8. Regulation of Calcium and Phosphate Metabolism Flashcards
What increases the absorption of Ca2+ from the intestine?
How is this increase in absorption accomplished?
1,25 dihydroxycholecalciferol. (PTH acts on the intestine only indirectly, through vitamin D.)
1,25 dihydroxycholecalciferol induces the synthesis of a vitamin D-dependent calcium binding protein called calbindin D-28K.
Calbindin D-28K binds calcium ions and assists in their uptake into the intestine.
Vitamin D also increases the presentation of the H+/Ca2+ ATPase and the sodium symbol/calcium symbol antiporter – both on the basolateral side.
[Note: 1,25 dihydroxycholecalciferol also increases phosphate absorption in the intestine.]
In secondary hyperparathyroidism as a result of renal failure, would we expect increased or decreased serum Pi?
We would expect increased serum phosphate as a result of diminished renal clearance of phosphate.
Would we see an increase or decrease in Pi in hypoparathyroidism?
↑ Pi
Because there will not be enough parathyroid hormone stimulating clearance of phosphate.
What is the role of RANK, RANK ligand, and OPG (osteoprotegerin) on osteoclast behavior?
RANK/RANK ligand increase osteoclast differentiation and activity.
OPG (osteoprotegerin) acts as a decoy receptor for RANK ligand, and inhibits RANK/RANK ligand interaction, therefore inhibiting osteoclast formation.
What is the short-term action of PTH on osteoblasts?
Increases bone formation.
(Slightly counterintuitive)
What are the functions of calbindin?
Acts as an intracellular buffer to keep intestinal Ca2+ levels from becoming harmful.
Acts as a shuttle to get calcium from the luminal side into the blood.
What is the general “job” of 1,25 dihydroxycholecalciferol in calcium and phosphate metabolism?
↑ Ca2+ & ↑ Pi
To increase new bone growth.
What is the primary circulating form of vitamin D?
Where is it synthesized, and by what enzyme?
25-dihydroxycholecalciferol.
It is synthesized in the liver by 25-hydroxylase.
How does a change in plasma protein concentration alter total Ca2+ concentration?
Plasma protein concentration will alter the amount of bound calcium in the same direction – increasing the total amount of calcium without changing the amount of free calcium.
What stimulates the production of parathyroid hormone?
Low serum Ca2+
In terms of blood calcium level, blood phosphate level, and blood vitamin D level, what are the effects of parathyroid hormone?
↑ Ca2+
↓ Pi
↑ Vitamin D
In terms of parathyroid hormone, blood and urine calcium, blood and urine phosphate, urine cAMP, vitamin D, and bone health – what would we expect to see in vitamin D deficiency?
↑ Parathyroid hormone
↓ Blood Ca2+ – ↑ Urine Ca2+
↓ Blood Pi – ↑ Urine Pi
↑ Urine cAMP
↓ Vitamin D (by definition)
↓ Bone health – due to reabsorption.
How does PTH inhibit phosphate absorption in the kidney?
PTH binds to its receptor -> uses a Gs pathway to increase cAMP -> causes phosphorylation of the Na+/Pi co-transporter.
In terms of calcium, phosphate, and vitamin D – what would we expect to see in secondary hyperparathyroidism?
↓ Ca2+
↓ Pi (in the case of vitamin D deficiency)
↑ Pi (in the case of renal failure)
↓ vitamin D (either because of vitamin D deficiency, or renal failure leading to an inability to produce vitamin D)
What is the normal range of extracellular phosphate?
2.5 – 4.5 mg/dL
What percentage of total Ca2+ is ionized Ca2+?
50%
Why are the levels of intracellular phosphate and free Ca2+ inversely related?
Because phosphate will bind calcium.
Where are early forms of vitamin D synthesized into 1,25 dihydroxycholecalciferol?
In the kidney.
How would an increase in blood anion concentration affect blood Ca2+ levels?
The total amount of Ca2+ in the blood would remain consistent, however we would see ↓ free calcium.
How does PTH cause bone reabsorption?
By acting on the osteoblasts to release signals to the osteoclasts to reabsorb bone.
In order to build and osteoclasts the osteoblasts release monocyte colony stimulating factor -> forms stem cells into osteoclast precursors -> osteoblasts release vitamin D -> osteoclast precursors become mononuclear osteoclasts -> along with IL-6 and RANK ligand, these mononuclear osteoclasts become a multinucleated osteoclast.
[Note that vitamin D also stimulates osteoblasts]
