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Systems: Endocrine AB > Calcium Homeostasis > Flashcards

Calcium Homeostasis Flashcards

1
Q

What are the roles of calcium?

A
  • Signalling
  • Blood clotting
  • Apoptosis
  • Skeletal strength
  • Membrane excitability
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2
Q

What role does Ca play in signalling?

A

Ca2+ important signalling molecules: exocytosis of synaptic vesicles e.g. neurotransmitters/ hormones etc, contraction of muscle fibres, alters enzyme function.

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3
Q

What role does Ca play in skeletal strength?

A

99% of calcium in the body is wrapped up in bone where it gives strength to the skeleton.

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4
Q

What role does Ca play in membrane excitability?

A

Ca2+ decreases Na+ permeability.

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5
Q

When is Ca role in membrane excitability most critical?

A

Short term homeostasis

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6
Q

How can hypocalcaemia lead to asphyxiation?

A

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

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7
Q

How can hypercalcaemia lead to cardiac arrhythmias?

A

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

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8
Q

How is calcium distributed within the body?

A
  • Bones 99%
  • ICF 0.9%
  • ECF 0.1%
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9
Q

How is Ca in the ICF distributed?

A

Mostly stored inside mitochondria and Sarcoplasmic Reticulum. Free [Ca2+ ]IC very low

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10
Q

How is Ca in the ECF distributed?

A

Nearly half ECF Ca2+ is bound to protein

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11
Q

What form is the Ca stored in the calcified extracellular matrix in?

A

~1Kg (99%) calcium is stored in the calcified extracellular matrix of bone, mostly in the form of hydroxyapatite (Ca10(PO4)6(OH)2)

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12
Q

Homeostasis of what other element is important in determining calcium balance?

A

Phosphate

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13
Q

How much calcium is found inside cells other than bone?

A

~24mM (0.9%) is found inside cells other than bone

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14
Q

How much calcium is in solution in the cytosol?

A

0.001mM in solution in the cytosol. Rest stored within mitochondria and SR

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15
Q

What are the calcium plasma levels?

A

2.2-2.6mM in plasma (0.1%)

[Ca2+ ]ECF is maintained within tight limits

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16
Q

Why is 40% of calcium in the blood bound to plasma proteins?

A

Calcium has a very high affinity for proteins (small positive charge attracted to large negative charge)

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17
Q

What does the binding of calcium to plasma proteins mean?

A

So while [Ca2+ ]plasma is ~2.5mM, free ionised, and therefore physiologically active [Ca2+ ] is only about 1.2mM and accounts for ~50% of plasma calcium

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18
Q

What do the remaining 10% of plasma calcium ions that are neither bound to plasma protein, nor free in solution bind to?

A

Plasma anions

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19
Q

What calcium is physiologically active?

A

Free calcium

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20
Q

What is an important consideration regarding Ca and binding to proteins?

A

An important consideration for Ca2+ is that the binding capacity of plasma proteins changes with pH.

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21
Q

What conditions increases binding capacity?

A

Alkalotic conditions

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22
Q

What can cause plasma pH to rise?

A

Hyperventilation

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23
Q

Why can hyperventilation lead to hypocalcaemic tetany?

A
  • Plasma pH rises
  • Plasma proteins bind more Ca2+ causing plasma concentration to fall and therefore may precipitate hypocalcaemic tetany.
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24
Q

What happens to Ca in acidosis?

A

Binding capacity reduces and free [Ca2+]plasma rises

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25
Q

What is total Ca determined by?

A

Total body Ca2+ is determined by the simple principle :

total body calcium = calcium in – calcium out

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26
Q

Distribution of calcium between what is crucial?

A

Bone and ECF

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27
Q

What is the function of bone?

A

Bone functions to provide mechanical support for the body but its role in maintaining Ca2+ balance takes precedence over this

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28
Q

What are osteoblasts?

A

Osteoblasts are the bone-building cells. They are highly active cells which lay down a collagen extracellular matrix which they then calcify.

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29
Q

What are osteocytes?

A

Differentiated osteoblasts

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30
Q

What do osteocytes do?

A

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

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31
Q

What are osteoclasts?

A

Osteoclasts are the cells that are responsible for mobilizing bone

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32
Q

What do osteoclasts do?

A

They secrete H+ ions (pH  4) to dissolve the calcium salts and also provide proteolytic enzymes to digest the extracellular matrix

33
Q

What 2 key hormones act to increase Ca concentration in the plasma?

A
  • 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
34
Q

Where are the parathyroid glands found?

A

There are usually 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!).

35
Q

What is PTH released in response to?

A

Released in response to decreases in free [Ca2+ ]plasma

36
Q

What does PTH act to do?

A

Acts to increase free [Ca2+ ]plasma

37
Q

How does PTH increase free [Ca]plasma?

A

-Stimulating osteoclasts to increase resorption (release) of Ca2+ and phosphate in bone (effects seen within 12-24hrs)

Inhibiting osteoblasts to reduce Ca2+ deposition in bone.

Increasing reabsorption of Ca2+ from the kidney tubules, therefore decreasing its excretion in the urine.
Increasing renal excretion of phosphate. This elevates free [Ca2+ ] by preventing it from being deposited back into bone, a process that requires phosphate.

Stimulates the kidney to synthesise calcitriol from vitamin D which promotes calcium absorption at the gut and kidney.

38
Q

What are other names for calcitriol?

A
  • Active Vitamin D3

- 1,25 dihydroxycholecalciferol (1,25(OH)2D3)

39
Q

What does calcitriol complement the action of?

A

Complements action of PTH - increases [Ca2+ ]plasma

40
Q

What is calcitriol?

A

A steroid hormone produced in two steps (1. liver, 2. kidneys) from dietary vitamin D or from precursors activated by sunlight on skin.

41
Q

What stimulates the formation of calcitriol in lactating women?

A

Prolactin

42
Q

How is active vitamin D3 formed?

A

Active vitamin D3 is formed from cholesterol derivatives by the action of UV light on the skin, but Vit D can also be gained from the diet.

43
Q

Give examples of fat soluble vitamin dietary sources of calcitriol.

A
  • Mackerel
  • Tuna
  • Fish liver oils
  • Egg yolks
44
Q

What does calcitriol bind to?

A

Binds to nuclear receptors in target tissues (intestine, bone and kidney)

45
Q

What are the actions of calcitriol?

A
  • Increase absorption of Ca2+ from the gut.
  • Facilitates renal absorption of Ca2+
  • Mobilises calcium stores in bone by stimulating osteoclast activity.
46
Q

What do the actions of calcitriol collectively complement?

A

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

47
Q

What happens to most of the calcium from our diet?

A

Much of the Ca2+ in the diet passes straight through and is excreted in the faeces

48
Q

The active transport system which moves Ca2+ from the intestinal lumen to the blood is under the control of …

A

Calcitriol

49
Q

How does the body correct low plasma [Ca]?

A

-In a situation of low plasma [Ca2+ ]: increases in PTH leads to increased calcitriol which leads to increases in intestinal absorption of Ca2+
-Alternatively:
Incresed levels of plasma Ca2+ inhibit PTH causing a shift to greater osteoblast deposition and less osteoclast resorption.

50
Q

What does prolactin stimulate calcitriol synthesis in association with?

A

Increased demand for Ca2+ for milk production in lactation.

51
Q

What controls the proportion of dietary calcium absorbed from the intestine?

A

Circulating level of 1,25(OH)2D controls proportion of dietary calcium absorbed from the intestine

52
Q

What condition has low levels of calcitriol?

A

Vitamin D deficiency

53
Q

When would you have high levels of circulating calcitriol?

A
  • Pregnancy
  • Lactation
  • Growth spurts
54
Q

What is the definition of vitamin D deficiency?

A

Circulating vitamin D levels fall to less than 20ng/ml

55
Q

Where is vitamin D stored extensively?

A

Fat

56
Q

What contributes to vitamin D deficiency?

A

Clothing, UVB sunscreen, diet all add to problem of lack of sunlight

57
Q

Who is vitamin D deficiency more prevalent in?

A

More prevalent in >65 years due to reduced gut absorption, reduced Ca2+ mobility.

58
Q

What is the direct effect of vitamin D3?

A

While direct effect of Vit D3 is to release Ca2+ from bone,

59
Q

What is the net vitamin D3 effect?

A

Its effect on Ca2+ absorption from gut/ reabsoption at kidneys, means the net Vitamin D3 effect is to increase plasma [Ca2+] and increased mineralization of bone.

60
Q

Why are bones soft/bent in vitamin D3 deficiency?

A

In Vit D deficiency PTH works hard to maintain plasma [Ca2+] and in doing so continually removes Ca2+ from bone resulting in bones which are soft and, if still growing, become bent. In adults, easily fractured.

61
Q

How can vitamin D3 deficiency manifest in children?

A

Rickets

62
Q

How can vitamin D3 deficiency manifest in adults?

A

Osteomalacia

63
Q

How does vitamin D3 deficiency lead to Ca loss from bone?

A

Vitamin D3 deficiency leads to intestinal malabsorption of Ca2+ , this decreases [Ca2+ ]plasma which increases PTH which then promotes phosphate deficiency – aggravates Ca2+ loss from bone.

64
Q

What factors are involved in increasing the risk of vitamin D3 deficiency in the elderly and Asian populations?

A

Chapatti flour contains phytate which binds dietary Ca2+ .
There may be dietary deficiency of vitamin D3
Pigmented skin is less able to make vitamin D3 in response to UV light.

65
Q

What is vitamin D3 deficiency implicated in?

A
  • MS
  • Cancer
  • Arthritis
  • CVD
66
Q

What key hormone acts to decrease [Ca]plasma?

A

Calcitonin

67
Q

What is calcitonin?

A

Peptide hormone produced by the thyroid gland

68
Q

What stimulates calcitonin secretion?

A

Its secretion is stimulated by increased [Ca2+]plasma

69
Q

What are the main actions of calcitonin?

A

Its main actions are to bind to osteoclasts and inhibit bone resorption as well as increase renal excretion so preventing a further increase in Ca2+ .

70
Q

Why is it believed that any effect of excess calcitonin is overridden by PTH?

A

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 excess calcitonin is overridden by PTH.

71
Q

When may calcitonin be used as a treatment?

A

Paget’s disease (overactive osteoclasts)

72
Q

What happens to Ca levels in patients with no calcitonin production?

A

Normal Ca levels

73
Q

What other hormones can effect Ca balance?

A
  • Cortisol
  • Insulin
  • Oestrogen
  • GH
  • Prolactin
74
Q

How does cortisol affect Ca balance?

A

Inhibits osteoblasts, increases renal excretion of Ca2+ and phosphate and reduces intestinal absorption of Ca2+ leads to decreased plasma [Ca2+ ] leads to increased PTH leads to increased bone resorption. This together with the reduced bone formation can, over time, produce osteoporosis.

75
Q

How does insulin affect Ca balance?

A

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

76
Q

How does oestrogen affect Ca balance?

A

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

77
Q

How does GH affect Ca balance?

A

Constant stimulus for bone formation

78
Q

How does prolactin affect Ca balance?

A

Promotes calcium absorption from the gut by stimulating synthesis of calcitriol.

79
Q

What plasma proteins does Ca bind to?

A
  • Albumin (80%)

- Globulin (20%)

Systems: Endocrine AB (25 decks)

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