Muscle and Neuromuscular Junction Dysfunction

Question 1

What are the symptoms of lower motor neuron disorders?

Answer 1

Weakness, low tone, fasciculations

Question 2

What innervates skeletal muscle fibres?

Answer 2

Motor neurons = these have their cell bodies arise in the ventral horn of the spinal cord

Question 3

What does the terminal portion of the motor neurons give rise to?

Answer 3

Very fine projections that run along the muscle cell

Question 4

What are motor end plates?

Answer 4

Synapses formed between motor neurons and muscle

Question 5

What is special about motor units?

Answer 5

A single motor neuron may control many muscle cells but each muscle cell only responds one motor neuron

Question 6

What initiates muscle contraction?

Answer 6

AP moves along nerve = voltage gated Ca2+ channels open allowing calcium influx which releases vesicles of ACh into the synaptic cleft

Question 7

What happens when ACh diffuses across the synaptic cleft?

Answer 7

Receptors open and render the membrane permeable to Na+/K+ = depolarisation starts an AP at the motor end plate

Question 8

What is curare?

Answer 8

Plant extract = occupies same position on ACH receptor but doesn’t open ion channel, stops muscle contraction so respiration ceases

Question 9

What are some presynaptic disorders?

Answer 9

Botulism and Lambert-Eaton myasthenic syndrome

Question 10

What causes botulism?

Answer 10

Clostridium botulinium = present in soil, wounds and food can become infected, common in IV drug users (black tar heroin)

Question 11

What occurs in botulism?

Answer 11

Cleaves presynaptic proteins involved in vesicle formation and blocks vesicle docking with the presynaptic membrane

Question 12

What is the presentation of botulism?

Answer 12

Rapid onset weakness without sensory loss

Question 13

What are some features of Lambert-Eaton myasthenic syndrome?

Answer 13

Antibodies to presynaptic Ca2_ channels leads to less vesicle release = strong association with small cell carcinoma, treated with 3-4 diaminopyridine

Question 14

What is myasthenia gravis?

Answer 14

Postsynaptic disorder = most common NMJ disorder, auto-immune with antibodies to ACh receptors

Question 15

What causes symptoms in myasthenia gravis?

Answer 15

Reduced number of functioning receptors leads to muscle weakness and fatiguability = symptoms occur when receptors reduced to 30% of normal

Question 16

What effect do ACh antibodies have in myasthenia gravis?

Answer 16

Found inn 80-90% = block binding of ACh, also trigger inflammatory cascade that damage the folds of postsynaptic membrane (causes flattening)

Question 17

How relevant is the thymus in myasthenia gravis?

Answer 17

Seems to play a role = 75% have hyperplasia or thymoma

Question 18

What is the epidemiology of myasthenia gravis?

Answer 18

Peaks in females in 30s and males age 60-70

More common in women

Question 19

What are the features of myasthenia gravis?

Answer 19

Weakness typically fluctuating = worse throughout day
Limb weakness is usually proximal
Most common presentation is extra-ocular, facial and bulbar weakness

Question 20

What is the acute treatment of myasthenia gravis?

Answer 20

Acetylcholinesterase inhibitor = pyridostigmine
IV immunoglobulin
Thymectomy = even in absence of thymus abnormality

Question 21

What is the general treatment of myasthenia gravis?

Answer 21

Immunomodulating, steroids, azathioprine or mycophenolate

Question 22

What drug should be avoided in myasthenia gravis?

Answer 22

Gentamicin

Question 23

What tends to cause death in myasthenia gravis?

Answer 23

Respiratory failure and aspiration pneumonia

Question 24

What are some features of skeletal muscle?

Answer 24

Highly organised = each muscle fibre surrounded by thin layer endomysium, 20-80 grouped together to form fascicle encapsulated by perimysium

Question 25

What is the smallest contractile unit of skeletal muscle?

Answer 25

The muscle fibre = long and cylindrical, contains nuclei, mitochondria and sarcomeres

Question 26

What are some features of smooth muscle?

Answer 26

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

Question 27

What are the types of smooth muscle fibre?

Answer 27

Type I = slow oxidative, dense capillary network, myoglobin, resist fatigue Type IIa = fast oxidative, aerobic metabolism Type IIb = fast glycolytic, easily fatigued

Question 28

What are fasciculations?

Answer 28

Visible, fast, fine, spontaneous twitches = occurs in denervated muscle which becomes hyperexcitable

Question 29

What do fasciculations mean?

Answer 29

Can occur in healthy muscle = stress, caffeine, fatigue | Usually a sign of motor neuron (not muscle) disease

Question 30

What are the symptoms of muscle disease?

Answer 30

Myalgia, wasting, hyporeflexia, muscle weakness

Question 31

What are some examples of immune mediated muscle disease?

Answer 31

Polymyositis and dermatomyositis

Question 32

What are some features of polymyositis?

Answer 32

Symmetrical progressive proximal weakness = develops over weeks, raised CK, responds to steroids

Question 33

What are some features of dermatomyositis?

Answer 33

Associated with skin lesions = heliotrope rash of face | Up to 50% have underlying malignancy

Question 34

What are some examples of congenital muscle diseases?

Answer 34

Congenital myasthenic syndromes | Congenital myopathies

Question 35

What are some examples of inherited muscle diseases?

Answer 35

Muscular dystrophies, dystrophinopathies, limb girdle muscular dystrophies, myotonic dystrophies

Question 36

What are some features of degenerative muscle diseases?

Answer 36

Inclusion body myositis = thought to be inflammatory but little response to steroids, slowly progressive weakness, begins in 60s, thumbs are spared

Question 37

What is the most common muscular dystrophy?

Answer 37

Myotonic dystrophy = autosomal dominant, trinucleotide repeat disorder with anticipation

Question 38

What are the features of muscular dystrophy?

Answer 38

Multisystem involvement = myotonia, weakness, cataracts, ptosis, frontal balding, cardiac defects

Question 39

What are some features of inherited muscular dystrophies?

Answer 39

Non-inflammatory and progressive = non central or peripheral nerve abnormality, Duchenne and Becker dystrophies are most common

Question 40

What occurs in rhabdomyolysis?

Answer 40

Dissolution of muscle = damage to skeletal muscle causes leakage of large quantities of toxic intracellular contents into plasma

Question 41

What are some causes of rhabdomyolysis?

Answer 41

Crush injuries, toxins, post convulsion, extreme exercise

Question 42

What are some features of rhabdomyolysis?

Answer 42

Triad of myalgia, muscle weakness and myoglobinuria | May lead to acute renal failure or DIC

Question 43

What is done when examining muscle?

Answer 43

Inspection and palpation, strength testing, neck and core strength assessment, fatiguability

Question 44

What are grades 0-2 of the MRC muscle power grading?

Answer 44

``` 0 = no movement at all 1 = flicker of movement when trying to contract muscle 2 = some movement if gravity removed but none against gravity ```

Question 45

What are grades 3-5 of the MRC muscle power grading?

Answer 45

``` 3 = movement against gravity but not resistance 4 = movement against resistance but not full strength 5 = Normal strength ```