Renal 2

Question 1

What is the function of the distal convoluted tubule?

Answer 1

• relatively impermeable to water
• reabsorb 5-10% of filtered Na+

Question 2

List all the transporters/channels on the apical side of the distal tubule. Which way do the ions flow?

Answer 2

• Na/Cl cotransporter (NCC); Na and Cl go into tubule cells
• Ca2+ selective channel (TRPV5); Ca goes into tubule cells

Question 3

List all the transporters/channels on the basolateral side of the distal tubule? Which way do the ions flow?

Answer 3

• Na/Ca exchanger (NCX); Na into cell, Ca into interstium/blood
• Ca2+/H+ antiport (ATP driven); Ca out of cell into interstium

Question 4

which diuretic drug targets the distal convoluted tubule? What class?

Answer 4

hydrochlorothiazide; class: thiazides

Question 5

What is the mechanism of thiazides?

Answer 5

inhibit NCC (apical) –> decrease Na and Cl reabsorption –> increase Ca reabsorption via NCX (basolateral)

Question 6

What are the therapeutic uses of thiazides?

Answer 6

hypertension, mild HF, severe resistant edema, reduce kidney stone formation in idiopathic hypocalciuria

Question 7

What are the adverse effects of thiazides?

Answer 7

hypokalemia, metabolic alkalosis, impaired glucose tolerance (due to decrease in in insulin release)

Question 8

What is the most important site for K+ excretion?

Answer 8

collecting tubules

Question 9

What are the 2 cell types in the collecting tubules?

Answer 9

principal and intercalated

Question 10

Describe the path of Na reabsorption in the principal cells. (use channels)

Answer 10

1) apical Na+ entry via epithelial Na+ channels (ENaC)
2) Na+ into interstitium via Na/K ATPase

Question 11

How does aldosterone affect ENaC and Na/K ATPase?

Answer 11

increase activity

Question 12

What drives K+ excretion into the lumen in the collecting tubules, in principal cells?

Answer 12

• lumen (-) potentials from Na+ exit from lumen via ENaC
• high [K+] inside cell (due to basolateral Na/K ATPase)

Question 13

What are the 2 types of intercalated cells in the collecting tubules?

Answer 13

type A (alpha) and type B (beta)

Question 14

Describe the events that occur at type A intercalated cells.

Answer 14

1) H+ excretion into lumen via apical proton pump
2) HCO3- reabsorption into interstitium via basolateral HCO3-/Cl- exchanger

Question 15

What enhances/drives H+ secretion in type A intercalated cells?

Answer 15

• lumen (-) potential (due to Na influx via ENaC)
• aldosterone increases number of apical proton pumps

Question 16

Which type of intercalated cells dominate in acidemia? alkalemia?

Answer 16

acidemia: type A - secrete excess H+
alkalemia: type B - secrete excess HCO3-

Question 17

Describe the events that occur at type B intercalated cells.

Answer 17

1) HCO3- excretion into lumen via apical HCO3-/Cl- exchanger
2) H+ reabsorption into interstitium via basolateral proton pump

Question 18

Which class of diuretic drugs targets the collecting tubules?

Answer 18

K+ sparing diuretics

Question 19

What are the different types of K+ sparing diuretics?

Answer 19

• inhibitors of Na+ influx through ENaC
• competitive antagonist of aldosterone

Question 20

What is the mechanism and function of amiloride? What class of diuretic is this?

Answer 20

• class: K+ sparing diuretic
• mech: inhibit Na+ influx through ENaC
• fxn: decrease in Na+ exit from lumen –> reduce (-) luminal potential –> less K+ excretion

Question 21

What is the mechanism and function of eplerenone? What class of diuretic is this? What receptor is this drug selective for?

Answer 21

• class: K+ sparing diuretic
• receptor: mineralocorticoid receptors
• mech: competitive antagonist of aldosterone
• fxn1: reduce activities of ENaC and Na/K ATPase in principal cells
  -fxn2: reduce proton pumps in type A intercalated cells

Question 22

How can eplerenone cause metabolic acidosis?

Answer 22

reduce proton pumps in type A intercalated cells –> less proton secretion

Question 23

What are the therapeutic uses of K+ sparing diuretics?

Answer 23

• use with K+ losing diuretics to prevent K+ loss in HF and hypertension treatment
• hyperaldosteronism (aldosterone antagonists)

Question 24

What is the adverse effect of K+ sparing diuretics?

Answer 24

hyperkalemia

Question 25

What is the role of ADH (antidiuretic hormone) on the collecting tubules?

Answer 25

1) ADH acts on basolateral V2 receptors
2) increase cAMP
3) increase insertion of AQP2 in apical membrane
4) increase water reabsorption
5) concentrated urine

Question 26

What is the function of a V2 receptor antagonist? What class of diuretic is this?

Answer 26

• inhibit effect of ADH in collecting tubules
• reduce water reabsorption
• increase plasma Na concentration

class: antidiuretic hormone (ADH)antagonist

Question 27

What are the therapeutic uses of V2 receptor antagonists?

Answer 27

• syndrome of inappropriate ADH secretion (water retention die to excessive ADH secretion)
• hyponatremia

Question 28

What are the adverse effects of V2 receptor antagonists?

Answer 28

• hypernatremia
• hypotension

Question 29

What are the edamatous states that diuretics can clinically treat?

Answer 29

• heart failure
• kidney disease and renal failure
• liver disease
• idiopathic edema

Question 30

What are the non-edematous states that diuretics can clinically treat?

Answer 30

• hypertension
• nephrolithiasis (kidney stone)
• hypercalcemia