Ca and P Regulation Flashcards
H+ and Ca2+
Compete for binding sites on plasma albumin
hyperalbuminemia–decreases plasma Ca2+
hypoalbuminemia–increases plasma Ca2+
In acidosis, there is more free calcium in circulation
In alkalosis, more calcium is bound to plasma proteins
- predisposed to hypocalcemic tetany
- acute alkalosis can induce sx mimicking hypocalcemia
Calcitriol/Vit D
Acts synergistically with PTH to resorb bone (stims osteoclasts)
Increases serum Ca2+ and Pi levels
Increases Ca2+ and phosphate plasma concentration via bone resorption
signals thru VDR (widely expressed)
Calcitriol acting on bone
Promotes osteoid mineralization
Osteoclastic-mediated bone resorption
Calcitriol acting in GI
Increases Ca2+ absorption (30% dietary calcium is absorbed)
Increases Pi absorption
Calcitriol acting in kidney
Increase Pi reabsorption
increase Ca2+ reabsorption
Upregs TRPV5
Calcitonin
Decreases serum Pi and Ca2+ concentrations
Acts on bone and kidney
Lowers serum calcium and phosphate levels by inhibiting bone resorption (high doses required to elicit effect)
Stimed by hypercalcemia
Decreases activity and number of osteoclasts
Promotes renal excretion of calcium and phosphate
PTH
Increases serum Ca and decreases serum Pi
PTH acting on bone
Increases osteoclastic resorption
PTH acting on GI
Increases Ca2+/Pi absorption indirectly via Vit D (Calcitriol) production
PTH acting on kidney
Increased reabsorption of Ca2+, primarily in DCT
decreased reabsorption of Pi in PCT
Decreased Na+/H+ antiporter activity
Upregs TRPV5 and Na+/Ca2+ exchanger
Decreased bicarb reabsorption
Calcium sensing receptor (CaSR)
Monitors calcium levels
Inhibits Ca2+ reabsorption
When plasma calcium is high, CaSR is activated on the interstitial space side of the cell, which inhibits reabsorption on the apical membrane
Proximal Tubule and Ca2+
65-7-% of filters calcium absorbed here
Transport is mostly passive and follows the local Na+ and water reabsorption
Primarily paracellular, some transcellular
-Exits cell via Ca2+ ATPase and Na+/Ca2+ antiporter
Volume contraction increases Ca2+ reabsorption
Thick ascending limb (TAL)
Lumen positive voltage that drives Ca2+ reabsorption via paracellular path (Primarily paracellular movement)
- Paracellular pores that conduct Ca2+ and Mg2+
- Have CaSR along their basolateral surface; increase in peritubular Ca2+ decreases Ca2+ reabsorption
ADH stims reabsorption
Loop diuretics inhibit Na+ reabsorption by TAL
Reduces magnitude of lumen positive transepithelial voltage
Reduces Ca2+ excretion, thus used to treat hypercalcemia
Distal Tubule
DT has a lumen negative transepithelial voltage
Ca2+ reabsorption is active transcellular transport
Crosses apical membrane via TRPV5 or 6
Crosses basolateral membrane via Na+/Ca2+ exchanger
Thiazide Diuretics
Inhibit Na+ reabsorption in DT and stim Ca2+ reabsorption
- Reduces Ca2+ excretion in urine
- Used to treat Ca2+ containing kidney stones
PTH and Calcitriol stim reabsorption
Acidemia
Increases Ca2+ excretion
Acidosis inhibits TRPV5
Alkalemia
Decreases Ca2+ excretion
Alkalosis stims TRPV5
Pi Reabsorption
Na+/Pi symporter
Na+ uptake across the apical membrane is couple with movement of another molecule (Pi)
-Driven by Na/K pump
Pi moves across BL membrane thru unknown transporter
PTH and Pi regulation
PTH inhibits the Na+/Pi transporters and Na+/H+ antiporter in apical membrane of TP cells
Chronic acidosis increases Pi excretion
Chronic alkalosis decreases Pi excretion
Regulatory Factors of Pi
FGF-23: Fibroblast growth factor 23 released by bone to increase Pi excretion
PTH: Lowers serum Pi by increasing renal excretion
1,25(OH)2D3: Increases serum phosphate by increasing intestinal Pi absorption
Insulin: Lowers serum levels by shifting Pi into cells
Dietary: Pi consumption
Renal function
Mg2+ reabsorption in PT
20% reabsorbed
Paracellular and follows Na+ and H2O
Mg2+ reabsorption in TAL
70% reabsorbed
Paracellular and depends on the uptake of Na+ and K+ via NKCC2, which depends on lumen-positive voltage of TAL
Mg2+ reabsorption in DT
10% reabsorbed, site of fine-tuning
Mg concentration is the same inside and outside the cell, so electrical potential is primary driver of cellular Mg2+ influx
Crosses apical border via TRPM6
Intracellular shuttling not well understood
Crosses BL membrane via unknown mechanism
