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AE > 2 - Calcium Homeostasis > Flashcards

2 - Calcium Homeostasis Flashcards

1
Q

What 3 symptoms occur from hypocalcaemia?

A

Tetany (spasms)
Cardiac arrhythmia
Asphyxiation (diaphragmatic spasm)

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2
Q

What effect on nerves does hypocalcaemia have?

A

Increased nerve excitability

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3
Q

What complication can occur from hypocalcaemia?

A

Death by asphyxiation (diaphragmatic spasm)

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4
Q

What effect does hypercalcaemia have on nerves?

A

Decreased neuromuscular excitability

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5
Q

What symptoms / features occur with hypercalcaemia?

A

Cardiac arrhythmias
Lethargy
Death

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6
Q

In the context of plasma calcium, what percentages are distributed where?

  • Bound to albumin?
  • Bound to HCO3 / PO4?
  • Free ionised?
A

Albumin: 35-40%
HCO/PO4: 5%
Free ionised: 50%

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7
Q

What % of calcium is hed within bones and teeth? and in what form?

A

99%

Hydroxyapatite

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8
Q

How much calcium is consumed per day on average?

A

1g

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9
Q

What percentage of dietary calcium passes straight through?

A

80%

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10
Q

How much calcium is absorbed on average?

A

35%

350mg

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11
Q

How much calcium is secreted from our gut?

A

15%

150mg

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12
Q

What two ways is calcium lost through the gut?

A

Bile salts

Sloughed off

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13
Q

What mass of calcium is in the blood (ECF) at any one moment?

A

1g

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14
Q

Which organ is the main regulator of calcium levels?

A

Parathyroid gland

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15
Q

What cells within the parathyroid gland produce parathyroid hormone (PTH) ?

A

Chief cells

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16
Q

What 2 cleavage steps results in PTH as a product?

A

Pre-pro PTH
Pro-PTH
PTH

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17
Q

How long is PTH’s half-life?

A

20 mins

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18
Q

Where does PTH cleavage occur in the body?

A

Liver

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19
Q

What relationship does PTH secretion have with serum calcium levels?

A

Inversely proportional

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20
Q

Structurally, what is the necessity behind constant bone formation and resorption?

A

Exposure to microfractures, which would accumulate over time.

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21
Q

Formation of bone requires 2 things - what are they?

A

Minerals (Ca2+)

Holes

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22
Q

How is PTH secreted from the parathyroid gland?

A

Pulsatile manner

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23
Q

What effect does PTH have on calcium levels?

A

Increases them

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24
Q

Through what 3 mechanisms does PTH stimulate the increase in circulating calcium levels?

A

1) Increase bone resorption
2) Increase renal reabsorption / decreasing excretion
3) Increasing production of vitamin D

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25
Q

PTH has what effect on phosphate within the kidney?

Why is this important?

A

Increases excretion.

Don’t want calcium / phosphate combining in blood = plaque formation.

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26
Q

What two minerals make hydroxyappatite?

A

Calcium

Phosphate

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27
Q

Graphically, what shape is the curve of calcium:PTH secretion?

A

steep-sigmoidal

28
Q

What value is the ‘Calcium set-point’? (mM)

A

1.2 mM

29
Q

Draw Vitamin D synthesis pathway.

A

Cholesterol

Intestine (pro-vitamin D3)

Skin - UVB (pre-vitamin D3 –> Vit D3)

Liver (+OH) (constitutive) –> Calcefidiol

Kidney (+OH) (PTH) (1alpha-hydroxlase) –> Calcitriol

30
Q

How does calcitriol increase serum calcium levels?

A

Increases calbindin expression.

Thus, increases GI uptake.

31
Q

Where else can calcitriol work?

A

Bone + kidney

amplifies effect of PTH

32
Q

What protein carries vitamin D around the blood?

A

Vitamin D binding-protein

33
Q

What is a deficiency of vitamin called?

A

Rickets

34
Q

What two causes of rickets exist?

A

Insufficient proVit D intake

Insufficient light exposure

35
Q

What two conditions can arise from chronic calcium deficiency?

A

Secondary hyperparathyroidism

Osteomalacia

36
Q

What receptor does PTH bind to?

A

Type 1 PTH-receptor

PTH1R

37
Q

What structure does PTH1R have?

A

7 transmembrane spanning protein

38
Q

What type of receptor is PTH1R?

A

G protein-coupled

Gs

39
Q

Through what mechanism does PTH1R work through?

A

Adenylate cyclase
cAMP
PKA pathway

40
Q

What is PTHrP and what type of effect does it have?

A

PTH-related peptide

Paracrine effects - causes proliferation

41
Q

Where is the PTH1R expressed?

A

Bone

Kidney

42
Q

What two conditions arise from PTH-receptor mutations?

A

Jansen’s metaphyseal…

Blomstrands…

Chrondodysplasia

43
Q

Jansen’s metaphyseal chondrodysplasia is what type of mutation?

What phenotype?

A

Activating

Short-limb dwarfism

44
Q

Blomstrands chondrodysplasia is what type of mutation?

Results in what phenotype?

A

Inactivating

Early lethality / advanced bone maturation.

45
Q

Mice K/o of PTH1-receptor results in what?

A

Early lethality

46
Q

Activating the calcium receptor has what effect on PTH secretion?

A

Inhibits it

47
Q

Low calcium levels have what effect on PTH secretion?

A

PERMITs it.

48
Q

What 3 modulatory substances have an effect on the calcium receptor?

A

Agonists

Positive allosteric modulators

Negative allosteric modulators

49
Q

Give 3 examples of Ca-receptor agonists

A

Cations (Ca2+ / Mg2+)

Spermine

Aminoglycosides (gentamycin)

50
Q

How do positive allosteric modulators function?

A

They increase the receptor’s sensitivity to an agonist

51
Q

Give two examples of positive allosteric modulators of the calcium receptor

A

Calcimimetics (Cinacalcet)

Aromatic amino acids

52
Q

How do negative allosteric modulators function?

A

Decrease a receptor’s sensitivity to an agonist

53
Q

Give an example class of allosteric receptor modulators to the calcium receptor?

A

Calcilytics

54
Q

What effect, therefore, do calcimimetics have on circulating calcium levels?

A

Decrease Ca levels

55
Q

What effect do calcilytics have on circulating calcium levels?

A

Increase Ca levels

56
Q

What conditions can be treated with calcimimetics?

A

Primary / Secondary hyperparathyroidism

57
Q

What conditions can be treated with calcilytics?

A

Osteoporosis

58
Q

Other than calcimimetis, what other supplement can you give to reduce PTH secretion?

A

Vitamin D

59
Q

What does vitamin D have to be given with as a result of the physiological response to it?

A

Phosphate binders

vitamin D increases phosphate

60
Q

What type of receptor is the vitamin D receptor?

A

Nuclear receptor

61
Q

Where in the cell is the Vitamin D receptor found?

A

Cytosol

62
Q

K/O of the vitamin D receptor results in what phenotype?

A

Rickets

infertility, alopecia

63
Q

Where are the calcium receptors most highly expressed?

A

Parathyroid gland

Kidneys

64
Q

Give two advantages of calcimimetics / calcilytics besides their function

A

1) Don’t alter plasma concentrations of endogenous ligands

2) Don’t alter endogenous pathways

65
Q

Give an example of a calcimimetic

A

Cinacalcet

66
Q

Give an example of a calcilytic

A

NPS-2143

AE (7 decks)

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