Calcium Homeostasis Flashcards

1
Q

What are some roles of calcium in the body?

A

Signalling

Blood clotting

Apoptosis

Skeletal strength

Membrane excitability

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2
Q

How does calcium have a signalling role?

A

Important for exocytosis of vesicles such as neurotransmitters and hormones

Or contractile muscle fibres

Or altering enzyme function

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3
Q

How does calcium have a membrane excitability role?

A

Calcium decreases sodium permeability

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4
Q

What effect does hypocalcaemia have on neuronal sodium pereability?

A

Increases Na permeability leading to hyperexcitation of neurons, in extreme cases tetany

If spreads to larynx and respiratory muscles causes asphyxiation

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5
Q

What effect does hypercalcaemia have on sodium permeability?

A

Decreases Na permeability which will reduce excitability and depress neuromusculae activity

In extreme cases will trigger cardiac arrhythmias

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6
Q

How is calcium distributed in the body?

A

Bone 99%

Intracellular 0.9%

Extracellular 0.1%

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7
Q

What does the weight of calcium in bone weigh?

A

About 1kg

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8
Q

How is calcium stored in bone?

A

Stored in calcified extracellular matrix mostly in the form of hydroxyapatite, so phosphate homeostasis is also important in determining calcium balance

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9
Q

Where is most of the intracellular calcium stored?

A

Inside mitochondria and sarcoplasmic reticulum

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10
Q

What percentage of extracellular calcium is bound to protein?

A

Nearly 50%

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11
Q

What calcium in the body is free and physiologically active?

A

The 50% of extracellular calcium that is not attached to proteins (0.05% of total body calcium)

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12
Q

Why does calcium have a very large affinity for proteins?

A

Small positive charge attrached to large negative charge

So in plasma 40% is bound to proteins

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13
Q

Explain the distribution of extracellular calcium stores?

A

Protein bound 40%

Free (ionised) 50%

Complexed 10%

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14
Q

What proteins is extracellular calcium bound to?

A

Albumin 80%

Globulin 20%

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15
Q

What changes the binding capacity of calcium to plasma proteins?

A

pH

Binding capacity is increased under alkalotic conditions

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16
Q

How does hyperventilation impact the binding of calcium to plasma proteins?

A

Hyperventilation raises plasma pH

Less calcium binds to proteins

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17
Q

Why do alkalotic conditions increase binding capacity of calcium to plasma proteins?

A

Less hydrogen ions to complete with for negative binding spots of plasma protein

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18
Q

What is increased pH known as?

A

Alkalosis

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19
Q

What is decreased pH known as?

A

Acidosis

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20
Q

What is the total body calcium determined by?

A

Calcium from diet and calcium excreted at kidneys and faeces

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21
Q

What is more important, calciums role in bone to provide mechanical support or maintaining calcium balance for physiological activites?

A

Maintaining calcium balance

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22
Q

What are osteoblasts?

A

Bone building cells, highly active cells which lay down a collagen extracellular matrix which will then calcify

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23
Q

What do osteoblasts differentiate into?

A

Osteocytes in established bone, which are much less active but appear to regulate the activity of osteoblasts and osteoclasts

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24
Q

What are osteoclasts?

A

Cells that mobilise bone, secrete H+ ions (pH about 4) to dissolve the calcium salts and produce proteolytic enzymes to digest extracellular matrix

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25
Q

What are the 2 key hormones that act to increase [Ca2+]plasma?

A

Parathyroid hormone (PTH)

Calcitol

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26
Q

What does PTH stand for?

A

Parathyroid hormone

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27
Q

What class of hormone of PTH?

A

Peptide hormone produced by parathyroid glands

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28
Q

What is calcitol?

A

Active form of vitamin D3

29
Q

What class of hormone is caltisol?

A

Steroid hormone produced from vitamin D by liver and kidneys

30
Q

What is caltisol produced from?

A

Vitamin D by liver and kidneys

31
Q

How many parathyroid glands are there?

A

Usually 4 but can vary

32
Q

What is parathyroid hormone released in response to?

A

Decrease in free [calcium]plasma

33
Q

Explain the effects of PTH?

A
  1. Stimulating osteoclasts to increase resorption (release) of calcium and phosphate in bone (effects seen within 12-24 hours)
  2. Inhibiting osteoblasts to reduce calcium deposition in bone
  3. Increasing reabsorption of calcium from kidney tubules, therefore decreasing its excretion in urine
  4. Increasing renal excretion of phosphate, elevating free calcium by preventing it from being deposited back into bone (a process that requires phosphate)
  5. Stimulates kidney to synthesis calcitriol from vitamin D which promotes calcium absorption at the gut and kidney
34
Q
A
35
Q

What effect does PTH have on bone?

A

Stimulate osteoclasts to increase resorption (release of calcium)

Stimulates osteoblasts to reduce calcium deposition in bone

36
Q
A
37
Q

What effect does PTH have on the kidneys?

A

Increase reabsorption of calcium from kidney tubules, decreasing its excretion in urine

Increase renal excretion of phosphate, elevating free calcium by preventing it from being deposited back into bone (process that requires phosphate)

Stimulates synthesis of calcitrol form vitamin D which promotes calcium absorption at the gut and kidney

38
Q

What is calcitriol also known as?

A

Also known as active vitamin D3 or 1, 25 dihydroxycholecalciferol (1,25(OH)2D3)

39
Q

What is the ultimate effect of calcitriol?

A

Compliments the action of PTH, so increases calcium in plasma

40
Q

Where does each stemp of calcitirol formation take place?

A

Step 1 in liver

Step 2 in kidneys

41
Q

What is formation of calcitriol stimulated by?

A

Sunlight on skin

Hormone prolactin in lactating woman

42
Q

What is active vitamin D3 formed from?

A

Cholesterol deriviatives from UV action on skin

Also from diet

43
Q

Is vitamin D a fat soluble vitamin?

A

Yes

44
Q

What are some diatery sources of vitamin D?

A

Fatty fish such as mackeral or tuna

Fish liver oils

Egg yolks

45
Q

What does calcitriol bind to?

A

Nuclear receptors in target tissues (intestine, bone and kidneys)

46
Q

What is the effect of calcitriol?

A

Increase absorption of calcium from gut

Facilitate renal absorption of calcium

Mobilises calcium stores in bone by stimulating osteoclast activity

47
Q

What are the active transport systems in the gut that moves calcium from intestine lumen to blood under the control of?

A

Calcitriol

48
Q

Why does prolactin stimulate calcitriol synthesis?

A

Increased demand for calcium for milk production in lactation

49
Q

What controls the proportion of dietary calcium absorbed from intestine?

A

Circulating levels of calcitriol

50
Q

When does vitamin D deficiency occur?

A

When circulating levels fall less than 20ng/ml

51
Q

Where is vitamin D normally stored?

A

Extensively in fat

52
Q

What percentage of Scots are vitamin D deficient?

A

75% in summer, rising to 92% in winter

53
Q

Is vitamin D deficiency more prevalent in older or younger people, and why?

A

People over 65 due to reduced gut absorption and reduced calcium mobility

54
Q

What impact does vitamin D3 deficiency have on bone?

A

PTH works hard to miantian plasma calcium and in doing so continually removes calcium from bone resulting in soft bone, and if still growing can become bent

55
Q

What bone conditions are caused by vitamin D3 deficiency in adults and children?

A

Adults - osteomalacia

Children - rickets

56
Q

How does vitamin D3 deficiency lead to phosphate deficiency?

A

Vitamin D3 deficiency -> intestinal malabsorption of calcium, lowering calcium in plasma which increases PTH -> which promotes phosphate deficiency – aggravating calcium loss from bone:

57
Q

Who is most at risk of vitamin D deficiency?

A

Asian populations and elderly:

  • chapatti flour contains phytate which binds to dietary calcium
  • pigmented skin is less able to make vitamin D3 in response to UV light
58
Q

What is the one key hormone that acts to decrease calcium plasma levels?

A

Calcitonin

59
Q

What class of hormone is calcitonin and what is it produced by?

A

Peptide hormone produced by thyroid gland

60
Q

What is secretion of calcitonin stimulated by?

A

Increased calcium in plasma

61
Q

What is the main action of calcitonin?

A

Bind to osteoclasts and inhibit bone resorption as well as increase renal excretion preventing further build up of calcium

62
Q

What can calcitonin be used to treat?

A

Paget’s diseae (overactive osteoclasts)

63
Q

Is calcitonin important in humans?

A

Research suggests not as its effects are overridden by PTH

64
Q

Other than PTH, calcitriol and calcitonin, what other hormones act to alter calcium balance?

A

Cortisol

Insulin

Oestrogen

Growth hormone

Prolactin

65
Q

How does cortisol affect calcium balance?

A

Inhibits osteoblasts, increases renal excretion of calcium and phosphate and reduces intestinal absorption of calcium (decreasing serum calcium, increasing PTH and increasing bone resorption)

Together with reduce bone formation over time can produce osteoporosis

66
Q

How does insulin affect calcium balance?

A

Increase bone formation and antagonises the action of cortisol

Diabetes have significant bone loss

67
Q

How does oestrogen affect calcium balance?

A

Promotes bone formation via oestrogen recceptors on osteoblasts

Post-menopausal osteoporosis is a major problem

68
Q

How does growth hormone impact calcium balance?

A

Constant stimulus for bone formation

69
Q

How does prolactin affect calcium balance?

A

Promotes calcium absorption from gut by stimulating synthesis of calcitriol