Tubular transport

Question 1

What type (permeability) of epithelia is present in the PCR?

Answer 1

Leaky

Question 2

Why do we filter and reabsorb?

Answer 2

Only transporters for specific solutes which must be reabsorbed are required.

Water balance is facilitated by using absorptive process for H2O rather than secretory one

Energetically advantageous, as many solutes can be reabsorbed in association with Na+ gradient generated.

Question 3

What are the key properties of the leaky proximal tubule?

Answer 3

Many carriers

Paracellular transport due to leaky epithelia

More substances are reabsorbed

Question 4

What are the anatomical subdivisions of the PCT?

Answer 4

S1, S2, S3

Question 5

What is the benefit of having brush border microvilli cells?

Answer 5

Larger surface are for more reabsorption

Question 6

What is the permeability to ions and water at the PCT?

Answer 6

High permeability to ions

High permeability to water through AQP1 and some through paracellular pathway

Question 7

Why is there not a large potential difference generated across the epithelia as ions move?

Answer 7

Low potential difference generated

Due to shunting of ions with electrochemical gradient via the paracellular pathway

Question 8

What differences of reabsorption occur at the proximal and distal ends of the PCT?

Answer 8

Primarily Na+ transport is coupled to uptake of organic solutes, phosphate and bicarbonate.

Chloride uptake occurs at the distal end of the PCT

Question 9

Why must chloride reabsorption happen at the distal end of the PCT?

Answer 9

The earlier steps help to set up a paracellular gradient for chloride.

Question 10

For reabsorption of glucose, which transporters are on the apical and basolateral membrane?

Answer 10

Basolateral: Na-KATPase, GLUT (facilitated diffusion of glucose), K+ leak channels

Apical: SGLT2 and SGLT1, sodium glucose symporter

Question 11

What is the stoichiometry of SGLT1/2?

Answer 11

SGLT2 1:1

SGLT1 2Na+: 1

Question 12

Which segments of the PCT are the different SGLT present in?

Answer 12

SGLT 2 present in S1 and S2

SGLT 1 present in S3

Question 13

Why is SGLT with a higher stoichiometry present in the distal part of the PCT?

Answer 13

Doubling the stoichiometry gives the square of the energetic power for moving glucose from the lumen into the cell.

This is especially important in the distal part of the PCT in order to scavenge for remaining glucose molecules that have yet to be absorbed.

Question 14

Why does reabsorption rate for glucose plateau?

Answer 14

Finite number of symporters, and once these are fully occupied, the rate of reabsorption cannot increase.

Question 15

Why does glucose end up in diabetic urine?

Answer 15

There is a limit in glucose concentration in which excretion exceeds reabsorption, explaining glucose in urine of a diabetic, who cannot control blood glucose concentration. This region is called overspill.

Question 16

How are amino acids reabsorbed?

Answer 16

Handled in a very similar fashion to glucose. After filtration they are reabsorbed in the PCT by mechanisms like the glucose system. Transporters are stereospecific for L-amino acids.

Question 17

What are four distinct groups of amino acid transporters ?

Answer 17

Cationic (basic), Anionic (acidic), neutral, glycine/proline

Question 18

Why is absorption of HCO3- indirect?

Answer 18

Bicarbonate does not have a specific transporter

Question 19

How is bicarbonate reabsorbed?

Answer 19

It begins with the active secretion of a hydrogen ion (H+) into the tubule fluid via a Na/H exchanger (antiporter)

In the lumen
The H+ combines with HCO3− to form carbonic acid (H2CO3)
Luminal carbonic anhydrase enzymatically converts H2CO3 into H2O and CO2

CO2 freely diffuses into the cell

In the epithelial cell
Cytoplasmic carbonic anhydrase converts the CO2 and H2O (which is abundant in the cell) into H2CO3

H2CO3 readily dissociates into H+ and HCO3−

HCO3− is facilitated out of the cell’s basolateral membrane by a Na+ HCO3- transporter

Question 20

What is the stoichiometry of the Na+/HCO3- transporter?

Answer 20

3HCO3-: 1Na+ (both move out, sodium against its electrochemical gradient)

Question 21

Why is the high bicarbonate stoichiometry necessary on the Na+/HCO3- transporter?

Answer 21

The high stoichiometry increases (cubes) driving force for movement of bicarbonate and to move Na+ against its gradient.

Question 22

What are the two pathways for Cl- absorption?

Answer 22

Paracellular

Transcellular

Question 23

What drives the paracellular absorption of Cl-?

Answer 23

Passive movement down electrochemical gradient

Driven by sodium movement through cells, water follows to maintain isotonicity, this increases [Cl-] in lumen increasing the chemical gradient.

Question 24

What two ways can Cl- move across the apical membrane of PCT?

Answer 24

Directly via Na/Cl symport

Indirectly driven by Na+/H+ antiport

Question 25

How does chloride move indirectly across the apical membrane?

Answer 25

Some H+ in the lumen (not converted to H2CO3) combines with anion (formate HCOO-) forming HA. This then enters the cell and dissociates into H+ and A-. Formate (HCOO-) is transported out the cell as Cl- is transported in (secondary active transport driven by Na+/H+ antiporter).

Question 26

How is chloride absorbed at the basolateral membrane?

Answer 26

With a chloride potassium transporter (both move out of cell)

Question 27

What is one example of a substance reabsorbed that is not driven by a sodium gradient?

Answer 27

Calcium

Question 28

How is calcium reabsorbed?

Answer 28

Some via solvent drag/diffusion paracellularly Transcellular pathway

Question 29

Explain what drives the transcellular absorption of Ca2+

Answer 29

Driven by basolateral CaATPase and NCX (partly driven by Na/KATPase)

Question 30

What are the apical calcium transporters?

Answer 30

ECaC

Question 31

What stimulates Ca2+ reabsorption?

Answer 31

Parathyroid hormone and vitamin D

Question 32

What is secreted in the PCT?

Answer 32

Organic anions and cations such as PAH

Question 33

How does the PCT secrete PAH?

Answer 33

Dicarboxylate sodium transporter on basolateral membrane moves 3Na+ into cell with 1 DC2-. This drives the DC2- para-amino hippurate (PAH) transporter (also basolateral), moving 1 DC2- out and 1 PAH in. Anions are then exchanged with PAH on the apical membrane. This leads to an overall secretion of PAH into the tubule.

Question 34

How is water reabsorbed across the PCT?

Answer 34

Water moves passively down its concentration gradient, secondary to the active transport of solutes and sodium.

Question 35

Why is water reabsorption across the PCT described as isotonic?

Answer 35

There is no discernable osmotic difference between the lumen and the interstitial fluid

Question 36

Why does water still get reabsorbed if it is isotonic between lumen and interstitium?

Answer 36

The PCT is highly permeable to water due to the presence of many AQP1 channels on the apical membrane, this means very small osmotic gradients (like this transient one) can drive large water flows.

Question 37

Na+-HCO3- co-transporters are expressed ...

Answer 37

In the basolateral membrane of proximal tubular epithelium

Question 38

Why does inhibition of CA cause decreased Na+ absorption at the PCT?

Answer 38

Less H+, Less action of NHE , less Na+ in

Question 39

How does inhibition of CA affect Na+ absorption and K+ secretion?

Answer 39

Reduces Na+ absorption (pct) | Increases K+ secretion (dct)

Question 40

Why does inhibition of CA cause increased K+ secretion at the DCT?

Answer 40

More Na+ in tubule as less has been absorbed More action of the NaKATPase - more work for distal tubule to reclaim Na+ Thus more K+ into cell and leaves apically by leak channels, hypokalemia