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endocrine system 1 > 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
  • exocytosis of synaptic vesicles eg 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 in bone giving strength to 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

increased neuronal Na+ permeability = hyperexcitation of neurons

  • can cause tetany
  • if spread to larynx and respiratory muscles -> asphyxiation.
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7
Q

How can hypercalcaemia lead to cardiac arrhythmias?

A

decreased neuronal Na+ permeability = reduce excitability and depress neuromuscular activity
- can 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

- only 0.05% of the calcium in the body is free in solution and physiologically active

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11
Q

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

A
  • ~1Kg (99%) 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%)

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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 (0.1%)

- 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

[Ca2+ ]plasma is ~2.4mM

  • 40% is bound to plasma proteins
  • 50% (~1.2mM) is physiologically active & free ionised
  • 10% binds to plasma anions
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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

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+
  • plasma Ca concentration falls
  • may precipitate hypocalcaemic tetany
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24
Q

What happens to Ca in acidosis?

A
  • binding capacity reduces

- free [Ca2+]plasma rises

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25
Q

What is total Ca determined by?

A

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
  • 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
  • bone-building cells

- highly active cells lay down a collagen extracellular matrix and then calcify it

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29
Q

What are osteocytes?

A

Differentiated osteoblasts

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30
Q

What do osteocytes do?

A
  • less active than osteoblasts

- regulate activity of osteoblasts and osteoclasts

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31
Q

What are osteoclasts?

A

cells responsible for mobilizing bone

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32
Q

What do osteoclasts do?

A
  • secrete H+ ions (pH 4) to dissolve calcium salts

- 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
  • usually 4 lying on the posterior surface of the thyroid gland
  • 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

decrease in free [Ca2+ ]plasma

36
Q

What does PTH act to do?

A

to increase free [Ca2+ ]plasma

37
Q

How does PTH increase free [Ca]plasma?

A
  • stimulates osteoclasts to increase resorption (release) of Ca2+ and phosphate in bone (effects seen within 12-24hrs)
  • inhibits osteoblasts to reduce Ca2+ deposition in bone
  • increases reabsorption of Ca2+ from the kidney tubules, decreasing its excretion in the urine
  • increases renal excretion of phosphate, elevating free [Ca2+ ] by preventing it from being deposited back into bone (process requires phosphate)
  • stimulates 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
  • active vitamin D3 is a steroid hormone produced in two steps 1. liver 2. kidneys
  • from inactive vitamin D3 (cholecalciferol) found in the diet or the skin
  • latter requires UV light on skin to form
41
Q

What stimulates the formation of calcitriol in lactating women?

A

Prolactin

42
Q

How is active vitamin D3 formed?

A
  • from cholesterol derivatives by the action of UV light on the skin
  • 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

complement those of PTH and increase [Ca2+ ]plasma

47
Q

What happens to most of the calcium from our diet?

A

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
  • increase in PTH -> an increase in calcitriol -> increase in intestinal absorption of Ca2+
    or
  • increase in levels of plasma Ca2+ -> inhibit PTH -> 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 (calcitriol)

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

> 65 years

  • reduced gut absorption
  • reduced Ca2+ mobility
58
Q

What is the direct effect of vitamin D3?

A

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+]
  • increase mineralization of bone
60
Q

Why are bones soft/bent in vitamin D3 deficiency?

A
  • PTH works hard to maintain plasma [Ca2+]
  • continually removes Ca2+ from bone
  • bones which are soft and still growing -> 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
  • intestinal malabsorption of Ca2+ -> decreases [Ca2+ ]plasma
  • increases PTH -> 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
  • increased [Ca2+]plasma
69
Q

What are the main actions of calcitonin?

A
  • bind to osteoclasts and inhibit bone resorption

- 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
  • no abnormalities of bone structure
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
  • reduces intestinal absorption of Ca2+
    = decreased plasma [Ca2+ ]
    = increased PTH
    = 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
  • 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%)

endocrine system 1 (25 decks)

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