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Medicine - Phase 1 > MSK > Flashcards

MSK Flashcards

1
Q

Purpose of the skeleton:
* Raises us from the ground against [a]
* Determines basic body [b]
* transmits body [c]
* Forms joint lever system for [d]
* [e] vital structures from damage
* Houses [f]
* [g] storarge

A

[a] gravity
[b] shape
[c] weight
[d] movement
[e] protects
[f] bone marrow
[g] mineral

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2
Q

How many apendicular bones do adults have?

A

126

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3
Q

how many axial bones do adults have?

A

80

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4
Q

how many bones does a newborn baby have?

A

350 - they then fuse

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5
Q

describe long bones.
example?

A

long tubular and hollow.
expanded at ends for articulation
femur, ulnar

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6
Q

what shape are short bones.
example?

A

cuboidal.
carpal bones.

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7
Q

describe the shape of flatbones.

A

flat, often curved, protective.
eg skull and ribs

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8
Q

give an example of an irregular bone

A

vertebrae

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9
Q

where are sesamoid bones found?

A

in the tendon
eg thumb, knee cap

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10
Q

where would a trabecular bone structure be found?

A

in the metaphysis of bone

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11
Q

where would compact bone structure be found?

A

in the diphysis of bone

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12
Q

which type of bone structure is made quickly?

A

woven bone
- disorganised
- no clear structure

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13
Q

which type of bone structure is made slowly?

A

lamellar - like tree rings
organised and layered

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14
Q

function of hollow long bone?

A

keep weight away from neutral axis
minimises deformation

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15
Q

function of trabecular bone?

A

give structural support while minimising weight

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16
Q

function of wide ends of bone?

A

to spread load over weak, low friction surface

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17
Q

what percentage of bone is made up from mineral particles?

A

50-70% mineral
- hydroxyapatite

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18
Q

what is hydroxyapatite?

A

crystalline form of calcium phosphate

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19
Q

what percentage of bone is made from organic matrix?

A

20-40% organic matric
-90% Type I Collagen
10% Non collagenous protein

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20
Q

what percentage of bone is water?

A

5-10% water

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21
Q

what is the purpose of collagen and minerals in bone?

A

minerals = stiffness
collagen = elasticity

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22
Q

label the cells of the bone

A
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23
Q

function of osteoclast?

A

to resorb bone

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24
Q

how does an osteoclast resorb bone?

A

dissolve mineralised matrix = acid
breakdown collagen in bone = enxymes
TRAP and Cathepsin K

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25
Q

what does an osteoclast derive from?

A

hematopoietic stem cells
(uses MCSF)

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26
Q

function of osteoblasts?

A

form bone - in form of osteoid

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27
Q

how do osteoblasts form bone?

A

produce type I collagen
mineralises extracellular matrix by depositing hydoxyapatite crystal within collagen fibrils.

high alkaline phosphatase activity

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28
Q

what do osteoblasts derive from?

A

mesenchymal stem cell

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29
Q

what is the function of osteocytes?

A

conductor of cells in bone - tell other cells what to do

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30
Q

5 steps of bone remodelling?

A
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31
Q

what is bone modelling?

A

adaptation (ie to sport)
gross shape of bone is altered, bone added or taken away

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32
Q

what is bone remodelling?

A

repair
all of the bone is altered, new bone replaces old bone

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33
Q

a human fully replaces its entire skeleton every…

A

10 years

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34
Q

explain what happens during trauma to a bone?

A
  1. periosteum tears = haematoma
  2. adjacent bone cell death
  3. soft tissue damage
  4. osteoblasts = new woven bone
  5. osteoclasts = mop up dead bone; remodel strong bone
  6. osteoblasts = new lamella bone
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35
Q

current treatments of osteogenesis issues?

A

anti-catabolic = stop the osteoclasts (more because easier)
anabolic = stimulate ostoblasts

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36
Q

function of collagen in bone?

A

allows elasticity in bone
creates structure for hydroxyapatite crystals

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37
Q

which enzyme is needed for bone mineralisation?

A

alkaline phosphate -
hydrolysis pyrophosphate

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38
Q

at what age is peak bone mass reached?

A

about age 25

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39
Q

what are collagen fibres made up from?

A

AA –> tropocollagen —> collagen fibrils –> collagen fibres

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40
Q

collagen molecule structure:

Molecular building block =
which forms
[a] Collagen chains =
which forms
[b] molecule
which is assembelled into a [c] via

A

collagen molecule structure: TRIPLE HELIX

Molecular building block = Gly-X-Y
which forms
[a] Collagen chains = 2 x 𝛂1 and 1 x 𝛂2
which forms
tropocollagen molecule
which is assembelled into a collagen fibril via covalent crosslinks

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41
Q

what are two biproducts of collagen synthesis?

A

P1NP and P1CP
biomarkers of collagen synthesis

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42
Q

osteogenesis imperfecta is a genetic disease causes by?

A

defects to Collagen chains = 2 x 𝛂1 and 1 x 𝛂2

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43
Q

joining collagen together requires many cofactors.
what is the role of vitamin C in joining collagen together?

A

Hydrogen bonds within tropocollagen require FE2+
Vitamin C reduces Fe3+ to Fe2+

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44
Q

what enzymes break dwon collagen?

A

proteinases: collagenases and cathepsin K

can be normal or pathological

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45
Q

what are the biomarkers of collagen breakdown?

A

NTX and CTX

46
Q

what happens in bone mineralisation?

A
47
Q

where does intramembranous ossification occur?

A

skull
clavicles

begins in utero, continues to adolescence
happens by remodelling of mesenchymal connective tissue.

48
Q

where does endochondral ossification occur?

A

more common ossification - in long bones

bone forms by replacing a hyaline cartilage precursor

49
Q

when does growth plate fusion occur?

A

around 16 (f)
18 (m)

50
Q

how does outward growth of bones occur?

A
51
Q

a woman who started her period late would have what bone proportions?

A

long legs and short torso
sine elongates most in puberty

52
Q

how much calcium do we have in our body?
where is the main resevoir?

A

1200g
skeleton main resevoir

53
Q

how much calcium is stored in exracellular space?
what is its functions?

A

only 1g
key for: muscle contractility; nerve function; normal blood clotting

54
Q

normal total serum calcium levels?
how much is metabollically active?

A

Total Serum Calcium 2.4mmol/L
Ionised serum calcium about 1.1 mmol/L (metabollically active)

55
Q

calcium is not metabollically active when?

A

Ionised = metabolically acrtive
Protein bound (albumin) = not metabolically active

56
Q

what happens to calcium levels if you hyperventilate?

A

hyperventilate = alkalotic
at high pH, albumin binds more strongly to calcium
LESS ionised (metabolically active) calcium
hypocalcaemia = tingling in fingers

57
Q

where in the body does calcium regulation/kinetics take place?

A

Gut = absorbtion/excretion
Bones = formation/resorbtion
Kidneys = reabsorbtion/excretion

58
Q

recommended daily calcium intake/day?

A

700 mg/day

59
Q

main sources of dietary calcium?

A

dairy products

60
Q

how much dietary calcium do we absorb?

A

30%

61
Q

where and how is clacium absorbed in the gut?

A

duodenum and jejunum = active absorbtion
ileum and colon = passive absorbtion

62
Q

when there is low dietary calcium availability, which type of calcium transport increases?
mediated by?

A

active transport
mediated by calcitriol

63
Q

what is calcitriol?

A

active form of Vit D

64
Q

What are the two processes in which calcium can be released from the bone?

A

Rapidly - from exchangeable calcium of the bone surface
Slowly - by osteoclasts during bone resorbtion

65
Q

the amount of calcium filtered by the glomerulus depends on?

A

glomerular filtration rate
ultrafiltrable calcium = ionised and complexed (not bound)

66
Q

what percentage of filtered calcium is reabosribed in the kidney?

A

98%

67
Q

what can increase the amount of calcium reabsorbed in the kidney?

A

Reabsorbtion increased by PTH

68
Q

what can decrease the amount of calcium reabsorbed in the kidney?

A

Reabsorbtion decreased by high Na+ levels

calcium follows the sodium to be excreted

saline can be used therapeutically in hypercalcaemia

69
Q

where in the nephron is calcium reabsorbed?

A

PCT = 65%, passive
Thick limb = 25%, passive
DRT = 8%, active

70
Q

a decrease in serum calcium has what affect on PTH?

A

Increases PTH

small decrease in Ca++, BIG increase in PTH

71
Q

how does PTH affect serum calcium levels?

A

Bones:
-increased bone resorbtion
-exchangeable calcium released from surface of bone

Kidney
-increased calcium reabsorbtion from kidney
↓
-increased 1,25(OH)2 vit D
↓
Gut
-increased calcium absorbtion in gut

72
Q

Calcitonin:
where is it produced?
what stimulates its secretion?
what is its action?

A
  • produced by thyroid c cells
  • secretion stimulated by increases serum calcium
  • effect to lower bone resorbtion
  • significance in humans uncertain
73
Q

vitamin D is a [?] of calcium

A

long term regulator

74
Q

Vitamin D synthesis:
[a] is converted into vitamin D3 under the influence of [b].
In the liver, vitamin D3 is converted into [c] by [d]. This is relatively inactive.
In the kidney, [e] converts [f] into [g], otherwise known as calcitriol. This is metabolically active.

A

7-dehydrocholesterol is converted into vitamin D3 under the influence of UV radiation.
In the liver, vitamin D3 is converted into 25-hydroxyvitamin-D by 25-hydroxylase. This is relatively inactive.
In the kidney, 1-α-hydroxylase converts 25-hydroxyvitamin-D into 1,25-dihydroxyvitamin-D, otherwise known as calcitriol. This is metabolically active.

75
Q

role of calcitriol on calcium?

A
  1. stimulates intestinal epithelial cells to increase the synthesis of calbindin-D proteins.
  2. Calbindin-D proteins increase the intestinal absorption of calcium by facilitating the transport of calcium from the intestinal brush border to the basolateral membrane, where it is released into the bloodstream.
76
Q

If levels of calcitriol become excessive, it is converted to

A

24,25-dihydroxycholecalciferol

77
Q

how much phosphate is usually present in a healthy body?
where is it mostly found?

A

500-800g = 1% of total body weight
90% found in bone mineral

78
Q

what is a normal serum phosphate level?

A

0.8-1.5 mmol/l

79
Q

what can low phosphate level lead to?

A

Poor bone mineralisation
- rickets/ osteomalacia
- pain, fractures

80
Q

what can high phosphate levels lead to?

A

excessive fomratiom of hydrocyapatite –>deposits in places other than bone eg arteries

81
Q

recommended adult daily intake of phosphate?

A

700mg

82
Q

dietary sourced of phosphate?

A

proteins
anima, seeds, dairy soy

fairly ubiquitous

83
Q

what percentage of unbound phsophate is filtered in the kidney?
where in the nephron?

A

90%:
80% in PCT (Na cotransport)
10% DCT

84
Q

name three things that regulate phosphate metabolism

A

parathyroid hormone
1,25 dihydroxyvitamin D
FGF-23

85
Q

what is FGF 23?

A

fibroblast growth factor 23
- the mahor regulator of phosphate metabolism

86
Q

where is FGF-23 produced?

A

osteocytes

87
Q

what stimlates osteocytes to prodcued FGF-23

A

rise in Pi levels
PTH
1,25 vitamin D

88
Q

action of FGF-23?

A

DECREASES PHOSPHATE:
* decreases expression of Na transported in renal tubule = increase renal excretion of phosphate
* decreases 1𝛂-hydroxylation of vitamin D = decreases gut absorbtion of phosphate

89
Q

an FGF mutation can lead to ?

A

Inherited rickets
Tumour Induced Osteomalacia

90
Q

summarise phosphate homeostasis

A
91
Q

calcium mostly regulated by hormones that [?] serum calcium =

A

calcium mostly regulated by hormones that increases serum calcium = PTH and VitD

92
Q

phosphate mostly regulated by hormones tha [?] serum phosphate =

A

phosphate mostly regulated by hormones tha decrease serum phosphate = FGF-23 and PTH

93
Q

outline the process of bone remodelling

A
94
Q

leabel the cells if the bone remodelling unit

A
95
Q

3 conditions that must be met for successful regulation of bone trunover (remodelling)

A
  1. osteoblasts and osteoclasts must be able to communicate withe eachother
  2. coupling
  3. balance
96
Q

what is coupling?

A

bone formation by osteoblasts occus at sites of previous bone resorbtion by osteoclasts

same place

97
Q

what is balance (in bone remodelling)

A

amount od bone removes by osteoclasts should be replaced by osteoblastic activity

same amount

this is impaired with age (osteoclasts>osteoblastic activity)

98
Q

osteoclasts are derived form?

A

hemopoietic progenitor

99
Q

the cytokine system demonstrates great redundancy and great pleiotropism.
what is meant by redundancy?

A

redundancy - if you remove/knock out the cytokine, nothing much happens

100
Q

the cytokine system demonstrates great redundancy and great pleiotropism.
what is meant by pleiotropism?

A

pleiotropism - if you move the cytokine to a different area, they have a different function due to the presence of other cells

101
Q

what is OPG?

A

osteoprotegrin, also known as
osteoclastogenesis inhibitory factor

102
Q

Mediators of oseoclast differentiation and actvity?

A

Hormones (PTH, vit D, etc.)
Paracrine/autocrine (prostaglandins)
**OSTEOPROTEGERIN **

103
Q

what is the function of OPG?

A

inhibits the differentiation of myeloid precursors into osteoclasts
= decreases resorbtion by osteoclasts

104
Q

how does OPG inhibit the differentiation of myeloid precursors into osteclasts?

A

binds to RANK-ligand
thus blocking the RANK-RANK ligand interaction between osteoblasts and osteoclast precursors. (blocks the digging)

105
Q

OPG knockout –> ?

A

thin bones

106
Q

OPG overexpression —>?

A

overly dense bones

107
Q

osteoblasts derive from?

A

mesenchymal cells

108
Q

why does our bone marrow yellow as we age?

A

as we age, more mesenchymal progenitors are directed down the adipocyte pathway = yellow

109
Q

what is the WNT pathway?

A

enhances differentiation of precursors into osteoblasts

110
Q

what is sclerostin?

A

regulates bone remodelling in osteocytes

Medicine - Phase 1 (16 decks)

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