn's syndrome) - Ascites and oedema in cirrhosis - In addition to loop diuretics in HF

Question 30

What groups of diuretics are not currently used?

Answer 30

- Inhibitors of carbonic anhydrase | - osmotic diuretics

Question 31

What is an adverse effects of carbonic anhydrase inhibitor diuretics?

Answer 31

-Metabolic acidosis as it decreases the resorption of HCO3

Question 32

When are carbonic anhydrase inhibitors used?

Answer 32

-Glaucoma as reduces aqueous humor formation

Question 33

What is IV mannitol used to treat?

Answer 33

-Cerebral oedema

Question 34

Why is there expansion of ECF in congestive heart failure?

Answer 34

- Increased systemic venous pressure -> oedema as fluid moves into ECF due to increased hydrostatic pressure - Decreased CO stimulates RAAS which increased Na and H2O retention

Question 35

Why does nephrotic syndrome lead to increased ECF?

Answer 35

- Increase in glomerular basement membrane to protein - proteins such as albumin lost in urine - Results in a lower oncotic pressure leading to peripheral oedema - causes low circulating volume and activation of RAAS - Na and water retention leads to more oedema

Question 36

Why does peripheral oedema ensue in liver cirrhosis?

Answer 36

-Reduced albumin synthesis in liver ->Low plasma oncotic pressure ->Peripheral oedema -> Decreased CO due to low blood volume activates RAAS -> worsening oedema

Question 37

Why does ascites occur in liver cirrhosis?

Answer 37

- Portal hypertension leads to an increased systemic pressure in GI circulation - Increased hydrostatic pressure, coupled with low oncotic pressure, causes fluid to move from peritoneal capillaries to peritoneal cavity - Decreased CO due to low blood volume activates RAAS -> worsening ascites

Question 38

What does the rate of K secretion in DCT depend on?

Answer 38

- Concentration gradient of K across apical membrane | - Rate of Na absorption

Question 39

How do loop and thiazide diuretics lead to K loss?

Answer 39

1) Increased Na and H2o delivery to late DCT and CD - Increased Na resorption by ENaC - Favours K secretion via creating lumen negative potential 2) increased flow rate -> increased removal of K in lumen -> increased conc gradient favours K secretion

Question 40

What can you do when giving diuretics to ensure that hyper/hypokalaemia doesnt develop?

Answer 40

- Monitor electrolyte levels | - Give a K sparing diuretic (amiloride/spironolactone) with a K loosing diuretic (loop/thiazide) to minimise K change

Question 41

Why can loop diuretics cause hypovolaemia?

Answer 41

- Decreases ECF volume by causing excretion of Na and H2O | - Loop diuretics are the most potent as the segments distal do not have capacity to resorb much water

Question 42

List some adverse effects of diuretucs

Answer 42

- Potassium disturbance - Hypovolaemia - Hyponatraemia - Gout

Question 43

Why can loop and thiazide diuretics lead to gout?

Answer 43

-Increase uric acid levels in the blood

Question 44

Name some substances with diuretic effects

Answer 44

- Alcohol - Coffee - Lithium

Question 45

Name some disease which cause diuresis

Answer 45

- Diabetes mellitus | - Diabetes insipidus

Question 46

What is a diuretic? When are they used?

Answer 46

-A substance/drug that increases urine formation via promoting renal excretion of water and sodium in order to reduce ECF volume