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part I > calcium + bones (biochem > Flashcards

calcium + bones (biochem Flashcards

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
Q

net effect of calcitriol on Ca2+ homeostasis

A

^^ serum Ca2+
^^ serum phosphate

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26
Q

caclitonin
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
  3. c cells in the thyroid glands
  4. high Ca2+
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27
Q

calcitonin physiological actions

A

Kidney: ^^ PO4
3– excretion
Kidney: decreases Ca2+ reabsorption
Bone: inhibits osteoclast
function

28
Q

calcitonin - net effect on Ca2+ homeostasis

A

vv serum Ca2+

29
Q

primary hyperparathyroidism

  1. what happens
  2. most common cause
A
  1. increased PTH secretion by parathyroid glands
  2. benign tumour
30
Q

secondary hyperparathyroidism

  1. what happens
  2. common cause
  3. cx
A
  1. low serum calcium stimulates PTH secretion/ production
  2. CKD
  3. serum calcium begins to rise causing tertiary hyperparathyroidism
31
Q

where is calcium reabsorbed?

by which mechanisms?

A

kidneys
1. proximal tubule (60-70%)
paracellular transport, active and passive

  1. TALH (20-25%)
    passive reabsorption
  2. DCT (5-10%)
    active transport
  3. collecting duct (0.5-1%)
    active transport
32
Q

what facilitates calcium absorption from the intestine?

A

vitamin D

33
Q

what are the 3 mechanisms of calcium reabsorption from the intestine:

A
  1. paracellular transport

(if hypocalcaemic also):
2. active uptake and extrusion
3. endo and exocytosis of Ca2+-CaBp complex

34
Q

what protein does calcium bind to when it is absorbed

A

CaBP - calcium binding protein

35
Q

which receptor is involved in calcium uptake from gut in hypocalcaemia?

where is this present?

A

TRPV6

luminal surface of intestine

36
Q

what are the 2 processes of active uptake and extrusion of calcium from the gut?

A

ATPase

ion exchange with 3 Na+

37
Q

vitamin D

  1. name of active form
  2. what kind of receptor does it bind to?
A
  1. calcitriol
  2. nuclear receptor - therefore has cell membrane and intracellular transport proteins
38
Q

which enzyme catalyses vitamin D3 –> calidiol in liver

A

25-hydroxylase

39
Q

which enzyme coverts calcidiol to calcitriol?

where does this act?

A

1a-hydroxylase

kidney

40
Q

what does vitamin D do?

A

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
Q

synthesis of vitamin D

A
  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
Q

normal vit D

how common is deficiency in UK?

A

> 50 nmol/L

30-50 = insufficient
<25-30 = deficient
<10 = severe deficiency

<50 requires supplementation

1 in 5

43
Q

how much vitamin D should be supplemented during pre-conception, pregnancy and lactation?

A

400 IU/ day

44
Q

phosphate

what’s its role?

A
  1. important for intracellular metabolism (e.g. ATP synthesis)
  2. needed for phosphorylation
  3. phospholipids in membrance
45
Q

what does phosphate balance depend on?

A
  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
Q

how much calcium does foetus contain?

what are it’s Ca levels vs mum

pg 100

A

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
Q

role of bone:

A
  • support/ protection
  • movement
  • haematopoesis
  • mineral homeostasis: buffering Ca2+ and PO4
48
Q

outside bone name

inside bone name

A
  1. cortical
  2. trabecular
49
Q

bone composition:

A

10% water

25% organic - type 1 collagen + NCPs

65% mineral - hydroxyapatite

50
Q

bone repair

A
  1. woven (weak) - rapid osteoid production, collagen haphazard
  2. lamella (strong) parallel collagen (lamellae - sheets_

woven–> lamellar bone requires bone remodelling

51
Q

BONE REMODELLING ….

A

osteoblasts trigger bone remodelling following injury by RANKL

osteoclasts eat up old bone

osteoblasts lay down new bone

52
Q

what do osteoclasts do?

A

reabsorb old bone

53
Q

what do osteoblasts do?

A

lay down new bone

54
Q

what do osteoblasts secrete?

what does it do?

A

RANKL

protein that stimulates osteoclasts

55
Q

what is secreted once there is adequate osteoclast activity?

(in bone remodelling)

A

OPG (osteoprotegerin)

binds to RANKL to reduce osteoclast activity

56
Q

what do osteocytes secrete?

A

sclerostin
FGF 23

57
Q

what is the role of sclerostin?

what is it inhibitted by?

A

stimulates osteoclastic activity

inhibited by mechanical force

58
Q

what is the role of FGF 23?

A

stimulates osteoblast activity

59
Q

bone disorders:

too much/ too little bone

A

too little bone = osteoporosis

too much bone = osteopetrosis

60
Q

bone disorders
changes in bone structure:

  1. mineral defect
  2. collagen defect
  3. rapid turnover due to overactive osteoclasts = poor quality woven bone
A
  1. osteomalacia/ rickets
  2. osteogenesis imperfecta
  3. Paget’s disease
61
Q

rickets signs:

A
  • bowing on weight bearing
  • growth plate elongated & widened
  • pigeon chest
  • short stature
  • misshaped skull
  • dental abnormalities
  • # s
62
Q

osteoporosis incidence in >50

A

1 in 2 female
1 in 5 male

63
Q

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

A

T score - standard deviations vs adult at peak bone density

> -1.0 normal
-1.0 to -1.5 osteopenia
<-2.5 osteopororsis

64
Q

RF for osteoporosis

A

low BMD
low body weight
RA
poor nutrition (vit D/ Ca2+ deficiency)
physical inactivity
smoking
alcohol
durgs - steroids, heparin

65
Q

endocrine disorders that cause low BMD

A

hypogonadism
hyperparathyroidism
hyperthyroidism
Cushing’s

66
Q

drug mgt osteoporisis

A
  • 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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