Regulation of Ca2+, Pi, and Mg2+ Flashcards
What is the total plasma level of Ca2+?
5.0 mEq/L
Where is Ca2+ distributed in the body?
99% in the bone
1% in ICF
0.1% in ECF
How is Ca2+ excreted?
90% excreted in feces
What state does Ca2+ exist in the body?
Ionized Calcium (45%)
Protein-bound (non-diffusible) Calcium (40%)
Diffusible Caclium Complexes (15%)
What effect does hypoalbuminemia have on Ca2+?
Ca2+ competes for binding sites on albumin with H+
When there’s fewer molecules of albumin in the blood, there are fewer binding sites for Ca2+, therefore ionized [Ca2+] in the blood INCREASES
What effect does hyperalbuminemia have on Ca2+?
Ca2+ competes for binding sites on albumin with H+
When there is plenty of circulating albumin, there is also plenty of binding sites for Ca2+, therefore ionized [Ca2+] in blood DECREASES
What effect does acidosis have on Ca2+?
Acidosis means there is greater plasma [H+] concentration.
Ca2+ and H+ compete for binding sites on albumin.
When there’s greater amount of H+ present, there are fewer binding sites for Ca2+ available.
Therefore, Acidosis INCREASES ionized [Ca2+] in the blood
What effect does alkalosis have on Ca2+?
Alkalosis means there is a reduction in plasma [H+]
Ca2+ and H+ compete for binding sites on circulating albumin.
When there is fewer amount of H+ present, there are a greater number of binding sites available for Ca2+
Therefore, alkalosis DECREASES ionized [Ca2+] in the blood
What is another name for Vitamin D?
Calcitriol
What does Calcitriol do?
Promotes osteoclastic-mediated bone Ca2+ resorption from bone
Promotes absorption of Ca2+ and Phosphorus from the intestines
Promotes reabsorption of Ca2+ and phosphorus in the kidney
What does calcitonin do?
Inhibits osteoclastic-mediated bone Ca2+ resorption by inhibiting osteoclast activity and reducing number of osteoclasts
Promotes Ca2+ and Phosphorus excretion in the kidney
What does PTH do?
Promotes bone Ca2+ resorption (increasing serum Ca2+)
PROMOTES Ca2+ absroption from intestines; INHIBITS Phosphorus absorption from the intestines
Promotes Ca2+ reabsorption in the DCT; inhibits phosphorus reabsorption in the PCT; decreases activity of Na+/H+ antiporter, decreases HCO3- reabsorption.
What is the CaSR and what does it do?
Ca2+ Sensing Receptor
It is a receptor found on the basolateral membrane of thick ascending limb tubule cells and it monitors Ca2+ levels
When serum [Ca2+] is high, Ca2+ binds to the receptor, it inhibits Ca2+ paracellular reabsorption from the tubule lumen
Also blocks the NKCCC2 channel and the K+ leak channel in the apical membrane
What nephron segment is the major site of Ca2+ regulation?
The distal tubule
What nephron segments are the sites of Ca2+ reabsorption?
Proximal tubule (56-70%)
Thick ascending limb (contains paracellular pores for Ca2+ and Mg2+ conduction)
Distal Tubule (8%) - major site of regulation
Describe how Ca2+ is reabsorbed in the Proximal Tubule (include the channels involved)
Primarily is reabsorbed paracellularly
Some reabsorbed transcellularly
Ca2+ channel on apical membrane allows passive movement of Ca2+ down its concentration gradient into the cell.
Ca2+-ATPase on basolateral membrane uses ATP to move Ca2+ into interstitium
Ca2+-Na+ antiporter on the basolateral membrane moves Ca2+ out into the interstitium by moving Na+ down its concentration gradient into the cell
Describe how Ca2+ is reabsorbed in the Thick Ascending Limb of the Loop of Henle
Primarily paraceullularly
Dependent on TEPD (LUMEN POSITIVE voltage)
ADH promotes reabsorption
What are the effects of Loop diuretics on Ca2+?
Loop diuretics block Na+ reabsorption in the thick ascending limb of the loop of henle.
Increased Na+ in lumen reduces the magnitude of the lumen-positive transepithelial voltage, which reduces paracellular Ca2+ reabsorption and increases Ca2+ excretion
Loop diuretics can therefore treat hypercalcemia
Describe how Ca2+ is reabsorbed in the Distal Tubule include the channels involved)
Distal tubule has a LUMEN-NEGATIVE transepithelial potential difference, meaning Ca2+ cannot passively leave the tubule lumen.
Ca2+ is actively removed from the tubule lumen via TRPV5 or TRPV6 Channels on the apical membrane
Once inside the cell, Ca2+ leaves via Na+-Ca2+ exchanger (NCE) on the basolateral membrane
What are the effects of Thiazide Diuretics on Ca2+?
Thiazide diuretics promote the TRPV5 channel in the distal tubule and inhibit Na+ reabsorption.
Reduces Ca2+ excretion
Used to treat Ca2+ containing kidney stones
What effect does Acidosis have on Ca2+?
Acidosis inhibits TRPV5/6 channel, blocking Ca2+ reabsorption in the distal tubule.
Promotes Ca2+ excretion
What effect does Alkalosis have on Ca2+?
Alkalosis promotes TRPV5/6 channel, increasing Ca2+ reabsorption in the distal tubule
Inhibits Ca2+ excretion
Is Ca2+ secreted in the kidney?
NO
What effect does DECREASED ECV have on Ca2+?
Decreased ECV causes activation of Sympathetics
Sympathetics promote Na+ reabsorption in the PCT which causes a the transepithelial potential to become more negative, which INHIBITS passive transcellular reabsorption of Ca2+
Describe renal handling of phosphate (where does it go at which point(s)?)
80% reabsorbed in the Proximal Tubule
Big Players: FGF-23, PTH & Ca2+, Na-Pi symporter
List the Na+ channels in the Proximal Tubule
Na-Glucose symporter
Na-amino acid symporter
Na-Pi symporter
Na-HCO3- symporter
Na-H exchanger
Na-organic solutes exchanger
What is the fate of Pi in the early Proximal Tubule?
Pi crosses the apical membrane via Na-Pi symporter
Pi crosses the basolateral membrane via an unknown channel
What is the effect of FGF-23 on Pi?
FGF-23 inhibits the Na-Pi symporter, decreasing Pi reabsorption; increasing Pi excretion
What is the kidney’s role in Calcitriol synthesis?
Proximal tubule contains an enzyme called 1(alpha)-hydroxylase (AKA CYP1(alpha)) which converts the circulating of vitamin D (created in the liver, low activity; 25-OHD3) into 1-25-(OH)2D3 (AKA Calcitriol)
What is Insulin’s role in Pi regulation?
Insulin decreases serum Pi levels by shifting Pi into cells
What effect does Acidosis have on Pi?
Acidosis increase Pi excretion
What effect does Alkalosis have on Pi?
Alkalosis decreases Pi excretion
Where is Mg2+ reabsorbed?
Proximal Tubule
Thick Ascending Limb of the Loop of Henle
Distal Tubule
Describe how the Mg2+ is reabsorbed in the proximal tubule
20% of filtered Mg2+ is reabsorbed in the proximal tubule
Paracellulary; follows Na+ and H2O
Describe how Mg2+ is reabsorbed in the Ascending Limb of the Loop of Henle
70% of filtered Mg2+ is reabsorbed in the Ascending Limb of the loop of Henle
Paracellulary; depends on the uptake of Na+ and K+ via NKCC2 channels (which depends on Lumen-positive voltage)
Describe how Mg2+ is reabsorbed in the Distal Tubule
10% of filtered Mg2+ is reabsorbed in the Distal Tubule (site of fine tuning)
[Mg2+] is approximately the same inside and outside the cell, thus electrical potential is the major driving force for cellular influx of Mg2+
Mg2+ crosses the apical membrane via a TRPM6 channel
How Mg2+ crosses the basolateral membrane is unknown
How does dietary depletion of Mg2+ affect Mg2+ regulation in the kidney?
Dietary depletion of Mg2+ promotes the reabsorption of Mg2+
How does PTH regulate Mg2+ in the kidney?
Promotes Mg2+ reabsorption
How does Metabolic Acidosis regualte Mg2+ in the kidney?
Metabolic acidosis inhibits reabsorption of Mg2+ (decreases paracellular permeability)
How does Metabolic Alkalosis regulate Mg2+ in the kidney?
Metabolic alkalosis promotes reabsorption of Mg2+ (increases paracellular permeability)
How does ECF expansion regulate Mg2+ in the kidney?
ECF volume expansion will inhibit Mg2+ reabsorption
How does ECF contraction regulate Mg2+ in the kidney?
ECF volume contraction will promote Mg2+ reabsorption
