8. Regulation of Calcium and Phosphate Metabolism

Question 1

What increases the absorption of Ca2+ from the intestine?

How is this increase in absorption accomplished?

Answer 1

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.]

Question 2

In secondary hyperparathyroidism as a result of renal failure, would we expect increased or decreased serum Pi?

Answer 2

We would expect increased serum phosphate as a result of diminished renal clearance of phosphate.

Question 3

Would we see an increase or decrease in Pi in hypoparathyroidism?

Answer 3

↑ Pi

Because there will not be enough parathyroid hormone stimulating clearance of phosphate.

Question 4

What is the role of RANK, RANK ligand, and OPG (osteoprotegerin) on osteoclast behavior?

Answer 4

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.

Question 5

What is the short-term action of PTH on osteoblasts?

Answer 5

Increases bone formation.

(Slightly counterintuitive)

Question 6

What are the functions of calbindin?

Answer 6

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.

Question 7

What is the general “job” of 1,25 dihydroxycholecalciferol in calcium and phosphate metabolism?

Answer 7

↑ Ca2+ & ↑ Pi

To increase new bone growth.

Question 8

What is the primary circulating form of vitamin D?

Where is it synthesized, and by what enzyme?

Answer 8

25-dihydroxycholecalciferol.

It is synthesized in the liver by 25-hydroxylase.

Question 9

How does a change in plasma protein concentration alter total Ca2+ concentration?

Answer 9

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.

Question 10

What stimulates the production of parathyroid hormone?

Answer 10

Low serum Ca2+

Question 11

In terms of blood calcium level, blood phosphate level, and blood vitamin D level, what are the effects of parathyroid hormone?

Answer 11

↑ Ca2+

↓ Pi

↑ Vitamin D

Question 12

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?

Answer 12

↑ Parathyroid hormone

↓ Blood Ca2+ – ↑ Urine Ca2+

↓ Blood Pi – ↑ Urine Pi

↑ Urine cAMP

↓ Vitamin D (by definition)

↓ Bone health – due to reabsorption.

Question 13

How does PTH inhibit phosphate absorption in the kidney?

Answer 13

PTH binds to its receptor -> uses a Gs pathway to increase cAMP -> causes phosphorylation of the Na+/Pi co-transporter.

Question 14

In terms of calcium, phosphate, and vitamin D – what would we expect to see in secondary hyperparathyroidism?

Answer 14

↓ 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)

Question 15

What is the normal range of extracellular phosphate?

Answer 15

2.5 – 4.5 mg/dL

Question 16

What percentage of total Ca2+ is ionized Ca2+?

Answer 16

50%

Question 17

Why are the levels of intracellular phosphate and free Ca2+ inversely related?

Answer 17

Because phosphate will bind calcium.

Question 18

Where are early forms of vitamin D synthesized into 1,25 dihydroxycholecalciferol?

Answer 18

In the kidney.

Question 19

How would an increase in blood anion concentration affect blood Ca2+ levels?

Answer 19

The total amount of Ca2+ in the blood would remain consistent, however we would see ↓ free calcium.

Question 20

How does hypocalcemia increase membrane excitability?

Answer 20

By decreasing the activation threshold for sodium channels.

Question 21

What is the phenotype of Albright hereditary osteodystrophy?

Answer 21

Short stature.

Short neck.

Obese.

Subcutaneous calcification.

Shortened metatarsals and metacarpals.

Question 22

What three things stimulate the activity of 1α-hydroxylase?

Answer 22

↓ Ca2+

↑ PTH

↓ Pi

Question 23

What is the cause of secondary hyperparathyroidism?

Answer 23

Calcium deficiency – possibly due to renal failure or vitamin D deficiency.

Question 24

What are the actions of vitamin D on the intestine?

Answer 24

Vitamin D (a steroid hormone) increases protein synthesis of the following:

Basolateral Na+/Ca2+ antiporter.

Basolateral Ca2+ ATPase.

Calbindin.

Question 25

What are the general symptoms of hypoparathyroidism?

Answer 25

The same symptoms as one might see from ↓ Ca2+. Spasticity – or numbness, tingling, or burning.. Seizures. Poor dental development. Dental deficiency.

Question 26

What percentage of Ca2+ is protein-bound?

Answer 26

40%

Question 27

What is the cause of pseudo-vitamin D deficient rickets type I?

Answer 27

Deficiency of 1α-hydroxylase.

Question 28

What do we expect to see in humoral hypercalcemia of malignancy?

Answer 28

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).

Question 29

What are the symptoms of hypercalcemia?

Answer 29

Decreased QT interval. Constipation. Lack of appetite. Polyuria. Polydipsia. Muscle weakness. Hyporeflexia. Lethargy. Coma.

Question 30

What is the basic function of calcitonin?

Answer 30

Decreases the activity and number of osteoclasts to prevent bone resorption.

Question 31

What is the usual cause of primary hyperparathyroidism?

Answer 31

Parathyroid adenoma.

Question 32

What is the Trousseau sign?

Answer 32

Carpopedal spasm upon inflation of a blood pressure cuff.

Question 33

What are the actions of PTH and vitamin D on RANK ligand and OPG?

Answer 33

PTH: ↑ RANK ligand, ↓ OPG. Vitamin D: ↑ RANK ligand.

Question 34

What is the Chvostek sign?

Answer 34

Twitching of the facial muscles upon striking the facial nerve.

Question 35

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?

Answer 35

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.

Question 36

What are the effects of estradiol on calcium metabolism?

Answer 36

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.

Question 37

How does PTH cause bone reabsorption?

Answer 37

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]

Question 38

What are the effects of adrenal glucocorticoids, like cortisol, on calcium metabolism?

Answer 38

Cortisol increases bone reabsorption of Ca2+. Cortisol increases renal wasting of Ca2+. Cortisol inhibits intestinal Ca2+ absorption.

Question 39

What is the cause of Albright hereditary osteodystrophy? What is the other name for this disease?

Answer 39

A defect in the Gs protein associated with the parathyroid hormone receptor. Pseudohypoparathyroidism type I.

Question 40

What intracellular mechanism is used by PTH to convey its signal?

Answer 40

G-protein receptor -\> ↑ cAMP. Pathological increases in PTH activity will show concomitant increases in cAMP.

Question 41

How does acidemia affect blood Ca2+ levels?

Answer 41

Acidemia ejects calcium from albumin and increases blood Ca2+ levels.

Question 42

In terms of calcium, phosphate, and vitamin D – what would we expect to find in hypoparathyroidism?

Answer 42

↓ Ca2+ ↑ Pi ↓ Vitamin D

Question 43

What is the normal level of Ca2+ in the extracellular fluid?

Answer 43

10 mg/dL Ca2+

Question 44

In terms of calcium, phosphate, and vitamin D – what would we expect to see in primary hyperparathyroidism?

Answer 44

↑ PTH ↑ Ca2+ ↓ Pi ↑ vitamin D

Question 45

What percentage of Ca2+ is ultrafilterable?

Answer 45

60%

Question 46

Chvostek sign and the Trousseau sign are both indications of what disease state?

Answer 46

Hypocalcemia

Question 47

What did the effect of PTH on 1,25 dihydroxycholecalciferol? How does this affect accomplished?

Answer 47

PTH stimulates 1,25 dihydroxycholecalciferol production. This is accomplished by the up regulation of the activity of the 1α-hydroxylase enzyme.

Question 48

In terms of calcium, phosphate, and vitamin D – what would we expect to see in Albright hereditary osteodystrophy (pseudohypoparathyroidism type I)?

Answer 48

↓ Ca2+ ↑ Pi ↓ Vitamin D

Question 49

What is the cause of pseudo-vitamin D deficient rickets type II?

Answer 49

↓ Vitamin D receptor.