10. Calcium + Phosphate Hormonal Regulation

Question 1

What is the normal blood calcium range?

Answer 1

8.5 to 10 mg/dl

Question 2

Name the 3 regulators of blood calcium levels.

Answer 2

1. PTH - ↑↑ Calcium
2. Vitamin D - ↑↑ Calcium
3. Calcitonin - ↓↓ Calcium

Question 3

Name the 3 regulators of blood phosphate levels.

Answer 3

1. PTH
2. Calcitriol
3. FGF-23

Question 4

Describe the production of active vitamin D.

Answer 4

1. 7-dehydroxycholesterol is synthesised directly from ingested cholesterol (found in fatty foods)
2. This is converted to Vitamin D3, facilitated by UVB radiation from the sun
3. Conversion of vitamin D3 to 25-hydroxyvitamin D (aka CALCIDIOL) in the liver, via the cytochrome P450 system
4. Conversion of 25-D to 1,25-dihydroxyvitamin D (aka CALCITRIOL, active vitamin D) in the presence of PTH in the kidney
5. The presence of calcitriol can then go on and promote gut calcium ion absorption

Question 5

Name 3 ways vitamin D increases blood calcium levels.

Answer 5

1. Bone
   - Acts synergistically with PTH -> stimulates osteoclast activity -> bone breakdown - ↑↑ calcium levels
2. Kidney
   - Stimulates calcium reabsorption
3. Intestines
   - ↑↑ calcium absorption

Question 6

Which is the most important regulator of serum PO4- concentration?

Answer 6

FGF-23

Question 7

Which cells in which gland release calcitonin?

Answer 7

Parafollicular cells / C cells in the thyroid gland

Question 8

What triggers calcitonin release?

Answer 8

High blood calcium levels (above the normal range)

Question 9

How does calcitonin lower blood calcium levels? State 2 ways.

Answer 9

1. In bones
   - Calcitonin binds to receptors on osteoclasts
   - Leads to decreased bone resorption and decreased blood calcium concentration
2. In kidneys
   - Decreased Calcium + Phosphate reabsorption by principle cells of the DCT

Question 10

Name the hormone released by the parathyroid.

Answer 10

Parathyroid hormone (PTH)

Question 11

Which cells release PTH?

Answer 11

Chief cells

Question 12

What is the function of PTH?

Answer 12

Increases serum Ca2+ concentration.

Decreases serum PO4- concentration.

Question 13

What inhibits PTH secretion?

Answer 13

1. High serum Ca2+ concentration
2. Calcitriol (active vitamin D)
3. Severely low Mg2+ concentration

Question 14

Name the 3 ways PTH increases blood calcium levels.

Answer 14

1. Bones

Directly stimulating osteoblasts and thereby indirectly stimulating osteoclasts (through RANK/RANKL mechanism)

For bone reabsorption/breakdown and releases calcium

2. Intestines

PTH increases gastrointestinal calcium absorption by activating vitamin D

3. Kidneys

↑↑ calcium reabsorption from urine

Question 15

How does PTH regulate PO4- levels?

Answer 15

Via actions on the kidney

It is an inhibitor of proximal tubular reabsorption of PO4-.

Through activation of vitamin D, the absorption (intestinal) of PO4- is increased.

Decreases serum PO4- concentration.

Question 16

Describe the mechanism of FGF-23 to decrease serum PO4- concentration.

Answer 16

1. Decreases expression of Na+ co-transporter in renal tubules
   - Increases renal excretion of phosphate + decreased reabsorption
2. Decreases 1α-hydroxylation of vitamin D (decreases calcitriol formation).
3. Decreases gut absorption of phosphate.

Decreases whole body phosphate

Question 17

Describe the mechanism of action of FGF-23.

Answer 17

Mechanism of action:

It binds to Klotho-FGF receptors.

Klotho – a transmembrane protein – makes the nonspecific FGF receptor bind to FGF-23.

Question 18

What inhibits FGF-23 secretion?

Answer 18

FGF-23 secretion is inhibited by PHEX when serum phosphate levels fall.