Calcium Homeostasis

Question 1

what is the role of calcium in the body?

Answer 1

Signalling – Ca2+ important signalling molecules: exocytosis of synaptic vesicles e.g. neurotransmitters/ hormones etc, contraction of muscle fibres, alters enzyme function.
Blood clotting – essential component of clotting cascade.
Apoptosis – programmed cell death
Skeletal strength – 99% of calcium in the body is wrapped up in bone where it gives strength to the skeleton.
Membrane Excitability – Ca2+ decreases Na+ permeability.

Question 2

what is the consequence of hypocalcaemia?

Answer 2

increases neuronal Na+ permeability leading to hyperexcitation of neurons. In extreme cases causes tetany, if spreads to larynx and respiratory muscles – asphyxiation.

Question 3

what is the consequence of hypercalcaemia?

Answer 3

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

Question 4

what is the calcium distribution in the body?

Answer 4

bones- 99%
intracellular - 0.9%
extracellular fluid - 0.1%

Question 5

does calcium have a high affinity for proteins?

Answer 5

yes v high

Question 6

true or false:

in plasma, 60% of calcium is bound to plasma proteins

Answer 6

false 40%

Question 7

what is the calcium distribution in the blood?

Answer 7

40% is protein bound, 50% is ionised and 10% is complexed

Question 8

is binding for calcium increased or decreased under alkalotic conditions?

Answer 8

increased

Question 9

what is total body calcium determined by?

Answer 9

calcium in - calcium out

Question 10

what are osteoblasts?

Answer 10

bone building cells

highly active cells which lay down a collagen extracellular matrix which they then calcify

Question 11

what are osteocytes?

Answer 11

osteoblasts differentiate to form them.

much less active than osteoblasts but appear to regulate the activity of osteoblasts and osteoclasts

Question 12

what are osteoclasts?

Answer 12

are the cells that are responsible for mobilizing bone. They secrete H+ ions (pH 4) to dissolve the calcium salts and also provide proteolytic enzymes to digest the extracellular matrix.

Question 13

what are the 2 key hormones that act ti control increase of concentration of calcium

Answer 13

Parathyroid hormone (PTH) polypeptide hormone produced by the parathyroid glands

Calcitriol (active form of Vit D3) steroid hormone produced from Vitamin D by the liver and kidneys

Question 14

how many parathyroid glands are there?

Answer 14

4 lying on the posterior surface of the thyroid gland, although variations in number and location of are common, 1 in 10 people have aberrant distribution, (important if need to remove overactive thyroid gland!). Essential for life!

Question 15

what is the trigger for release of parathyroid hormone?

Answer 15

in response to decrease in free calcium

Question 16

how does the release of PTH increase free calcium?

Answer 16

1. Stimulating osteoclasts to resorption (release) of Ca2+ and phosphate in bone (effects seen within 12-24hrs)
2. Inhibiting osteoblasts to reduce Ca2+ deposition in bone.
3. Increasing reabsorption of Ca2+ from the kidney tubules, therefore decreasing its excretion in the urine.
4. Increasing renal excretion of phosphate. This elevates free [Ca2+ ] by preventing it from being deposited back into bone, a process that requires phosphate.
5. Stimulates the kidney to synthesise calcitriol from vitamin D which promotes calcium absorption at the gut and kidney.

Question 17

what is calcitriol also known as?

Answer 17

active vitamin D3

Question 18

what is active vitamin D3 formed from?

Answer 18

cholesterol derivatives by the action of UV light on the skin, but Vit D can also be gained from the diet.

Question 19

what is the action of calcitriol?

Answer 19

biinds to nuclear receptors in target tissues

Question 20

how does calcitriol increase absorption of ca from the gut?

Answer 20

The active transport system which moves Ca2+ from the intestinal lumen to the blood is under the control of calcitriol.
In a situation of low plasma [Ca2+ ]:
increase in PTH leads to increase of calcitriol which leads to increase in intestinal absorption of Ca2+

Alternatively:
increase levels of plasma Ca2+ inhibit PTH causing a shift to greater osteoblast deposition and less osteoclast resorption.

Question 21

what are the functions of calcitriol?

Answer 21

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

Collectively these actions, complement those of PTH and increase [Ca2+ ]plasma

Question 22

what does vitamin D deficiency cause?

Answer 22

Rickets in children
Osteomalacia in adults

leads to calcium and phoshpate deficiency

Question 23

what is a key hormone that acts to decrease [Ca2+ ]plasma

Answer 23

Calcitonin

Question 24

what are the actions of calcitonin?

Answer 24

Its main actions are to bind to osteoclasts and inhibit bone resorption as well as renal excretion so preventing a further in Ca2+ .
HOWEVER, there is little evidence that it is important humans. In thyroid disease such as tumours where calcitonin levels are very high, plasma calcium levels are normal and there are no abnormalities of bone structure. So any effect of XS calcitonin is overridden by PTH.
Similarly, patients with no calcitonin secretion have normal Ca2+ levels.
May be used, rarely, to treat Paget’s disease (overactive osteoclasts

Question 25

what are othre endocrine hormones altering calcium balance?

Answer 25

Cortisol 
Insulin 
Oestrogen 
Growth Hormone 
Prolactin

Question 26

whats the action of cortisol?

Answer 26

inhibits osteoblasts, increases renal excretion of Ca2+ and phosphate and reduces intestinal absorption of Ca2+ leads to decreasevplasma [Ca2+ ] which leads to increase in PTH  which leads to increase in bone resorption. This together with the reduced bone formation can, over time, produce osteoporosis.

Question 27

whats the action of insulin? with regards to ca balance

Answer 27

increases bone formation, and antagonises the action of cortisol. Diabetics may have significant bone loss.

Question 28

whats the action of oestrogen with regards to ca balance?

Answer 28

promotes bone formation via oestrogen receptors on osteoblasts. Post-menopausal osteoporosis a major problem.

Question 29

whats the action of growth hormone regarding bone formation

Answer 29

constant stimulus for bone formation

Question 30

whats the action of prolactin with regards to ca balance?

Answer 30

promotes calcium absorption from the gut by stimulating synthesis of calcitriol