MSK - Phase 1 Flashcards
Gross anatomy + types of bone
Features of bone include:
- diaphysis/shaft
- epiphyses at ends
- metaphysis between, contains epiphyseal plate or growth plate
- rich blood supply
- marrow fills hollow interior
- surrounding layer of periosteum on the outside with endosteum lining the interior
- Woven bone* – common initial stage with randomly arranged collagen fibres found in foetuses, post-fracture and other pathological states, much weaker
- Lamellar bone* – much stronger layered form of bone remodelled from woven bone
- compact: layers of Haversian systems on the outside of bone
- spongy: branches of trabeculae that form along lines of mechanical stress
Mechanisms of bone growth
- intramembranous ossification* – for flat bones, layers of mesenchymal cells form a template for growth with spongy bone forming first before peripheral remodelling to create compact bone
- Endochondral ossification* – all other bones develop in this way e.g. long bones
- chondrocytes form a template of hyaline cartilage in the rough shape of the bone
- calcification causes chondrocytes to die
- osteoblasts invade cartilage scaffolding to form an ossification centre (primary centre in diaphysis and secondary centres in epiphyses)
- cartilage persists in the epiphyseal plate until adolescence when fusion prevents further growth
Overview of bone remodelling
Bone is a dynamic tissue with constant turnover and remodelling involving three cell types:
- osteoblasts – mesenchymal cells that produce osteoid, the collagen matrix that acts as a scaffold for bone and becomes mineralised through positive feedback + seed crystals
- osteocytes – trapped osteoblasts that reside in lacunae of Haversian systems, connected to each other by canaliculi, act as stress transducers
- osteoclasts – haematopoietic cells that produce enzymes and HCl to degrade bone and resorb the mineral components
Turnover of bone is regulated by a number of physical and chemical factors including hormones, mechanical stress, drugs, temperature, inflammation
Hormones + processes of calcium and phosphate metabolism
RANK/RANK-L/OPG signalling pathway in osteoporosis
- RANK-L produced by osteoblasts binds to RANK expressed on osteoclast to promote their recruitment and activity
- OPG also produced by osteoblasts binds to RANK-L to prevent it activating RANK, thereby suppressing osteoclasts from being overactivated
- Oestrogen normally limits RANK-L production, following menopause there is an increase in RANK-L which overwhelms OPG resulting in excess bone resorption
Pathophysiology of osteoporosis
Osteoporosis is a disease of ageing in which there is excessive osteoclast activity causing net resorption, factors contributing to this include:
- relative vitamin D deficiency, prompting osteoclasts to access Ca2+ by resorbing bone
- decline in recruitment and activity of osteoblasts
- further increase in osteoclast activity due to reduced circulating oestrogen via RANK-L
The result of these changes is net resorption of bone leading to a brittle skeleton that is easily fractured, further confounded by – vision loss, cognitive deficits etc.
Most common fractures: neck of femur, humerus, scaphoid (wrist), vertebrae
Pharmacological management of osteoporosis
Definitions of osteoporosis
osteopaenia = 1–2.5 SDs below the mean in young people
osteoporosis = >2.5 SDs below the mean in young people
Overview of osteomalacia
Osteomalacia = disease of bone mineralisation rather than resorption, osteoid is being produced at a normal rate however mineral deposition is not occurring to create strong bone, results in weakness and growth defects in children (bowed legs, skull thinning)
Causes include:
- vitamin D deficiency
- gastric surgeries
- coeliac disease
Classification of fractures
Open: skin or other external surface (includes GIT) is pierced by broken bone
Closed: all surfaces remain intact and broken bone is contained
Further classification based on morphology of break
- bone – which bone is involved
- site – where in the bone is the fracture
- appearance – transverse, oblique, spiral, comminuted, segmented etc.
- relationship of bone parts – displacement, angulation, translation
- relationship to joints – intraarticular vs. extraarticular
- relationship to skin – tenting, open/compound, closed
Types of joints with examples of each
Components of a synovial joint
Articular cartilage – thin plates of hyaline cartilage that transition from spongy bone to cover the articular surfaces of bone to provide smooth movement, avascular/aneural/alymphatic
Fibrous capsule – surrounds the ends of both bones and contains the joint, stabilises and limits movement in all directions equally
Synovial membrane – thin vascular inner lining of joint capsule that produces synovial fluid
Synovial fluid – plasma filtrate containing hyaluronic acid, lubricin, proteinase, collagenase that forms a thing layer at the surface of cartilage to nourish and absorb shock
may also have bursa, meniscus, fat pads etc. depending on joint
Types of muscle fibres
Connective tissue in muscles
epimysium – surrounding muscles
perimysium – surrounding muscle fibre fascicles
endomysium – surrounding individual muscle fibres
Acute vs. chronic muscle injuries
Acute
- strain: over-elongation or excess force causing a tear, often at muscle/tendon junction
- contusion: direct impact to muscle which causes bruising
Chronic
- overuse: repeated small amounts of force → microtrauma → tissue failure
- tendinopathy: damage to tendon resulting in thickening/nodules
Models of postural control
Feedback = balance is disturbed, muscle programs are activated to restore it
- ankle strategy used in younger people
- hip strategy used by the elderly
Feedforward = awareness of a balance disturbance before it occurs, allows for internal prediction and anticipatory postural adjustment to minimise disturbance
Components of the extracellular matrix
Disorders associated with connective tissue + ECM
Phases of wound healing
First intentions: thin, clean surgical wound that is sutured resulting in minimal scarring
Second intentions: complicated with inflammation + scarification
- inflammation – blood clotting, immune response
- proliferation – granulation tissue forms, angiogenesis occurs, macrophages/fibroblasts multiply
- maturation – formation of a fibrous scar, wound contraction, tissue remodelling
Overview of osteomyelitis
Osteomyelitis = inflammation of bone due to microbial infection, most commonly occurs at extremes of age and can be either acute or chronic
Two major routes of infection:
- direct spread (80%) – from adjacent sites including soft tissue, prosthetics, ulcers, penetrating wounds – typically S. aureus, can be polymicrobial
- haematogenous spread (20%) – typically caused by a single organism such as Staphylococcus, H. influenzae, E. coli, P. aeruginosa, GAS, GBS
Can result in abscess formation, ischaemic necrosis of bone, septicaemia, cellulitis, failure to thrive
Pathophysiology of rheumatoid arthritis
rheumatoid arthritis = peripheral, symmetrical, deforming polyarthropathy
- Citrullination = arginine → citrulline within some proteins (e.g. collagen, vimentin), this process can be accelerated due to smoking and results in self-antigens being seen as foreign by some HLA alleles (DR1/DR2)
-
Immune response is initiated against citrullinated proteins
- autoantibodies produced: anti-CCP + rheumatoid factor, these initiate the complement cascade and promote inflammation
- immune cell infiltrate and production of cytokines
- proliferation of synovial membrane → fibrous pannus which damages joint
- T cells express RANK-L which promotes osteoclast activity
- Ongoing immune response spreads systemically resulting in extra-articular manifestations
Extra-articular manifestations of RA
Mneumonic : A Pulmonary CVRS
Most common systemic signs include:
- Rheumatoid nodules = foci of central fibrinoid necrosis within skin
- Anaemia of chronic disease
- Pulmonary: fibrosis, pleural effusion
- Cardiovascular: atherosclerosis, myocardial infarction, pericarditis + effusion
- Sjogren’s syndrome
- Vasculitis
X-ray signs of RA
Mneumonic: JOMS
- marginal erosions
- joint space narrowing
- osteoporosis
- soft tissue swelling
Characteristic deformities of RA
- Ulnar deviation of MCP joints
- Boutonniere: PIP flexion, DIP extension
- Swan-neck: PIP extension, DIP flexion
Pharmacological management of RA
Pathophysiology of osteoarthritis
Osteoarthritis is a degenerative joint disease resulting from wear and tear of joint structures, poor vascular supply → poor capacity for healing
Contributing factors may include:
- obesity
- traumatic damage
- occupation or sport
- connective tissue disorders or other diseases of cartilage
X-ray signs of osteoarthritis
- reduced joint space
- osteophytes
- subchondral cysts
- subchondral sclerosis
Other types of arthritis/arthropathies
Seronegative spondyloarthropathies: spectrum of inflammatory joint diseases that primarily affect entheses
- ankylosing spondylitis – inflammation of the sacroiliac joint + lumbar spine
- psoriatic arthritis – associated with psoriasis
- reactive arthritis – associated with infection e.g. gastroenteritis, UTI, Chlamydia
- enteropathic arthritis – associated with IBD
Crystal arthropathies: result from deposition of precipitated crystals within the joint space
- gout – uric acid
- pseudogout – calcium pyrophosphate
septic arthritis: active infection within joint from direct or haematogenous spread most commonly due to S. aureus infection
Types of pain
(three N’s)
nociceptive → activation of nociceptors reflective of tissue damage
neuropathic → damage to sensory nerves
neuroplastic → issues with peripheral or central pain processing
Pain receptors + fibres
Radiculopathy overview
Radiculopathy = damage to spinal nerves resulting in pain/numbness and muscle weakness in dermatome and myotome distribution, usually due to compression in IV foramen
- disc herniation
- lumbar: central herniation will impinge on cauda equina (SN below) while far lateral herniation will impinge on the exiting spinal nerve (SN above) e.g. L4/5 disc: central L5 radiculopathy, lateral L4 radiculopathy
- cervical will impinge on the nerve root leaving at that level
- osteoarthritis of facet joints or ligament pathology
Spectrum of peripheral nerve injuries
neuropraxia → stretching or nerve that damages sheath
axonotmesis → severance of axons while sheath remains intact
neurotmesis → complete transection of nerve including axon + sheath
Intervertebral disc structure + pathology
IV-disc structure consists of:
- annulus fibrosis – fibrous laminar rings, poorly-localised pain innervation
- nucleus pulposus – hydrated gel distributes force and resists compression
- herniation* → results when unbalanced mechanical pressures deform the annulus fibrosis allowing the nucleus pulposus to protrude, usually central or lateral
- discitis* → inflammation, linked to vertebral osteomyelitis
Spondylolysis vs. spondylolisthesis
Spondylolysis = vertebral stress fracture
Spondylolisthesis = shifting of vertebrae out of alignment due to weakening by stress fractures
Types of hypersensitivity reaction
Brief outline of SLE, scleroderma, Sjogren’s syndrome
systemic lupus erythematosus = autoimmune reaction against nuclear antigens such as DNA and histones resulting in production of anti-nuclear antibodies which form immune complexes that deposit throughout the body causing systemic effects
- specific organ manifestations: pleuritis, pericarditis, arthritis, renal disease, seizures
scleroderma = group of autoimmune diseases characterised by increased collagen production, results in skin thickening, Raynaud’s phenomenon other systemic effects e.g. GORD
Sjogren’s syndrome = autoimmune disease affecting exocrine glands resulting in dry eyes and mouth, progresses to systemic effects and often associated with SLE and RA
Stages of anaesthesia
Different drugs and adjuvants can be used at each stage, with different pros/cons
- induction
- maintenance
- emergence
Common IV and inhaled anaesthetics
Intravenous
- propofol, binds to beta subunit of GABA receptor to increase binding affinity of endogenous GABA
- benzodiazepines also commonly used e.g. midazolam, these bind to alpha and beta subunits of the GABA receptor to increase affinity
Inhaled
sevoflurane, believed to have actions as a GABA receptor modulator as well as an NMDA receptor antagonist
Four major postural problems in childhood orthopaedics
Generally these postural problems are physiological and will correct with age, suspect pathological cause if painful, age inappropriate, asymmetrical or affecting function
- flat feet: painless normal childhood variation
- intoeing: levels of origin – metatarsus adductus, tibial torsion, femoral anteversion
- bowlegs/knock-knees: knee alignment varies over time but can be associated with rickets or Blount’s disease
- scoliosis: idiopathic adolescent scoliosis most common in teenage females
Other common presentations in childhood orthopaedics
Developmental dysplasia of the hip = shallow acetabulum → congenital dislocation
Talipes equinovarus = club foot from dislocated talonavicular joint
Perthe’s disease = avascular necrosis of femoral head with unknown cause
Osgood-Schlatter’s disease = traction injury of tibial tuberosity → microfractures or avulsion
Salter-Harris classification of paediatric fractures
WHO analgesic ladder
- non-opioid analgesics + adjuvants
- mild opioids + adjuvants
- strong opioids + adjuvants
Types of muscular dystrophy
Muscular dystrophies arise from X-linked genetic mutations in the genes that encode the dystrophin protein which has a role in supporting the sarcolemma of muscle cells
- Duchenne – dystrophin is completely absent
- Becker’s – some dystrophin present but not enough for normal function
Result is muscle weakness + fatigue, abnormal gait, pseudohypertrophy and eventual failure of the heart and breathing muscles
Overview of Guillain-Barré syndrome
Type IV hypersensitivity reaction in which there is an immune response direct towards the Schwann cells that form the myelin sheath of peripheral nerves
- triggered by infection (URTI or gastroenteritis) or vaccination (rare)
- presents with progressive numbness, tingling, pain, weakness and ataxia
- most cases will make a full recovery but some fatalities occur due to breathing failure
Tumours of nerves, muscles, cartilage and bone
Nerves
- neurofibroma
- Schwannoma
- MPNST = malignant peripheral nerve sheath tumour
Muscle
- rhabdomyosarcoma
Cartilage
- benign – enchondroma
- malignant – chondrosarcoma
Bone
- benign – osteoblastoma, osteoid osteoma
- malignant – osteosarcoma, secondary metastases
Overview of myasthenia gravis
Type II hypersensitivity reaction in which there is a chronic autoimmune response initiated by circulating antibodies against the nicotinic acetylcholine receptor of the NMJ
- typically affects the muscles of the eyes (ptosis, diplopia) and face
- prognosis is generally good with effective treatment
Components of the cytoskeleton
Types of motor proteins
ATP driven enzymes which migrate along the cytoskeleton to perform essential functions such as muscle contraction, intracellular transport, motility and cell division
- myosins – bind and move along actin filaments
- kinesins – move towards plus end of microtubules, generally anterograde to periphery
- dyneins – move towards minus end of microtubules, generally retrograde to centre
Sensory receptors of proprioception
Muscle spindle → detects muscle stretch
spindles arranged parallel to fibres within muscle, innervated by gamma motor neurons which contract the spindle to reset its length so that it remains sensitive to stretch
Golgi tendon organ → detects muscle tension
innervated collagen fibres in the musculotendinous junction, will terminate contraction if muscle tension becomes excessive
Overview of motor neurone disease
MND = progressive neurological disease characterised by degeneration of motor neurons with sensory sparing, results in wasting of voluntary muscles and death due to breathing failure
Classification of MND is based on part of the body affected and pattern of involvement
-
Global type: 90% of all cases, affects UMNs and LMNs
- ALS – muscle weakness and stiffness later spreading to muscles of speech and swallowing
- bulbar palsy – begins in muscles of speech and swallowing
- Progressive muscular atrophy: LMN signs initially which may become ALS with later involvement of UMNs, often called flail arm or flail leg depending on where affected
- Primary lateral sclerosis: rare form that only affects UMNs
Major causes of peripheral neuropathy
Pneumonic = “Do Alcoholics Giggle Before Producing _T_heir CV”
Peripheral neuropathy = pathology of the peripheral nerves which may include sensory, motor or autonomic effects
- Diabetes – microvascular damage from hyperglycaemia results in nerve hypoxia
- Alcohol – damage due to acetaldehyde + ROS from alcohol
- B12 deficiency – essential vitamin for neurological function
- Compression/entrapment e.g. carpal tunnel syndrome
- Guillain-Barré syndrome – autoimmune damage to nerve sheath
- Toxins e.g. drugs, heavy metals
- Vasculitis – may be associated with SLE, Sjogren’s
- Paraneoplastic effects – usually from SCLC
Stages of transmission at the neuromuscular junction
- Nerve action potential: opening of VGSCs propagates AP along axon towards terminal
- Release of acetylcholine: AP reaches axon terminal and causes calcium influx which triggers release of ACh stored in synaptic vesicles, this is then recycled via enzymatic degradation by acetylcholinesterase
- End plate depolarisation: ACh acts on nicotinic receptors of the motor endplate which are ion channels that allow sodium influx causing depolarisation
- Muscle action potential: depolarising current from endplate travels across sarcolemma and down T-tubules where it induces calcium release from the SR and contraction
Major types of muscle relaxants
Inflammatory myopathies
Polymyositis = direct immune destruction of muscle fibres
Dermatomyositis = immune cells attack small blood vessels of the muscles and skin
Lumbar Plexus
Brachial Plexus
Mnemonic: READ THAT DAMN CADAVERIC BOOK !!!!
R - root (C5-T1)
T - trunk (sup, mid, inf)
D - division (anterior & posterior)
C - cord (lat, pos, med)
B - branches (musculocutaneous, axillary, radial, ulna, median)
Cervical Plexus
From Week 6 MSK anatomy lab manual
Upper Limb Nerve Pathway
Lower limb muscles
Lower leg muscles
Plantar muscles
From https://www.orthobullets.com/foot-and-ankle/7003/layers-of-the-plantar-foot
Explain the motor and sensory functions of the branches of the brachial plexus
Mnemonic:
3 musketeers (C5-C7)
(gun/2) assassins (C5-C6)
5 rats (C5-T1)
5 mice (C5-T1)
2 unicorns (C8-T1)
Myotomes and Motor Peripheral innervation of the upper limb
Sensory PNS Upper Limb nerves
Dermatomes of Upper Limb
Muscles of forearm
Motor testing of upper limbs
Myotomes and Motor Peripheral Nerve Innervation of Lower Limb
Dermatomes and Sensory Peripheral Nerves of Lower Limb
Radiculopathy Vs Peripheral Neuropathy
Acute pain Vs Chronic Pain
-
acute
- immediate onset, duration of minutes/hours/days/weeks
- due to immediate/direct injury or insult to the tissue (AMI/trauma/sprain)
- specific known cause
- readily responsive to analgesia
- will resolve once cause is fixed/treated
-
chronic
- prolonged duration -> weeks/months/years/lifelong
- often unclear cause
- diffuse in nature
- resistant/unresponsive to analgesia (will require weak-stronger opioid)
- reliant on opioid in order to carry on with ADLs & maintain QOL
- potentially psychosomatic (previous trauma/PTSD/transferrance etc)
Reflexes and corresponding spinal cord level
