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 hypocalcemia increase membrane excitability?
By decreasing the activation threshold for sodium channels.
What is the phenotype of Albright hereditary osteodystrophy?
Short stature.
Short neck.
Obese.
Subcutaneous calcification.
Shortened metatarsals and metacarpals.
What three things stimulate the activity of 1α-hydroxylase?
↓ Ca2+
↑ PTH
↓ Pi
What is the cause of secondary hyperparathyroidism?
Calcium deficiency – possibly due to renal failure or vitamin D deficiency.
What are the actions of vitamin D on the intestine?
Vitamin D (a steroid hormone) increases protein synthesis of the following:
Basolateral Na+/Ca2+ antiporter.
Basolateral Ca2+ ATPase.
Calbindin.
What are the general symptoms of hypoparathyroidism?
The same symptoms as one might see from ↓ Ca2+.
Spasticity – or numbness, tingling, or burning..
Seizures.
Poor dental development.
Dental deficiency.
What percentage of Ca2+ is protein-bound?
40%
What is the cause of pseudo-vitamin D deficient rickets type I?
Deficiency of 1α-hydroxylase.
What do we expect to see in humoral hypercalcemia of malignancy?
Presence of PTHrP
Increased blood and urine calcium.
Decreased blood phosphate with increased urinary phosphate.
Decreased PTH levels.
Decreased vitamin D levels (cancer inhibits vitamin D somehow).
What are the symptoms of hypercalcemia?
Decreased QT interval.
Constipation.
Lack of appetite.
Polyuria.
Polydipsia.
Muscle weakness.
Hyporeflexia.
Lethargy.
Coma.
What is the basic function of calcitonin?
Decreases the activity and number of osteoclasts to prevent bone resorption.
What is the usual cause of primary hyperparathyroidism?
Parathyroid adenoma.
What is the Trousseau sign?
Carpopedal spasm upon inflation of a blood pressure cuff.
What are the actions of PTH and vitamin D on RANK ligand and OPG?
PTH: ↑ RANK ligand, ↓ OPG.
Vitamin D: ↑ RANK ligand.
What is the Chvostek sign?
Twitching of the facial muscles upon striking the facial nerve.
In terms of parathyroid hormone, blood in urine calcium, blood phosphate levels, and vitamin D levels – what would we expect to see in familial hypocalciuric hypercalcemia?
Normal or increased parathyroid hormone levels.
Blood calcium will be high, urinary calcium will be low.
Pi is usually normal.
Vitamin D content is usually normal.
What are the effects of estradiol on calcium metabolism?
Estradiol stimulates intestinal Ca2+ absorption as well as renal tubular Ca2+ reabsorption.
Estradiol also promotes survival of osteoblasts and death of osteoclasts – favoring bone formation.
Estradiol decreases during menopause.
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]
What are the effects of adrenal glucocorticoids, like cortisol, on calcium metabolism?
Cortisol increases bone reabsorption of Ca2+.
Cortisol increases renal wasting of Ca2+.
Cortisol inhibits intestinal Ca2+ absorption.
What is the cause of Albright hereditary osteodystrophy?
What is the other name for this disease?
A defect in the Gs protein associated with the parathyroid hormone receptor.
Pseudohypoparathyroidism type I.
What intracellular mechanism is used by PTH to convey its signal?
G-protein receptor -> ↑ cAMP.
Pathological increases in PTH activity will show concomitant increases in cAMP.
How does acidemia affect blood Ca2+ levels?
Acidemia ejects calcium from albumin and increases blood Ca2+ levels.
In terms of calcium, phosphate, and vitamin D – what would we expect to find in hypoparathyroidism?
↓ Ca2+
↑ Pi
↓ Vitamin D
What is the normal level of Ca2+ in the extracellular fluid?
10 mg/dL Ca2+
In terms of calcium, phosphate, and vitamin D – what would we expect to see in primary hyperparathyroidism?
↑ PTH
↑ Ca2+
↓ Pi
↑ vitamin D
What percentage of Ca2+ is ultrafilterable?
60%
Chvostek sign and the Trousseau sign are both indications of what disease state?
Hypocalcemia
What did the effect of PTH on 1,25 dihydroxycholecalciferol?
How does this affect accomplished?
PTH stimulates 1,25 dihydroxycholecalciferol production.
This is accomplished by the up regulation of the activity of the 1α-hydroxylase enzyme.
In terms of calcium, phosphate, and vitamin D – what would we expect to see in Albright hereditary osteodystrophy (pseudohypoparathyroidism type I)?
↓ Ca2+
↑ Pi
↓ Vitamin D
What is the cause of pseudo-vitamin D deficient rickets type II?
↓ Vitamin D receptor.
