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*Diabetes & Endocrinology > Calcium Homeostasis > Flashcards

Calcium Homeostasis Flashcards

1
Q

Give 5 roles of calcium in the body

A
  1. Signalling
  2. Blood clotting
  3. Apoptosis
  4. Skeletal strength
  5. Membrane excitability
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2
Q

Expand on calciums role in signalling

A

Important signalling molecules: exocytosis of synaptic vesicles e.g. insulin from B cell; contraction of msucle fibres, alters enzyme function

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3
Q

How does calcium influence membrane excitability?

A

Ca2+ decreases Na+ permeability

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4
Q

Which of calcium’s function is most critical in short term homeostasis?

A

Membrane excitability - the body is working to maintain this at all times

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5
Q

What happens with membrane excitability in hypocalcaemia?

A

Increases Na+ permeability leading to hyperexcitation of neurons

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6
Q

In extreme cases of hypocalcaemia what can occur?

A

Tetany

If spreads to larynx + resp muscles = asphyxiation and death

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7
Q

What happens with membrane excitability in hypercalcaemia?

A

Decreases Na+ permeability which will reduce excitability and depress neuromuscular activity

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8
Q

In extreme cases of hypercalcaemia what can occur?

A

Cardiac arrythmias (depression of cardiac muscle activity)

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9
Q

How much of the body’s calcium is found in the bones?

A

99%

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10
Q

How much of the body’s calcium is intracellular?

A

0.9%

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11
Q

Where is IC calcium mostly stored?

A

Mitochondria and SR (free IC calcium is v low)

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12
Q

How much of body’s calcium is in extracellular fluid (/plasma)?

A

0.1%

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13
Q

How much of ECF plasma is bound to protein?

A

Nearly half

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14
Q

So how much of the body’s calcium is free in solution and is therefore physiologically active?

A

0.05% - this is why it needs to be so tightly regulated

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15
Q

In what form is calcium stored in the bone?

A

In the form of hydroxyapatite (calcium + phosphate)

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16
Q

Due to calcium being stored as hydroxyapatite in bone, homeostasis of what other chemical is important in determining calcium balance?

A

Phosphate

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17
Q

What is the calcium level in plasma?

A

2.2 - 2.6mM (0.1%)

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18
Q

What does calcium have a v high affinity for?

A

Proteins

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19
Q

Why does calcium have a high affinity for proteins?

A

Small positive charge attracted to large negative charge

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20
Q

Around how much calcium in plasma is bound to proteins?

A

40%

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21
Q

So, what is the level of physiologically ACTIVE calcium (free ionised, unbound) in the blood?

A

1.2mM (~50%)

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22
Q

In what form is the remaining 10% of plasma calcium found?

A

Bound to plasma anions e.g. bicarbonate and phosphate

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23
Q

What exists between the 3 forms of plasma calcium? But what is important to remember about this?

A

A dynamic equilibrium

Important to remember that it is constantly still working to maintain that holy 1.2mmol free calcium

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24
Q

How does pH affect calcium?

A

It affects the binding capacity of plasma proteins for calcium

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25
Q

What happens to binding capacity under alkalotic conditions?

A

It increases

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26
Q

Why does binding capacity increase under alkalotic conditions?

A

Increased pH = decrease in H+ ions = deprotonated = overall neg charge on protein ‘frees up space’ and allows calcium to bind = decreases plasma calcium

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27
Q

So if a patient hyperventilates, what happens to their calcium levels?

A

Plasma pH rises in hyperventilation (blowing off CO2)
Plasma proteins bind to more Ca2+, decreasing plasma conc
= hypocalcaemic tetany

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28
Q

What happens to binding capacity under acidotic conditions?

A

Decreases

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29
Q

Why does binding capacity decrease under acidotic conditions?

A

Decreased pH = increase in H+ ions = H+ ions bind to proteins and displace calcium ions = increased plasma calcium = hypercalcaemia

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30
Q

Total body calcium =

A

calcium in - calcium out

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31
Q

How does the body balance calcium in v calcium out?

A

Ca2+ in from diet

Ca2+ excretion at kidney and faeces

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32
Q

What is the PRIMARY function of bone?

A

Its role in maintaining calcium balance

33
Q

So what happens to the bone when calcium levels are disrupted?

A

Bone integrity will be sacrificed as it is secondary to calcium homeostasis

34
Q

What are osteoblasts?

A

Bone-buidling, highly active cells which lay down collagen extracellular matrix which they then calcify

35
Q

What do osteoblasts differentiate to form in established bone?

A

Osteocytes, which regulate the activity of osteoblasts and osteoclasts

36
Q

What are osteoclasts?

A

Cells responsible for mobilizing bone

37
Q

How do osteoclasts perform their function?

A

Secrete H+ ions to dissolve calcium salts and provide proteolytic enzymes to digest extracellular matrix

38
Q

What are the 2 key hormones which act to increase plasma calcium?

A

Parathyroid hormone

Calcitriol

39
Q

What is parathyroid hormone (PTH)?

A

Polypeptide hormone produced by parathyroid glands

40
Q

What is calcitriol?

A

Active form of vitamin D3; steroid hormone produced from vitamin D by the liver and kidneys

41
Q

Describe the anatomy of the parathyroid glands

A

Usually 4

Posterior surface of thyroid gland

42
Q

How essential are parathyroid glands for life?

A

Absolutely !

Thyroid glands can be removed but you die without parathyroids; if being surgically removed need to leave at least 1

43
Q

What is PTH secreted in response to?

A

Decreased free plasma calcium

44
Q

Give the 4 mechanisms by which PTH increases free plasma calcium

A
  1. Stimulate osteoclasts to increase calcium and phosphate release in bone
  2. Inhibits osteoblasts
  3. Increases reabsorption of Ca from kidney tubules (decrease excretion)
  4. Increases renal excretion of phosphate
  5. Stimulates calcitriol synthesis from vit D in kidney
45
Q

Why does increased renal excretion of phosphate result in higher plasma calcium?

A

Phosphate combines with calcium to make hydroxyapatite; with less phosphate, less calcium is laid down in bone and plasma levels are elevated

46
Q

Where is PTH primary action v calcitriol primary action?

A

PTH - kidney + bone

Calcitriol - gut (+ kidney)

47
Q

What 2 other names is calcitriol known by?

A

Vitamin D3

1,25 dihydroxycholecalciferol

48
Q

What type of hormone is calcitriol?

A

Steroid

49
Q

What is calcitriol produced from?

A

Dietary vit D or cholesterol precursors activated by sunlight on skin

50
Q

How is calcitriol produced?

A

Inactive vit D goes through liver
Converted to still inactive 25-hydroxycholecalciferol which then goes through kidney
Kidney turns it into ACTIVE vit D3 = calcitriol

51
Q

What stimulates the formation of calcitriol?

A

PTH (therefore low plasma calcium)

Prolactin in lactating women

52
Q

Where does PTH stimulate secretion of calcitriol?

A

kidney

53
Q

What halts PTH stimulation of calcitriol release?

A

Increased plasma Ca2+

54
Q

Where does calcitriol affect?

A

Bone, distal nephron, intestine (primarily gut)

55
Q

What is calcitriol’s most important effect?

A

Increase absorption of Ca2+ from the gut

56
Q

How does calcitriol increase Ca2+ absorption from gut?

A

It controls the active transport system which moves calcium from intestinal lumen to the blood - stimulates expression of transport proteins (steroid hormone so changes protein synthesis)

57
Q

Give 2 other functions which calcitriol binds to nuclear receptors in target tissues (intesine, bone, kidney) to carry out

A
  • Facilitates renal absorption of Ca2+

- Mobilises calcium stores by stimulating osteoclast activity

58
Q

How much calcium is absorbed from the intestine in a healthy individual?

A

30%

59
Q

What levels of vit D is described as a deficiency?

A

> 20ng/ml

60
Q

What is the net effect of vit D3?

A

Increased plasma calcium and increased mineralisation of bone

61
Q

What happens in vit D deficiency?

A

PTH works hard to maintain plasma calcium + in doing so continually removed calcium from bone resulting in soft bones (bent if still growing; easily fractured in adults)

62
Q

What condition in children results from vit D deficiency?

A

Rickets

63
Q

What condition in adults results from vit D deficiency?

A

Osteomalacia

64
Q

Deficiency of what other substance is promoted by vit D deficiency?

A

Phosphate

65
Q

How does vit D deficiency promote phosphate deficiency?

A

Intestinal malabsorption of calcium = decreased plasma calcium = increased PTH which promotes phosphate deficiency and aggravates Ca loss from bone

66
Q

What other conditions is vit D deficiency possibly implicated in?

A

MS
cancer
arthritis
CVD

67
Q

What is the key hormone which decreases plasma calcium?

A

Calcitonin

68
Q

What is calcitonin?

A

peptide hormone produced by clear cells in the thyroid gland

69
Q

What is calcitonin secretion stimulated by?

A

Increased plasma calcium

70
Q

What are calcitonins main functions?

A

Bind to osteoclasts and inhibit bone resorption (release)

Increase renal excretion of calcium

71
Q

How important is calcitonin to humans?

A

Little evidence to support its importance; increase or decrease still results in normal calcium levels (PTH steps in); last resort treatment for Paget’s

72
Q

Give 5 other endocrine hormones altering calcium balance

A
  1. Cortisol
  2. Insulin
  3. Oestrogen
  4. Growth hormone
  5. Prolactin
73
Q

How does cortisol affect calcium balance?

A

reduces plasma calcium (inhibits osteoblasts, increases renal excretion, reduces intestinal absorption)

74
Q

What condition is cortisol linked with?

A

Osteoporosis

75
Q

What effect does insulin have on calcium balance?

A

increases plasma calcium (increases bone formation; diabetics may have significant bone loss)

76
Q

How does oestrogen affect calcium balance?

A

Promotes bone formation via oestrogen receptors on osteoblasts (linked with post-menopausal osteoporosis)

77
Q

How does GH affect calcium balance?

A

Constant stimulus for bone formation

78
Q

How does prolactin affect calcium balance?

A

Promotes calcium absorption from gut by stimulating synthesis of calcitriol

*Diabetes & Endocrinology (24 decks)

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