Nephron Physiology - 1: Proximal tubule

Question 1

What is the first portion of the renal tubule?

Answer 1

proximal convoluted tubule

Question 2

How is glucose reabsorbed in the PCT?

Answer 2

• 98% reabsorbed in the PCT
• Apical SGLT2 transporter (Na+ and Glu together into cell)
• Basolateral GLUT2 transporter

Question 3

At what plasma level of glucose does glucosuria begin? At what level are all transporters fully saturated?

Answer 3

Glucosuria begins at 200mg/dL

Transporters are fully saturated at 375mg/dL

Question 4

How are amino acids reabsorbed in the PCT?

Answer 4

~100% absorbed in the PCT

• Primary transporters for each type of amino acid (neutral/acidic/basic) - generally Na+ dependent
• Different transporters on apical and basolateral membranes

Question 5

What disorder affects the transporter of neutral amino acids and what are the consequences of this.

Answer 5

Hartnup’s disease; auto R mutation in neutral transmitter (eg tryptophan) in PCT and enterocytes

• aminoaciduria and decreased absorption
• decreased tryptophan for conversion to niacin –> pellagra

Question 6

How is phosphate absorbed in the PCT?

Answer 6

80% of Phos reabsorbed in the PCT via Na+/Phos cotransport.

Question 7

What affects phosphate reabsorption?

Answer 7

PTH decreases Na+/Phos reabsorption by decreasing expression of transporters.

Question 8

How is sodium absorbed in the PCT?

Answer 8

65-80% of Na+ absorbed in PCT.
Basolateral Na/K+ ATPase creates low intracellular Na+
Na+ comes into cell via Na+/H+ exchanger
ATII stimulates Na+/H+ exchange

Question 9

How is bicarb absorbed in the PCT?

Answer 9

80% is reabsorbed in the PCT.

• Dependent on H+ secretion.
• H+ secreted by Na+/H+ exchanger, and by H+/ATPase
• In the lumen, H+ combines with bicarb to make H2CO3
• Carbonic Anhydrase 4 converts H2CO3 to CO2 and H20
• CO2 diffuses freely into cell
• Carbonic Anhydrase 2 converts CO2 + H20 -> H2CO3 which dissociates to H+ and bicarb
• H+ removed by Na+/H+
• Bicarb passes through basolateral membrane via Na/bicarb cotransporter

Question 10

What is the effect of acetazolamide?

Answer 10

Acetazolamide blocks carbonic anhydrase, thus preventing conversion to diffusable CO2.

• Urine keeps bicarb (is alkalinized)
• Plasma doesn’t get it - is effectively acidified.

Question 11

How is K+ reabsorbed in the PCT?

Answer 11

K+ is reabsorbed and secreted in the PCT, mainly through paracellular route.

Question 12

What is the force driving K+ reabsorption in the early proximal tubule?

Answer 12

Solvent drag pulls K+ into tubules.

Question 13

What is the force driving K+ reabsorption in the late proximal tubule?

Answer 13

Positive lumen charge drives K+ into tubules.

Question 14

How is Cl- handled in the PCT? Is Cl- coupled to Na+ in the PCT?

Answer 14

Cl- has many ways of getting out of the lumen:
- Paracellular
- Late proximal tubule has Cl-/HCO3 exchanger (Cl to cell, bicarb to lumen)
- basolateral Cl transporter
… etc
- Na and Cl are NOT coupled in the PCT

Question 15

How is H2O absorbed in the PCT?

Answer 15

60% of H20 is reabsorbed – mostly ISOTONIC.
Water moves w/ sodium due to high permeability.
Highest permeability in PCT and thin desc loop.
Moves mostly transcellular via aquaporins, some paracellular movement as well.

Question 16

The PCT secretes NH3 as a buffer for secreted H+. Where does it get that??

Answer 16

Absorbs glutamine, which goes to PCT mitos and gets two NH4s pulled off of it –> glumate, –> aKG.
Two NH4s generated: H+ goes out via the Na+/H+ exchanger, NH3s (ammonia) diffuses out across apical membrane.
a-KG will go on to generate two bicarbs in TCA.

Question 17

What happens if NH3 doesn’t diffuse across membrane into lumen?

Answer 17

Will go to liver, where it will be converted to urea via the urea cycle.
Bicarb gets used up here, so no net gain of bicarb.

Question 18

How is urea handled by the kidney?

Answer 18

Filters freely, is inert. No specific transporters for urea; about 50% is passively reabsorbed via paracellular route.

Question 19

When blood urea nitrogen rises, what does this indicate?

Answer 19

Less is being filtered by glomerulus. Indicates decreasing GFR.

Question 20

What is the effect of ATII on the PCT?

Answer 20

Stimulates Na+/H+ exchange.

• Increases Na+
• Increases H20
• Increases bicarb reabsorption (this contributes to contraction alkalosis).

Question 21

What enzyme in the PCT facilitates the conversion of 25-OH Vitamin D to the active 1,25-OH2 vitamin D form?

Answer 21

1alpha-hydroxylase

Question 22

What enhances the activity of 1-alpha-hydroxylase

Answer 22

PTH