Normal Bone Function Flashcards

1
Q

Purpose of the skeleton

A

Raises us from the ground against gravity
Determines basic body shape
Transmits body weight
Forms jointed lever system for movement
Protects vital structures from damage
Houses bone marrow
Mineral storage- calcium, phosphorus, magnesium

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2
Q

Which minerals are stored in bone

A

Calcium
Phosphorus
Magnesium

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3
Q

Number of bones in appendicular skeleton

A

126

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4
Q

Number of bones in axial skeleton

A

80

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5
Q

What is the skeleton divided into

A

Axial
Appendicular

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6
Q

Bone classification by shape

A

Long bones
Short bones
Flat bones
Irregular bones
Sesamoid bones

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7
Q

Long bones

A

Tubular shape with hollow shaft and ends expanded for articulation with other bones

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8
Q

Short bones

A

Cuboidal in shape

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9
Q

Flat bones

A

Plates of bones
Often curved
Protective function

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10
Q

Sesamoid bones

A

Round, oval nodules in a tendon

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11
Q

Irregular bones

A

Various shapes

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12
Q

Types of bone structure- macro

A

Cortical
Trabecular

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13
Q

Cortical bone structure

A

Compact
Dense, solid, only spaces are for cells and blood vessels

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14
Q

Trabecular bone structure

A

Cancellous
Spongy
Network of bony struts (trabeculae) , looks like sponge, many holes filled with bone marrow
Cells reside in trabeculae and blood vessels in holes

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15
Q

Types of bone structure- micro

A

Woven
Lamellar

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16
Q

Woven bone

A

Made quickly
Disorganised
No clear structure

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17
Q

Lamellar bone

A

Made slowly
Organised
Layered structure

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18
Q

Function of hollow long bone

A

Keeps mass away from neutral axis
Minimises deformation

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19
Q

Function of trabecular bone

A

Gives structural support while minimising mass

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20
Q

Number of baby bones in body

A

350

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21
Q

Number of adult bones in body

A

206

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22
Q

Wide ends of bone function

A

Spreads load over weak, low friction surface

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23
Q

Flat bones function

A

Protective

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24
Q

Bone composition

A

50-70% mineral
20-40% organic matrix
5-10% water

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25
Bone composition- mineral
Hydroxyapatite A crystalline form of calcium phosphate
26
Hydroxyapatite
A crystalline form of calcium phosphate
27
Bone composition - organic matrix
Collagen type 1- 90% of all protein Non-collagenous protein - 10%
28
What type of collagen composes bone
Type 1
29
How does collagen assemble in bone
Assembles in fibrils with mineral crystals situated in ‘gap’ regions between them
30
Function of mineral in bone
Stiffness
31
Structure of collagen in bone
Elasticity
32
Cells of bone
Osteoclasts Osteoblasts Osteocytes Bone lining cell
33
Osteoclasts structure
Mutlinucleated
34
Osteoblasts shape
Plump Cuboidal
35
Osteocyte shape
Stellate Entombed in bone
36
Bone lining cell shale
Flattened Lining the bone
37
Origins of osteoblasts
Mesenchymal stem cell
38
Function of osteoblasts
Form bone- in form of osteoid Produce type 1 collagen and mineralise the extracellular matrix by depositing hydroxyapatite crystal within collagen fibrils High alkaline phosphatase activity Make non-collagenous proteins Secreted factors that regulate osteoclasts - RANKL
39
Origins of osteoclasts
Haematopoietic stem cells
40
Function of osteoclasts
Resorb bone Dissolved the mineralised matrix (acid) Breakdown the collagen in bone (enzymatic) High expression of TRAP and cathepsin K
41
How is the mineralised matrix dissolved
Acid
42
How is the collagen in bone broken down
Enxymes
43
Bone modelling
Gross shape is altered Bone added or taken away
44
Bone remodelling
All of the bone is altered, new bone replaces old bone
45
Bone remodelling
Resting phase Activation Resorption Reversal phase Formation
46
Age of bone development -modelling
0-20
47
Age of bone maintenance- remodelling
20-50
48
Age of bone osteoporosis- acquired pathology
50+
49
Reasons for bone remodelling
Form bone shape Replace woven bone with lamellar bone Repair damage Obtain calcium Response to loading (exercise) Reorientate fibrils and trabeculae in favourable direction for mechanical strength
50
Long bone examples
Humerus Femur
51
Where are Sesamoid bones found
Hand Feet Knee cap
52
What can mesenchymal stem cells become
Adipocytes Osteoblasts Chondrocytes Fibroblasts Myoblasts
53
What factors regulate osteoclasts
RANKL
54
What do osteoclasts have a high expression of
TRAP Cathepsin K
55
How often do you fully replace your skeleton
Every 10 years
56
Which hormone controls osteoclasts —-> leading to osteoporosis
Oestrogen
57
What type of bone is the skull
Flat
58
What type of bone is vertebrae
Irregular
59
Where would you predominantly find trabecular bone
Metaphysis of long bone Irregular bones
60
Where would you predominantly find trabecular bone
Metaphysis of long bone Irregular bones
61
Building a collagen fibres
Tropocollagen Collagen fibrils Collagen fibres
62
Amino acid sequence of collagen molecule
Glycine - X - Y Up to about 1000 amino acids X and U are often proline, hydroxyproline or hydroxylysine Allows formation of alpha helix
63
What is a biomarker of collagen synthesis
P1NP P1CP
64
Which amino acid is the 3rd amino acid in a collagen molecule
Glycine
65
What forms the tropocollagen molecule
3 collagen chains 2 alpha-1 One alpha-2
66
Number of residues per turn of collagen
3
67
What holds the tropocollagen molecules and fibril together
Covalent crosslinks derived from lysine/hydroxylysine side-chains
68
Processing of type 1 collagen
N-terminal propeptide and C-terminal propeptide cleaved to create correct length of collagen
69
Structure of collagen
Triple helic
70
Covalent cross-links within and between tropocollagen
-OH-lysine x2 Lysyl oxidase
71
What does lysyl oxidase require
Copper
72
Biomarkers of type 1 collagen breakdown
NTX CTX
73
Hydrogen bonds within tropocollagen
Between hydroxyproline molecules OH-proline from proline requires Fe2+
74
What does the conversion of Fe3+ to Fe2+ require
Vitamin C
75
Cross-links between tropocollagen
OH-lysine x3 = pyridinolines
76
Which enzymes break down collagen
Proteinases especially collagenases and cathepsin K
77
Type 1 collagen
Bone, tendon, ligaments , skin
78
Type 2 collagen
Articular cartilage Vitreoud
79
Type 3 collagen
Wound healing
80
Type 4 collagen
Basal lamina
81
Type 5 collagen
Cell surfaces
82
Type 10 collagen
Growth plate
83
What synthesises the bone matrix
Osteoblasts
84
Other proteins found in bone matrix
Osteocalcin Osteonectin Osteopontin Fibronectin Bone sialoprotein Bone morphogenetic proteins
85
Function of other proteins in bone matrix
Contribute to structure Regulate bone cell activity
86
Bone mineralisation
Alkaline phosphatase hydrolyses pyrophosphate Inorganic phosphate complexes with calcium to form hydroxyapatite Hydroxyapatite crystals propagate along colagen
87
What stimulates growth plate fusion
Oestrogen
88
Which bones are formed by intramembranous ossification
Skull Clavicles
89
Which bones are formed by endochondral ossification
Long bones
90
Appositional growth
Growth of bone diameter Osteoblasts deposit bone Osteoclasts resorb bone in the centre
91
How many tropocollagen molecules pleat together
5
92
Examples of short bones
Carpals Tarsals
93
At what age is peak bone mass reached
25
94
Which enzyme is needed for bone mineralisation
Alkaline phosphatase
95
Function of collagen in bone
Allows deformation (toughness) Creates structure for hydroxyapatite
96
What is common to all collagens
Triple helix
97
Function of osteocytes
Maintain mineral concentration of matrix
98
Woven bone
woven bone (primary) - appears in embryonic development and fracture repair. Consists of osteoid with the collagen fibres arranged randomly
99
Lamellar bone
Lamellar bone (secondary) - bone of the adult skeleton. Consists of highly organised sheets of mineralised osteoid making it much stronger. It can be further subdivided into 2 types: 1. Compact bone - lamellae are organised into concentric circles which surround a vertical Haversian canal (which transmits small Neurovascular and lymphatic vessels) = osteon. Osteocytes are located between the lamellae within lacunae , and the lacunae are interconnected by canaliculi 2. Spongy bone - contains many large spaces. The bony matrix consists of a 3D network of fine columns which cross link to form irregular trabeculae- producing a light porous bone. The spaces between trabeculae are filled with bone marrow.
100
Osteocytes
as the osteoid mineralises, osteoblasts become entombed between lamellae in lacunae where they mature into osteocytes which monitor the minerals and proteins to regulate bone mass
101
Organic components of bone
include mainly type 1 collagen (providing tensile strength and elasticity); proteoglycans (responsible for compressive strength); matrix proteins, including osteocalcin, osteonectin and osteopontin (which promote mineralisation and bone formation); cytokines and growth factors.
102
Inorganic components of bone
include calcium hydroxyapatite (providing compressive strength)and osteocalcium phosphate.
103
Percentage of organic and inorganic components of bone
40% organic 60% inorganic
104
Joe, a 7 year old male, comes into clinic with unexplained muscle pain and weakness. He presents with signs of scurvy - a vitamin C deficiency disease. Fe(III) is converted to Fe(II) by vitamin C and is crucial in the hydroxylation step of collagen synthesis in muscles. What is the molecule that forms hydrogen bonds within tropocollagen?
Hydroxyproline
105
Srinath the world’s best badminton player goes to his physiotherapist with pain in what he thinks is his ligaments. However, the physiotherapist says the pain is more likely to come from tendons and she tries to explain to Srinath why this is. Which one of these is not a property of tendons?
High elastin content
106
Strain variables
Rate Magnitude Frequency Dwell (hold/rest periods) Number of cycles
107
What is bone formation response affected by
Sex Age Hormone Cytokines Drugs/medicines.nutraceuticals
108
The mechanostat theory
There is not a single mechanostat Our skeletons contain vast number of small units of bone, each of which has its own dynamically regulated mechanostat
109
Maximising response to loading
Bone responds maximally to only a few loading cycles each day Exercise in the previous 4 hours increases the response to subsequent loading Bone responds to very brief mechanical events Rest periods between single loading events (-10 s) increase their effect
110
Which cells sense loading
Osteocytes
111
How do osteocytes sense loading
Fluid flow shear stress
112
Loading
Increases bone formation
113
Off-loading
Decreases bone formation
114
What happens to bone when they are loaded
Deformation and strain
115
Strain
Change in length/ length
116
Deformation
Force causes deformation- change in length
117
How do osteocytes sense mechanical strain
detecting fluid shear around their dendrites in canaliculae
118
How do osteocytes manage the activity of osteoblasts and osteoclasts
partly through direct contact with dendrites to cells on the bone surface partly by secretion of signalling proteins such as RANKL, OPG sclerostin (there are now drug treatments for osteoporosis based on OPG and sclerostin). Osteocytes also secrete FGF-23 which regulates phosphate excretion.
119
Which of these are dietary sources of phosphate?
meat, dairy, soy, seeds and nuts. Carbonated soft drinks can also have high phosphate content.
120
Which component of bone confers the mechanical property of stiffness?
Mineral
121
Which hormone is the main regulator of serum calcium concentration?
Parathyroid hormone
122
Which is a physiological function of synovial fluid?
Reduce friction of joint movement
123
Which of the following is a source of uric acid?
Adenine