Proximal Tube Transport

Question 1

Review: 2 types of gradients that make water move across a membrane?

Answer 1

Hydrostatic and oncotic pressure gradients.

Question 2

4 things that make solutes move across an epithelium?

Answer 2

Active transport.
Transepithelial (i.e. paracellular) electrochemical gradients.
Apical membrane-cell and basolateral membrane-cell electrochemical (i.e. transcellular).
“Solvent drag.”

Question 3

Do tight junctions play a role in transepithelial ion transport? Which ones, specifically?

Answer 3

Yes. Claudins and E-cadherin mediate paracellular Ca++ transport.

Question 4

If the Na+/K+ ATPase on the basolateral membrane of proximal convoluted tubule (PCT) epithelium is “primary active transport”, what is “secondary active transport”?
How about “tertiary active transport”?

Answer 4

Secondary: H+/Na+ exchanger on apical membrane (brings Na+ in from lumen, moves H+ out).
Tertiary: HCO3-/Cl- exchanger (bicarb follows H+ out into lumen, Cl- comes in).

Note these steps don’t require energy.

Question 5

What are the most metabolically active areas of the nephron?

Answer 5

The most hard-working areas are the medullary thin and thick ascending limbs and the distal convoluted tubule.
But the PCT does a lot of work too.

Question 6

What 2 solutes are reabsorbed earliest and most avidly in the PCT?

Answer 6

Glucose and amino acids

lots of bicarb is reabsorbed, but that occurs more slowly

Question 7

How does the ratio of tubular [Na+] vs. plasma [Na+] change along the length of the PCT?

Answer 7

As both Na+ and water are reabsorbed, the [Na+] stays pretty similar to that in the plasma throughout the PCT… but it does increase slowly.

Question 8

How does [Cl-] vary across the length of the PCT?

Answer 8

Cl- is not reabsorbed much at first, so the concentration increases like that of inulin would (due to water reabsorption).
Further downstream Cl- begins to be absorbed, and the concentration increases at a much slower rate.

Question 9

Is PCT water permeability determined by vasopressin?

Answer 9

Nope. It’s just always very permeable to water.

and thus urine remains nearly isotonic to plasma along the PCT - any movement of solute is followed by water

Question 10

What membrane molecules make the PCT so permeable to water?

Answer 10

Aquaporins, specifically AQP1 (and AQP7)

Question 11

What would a defect in AQP1 cause?

Answer 11

Large volumes of dilute urine, as water could not be absorbed from the PCT (and the thin descending loop of Henle).

Question 12

Is most of the water reabsorption in the PCT transcellular or paracellular?

Answer 12

Transcellular.

Question 13

Is there a Na/Cl cotransporter in the PCT?

Answer 13

No. Cl- transport is largely paracellular, driven by an electrochemical gradient that’s positive in the lumen of the late PCT.

Question 14

2 apical transporters involved in glucose reabsorption? Where are they? How are they different?

Answer 14

SGLT2 - in the PCT - high capacity, low affinity (Coupled to 1 Na+).
SGLT1 - the pars recta - low capacity, high affinity (coupled to 2 Na+).

Question 15

What 2 basolateral glucose transporters are used? Where are they?

Answer 15

PCT: GLUT2

Pars recta: GLUT1

Question 16

About high does plasma glucose have to be in order for glucose to appear in the urine?

Answer 16

About 250mg/dL.

urine glucose isn’t a great way to monitor diabetes

Question 17

What drives phosphate resorption?

Answer 17

Cotransport with Na+.

Question 18

3 things that decrease phosphate reabsorption?

Answer 18

PTH (parathyroid hormone).
High phosphate intake.
FGF-23

Question 19

2 things that increase phosphate reabsorption?

Answer 19

Phosphate deficiency.

Growth hormone.

Question 20

Failure to reabsorb what amino acid will give you really bad kidney stones?

Answer 20

Cysteine.

Question 21

What’s weird about urate handling in the kidney?

Answer 21

It’s all reabsorbed, then it’s secreted, then mostly it’s reabsorbed again.
(too much reabsorption -> gout. Too much excretion -> kidney stones)

Question 22

Is bicarb reabsorbed as bicarb?

Answer 22

Nope, it’s converted with a H+ by carbonic anhydrase to CO2 + H2O.
CO2 + H2O enter the PCT cell, where another carbonic anhydrase converts it back to bicarb. Bicarb and Na+ are cotransported into the blood.

Question 23

How is Ca++ reabsorbed in the PCT, and where within the PCT does this happen?

Answer 23

Ca++ is reabsorbed paracellularly via Claudin-2.
This happens in the late PCT, when the lumen has a + charge.
(50-60% of Ca++ reabsorption happens in the PCT.)

Question 24

What percentage of Mg++ is reabsorbed in the PCT?

Answer 24

Only 5-15%

Question 25

What happens to K+ in the PCT?

Answer 25

A small amount is secreted.
Mostly it’s absorbed paracellularly (via “solvent drag” early in PCT, passively in late PCT when there’s more luminal + charge)

Question 26

How are big molecules reabsorbed in the PT?

Answer 26

Endocytosis via the AMN-Megalin-Cubulin complex…

Question 27

Where is the ammonia (NH4+) that reaches PCT lumen made?

How does it then get to the urine?

Answer 27

Largely in the mitochondria of PCT cells.
The mitochondria convert glutamine to glutamate to alpha-ketoglutarate, producing 2 NH4+…
Ammonia enters the urine either by an Na+/NH4+ exchanger, or diffusing as NH3.

Question 28

What happens to NH4+ made by kidney that gets into the blood?

Answer 28

It’s transported to the liver, where it’s made into urea.

Question 29

2 types of proximal tubule diuretic?

Answer 29

Osmotic diuretics (mannitol, high levels of glucose)
Carbonic anhydrase inhibitors (more on this later, I assume)

Question 30

What’s Fanconi syndrome? What’s thought to cause it?

Answer 30

General dysfunction of the proximal tubule, causing wasting of phosphate, glucose, amino acids, and bicarb.
Has a variety of causes, but dysfunction of the Na+/K+ ATPase could cause this.