Osteo-articular Pathology Flashcards
1
Q
Name developmental osteo-articular disorders (x3)
A
- Osteogenesis imperfecta
- achondroplasia
- osteopetrosis
2
Q
Name systemic / generalised osteo-articular disorders (x5)
A
- infections - osteomyelitis
- osteoporosis
- rickets / osteomalacia
- hyperparathyroidism (skeletal effects)
- Paget’s disease
3
Q
Name neoplastic osteo-articular disorders (x4)
A
- bone forming tumours
- cartilage tumours
- fibrous tumours
- tumours of uncertain histogenesis
4
Q
Name joint osteo-articular diseases (x2)
A
- osteoarthritis
- rheumatoid arthritis
5
Q
What is the outer section of bone called?
A
Cortex
- compact bone
6
Q
What is the inner section of bone called?
A
Medulla
- cancellous bone
- spongy
- trabeculae
7
Q
What is in the trabeculae?
A
Bone marrow
8
Q
What does bone marrow do?
A
makes RBC / WBC
9
Q
What are the functions of bone? (x4)
A
- support
- protect organs
- host and protect bone marrow
- supplies calcium and phosphate
10
Q
Describe intramembranous ossification
A
- ossification centre in fibrous connective tissue membrane
- mesenchymal cells differentiate into osteoblasts - Bone matrix (osteoid) is secreted within fibrous mem
- osteoblasts secrete osteoid
- osteoid is mineralised / calcified within a few days = bone matrix
- trapped osteoblasts become osteocytes - Woven bone and periosteum form
- osteoid laid down between embryonic blood vessels - random network = trabeculae
- vascularised mesenchyme condenses on external surface of woven bone to become periosteum - bone collar of compact bone forms and red marrow appears
- trabeculae thicken just deep to periosteum = woven bone collar - later replaced by mature lamellar bone
- spongy bone remains internally and its vascular tissue becomes red bone marrow
11
Q
What bones are created by intracmembranous ossification?
A
Flat bones
- skull (not occipital bone)
- part of mandible / maxilla
- part of clavicles
12
Q
How long does is take for ostoid to become calcified once secreted from osteoblasts?
A
a few days
13
Q
What bones are created by endochondrial ossification?
A
long bones
14
Q
How are bone created by endochondrial ossification?
A
- Mesenchymal cells form hyaline cartilage
- bone collar forms on sides of long bone
- Blood vessels enter central ossification centre (cartilage can’t survive if O2 present, so bone forms) from periosteal bud
- spongy bone formed
- medullary cavity forms
- secondary ossification centres form
- epiphyseal blood vessels enter secondary ossification centres
- ossification of the epiphyses
- hyaline cartilage remains on epiphyseal plate and articular cartilage
15
Q
What is a periosteal bud?
A
Blood vessels from the periosteum which enter the centre of ossification in endochondrial ossification
16
Q
What is the medullary cavity?
A
aka marrow cavity
- central part of bone where marrow stored
17
Q
What are the following:
- diaphysis
- epiphysis
- epiphyseal
A
diaphysis
- bone between epiphyseal plates (middle part)
epiphysis
- bone above eiphyseal plates (top / bottom)
epiphyseal
- plate of cartilage
18
Q
Describe the growth plate in bone
A
aka epiphyseal plate
- well ordered columns of chondrocytes
- chondrocytes release matrix (proteoglycans, water, collagen)
- hypertrophy of chondrocytes are they get closer to zone of bone formation - reduced proteoglycan release, increased alkaline phosphatase - therefore increased calcification
- then they become calcified
- then converted to bone
19
Q
What happens if bone does not calcify in growth plate?
A
bone does not grow
20
Q
Where does alkaline phosphatase come from and what does it do in bone formation?
A
from chondrocytes in growth plates
causes calcification of hypertrophy chondrocytes to form bone
21
Q
Name condition associated with short limbs
A
achondroplasia
22
Q
What are physical symptoms of achondroplasia?
A
- short limbs
- trident hands
- smaller occipital bone / contracted base of skull
Normal - trunk/thorax
23
Q
What are trident hands?
A
- fingers all similar length
- fingers splay at 1st joint
24
Q
What type of bone formation is faulty in achondroplasia?
A
endochondrial ossification
25
how many births have achondroplasia?
1 in 30,000 live births
26
What % of achondroplasia is
- hereditary
- sporadic
hereditary = 25%
- autosomal dominant trait
Sporadic = 75%
- new mutations
27
Name long bones
humerus, ulna, radius
| femur, fibula, tibia
28
How is cartilage different in long bones in achondroplasia|
epiphyseal plates don't develop normally
| cartiage at end of long bones is enlarged
29
What happens in achondroplasia endochondrial ossification?
- disrupted columns of chondrocytes
- chondrocytes fail to hypertrophy
- defective calcification
- bone not formed
30
Which gene is responsible for achondroplasia and what is the type of mutation?
What does this gene do?
Fibroblast growth factor receptor 3 (FGFR3)
- point mutation
- in achondroplasia, FGFR3 is always active, so chondrocytes aren't switched on for hypertrophy
31
What are three conditions caused by faulty FGFR3?
- achondroplasia (dwarfism)
- craniosynostosis (abnormal scalp/sutures)
- lethal dwarism (foetus doesn't grow)
32
What is osteogenesis imperfecta?
aka brittle bones
- defective connective tissue
- abnormal synthesis of type 1 collagen
33
What % of ORGANIC matter of bone is made of collagen?
90%
34
What makes up 90% of organic matter of bone?
Collagen
35
What mutations cause osteogensis imperfecta?
point mutations of many genes.
| mainly - COL1A1 and COL1A2
36
how many types of osteogensis imperfecta are there?
8
| mild - severe
37
What determines the severity of osteogenesis imperfecta?
- number of point mutations
| - type of point mutations (amino acid substitution at point mutation)
38
What is the pattern of inheritance for osteogensis imperfecta?
autosomal dominant or recessive
39
What is the organic matrix in bone?
collagen / osteoid
40
What is the inorganic matrix in bone?
Calcium
41
What are symptoms of mild osteogenesis imperfecta?
- delicate bones
| - early osteoporosis
42
What are symptoms of severe osteogenesis imperfecta?
- can be lethal perinatally (just before / after birth)
- foetus can get fractures
Adults
- abnormal bone structure
- defective mineralisation
43
What are bones like in adults with osteogenesis imperfecta?
thin cortex = weak, bendy
| epiphyseal cartilage is fine, so normal length bones
44
What other symptoms can be present in osteogenesis imperfecta? (none bone related)
blue/grey eyes
- sclera is thin, so choroidal veins below show through
Dentogenesis imperfecta
- irregular dentine formation (NB enamel = no collagen)
- blue /grey hue
- in type III and IV osteogenesis imperfecta?
- loose joints for slender weak tendons
- poor muscle tone
- early loss of hearing in some children (middle ear bones)
- protrusion of the eyes
45
What type of osteogenesis imperfecta gets dentogenesis imperfecta?
types Ib, III and IV
46
What is the most common type of osteogenesis imperfecta?
type I
47
What are symptoms of osteogenesis imperfecta type I?
- fragile bones (fracture, slight spinal curvature)
- loose joints for slender weak tendons
- poor muscle tone
- blue-grey sclera in eye (choroidal veins below show through)
- early loss of hearing in some children (middle ear bones)
- protrusion of the eyes
- type 1A = no dentogenesis imperfecta
- type IB = dentogenesis imperfecta
- reduced life exp (risk fatal bone fracture)
48
Why does life exp reduce in osteogenesis imperfecta?
risk of fatal bone fracture
49
Which type 1 osteogenesis imperfecta is associated with dentogenesis imperfecta?
Type IB (not type 1A)
NB type III and IV collagen issues are also linked to dentogenesis imperfecta
50
What is disorder with v dense bone?
osteopetrosis
51
What is osteopetrosis?
```
osteoclast defect
bone formation > resorption
become become denser
reduced medullary cavity / space for marrow
reduced haemoposesis, inc WBC
increased risk infection
```
52
What is inhertiance pattern of osteopetrosis?
| How common is it?
inherited
| rare
53
What is haemoposesis?
Formation of blood cells in bone marrow
54
What does xray of osteopetrosis look like?
dense, bright white bone
| can't see medulla
55
with thick bone of osteopetrosis, is there an increase or decrease in risk of fracture?
increase
56
How many men / women get osteoporosis?
1 in 3 women (over 50)
1 in 10 men (over 50)
get fractures from osteoporosis
57
How many hip fractures are caused by osteoporosis each year?
70,000
58
How many wrist fractures are caused by osteoporosis each year?
50,000
59
How many spinal fractures are caused by osteoporosis each year?
40,000
60
What is most common fracture associated with osteoporosis?
hip (70,000 / year) - neck of femur fractures
```
then wrist (50,000) - radius in wrist - Colles fracture
then spine (40,000) - vertebral crush
```
61
How much does osteoporosis cost the NHS each year?
£1.7billion!
62
Define osteoporosis
reduced bone mass / density
- thinner cortex
- increased trabeculae spaces
63
What is main cause of osteoporosis?
post-menopause
64
What are other causes of osteoporosis?
```
Disuse
- prolonged bed rest
- paralysis
- weightlessness (space travel)
Diet
- Vit D, vit C, calcium, protein deficiency
- anorexia
Drugs
- heparin
- ethanol (poor diet)
- steroids - reduces bone mass
Endocrine
- adrenal failure
- testicular / ovarian failure
```
65
Name of form of protection against osteoporosis?
exercise
66
What is a Colles fracture?
fracture of radius in wrist, common in osteoporosis
67
What part of hip is likely to fracture?
neck of femur
68
How does spine fracture in osteoporosis?
vertebral crush
69
How do steroids cause osteoporosis?
reduces bone mass
70
What factors affect bone density?
- ethnicity
- age
- gender
71
What age is max bone density reached? and until what age is this level maintained?
18yrs
| to 25yrs
72
What age does bone density deteriorate?
30+yrs
73
What is max bone density? (g/cm2)
1 - 1.1g/cm2
74
What is bone density for someone with osteopenia?
0.7 - 0.9g/cm2
75
What is bone density of someone with osteoporosis?
76
At what age is the decreasing bone density levels most critical?
30-70yrs
| - early menopause / fast density losers = increased risk
77
How many times faster can some individuals lose bone density?
10x faster
78
What is the adult version of rickets?
osteomalacia
79
What is rickets?
inadequate bone mineralisation of existing organic bone matrix in growing bones
- lack of vit D
80
What is osteomalacia?
inadequate bone mineralisation of existing organic bone matrix in adult bones
81
What is most common cause of rickets / osteomalacia?
lack of vit D
82
What is high risk profile for rickets?
- lack of vit D / sunlight / use of sunscreen
- lack of calcium
- poor background
83
What are symptoms of rickets?
mechanical weakness in long bones in LOWER limbs
| bending / deformed lower limb long bones
84
What are causes of rickets / osteomalacia?
Intrinsic Vit D
- lack in diet
- poor absorption
- metabolism of vit D
- lack of sunlight
Kidney disease
- chronic kidney disease
- renal tubular disorders
Inborn errors metabolism
- familial hypophosphataemia
- hypophosphatasia
85
What bone disease does familial hypophosphataemia and hypophosphatasis cause and why?
Rickets / osteomalacia
- reduced phosphate in body
- therefore reduced alkaline phosphatase
- therefore deficient chondrocytes and osteoblasts
- therefore reduced bone mineralisation
- causes rickets
86
What happens to the epiphyseal plate in rickets?
- chondrocytes become disorganised / lines lost
- fibrous proliferation
- no calcification
87
How is vit D activated in body?
- skin
- liver (Vit D hydroxlyated)
- kidney (Vit D hydroxylated again)
88
What does vit D do?
promotes calcium absorption from gut and kidney
| - therefore increases calcium for bones
89
What happens to bones if lack of vit D?
```
cartilage forms (osteoid) instead of bone
- bendy, deformed, easily fractured
```
90
What bones are affected by osteomalacia?
- adults
- sites with active turnover
- structural weakness here
91
What type of fractures are common in osteomalacia?
Looser's zones
| - micro-fractures at sites with active bone turnover
92
What are micro-fractures at sites with active bone turnover called?
Looser's zones
- seen on xray
eg hip, neck of femur
93
What are other names for hyperparathyroidism?
Osteitis fibrosa cystica
| von Recklinghausen's disease
94
What is von Recklinghausen's disease?
hyperparathyroidism
95
What is Osteitis fibrosa cystica?
hyperparathyroidism
96
What does parathyroid hormone regulate?
Blood calcium and phosphate levels
97
What is primary hyperparathyroidism?
Issue with 1-4 parathyroids
eg tumour - adenoma / carcinoma
excess PTH produced
98
What is an adenoma?
benign cancer from glandular cells in epithelial tissue
99
What is a carcinoma?
cancer from epithelial cells
100
What is secondary hyperparathyroidism?
response to hypocalcemia
- due to vit D deficiency
- chronic renal disease
101
How is hyperparathyroidism diagnosed?
blood test - raised plasma calcium
102
What happens to PTH release if blood calcium high?
reduces
103
What happens to PTH release if blood calcium low?
increases
104
Do most patients with hyperparathyroidism have bone disease symptoms?
no, only a small number
105
What happens if hyperparathroidism is mistaken for bone disease?
issues will continue in other bone areas until hyperparathyroidism is diagnosed and treated
106
What is Paget's disease?
Excessive breakdown and formation of bone
with disorganised remodelling
irregular scalloped edges
multiple reversal lines
Chronic condition
usually localised (one / few bones)
usually asymptomatic
increase of serum alkaline phosphatase
107
What happens to bone in excessive osteoblasts activity in Paget's disease?
- excessive bone formation
- increase bone deformity
- reduced joint movt
108
What happens to bone in excessive osteoclast activity in Paget's disease?
- excessive resorption
- risk of fracture
- pain
109
Is Paget's disease symmetrical or unsymmetrical?
unsymmetrical
| - can occur anywhere
110
what is associated with Paget's disease?
parasytic infection
111
What can Paget's disease lead to? (another disease)
| Who is most at risk of this?
osteocarcinoma (malignant)
| - young people
112
What disease can cause the scalp to enlarge?
Paget's disease
113
What changes in blood serum in Paget's disease?
increase in serum alkaline phosphatase
114
What age is most susceptible to Paget's disease?
middle age
NB younger ppl more likely to progress to osteocarcinoma
115
What happens if bones of the skull are affected by Paget's disease?
middle ear bones = loss of hearing
| skull = uneven thickness, extensive sclerosis and enlargement
116
Which bone disease can cause loss of hearing and why?
Paget's disease
| - middle ear bones have excessive resorption / formation
117
Is fibrous dysplasia genetic or non-genetic?
genetic
| - specific mutations
118
What is fibrous dysplasia?
intramedullary fibro-osseous lesion
119
Who is affected by fibrous dysplasia?
```
all ethnic groups
adults and children
men and women
- men = skull and ribs
- women = long bones
```
120
Which bone disease has wonky eyes and lips?! (forming a > sign!)
fibrous dysplasia
121
Name and describe the two forms of fibrous dysplasia
Monostotic - only one bone involved
- skull - 35%
- femur/tibia - 33%
- ribs - 20%
Polyostotic - many bones affected
- femur / pelvis / tibia - >60% of cases
- one extremity or one side of body
- earlier onset cf monostotic
- associated with
- McCune-Albright syndrome (endocrine abnormalities and skin pigmentation)
- Mazabraud syndrome (intramuscular myxomas)
122
Which form of fibrous dysplasia has the later onset?
monostotic fibrous dysplasia
123
What bone disease is associated with McCune-Albright syndrome?
polyostotic fibrous dysplasia
McCune-Albright syndrome (endocrine abnormalities and skin pigmentation)
124
What bone disease is associated with Mazabraud syndrome?
polyostotic fibrous dysplasia
Mazabraud syndrome (intramuscular myxomas)
125
What is most common area for surgery for people with fibrous dysplasia?
gnathic (jaw) surgery
126
What is a lytic lesion?
| Which bone disease is it associated with?
radiolucent area on xray of bone, suggesting it's been destroyed
- bone expands and looks like 'ground glass'
- can be solid or partly cystic
Found in fibrous dysplasia
127
Where does a lytic lesion in bone spread to?
- remains in the bone - expands the bone
| - does NOT cause a periostial reaction or enter soft tissue
128
What is a periosteal reaction?
Formation of new bone by the periosteum
| Usually due to trauma / bone healing
129
What are the symptoms of fibrous dysplasia?
- usually asymptomatic
- pain
- risk of fracture
130
What % of tumours are bone tumours?
| Incidence rate?
1% (ie rare)
| 1000 new cases per year
131
What % of bone tumours are osteosarcoma?
| Incidence rate?
15%
| 150 new cases per year
132
Name a type of bone tumour
osteosarcoma
133
What age get osteosarcoma?
under 30yrs
| Mainly 12-25yrs
134
Is osteosarcoma usually benign or malignant?
benign
| malignant = rare
135
What is a classic sign of osteosarcoma?
periosteal reaction (ie new bone formation)
- 'sunburst' on xray
- ie perpendicular ossifications from osseous matrix streams from bone
- can have skip metastases (to other bone / lung)
136
Where does high grade intramedullary osteosarcoma occur most often in the body?
>50% in knees
- distal femur (32%)
- proximal tibia (15%)
137
Where does osteosarcoma occur in the bone?
>90% in metaphyseal (contains epiphyseal plate)
138
Where is osteosarcoma unlikely to occur in the body?
ribs
vertebrae
peripheral limbs
head and neck
139
What are the three types of osteosarcoma and what % for each?
high grade intramedullary osteosarcoma - 80%
periosteal osteosarcoma - 2%
parosteal - 5%
140
What other bone disease is linked to osteosarcoma?
osteoporosis
141
What is visible by bone in osteosarcoma?
woven bone
| cartilage
142
What is high grade intramedullary osteosarcoma?
tumour starts in medulla of bone and progresses towards metaphysis at one end
- v. aggressive
- both bone destruction (moth eaten) and formation on xrays
- bone can completely disappear
143
What is the treatment for high grade intramedullary osteosarcoma?
Chemotherapy and resection.
144
What is treatment for parosteal osteosarcoma?
'sharp bite' - remove tumour on the surface of the bone and part of cortex.
- no chemotherapy
- no full resection
145
What is parosteal osteosarcoma?
bone tumour on surface of the bone
| low grade malignancy
146
Where is the new bone formation most easily seen in high grade intramedullary osteosarcoma on xrays?
subperiosteal / above cortex
147
What is Codman's triangle?
Visible on xrays in high grade intramedullary osteosarcoma
| - area where periosteum is detached from cortex (acute angled triangle)
148
What does high grade intramedullary osteosarcoma look like histologically?
osteoblasts
- disorganised
- pleomorphic (cells change size/shape)
- nuclear hyperchromatism
Osteoid / bone
- disorganised
149
What is osteoarthritis?
disorder of synovial joints
- cartilage degeneration / articular cartilage breakdown
- secondary changes in neighbouring bone
reduced capillaries in joint, therefore reduced cartilage (needs nutrients from external blood vessels), subchondral bone exposed, osteophytes created to replace cartilage
Not a single disease, but a common response to physiologic and metabolic conditions
150
Which part of long bone isn't vascularised?
cartilage
151
What are osteophytess?
new bone formation at joint to replace lost cartilage
| - reduced joint movt
152
Where does osteoarthritis occur?
anywhere
| - esp knees / femur (hip) / hands / first metatarsophalangeal joint
153
What are the two types of osteoarthritis?
Primary osteoarthritis
- generalised or erosive
- unknown aetiology
Secondary osteoarthritis
- joints previous damaged (eg gout, rheumatoid arthritis)
154
What are three main symptoms of osteoarthritis?
- pain
- stiffness in morning (improves throughout day)
- joint may 'gel' with immobility
155
Who is likely to get osteoarthritis?
50+yrs
| obese
156
What can cause articular cartilage breakdown in the jaw in osteoarthritis? (x4)
- parafunction
- poor occlusion
- trauma
- genetics
157
What are symptoms of articular cartilage breakdown in the jaw in osteoarthritis? (x4)
- crepitation (crackling sound)
- pain around the ear
- limited movt
- bite shifting
158
What happens to the joint space in osteoarthritis?
Joint space narrows
- subchondrial sclerosis
- subchondrial cyst formation
- osteophytes
159
What happens when joint space is reduced?
reduced movt
