Renal Tubular Function

Question 1

How is the proximal tubule divided?

Answer 1

• The first 60% is the proximal convoluted tubule.

- The last 40% is the proximal straight tubule.

Question 2

In which layer of the kidney is the proximal tubule?

Answer 2

The renal cortex.

Question 3

What lines the surface of the proximal convoluted tubule?

Answer 3

Microvilli, forming a brush border.

Question 4

How is directional ion movement controlled in the proximal convoluted tubule?

Answer 4

The ion channels, exchangers, cotransporters (secondary active) and pumps (primary active) are selectively distributed on the apical and basolateral membranes.

Question 5

List the primary routes of transport for ions and water.

Answer 5

1 - Transcellular (through cells).

2 - Paracellular (between cells).

Question 6

If the proximal tubule is water permeable, what can be said about the tonicity of the interstitial space?

Answer 6

The interstitial space is ~isotonic with the filtrate passing through it.

Question 7

How much water is reabsorbed by the end of the proximal convoluted tubule?

Answer 7

~70%.

Question 8

List the substances for which absorption in the proximal convoluted tubule is driven by movement of Na+.

Answer 8

1 - Water.

2 - Glucose

3 - Amino acids.

Question 9

How is Na+ extruded from an endothelial cell in the proximal convoluted tubule?

Answer 9

Via the Na+/K+ ATPase on the basolateral membrane.

Question 10

Through which channels does water pass to cross cell membranes in the proximal tubule?

Answer 10

Aquaporin 1.

Question 11

List 2 molecules that are not reabsorbed along the proximal tubule.

Answer 11

1 - Inulin (a polysaccharide).

2 - Creatinine.

Question 12

List 2 molecules that are reabsorbed along the proximal tubule to a lesser extent than water.

How will the concentration of these molecules change along the proximal tubule?

Answer 12

1 - Urea.

2 - Cl-.

• The concentration of these molecules at the end of the tubule will be higher than at the start.

Question 13

List 2 molecules that are reabsorbed along the proximal tubule to approximately the same extent as water.

Answer 13

1 - Na+.

2 - K+.

• The concentration of these molecules at the end of the tubule will be the same as that at the start.

Question 14

List 3 molecules that are reabsorbed along the proximal tubule to a greater extent than water.

Answer 14

1 - HCO3-.

2 - Amino acids.

3 - Glucose.

• The concentration of these molecules at the end of the tubule will be lower than that at the start.

Question 15

Describe the process by which glucose is reabsorbed in the proximal tubule.

Answer 15

• The active extrusion of Na + on the basal side of the cell by the Na + K + ATPase generates an electrochemical gradient for Na+ entry into the cell from the tubule, across the apical membrane.
• Na+ enters the cell with glucose via glucose symporters known as SGLT2 in the early proximal tubule and SGLT1 in the late proximal tubule. This creates a gradient for glucose movement out of the cell.
• Glucose exits the cell on the basolateral side of the cell via GLUT2 in the early proximal tubule and GLUT1 in the late proximal tubule.

Question 16

What is the difference between SGLT2 and SGLT1?

Answer 16

• SGLT2 transports 1 Na+ for each glucose, whereas SGLT1 transports 2 Na+ for each glucose.
• SGLT2 transporters are low affinity, but high capacity.
• SGLT1 transporters are high affinity, but low capacity.

Question 17

Why is SGLT2 found in the early proximal tubule whereas SGLT1 is found in the late proximal tubule?

Answer 17

• Early in the proximal tubule, the concentration of glucose in the tubule lumen is higher than in the late tubule.
• Therefore less energy is required to move glucose up its concentration gradient into the cell at the early tubule, as the gradient is shallower.
• Therefore, in the early tubule, 1 Na+ is sufficient to move glucose into the cell using secondary active transport (SGLT2), whereas 2Na+ are required in the late tubule (SGLT1).

Question 18

What is the maximum transport for glucose in adults?

Answer 18

380 mg min^-1.

Question 19

What type of drugs are canagliflozin and dapagliflozin?

What is their purpose and how do they work?

Answer 19

• Canagliflozin and dapagliflozin are SGLT2 inhibitors.
• They are used for the treatment of diabetes.
• They work by preventing glucose reabsorption, therefore causing glucosuria and increasing glucose excretion.

Question 20

List 2 side effects of SGLT 2 inhibitors

Answer 20

1 - Genital yeast and urinary tract infections (UTIs due to stagnant urine).

2 - Polyuria.

Question 21

What is the plasma amino acid concentration?

Answer 21

2.5-3.5mM.

Question 22

What is the plasma glucose concentration?

Answer 22

3.9-7.1mM.

Question 23

How are most amino acids transported from the tubule lumen into the intracellular spaces?

Answer 23

By various cotransporters that use the Na+ gradient (analogous to SGLTs for glucose).

Question 24

Describe the process by which HCO3- is reabsorbed in the proximal tubule.

Answer 24

1 - H+ ions are pumped out of the epithelial cells by a Na+/H+ exchanger.

2 - In the tubule lumen, H+ and HCO3- form H2CO3.

3 - Carbonic anhydrase converts H2CO3 -> H2O and CO2, which can diffuse freely into the epithelial cells.

4 - Carbonic anhydrase reconverts H2O and CO2 into H2CO3.

5 - H2CO3 dissociates into H+ and HCO3-.

6 - HCO3- exits the cell via HCO3- / Na+ cotransporters on the basolateral membrane, which cotransports 1 HCO3- ion and 3 Na+ ions (both out of the basolateral membrane).

Question 25

How is a concentration gradient maintained for Na+ entry into epithelial cells?

Answer 25

A Na+/K+ ATPase is present on the basolateral surface of the epithelial cells, which transports 3 Na+ out of the cell for every 2 K+ in.

Question 26

What is acetazolamide?

What is its purpose and how does it work?

Answer 26

• Acetazolamide is an inhibitor for carbonic anhydrase.
• It is used as a weak diuretic (increases urine production).
• It works by decreasing Na+ and HCO3- reabsorption, which therefore reduces reabsorption of water.

Question 27

How does acetazolamide affect pH of the urine and blood?

Answer 27

1 - Urine becomes alkaline.

2 - Causes metabolic acidosis.

Question 28

List 2 conditions that may be treated using acetazolamide.

Answer 28

1 - Glaucoma.

2 - Mountain sickness.

Question 29

What is the concentration of HCO3- in the filtrate?

Answer 29

25mM.

Question 30

How does caffeine produce a diuretic effect?

Answer 30

• Caffeine is an adenosine receptor antagonist, and therefore suppresses the sodium-bicarbonate cotransporter.
• By inhibiting Na+ and HCO3- reabsorption, water reabsorption is inhibited, causing diuresis.

Question 31

Describe the active process by which Cl- is reabsorbed in the proximal tubule.

Answer 31

1 - Cl- is transported into endothelial cells via antiporters for HCO3- and HCOO-.

2 - The Na+/H+ antiporter transports H+ out of the endothelial cell into the lumen in exchange for Na+.

3 - HCOO- in the lumen combines with H+ to form HCOOH, which can freely diffuse into the endothelial cell.

4 - HCOOH dissociates into HCOO- and H+ in the endothelial cell, where HCOO- can be exchanged for more Cl- and H+ can be exchanged for more Na+.

5 - Cl- exits the cell via Cl-/K+ symporters on the basolateral membrane and through Cl- channels.

Question 32

Describe the passive process by which Cl- is reabsorbed in the proximal tubule.

Where in the proximal convoluted tubule does this happen at the highest rate?

Answer 32

• Cl- diffuses through the paracellular route.

- This happens at the highest rate in the late proximal tubule, as the Cl- concentration is higher.

Question 33

Why is less Cl- absorbed than Na+ in the early proximal tubule?

Why is this significant for Cl- movement late in the tubule?

Answer 33

• Because Na+ is also required for the absorptions of other solutes.
• This is significant as Cl- concentration will modestly increase down the tubule, driving passive movement of Cl- paracellularly.

Question 34

How is albumin reabsorbed in the proximal tubule?

Answer 34

1 - Albumin binds to the plasma membrane of the tubule endothelial cells.

2 - It is then endocytosed.

3 - It is then catabolised to its amino acids for recycling in the body.

Question 35

Where does organic acid and base secretion occur along the tubule?

Answer 35

• Organic acid secretion takes place in the proximal straight tubule.
• Organic base secretion occurs in the proximal convoluted tubule.

Question 36

List 3 organic anions that are actively secreted in the proximal tubule.

Answer 36

1 - Penicillin.

2 - PAH (used to measure renal function).

3 - Furosemide (a diuretic).

Question 37

How do organic anions enter the endothelial cells of the proximal tubule for excretion?

Answer 37

Via organic anion transporters (OATs) on the basolateral membrane of the cell.

Question 38

How do organic anions exit the endothelial cells of the proximal tubule for excretion?

Answer 38

Via multidrug resistance-associated proteins (MRPs).

Question 39

Describe the process of Na+ reabsorption into renal endothelial cells.

Answer 39

• Down a large electrochemical gradient; Na+ reabsorption is passive (as long as its concentration gradient is maintained).
• However, entry of Na+ is carrier mediated; many other solutes are transported by Na+ symport and antiport.
• Most Na+ entry is via Na+/H+ antiport.