Biochem - Fracture and Dislocation Flashcards
1
Q
Types of bone
A
Compact/ cortical bone
Cancellous, spongy or trabecular bone
2
Q
Cortical bone
A
High proportion of bone w/ few spaces
3
Q
Trabecular bone
A
Low proportion of bones and a lot of space. Composed of a network of rods and plates called trabeculae
4
Q
Bone matrix component
A
Type I collagen, bone proteoglycan, osteocalcin
Hydroxyapatite
5
Q
Hydroxypapatite
A
A complex calcium phosphate salt helps mineralise the bone and bind the calcium into the bone
6
Q
Patterns in which collagen can be laid down in
A
Woven bone
Lamellar bone
7
Q
Woven bone
A
An immature form w/ random fibre orientation
Laid down during rapid growth and fracture repair
8
Q
Lamellar bone
A
Composed of successive layers of collagen fibres w/ distinct orientation
Gives a strong structure
9
Q
Long bones are composed of
A
Diaphysis
Epiphyses
10
Q
Diaphysis
A
Cyclindical shaft
11
Q
Epiphyses
A
Expanded ends of the bones
Sometimes called growth plate
12
Q
When can bone growth occur
A
As long as the growth plate hasn’t fused
13
Q
Bone cells
A
Osteoblasts
Osteocytes
Osteoclasts
Lining cells
14
Q
Osteoblasts principal function
A
Bone formation, synthesising bone matrix and priming it for subsequent mineralisation
15
Q
Osteoblasts characteristics
A
Plump cuboidal cells w/ abundant organelles for synthesis and secretion of proteins
Single nucleated
Form an epithelial layer on the bone surface
16
Q
Lining cells
A
Osteoblasts which have completed phase of synthetic activity
Can be reactivated
Important function in bone remodelling
Possibly co-operate w/ osteocytes (communication) in regulating calcium exchange from bone
17
Q
Osteocytes
A
Osteoblasts engulfed in bone matrix during appposition and eventually entombed within
18
Q
Apposition
A
Laying down lamellar structure on the outer aspect of the bone
19
Q
Most abundant cells in bone
A
Osteocytes
20
Q
What do osteocytes rely on canaliculi for
A
Maintain junctions w/ other entombed cells and w/ bone surface therefore requires vascular supply
21
Q
Main function of osteocytes
A
Regulation of calcium homeostasis and last act as strain gauge to monitor and record the extent of physical loading
22
Q
Osteoclasts
A
Large multinucleate cells responsible for resorption of bone
Distinctive appearance and contains unique organelles
23
Q
Unique organelles in osteoclasts
A
Ruffled border
Clear zone
24
Q
Why are women bones more fragile and prone too cortical fracture
A
More endosteal resorption as opposed to periosteal apposition - men
25
How does trabecular bone change w/ age
Tends to diminish
26
How does cortical bone change w/ age
Thins
27
How is the capacity for longitudinal growth maintained
Persistence of epiphyseal growth cartilages
| Cartilage undergoes interstitial growth and is replaced by (not transformed into) bone
28
How is the bone exposed
IL-6 is detected by receptors on lining cells and causes retraction
29
What happens when osteoblasts receive the signal from cytokines
They produce RANK ligands
RANK ligands stimulate surface receptors to produce more osteoclasts
As more are produced, osteoclasts get bigger and bigger and start resorption
30
Increased RANK ligand/ OPG ratio
Promotes bone loss
31
OPG production
Produced by osteoblasts which prevents osteoclast activation
Needs to balance w/ RANK ligand
32
Osteomalacia
Occurs when the bone doesn't mineralise correctly due to vit D deficiency
Less mineralisation --> reduction in rigidity and propensity for bone to fracture
33
Defining osteoclast cell function
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Acid phosphatase
Glucoronidase
Collagenase
Metalloproteinase
Cathepsins
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34
Defining osteoblast cell function
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Alkaline phosphatase
Osteocalcin
Pro-collagen peptides
Cytokines
PTHrP
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35
Body calcium
1 Kg is stored in the bone - broken down if body in dire need
Extracellular fluid stores 10mg/l
36
Storage form of bone
Calcium is stored in bone as hydroxyapatite
| Phosphate is also bound in bone w/ Ca and will released when bone is broken down
37
Calcium in blood
Measure total calcium in blood because its cheaper
Calcium is bound to proteins in the blood
But only ionised calcium is physiologically important
38
Total [Ca]
2.2 -2.6 mmol/L
39
Total [Ca 2+]
1.1 - 1.3 mmol/L
40
Adjusted Ca =
Total Ca + 0.02(40-[Albumin])
41
Effect on calcium binding to proteins
Acidosis decreases binding, more CaPr
| Alkalosis increased binding, more Ca 2+
42
Regulation of plasma calcium
Parathyroid hormone - most important
Binding to proteins/ PO4
Vit D
Calcitonin
43
PTH action - medium term
Acts on bone to stimulate osteoclast resorption
44
PTH action - rapidly
Acts on kidneys to promote Ca being reabsorbed via the tubules so Ca re-enters the bloodstream
45
PTH action - long term
Acts on kidney to reduce active form of vitamin D, vit D125 ---> acts on intestines to improve calcium absorption in the blood
46
What happens when levels of calcitonin drops
Removes inhibitory effect on osteoclasts allowing PTH stimulation to result
47
Calcium sensing receptor modulation
Ca binds to Trans-membrane receptor
Acts as an antagonist decreasing PTH release
When Ca low in the presence of normal intracellular Mg PTH released from vesicles fusing w/ csm
48
Calcium sensing receptor defects
Genetic defects can occur where the calcium sensing receptor ‘resets’ the prevailing circulating ionised (adjusted) calcium
The commonest and most important of these is where the circulating calcium is elevated in the condition Familial Benign Hypercalcaemic Hypercalciuria (FBHH) but have low Ca in urine
49
The importance of RANKL
Tumour necrosis family
Decoy receptors osteoprotegrin
Regulates skeletal remodelling and immune function
MCSF + RANKL = osteoclastogenesis
50
Roles of RANKL and OPG
PTH stimulates osteoblasts to produce RANKL --> stimulating osteoclasts
Oestrogen stimulates the osteoblasts to produce OPG, decreasing activity of osteoclasts
51
Symptoms of hypercalcaemia
Aca > 2.6 mmol/L
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Nausea
Peptic ulcers
Constipation
Renal calculi (kidney stones)
Polyuria
Renal failure
Deposition of Ca in aorta, skin etc
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52
Causes of hypercalcemia
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Hyperparathyroidism
Hypercalcemia of Malignancy
Toxicosis
Sarcoid
Vit A excess
Addisons' disease
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53
Symptoms of hypocalcaemia
Aca < 2.6 mol/L
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Paresthesia
Muscle spasms
Tetany
Cataracts
Neurotransmission at neuromuscular junction disrupted
Chvostek's and Trousseau's sign
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54
Causes of hypocalcemia
Hyoparathyroidism
| Vit D deficiency
55
Treatment of primary hyperparathyroidism
Surgery - only definitive treatment
56
Causes of Hypercalcaemia of Malignancy (HCM)
Tumours produce a factor that acts like PTH but is slightly diff, Parathyroid hormone related protein, PTHrP
More potent --> more severe hypercalcaemia
57
Causes of hypothyroidism
Post-op (parathyroid, thyroid, cancer) - removed by accident
Idiopathic
58
Why do we use Adjusted Ca
Of particular value in chronic disease states e.g. cancer where the decrease in albumin may mask hypercalcaemia
59
Endosteum
Site of formation for new bone and contains osteogenic precursor cells
60
Medullary cavity
Space within diaphysis that contains red and yellow bone marrow
61
Red bone marrow
Produces RBC's and WBC's
62
Yellow bone marrow
Contains adipose and connective tissue
| Produces some WBC's
63
Metaphysis
Spongy bone in between epiphysis and diaphysis
64
Periosteum
Composed of an inner layer of osteogenic cells and an outer fibrous layer
65
Function of periosteum
Helps protect the bone
Assists in fracture repair
Helps nourish the bone tissue
Attachment point for tendons and ligaments
66
Bone growth in length
Zone 1 - resting cartilage
Zone 2 - proliferating cartilage
Zone 3 - hypertrophic cartilage
Zone 4 - calcified cartilage
67
Zone 1 - resting cartilage
Closest to epiphysis and made up of relatively quiescent cells
Anchors epiphyseal growth plate to the bone of the epiphysis
High matrix:cell volume allows diffusion of nutrients ---> maintains chondrocytes in deeper layers
68
Zone 2 - proliferating cartilage
Slightly larger chondrocytes – dividing and replacing ones dying at diaphyseal side of epiphyseal growth plate
Produce matrix and are responsible for longitudinal growth of the bone
69
Zone 3 - hypertrophic cartilage
Contains 3 zones:
Maturation
Degeneration
Provisional calcification
70
Maturation zone
Chondrocytes increase in size
| Accumulate calcium within Mt
71
Degeneration zone
Deteriorate and die
| Ca is released from vesicles impregnating matrix w/ Ca salt
72
Provisional calcification zone
No active cell growth
Necessary for invasion of metaphyseal blood vessels, destruction of cartilage cells, formation of bone along walls of calcified cartilage matrix
73
Zone 4 - calcified cartilage
Only a few cells thick composed of dead chondrocytes (surrounded by calcified matrix)
Calcified matrix removed by osteoclasts and invaded by osteoblasts laying down new bone matrix ----> diaphyseal border firmly attached to epiphyseal growth plate
74
HGF
Human Growth Factor
| Main stimulus for growth by epiphyseal growth plates
75
What is ALP a marker of
Bone formation
76
When to check creatinine kinase levels
Dx of myopathies and myositis
77
OPG
Osteoprotegrin
78
Stages of normal fracture healing
1. Haematoma formation
2. Fibrocartilaginous callus formation
3. Bony callus formation
4. Bone remodelling
79
When does haematoma formation occur
Between days 1-5 of the fracture healing
80
Haematoma formation - fracture healing
Blood vessels are ruptured causing a haematoma, this clots and forms the temporary frame for subsequent healing
Pro-infl cytokines & VEGF are secreted
81
Fibrocartilaginous callus formation - fracture healing
VEGF → angiogenesis and stem cells are recruited
Chondrogenesis occurs
Osteoprogenitor cells lay down a layer of woven bone
82
Bony callus formation - fracture healing
RANKL is expressed so the cartilaginous callus is resorbed and begins to calcify
Woven bone continues to be laid down, forming a hard, calcified callus of immature bone
83
Bone remodelling - fracture healing
Balance between resorption by osteoclasts and new bone formation by osteoblasts
Centre of callus replaced by cortical bone and edges replaced by trabecular bone
84
When does the fibrocartilaginous callus form
Between days 5-11 of the fracture healing
85
When does the bony callus form
Between days 11-28 of the fracture healing
86
When does bone remodelling occur after a fracture
28 days and onwards
87
Bone remodelling cycle
Activation
Resorption
Reversal
Formation
88
Bone remodelling - activation
Recruitment and activation of osteoclast precursors (RANKL) and fusion of multiple mononuclear cells to form multinucleated preosteoclasts
89
Bone remodelling - resorption
Osteoclasts lower the pH in the bone and secrete chemicals to digest the organic matrix resulting in Howships lacunae
90
Bone remodelling - reversal
Regulator cytokines switch off osteoclasts
91
Bone remodelling - formation
Osteoblasts move in and produce osteoid
92
Prerequisites for normal fracture healing
Viability of fragments e.g. intact blood supply
Mechanical rest - either immobilisation or internal fixation
Absence of infection
93
Examples of abnormal fracture healing
Delayed union
Non-union
Man union
94
Delayed union
Fracture healing can take 2x as long
95
Types of non-union
Atrophic
| Hypertrophic
96
Atrophic non-union
Too little callus has formed
97
Hypertrophic non-union
There is obvious callus but continued instability
98
Common sites of non-union
Scaphoid
Femoral neck
Tibial shaft
99
Psuedoarthrosis
When a broken bone fails to heal after a fracture
| The fracture structurally resembles a fibrous joint
100
Common benign tumours
Osteoma
Osteochondroma
Giant cell tumour
101
Osteoma
Benign ‘overgrowth’ of bone, most typically occurring on the skull
102
Osteochondroma
Most common benign bone tumour
Cartilage-capped bony projection on the external surface of a bone
Usually in males <20 yrs
103
Giant cell tumour
Tumour of multinucleated giant cells within a fibrous stroma
Occurs most frequently in the epiphyses of long bones
X-rays show a ‘double bubble’ appearance
104
Osteosarcoma
Most common primary malignant bone tumour
Seen mainly in children & adolescents
Occurs most frequently in metaphyseal region of long bones prior to epiphyseal closure e.g. femur, tibia, humerus
X-rays show Codman’s triangle & sunburst pattern
105
Ewing's sarcoma
Small round blue cell tumour
Seen mainly in children and adolescents
Occurs most frequently in pelvis and long bones - causes severe pain
X-ray shows ‘onion skin’
106
Chondrosarcoma
Malignant tumour of cartilage
Most commonly affects axial skeleton - palpable mass grows causing pain
More common in middle age
