Physiology 4 - Calcium Balance

Question 1

What are the roles of calcium in the body?

Answer 1

Signalling
Blood clotting
Apoptosis
Bone strength
Membrane excitability (most obviously in muscle contraction)

Question 2

What happens to your muscle if your hypo or hypercalcaemic?

Answer 2

Hypocalcaemia

• > Increased neuronal Na permeability
• > Hyperexcitation
• > Tetany & Asphyxiation in extreme cases

Hypercalcaemia

• > Depressed excitation
• > Cardiac arrythmias in extreme cases

Question 3

Describe the distribution of calcium in the body?

Answer 3

99% stored in bones as hydroxyapatite

0. 9% is in the ICF (mainly mitochondria)
1. 1% is found in the ECF/plasma

Of the 0.1% in the plasma 40% is bound to plasma proteins, 10% is bound to anions and only 50% (~1.2mM) is free and physiologically active

Question 4

What is the relevance of the protein bound Ca2+ in the blood?

Answer 4

The degree of protein binding is pH determined.
Therefore in alkalosis (E.g. hyperventilating), binding increases and hypocalcaemia can occur.

Vice versa acidosis can cause hypercalcaemia

Question 5

What is the relevance of phosphate to calcium homeostasis>

Answer 5

Calcium is bound with phosphate into Hydroxyapatite making up bone.

This means phosphate is essential for calcium storage in bone

Question 6

List the hormones involved in calcium homeostasis

Answer 6

Raises Ca2+:
PARATHYROID HORMONE (PTH)
CALCITRIOL

Lowers Ca2+
CALCITONIN

Other:
Cortisol
Insulin
Oestrogen
Prolactin
Growth Hormone

Question 7

Describe PTH?

Answer 7

A peptide hormone produced in 4 parathyroid glands posterior to the thyroid and released in response to low free plasma Ca2+

Question 8

What are the functions of PTH?

Answer 8

IT serves to raise serum free Ca2+ by:

1) Stimulating osteoclasts
2) Inhibits osteoblasts
3) Increases renal reabsorption of Ca2+
4) Increases renal excretion of phosphate (preventing bone deposition)
5) Stimulates renal synthesis of Calcitriol

Question 9

Describe calcitriol:

Answer 9

A steroid hormone produced from Vit D in the liver and kidneys in response to PTH (and in lactating women - Prolactin)
Also known as Active Vit D3 or 1,25-dihydroxycholecaliferol

Question 10

How does calcitriol work?

Answer 10

Serves to raise free plasma Ca2+ by binding to nuclear receptors in the intestine, bone & kidney to:

• Stimulates osteoclasts
• Increases renal reabsorption of Ca2+
• Increases Ca2+ absorption in the gut

Question 11

How much dietary Ca2+ is absorped in the gut?

Answer 11

30% in a healthy person
10-15% in a vit d deficient person
50% in pregnancy, lactation of growth spurts.

Question 12

Describe Calcitonin

Answer 12

A peptide hormone produced by the thyroid and released when theres a high free plasma Ca2+

Question 13

How does Calcitonin work?

Answer 13

IT lowers plasma Ca2+ by:

• Inhibiting Osteoclasts
• Increasing Ca2+ renal excretion

Question 14

Why isnt calcitonin that relevant clinically?

Answer 14

Patients with raised or absent calcitonin don’t get abnormal calcium levels.
PTH seemingly overrides the effects of calcitonin anyway

Question 15

How is cortisol involved in calcium homeostasis?

Answer 15

• Inhibits osteoblasts
• Increases renal excretion of Ca2+
• Decreases Intestinal absorption of Ca2+

Decreasde absorption means more PTH is secreted which means more bone is broken down, combined with the inhibition of osteoblasts this can lead to osteoporosis

Question 16

How is Insulin involved in calcium homeostasis?

Answer 16

Insulin antagonizes cortisol -> Increased bone formation

Hence diabetics have significant bone loss

Question 17

How is Oestrogen involved in calcium homeostasis?

Answer 17

Promotes osteoblasts

Thus post-menopausal osteoporosis is possible

Question 18

How is Growth Hormone involved in calcium homeostasis?

Answer 18

Stimulates osteoblasts

Question 19

How is prolactin involved in calcium homeostasis?

Answer 19

Stimulates calcitriol synthesis -> Increased Ca2+ absorption from gut

Question 20

Which hormones raise/lower Calcium in the blood and bone?

Answer 20

PTH & Calcitriol raise Serum Ca2+ at the expense of bone

Calcitonin inhibits bone resorption and excretes Ca2+

Cortisol lowers bone and plasma Ca2+

Insulin, oestrogen & GH all raise Bone Ca2+

Prolactin increases plasma & decreases bone Ca2+ by stimulating calcitriol

Question 21

Who is most likely to suffer from a Vit D deficiency?

Answer 21

Over 65s due to reduced gut absorption
Darker skinned people and/or living in low light countries
Asian populations due to dietary Vit D3 deficiency and consumption of chapatti flour which contains phytate that binds dietary Ca2+ preventing absorption

Question 22

How does a vitamin d deficiency present/how does it cause these presentations?

Answer 22

Soft, easily fractured bones:
Osteomalacia in adults
Rickets in kids

Calcitriol isn’t absorbing extra Ca2+ so PTH has to drain more from bone.
The high phosphate excretion due to high PTH exacerbates bone loss

Question 23

How is calcitriol produced?

Answer 23

2 step process: liver then kidneys

• Produced from cholesterols from diet OR
• Produced from Vitamin D3 being exposed to UV light
• Vitamin D3 in liver formed
• Transported to kidney.
• released up release of PTH when plasma calcium is LOW
• Causes bone to release calcium

Question 24

How does calcium affect cell membrane?

Answer 24

Decreases permeabilty of cell membranes to Sodium
In hypocalcemia: increases membrane permeability to NA= hyper-excitation of neurones.
In hypercalcemia: decreases membrane permeability to NA= hypo-excitation of neurones

Question 25

How much calcium in body

Answer 25

1kg in the bones
2.2-2.6mM in the ECF of which 40% bound to plasma proteins, 10% anions and 50% free
24mM in the mitochondria