Calcium Homeostasis

Question 1

What processes involve Ca2+?

Answer 1

Bone mineral formation as hydroxyapatite.
Blood clotting.
Muscle contraction - activate or inhibit enzymes.
Excitability of the NMJ.

Question 2

What should the normal Ca++ intake be?

Answer 2

1g per day. Less if female and more if lactating.

Question 3

When is the absorption of calcium highest?

Answer 3

Childhood, pregnancy and lactation.

Question 4

What are 3 promoters of calcium absorption?

Answer 4

Lactose
basic AA
Vit D

Question 5

Name an inhibitor of Ca++ absorption

Answer 5

Phytic acid (IP6)

Question 6

What is plasma concentration of Ca++ (and breakdown values).

Answer 6

2.5mM.

1.2mM = free,
1mM = plasma proteins
0.3mM = in complexes (eg with citrate).

Question 7

Hypocalcaemia and it’s effects - what is lethal?

Answer 7

Hyperexcitability of NS, tetany, <1.5mM lethal.

Because at low [Ca] Na+ channels work best.

Question 8

Hypercalcaemia and it’s effects - what is lethal?

Answer 8

Sluggish NS responses, ectopic calcification

>3.75mM lethal.

Question 9

Explain parathyroid hormone release.

Answer 9

Released when blood Ca++ is low.
2 pathways - 1 inhibited and one activated.
1) PLC - IP3 - inhibition of secretion
2) AD-Cyc - cAMP = PTH secretion.

Low Ca++ - PLC pathway inhibited and AC pathway activated - PTH secretion

Question 10

Explain how secreted PTH has its effects on bone…

Answer 10

PTH binds to osteoblast receptor…activates AC…increase cAMP…collagen synthesis is inhibited and osteoblasts release cytokines which bind to receptors in osteoclasts…release Ca++ and PO4-…release H+ and collagenase…resorbs bone…blood Ca++ increased. As is Pi…but effect on kidney….

Question 11

Explain PTH effect on kidney

Answer 11

Increase Ca reabsorption.
Decrease Pi reabsorption. Increase excretion.
activate 1alphahydroxylase - which activates vitamin D.

Question 12

Hyperparathyroidism?

Answer 12

Due to gland hyperfunction/hyperplasia

Hypercalcification due to excessive bone resorption. And ectopic calcification.

Question 13

Hypoparathyroidism?

Answer 13

surgical removal of parathyroid glands.
Pseudoidiopathic - mutant PTH
Pseudohypoparathyroidism - post receptor defect

Hypocalcaemia.

Question 14

Explain the action of calcitonin.

Answer 14

Decrease blood Ca++ and decrease blood Pi.
Formed in C/parafollicular cells of thyroid.
Released in response to high Ca++.
Act on osteoclasts via cAMP - suppress activity - no bone resorption.

In pregnancy - protect maternal skeleton.
Neonate (milk diet) - protect against sudden ca influx.

Question 15

Explain how RANKL is produced and acts.

Answer 15

if low blood Ca++…osteoblasts produce RANKL which binds to RANK and causes osteocytes to activate and resorb bone…increasing Ca++.

Question 16

What happens if oestrogen is present?

Answer 16

Increase in osteoprotegrin…binds RANKL so it can’t bind RANK and it can’t resorb bone.

Question 17

What does RANK stand for?

Answer 17

Receptor activator of nuclear factor kappa-B.

Question 18

Explain how vitamin D has its effects.

Answer 18

VItamin is either obtained via UV to the skin or in the diet. It is then converted by 25 hydroxylase in the liver to 25-OH-D. It is then converted in the kidney by 1 alpha hydroxylase to 1-25 (OH)2-D or if Ca++ excess and Pi excess to 24,25-(OH)2-D…

1,25-(OH)2-D inhibits growth and increase Ca and Pi.

Question 19

How does vitamin D act on bones?

Answer 19

Vit D binds to receptors on osteoblasts….production of cytokines which bind to osteoclasts - bone resoprtion!
Also cause the differentiation of precursors to osteoblasts and osteoclasts.

Question 20

What are the actions of Vit D on the kidney.

Answer 20

Genomic - steroid hormone - intracellular receptor…DNA…promote synthesis of proteins (including calbindins).

Non-genomic - direct effect on cell membrane to activate VOCC and increase Ca entry.

Question 21

What is a Vit D deficiency in childhood?

Treatment?

Answer 21

Rickets - protruding forehead, pigeon chest, kyphosis and bending of long legs.

Treatment - fish oils and sun exposure.

Question 22

Vit D deficiency in adulthood?

Answer 22

Osteomalacia.
Primary - dietary deficiency - low synthesis in skin.
Secondary - vit D resistant…bile duct obstruction, coeliac disease, liver disease and renal disease.

Question 23

Who are at risk of vitamin D deficency?

Answer 23

Infant born in north negland or scotland in the winter and are breast fed by vit D resistant mothers.

Too much suncream.

Asian women and children.

Elderly and house bound - 10mg/day supplementation.

Question 24

What other hormones affect Ca++ homeostasis?

Answer 24

Oestrogen deficiency (menopause) = osteoporosis.
Testosterone deficiency.
GCS - decrease Ca absorption and increase excretion.
Thyroid hormones - increase bone resorption.

Question 25

Compare and contrast osteomalacia and osteporosis.

Answer 25

Osteomalacia - normal amount of bone, low mineral:matrix ration.
Osteoporosis: less bone but normal mineral:matrix ratio.

Question 26

What are the risk factors for osteoporosis?

Answer 26

Menopause
Race - affects bone density (black>white>asain)
Family history
Physical activity
Nutrition (calcium is good. sodium, high protein and caffeine are bad).
Corticosteroids (inhibit osteoblasts).

Question 27

What is the treatment for osteoporosis?

Answer 27

1200mg/day Ca++
Oestrogen replacement therapy.
Oestrogen receptor modulators.
Bisphosphonates (inhibit osteoclasts).