Endocrine Physiology - Endocrine Control of Calcium Balance

Question 1

What are the roles of calcium?

Answer 1

• Signalling
• Blood clotting
• Apoptosis
• Skeletal strength
• Membrane excitability (Ca2+ decreases Na+ excitability)

Question 2

How is membrane excitability affected in hypocalcaemia?

Answer 2

Increases neuronal Na+ permeability leading to hyperexcitation of neurones. In extreme cases it causes tetany, if it spreads to the larynx and respiratory muscles → asphyxiation.

Question 3

How is membrane excitability affected by hypercalcaemia?

Answer 3

Decreases neuronal Na+ permeability which will reduce excitability and depress neuromuscular activity and in extreme cases, trigger cardiac arrythmias.

Question 4

Calcium distribution in the body.

Answer 4

• bones 99%
• intracellular 0.9%
• extracellular fluid 0.1% (neraly half ECF Ca2+ is bound to protein. So only 0.05% of the calcium in the body is free in solution and physiologically active)

Question 5

How does pH affect Ca2+ binding?

Answer 5

Binding capacity increases under alkalotic conditions. (So if someone hyperventialates, plasma pH rises and plasma proteins bind more Ca2+ causing plasma concentration to fall and therefore may precipitate hypocalcaemic tetany).

The oppostie occurs with acidosis where binding capacity reduces and free [Ca2+] plasma rises.

Question 6

What are the three cell types involved in bone?

Answer 6

• Osteoblasts are the bone building cells.
• They differentiate to form osteocytes in established bone.
• Osteoclasts are the cells that are responsible for mobilising bone.

Question 7

What is the function of osteocytes?

Answer 7

They appear to regulate the activity of osteoblasts and osteoclasts.

Question 8

How do osteoclasts mobilise bone?

Answer 8

They secrete H+ ions to dissolve the calcium salts and also provide proteolytic enzymes to digest the extracellular matrix.

Question 9

Which two key hormones act to ↑ [Ca2+] plasma?

Answer 9

• Parathyroid hormone (PTH) - polypeptide hormone produced by the parathyroid glands
• Calcitrol - (active form of viatmin D3) steroid hormone produced from vitamin D3 by the liver and kidneys

Question 10

What stimulus results in the release of parathyroid hormone?

Answer 10

↓ in free [Ca2+] plasma

Question 11

How does parathyroid hormone act to increase free [Ca2+] plasma?

Answer 11

• Stimulating osteoclasts to ↑ resorption of Ca2+ and phosphate in bone (effects seen within 12-24 hours)
• Inhibiting osteoblasts to reduce Ca2+ deposition in bone
• Increasing reabsorption of Ca2+ from the kidney tubules, therefore decreasing its excretion in the urine
• Increasing renal excretion of phosphate (this elevates free [Ca2+] by preventing it from being deposited back int bone, a process that requires phosphate)
• Stimulates the kidneys to synthesise calcitrol from vitamin D which promotes Calcium absorption at the gut and kidney

Question 12

Actions of calcitrol:

Answer 12

• Increases absorption of Ca2+ from the gut
• Facilitates renal absorption of Ca2+
• Mobilises calcium stores in bone by stimulating osteoclast activity

Question 13

At what level does someone become vitamin D deficient/insufficient?

Answer 13

Less than 20ng/ml

Question 14

What is the effect of vitamin D on Ca2+?

Answer 14

While the direct effect of vitamin D is to release Ca2+ from the bone, its effects on Ca2+ absorption from gut and reabsorption at the kidneys means the net Vitamin D effect is to ↑ plasma [Ca2+] and ↑ mineralisation of bone.

Question 15

Which conditions does a vitamin D deficiency result in?

Answer 15

• Rickets in children
• Osteomalacia in adults

Question 16

Pathophysiology of rickets and osteomalacia.

Answer 16

Vitamin D deficiency → intestinal malabsorption of Ca2+ → ↓ [Ca2+] plasma → ↑PTH which then promotes phosphate deficiency which aggrivates Ca2+ loss form bone.

Question 17

Which key hormone acts to decrease [Ca2+] plasma?

Answer 17

Calcitonin - a peptide hormone produced by the thyroid gland.

Question 18

What are calcitonin’s main actions?

Answer 18

It binds to osteoclasts and inhibits bone resorption as well as increases renal excretion so preventing a further rise in Ca2+.

Question 19

How does cortisol alter Ca2+ balance?

Answer 19

↓plama [Ca2+]

Inhibits osteoblasts, increases renal excretion of Ca2+ and phosphate and reduces intestinal absorption of Ca2+.

This can, over time, produce osteoporosis.

Question 20

How does insulin alter Ca2+ balance?

Answer 20

Increases bone formation and antagonises the action of cortisol. Diabetics may have signigicant bone loss.

Question 21

How does oestrogen alter Ca2+ balance?

Answer 21

Promotes bone formation via oestrogen receptors on osteoblasts. This explains post menopausal osteoporosis.

Question 22

How does growth hormone alter Ca2+ balance?

Answer 22

Growth hormone is a constant stimulus for bone formation.

Question 23

How does prolactin alter Ca2+ balance?

Answer 23

Promotes calcium absorption from the gut by stimulating synthesis of calcitrol.