Metabolism - Calcium

Question 0

How is calcium balance maintained in the bone?

Answer 0

Calcium + Pi —> hydroxyapatite crystals (found in collagen fibrils)

In deposition, osteoblasts produce collagen matrix which is mineralised = hydroxyapatite

In reabsorption, osteoclasts produce an acidic micro environment that dissolves hydroxyapatite to give calcium and Pi.

Question 1

How is calcium balance maintained in the intestine?

Answer 1

It is taken up against a concentration gradient by carriers on the luminal membrane, using ATP.
The guts secretions are also rich in calcium, so it is secreted into the lumen down a concentration gradient.

Question 2

How is calcium balance maintained in the kidney?

Answer 2

99% of ionised calcium is reabsorbed after filtration (bound calcium doesn’t fit through filter in first place).

Question 3

What are the 3 hormones involved in calcium regulation and their function?

Answer 3

1) . PTH - raises calcium levels.
2) . Calcitriol - raises calcium levels.
3) . Calcitonin - thought to lower calcium levels.

Question 4

Where is PTH secreted from?

Answer 4

The chief cells of the parathyroid gland.

Question 5

How is PTH synthesised and how is this regulated?

Answer 5

It is synthesised as prePTH then cleaved to 84 a/a long.
It is regulated at transcriptional and post transcriptional levels.

Low serum Ca2+ = up regulates transcription and promotes mRNA survival

High serum Ca2+ = down regulates transcription and stimulates chief cells to degrade PTH via cleavage.

Question 6

How is secretion of Ca2+ controlled?

Answer 6

Chief cells have a G protein calcium receptor on surface.
Increased Ca2+ binds and stimulates PLC inhibiting adenylate cyclase
=less cAMP
=less PTH release

Question 7

What should serum calcium levels be?

Answer 7

2.2-2.5mM/L

Question 8

How does PTH act on kidneys?

Answer 8

Affects tubular cells of the kidney

1) . Increases Ca2+ resorption in distal convoluted tube.
2) . Removes Pi from circulation = no calcium stone formation due to Pi and Ca2+ crystallising in blood.

Question 9

How does PTH act on bone?

Answer 9

1) . Stimulates osteoblasts to release cytokines which cause osteoclasts to be stimulated, and protect osteoclasts from apoptosis.
2) . It decreases osteoblasts activity.

= resorption of mineralised bone, releasing Ca2+ and Pi into extra cellular fluid.

Question 10

How is calcitriol formed?

Answer 10

2 forms of VitD are hydroxylated first in the liver, then the kidney to give 25hydroxyVitD.

Question 11

How is calcitriol transported?

Answer 11

It is bound to CBP protein in the blood and can be stored.

Question 12

How is calcitriol regulated?

Answer 12

Only the final conversion in the kidney is regulated by PTH.

Question 13

What are the actions of calcitriol in the gut?

Answer 13

Increases absorption of Ca2+

Question 14

What are the actions of calcitriol on the bone?

Answer 14

VitaminD stimulates osteoclasts activity and differentiation, therefore more bone erosion occurs. At the same time it inhibits osteoblasts, so more bone is broken down = release of Ca2+

Question 15

What is hypocalcaemia and its symptoms?

Answer 15

Low serum Ca2+ levels.

1) . Hyper excitability of the neuromuscular junction - lowers axon threshold but still has the same resting potential = easier to trigger.
2) . Pins and needles
3) . Tetany/Paralysis
4) . Convulsions
5) . Death
6) . Rickets in children

Question 16

What can cause hypocalcaemia?

Answer 16

A PTH deficiency due to removal of parathyroid glands or due to a failure to maintain Ca2+ levels.

Question 17

What is hypercalcaemia and its symptoms?

Answer 17

High calcium levels.

1) . Renal calculi (kidney stones) = kidney damage
2) . Constipation
3) . Dehydration
4) . Tiredness/depression

Question 18

What is the treatments for hypercalcaemia?

Answer 18

Fluids to tackle dehydration.

Treating the root of the cause of the hyperparathyroidism e.g. Removal of a benign tumour secreting PTH.

Question 19

How does PTH act on intestines?

Answer 19

Stimulates the conversion of VitD to its active form = uptake of Ca2+ increases in the gut.

Question 20

Where is calcitonin secreted from?

Answer 20

The parafollicular cells of the thyroid gland.

Question 21

How is Pi regulated?

Answer 21

Co regulation:

• Vit D stimulates uptake of Ca2+ and Pi in gut
• PTH and VitD cause bone to release Ca2+ and Pi

BUT
- In the kidney, PTH causes uptake of Ca2+ whilst excreting Pi.

Question 22

What is calcitonin thought to have a role in?

Answer 22

Lowering C2+ levels.

Maintaining the maternal skeleton during pregnancy.

Question 23

What are the actions of calcitriol on the kidney?

Answer 23

It stimulates the reabsorption of Ca2+ = less urinary loss.