Lecture 4- Renal Transport II Flashcards Preview

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Flashcards in Lecture 4- Renal Transport II Deck (37):
1

What is the typical intake of K+ per day ?

100 mEq
varies a lot on diet

2

How much K+ is excreted by the kidney?

92% of ingested K+

3

Having perturbation of extracellular K+ will lead to...

nerve misfiring and or cardiac arrythmias

4

insulin stimulates

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

5

How much filtered K+ is reabsored in proximal tubule?

67%
paracellular; solvent drag

6

How much K+ is reabsorbed in thick ascending limb?

20%
Na/K/2Cl cotransporter) not regulated

7

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

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

8

K+ secretion via principal cells via

apical K+ channels (in DT and CD)

9

How is high cytoplasmic K+ maintained?

by Na/K ATPase

10

What are the main secretion regulation factors?

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

11

If you increase [K+]plasma

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

12

Furosemide

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

13

Bartter's syndrome

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

14

Thiazide

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

15

Giltman's syndrome

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

16

Amiloride

↓ 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"

17

How much of body Ca++ is intracellular?

1%
mainly in ER and in mitochondria; sequestered in SR of muscles

18

How much of total Ca++ is extracellular?

0.1%

19

What does cytoplasmic Ca++ do?

functions in signaling, muscle contraction, NT release

20

How much Ca++ is filtered a day?

540 mEq Ca++/day
(40% of plasma Ca++ is bound to protein & not filtered)

21

Ca++ Reabsorption by Proximal Tubule

-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)

22

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

-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)

23

Where is the majority of Ca++ transport occur?

in the proximal tubule via paracellular route

24

↓ plasma Ca++ effect on calcitiol secretion

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

25

↓ plasma Ca++ effect on PTH secretion

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

26

↑ plasma Ca++ effect on calcitonin secretion

↑ calcitonin secretion > ↑ bone formation

27

PO43- Function and Distribution

buffer; in formation of bone
86% is in the bone, 14% intracellular

28

PO43- Reabsorption in the Proximal Tubule

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

29

↓ plasma PO43- effect on calcitriol

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

30

↑ calcitonin effect on PO43-

↑ PO43- incorporation into bone, ↓ reabsorption in kidney

31

Organic anions secreted by renal tubule

endogenous- prostaglandins, uric acid

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

*all of then are competing for the same transport system*

32

Organic cations secreted by renal tubule

endogenous- epinephrine, norepinephrine

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

33

Organic Anion Secretion in Proximal Tubule

-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

34

Competition between PAH and Penicillin

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

35

MDR-related transporters

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

36

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

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

37

Fanconi's syndrome

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