Proximal Tubule

Question 1

Solutes that are reabsorbed via active transport … have 3 distinct characteristics?

Answer 1

1. Competitive inhibition - compete with other solutes for transporter
2. Metabolic inhibition
3. Transport maximum - transporters get saturated (glucose)

Question 2

How is urea reabsorbed (passive or active)

Answer 2

Passive

As water is reabsorbed… the concentration of urea increases…thus generating a gradient for passive reabsorption

Question 3

Major characteristic of passive solutes

Answer 3

Rate or reabsorption decreases and rate of excretion in the urine INCREASES as the urine flow increases

Question 4

Are urine flow increases why does urea reabsorption decrease

Answer 4

Water reabsorption decreased…so there is less of a urea gradient to drive passive reabsorption

Question 5

Proximal tubule reabsorption levels for key solutes

Answer 5

67% NaCl and water

80-85% HCO3-

All of filtered glucose and amino acids, and inorganic ions like phosphate and sulfate, and organic acid anions like lactate, acetate, succinate, and citrate

Also sire for isosmotic fluid reabsorption

Question 6

Location of Na/K ATPase

Answer 6

Basolateral membrane in early and late PT

Question 7

Location of Na/H exchanger

Answer 7

Early and late PT (apical membrane)

Mediates reabsorption of HCO3

Question 8

Net lumen transepithelial potential gradient in early proximal tubule

Answer 8

Negative (-4mV)

Net effect from Na+/solute cotransporter and Na/H exchanger

Helps drive a small amount of passive Cl- reabsorption by the EARLY PT

Question 9

Major mechanism of Na cell entry in LATE proximal tubule

Answer 9

Na/H exchanger

Working in parallel with the an apical membrane Cl/anion exchanger

Anions = OH, HCO3, and formate…

These anions combine with the H+ that was pumped out and recycle back into the cell…dissociate…and thus continue to drive Na+ entry into the (Na/H exchanger)

Question 10

What drive the Cl-/anion exchanger in the LATE proximal tubule?

Answer 10

The early proximal tubule…the major players are the Na/solute and Na/HCO3 reabsorption…

Thus there is high concentration of Cl- in the LATE proximal tubule

Thus…driving the Cl-/anion exchanger
—Cl into cell and anion into tubule
…also drives passive Cl reabsorption through paracellular pathway (with Na+)

Question 11

Lumen transepithelial potential gradient in the LATE proximal tubule

Answer 11

Positive (+4mV)

Due to the increase reabsorption of Cl-

Question 12

Mechanism for HCO3 reabsorption in the proximal tubule

Answer 12

1. H+ secreted into tubule lumen (Na/H+)
2. Combine with filtered HCO3 —> carbonic acid (H2CO3)
3. Carbonic anhydrase (apical membrane): H2CO3 —> H2O + CO2
4. CO2 diffuses into cell…where it is hydroxylated (addition of OH-) by CA in cyotplasm —> HCO3
5. HCO3 exit through basolateral membrane via Cl/HCO3 exchangers and Na/HCO3 cotransporters

Question 13

Carbonic anhydrase inhibitors

Answer 13

Class of diuretic

Acetazolamide

Inhibit CA that is located in the apical membrane and cytoplasm

So…inhibit the reabsorption of Na+HCO3-; NaCl, and water

Results in an increase in urine flow and urinary sodium excretion

Question 14

Luminal hypotonicity mechanism of water reabsorption

Answer 14

As Na+ and other solutes are reabsorbed from the tubular fluid into the interstitial fluid…

The tubular fluid becomes hypotonic, with respect to the intersitial fluid and the plasma

Thus the PT generates a water gradient for passive movement into interstitial fluid…

Then it is pick up into peritubular capillary plasma due to oncotic pressure in capillary

Question 15

Axial anion asymmetry mechanism for water reabsorption

Answer 15

Consequence of the differences in the Na/solute transport in the early and late PTs

Early = Na+ mostly reabsorbed with glucose, amino acids, inorganic anions, and organic acids anions and HCO3….

Creates a low HCO3 and high Cl- in LATE proximal tubule…

The HCO3 in the interstitial fluid provides a osmotic driving force for water to be reabsorbed

Question 16

Effect of vasoconstrictor hormones

ANGII, catecholamines

Answer 16

Stimulate PT reabsorption of NaCl, NaHCO3, and water

Question 17

Vasodilator hormones (renal) effect

Dopamine

Answer 17

Inhibit PT reabsorption of salt and water

Question 18

starling forces =

Answer 18

The oncotic pressure in capillaries that will bring water and things dissolved in that water in the interstitial fluid into the capillaries

Question 19

Factors that decrease plasma protein levels =

Answer 19

Like ECF expansion,

Inhibit movement of water from interstitium into the capillaries…

This increases hydrostatic pressure in the interstitial fluid … which is thought to increase the permeability of the tight junctions between the proximal tubule cells

…increasing solutes and fluid diffusing back into the tubule and excreted back into urine

NET effect = decrease salt and water reabsorption

Major mechanism for isotonic saline to increase ECF and urine flow and urinary Na excretion

Question 20

PT reabsorption of water and salt is particulary determine by what

Answer 20

GFR..

Increased GFR = increase PT reabsorption rate

Does this to maintain a fractional reabsorption rate of ~67%

Question 21

2 major mechanism that PT to maintain constant fractional reabsorption of water and salt

Answer 21

1. Changes in the delivery of NaCl and solutes in the apical membrane …. more delivered —> more transporters are stimulated to reabsorb
2. Involves changes in Starling Forces…

Ex: if GFR increase 50% but RPF constant…GFR/RPF increases (filtration fraction)
….so more oncotic pressure in capillaries….increase in net solute and fluid reabsorption in PT

Question 22

Increases in filtration fraction —>

Answer 22

Increases in PT solute and fluid reabsorption