Calcium and its control Flashcards

1
Q

What is normal serum calcium conc.?

A

2.2 - 2.6 mM

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2
Q

What are the different forms of serum calcium?

A

Free ionised calcium

Bound to plasma proteins

Bound to citrate

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3
Q

What is the concentration of free ionised calcium in the blood?

A

1 - 1.3mM

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4
Q

Which form of serum calcium is the biologically active one?

A

Free ionised calcium is biologically active

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5
Q

What is the mass of calcium in a human adult?

A

1kg = 1000g

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6
Q

Where is most of the calcium in the human body contained?

A

Bones forming the skeleton

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7
Q

In what form is calcium stored in bones?

A

Calcium hydroxyapatite crystals

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8
Q

What is the function of the skeleton? Which function is more improtant?

A

Structural support

Reserve of calcium - priority

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9
Q

How does the skeleton act as a reserve of calcium?

A

Exchange of calcium phosphate between the bones and the interstitial fluid

  • bones release it
  • bones take it up
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10
Q

What is the normal daily intake of calcium?

A

1g

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11
Q

How is calcium lost from the body? How much?

A

Urinary loss - 175mg

GI loss - 825mg

altogether 1g is lost

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12
Q

What are the molecules involved in the regulation of calcium levels?

A

Parathyroid hormone

Vitamin D

Calcitonin

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13
Q

What types of cells is the parathyroid gland made up of? Which cells form most of it?

A

Chief cells - form most of parathyroid gland

Oxyphil cells

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14
Q

What do chief cells look like?

A

Darker pink
Visible nuclei
Less cytoplasm

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15
Q

What do oxyphil cells look like?

A

Lighter pink

More cytoplasm

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16
Q

What additional structures do the parathyroid glands have?

A

Outer capsule

Inner adipose tissue

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17
Q

What is the function of chief cells?

A

Produce PTH

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18
Q

How often is PTH synthesised?

A

Continuously

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19
Q

How often is PTH stored?

A

Not stored

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20
Q

What type of hormone is PTH?

A

Polypeptide hormone

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21
Q

What is the structure of PTH?

A

Straight chain

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22
Q

Briefly outline how PTH is produced

A

Pre-pro-PTH is produced
cleaved twice to remove signal peptide, remove other parts of it
to give PTH

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23
Q

How is PTH carried in the blood?

A

Is water-soluble

dissolves in plasma

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24
Q

What is the half life of PTH?

A

Approx 5 mins - relatively short

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25
Q

What are the target organs of PTH?

A

Bone

Gut

Kidney

26
Q

How does PTH affect bone?

A

Increases resorption of bone

27
Q

How does PTH give resorption of bone?

A

Stimulates osteoblasts to produce cytokines

  • cytokines cause osteoclasts to differentiate and increase in activity
  • cytokines protect osteoclasts from apoptosis

Decreases activity of osteoblasts

28
Q

How long goes it take for PTH to give bone resorption?

A

1-2 hours

29
Q

What effect does PTH have on the gut?

A

Indirect effects on the gut

because stimulates second hydroxylation reaction
25-hydroxyvitamin D —–> calcitriol

and calctriol increases calcium absorption in the gut

30
Q

How is calcium normally absorbed in the gut?

A

Paracelullar uptake

31
Q

Is paracellular uptake of calcium in the gut effective?

A

No, is ineffective

32
Q

How does calcitriol give increased calcium absorption in the gut?

A

Increases transcellular uptake

33
Q

How does PTH affects the kidneys?

A

Stimulates reabsorption of calcium from the ascending limb and distal convoluted tubule

Gives excretion of phosphate

Affects magnium reabsorption, excretion

34
Q

What is the purpose of PTH increasing phosphate excretion?

A

To prevent calcium phosphate forming in the kidneys

would form stones in the kidneys

35
Q

How is secretion of PTH controlled?

A

Serum calcium levels

36
Q

What type of receptor is the parathyroid gland calcium receptor? What cascade of events does it cause?

A

GPCR Gaq

Increased intracellular calcium

37
Q

How do high serum calcium levels affect PTH secretion?

A
Increased GPCR activation 
increase in intracellular calcium
decreases PTH secretion
-decrease gene transcription 
-inhibit release of PTH
38
Q

How do low serum calcium levels affect PTH secretion?

A

Decreased GPCR activation
decrease in intracellular calcium
increases PTH secretion
-increases survival of mRNA

39
Q

How is PTH degraded?

A

PTH in parathyroid gland cleaved by chief cells

Released PTH is cleaved by the liver

40
Q

How do serum calcium levels affect PTH degradation?

A

High serum calcium levels

increases PTH cleavage by chief cells in parathyroid gland

41
Q

What are the inactive forms vitamin D?

A

D3 cholecalciferol

D2 ergocalciferol

42
Q

What is the body’s source of D3 cholecalciferol?

A

Exposed to sunlight

cholesterol used to synthesise D3 cholecalciferol

43
Q

What is the body’s source of D2 ergocalciferol?

A

D2 ergocalciferol from yeast and fungi
added to foods
e.g. margarine, butter, cheese

44
Q

What is the active form of vitamin D?

A

Calcitriol

45
Q

What are D3 cholecalciferol and D2 ergocalciferol converted into?

A

Calcitriol

46
Q

How are D3-cholecalciferol/D2-ergocalciferol converted into calcitriol?

A

Two hydroxylation reactions
D3-choleciferol/D2-ergocalciferol —–> 25-hydroxyvitamin D
25-hydroxyvitamin D ——> calcitriol

47
Q

Where does the first hydroxylation reaction
D3-cholecalciferol/D2-ergocalciferol —–> 25-hydroxyvitamin D
occur?

A

Liver

48
Q

How long can 25-hydroxyvitamin D stay in the liver?

A

2 weeks

49
Q

Where does the second hydroxylation reaction

25-hydroxyvitamin D —–> calcitriol occur?

A

Kidney

proximal convoluted tubule

50
Q

How does 25-hydroxyvitamin D reach the PCT in the kidneys?

A

Bound to carrier protein

small enough to be filtered by glomerulus

51
Q

What enzyme catalyses the reaction 25-hydroxyvitamin D —–> calcitriol?

A

1alpha-hydroxylase

52
Q

What is the half life of calcitriol?

A

6 hours

53
Q

How do serum calcium levels affect vitamin D formation?

A

High serum calcium levels inhibit second hydroxylation reaction
25-hydroxyvitamin D —–> calcitriol

54
Q

How does PTH affect calcitriol formation?

A

High PTH levels stimulate second hydroxylation reaction

25-hydroxyvitamin D —–> calcitriol

55
Q

How is active vitamin D3 transported in the blood?

A

Bound to carrier protein transcalciferin

Small amount is free

56
Q

What are the target organs of active vitamin D? How does it affect them?

A

Bone - stimulates resorption of bone

Kidneys - stimulates reabsorption of calcium

GI - stimulates absorption of calcium by transcellular uptake

57
Q

What produces calcitonin?

A

Parafollicular cells in the thyroid gland

58
Q

What is the function of calcitonin?

A

Reduces serum calcium conc.

59
Q

How effective is calcitonin in humans?

A

Has limited effect

60
Q

How fast or slow does calcitonin have effects?

A

Rapid acting

61
Q

How is calcitonin used clinically?

A

In hypercalcaemia, to rapidly lower serum calcium concs.

62
Q

What effect does calcitonin have in pregnancy?

A

Maintains maternal bones of skeleton maybe