Endocrine Calcium-Phosphate

Question 1

State the physiologic plasma concentration of calcium and phosphate in humans.

Answer 1

calcium plasma concentration - 2.1-2.6mM

phosphate plasma concentration - 0.75-1.5mM

Question 2

State how calcium is found in the body. (mention the different states of calcium)

Answer 2

1. 5% complexed with bicarbonate/citrate
2. 45% protein-bound (with albumin) - increased pH increases binding (less in ionised form)
3. 50% ionised (ca2+)

Question 3

State the cells used in bone…
- composition
- formation
- resorption
- growth

Answer 3

BONE COMPOSITION - hydroxyapatite (mineral) + osteoids (matrix)

BONE FORMATION - osteoblasts/osteocytes

BONE RESORPTION - osteoclasts

BONE GROWTH - chondrocytes (found at the ends of long bones)

Question 4

With regard to the PARATHYROID HORMONE, state…
- Type of hormone
- Secreted by ____
- Stimulated by ____ and ____
- Actions of PTH

Answer 4

With regard to the PARATHYROID HORMONE, state…
- Amino acid hormone
- Secreted by PARATHYROID GLAND (follicular cells)
- Stimulated by LOW [CA2+] and HIGH [PO42-]
- Actions of PTH = increase [Ca2+] and decrease [PO42-]

1. Stimulates bone resorption to increase [ca2+]
2. Increases Ca2+ absorption at DCT
3. Increases Vitamin D production at PCT
4. Decreses PO42- absorption at PCT
5. Acts via Vitamin D at gut to indirectly increase Ca2+ and PO42- ion absorption

Question 5

Explain how PTH hormone is stimulated to be released.

Answer 5

1. stimulus: [Ca2+] low (from alkalosis which stimulates Ca2+-albumin binding) and/or [PO42-] high (from late CKD –> poor excretion)
2. At high [Ca2+], Ca2+ binds to calcium recepotors (GPCR) on parathyroid cell and sends signal to the nucleus
3. Nucleus sends signal to inhibit PTH secretion from parathyroid cell
4. When [Ca2+] low or [PO42-] high –> binding to GPCR is absent and PTH levels rise as inhibition is removed

Question 6

With regard to VITAMIN D, state
- Type of hormone
- Secreted by ____
- Actions of Vitamin D

Answer 6

With regard to VITAMIN D, state
- Cholesterol-derived hormone
- Secreted by SKIN OR FOUND IN DIET
- Actions of Vitamin D = increase [Ca2+] and [PO42-]

1. Promotes PTH effect of bone resorption to increase [Ca2]
2. Increases Ca2+ and PO42- absorption at gut
3. Increase Ca2+ and PO42- reabsorption at kidneys

Question 7

State the steps involved in the activation of vitamin D

Answer 7

ACTIVATION OF VITAMIN D:
1. 7-DEHYDROCHOLESTEROL (from skin)* undergoes exposure to sunlight (UV) to be converted to CHOLECALCIFEROL (VIT-D3)
2. CHOLECALCIFEROL is converted to 25-HYDROXYCHOLECALCIFEROL via 25-hydroxylase in the LIVER
3. 25-HYDROXYCHOLECALCIFEROL is converted into 1,25-DIHYDROXYCHOLECALCIFEROL via 1a-hydroxylase in the KIDNEY (stimulated by PTH and low phosphate)

Question 8

How are PTH and Vitamin D related?

Answer 8

when [Ca2+] low –> PTH secretion is high –> stimulates vitamin D production to aid in increasing [Ca2+]

Question 9

With regard to CALCIUM REABSORPTION AT KIDNEYS, state…
- which part of the glomerulus and bowman’s capsule
- what percentage of calcium is reabsorbed

Answer 9

glomerulus - 60% reabsorbed by calcium channels (stimulated by vitamin D)

collecting ducts (bowman’s capsule) - 39% reabsorbed by calcium channels (stimulated by PTH)

1% of calcium excreted

Question 10

With regard to CALCIUM ABSORPTION AT INTESTINES, state…
- channels involved
- stimulus

Answer 10

CALCIUM ABSORPTION AT INTESTINES
- Channels involved - sodium-calcium exchanger + calcium ATPase
- Stimulus - 1,25-DIHYDROXYCHOLECALCIFEROL

Question 11

Explain how calcium levels are regulated in humans (reference PTH and vitamin D).

Answer 11

Scenario: LOW CALCIUM
(1) Low [Ca2+] stimulates follicular cells to remove inhibition of PTH secretion to allow for increased PTH
(2) PTH stimulates 1a-hydroxylase to convert 25-HYDROXYCHOLECALCIFEROL TO 1,25-DIHYDROXYCHOLECALCIFEROL (vit d) in the kidney –> stimulate increased intestinal Ca2+ absorption by sodium-calcium exchanger and calcium ATPase
(3) PTH stimulates increased renal reabsorption of Ca2+ (60% stimulated by vitd at glomerulus, 39% stimulated by PTH at collecting ducts)
(4) PTH and VitD stimulate bone resorption

Question 11

Why is the change in phosphate concentration due to PTH and Vitamin D negligible?

Answer 11

PTH decreases phosphate reabsorption in PCT while Vitamin D (1,25-HYDROXYCHOLECALCIFEROL) increases phosphate reabsorption in PCT

Question 11

With regard to CALCITONIN, state…
- Type of hormone
- Secreted by ____
- Stimulated by ____
- Actions of calcitonin

Answer 11

With regard to CALCITONIN, state…
- Amino acid hormone
- Secreted by PARAFOLLICULAR/ C CELLS OF THYROID GLAND
- Stimulated by HIGH PLASMA [Ca2+]
- Actions of calcitonin: Decrease [Ca2+]

1. Decreases bone resorption to prevent further decrease in Ca2+
2. Decreases calcium reabsorption at kidneys
3. No effect at the gut

Question 12

Explain how phosphate levels are regulated in humans. (recall the hormone involved here!)

Answer 12

1. Stimulus: high [PO42-]
2. Stimulates bone to secrete and release FGF23 (fibroblast-growth factor 23) which
3. Decreases renal phosphate reabsorption, decreases gut phosphate reabsorption and decreases active 1,25-DIHYDROXYCHOLECALCIFEROL (VitD)
4. Net decrease in phosphate, calcium remains almost unchanged