Proximal tubule

Question 1

Where is the proximal tubule located?

Answer 1

In the cortex

Question 2

What are the two parts that form the proximal tubule?

Answer 2

Convoluted (first 60%)

Straight (last 40%)

Question 3

What forms the brush border and what is its function?

Answer 3

Formed by microvilli creating a large SA to form the major site of reabsorption.

Question 4

What substances are absorbed in the proximal tubule and by how much?

Answer 4

Water - 70%
Na - 70%
K - 80%
Ca - 65%
AA - 100%
Glucose - 100%
Urea - 50%
Hco3 - 90%

Question 5

What substances are secreted in the proximal tubule?

Answer 5

Uric acid

Organic acids / drugs

Question 6

What is primary active transport?

Answer 6

Generates a gradient due to its movement e.g. Na/K ATPase

Question 7

What is secondary active transport?

Answer 7

Movement of substances using a gradient generated by primary transport.

Question 8

How can ions move?

Answer 8

Transcellularly or paracellularly through channels, pumps or cotransporters

Question 9

How does Na move in the proximal tubule?

Answer 9

Na/K ATPase produces a gradient by tranporting Na out. Na moves DOWN its electrochemical gradient to drive the movement of other substances.

Question 10

Where is Na/K ATPase located?

Answer 10

On the basolateral membrane

Question 11

How is water reabsorbed?

Answer 11

Movement of water follows the movement of Na as it creates an osmotic gradient both trans and paracellular.
The filtrate remains isotonic with plasma and interstitial fluid as the tubule is permeable to water.
Water moves through AQP1 channels on the apical membrane
or
Moves paracellular due to outward hydrostatic and osmotic forces.

Question 12

How is glucose reabsorbed?

Answer 12

Sodium-glucose linked transporter:
In the early stages 90% of glucose uses low affinity, high capacity SGLT2 on apical, coupled with GLUT2 on basal.
As the conc falls along the tubule it is harder to move and requires more energy so uses a high affinity, low capacity SGLT1 on apical, coupled with GLUT1 in basal. SGLT1 uses 2xNa to drive movement of glucose.

Question 13

What is the Tm of glucose? What happens once Tm is reached?

Answer 13

380mg.min.

Glucose will pass into the urine

Question 14

What is the concentration of glucose on entering the tubule?

Answer 14

Equal to plasma concentration as it is freely filtered.

Question 15

Is glucose absorbed faster or slower than water?

Answer 15

Glucose is absorbed FASTER so the concentration FALLS along the tubule, making reabsorption more difficult.

Question 16

Why might a SGLT2 inhibitor be used?

Answer 16

Caues glucosuria to reduce blood glucose levels in DM.

But increases risk of UTI

Question 17

How are AA reabsorbed? Are they Tm limited?

Answer 17

AA are cotransported with Na or via H gradient. Tm limited.

Question 18

What is the plasma concentration of AA?

Answer 18

2.5-3.5mM

Question 19

Are AA absorbed faster or slower than water?

Answer 19

FASTER - concentration falls along the tubule

Question 20

How is Hco3 reabsorbed in the tubule?

Answer 20

There is 25mM in the filtrate. 90% is reabsorbed in proximal.
H is secreted into the tubule via Na-H exchanger allowing Hco3 to from H2O and CO2 via Carbonic anhydrase. H2O and CO2 can cross the membrane where they redissociate.
As Hco3 moves down its gradient it facilitates Na movement up its gradient for reabsorption on basal. 3xHco3:Na
Na/K ATPase and K channel maintain the gradients.

Question 21

What determines the rate of equilibrium of Hco3 reabsorption?

Answer 21

Carbonic Anhydrase

Question 22

What is Azetazolamide?

Answer 22

A diuretic that inhibits CA to prevent Na and Hco3 reabsorption and therefor reducing H2O reabsorption.
Causes alkaline urine so metabolic acidosis as Hco3 is lost in urine. - Can be used to reverse alkalotic effects of altitude.
Can treat glaucoma and mountain sickness.

Question 23

How is Cl reabsorbed?

Answer 23

Moves actively and passively.
Antiport exchange with other anions such as Hco3 and Hcoo. The anion can combine with H secreted into the filtrate via Na-H antiporter, which can then cross the membrane and redissociate for a continuous cycle.
As Cl is absorbed slower than water its concentration increases along the tubule, driving passive paracellular and transcellular movement down the gradient.
This movement generates an electrical gradient and 20% Na follows passively in the late PT.

Question 24

How is albumin reabsorbed?

Answer 24

6% of albumin will enter the filtrate and 100% will be reabsorbed. Via absorptive endocytosis. Albumin binds to sites on the apical membrane that contain megalin and cubilin causing endocytosis. Albumin is the cleaved into AA to be exchanged acorss the BL membrane with Na or H gradient.

Question 25

What does hyperalbuminuria show?

Answer 25

Glomerular damage

Question 26

Why are organic anions secreted?

Answer 26

For excretion in the urine. Used to reomve drugs.

Question 27

Where does acid and base secretion occur?

Answer 27

Acid in the pars recta / straight e.g. penicillin, thiazides, PAH, uric acid
Base in the pars convuluta / convulted e.g. histamine, choline, creatinine, ammonium, guanidine

Question 28

How is PAH, an anion, secreted?

Answer 28

Transported across BL into the cell in exchange for alphaKG via OAT (organic anion transporter). AplhaKG moves into the cell with Na, to keep a continuous supply for OAT.
PAH is then exchanged on the apical membrane for other anions via MRP.

Question 29

What happens in the Pars recta?

Answer 29

Na can move via ENAC down its gradient
K is passively reabsorbed paracellularly through tight junctions due to the low extracellular concentration of 4mM. 80-90% occurs this way.

Question 30

Why are ENAC only present in the late tubule?

Answer 30

It allows secondary active transport to dominate in the early tubule by utilising the Na in the tubule to aid transport. If ENAC was present there would be less Na to aid.