Flashcards in Week 6 - Ageing Deck (77):
What is calcification?
What is ossification?
What is an osteoid/callus and what are the 2 types?
-protein mould of future bone --> embryo/fracture
1. soft callus --> no calcium (early)
2. hard callus --> with calcium (late)
*soft = not seen on xray, hard callus is
Which cells produce, lyse and mantain the bone?
production --> osteoblast
lysis --> osteoclast
maintain --> osteocyte
Which artery supplies bones?
nutrient artery in nutrient foramen (diaphysis/metaphysis) --> epiphysis has a different blood supply
How are lamellae orientated?
along lines of stress
What is at the centre of lamellae?
What is the name of the crystal found in bone?
calcium hydroxyapatite in collgen protein framework (matrix)
What % of bone is recycled per year?
At what age do we begin to lose bone each year and what % is it?
>30yrs, 0.5% bone loss per year (physiological ageing)
What is osteoporosis?
-excess lysis of bone or less production --> loss of bone density --> osteoporosis
What is new bone formation AKA and what is mature bone AKA?
woven bone - irregular, immature, fetus/growth plate/fracture (no lamellae)
lamellar bone - mature, regular bone (compact, solid + spongy with marrow)
What hormones/vitamins/minerals are involved in the control of bone recycling?
Outline the pathology of fracture healing
-1 week --> haematoma, inflammation
-1-3wks --> soft callus (osteoid - not seen on xray)
-3-6wks --> hard callus (seen on xray)
-8wks --> remodelling (*stress - normal bone again)
True or False?
Remodelling only occurs with stress
-i.e. required to remove support after a fracture (~8wks)
What is the microscopy of woven bone - osteoid?
1. irregular osteoid trabeculae
2. lack of lamellae
3. prominent lining by osteoblasts
4. irregularly arranged osteoclasts
5. granulation tissue
What is microscopy of lamellae/mature bone?
What are the systemic factors affecting bone healing?
-systemic diseases --> chronic disease; diabetes*
-drugs --> steroids
-genetic disorders --> hemophilia, etc
What are the local factors affecting bone healing?
-alignment --> improper reduction
-infection - debris, dead tissue in wound
-damage to nerves/BVs
-bone pathology --> tumours, osteoprosis, etc
What are the short term complications of bone healing?
-haemorrhage, vascular injury*
-infection --> septicemia
-tetanus, gas gangrene
What are the long term complications of bone healing?
-mal-union --> deformity
-pseudoarthrosis (false joint formation)
What terms are used for dead bone and new bone formation in bone necrosis following a fracture?
dead bone --> sequestrum
new bone --> involucrum
True or False?
CT neoplasms (sarcomas) are characterised by cells in a matrix/stroma with no tight junctions
What is the commonest malignant CT tumour?
#2 = Ewing's sarcoma
What is the commonest benign bone tumour?
What is the commonest benign and malignant soft tissue tumour?
benign --> lipoma
malignant --> liposarcoma
What are the typical gross and microscopic features of sarcomas?
-pleomorphic spindle cells
What does a single vs multiple osteochondromas on a patient suggest?
single --> acquired
multiple --> familial
What do osteochondromas typically present like?
-outpocket of hard nodules (bone) with a cartilage cap
-marrow can sometimes enter the nodule
What is the microscopy of giant cell tumour?
-cystic lesions with plenty of osteoclasts/giant cells ("osteoclastoma")
How does a patient with osteosarcoma typically initially present?
-pain + fever
Which body part is most commonly affected by osteosarcoma and where specifically in the bone is affected commonly?
-knee (60% cases) --> #2= shoulder
-affects METAPHYSIS of long bones
What gene mutation is commonly associated with osteosarcoma cases?
Rb gene mutations in >60% of cases
What are the microscopic and characteristic radiographic features of osteosarcoma?
-irregular fine lacy osteoid
-microcalcification (pulmonary spread)
-particularly on metaphysis (epiphysis = spared)
What is Codman's triangle?
-in osteosarcoma, there is swelling of tissue around bone causing lifting of periosteum
-lifting of periosteum --> reactive bone formation in a triangular-shaped fashion (Codman's triangle)
Which cells are affected in Ewing's sarcoma?
-primitive blast cells (like neuroblastoma) --> embryonic bone tumour
-small blue cells in sheets, no osteoid
Which mutation is commonly seen in pts. with Ewing's sarcoma?
95% pts. have a translocation --> t(11;22)
What is normal degeneration from ageing known as?
-senile atrophy (physiologic)
What are some examples of pathologic causes of degeneration?
-decreased workload --> disuse atrophy of muscles
-loss of nerve --> denervation atrophy
-decr. blood supply --> brain atrophy
-malnutrition --> marasmus
-loss of endocrine support --> Addison's
Which chromosome are the biological clock genes located on?
What % of our ageing is genetically determined vs. acquired causes?
genetic (biological clock genes) --> 60%
acquired --> 40%
What happens to telomeres with each cell division?
-progressively lost with each division until they disappear
What is progeria?
-disorder of ageing
-Hutchinson-Gilford synd, Werner synd, etc
-normal at birth but develop accelerated ageing
-develop AS, scleroderma, CVS disorders, dementia, etc. in childhood --> live till late teen
*Down's synd = another example of ageing disorder
What are the senile changes?
-loss of teeth
-prostatic hyperplasia (M)
-degenerative joint disease
-ankle oedema (heart failure)
*decreased height, weight, muscle
*increased fat, wrinkles
What is solar elastosis?
-loss of elastin and collagen in the superficial dermis --> replaced by amorphous protein (hard) --> loss of skin turgor (elasticity)
What is osteoporosis?
-reduced bone mass --> normal composition
-osteoblast/clast function imbalance
-loss of strength --> deformity --> fractures
What are the 2 types of primary osteoporosis?
Type 1 --> post-menopausal
Type 2 --> senile
What are the secondary causes of osteoporosis?
-immobilisation (i.e. post-fracture)
-drugs (steroids; chemo)
What happens to bone in osteoporosis?
-thinning of vertical trabeculae
-loss of horizontal trabeculae
Where is osteoporosis more common in postmenopausal women?
-neck of femur
What is the pathophysiology of osteoporosis?
-genetics + physical activity + endocrine/nutrition/drugs --> PEAK BONE MASS
-Menopause (1) + Ageing (2) contribute to loss of peak bone mass --> osteoporosis
-menoupause --> decreased serum estrogen, increased inflammatory cytokines, increased RANK/RANKL expression
-increased osteoclast activity
-ageing --> decreased replicative activity of osteoprogenitor cells/synthetic activity of osteoblasts/biologic activity of matrix-bound growth factors/physical activity
What is compartment syndrome?
inflammation --> increased osteofascial compartment pressure --> muscle ischaemia + necrosis (due to i.e. trauma, bleeds, insect bites, etc)
What is crush syndrome?
-muscle crush common in limbs
-road traffic accidents
-pressure --> necrosis --> inflammation
**c.f. compartment syndrome where inflammation causes an increased compartment pressure, crush syndrome is initiated by direct pressure leading to inflammation
What are the clinical features of compartment + crush syndrome?
-pain, swelling, inflammation, mottling (necrosis), blisters
-toxins enter circulation
What are the complications of compartment/crush syndrome?
-DIC (due to toxins)
-acute renal failure (myoglobin has nephrotoxic metabolites)
What is the Tx for compartment/crush syndrome?
-to releave osteofascial pressure
What are the 2 types of skeletal muscle fibres?
"One Slow Fat Red Ox"
What is myositis and muscular dystrophy?
myositis = inflammation of muscle
dystrophy = embryonic disorganisation (congenital)
What is myopathy?
-toxic/congenital (alcohol, drugs)
What gene mutation is present in muscular dystrophy?
-mutation of dystrophin on X chromosome p21
Why is muscular dystrophy known as pseudohypertrophy?
-initially there is hypertrophy due to fat + fibrosis --> then atrophy
What are the 2 types of muscular dystrophy?
Duchenne MD (DMD)
-severe --> death by 20yrs
Becker MD (BMD)
How does muscular dystrophy typically present?
-normal at birth
-starts with pelvic + limb weakness (even though muscles appear large) --> characteristic ladder sign (pt. has to climb on themselves to stand up from the ground)
-death typically by heart failure
What are the 3 types of myositis and which is most common?
1. polymyositis (rheumatica)***
3. inclusion body myositis
What is polymyositis?
-autoimmune (usually seen with other autoimmune disorders)
-CD8 cytotoxic T cell mediated myofibre necrosis
-Tx. with steroids
What is dermatomyositis?
-common in children
-paraneoplastic (esp. lung) in adults
-periseptal (outer) fibre inflammation + SKIN inflammation
What is inclusion body myositis?
-old age (>60)
-amyloid + tau protein deposition in muscle fibres
-age-associated degeneration --> like alzheimer's*
What can cause toxic myopathy?
-alcohol --> binge drinking
-drugs --> statins
What is myasthenia gravis?
-autoimmune disorder (Ab to acetylcholine receptors at NMJ) --> block receptors resulting in muscle paralysis
-muscle weakness --> esp. extra occular muscles (ptosis/diplopia) --> then becomes generalised
-Tx. = acetylcholine esterase, immunosuppression
-assoc. with thymic hyperplasia (65%)/thymoma (15%)
What is osteogenesis imperfecta?
-congenital bone disorder
-brittle bone, type 1 collagen
What is osteopetrosis?
-congenital bone disorder
What is the commonest cause of dwarfism?
-congenital bone disorder
-chondrocyte abnormality --> cartilage deficiency
-central body normal, limbs affected --> disproportionate growth
What is paget's disease?
-pain, sclerosis, deformity, fracture, nerve compression/deafness (if skull affected)
-can led to secondary osteosarcoma (late stage)
1. excess osteoclastic activity (osteolytic stage)
2. excess osteoblastic activity (osteoblastic stage)
3. finally, exhaustion of cellular activity (osteosclerotic stage)
What are the gross + microscopic features of paget's disease?
-increased osteoclasts + blasts
What is vitamin D deficiency referred to as in children vs. adults?
children (before closure of epiphyseal plates) --> rickets
adults --> osteomalacia
What is vitamin d deficiency and what are the features of it?
-more osteoid (protein)/less calcium --> bones are soft
*bowing of legs, lumbar lordosis, rachitic rosary, harrison groove, pigeon breast, frontal bossing