Lecture 4- Renal Transport II

Question 1

What is the typical intake of K+ per day ?

Answer 1

100 mEq

varies a lot on diet

Question 2

How much K+ is excreted by the kidney?

Answer 2

92% of ingested K+

Question 3

Having perturbation of extracellular K+ will lead to…

Answer 3

nerve misfiring and or cardiac arrythmias

Question 4

insulin stimulates

Answer 4

K+ uptake

-slower effect, whereas immediate response occurs from Na+/K+ ATPase

Question 5

How much filtered K+ is reabsored in proximal tubule?

Answer 5

67%

paracellular; solvent drag

Question 6

How much K+ is reabsorbed in thick ascending limb?

Answer 6

20%

Na/K/2Cl cotransporter) not regulated

Question 7

How much K+ is reabsorbed in the distal tubule and CD?

Answer 7

12% (apical H+/K+ ATPase) regulated

Question 8

K+ secretion via principal cells via

Answer 8

apical K+ channels (in DT and CD)

Question 9

How is high cytoplasmic K+ maintained?

Answer 9

by Na/K ATPase

Question 10

What are the main secretion regulation factors?

Answer 10

[K+]plasma, aldosterone, K channel activity, Na channel activity, Na delivery to Principal cells

Question 11

If you increase [K+]plasma

Answer 11

↑ aldosterone secretion > ↑ Na+/K+ ATPase > ↑ K+ channel activity (& Na+ channel activity > ↑ K+ secretion

Question 12

Furosemide

Answer 12

↓ activity of Na/K/2Cl cotransporter in thick ascending limb of Loop of Henle > ↓ K+ reabsorption, ↑ K+ excretion
aka “K+ wasting” diuretic

Question 13

Bartter’s syndrome

Answer 13

Na/K/2Cl transporter is defective – characterized by hypokalemia

Question 14

Thiazide

Answer 14

↓ activity of Na/Cl cotransporter in distal tubule > ↑ Na+ delivery to Principal cells in DT/CD > ↑ K+ secretion
aka “K+ wasting” diuretic

Question 15

Giltman’s syndrome

Answer 15

characterized by hypotension (due to increase excretion of NaCl) and hypokalemia

Question 16

Amiloride

Answer 16

↓ activity of Na+ channels in Principal cells of DT/CD > Na+ stuck in tubule opposes K+ efflux across apical surface into tubule > ↓ K+ secretion

“K+ sparing”

Question 17

How much of body Ca++ is intracellular?

Answer 17

1%

mainly in ER and in mitochondria; sequestered in SR of muscles

Question 18

How much of total Ca++ is extracellular?

Answer 18

0.1%

Question 19

What does cytoplasmic Ca++ do?

Answer 19

functions in signaling, muscle contraction, NT release

Question 20

How much Ca++ is filtered a day?

Answer 20

540 mEq Ca++/day

40% of plasma Ca++ is bound to protein & not filtered

Question 21

Ca++ Reabsorption by Proximal Tubule

Answer 21

• 20% by apical Ca++ channels
• Ca++ leaves cell via Ca-ATPase and Na+/Ca++ antiporter in basolateral membrane
• 80% occurs by paracellular route (solvent drag, lumenal positive transepithelial potential)

Question 22

Ca++ Reabsorption by Thick Ascending Limb of Loop of Henle and DT

Answer 22

-20% reabsorbed by thick ascending limb
mechanism similar to that in proximal tubule (no solvent drag)
-10% reabsorbed by distal tubule and CD
only transcellular reabsorption (uses ATP)

Question 23

Where is the majority of Ca++ transport occur?

Answer 23

in the proximal tubule via paracellular route

Question 24

↓ plasma Ca++ effect on calcitiol secretion

Answer 24

↑ calcitriol secretion > ↑ Ca++ reabsorption in gut and distal tubule

Question 25

↓ plasma Ca++ effect on PTH secretion

Answer 25

↑ PTH secretion > ↑ bone resorption & Ca++ reabsorption by loop of Henle and distal tubule

Question 26

↑ plasma Ca++ effect on calcitonin secretion

Answer 26

↑ calcitonin secretion > ↑ bone formation

Question 27

PO43- Function and Distribution

Answer 27

buffer; in formation of bone

86% is in the bone, 14% intracellular

Question 28

PO43- Reabsorption in the Proximal Tubule

Answer 28

• entry via Na+/PO43- cotransporter
• Crosses basolateral membrane via PO43-/anion antiporter
• Hormone changes respond to changes in proximal tubule reabsorption

Question 29

↓ plasma PO43- effect on calcitriol

Answer 29

↑ calcitriol secretion > ↑ PO43- reabsorption in kidney and gut

Question 30

↑ calcitonin effect on PO43-

Answer 30

↑ PO43- incorporation into bone, ↓ reabsorption in kidney

Question 31

Organic anions secreted by renal tubule

Answer 31

endogenous- prostaglandins, uric acid

anionin drugs- penillin, salicylate, ibuprofin, adefovir (anti-HIV)

all of then are competing for the same transport system

Question 32

Organic cations secreted by renal tubule

Answer 32

endogenous- epinephrine, norepinephrine

cationic drugs- morphine, amiloride, verapmil (Ca channel blocker), Vinblastine (anti-cancer drug)

Question 33

Organic Anion Secretion in Proximal Tubule

Answer 33

• Anions taken up from blood by anion/α-ketogluterate antiporter (α-kg recycled via Na+ coupled transporter)
• Anions leave via Cl-/anion exchanger
• Cations enter from blood via passive transporters
• Cations enter renal fluid via cation/H+ antiporter and MDR-related transporter
• Competition between cationic drugs (i.e. morphine) can result in drug toxicity

Question 34

Competition between PAH and Penicillin

Answer 34

Compete for secretion by organic anion transporter led to increased half-life of penicillin in circulation

Question 35

MDR-related transporters

Answer 35

• Belongs to ABC family of transporters
• 2 ATP binding domains, 2 membrane domains w/ 6 transmembrane helices each
• Broad specificity for solutes transported

Question 36

Receptor-mediated endocytosis of peptides and small proteins in Proximal Tubule

Answer 36

Peptides/small proteins not removed during filtration get taking up by endocytosis using megalin and cubulin receptors
Endocytosed materials brought to lysosome for degradation to AAs

Question 37

Fanconi’s syndrome

Answer 37

Defect in receptors or v-ATPase in PT; protein in urine (proteinuria)