Distal Tube Transport

Question 0

Do thin limbs of the loop of Henle do much active transport?

Answer 0

Nope, not much at all. It’s all passive transport.

Question 1

3 things that are at higher concentration in the pars recta than in the blood (i.e. right before entering the thin descending limb of the loop of Henle)?
Why are they higher?

Answer 1

Cl-, due to bicarb resorption in PCT.
K+, due to K+ secretion into pars recta.
NH4+, due to synthesis in PCT.

Question 2

What are the permeabilities to water and solutes like in the thin descending and thin ascending limb?

Answer 2

Thin descending: very permeable to water, not permeable to salts (water comes out, concentrating urine).
Thin ascending: not permeable water, very permeable to salts (Na/Cl comes out).

Question 3

What, broadly, is the function of the thick ascending limb?

Answer 3

Dilute the urine.

Question 4

What’s the notable, powerful transporter in the thick ascending tubule? What does it do?

Answer 4

NKCC2.

Na+, K+, and 2 Cl- symporter.

Question 5

What creates a + charge in the lumen of the thick ascending tubule? What transporter mediates this?

Answer 5

K+ leaking from cytosol back into lumen.

This happens via ROMK channels.

Question 6

What creates the Na+ gradient that allows NKCC2 to work?

Answer 6

Na+ pump in the basolateral membrane.

Question 7

What’s a drug that inhibits NKCC2?

Answer 7

Furosemide -it’s a very powerful diuretic.

Question 8

If a patient has a defect in ROMK, what would be effect on urinary Ca++? Why?

Answer 8

Urinary Ca++ would be increased.
ROMK contributes to the positive charge in the distal tubule lumen. If the lumen charge is too negative, Ca++ won’t be driven to leave the lumen.

Question 9

What does NKCC2 sometimes transport instead of K+?

Answer 9

NH4+

Question 10

What percentage of filtered Mg++ is reabsorbed in the the ascending tubule?

Answer 10

70%

Question 11

What percentage of synthesized ammonia is reabsorbed in the thick ascending limb?

Answer 11

90%

Question 12

How does ascending limb dysfunction lead to hypokalemia and alkalosis?

Answer 12

If NaCl isn’t absorbed in thick ascending limb, less water will be absorbed from the distal convoluted tubule.
Reduced ECF + increased distal tubule flow -> renin release -> aldosterone.
Aldosterone will increase H+ and K+ secretion -> hypokalemia and alkalosis.
(Ascending limb dysfunction will also lead to reduced Ca++ reabsorption.)

Question 13

What is the tonicity (high or low) of fluid entering the distal convoluted tubule?

Answer 13

Low -it has been diluted by the powerful transporters.

Question 14

What approximate levels of Na+, K+, NH4+, HCO3-, Ca++, and Mg++ entering the distal convoluted tubule? (normally)

Answer 14

Na+: about 10% of filtered Na+ remains.
K+ and NH4+: very low.
HCO3-: very low.
Ca++ and Mg++: moderate

Question 15

How is Na+ reabsorbed in the distal convoluted tubule?

How is this gradient established?

Answer 15

Apical Na+/Cl- cotransport, driven by basolateral Na+ pump.

Question 16

What class of drugs inhibits Na+ reabsorption in the distal convoluted tubule? What’s the molecular target?

Answer 16

Thiazide diuretics, by inhibiting the Na+/Cl- cotransporter.

Question 17

What transporter is used for Mg2++ reabsorption?

What creates the gradient that drives this?

Answer 17

TRPM6 is the apical transporter. (the basolateral transporter is unknown?)
This is driven by + charge in the lumen, created by K+ leak channels (Kv1.1 -probably not important.)

Question 18

Where is Mg2++ mostly absorbed?

Answer 18

DCT1 and DCT2…

Question 19

What signaling molecule promotes Mg++ reabsorption?

Answer 19

EGF

Question 20

What transporter is used for Ca++ reabsorption?

What are 2 hormones that promote the expression of this transporter?

Answer 20

TRPV5

PTH and 1,25-(OH)2-D3 (activated vitamin D) promote TRPV5 expression, and thus Ca++ reabsorption.

Question 21

What is the tonicity and pH of fluid leaving the distal convoluted?

Answer 21

Dilute and acidic.

Question 22

How does the collecting duct get the last bit of sodium out of the filtrate?
How is this regulated?

Answer 22

ENaC brings Na+ in from the lumen. The concentration is made by the Na+/K+ ATPase on the basolateral membrane.
Aldosterone promotes ENaC expression on the membrane.

Question 23

to be continued

Answer 23

soon

Question 25

Review: What’s the syndrome with constituitively active ENaC?

Answer 25

Liddle’s syndrome. Too much Na+ reabsorbed in collecting ducts -> hypervolemia, K+ wasting, alkalosis.

Question 26

Which cells in the collecting duct transport H+?

Answer 26

Intercalated cells.

Question 27

How do intercalated cells transport H+?

Answer 27

H+/K+ ATPase and H+ ATPase both pump protons out the apical membrane
The protons come from CO2 + H2O… bicarb is moved into blood in exchange for Cl-.

Question 28

Urea… is an important solute in the medulla that drives H2O reabsorption from the collecting duct.

Answer 28

Okay.

Question 29

How does aldosterone promote H+ secretion, and at high levels cause alkalosis?

Answer 29

ENaC mediated Na+ reabsorption leaves a negative charge in the lumen that drives proton secretion/excretion.

Question 30

Which cells in the collecting duct have ENaC?

Answer 30

Principal Cells