4: Renal Transport II: K, Ca, P04, organic acid and peptide transport Flashcards
(32 cards)
How much K+ is reabsorbed by the PT and thick ascending limb of the loop?
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
How are potassium intake and excretion balanced by the kidney?
- 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.
K+ depleted state: what if we need to absorb more K than the constant amount retrieved by the PT and thick ascending limb?
- 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.
Potassium reabsorption and secretion by the RT in normal and excess K+ states
- 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)
How is potassium secreted by principal cells?
- 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
How is K+ secretion in principal cells modulated?
- increase K+ channel activity
- Increase Na+ channel activity
- Increase Na/K ATPase activity
*Aldosterone causes all three mechanisms to occur. So increased aldosterone favors increased K+ secretion.
What effect does furosemide have on K+ secretion?
- 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
Effect of Thiazide Diuretics on K+ secretion
Thiazide:
- decreases Na/Cl cotransporter activity in early DT
- Increased Na+ delivery to principal cells
- 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)
Effect of Amiloride on K+ secretion
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
What effect does Liddle’s syndrome have on Potassium levels?
Liddle’s syndrome: GOF mutation: increases activity of apical Na+ channels in principal cells
-This will increase potassium secretion and excretion, resulting in hypokalemia
Ca2+ function and distribution
- 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
Ca reabsorption in the proximal tubule
- 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)
Ca reabsorption by the thick ascending limb of the loop of henle
-20% of filtered calcium reabsorbed by thick ascending limb of the loop via the same mechanisms as in the PT (but no solvent drag)
Ca reabsorption by the late DT and collecting duct
- 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
Hormonal regulation of Ca excretion: Calcitriol
Decreased plasma Ca triggers:
- increased calcitriol
- increased Ca reabs. in gut
- Increased Ca reabsorption by DT
Hormonal regulation of Ca excretion: PTH
Decreased plasma Ca triggers:
- increased PTH
- Increased bone resorption (osteoclasts)
- increased Ca reabs. by loop and DT
Hormonal regulation of Ca excretion: Calcitonin
Increased plasma Ca triggers:
- Increased calcitonin
- which causes increased bone formation (osteoblasts)
P043- reabsorption in PT
-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)
How does hormonal regulation of P04 excretion occur?
-occurs through changes in PT reabsoption.
Hormonal regulation of P04 homeostasis: Calcitriol
decreased plasma P04 triggers:
- increased calcitriol
- increased P04 abs. in gut
- increased P04 reabs. in kidney
Hormonal regulation of P04 homeostasis: Calcitonin
Increased plasma Ca triggers:
- increased calcitonin
- Increased P04 incorporation into bone
- Decreased P04 reabs. in kidney (increased excretion)
Hormonal regulation of P04: PTH
Decreased plasma Ca triggers:
- Increased PTH
- Increased P04 release from bone* BUT
- decreased P04 reabs. in Kidney*
* Effects cancel: PTH has minimal effects on phosphate levels
What are two endogenous anions?
- prostaglandins
2. Uric Acid
What are four anionic drugs?
- penicillin
- Salicylate
- Ibuprofen
- Adefovir (Anti-HIV)
