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2 - Calcium Homeostasis Flashcards

(66 cards)

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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
PTH has what effect on phosphate within the kidney? Why is this important?
Increases excretion. Don't want calcium / phosphate combining in blood = plaque formation.
26
What two minerals make hydroxyappatite?
Calcium | Phosphate
27
Graphically, what shape is the curve of calcium:PTH secretion?
steep-sigmoidal
28
What value is the 'Calcium set-point'? (mM)
1.2 mM
29
Draw Vitamin D synthesis pathway.
Cholesterol Intestine (pro-vitamin D3) Skin - UVB (pre-vitamin D3 --> Vit D3) Liver (+OH) (constitutive) --> Calcefidiol Kidney (+OH) (PTH) (1alpha-hydroxlase) --> Calcitriol
30
How does calcitriol increase serum calcium levels?
Increases calbindin expression. Thus, increases GI uptake.
31
Where else can calcitriol work?
Bone + kidney | amplifies effect of PTH
32
What protein carries vitamin D around the blood?
Vitamin D binding-protein
33
What is a deficiency of vitamin called?
Rickets
34
What two causes of rickets exist?
Insufficient proVit D intake Insufficient light exposure
35
What two conditions can arise from chronic calcium deficiency?
Secondary hyperparathyroidism Osteomalacia
36
What receptor does PTH bind to?
Type 1 PTH-receptor | PTH1R
37
What structure does PTH1R have?
7 transmembrane spanning protein
38
What type of receptor is PTH1R?
G protein-coupled Gs
39
Through what mechanism does PTH1R work through?
Adenylate cyclase cAMP PKA pathway
40
What is PTHrP and what type of effect does it have?
PTH-related peptide Paracrine effects - causes proliferation
41
Where is the PTH1R expressed?
Bone | Kidney
42
What two conditions arise from PTH-receptor mutations?
Jansen's metaphyseal... Blomstrands... Chrondodysplasia
43
Jansen's metaphyseal chondrodysplasia is what type of mutation? What phenotype?
Activating Short-limb dwarfism
44
Blomstrands chondrodysplasia is what type of mutation? Results in what phenotype?
Inactivating Early lethality / advanced bone maturation.
45
Mice K/o of PTH1-receptor results in what?
Early lethality
46
Activating the calcium receptor has what effect on PTH secretion?
Inhibits it
47
Low calcium levels have what effect on PTH secretion?
PERMITs it.
48
What 3 modulatory substances have an effect on the calcium receptor?
Agonists Positive allosteric modulators Negative allosteric modulators
49
Give 3 examples of Ca-receptor agonists
Cations (Ca2+ / Mg2+) Spermine Aminoglycosides (gentamycin)
50
How do positive allosteric modulators function?
They increase the receptor's sensitivity to an agonist
51
Give two examples of positive allosteric modulators of the calcium receptor
Calcimimetics (Cinacalcet) Aromatic amino acids
52
How do negative allosteric modulators function?
Decrease a receptor's sensitivity to an agonist
53
Give an example class of allosteric receptor modulators to the calcium receptor?
Calcilytics
54
What effect, therefore, do calcimimetics have on circulating calcium levels?
Decrease Ca levels
55
What effect do calcilytics have on circulating calcium levels?
Increase Ca levels
56
What conditions can be treated with calcimimetics?
Primary / Secondary hyperparathyroidism
57
What conditions can be treated with calcilytics?
Osteoporosis
58
Other than calcimimetis, what other supplement can you give to reduce PTH secretion?
Vitamin D
59
What does vitamin D have to be given with as a result of the physiological response to it?
Phosphate binders | vitamin D increases phosphate
60
What type of receptor is the vitamin D receptor?
Nuclear receptor
61
Where in the cell is the Vitamin D receptor found?
Cytosol
62
K/O of the vitamin D receptor results in what phenotype?
Rickets | infertility, alopecia
63
Where are the calcium receptors most highly expressed?
Parathyroid gland | Kidneys
64
Give two advantages of calcimimetics / calcilytics besides their function
1) Don't alter plasma concentrations of endogenous ligands | 2) Don't alter endogenous pathways
65
Give an example of a calcimimetic
Cinacalcet
66
Give an example of a calcilytic
NPS-2143

AE (7 decks)

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