Flashcards in Lecture 4- Renal Transport II Deck (37):
What is the typical intake of K+ per day ?
varies a lot on diet
How much K+ is excreted by the kidney?
92% of ingested K+
Having perturbation of extracellular K+ will lead to...
nerve misfiring and or cardiac arrythmias
-slower effect, whereas immediate response occurs from Na+/K+ ATPase
How much filtered K+ is reabsored in proximal tubule?
paracellular; solvent drag
How much K+ is reabsorbed in thick ascending limb?
Na/K/2Cl cotransporter) not regulated
How much K+ is reabsorbed in the distal tubule and CD?
12% (apical H+/K+ ATPase) regulated
K+ secretion via principal cells via
apical K+ channels (in DT and CD)
How is high cytoplasmic K+ maintained?
by Na/K ATPase
What are the main secretion regulation factors?
[K+]plasma, aldosterone, K channel activity, Na channel activity, Na delivery to Principal cells
If you increase [K+]plasma
↑ aldosterone secretion > ↑ Na+/K+ ATPase > ↑ K+ channel activity (& Na+ channel activity > ↑ K+ secretion
↓ activity of Na/K/2Cl cotransporter in thick ascending limb of Loop of Henle > ↓ K+ reabsorption, ↑ K+ excretion
aka "K+ wasting" diuretic
Na/K/2Cl transporter is defective -- characterized by hypokalemia
↓ activity of Na/Cl cotransporter in distal tubule > ↑ Na+ delivery to Principal cells in DT/CD > ↑ K+ secretion
aka "K+ wasting" diuretic
characterized by hypotension (due to increase excretion of NaCl) and hypokalemia
↓ activity of Na+ channels in Principal cells of DT/CD > Na+ stuck in tubule opposes K+ efflux across apical surface into tubule > ↓ K+ secretion
How much of body Ca++ is intracellular?
mainly in ER and in mitochondria; sequestered in SR of muscles
How much of total Ca++ is extracellular?
What does cytoplasmic Ca++ do?
functions in signaling, muscle contraction, NT release
How much Ca++ is filtered a day?
540 mEq Ca++/day
(40% of plasma Ca++ is bound to protein & not filtered)
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)
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)
Where is the majority of Ca++ transport occur?
in the proximal tubule via paracellular route
↓ plasma Ca++ effect on calcitiol secretion
↑ calcitriol secretion > ↑ Ca++ reabsorption in gut and distal tubule
↓ plasma Ca++ effect on PTH secretion
↑ PTH secretion > ↑ bone resorption & Ca++ reabsorption by loop of Henle and distal tubule
↑ plasma Ca++ effect on calcitonin secretion
↑ calcitonin secretion > ↑ bone formation
PO43- Function and Distribution
buffer; in formation of bone
86% is in the bone, 14% intracellular
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
↓ plasma PO43- effect on calcitriol
↑ calcitriol secretion > ↑ PO43- reabsorption in kidney and gut
↑ calcitonin effect on PO43-
↑ PO43- incorporation into bone, ↓ reabsorption in kidney
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*
Organic cations secreted by renal tubule
endogenous- epinephrine, norepinephrine
cationic drugs- morphine, amiloride, verapmil (Ca channel blocker), Vinblastine (anti-cancer drug)
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
Competition between PAH and Penicillin
Compete for secretion by organic anion transporter led to increased half-life of penicillin in circulation
-Belongs to ABC family of transporters
-2 ATP binding domains, 2 membrane domains w/ 6 transmembrane helices each
-Broad specificity for solutes transported
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