SM 191-192: Renal Tubule Function

Question 1

What are the main functions of the PT?

Answer 1

1. Reabsorption: Na, Cl, H2O, bicarb, Glucose, Amino Acids, K, Phos, Ca, Mg, Urea, Uric Acid
2. Production of Ammonia (from Glutamine metabolism)
3. Secretion: OAT, OCT, Protein-bound drugs
4. Glomerulotubular Balance (more filtration = higher oncotic pressure in Ptc = more reabsorption)

Question 2

How does the PT reabsorb bicarb?

Answer 2

1. CA in filtrate produces H2CO3
2. H2CO3 diffuses into PT cell
3. CA in PT cell produces H+, HCO3
4. Basolateral Na/HCO3- cotransporter carries HCO3 out of cell (HCO3 is driving force against Na gradient!)
5. H+ sent out apical side via Na/H exchanger and is RECYCLED

Question 3

How does proton trapping occur in PT?

Answer 3

1. In PT Cell, glutamine metabolized to ammonia
2. ammonia diffuses across apical membrane to filtrate
3. ammonia reacts with H+ in filtrate (s/o to Na/H exchanger) to form ammonium
4. ammonium can’t diffuse or be transported back, trapping proton in urine

Question 4

How is Cl reabsorbed in the PT?

Answer 4

1. Apical anion exchanger carries Cl- into cell and moves formate- into filtrate
2. formate- reacts with H+ in filtrate to formic acid, diffuses back into cell (RECYCLING)
3. Cl- moved across basolateral membrane via K/Cl- cotransporter

Question 5

What are the functions of the TAL?

Answer 5

1. Reabsorption: 15-25% Na and Cl
2. Countercurrent Multiplier
3. Ca/Mg Reabsorption

Question 6

What is the mechanism of Na and Cl reabsorption in the TAL?

Answer 6

1. NKCC2 co-transports NKCC across apical membrane into cell
2. Apical K+ channel (ROMK) moves K+ back into filtrate (RECYCLING)
3. Na+ moved across basolateral membrane via Na/K ATPase
4. Cl- moved across basolateral membrane via Cl Channel

Question 7

What is the mechanism of Ca/Mg transport in the TAL? How is this regulated?

Answer 7

Paracellular reabsorption of Ca/Mg through Claudin-16 (Na Reabsorption creates driving force)

1. High Na reabsorption = High Ca reabsorption
2. High Serum Ca = binds CaSR = blocks NKCC2 = removes driving force for Ca Reabsorption

Question 8

What drug acts on the TAL? How does the drug act?

Answer 8

Loop Diuretic: blocks NKCC2 = less Na Reabsorption = more water excretion

Question 9

What are the functions of the DCT?

Answer 9

1. Reabsorption: Na Cl Mg Ca

Question 10

What are the mechanisms of reabsorption in the DCT?

Answer 10

1. Na/Cl Cotransport into cell from apical membrane
2. TRPM6 (Mg2+) and TRPV5 (Ca2+) channels on apical membrane bring ions into cell
3. Na/K ATPase gets Na out of cell from basolateral membrane
4. Cl- channel gets Cl out of cell from basolateral membrane
5. 3Na/Ca exchanger drives Ca reabsorption on basolateral membrane

Question 11

How is Calcium Reabsorption regulated in the DCT?

Answer 11

1. Low Na Reabsorption = larger ICF/ECF Na Gradient = more active 3Na/Ca exchanger = more active Ca reabsorption

Question 12

What drug acts on the DCT? How can side effects of this drug arise?

Answer 12

Thiazides: block Na-Cl Co-transporter, more water stays with more solute in filtrate
Side Effect: Hypercalcemia due to more active Na/Ca cotransporter on basolateral side driving more Ca reabsorption in the presence of this diuretic

Question 13

What is the function of the Principal Cell in the Cortical CD?

Answer 13

Function: Na Reabsorption, Cl Reabsorption, K Secretion, Aldosterone

Question 14

How do Principal Cells Reabsorb Na, Secrete K?

Answer 14

ENaC: apical Na Channel, gets Na into Cell
K+ Channel on apical side secretes K

Na/K ATPase reabsorbs Na and secretes K on basolateral side

More Na Reabsorption = More K Secretion

Question 15

What drugs/biomolecules act on Principal Cells? How do they work?

Answer 15

K+ Sparing Diuretics
Amiloride - blocks ENaC: less Na Reabsorption (results in less K Secretion)
Eplerenone/Spironolactone - blocks Aldosterone Receptor

Aldosterone
Binds mineralocorticoid receptor in cytoplasm - activates transcription. Early: makes SGK1 (blocks ENaC degradation). Late: increases ENaC and K Channel production

ADH
binds V2R, activates cAMP, increases AQP trafficking to both membranes for more water reabsorption

Question 16

What are the functions of the Intercalated cells in the cortical collecting duct?

Answer 16

Type A: Acid Secreting (Base reabsorption)

Type B: Base Secreting (acid reabsorption)

Question 17

How do Type A Cells perform their function? What are the structural differences between Type A and Type B cells?

Answer 17

Type A
Apical H+ ATPase and H+/K+ Exchanger ATPase secrete H+
Basolateral Anion Exchanger reabsorbs HCO3- and takes in Cl-
Na/K ATPase on basolateral membrane helps preserve charge

Type B
Apical/Basal Polarity Flipped
Na/K ATPase still on basolateral membrane

Question 18

What is the function of Inner Medullary CD Cells?

Answer 18

1. Urea Reabsorption (Medullary Interstitial Gradient)

2. Water Reabsorption (if +ADH)

Question 19

How do Inner Medullary CD Cells perform their function?

Answer 19

1. Apical urea transporter
2. Apical Na Channel (reabsorbing) and K Channel (secreting)
3. Basolateral Na/K ATPase to reabsorb 3 Na and secrete 2 K

Question 20

What drugs act on the inner medullar CD?

Answer 20

ANP
Binds ANP-R on basolateral membrane, activates cGMP, BLOCKS apical Na channel activity = more Na excretion (natrium-diuretic)

ADH
Binds V2R on basolateral membrane, activates cAMP, increases trafficking of AQPs to both membranes for more water reabsorption