LOCO2 OVERVIEW Flashcards

1
Q

Osteoclasts

A

Cell that breaks down the bone - secrete digestive enzymes

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2
Q

How to recognise osteoclast from image

A

Sits in a depression
LARGE cells
Multinucleated

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3
Q

NB NOT LOCO - where is collagen type III found?

A

Reticular fibres - supporting network of tissues for e.g. liver, bone marrow

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4
Q

Collagen type found in bone

A

Collagen I

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5
Q

Components of ECM of bone

A

Collagen I and proteoglycans

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6
Q

Osteoclast is a relative of which cell type?

A

Macrophage

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7
Q

Osteoprogenitor cells

A

Can differentiate into osteblasts

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8
Q

Osteoprogenitor cells - cell type

A

Mesenchymal cells

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9
Q

Where are osteoprogenitor cells found?

A

Endosteum

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10
Q

What is the endosteum?

A

Thin, vascular membrane of connective tissue lining the inner component of the bone

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11
Q

Recognise osteoblast from image

A

Cuboidal like cell

Sat at the surface of the bone matrix

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12
Q

Recognise osteocyte from image

A

Little black dots - look like pits

Sat within lacunae (surrounds the black dot)

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13
Q

Types of bone

A

Lamellar (mature) - have the cortical and the cancellous/spongy/trabecuale
Woven - immature bone

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14
Q

What is found within trabeculae bone?

A

Bone marrow - important for production of RBCs

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15
Q

Why is woven bone weak?

A

Mechanically weak due to random organisation of the collage fibres
Laid down very quickly - lack of organisation

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16
Q

Organic vs. inorganic components of bone

A

35-40% organic ECM - proteoglycans, collagen I, cytokines
60% - inorganic salt - calcium hydroxyapatite
5% - water

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17
Q

Canaliculi - what are they and what cell are they found on?

A

Little black processes present osteocytes - these sense the surrounding environment for any signs of stress that the surrounding bone may be under

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18
Q

‘Scerostin’

A

Secreted by happy osteocytes that are under no stress

Prevents production of new bone by osteoblasts

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19
Q

Effect of PTH on sclerostin

A

PTH - stress hormone released by osteocyte
Inhibits secretion of sclerostin
Induces bone production

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20
Q

RANKL

A

Ligand that stimulates bone resorption

Produced by osteocytes and osteoblasts

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21
Q

RANK

A

Receptor for RANK found on osteclasts and precursors

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22
Q

‘Osteoid’

A

Unmineralised bone matrix

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23
Q

How is osteoid mineralised and when?

A

By calcium hydroxyapatite - about one week after it is laid down

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24
Q

How long does bone remodelling take from start to finish?

A

About three months

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25
Normal serum calcium levels
2.2-2.6mmol/L
26
What is the recommended daily intake of calcium?
500-1300mg
27
Normal plasma concentration of phosphate
0.8-1.5mmol/L
28
PTH receptor found on which cell?
Osteoblast
29
Action of PTH on osteoblast?
Release of RANKL - acts of onsteoclasts
30
Action of 1,25-dihydroxyvitamin D in calcium regulation
Increases calcium reabsorption from the gut
31
Calcitonin
Released from thyroid gland when calcium levels are too high (>2.6mmol/L)
32
'Osteoporosis'
Reduced bone density due to reduced levels of tissue resulting from calcium or vitamin D deficiency
33
What does a DEXA scan measure?
Bone density/bone mass
34
Mechanism of action of bisphosphonates
Drug incorporated into the bone when taken Taken up into osteoclasts as they break down the bone Promotes apoptosis of the osteoclasts
35
Teriparatide
Short term PTH - increases action of osteoblasts - so builds up bone for osteoporosis NB. PTH activates osteoblasts in short term and osteoclasts in long term
36
Denozumab
Antibody for osteoporosis treatment | Binds to RANKL to prevent it from binding to osteoclasts - reduces the action of osteoclasts
37
'Osteomalacia'
Lack of bone mineralisation due to insufficient levels of vitamin D Insufficient calcium and phosphate to mineralise the bone
38
Define pseudofractures
Regions of unmineralised bone (osteoid)
39
How much sun exposure should an individual have to get sufficient levels of vitamin D?
15 minutes of sun on the hands and face 2-3 times a week
40
Treatment of osteoporosis
Vitamin D and calcium supplements HRT for menopausal women Bisphosphonates Antibodies
41
Five foods high in calcium
``` Bread Leafy green veg Beans and pulses Milk Dried fruit ```
42
Osteosarcoma and Paget's disease
Osteosarcoma is a rare complication of Paget's - due to the high stage of compensatory proliferation of woven bone
43
'Paget's disease'
Disruption to the cycle of bone renewal and repair
44
Type a vs. Type b synoviocytes
a
45
Tissue type of the subintima
a
46
Composition of synovial fluid
a
47
Leucocytes present in RA
Lymphocytes - infiltrate the synovial membrane | Neutrophils - enter the synovial fluid
48
Leucocytes present in RA
Lymphocytes - infiltrate the synovial membrane | Neutrophils - enter the synovial fluid
49
Components responsible for the viscosity of hyaluronic acid
a
50
Function of synovial fluid
a
51
Antibodies produced in RA and their action?
Anti-citrullinated protein antibodies (ACPA) | Stimulates osteoclast differentiation and proliferation
52
DKK-1 and their actions
Produced by Th17 where there are no osteoclasts - induces production of sclerostin - osteoblasts are switched off
53
Action of neutrophils in synovial fluid
Respiratory burst - production of free radicals - damage to hyaluronic acid, synovial fluid, subchondral exposed bone, articular cartialge
54
Action of neutrophils in synovial fluid
Respiratory burst - production of free radicals - damage to hyaluronic acid, synovial fluid, subchondral exposed bone, articular cartialge
55
Prevalence of RA
1%
56
RA symmetrical or non-symmetrical?
Symmetrical
57
Joints affected in the hands in RA?
MCP and PIP joints
58
First line management for RA
Pain relief - analgesic ladder
59
First line management for RA
Pain relief - analgesic ladder
60
Gold standard conventional DMARD
Methotrexate
61
Mechanism of action of conventional DMARDs
Immune suppressants
62
Mechanism of action of methotrexate
Folic acid/folate inhibitor - NOT to be used in pregnant women Targets any proliferating cells - not just the proliferating immune cells SO has systemic effects
63
How long before methotrexate has an effect?
3-12 weeks
64
Adverse effects of methotrexate
Hepatic problems - liver failure | Stem cell problems
65
Direct action of methotrexate
Dihydrofolate synthetase
66
Indirect action of methotrexate
Thymidate synthetase
67
Indirect action of methotrexate
Thymidate synthetase
68
Main site of action of sulfasalazine and why?
a
69
Metabolite of sulfasalazine and site of action of this
a
70
Hydroxychloroquine and mechanism of action
Animalarial Accumulates in lysosomes to reduce pH - reduces protein modifications Blocks toll-like receptor 9 - reduced activation of dendritic cells
71
Hydroxychloroquine should be avoided in who?
In patients with psoriatic arthritis - makes their skin condition worse
72
Patients that cannot take methotrexate should be given what?
Leflunomide
73
How long for gold to have an effect in the treatment of RA?
4-6 months
74
Name three biological TNFa blockers
Entanercept Infliximab Adalumumab
75
Name a biological that has an action of B cells nad what is the target?
Rituximab | CD20 on B cells
76
Name a biological that has an action on T cells and what is the target?
Abatacept | CD28 on T cells
77
Nerve roots of the femoral nerve
L2, L3, L4
78
Nerve roots of the obturator nerve
L2, L3, L4
79
Nerve roots of the sciatic nerve
L5, S1, S2
80
Order of nerves in the lumbar plexus
``` Subcostal Iliohypogastric Ilioinguinal Genitofemoral Lateral cutaneous Obturator Femoral ```
81
Nerve roots of the lumbar plexus
L1-L4
82
Borders of femoral triangle
Inguinal ligament Sartorius Adductor longus
83
Three bones involved in the ankle joint
Tibia Fibula Tallus
84
Name of heel bone
Calcaneus
85
On which side of the arm are the cephalic and basilic veins located?
Cephalic - radial side | Basilic - ulnar side
86
Muscles responsible for abduction of the arm
Supraspinatous - first ten degrees | Deltoid - rest of the movement
87
Nerve roots of the brachial plexus
C5-T1
88
Two nerves that can cause winging of the scapula and what do these innervate?
Long thoracic nerve - serratous anterior | Spinal accessory nerve - trapezius
89
Presentation of radial nerve damage
Wrist drop
90
Presentation of median nerve damage
Hand of bennidiction
91
Define osteoid
Unmineralised organic component of bone
92
Presentation of Duputren's contracture vs. trigger finger
Trigger finger closer to the palm of the hand
93
Dupuytren's contracture is common in who?
``` Men Heavy drinkers Diabetes Smokers Classically: HEAVY DRINKERS ```
94
What is Dupuytren's contracture?
Palmar aponeurosis
95
Protein involved in genetic aspect of OA
HMGB2 - early onset OA
96
Chondromalacia and how does this occur in OA?
Softening cartilage Lack of proteoglycans Increased water moves into the collagen and causes chondromalacia NB. water than moves out again due to lack of proteoglycans to hold the water in place
97
What happens following chondromalacia of the cartilage
Chondromalacia followed by fibrilation (and then erosion and cracking and then eburnation)
98
Collagen type found in bone
Collagen type I
99
Collagen type found in articular hyaline cartilage of synovial joint?
Mainly collagen type II | Deeper radial layer - collagen type X
100
Main proteoglycan in the body?
Aggrecan
101
Function of proteoglycans in articular cartilage?
Negative side chains - attracts water from the synovial fluid
102
OA bilateral or unilateral and why?
OA can be either - starts of as unilateral - person uses joints on the other side of the body to compensate for their weakening joints - becomes bilateral
103
OA or RA more common?
OA
104
Age of onset OA vs. RA
OA - rare prior to 45 years | RA - peak age of onset between 20 and 40 years
105
Almost everyone develops OA or RA?
OA
106
Morning joint stiffness presentation in OA
Tender and aching joints - don't tend to be that swollen Morning stiffness lasting less than one hour Stiffness returns at the end of the day/after periods of activity
107
Morning joint stiffness presentation in RA
Very stiff, swollen, inflamed joints Morning stiffness lasting more than one hour Due to lack of movement in the night and formation of gel in the synovial fluid
108
Systemic symptoms of OA vs. RA
OA - no systemic symptoms | RA - feeling ill and fatigue
109
Heberden's vs. Bouchard's nodes
Both are osteophyte formation in OA Bouchard's - PIP Heberden's - DIP
110
Four signs of OA on x-ray
Loss of joint space Osteophyte formation Subchondral sclerosis Trabeculae fractures
111
Effect of IL17 on synovial macrophages
IL17 causes a switch in the phenotype of synovial macrophages to osteotype macrophages
112
Primary curves
Kyphoses - thoracic and sacral
113
Secondary curves
Lordoses - lumbar and cervical
114
Increased thoracic kyphoses - three causes
Osteoporosis Erosion Fracture
115
Treatment of osteoporotic kyphosis
Vertebral augmentation
116
Scheurmann's disease + presentation
Thoracic kyphosis present in adolescants | Pain in the back and difficulty breathing
117
Cause of lumbar lordosis x2
Weakness of the trunk muscles | Psoas dysfunction
118
Dermatomes of sciatic nerve
L5 and S1
119
Other than at the back - common presentation of flat back syndrome
Slight bend in the knees (due to internal rotation of the thigh)
120
Schmall's does and condition in which these are present?
Depression in the vertebra at the nucleus propulsus due to Scheurmann's disease
121
Most common region for scoliosis
Thoraco-lumbar region - thoracic abnormal curve and this then compensated for by lumbar curve
122
Different stages of scoliosis and when you treat these
<20 degrees - do nothing 20 - 40 degrees - wear a brace >40 degrees - surgical options
123
'Syndesmophyte'
Osteophyte present at the verterbral column | NB. Osteophyte technically only present at synovial joints
124
'Cauda equina syndrome'
Posterior dislocation of vertebral body - compression of the cauda equina - multiple nerve endings
125
'Discectomy/
Removal of the IV disc
126
'Laminectomy'
Removal of lamina of the spinous process
127
'DISH'
Diffuse idiopathic skeletal hyperostosis | Ossification of the anterior longitudinal ligament