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part I > calcium + bones (biochem > Flashcards

calcium + bones (biochem Flashcards

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1
Q

physiological roles of calcium:

A
  • bone & teeth formation
  • muscle contraction
  • enzyme co-factor
  • essential formal blood clotting
  • intra- and extracellular messaging
  • stabilisation of membrane potentials
  • regulation of cell division, prolifertaion and apoptosis
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2
Q

where is calcium distributed?

A

99% skeleton
intracellular 1%
extracellular 0.1%

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3
Q

normal calcium range

A

2.2 - 2.6

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4
Q

how much calcium circulates round body freely (%)?

A

45%

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5
Q

which plasma proteins does calcium bind to?

A

albumin (80%)
globulins (20%)

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6
Q

average adult daily calcium requirement

which groups is this higher in?

A

700mg/ day

older adults, teenagers, lactating/ post menopausal women

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7
Q

which 3 hormones regulate calcium levels?

what is the effect on free serum calcium by each hormone?

A

PTH
vitamin D (calcitriol)
^^ increase serum Ca2+

calcitonin
decreases free serum Ca2+

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8
Q

calcium homeostasis diagram

A
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9
Q

which enzyme does PTH affect?

A

1a-hydroxylase

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10
Q

what reaction dose a1-hydroxylase catalyse

A

calcidiol to calcitriol

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11
Q

what does calcitriol do
1. in bone
2. intestine
3. kidney

A
  1. increases bone turnover (i.e. release of Ca2+)
  2. increases calcium absorption
  3. enhances Ca2+ and phosphate reabsorption in kidney
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12
Q

calcitonin role

where is it produced?

A

decreases serum Ca2+ concentration

c-cells of the thyroid gland

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13
Q

what is the role of fibroblast growth factor 23

A

^^bone reabsorption of calcium

reduces phosphate reabsorption

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14
Q

parathyroid glands:

  1. what do they produce
  2. embryological origin
  3. blood supply
A
  1. PTH
  2. pharyngeal pouches
  3. inferior thyroid arteries
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15
Q

which 2 types of cell do parathyroid glands contain?

A

oxyphil cells

chief cells - these synthesise and secrete PTH

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16
Q

PTH

what kind of hormone?

what receptor does it bind to?

which kind of cells secrete and synthesise PTH?

what is required for sustained release?

A

peptide hormone - therefore v short half-life

G-coupled protein receptor

chief cells

upregulation of gene expression (this increases gland size)

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17
Q

what initiates release of PTH?

A

CaSR - calcium sensing receptor

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18
Q

physiological action of PTH in kidney

pg 96

A
  1. increases Ca2+ absorbption in distal convuluted tubule (mediated by TRPV5)
  2. inhibits absorption of PO4 at proximal and distal convuluted tubule -
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19
Q

PTH
1. type of hormone
2. receptor
3. site of synthesis
4. signal for synthesis and/ or secretion

A
  1. peptide
  2. G protein coupled receptor (PTHR1 - parathyroid hormone receptor 1)
  3. chief cells in parathyroid
  4. low Ca2+
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20
Q

PTH physiological actions

on bone (1)
in kidney (3)

A

Bone: ^^ bone resorption
Kidney: ^^ PO4 excretion
Kidney: decreases Ca2+ excretion
Kidney: ^^ vitamin D activation

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21
Q

PTH net effect on calcium homeostasis

A

^^ Ca2+
decreases PO4 3-

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22
Q

calcitriol (vitamin D)
1. type of hormone
2. receptor
3. site of synthesis
4. signal for synthesis and/ or secretion

A
  1. secosteroid
  2. nucleor receptor (VDR)
    Hydroxylated
    (activated) in the
    proximal convoluted
    tubules of the kidney
    Extra-renal activation
    of vitamin D can also
    occur
  3. low Ca2+, low phosphate, PTH
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23
Q

normal vit D level

A

> 50

supplement if any less

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24
Q

physiolocial actions of calcitriol

bone(2)
GI tract (1)
kidney (1)

A

Bone: ^^ bone formation and
mineralisation
Bone: ^^ bone remodelling
GI tract: ^^ Ca2+ absorption
Kidney: ^^ Ca2+ and PO4
3–
reabsorption

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25
net effect of calcitriol on Ca2+ homeostasis
^^ serum Ca2+ ^^ serum phosphate
26
caclitonin 1. type of hormone 2. receptor 3. site of synthesis 4. signal for synthesis and/ or secretion
1. peptide 2. G-protein coupled receptor 3. c cells in the thyroid glands 4. high Ca2+
27
calcitonin physiological actions
Kidney: ^^ PO4 3– excretion Kidney: decreases Ca2+ reabsorption Bone: inhibits osteoclast function
28
calcitonin - net effect on Ca2+ homeostasis
vv serum Ca2+
29
primary hyperparathyroidism 1. what happens 2. most common cause
1. increased PTH secretion by parathyroid glands 2. benign tumour
30
secondary hyperparathyroidism 1. what happens 2. common cause 3. cx
1. low serum calcium stimulates PTH secretion/ production 2. CKD 3. serum calcium begins to rise causing tertiary hyperparathyroidism
31
where is calcium reabsorbed? by which mechanisms?
kidneys 1. proximal tubule (60-70%) paracellular transport, active and passive 2. TALH (20-25%) passive reabsorption 3. DCT (5-10%) active transport 4. collecting duct (0.5-1%) active transport
32
what facilitates calcium absorption from the intestine?
vitamin D
33
what are the 3 mechanisms of calcium reabsorption from the intestine:
1. paracellular transport (if hypocalcaemic also): 2. active uptake and extrusion 3. endo and exocytosis of Ca2+-CaBp complex
34
what protein does calcium bind to when it is absorbed
CaBP - calcium binding protein
35
which receptor is involved in calcium uptake from gut in hypocalcaemia? where is this present?
TRPV6 luminal surface of intestine
36
what are the 2 processes of active uptake and extrusion of calcium from the gut?
ATPase ion exchange with 3 Na+
37
vitamin D 1. name of active form 2. what kind of receptor does it bind to?
1. calcitriol 2. nuclear receptor - therefore has cell membrane and intracellular transport proteins
38
which enzyme catalyses vitamin D3 --> calidiol in liver
25-hydroxylase
39
which enzyme coverts calcidiol to calcitriol? where does this act?
1a-hydroxylase kidney
40
what does vitamin D do?
has endocrine and paracrine/ autocrine actions: 1. regulates Ca2+ uptake from gut and Ca2+ and PO4 reabsorption/ excretion 2. regulates immune system's response to infection/ inflammation
41
synthesis of vitamin D
1. dietary - D2&D3 (10%) 2. sunlight - 7-dehydrocholesterol to D3 (90%) both converted to calcidiol in liver then to calcitriol in: 1. kidney - endocrine - depends on serum vit D - bone calcium effects 2. non-renal tissues - paracrine/ autocrine - ? independent of serum D3 - immune system
42
normal vit D how common is deficiency in UK?
> 50 nmol/L 30-50 = insufficient <25-30 = deficient <10 = severe deficiency <50 requires supplementation 1 in 5
43
how much vitamin D should be supplemented during pre-conception, pregnancy and lactation?
400 IU/ day
44
phosphate what's its role?
1. important for intracellular metabolism (e.g. ATP synthesis) 2. needed for phosphorylation 3. phospholipids in membrance
45
what does phosphate balance depend on?
1. diet and uptake from gut 2. intracellular: extracellular movement 3. in and out of bone 4. urinary excretion - actively reabsorbed by PCT - only place of excretion = kidney
46
how much calcium does foetus contain? what are it's Ca levels vs mum pg 100
20-30g relatively hypercalcaemic To cope with the requirements of the fetus, the mother has decreased/normal levels of PTH, increased levels of calcitonin and increased levels of vitamin D
47
role of bone:
- support/ protection - movement - haematopoesis - mineral homeostasis: buffering Ca2+ and PO4
48
outside bone name inside bone name
1. cortical 2. trabecular
49
bone composition:
10% water 25% organic - type 1 collagen + NCPs 65% mineral - hydroxyapatite
50
bone repair
1. woven (weak) - rapid osteoid production, collagen haphazard 2. lamella (strong) parallel collagen (lamellae - sheets_ woven--> lamellar bone requires bone remodelling
51
BONE REMODELLING ....
osteoblasts trigger bone remodelling following injury by RANKL osteoclasts eat up old bone osteoblasts lay down new bone
52
what do osteoclasts do?
reabsorb old bone
53
what do osteoblasts do?
lay down new bone
54
what do osteoblasts secrete? what does it do?
RANKL protein that stimulates osteoclasts
55
what is secreted once there is adequate osteoclast activity? (in bone remodelling)
OPG (osteoprotegerin) binds to RANKL to reduce osteoclast activity
56
what do osteocytes secrete?
sclerostin FGF 23
57
what is the role of sclerostin? what is it inhibitted by?
stimulates osteoclastic activity inhibited by mechanical force
58
what is the role of FGF 23?
stimulates osteoblast activity
59
bone disorders: too much/ too little bone
too little bone = osteoporosis too much bone = osteopetrosis
60
bone disorders changes in bone structure: 1. mineral defect 2. collagen defect 2. rapid turnover due to overactive osteoclasts = poor quality woven bone
1. osteomalacia/ rickets 2. osteogenesis imperfecta 2. Paget's disease
61
rickets signs:
- bowing on weight bearing - growth plate elongated & widened - pigeon chest - short stature - misshaped skull - dental abnormalities - #s
62
osteoporosis incidence in >50
1 in 2 female 1 in 5 male
63
diagnostic criteria for osteoporosis = DEXA score (T score) what is t score? what is: i) normal t score ii) osteopenic t score iii) osteoporotic t score
T score - standard deviations vs adult at peak bone density >-1.0 normal -1.0 to -1.5 osteopenia <-2.5 osteopororsis
64
RF for osteoporosis
low BMD low body weight RA poor nutrition (vit D/ Ca2+ deficiency) physical inactivity smoking alcohol durgs - steroids, heparin
65
endocrine disorders that cause low BMD
hypogonadism hyperparathyroidism hyperthyroidism Cushing's
66
drug mgt osteoporisis
- bisphosphonates - SERMs - PTH (small pulses increase osteoblast activity) - denosumab HRT - only if other treaments fail , not licensed for osteoporosis specifically

part I (12 decks)

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