Disorders of the neuromuscular junction and muscle Flashcards
What are the disorders of muscle?
Myopathies
Myositis
Myotonic dystrophy
What may be seen in LMN disorders?
Weakness
Low tone
Fasciculations
Skeletal muscle fibres are innervated by _____ ______ whose cell _____ arise in the ______ horn of the spinal cord
Skeletal muscle fibres are innervated by motor neurons whose cell bodies arise in the ventral horn of the spinal cord
The terminal portion of these motor neurones give rise to very fine _________ that run along the muscle cell.
The synapses formed between motor neurons and muscle are called the _____ ___ plate
The terminal portion of these motor neurones give rise to very fine projections that run along the muscle cell.
The synapses formed between motor neurons and muscle are called the motor end plate
A single motor neurone may control ____ ______ cells but each muscle cell response to ____ ____ motor neuron
A single motor neurone may control many muscle cells but each muscle cell response to only one motor neuron
What is found on the end of the motor neurone?
ACh vesicles
What receptor are present on the muscle ?
ACh receptors
______ ______ moves along the nerve, _____ gated ______ channels open allowing influx of _____. Vesicles of _____ ______ are released into ______ ____.
action potential moves along the nerve, voltage gated calcium channels open allowing influx of calcium. Vesicles of acetyl choline are released into synaptic cleft.
____ _____ diffuses across the _____ ____. The _______ receptor opens and renders the membrane permeable to __/_ ions.
The ________ starts an ____ potential at the ____ ___ ___
Acetyl choline diffuses across the synaptic cleft. The acetylcholine receptor opens and renders the membrane permeable to Na/K ions.
The depolarisation starts an action potential at the motor end plate
__________ splits acetylcholine into _____ and ______ which is then sequestered into _______ _____
Acetylcholinesterase splits acetylcholine into acetate and choline which is then sequestered into presynaptic vesicles
What is curare?
d tubocurarine
A plant which occupies the same position on the ACh receptor but does not open ion channel
What does curare result in?
No muscle contraction- so no respiration
When is curare toxic?
IV or IM (1-15mins)
How does novichok work?
Inhibits cholinesterase
What conditions cause problems at the presynaptic motor neurone?
Abnormality of calcium, sodium or magnesium
Botulism
Lambert eaton myastheniac syndrome
Where is clostridium botulinum found?
In soil
What are the common mechanisms of becoming infected with botulinum clostridium?
Food and wounds can become infected.
IV drug users- black tar heroine
What does botulinum clostridium do?
Cleaves presynaptic proteins involved in vesicle formation and blocks vesicle docking with the presynaptic membrane
What are the symptoms of botulinum clostridium infection?
Rapid onset weakness without sensory loss/ Some medical and cosmetic uses)
What happens in LEMS?
Antibodies to presynaptic calcium channels leads to less vesicle release.
What is associated with Lambert eaton myasthenia syndrome?
Strong association with underlying small cell carcinoma.
What can Lambert eaton syndrome be treated with?
3-4 diaminopyridine
Myasthenia gravis is a ________ disorder, it is the _____ common disorder of the NMJ.
Myasthenia gravis is a postsynaptic disorder, it is the most common disorder of the NMJ.
What is the pathophysiology of MG?
Antibodies to acetylcholine receptors (AChR)
Recuded number of ACh receptors and flattening of endplate folds
Transmission becomes inefficient
What is the presentation of MG?
muscle weakness and fatiguability
When do symptoms of MG start?
When ACh receptors reduced to 30% of normal
ACh receptor antibodies are found in __-__% of patients
ACh receptor antibodies are found in 80-90% of patients
AChR antibodies block binding of Each but also trigger what?
Inflammatory cascade that damage the folds of postsynaptic membrane
The ______ plays a role in MG; __% of patients have _______ or _____
The thymus plays a role in MG; 75% of patients have hyperplasia or thymoma
When are the peaks of incidence of MG?
Females in 30s
Males in 60s or 70s
Female:Male ratio of MG
3:2
What are the clinical features of MG?
Weakness typically fluctuating- worse through the day
Most common presentation is with extra-ocular weakness, facial and bulbar weakness
Limb weakness is typically proximal
What is the acute medical treatment of MG?
Acetylcholinesterase inhibitor- pyridostigmine
IV immunoglobulin
What is the acute surgical treatment of MG?
Thymectomy- even in absence of thymus abnormality
What is the chronic medical treatment of MG?
- Immunomodulating
- Steroids
- Steroid sparing agents- azathioprine/mycophenolate
- Emergency treatment with plasma exchange or immunoglobulin
What drug should be avoided in MG?
Gentamicin
What do people with MG die of?
Respiratory failure and aspiration pneumonia
Skeletal muscle is _____ organised.
Skeletal muscle is highly organised.
What is the smallest contractile unit of skeletal muscle?
Muscle fibre- long, cylindrical, containing nuclei, mitochondria and sarcomeres
What grounds the muscle fibre?
Endomysium
__-__ muscle fibres are grouped to form ______ encapsulated by _______
20-80 muscle fibres are grouped to form fascicle encapsulated by perimysium
A large number of fascicles ensheathed in epimysium forms
An individual muscle
Describe smooth muscle
- cell lay out
- nucleus
- junctions
- surrounding tissue
- cell structure
- actin:myosin ratio
Not striated Single central nucleus Gap junctions Significant connective tissue No sarcomeres Actin myosin ration 10:1
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
What can precipitate fasciculations?
Stress, caffeine, fatigue
When do fasciculations occur pathologically?
In denervated muscle which becomes hyper excitable
What are fasciculations usually a sign of?
Disease in the motor neurone not the muscle
What is myotonia and what causes it?
Failure of muscle relaxation after use
Chloride channel
What are the symptoms/signs of muscle disease?
Myalgia
Muscle weakness
Wasting
Hyporeflexia
List the immune mediated muscle conditions?
Dermatomyositis
Polymyositis
List the inherited muscle conditions?
- Muscular dystrophies
- Dystrophinopathies
- Limb girdle muscular dystrophies
- Myotonic dystrophy
List the congenital muscle conditions?
- congenital myasthenia syndromes
- congenital myopathies
Describe the presentation of polymyositis?
Symmetrical, progressive proximal weakness developing over weeks to months
Raised CK
What does polymyositis respond to?
Steroids
Describe the presentation of dermatomyositis?
Clinically similar to polymyositis but associated with skin lesions- heliotrope rash on face
What % of people with dermatomyositis have an underlying malignancy?
50%
What is inclusion body myositis?
Degenerative disease, typically slowly progressive weakness in 6th decade of life with characteristic thumb sparing
What is the prevalence myotonic dystrophy?
Commonest muscular dystrophy
What is the genetic inheritance of myotonic dystrophy?
Autosomal dominant
Trinucleotide repeat disorder
What is the presentation of myotonic dystrophy?
Multisystem involvement
Myotonia, weakness, cataracts, ptosis, frontal balding, cardiac defects
What are muscular dystrophies?
Inherited noninflammatory progressive diseases. They have no central or peripheral nerve abnormality. DMD and BMD are the most common
What are the infectious causes of muscle disease?
Viral- coxsacchie
Trypanosomiasis
Cistercercosis- uncooked pork
Borrelia
What are the toxic causes of muscle disease?
Drugs
Venoms
What are the congenital causes of muscle disease?
Congenital myasthenia syndrome, congenital myopathies
Which drugs cause necrotising myopathies?
HMG-CoA reductase inhibitors (stains), fibres, nicotinic acid
What are necrotising myopathies?
Reduced essential co-enzyme production, myocyte membrane changes and increased oxidation
What are corticosteroid myopathies?
Disruption of RNA synthesis
Which drugs cause corticosteroid myopathies?
Fluorinated steroids such as dexamethasone and triamcinolone
What are mitochondrial myopathies?
Inhibition of mitochondrial DNA polymerase
Which drugs cause mitochondrial myopathies?
Zidovudine
What are lysosomal storage myopathies?
Increased lysosomal activity degrading muscle fibres
Which drugs cause lysosomal storage myopathies?
Hydroxychloroquine, amiodarone
Which drugs cause antimicrotubular myopathies?
Colchicine, vincristine
What are antimicrotubular myopathies?
Accumulation of lysosomes and autophagic vacuoles
Which drugs cause hypokalaemic myopathies?
Diuretics, oral contraceptives
What are hypokalaemic myopathies?
Disruption of water and electrolyte homeostasis
What are inflammatory myopathies?
Activation of immune system, resembles autoimmune disease
Which drugs cause inflammatory myopathies?
D-penicillamine and interferon-a
What is Rhabdomyolysis?
Dissolution of muscle
Damage of skeletal muscle causes leakage of large quantities of toxic intracellular contents into plasma
What are the causes of rhabdomyolysis?
Crush injuries, toxins, post convulsion, extreme exercise
What is the triad of rhabdomyolysis?
Triad of myalgia, muscle weakness and myoglobinuria
What are the complications of rhabdomyolysis?
Acute renal failure and DIC
What should be looked for when examining muscle?
Inspection- thin, wasted, fasciculation Palpation Strength resting- power across joints Neck strength Core strength Fatiguability
What is the MRC muscle power grading?
0 - no movement at all
1- flicker of movement when attempting to contract muscle
2- some muscle movement if gravity removed but none against gravity
3- movement against gravity but not against resistance
4- movement against resistance but not full strength
5- normal strength
