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1

What are diuretics?

Drugs that act on the renal tubule to promote excretion of Na+, Cl- and H2O

2

What percentage of filtered fluid is reabsorbed in the proximal tubule?

65-70%

3

How does water move into the epithelial cells from the lumen inthe proximal tubule?

Osmosis – it will follow the diffusion of Na+ into the cell

4

What important protein is present on the basolateral membrane of epithelial cells along most of the tubule and is responsible for maintaining the concentration gradient that allows sodium reabsorption?

Na+/K+ ATPase

5

What other force is present, within the interstitium, that helps draw water in from the tubule?

Oncotic pressure – proteins in the blood in the arterioles

6

Other than through the cell, what other route is there for the movement of ions and water?

Paracellular pathway

7

What is the paracellular pathway dependent on?

Gap junctions

8

What two other molecules in the filtrate are reabsorbed in the proximal tubule and are coupled with Na+ reabsorption?

Glucose Amino acids

9

Explain how sodium exchange is linked to carbonic anhydrase?

HCO3- and H+ are filtered in the glomerulus They are then converted, by carbonic anhydrase, to H2O and CO2, which freely diffuse into the proximal tubule epithelial cell Inside the epithelial cell, carbonic anhydrase converts the H2O and CO2 to H+ and HCO3- HCO3- is then cotransported with Na+ into the interstitium H+ is exchanged for Na+ at the apical membrane via the Na+/H+ exchanger

10

How are exogenous agents removed in the kidneys?

Drugs are removed by transport proteins that pick up drugs as they pass through the kidneys and transport them into the lumen

11

Describe the permeability of the loop of Henle to water.

The descending limb is freely permeable to water but not to ions The ascending limb is impermeable to water but is permeable to ions

12

What is the main channel present on the apical membrane of theepithelial cells of the ascending limb of the loop of Henle?

Na+/K+/2Cl- cotransporter

13

What are the channels that are present on the basolateral membrane of the epithelial cells of the ascending limb of the loop of Henle?

Na+/K+ ATPase K+/Cl- cotransporte

14

Describe how the counter-current system is established.

The filtrate would travel down the loop of Henle and as it goes up the ascending limb (impermeable to water but permeable to ions), Na+ moves from the tubule to the interstitium thus making the interstitium hypertonic and the tubular fluid hypotonic. Then, more fluid will come down the descending limb (permeable to water) and the hypertonic interstitium will attract water and increase the reabsorption of water from the tubule into the interstitium This will increase the concentration of fluid reaching the ascending tubule where even more Na+ will be reabsorbed and move into the interstitium This occurs repetitively and you end up with a hypertonic interstitium and hypotonic tubular fluid leaving the loop of Henle This hypertonic interstitium is also responsible for increasing water reabsorption in the collecting duct (mediated by vasopressin)

15

What are the main channels on the apical membrane of epithelial cells of the early distal tubule?

Na+/Cl- cotransporter

16

What are the channels you tend to find in the later DCT

Aldosterone dependent Na channels

17

Which channels are found on the basolateral membrane of the epithelial cells of the distal tubule?

Na+/K+ ATPase K+/Cl- cotransporter

18

Describe the effect of aldosterone on collecting duct cells.

Aldosterone stimulates the production of Na+ channels and the production of Na+/K+ ATPases

19

Describe the effect of vasopressin on collecting duct cells.

Vasopressin stimulates the production and assembly of AQP2 molecules thus increasing the ability of the collecting duct to reabsorb water

20

List the five groups of diuretics.

Osmotic Diuretics Carbonic Anhydrase Inhibitors Loop Diuretics Thiazide Diuretics Potassium Sparing Diuretics

21

Give an example of an osmotic diuretic.

Mannitol

22

Give an example of a carbonic anhydrase inhibitor

Acetazolamide

23

Give an example of a loop diuretic.

Frusemide (furosemide)

24

How much fluid loss can loop diuretics cause?

15-20%

25

What is the target of loop diuretics?

Na+/K+/2Cl- cotransporter

26

Explain how loop diuretics exert their diuretic effect.

They block the triple transporter thus reducing the reabsorption of Na+ in the ascending tubule This increases the tubular fluid osmolarity thus reducing water reabsorption from the tubular fluid so the urine fluid volume increases

27

Explain why loop diuretics cause an increase in urinary excretionof Mg2+ and Ca2+.

Potassium recycling, under normal conditions, means that there is a certain amount of K+ in the tubular fluid that can maintain the positive lumen potential and drive other positively charged ions (Mg2+ and Ca2+) into the interstitium via the paracellular pathway Loop diuretics cause the loss of potassium recycling meaning that there is insufficient K+ in the lumen to drive the other positive ions through the paracellular pathway so you get increased urinary excretion of Mg2+ and Ca2+

28

Why do loop diuretics cause an increase in K+ loss?

Loop diuretics increase the concentration of Na+ in the tubular fluid that is reaching the distal tubule This means that there is increased Na+/K+ exchange is the distal tubule --> increased K+ loss

29

What is the main use of loop diuretics?

Oedema

30

What are the unwanted effects of loop diuretics?

Hypovolaemia Hypotension Hypokalaemia Metabolic Alkalosis