Week 6 - Trauma, Fractures, Disorders & Tumours Flashcards
Describe bone structure.
• Calcification - Ca+ deposition.
• Ossification - bone formation.
• Osteoid/callus - protein mould of future bone (embryo/fracture - during embryo stage or healing of a fracture).
- Soft callus - no Ca+, early (not seen on X-ray).
- Hard callus - with Ca+, later (seen on X-ray).
• Osteoblast/osteoclast - produce/lysis.
• Osteocyte - maintains bone.
• Nutrient artery - blood supply.
• If there is a fracture at the site of the blood vessel → whole bone undergoes necrosis.
• Epiphyseal blood supply is different to metaphyseal blood supply.
• Location of nerves and blood vessels with the bone is very intimate so fractures do cause damage to the blood vessels and nerves.
• Cross section from bone
- Outer periosteum
- Compact bone
- Spongy bone
- Only difference between compact and spongy bone is the presence of marrow. Both are lamellated lamella - small spaces where osteocytes live.
Describe bone histology.
- Cut section of bone (unstained) - see systems where there are blood vessels in the centre surrounded by lamella
- Lamella - plates of calcium bone - hydroxyapatite crystals. There is continuous recycling - cells have cytoplasmic processes and constantly receiving nutrition from the blood vessels.
- Bone is composed of lamella - plates consisting of Haversian systems.
- They are orientated along lines of stress.
- Closer view of X-ray - can see lines in various orientations - due to normal stress that the bone is exposed too - important for normal bone function.
Outline bone metabolism.
• Calcium Hydroxyapatite (crystal) in collagen protein framework (matrix) - like RCC/concrete in buildings.
- Normally bone consists of calcium hydroxyapatite crystals similar to concrete in building. Collagen fibres are the metal rods. Collagen fibres provide tensile strength - can bend to a certain extent.
• Osteoid (collagen and protein matrix) is necessary for ossification.
• Continuous recycling of bone: 5-10%/year.
- Continuous recycling throughout life. Osteoclasts remove mature bone with dying osteocytes. New bone produced by osteoblasts. Some of the osteoblasts become osteocytes → get entangled and continuously maintain bone.
• Controlled by genetic, physical activity, age, nutrition, (vit D, Ca+), hormones, growth factors, IL-1, TNF, TGF-β.
• Excess lysis or less production → loss of density → osteoporosis (ageing: >30 years, 0.5% per year loss).
- After 30 years, loss 0.5% of bone every year - normal physiological ageing. When it increases → osteoporosis.
Differentiate between new/woven bone (embryo/healing fracture) and trabecular bone and marrow.
New/woven bone:
• Lined by large plump cells - osteoblasts.
• Centre is protein matrix - osteoid
• Woven bone - irregular, immature, fetus/growth plate/fracture (no lamellae). Prominent osteoblasts and granulation tissue inbetween.
Trabecular bone:
• Mature bone appears like fine lines - not many osteoblasts or osteoclasts. Similar to a completed building.
• Lamellar bone - mature, regular bone (compact, solid and spongy with marrow).
Outline bone recycling (osteoclasts, osteoblasts and osteocytes).
- Bone recycling occurs continuously through the action of osteoclasts (lysis) and osteoblasts (deposition). Controlled by various hormones, vitamins and minerals.
- Bone health maintained by activity - no exercise → bones become weak. An individual at prolonged bed rest quickly begins to lose bone mineral density (BMD). Conversely, physical activity increases BMD.
Control: • Growth hormone. • Insulin. • Vitamin D. • Vitamin C. • Calcium. • PTH. • Calcitonin.
Identify the clinical types of fractures.
- Clinically, there are many different types of fractures.
- Discontinuity in the bone.
- Simple/compound, comminuted.
- Horizontal, oblique, spiral.
- Greenstick/torus - children (incomplete fractures in children).
Describe the stages of fracture healing.
- 1 week - Haematoma formation.
- 1-3 week - Soft callus.
- 3-6 weeks - Hard callus.
- ~8 weeks - Remodelling (stress*).
- Broken bone - first thing to occur is a blood clot → inflammation. Approximately 1 week - acute inflammatory cells, macrophages come in.
- After 1 week, instead of scar formation, there is formation of a soft callus. The callus is the osteoid protein and it builds the bridge between the broken ends. Not seen on X-ray because there is no calcium.
- 3-6 weeks - gradual deposition of calcium (hydroxyapatite crystals) forming a hard callus. Seen on X-ray.
- 6-8 weeks - remodeling - occurs only with exposure to stress. No exposure to stress → no remodeling even for many years. Normally fracture heals back to normal in ~8 weeks but can be variable.
What are the factors affecting bone healing?
Local factors:
• Immobilisation* - proper immobilisation is important for bone healing.
• Alignment - improper reduction. Has to be aligned properly for quick healing/reduce the space.
• Infection - debris, dead tissue in wound.
• Joint involvement.
• Damage to nerves/blood vessels.
• Bone pathology - tumours, osteoporosis etc.
Systemic factors: • Age* • Nutrition, vitamin/mineral. • Immune status. • Systemic diseases - chronic disease, diabetes*. • Drugs - steroids. • Genetic disorders - haemophilia etc.
What are the complications of bone healing?
Short term: • Haemrrhage, vascular injury* • Nerve/visceral injury* • Crush Syndrome* • Fat embolism - bone marrow veins are still patent - fat gets embolised due to negative pressure in the venous system. • Renal failure. • Shock, DIC. • Thromboembolism. • Infection - septicaemia. • Tetanus, gas gangrene.
Long term:
• Delayed union.
• Non-union.
• Mal-union - deformity.
• Growth disturbances - when it involves epiphysis.
• Contractures.
• Avascular necrosis.
• Osteomyelitis - infection.
• Pseudoarthrosis - false joint formation (artificial joint).
• Osteoarthritis - damage to joint surface.
Outline bone necrosis and osteomyelitis.
- Common in compound fractures.
- Infection that enters the bone is very difficult to treat. Antibiotics do not enter → leads to delayed healing or necrosis can occur.
- Centre portion known as sequestrum (dead bone). When the dead bone is present in the wound, does not allow healing. Tube of new bone formation occurs on the outside - involucrum.
Outline connective tissue neoplasms.
• Connective tissue also known as soft tissue. Sarco = soft
• Carcinoma - hard tumour of epithelial cells (hard cancer). Sarcoma - soft tissue malignancy (soft cancer).
• Connective tissue characterised by cells separated by protein matrix/stroma. No tight junctions.
• Examples include fat, fibrous, cartilaginous, muscle tissue, bone, blood*. Most of body is CT apart from epithelium and nervous tissue.
• Benign tumours very common. Carcinomas rare. Common in young age unlike epithelial cancers common in the aged. Nearly 10% of younger age tumours are CT tumours.
• Childhood cancer - leukaemia, lymphoma, CNS tumours. Approx. 6% soft tissue and 4% bone tumour - together CT tumours (10% in children). Very rare in adults (<1%).
• 2 types of CT that lines surfaces (e.g. joint, pleura, peritoneum, pericardium) like epithelium. Both have no benign tumours, all malignant - synovial sarcoma and mesothelioma.
- Synovium - joint cavity.
- Mesothelium - pleura, peritoneum, pericardium.
Identify the common bone/soft tissue tumours.
Bone tumours:
• Benign - osteochondroma (benign tumour of bone).
• Malignant - commonest is osteosarcoma (malignant tumour of bone), then Ewing’s sarcoma.
Soft tissue tumours:
• Benign - commonest are lipomas, angiomas and leiomyoma - well demarcated.
• Malignant - liposarcoma, malignant fibrous histiocytoma (MFH - like fibrosarcoma), angiosarcoma - infiltrative.
• Osteosarcoma most common overall (60%).
Outline sarcomas.
- Sarcoma - usual presentation is in the lower limbs (e.g. thigh), deep swelling/tumour. Large or small. Fibrous, fat etc.
- Cut section shows tumour or in the subcutaneous fatty tissue.
Morphology:
• Gross (all sarcomas) - fleshy, soft, grey, infiltrative. May show haemorrhage but not common.
• Microscopy - pleomorphic spindle cells (elongated).
- Fibrous (spindle shaped cells in bundles - most sarcomas look well differentiated like this) or fat tissue (poorly differentiated, irregularities and fat).
Outline benign bone tumours.
• >100 times common than malignant.
• Osteochondroma (Exostoses) - common, benign, single (acquired condition), multiple (familial).
- Both bone and cartilage
- Usually appears as an outgrowth with a cartilage cap (the marrow can enter as well → forms a tumour).
• Produces prominent hard swellings from the bone - osteochondroma.
Giant cell tumour - aggressive, cystic, giant cells, osteoclasts.
• In between benign and malignant.
• Locally aggressive, does not spread or metastasise.
• Common in lower limb.
• Produces cystic lesions. Within the tissue shows plenty of osteoclasts, multinucleated giant cells.
• AKA osteoclastoma. Also common in younger age groups.
• Produces swelling.
Outline osteosarcoma.
• Common, genetic rare, pain and fever*
- Most common CT tumour.
- Sporadic form more common - genetic rare.
- Present with pain and fever (presents like an inflammation).
- Primary 10-20y, (secondary* in aged).
- Knee (60%)* and shoulder*
- Commonest usually occurs around the knee - lower end of femur/upper end of tibia.
- Around shoulder second common.
- Usually involves metaphysis of long bones.
- Rb gene mutation in >60%.
• Pleomorphic cells, fine lacy osteoid.
- Normal - mould of future bone (osteoid) lined by a single layer of osteoblasts. In this case, irregular pleomorphic osteoblasts with fine lacy osteoid with micro-calcification.
• Micro-calcification. Pulmonary spread.
- Micro-calcification very important feature. Seen on X-ray to diagnose osteosarcoma.
- Spread through blood vessels to lungs more commonly.
- Metaphysis, epiphysis sparing.
- “Mutton leg” appearance.
• Gross: grey, infiltrative, Codman’s triangle
- Lifts periosteum, reactive formation of bone on either side of tumour - known as Codman’s triangle. Tearing of periosteum from the bone → new bone formation. Appears like a triangular area of bone. Diagnosis feature of osteosarcoma.
• Micro: irregular pleomorphic cells, fine lacy osteoid, microcalcification*
Outline Ewing’s sarcoma.
- Second most common (after osteosarcoma). ~10%.
- Boys, blacks, <20 years, pelvis, thigh, leg.
- Undifferentiated sarcoma of primitive blast cells (like neuroblastoma).
- 95% of patients with Ewing tumour t(11;22) or t(21;22).
- Embryonic cells - small blue cells in sheets, no osteoid.
Outline ageing and the 2 types of degeneration.
• Ageing: progressive, irreversible, time dependent, physiological decline in structure and function (degeneration).
• Normal lifespan: 90-95 years* (120y max).
- Determined by many factors.
• Causes of ageing: age, genetic, stress and disease.
Degeneration - can be physiologic or pathologic.
• Physiologic:
- Ageing - senile atrophy (physiologic).
• Pathologic:
- Decreased workload - disuse atrophy of muscles.
- Loss of nerve - denervation atrophy.
- Decreased blood supply - brain atrophy.
- Malnutrition - marasmus.
- Loss of endocrine support - Addison’s.
Ageing
• Progressive, irreversible, time dependent, physiological degeneration.
• Loss of body mass, bone mass, elasticity of skin.
• Diseases, stress effect early ageing.
Describe the mechanism of ageing.
- Proliferation → differentiation → apoptosis/degeneration.
- Our age depends on our cell age.
- Mechanism of age depends on our cellular age
- In every tissue, the stem cells gradually mature and they eventually undergo degeneration - controlled by many genes and important biological clock genes on chromosome 1 → determines 60% of our age. 40% determined by our acquired features - damages, diseases, nutrition, hormones, environment.
Genetic - 60%. Acquired - 40%. 1. Proto-oncogenes (growth factors). 2. Growth/tumour suppressor genes. 3. Genes controlling apoptosis. 4. Genes controlling DNA repair. 5. Biological clock genes (Chr. 1)*
• Normal cells gradually decline in their capacity to divide and finally they die unlike cancer cells that continue to divide like stem cells.
• Many mechanisms - DNA damage, cellular replication, damaged proteins, nutrition (glucose, insulin) → all determine our cellular ageing.
• Every chromosome has an ending of telomeres. With every cell division, part of the telomere is loss. Finally when there is no more telomere, chromosome cannot divide.
*See diagram.
What are the theories of ageing?
• Still not sure of exact mechanism but there is evidence to suggest that there are multiple causes of ageing.
- Error Catastrophe Theory: accumulated errors in metabolism.
- Cross-Linking Theory: cross-linking of large molecules such as lipofuscin, amyloid etc. (non digestible).
• Production of large non digestible proteins e.g. lipofuscin, amyloid (increase in old age). - Wear and Tear Theory: accumulates repeated damage to DNA.
• The more the damage → less life. - Free Radical Theory: accumulation of oxidative injury.
- Pacemaker/biological clock Theory: organ systems have a biological clock that involute with age.
• Chromosomes have a biological clock, particularly chromosome 1. - Genetic Theory: familial longevity, genetic.
- Telomerase Theory: telomere shortening.
What is Progeria?
Disorders of Ageing: Progeria
• Progeria: Hutchinson-Gilford syndrome, Werner syndrome etc.
- Quite a few conditions that are very rare where in the child is normal at birth but they age very fast.
• Rare, genetic, normal at birth but develop accelerated aging.
• Develop atherosclerosis, scleroderma, CVS disorders, dementia etc. at childhood.
• Live until late teens.
• Down’s syndrome* - another condition where there is early ageing.
Identify senile changes.
- Decreased height, weight.
- Decreased muscles.
- Increased fat, wrinkles.
- Balding.
- Senile dementia*
- Cataracts.
- Deafness.
- Loss of teeth.
- Dermal elastosis.
- Hypertension and IHD.
- Osteoporosis*
- Osteoarthritis*
- Prostatic hyperplasia.
- Degenerative joint disease.
- Diverticular disease of colon.
- Ankle oedema due to heart failure.
• Senile dementia, osteoarthritis, osteoporosis, diverticulitis, prostatic hyperplasia, hypertension, IHD, skin changes, soft tissue changes, loss of teeth → together result in decreased height/weight, decreased muscle, altered posture, increased fat/wrinkles.
Describe solar elastosis of skin.
• Loss of elastin and collagen in the superficial dermis - solar elastosis (loss of elastic and collagen tissue replaced by amorphous protein which is hard → results in loss of skin turgor - elasticity).
Outline osteoporosis.
• Ageing of old bones.
• Reduced bone mass → normal composition
- Unlike rickets or osteomalacia. Normal composition with reduced quantity due to alteration in the osteoblast/osteoclast function.
• Osteoblast/osteoclast function imbalance (>30y resorption 0.5%/year).
- Normally there is continuous production of new bone and destruction of mature bone - recycling. After age of 30 years, resorption increases more then the production. Results in loss of bone mass - approx. 0.5%/year. Loss gradually accumulates resulting in osteoporosis.
• Localised/generalised (primary/secondary) - just like ageing, osteoporosis also affected by secondary/environmental factors.
- Primary: post menopausal (type 1), senile (type 2) - generalised loss of bone tissue all over body due to age.
- Secondary: immobilisation, endocrine, myeloma, nutrition, drugs (steroids, chemotherapeutic agents), alcohol etc.
Usually in one location due to many factors e.g. immobilisation of the leg following a fracture - loses bone density very quickly.
• Results in loss of strength → deformity (cannot withstand stress) → fractures.
• Post menopausal - vertebrae and neck of femur*
• Thinning of vertical and loss of horizontal trabeculae (very typical feature of osteoporosis - loss of bone tissue - results in deformities and minute or complete compression fractures of vertebrae).
- Thinning of vertical trabeculae.
- Loss of transverse trabeculae.
Explain the pathogenesis of osteoporosis.
- Genetic factors, physical activity, endocrine, nutrition, drugs altogether effect peak bone mass.
- Loss of bone mass also affected by menopause due to decreased oestrogen which leads to more spinal manifestations of osteoporosis (vertebral bodies)
- Bone mass also affected by ageing in general.
- Generalised reduction on bone mass leads to osteoporosis.
- Type 1 - females. Type 2 - others.
