Muscle and the NMJ Flashcards
What characterises LMN disorders?
Weakness
Low tone
Fasiculations
Where do the cell bodies of motor neurons which innervate skeletal muscle fibres arise from?
The ventral horn of the spinal cord
What do the terminal portion of skeletal muscle fibres give rise to?
Very fine projection ions that run along the muscle cell
What are the synapses formed between motor neurons and muscle called?
The motor end plate
What is the rule regarding motor neurons and muscle cells?
A single motor neuron may control many muscle cells, but each cell responds to only one motor neuron
Describe neurotransmission at the NMJ
AP moves along nerve
Voltage-gated Ca+ open allowing Ca+ influx
Vesicles of acetylcholine released into cleft
Acetylcholine diffuses across cleft
Acetylcholine receptor opens and renders the membrane permeable to Na+/K+ ions
Depolarisation starts an AP at the motor end plate
What is the action of acetylcholinesterase?
Splits acetylcholine into acetate and choline
Choline is then sequestered into presynaptic vesicles
Describe curare
D tubocurarine
Occuies same position on ACh receptor but does not open ion channels
No muscle contraction- so no respiration
Only toxic IV/IM (1-15min)
Where is clostridium botulinum found?
Soil
Food and wounds can become infected
IV drug users- black tar heroin
What does botulinum toxin do?
Cleaves presynaptic proteins involved in vesicle formation and block vesicle docking with the presynaptic membrane.
Rapid onset weakness without sensory loss.
Some medical and cosmetic uses
What is Lambert Eaton Myasthenic Syndrome?
Antibodies to presynaptic calcium channels leads to less vesicle release. Strong association with underlying small cell carcinoma
What are some presynaptic disorders?
Botulism
Lambert Eaton Myasthenic Syndrome
What is an example of a post synaptic disorder?
Myasthenia Gravis
Describe Myasthenia Gravis
Most common NMJ disorder
AI- antibodies to acetyl choline receptors (AChR)
Reduced number of functioning receptors leads to muscle weakness and fatiguability
What is the pathophysiology of Myasthenia Gravis?
Reduced number of ACh receptors and flattening of endplate folds
Even with normal amounts of ACh transmission becomes inefficient
Symptoms start when AChR reduced to 30% of normal
What do ACh antibodies do?
Block binding of ACh but also trigger inflammatory cascades that damage the fold of the postsynaptic membrane (thymus plays a role, 75% have hyperplasia or thymoma)
When does myasthenia usually present in females and males?
Females 3rd decade
Males 6/7th decade
F:M 3:2
What are the clinical features of Myasthenia Gravis?
Weakness typically fluctuating-worse through day
Extraocular, facial and bulbar weakness
Limb weakness typically proximal
What is the treatment for MG?
Acetylcholinesterase inhibitor-pyridostigmine Thymectomy Immunomodulating Steroids/azathioprine Emergency- plasma exchange or Ig
What usually causes morbidity in MG patients?
Resp failure
Aspiration pneumonia
Describe skeletal muscle
Smallest contractile unit is the muscle fibre-long, cylindrical, containing nuclei, mitochondria, sarcomeres
Each surrounded by endomysium
20-80 group to form fascicle encapsulated by perimysium
Large number of these ensheathed in epimysium-forms individual muscle
Describe smooth muscle
Non-striated cells Single central nucleus Gap junctions between cells Connective tissue around them No sarcomeres Actin:myosin 10:1
What are the 3 muscle fibre types?
Type I, IIa, IIb
Describe Type I muscle fibres
Slow oxidative
Dense capillary network, myoglobin, resist fatigue
Describe Type IIa muscle fibres
Fast oxidative
Aerobic metabolism
Describe Type IIb muscle fibres
Fast glycolytic
Easily fatigued
What are fasciculations?
Visible, fast, fine spontaneous twitch
When may fasciculations occur?
In healthy muscle-precipitated by stress, caffeine, fatigue
In denervated muscle which may become hyperexcitable
Usually a sign of disease in motor neurone, not muscle
What is myotonia?
Failure of muscle relaxation after use
Due to chloride channel dysfunction
What are some symptoms/signs of muscle disease?
Myalgia
Muscle weakness- often specific patterns of weakness depending on cause e.g. proximal limbs in polymyositis
Wasting
Hyporeflexia
What are some inflammatory muscle diseases?
Dermatomyositis
Polymyositis
What are some inherited muscle diseases?
Muscular dystrophies
Dystrophinopathies
Limb girdle muscular dystrophies
Myotonic dystrophy
What are some congenital muscle diseases?
Congenital myasthenic syndromes
Congenital myopathies
Describe polymyositis
Symmetrical, progressive proximal weakness developing over weeks to months
Raised CK- responds to steroid
Describe dermatomyositis
Clinically similar to polymyositis but assoc with skin lesions
Heliotrope rash on face
Up to 50% have underlying malignancy
Describe inclusion body myositis
Degenerative
Little response to steroid
Typically slowly progressive weakness in 6th decade of life with characteristic thumb sparing
Describe myotonic dystrophy
Commonest muscular dystrophy
AD
Multisystem
Trinucleotide repeat disorder with anticipation
What are the clinical features of myotonic dystrophy?
Myotonia Weakness Cataracts Ptosis Frontal balding Cardiac defects
Describe muscular dystrophies
Inherited Non-inflammatory Progressive No central or peripheral nerve abnormality Duchenne/Becker most common
What are some infective muscular diseases?
Viral- Coxsacchie
Trypanosomiasis
Cistercercosis- uncooked pork
Borrelia
What is rhabdomyolysis?
Damage to skeletal muscle causes leakage of large quantities of toxic intracellular contents into plasma
What are the clinical features of rhabdomyolysis?
Myalgia, muscle weakness and myoglobinuria
Complications of acute renal failure and DIC
