Tubular Transport II

Question 1

What is the difference between clearance and excretion?

Answer 1

• clearance= the amount plasma that is completely cleared of a substance (ml/min).
• excretion= the amount of a substance expelled in the urine (mg/min).
• Thus beyond Tm, as the plasma concentration of PAH increases, CLEARANCE will plateau/DECREASE, but EXCRETION will INCREASE!

Question 2

What is the major buffer for H+ in our body?

Answer 2

bicarb (HCO3-), and 80% is reabsorbed by the kidney at the PCT.

Question 3

What is the equation of HCO3- exchange?

Answer 3

HCO3- + H+ > H2CO3 > H2O + CO2

Question 4

Is the PCT an active area of H+ SECRETION?

Answer 4

YES via the Na+/H+ ion exchanger, but this H+ is NOT EXCRETED; it is only recycled (remember sketchy pharm). The electrogenic H+ pump that also is found here, is responsible for H+ EXCRETION.

Question 5

Is NaHCO3 freely filtered at the glomerulus?

Answer 5

YES and enters the PCT

Question 6

What happens to the secreted H+?

Answer 6

it immediately binds to HCO3- forming carbonic acid. Carbonic acid is then immediately converted to CO2 + H2O via EXTRACELLULAR carbonic anhydrase, and they are able to passively diffuse through the luminal membrane.

Question 7

What happens once the H2O and CO2 enter the cell?

Answer 7

INTRACELLULAR carbonic anhydrase combines them to reform H2CO3, which then immediately dissociates into HCO3- and H+.

Question 8

How does the HCO3- then get back into the blood from the intracellular space?

Answer 8

• it is transported with Na+ across the basolateral membrane by electrogenic cotransport of 3 bicarbs for every 1 Na+.
• there is also a HCO3-/Cl- antiporter that exists as well.

Question 9

What diuretic acts to inhibit EXTRACELLULAR carbonic anhydrase in the PCT?

Answer 9

acetazolamide

Question 10

Does the DCT also have the Na+/H+ exchanger and EXTRACELLULAR carbonic anhydrase in order to reabsorb bicarb that has made it past the PCT?

Answer 10

It has the Na+/H+ exchanger, but NO EXTRACELLULAR carbonic anhydrase. So H2CO3 can form, but it will dissociate to H2O and CO2 SLOWLY, since it lacks this enzyme. Also, the same exchangers exist on the basolateral side of the DCT cells as the PCT cells.

Question 11

Since more K+ can leak into the lumen at the DCT, what will happen in cases of alkalosis?

Answer 11

K+ will bind with excess HCO3- in the lumen, forming KHCO3-, which cannot dissociate, and it will be excreted in the urine :)

Question 12

** What are the 2 mechanisms that the kidney has to excrete excess acid?

Answer 12

1. titratable acids= phosphoric and sulfuric acid

2. non-titratable acids= NH4+

Question 13

** How do the titratable acids (phosphoric acid) work?

Answer 13

Na2HPO4 dissociates in the tubular fluid at the DCT, leaving NaHPO4 in the lumen. As Na+ is exchanged for H+, the H+ will bind forming NaH2PO4 to be excreted in the urine :)
*However, this will acidify the urine, slowing the amount of electrogenic H+ pumps that exist along the tubular membrane. Thus, this is why the non-titratable acids also exist!

Question 14

** What specific cells are most important in H+ excretion?

Answer 14

the alpha intercalated cells at the collecting tubule and duct. These cells posses both an electrogenic H+/K+ ATPase on their luminal membrane and a Na+/HCO3- co-transporter on their basolateral membranes, to reabsorb generated bicarbonate ion.
*Limit is a pH of 4.4 that these can function effectively.

Question 15

** How do the non-titratable acids (NH4+) work?

Answer 15

• glutamine gets deaminated to form free NH3 in the PCT. NH3 is freely diffusible and will enter the filtrate to combine with H+, forming NH4+ and/or combing the ammonium ion with sulfate (trapping it to be excreted) :).

Question 16

What happens to the NH4+ as it enters the thick ascending limb of the loop of henle?

Answer 16

NH4+ is reabsorbed by replacing K+ on the Na+/K+/2Cl- cotransporter. It will then dissociate in the cell to form H+ and NH3. NH3 diffuses into the medullary collecting duct where it combines with H+ secreted by the alpha-intercalated cells of the collecting duct to form NH4+ and is excreted :)

Question 17

Will the kidney reabsorb almost all of the filtered Ca2+?

Answer 17

YES (65% reabsorbed in PCT, 25% in thick ascending limb, 8% in DCT, and 1.5% in the collecting duct).

Question 18

How is Ca2+ reabsorbed in the PCT?

Answer 18

• 2/3 paracellularly

- 1/3 transcellularly (through Ca2+ channel down its chemical gradient).

Question 19

How does Ca2+ get out of the cells (out the basolateral membrane)?

Answer 19

• because it is now going against its gradient, it uses the energy of 3 Na+ for every Ca2+ exchanger.
• or the 2 H+/Ca2+ ion exchanger.

Question 20

Is there any hormonal influences on Ca2+ transport in the PCT?

Answer 20

NO

Question 21

What drives Ca2+ paracellularly in the thick ascending limb?

Answer 21

the positive potential driven by the slow leakage of K+ across the luminal membrane

Question 22

*** What senses Ca2+ transport in the thick ascending limb?

Answer 22

calcium sensing receptor (CaSR) located within the basolateral membrane. It is directly sensitive to interstitial Ca2+ and will cause an increase in cAMP intracellularly, which inhibits the luminal Na+/K+/2Cl- cotransporter, thus indirectly reducing the amount of paracellular Ca2+ reabsorption.

Question 23

*** What regulates Ca2+ in the DCT?

Answer 23

• This is the major site of Ca2+ regulation (despite there only 10% of the original filtered Ca2+ load that remains).
• Here it is 100% transcellular and has a unique calcium channel on the luminal membrane, termed the epithelial Ca2+ channel (ECaC), which is regulated on the basolateral side via PTH binding to its receptor (which will activate adenylate cyclase to increase the permeability of the ECaCs on the luminal membrane when Ca2+ levels in the blood are low).

Question 24

Where is most phosphate reabsorbed?

Answer 24

PCT via Na+/phosphate cotransport. Because distal segments of the nephron do not reabsorb phosphate, 15% of the filtered load is excreted in the urine.

Question 25

What does PTH do to phosphate reabsorption?

Answer 25

inhibits it in the PCT, by activating adenylate cyclase, generating cAMP and inhibiting Na+/phosphate cotransport. Therefore PTH causes phosphaturia and increased urinary cAMP.

Question 26

Is there any phosphate reabsorbed in the loop of henle?

Answer 26

NO, nor do the collecting ducts.

*DCT may absorb up to 10%