Proximal Tubular Transport

Question 1

What is the opposite of nephron reabsorption?

Answer 1

Nephron secretion - it’s where the nephron adds more of something to the tubule instead of taking it back in - we do this with waste products

Question 2

The solutes that are reabsorbed from the tubule go into what?

Answer 2

the peritubular capillary

Question 3

How does Na+ get from the lumen into the renal tubule epitheliual cells?

Answer 3

It just travels down it’s concentration gradient, mediated by transports or ENaC channels

Question 4

Once the Na+ gets into the renal tubule epithelial cells, how does it get into the blood?

Answer 4

It can’t just travel down it’s concentration gradient anymore because the Na+ concentration in the blood is higher than in the cell. Thus, it uses the Na/K ATPase to pump it out of the cell. After that, it can just diffuse across the endothelium into the peritubular capillary

Question 5

In general terms, what happens to the K+ that gets pumped into the cell via the Na/K ATPase?

Answer 5

It just flows back out down it’s concentration gradient using a channel

Question 6

Secondary active transport is the most important transport system in the nephron. What is it?

Answer 6

It’s basically carrier mediated transport - look it up emily!

Question 7

Why is there a net negative transtubular potential difference of about 4 mG in the early proximal tubule?

Answer 7

electrogenic transport of glucose and amino acids into the epithelial cells. - in other words, transports that gets a net charge into the cell

dont’ worry - it will balance later

Question 8

How do glucose and amino acids get into the epithelial cells from the lumen? How does H+ get out of the epithelial cells into the lumen?

Answer 8

They get pumped up their electrochemical gradients by secondary active transport as Na+ moves down it’s electrochemical gradient

(H+ by an antiporter and glucose and AAs by symporters)

Question 9

What anion builds up in concentration in the early proximal tubule because it’s not reabsorbed until the late proximal tubule?

Answer 9

Cl-

Question 10

How does glucose get out of the empithelial cell into the interstitial space and then peritubular capillaries?

Answer 10

facilitated diffusion - it’s going down it’s concentration gradient, but it’s so big that it needs a door (a channel) to get through the membrane (Katz bumping into wall)

Question 11

What are the “4 masters” of the luminal Na/H secondary active antiporter?

Answer 11

it will increase with:

increased intracellular CO2
decreased intracellular pH (acidic)
Increased angiotensin II
increased sympathetic nerve activity

Question 12

What symporter is used to transport glucose out of the early proximal tubule? What percent of the glucose gets reabsorbed?

Answer 12

the luminal 1 Na+/1 glucose secondary active symporter

normally 100% of the filtered glucose gets reabsorbed this way! Unless the patient is hypperglycemic, in which case the symporter can become saturated

Question 13

At what concentration of glucose do all the symporters become completely saturated? I.e. when does the kidney reach it’s transport maximum for glucose?

Answer 13

at 20 mM (up from the normal 5 mM)

Question 14

What’s the most important mechanism for getting Cl- reabsorbed?

Answer 14

Cl-/Formate antiporter system

Question 15

Describe the Cl-/Formate antiporter system.

Answer 15

1. formate inside the cell travels down it’s gradient via the antiporter and pumps Cl in
2. formate in the lumen then joins with H+ (which was exchanged for Na+ - remember?) and forms non-ionized formate
3. Nonionized formate isn’t charged, so it can passively diffuse across the membrane back into the epithelial cell
4. there is low H+ in the epithelial cell, so the nonionized format is converted back to formate so it can be used for pump for Cl in and the H+ is exchanged for Na+ again

Question 16

What are the two ways the Cl_ leads the epithelial cell and enters the interstitial space to reach the peritubular capillary?

Answer 16

1. facilitated diffusion

2. through a Cl channel

Question 17

How does Cl- reach the interstitial space without passing through the epithelial cell?

Answer 17

can pass through the tight junction down it’s electrochemical gradient

Question 18

What happens to the charge of the lumen after Cl moves and how does this affect Na?

Answer 18

The lumen becomes progressively more positive and this means some Na+ can follow the Cl- throguh the tight junction

Question 19

What proportion of water is reabsorbed in the proximal tubule?

Answer 19

2/3! It just follows the reabsorbed solute

and 2/3 of the Na is reabsorbed and 2/3 of the Cl is reabsorbed

Question 20

If 2/3 of water, Na and Cl are reabsorbed, what happens to osmolarity of the lumen?

Answer 20

Nothin - it stays balanced at about 300 mOsm

Question 21

How does water get from the lumen to the cell and then to the interstitial space?

Answer 21

mainly through aquaporin 1, but about 1/3 goes directly through the tight junctions
there is some diffusion through the lipid bilayer, but not as much

Question 22

How is bicarbonate “reabsorbed” in the proximal tubule?

Answer 22

1. bicarbonate is filtered into the lumen by the glomerular apparatus and it combines with the H+ (exchanged for Na) in the proximal tubule to form carbonic acid
2. The carbonic acid is converted to CO2 and H20 by carbonic anhydrase (attached to the epithelial cell membrane)
3. Because the H+ is being exchanged for Na+, that means [H+] in the cell remains low. This means that the in the cell (made from CO2 and H2o by CA) will convert to H+ and bicarb in the cell
4. the bicarb will then be transported out of the cell into the interstitial space by the NBC transporter with Na+

Question 23

What is the net effect on CO2 and H20 in bicarbonate reabsorption?

Answer 23

Nothing - no net change

Question 24

How many bicarbs get pumped out of the cell per 1 Na+ with the NBC transporter?

Answer 24

3

Question 25

Describe how the starling forces in the peritubular capillary favor reabsorption?

Answer 25

The hydrostatic pressure in the capillary is 20 mmHg while the hydrostatic pressure in the interstitial fluid is only 3 mmHg, so this favors filtration out of the capillary
BUT…..
The oncotic pressure in the capillary is very high - 33 mHg! - because the albumin wasn’t filtered in the glomerular apparatus while the oncotic pressure in the IF is only 6 mmHg

These factors combine to make the peritubular capillaries favor reabsorption (they suck!)

Question 26

What is solute filtered load minus solute excretion rate?

Answer 26

the rate of reabsorption of a solute…
so a positive number means you had net reabsorption
a negative number means you had net secretion

Question 27

Describe polar molecular trapping

Answer 27

because H2O is being reabsorbed, polar molecules want to also be reabsorbed. But it’s charged! It can’t cross without help and if it doesn’t have help, it becomes trapped.

This is why we like toxins and waste products to be polar. It helps in excretion.

Question 28

What are some examples of polar molecules we don’t want to excrete though?

Answer 28

weak organic acids like monocarboxylic acids such as lactate, pyruvate, ketone bodies, etc.

Question 29

If the weak organic acids acids are actively pumped out of the blood into the lumen (secretion), how do we get the monocarboxylic acids back in?

Answer 29

they ahve an MCA tag which makes them have affinity for the MCA transporter, which uses secondary active transport with Na+
(then it uses facilitated diffusion to get back to the blood)