Muscle and Neuromuscular Junction Dysfunction Flashcards
What are the symptoms of lower motor neuron disorders?
Weakness, low tone, fasciculations
What innervates skeletal muscle fibres?
Motor neurons = these have their cell bodies arise in the ventral horn of the spinal cord
What does the terminal portion of the motor neurons give rise to?
Very fine projections that run along the muscle cell
What are motor end plates?
Synapses formed between motor neurons and muscle
What is special about motor units?
A single motor neuron may control many muscle cells but each muscle cell only responds one motor neuron
What initiates muscle contraction?
AP moves along nerve = voltage gated Ca2+ channels open allowing calcium influx which releases vesicles of ACh into the synaptic cleft
What happens when ACh diffuses across the synaptic cleft?
Receptors open and render the membrane permeable to Na+/K+ = depolarisation starts an AP at the motor end plate
What is curare?
Plant extract = occupies same position on ACH receptor but doesn’t open ion channel, stops muscle contraction so respiration ceases
What are some presynaptic disorders?
Botulism and Lambert-Eaton myasthenic syndrome
What causes botulism?
Clostridium botulinium = present in soil, wounds and food can become infected, common in IV drug users (black tar heroin)
What occurs in botulism?
Cleaves presynaptic proteins involved in vesicle formation and blocks vesicle docking with the presynaptic membrane
What is the presentation of botulism?
Rapid onset weakness without sensory loss
What are some features of Lambert-Eaton myasthenic syndrome?
Antibodies to presynaptic Ca2_ channels leads to less vesicle release = strong association with small cell carcinoma, treated with 3-4 diaminopyridine
What is myasthenia gravis?
Postsynaptic disorder = most common NMJ disorder, auto-immune with antibodies to ACh receptors
What causes symptoms in myasthenia gravis?
Reduced number of functioning receptors leads to muscle weakness and fatiguability = symptoms occur when receptors reduced to 30% of normal
What effect do ACh antibodies have in myasthenia gravis?
Found inn 80-90% = block binding of ACh, also trigger inflammatory cascade that damage the folds of postsynaptic membrane (causes flattening)
How relevant is the thymus in myasthenia gravis?
Seems to play a role = 75% have hyperplasia or thymoma
What is the epidemiology of myasthenia gravis?
Peaks in females in 30s and males age 60-70
More common in women
What are the features of myasthenia gravis?
Weakness typically fluctuating = worse throughout day
Limb weakness is usually proximal
Most common presentation is extra-ocular, facial and bulbar weakness
What is the acute treatment of myasthenia gravis?
Acetylcholinesterase inhibitor = pyridostigmine
IV immunoglobulin
Thymectomy = even in absence of thymus abnormality
What is the general treatment of myasthenia gravis?
Immunomodulating, steroids, azathioprine or mycophenolate
What drug should be avoided in myasthenia gravis?
Gentamicin
What tends to cause death in myasthenia gravis?
Respiratory failure and aspiration pneumonia
What are some features of skeletal muscle?
Highly organised = each muscle fibre surrounded by thin layer endomysium, 20-80 grouped together to form fascicle encapsulated by perimysium
What is the smallest contractile unit of skeletal muscle?
The muscle fibre = long and cylindrical, contains nuclei, mitochondria and sarcomeres
What are some features of smooth muscle?
Cell not striated and gap junctions between cells
Single central nucleus and no sarcomeres
Actin to myosin ratio is 10:1
Significant connective tissue around them
What are the types of smooth muscle fibre?
Type I = slow oxidative, dense capillary network, myoglobin, resist fatigue
Type IIa = fast oxidative, aerobic metabolism
Type IIb = fast glycolytic, easily fatigued
What are fasciculations?
Visible, fast, fine, spontaneous twitches = occurs in denervated muscle which becomes hyperexcitable
What do fasciculations mean?
Can occur in healthy muscle = stress, caffeine, fatigue
Usually a sign of motor neuron (not muscle) disease
What are the symptoms of muscle disease?
Myalgia, wasting, hyporeflexia, muscle weakness
What are some examples of immune mediated muscle disease?
Polymyositis and dermatomyositis
What are some features of polymyositis?
Symmetrical progressive proximal weakness = develops over weeks, raised CK, responds to steroids
What are some features of dermatomyositis?
Associated with skin lesions = heliotrope rash of face
Up to 50% have underlying malignancy
What are some examples of congenital muscle diseases?
Congenital myasthenic syndromes
Congenital myopathies
What are some examples of inherited muscle diseases?
Muscular dystrophies, dystrophinopathies, limb girdle muscular dystrophies, myotonic dystrophies
What are some features of degenerative muscle diseases?
Inclusion body myositis = thought to be inflammatory but little response to steroids, slowly progressive weakness, begins in 60s, thumbs are spared
What is the most common muscular dystrophy?
Myotonic dystrophy = autosomal dominant, trinucleotide repeat disorder with anticipation
What are the features of muscular dystrophy?
Multisystem involvement = myotonia, weakness, cataracts, ptosis, frontal balding, cardiac defects
What are some features of inherited muscular dystrophies?
Non-inflammatory and progressive = non central or peripheral nerve abnormality, Duchenne and Becker dystrophies are most common
What occurs in rhabdomyolysis?
Dissolution of muscle = damage to skeletal muscle causes leakage of large quantities of toxic intracellular contents into plasma
What are some causes of rhabdomyolysis?
Crush injuries, toxins, post convulsion, extreme exercise
What are some features of rhabdomyolysis?
Triad of myalgia, muscle weakness and myoglobinuria
May lead to acute renal failure or DIC
What is done when examining muscle?
Inspection and palpation, strength testing, neck and core strength assessment, fatiguability
What are grades 0-2 of the MRC muscle power grading?
0 = no movement at all 1 = flicker of movement when trying to contract muscle 2 = some movement if gravity removed but none against gravity
What are grades 3-5 of the MRC muscle power grading?
3 = movement against gravity but not resistance 4 = movement against resistance but not full strength 5 = Normal strength
