4: Renal Transport II: K, Ca, P04, organic acid and peptide transport

Question 1

How much K+ is reabsorbed by the PT and thick ascending limb of the loop?

Answer 1

PT: 67% of K+ reabsorbed
Thick ascending limb: 20% of K+ reabsorbed

*K reabsorption is not regulated in the PT and thick AL of the loop so these numbers are constant

Question 2

How are potassium intake and excretion balanced by the kidney?

Answer 2

• Regulation of K+ secretion by the principal cells of the late DT and CD is the main mechanism by which K+ intake and excretion are balanced
• This is UNUSUAL: all other ions are balanced by modulating reabsorption.

Question 3

K+ depleted state: what if we need to absorb more K than the constant amount retrieved by the PT and thick ascending limb?

Answer 3

• Intercalated cells can reabsorb K+
• Have proton-potassium ATPase which couples acid secretion to potassium uptake
• But in western diets we usually have excess potassium so this isn’t active often.

Question 4

Potassium reabsorption and secretion by the RT in normal and excess K+ states

Answer 4

• Reabs in PT and thick ascending limb unchanged (67% and 20%)
• K+ Secretion by intercalated cells can range from 1% to 42% in the DT and 1% to 25% in the collecting duct

(Doubt we need to know the secretion numbers)

Question 5

How is potassium secreted by principal cells?

Answer 5

• Principal cells have apical K+ channels which allow potassium to be secreted passively
• Remember potassium is maintained at a high intracellular concentration by the Na/K ATPase

Question 6

How is K+ secretion in principal cells modulated?

Answer 6

1. increase K+ channel activity
2. Increase Na+ channel activity
3. Increase Na/K ATPase activity

*Aldosterone causes all three mechanisms to occur. So increased aldosterone favors increased K+ secretion.

Question 7

What effect does furosemide have on K+ secretion?

Answer 7

• Furosemide inhibits the Na/K/2Cl cotransporter in the thick ascending limb of the loop which results in:
  1. decreased K reabsorption
  2. Increased Na delivery (principal cells “see” more sodium–>more sodium going in, more potassium going out)
  3. Therefore, results in increased K+ excretion for two reasons
• Thus Furosemide is a K+ “wasting diuretic”. These reasons also explain why Bartter’s syndrome is characterized by hypokalemia

Question 8

Effect of Thiazide Diuretics on K+ secretion

Answer 8

Thiazide:

1. decreases Na/Cl cotransporter activity in early DT
2. Increased Na+ delivery to principal cells
3. More Na in RT lumen, more Na flowing into principal cells and more K+ flowing out into RT lumen
   - Results in more K+ excretion (another K “wasting” diuretic)

Question 9

Effect of Amiloride on K+ secretion

Answer 9

Amiloride: K+ “sparing” diuretic

• Decreases activity of sodium channels in principal cells of DT/CD
• So More sodium in RT lumen, making it harder for K+ to flow out of principal cells and into the lumen, decreasing K+ secretion

Question 10

What effect does Liddle’s syndrome have on Potassium levels?

Answer 10

Liddle’s syndrome: GOF mutation: increases activity of apical Na+ channels in principal cells
-This will increase potassium secretion and excretion, resulting in hypokalemia

Question 11

Ca2+ function and distribution

Answer 11

• Bones contain 99% of the bodies Ca
• 1% of total body Ca is intracellular, and its in the ER or mito
• cuz cytoplasmic Ca functions in signaling, muscle contraction and NT release.
• 40% of plasma Ca bound to proteins and thus isn’t filtered
• 98% of filtered calcium is reabsorbed

Question 12

Ca reabsorption in the proximal tubule

Answer 12

• 70% of filtered calcium is reabsorbed in the PT
• 20% of this via apical Ca channels driven by: 1 Ca concentration gradient and 2 cytoplasmic negative membrane potential
• 80% via paracellular route: 1 lumenal positive transepi pot. created by Cl- reabs 2 solvent drag
• Ca then exits via Ca-ATPase and Na/Ca antiporter

(probably just know relative amounts)

Question 13

Ca reabsorption by the thick ascending limb of the loop of henle

Answer 13

-20% of filtered calcium reabsorbed by thick ascending limb of the loop via the same mechanisms as in the PT (but no solvent drag)

Question 14

Ca reabsorption by the late DT and collecting duct

Answer 14

• 10% of filtered Ca reabsorbed here
• Again, using apical Ca channels and basolateral Na/Ca antiporter and Ca-ATPase
• but only transcellular reabsorption in late DT/CD cuz transepithelial potential is lumenal negative here

Question 15

Hormonal regulation of Ca excretion: Calcitriol

Answer 15

Decreased plasma Ca triggers:

1. increased calcitriol
2. increased Ca reabs. in gut
3. Increased Ca reabsorption by DT

Question 16

Hormonal regulation of Ca excretion: PTH

Answer 16

Decreased plasma Ca triggers:

1. increased PTH
2. Increased bone resorption (osteoclasts)
3. increased Ca reabs. by loop and DT

Question 17

Hormonal regulation of Ca excretion: Calcitonin

Answer 17

Increased plasma Ca triggers:

1. Increased calcitonin
2. which causes increased bone formation (osteoblasts)

Question 18

P043- reabsorption in PT

Answer 18

-80% of filtered P04 reabs. here
-P04 entry from renal fluid via 2Na/P04 cotransporter
-P04 crosses basolateral membrane via P04/Anion antiporter
(don’t know number)

Question 19

How does hormonal regulation of P04 excretion occur?

Answer 19

-occurs through changes in PT reabsoption.

Question 20

Hormonal regulation of P04 homeostasis: Calcitriol

Answer 20

decreased plasma P04 triggers:

1. increased calcitriol
2. increased P04 abs. in gut
3. increased P04 reabs. in kidney

Question 21

Hormonal regulation of P04 homeostasis: Calcitonin

Answer 21

Increased plasma Ca triggers:

1. increased calcitonin
2. Increased P04 incorporation into bone
3. Decreased P04 reabs. in kidney (increased excretion)

Question 22

Hormonal regulation of P04: PTH

Answer 22

Decreased plasma Ca triggers:

1. Increased PTH
2. Increased P04 release from bone* BUT
3. decreased P04 reabs. in Kidney*
   * Effects cancel: PTH has minimal effects on phosphate levels

Question 23

What are two endogenous anions?

Answer 23

1. prostaglandins

2. Uric Acid

Question 24

What are four anionic drugs?

Answer 24

1. penicillin
2. Salicylate
3. Ibuprofen
4. Adefovir (Anti-HIV)

Question 25

What are two endogenous cations?

Answer 25

1. Epinephrine

2. Norepinephrine

Question 26

What are four cationic drugs?

Answer 26

1. morphine
2. amiloride
3. verapamil (Ca channel blocker)
4. Vinblastine (chemotherapeutic)

Question 27

What’s important to remember about secretion of organic cations and anions in the kidney?

Answer 27

All organic anions are secreted by the same transporter
Similarly, all organic cations are secreted by the same transporter

*So what? Competition occurs! (This is why drug interactions are so important to consider)

Question 28

Organic Anion Secretion in the PT

Answer 28

• Anions taken up from the blood via anion/alpha keto-glutarate antiporter
• Alpha ketoglutarate recycled via na coupled cotransporter
• Anions secreted into RT via Cl-/anion exchanger

Question 29

Organic Cation Secretion in the PT

Answer 29

• Organic cations taken up from the blood via passive transporter
• cations enter renal fluid via cation/H+ antiporter and MDR-related transporters

Question 30

Properties of MDR-related transporters

Answer 30

• Belongs to the ABC family of transporters (ATP binding cassette)
• Includes MDR1 responsible for multidrug resistance of cancer cells

Question 31

Why does the kidney need receptor-mediated endocytosis?

Answer 31

-Peptides and small proteins small enough to slip through filtration barrier need to be taken back up

Question 32

What is Fanconi’s Syndrome?

Answer 32

• Defect in receptors or V-ATPase in PT cause it

- leads to proteinuria (cuz cant reabs. small proteins that get through filter into Bowman’s space and the renal tubule)