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imed3003 > Bone physiology and Calcium Metabolism > Flashcards

Bone physiology and Calcium Metabolism Flashcards

1
Q

What is bone composed of?

A

Bone comprises the largest proportion of the body’s connective tissue mass.

Consists of:

Cellular component

and

Extracellular matrix

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2
Q

How is bone different to other connective tissue matrices?

A

It is physiologically mineralised and constantly regenerates throughout life

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3
Q

What are the functions of bone?

A

Structural: providing mobility for muscle attachments as well as mechanical support

Protection: cranial and thoracic

Primary mineral reservoir

Haematopoiesis

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4
Q

What kind of material is bone?

A

It is a composite material Consisting of mineral, collagen and non-collagenous protein and lipids

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5
Q

What is the inorganic (mineral) phase of bone for?

A

Strength and rigidity

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6
Q

What is inorganic phase of bone made up of?

A

Nanocrystalline analogue of hydroxyapatite

Mineral substitutes Mg, Na, K, CO3, Fl, heavy metals

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7
Q

What is the organic phase made up of?

A

Predominantly type 1 collagen

Non-collagenous proteins

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8
Q

What is the purpose of the organic phase?

A

Resilience and flexibility

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9
Q

What are the types of bones?

A

Cortical (80% of skeleton)

Cancellous (trabecular/spongy)

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10
Q

What is contained in the cortical bone?

A

Osteons or haversian systems

Outer border defined by cement lines

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11
Q

What is the size and shape of bone suited for?

A

Size and shape of bone best fits function

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12
Q

What guide changes in bone?

A

Modelling (shaping)

Remodelling (resurfacing)

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13
Q

What is the formation of new bone at one site and removal of old bone from another site within the same bone called?

A

Modelling

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14
Q

What is removal and replacement of bone at the same site called?

A

Remodelling

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15
Q

When does modelling take place?

A

Bones grow in size and shift in space via this process

During childhood formation of new bone occurs in outer periosteal surface

At puberty bones get thicker and formation of bone on both the outer and inner surfaces

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16
Q

When does remodelling occur?

A

Remodelling occurs throughout life

Bone reaches peak mass by the early 20s

Most of the adult skeleton is replaced every 10 years

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17
Q

What is the purpose of bone remodelling?

A

Allows repair of microscopic areas of damage within bone to maintain skeletal strength

Allows release of calcium to maintain serum calcium levels

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18
Q

What is cellular communication coupling between resident cells?

A

Intercellular communication that occurs directly or indirectly which can initiate various responses within different cells.

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19
Q

What is a basic multicellular unit (BMU)?

A

Local collection of osteocytes, osteoblasts and osteoclasts work together to control bone formation and resorption creating a functional unit.

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20
Q

What are osteoblasts?

A

Mesenchymal “osteoprogenitor” cells and bone-lining cells

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21
Q

What is the morphology of osteoblasts like?

A

Plump and polygonal

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22
Q

What is the function of osteoblasts?

A

To synthesize bone matrix. They lay down ECM and that is then mineralized to form bone.

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23
Q

What is a new bone matrix that hasn’t been mineralised yet called?

A

Osteoid

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24
Q

How do osteoblasts regulate osteoclast formation?

A

Osteoblasts produce M-CSF and RANKL which bind to c-fms and RANK receptors respectively.

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25
Q

How do osteoblasts communicate with osteocytes?

A

Via gap junctions

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26
Q

What are the types of bone deposition?

A

Woven: primary bone, random collagen weave, mechanically weak

Lamellar bone: Secondary bone created by remodelling of woven bone into sheets that are mechanically strong.

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27
Q

Where do osteocytes come from?

A

Entombed osteoblasts residing in bone matrix residing in lacunae become osteocytes.

28
Q

What do osteocytes look like?

A

Spider like dendritic processes which radiate through the bone in tiny canals called canaliculi

29
Q

What are osteocytes?

A

Most abundant bone cells

30
Q

What do osteocytes do?

A

They function as a network

They regulate bone formation

Control calcium and phosphate levels

Mechanotransduction

Inhibit bone formation via sclerostin

31
Q

What does sclerostin do?

A

Inhibits bone formation

32
Q

How do osteocytes communicate and exchange nutrients with each other?

A

Via gap junctions and hemichannels (called connexin 43 found in dendrites of osteocytes)

33
Q

What is the origin of osteoclasts?

A

Haematopoietic (fused mononuclear progenitors (monocytes - macrophages)

34
Q

What cytokines drive osteoclast formation?

A

Macrophage colony stimulating factor (M-CSF)

Receptor Activator of NFkappaB ligand (RANKL) binds to RANK receptor and drives cell differentiation and fusion.

35
Q

How is formation of osteoclasts regulated?

A

By RANK/RANKL/OPG signalling axis

36
Q

What is OPG?

A

Osteoprotegerin - a soluble decoy receptor for RANKL expressed by osteoblasts to decrease number of osteoclasts

37
Q

How do osteoclasts differentiate?

A

Stem cell (osteoclast progenitor stem cell) contains RANK receptor

Osteoblast contains M-CSF which binds to c-FMS on osteoclast progenitor receptor.

M-CSF binds to C-Fms on osteoclast progenitor which converts it into osteoclast precursor and then into osteoclast

RANKL activates NFkappaB ligand by binding to RANK receptor which drives cell differentiation and fusion

Osteoprotegrin is produced by osteoblasts to decrease binding of RANKL to RANK thus decreasing osteoclast formation

38
Q

What is the bone resorption cycle?

A

Attachment (attachment of RGD peptides and integrins to bone surface) sealing zone or active zone is formed

Polarization (Cytoskeleton reorganisation or sealing zone, a ruffled border is formed because of cytoskeleton changes increasing surface area of osteoclast degradation)

Resorption (Inorganic/organic phase degraded to form different metabolites)

Removal (Transcytosis of products)

39
Q

How are the inorganic and organic borders degraded by osteoclasts?

A

Inorganic matrix degradation: Dimineralisation of hydroxyapatite via H+ and Cl-

Organic matrix degradation: Cathepsins (K) - Type I collagenase and TRAP - Tartrate Resistant Acid Phosphatase

40
Q

How does bone remodelling occur?

A

In a cyclical manner: Activation - Resorption - Formation (ARF) cycle.

Activation triggered by osteocyte cell death followed by osteoclast resorption of bone and then formation of new bone.

41
Q

How is activation stage of bone remodelling initiated?

A

Mediated by osteocyte cell death near micro fractures due to recruitement of osteoclasts by RANKL release.

42
Q

How do osteoblasts communicate with surrounding cells?

A

Osteoblasts communicate either through formation of hormones or directly through the gap junctions (with osteocytes)

43
Q

How does bone resorption occur?

A

Osteoclasts attach and degrade bone making them undergo apoptosis and switch between resorption and formation called the reversal phase

44
Q

How does bone formation occur?

A

Osteoblasts are recruited and lay down new bone (osteoid) This process is terminated by osteocytes via sclerostin

45
Q

What percentage of calcium is in the bones

A

99%

46
Q

Where is the rest of the calcium located?

A

<1% in cells and soft tissues

0.1% in the blood (10^-3M) and ECF

47
Q

What is the concentration of calcium in cells?

A

10^-6M

48
Q

Where in cells is calcium stored?

A

Mitochondria

ER

49
Q

How is calcium carried in the blood?

A

45% is bound to plasma proteins (albumin) or to small anions (PO4 and citrate) and partly ionized

Only ionized Ca2+ can move in and out of cells

50
Q

What is the concentration of normal total calcium in the blood?

A

2.12 - 2.62mM

51
Q

What is the concentration of normal ionized calcium in the blood?

A

1.16 - 1.31 mM

52
Q

How much calcium is taken in by the kidneys each day and how much of it is reabsorbed?

A
  1. 0g/day taken in

9. 8g/day reabsorbed

53
Q

How much calcium is absorbed by the intestines each day and how much of it is excreted?

A

1g/day absorbed

0.8g/day excreted

54
Q

What systems regulate calcium homeostasis?

A

Calciostat system (CaSR)

Parathyroid hormone (PTH) - increases plasma [Ca2+]

Vitamin D3 (1,25 D) - increase in plasma [Ca2+]

Calcitonin decreases plasma [Ca2+]

55
Q

How is plasma [Ca2+] regulated?

A

3 hormones:

Calcitriol (active form of D3) from kidney = Increase

PTH from parathyroid = Increase

Calcitonin from thyroid = Decrease

56
Q

How does D3 increase Calcium levels in the blood?

A

It promotes GIT Ca2+ absorption and reduces Ca2+ excretion

It also exerts negative control of PTH synthesis and further calcitriol synthesis

57
Q

What does PTH do to D3 metabolism/

A

It activates 25-OH-D3 (inactive D3) to form active 1,25(OH)2 D3

58
Q

How is PTH production controlled?

A

Regulated by ECF calcium. Low calcium is sensed by CaSR and PTH production is increased in response.

59
Q

What is the principle effect of PTH?

A

Increases ECF calcium concentration by:

Mobilising calcium from bone

Increasing tubular reabsorption

Indirectly on the gut by increasing calcitriol synthesis

60
Q

How is PTH effect antagonised?

A

Calcitonin release

61
Q

What is the effect of PTH on bone?

A

Increases bone degradation in 2 ways:

Rapidly via increasing osteocyte membrane permeability for Ca2+ -> liquid Ca2+ enters the cells -> Ca2+ pump transports Ca2+ to the ECF -> increased serum [Ca2+]

Delayed action is via increasing osteoclast activity and producing more osteoclasts which increase serum [Ca2+]

Overall result in increase in release of Ca2+ from bone

62
Q

Where is calcitonin synthesized?

A

Synthesized and secreted by parafollicular “C” cells of the thyroid gland

63
Q

When is calcitonin secreted?

A

It antagonises PTH in Ca homeostasis and is produced when [Ca2+] is too high in the plasma

64
Q

What is the target cell for calcitonin?

A

Bone osteoclasts

65
Q

What receptor does calcitonin bind to?

A

Calcitonin receptor (CTR) (cAMP mechanism)

66
Q

What does calcitonin do?

A

Inhibits osteoclast formation

Decreases kidney Ca2+ reabsorption (more calcium lost from kidneys than normal)

Inhibits Ca2+ absorption by intestines

PTH does the opposite

imed3003 (48 decks)

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