Diuretics

Question 1

Describe the general route of flow through he kidney

Answer 1

Bowman capsule 
Proximal tubule 
Descending loop of Henle 
Ascending loop of Henle (impermeable to water)
Distal tubule 
Collecting duct

Question 2

Explain sodium are reabsorbed from the proximal kidney tubules

Answer 2

Sodium transported through the apical membrane into the proximal tubule cell
The sodium potassium ATPase on the basal membrane ensures that sodium is reabsorbed into the blood very quickly, maintaining the concentration gradient.

Question 3

Explain the movement of water through the proximal kidney tubules

Answer 3

Water can either move transcellularly (via aquaporins) or paracellularly
Transported through the apical membrane into the proximal tubule cell
In the lumen there is no protein. The oncotic pressure of proteins in the blood will draw water into the blood.

Question 4

Explain how glucose and amino acids are reabsorbed from the kidney tubules

Answer 4

Sodium and hydrogen exchange at the apical membrane

Sodium here is coupled with glucose and amino acids to allow for their reabsorption

Question 5

Explain how bicarbonate is reabsorbed from the kidney tubules

Answer 5

1. Bicarbonate and H+ conversion to CO2 + H2O by carbonic anhydrase
2. Transport into the tubule cell
3. Conversion by carbonic anhydrase into H+ + HCO3-
4. H+ exchanged with Sodium the apical membrane
5. Bicarbonate transported through the basal membrane with sodium into the interstitium

Question 6

Describe the excretion of drugs in the kidney

Answer 6

Excretion of drugs largely to take place in the proximal tubule. Recognition of groups e.g. glucuronide of drugs and excretion into the urine

Question 7

Describe the transcellular transport occurring in the ascending loop of Henle

Answer 7

Impermeable to water - Sodium Chloride reabsorption

1. Apical membrane protein allows movement of sodium, potassium and chloride
2. Sodium exchanged with potassium at the basal membrane
3. Potassium efflux back out at the basal membrane with chloride

Question 8

Explain the countercurrent effect of the Loops of Henle

Answer 8

1. The ascending limb is impermeable to water and sodium leaves to enter the medullary interstitium
2. Decrease in ascending limb fluid osmolarity
3. Water is drawn from the descending limb due to the concentration of medullary interstitial
4. Fluid in the descending limb increases in osmolarity
5. More fluid enters and forces fluid form descending to ascending limb
6. This fluid is greater in osmolarity

The high osmolarity of the interstitium will allow for reabsorption of water from the collecting duct

Question 9

Describe the transport of water through the distal tubule of the kidney

Answer 9

H20 enters the cell via AQP2
Enters intersititum via to AQP3/4
AQP synthesis stimulated by ADH binding to V2

Question 10

Describe the transport of sodium through the distal tubule of the kidney

Answer 10

Early - Sodium chloride co-transport protein at the apical membrane -> sodium chloride reabsorption
Potassium levels balanced by symport with chloride at the basal membrane

Late - more permeable to water due to AQP

Question 11

Describe the reabsorption of sodium in the collecting duct of the kidney

Answer 11

Sodium transport through a channel (apical)
Exchange with potassium
Potassium excreted into the tubule
Chloride enters from tubule -> interstitium

Question 12

how do diuretics work

Answer 12

Inhibit the reabsorption of Na+ and Cl- (increase excretion)

Increase the osmolarity of tubular fliud (decreases the osmotic gradient across the epithelia)

Question 13

What are the 5 main classes of diuretics and give an example of each

Answer 13

Osmotic diuretics - mannitol

Carbonic anhydrase inhibitors - acetazolamide

Loop diuretics - frusemide (furosemide)

Thiazides - bendrofluazide (bendroflumethiazide)

Potassium sparing diuretics - amiloride, spironolactone

Question 14

Explain the mechanism of action of loop diuretics

Answer 14

Acts on the ascending loop of Henle, inhibiting the transport of sodium and chloride (30%)

There is an increase in tubular fluid osmolarity, while interstitium osmolarity decreases and water reabsorption from the collecting duct decreases

Question 15

What are some other effects of loop diuretics

Answer 15

Increase in sodium delivery to the distal tubule
Increase in potassium loss
Calcium and magnesium reabsorbed- loss of potassium recycling

Question 16

Explain the mechanism of action of thiazide diuretics

Answer 16

Inhibit sodium and chloride reabsorption in the early distal tubule (5-10%）
Increasing tubular fluid osmolarity and reducing water reabsorption in the collecting duct.
Less powerful than loop diuretics as there is a reduced effect on the interstitium

Question 17

What are some other effects of thiazide diuretics

Answer 17

Increase in sodium delivery to distal tubule
Increase in potassium exchange
Magnesium loss
Calcium reabsorption

Question 18

What is the problem with thiazide and loop diuretics

Answer 18

Long-term they activate the RAAS as they cause water and sodium loss. This is recognised by the macula densa cells.
This is a problem with loop diuretics as the protein that puts sodium into the macula densa cell is the one that is stopped by these loop diuretics so the macula densa cell activates RAAS

Question 19

What are the classes of potassium sparing drugs and give an example of each

Answer 19

Aldosterone receptor antagonists
e.g. spironolactone

Inhibitors of aldosterone-sensitive Na+ channels
e.g. amiloride

Question 20

Explain the mechanism of action of potassium sparing diuretics

Answer 20

Spironolactone causes a reduction in sodium channels and Na-K-ATPase and therefore less potassium loss due to inhibition of aldosterone receptors in the early distal tubule (5%)
Amiloride inhibits the entry of sodium
Reduced water reabsorption in collecting duct

Question 21

What are some other effects of potassium sparing diuretics

Answer 21

reduction in reabsorption of Na+ to distal tubule

Increased H+ retention (reduced Na+/H+ exchange)

Question 22

Give some common side effects of loop and thiazide diuretics

Answer 22

Hypovolaemia 
Metabolic alkalosis 
Hyponatraemia 
Hypokalaemia 
Hyperuricemia

Question 23

What causes uric acid build up in the use of diuretics

Answer 23

The transport protein that moves diuretics across the basal membrane is the same that transports uric acid. With increased diuretic movement, less uric acid is excreted resulting in hyperuricemia

Question 24

Give some common side effects of potassium sparing diuretics

Answer 24

Hyperkalaemia

Question 25

What are the uses of diuretics

Answer 25

Thiazides are 1st line treatment of hypertension (salt sensitive)
Heart failure treatment

Question 26

Why are thiazides used in hypertension treatment instead of other diuretics

Answer 26

Other diuretics
Initial response (4-6 weeks) due to decreased plasma volume 
After 4=6 weeks - plasma volume restored

Chronic thiazides (in contrast with other diuretics) - causes vasodilation and reduces TPR

Question 27

What is given along diuretics to inhibit the counter effect of RAAS

Answer 27

ACE inhibitors

Question 28

Explain why diuretics can be used in heart failure treatment

Answer 28

The heart becomes less efficient at pumping blood so CO falls. RAAS and sympathetic system activation to increase blood pressure.
However, there is also cardiac remodelling which would input a greater load on the heart
There is also congestion of blood in the venous system
Diuretics would cause sodium reduction and fluid loss

Question 29

What is the problem with using loop diuretics in heart failure and how is it overcome

Answer 29

Loop diuretics would cause sodium reduction and fluid loss, but it would also activate the RAAS.
To overcome this, a potassium sparing diuretic can be administered alongside.