Muscle and Neuromuscular Junction

Question 1

what are three characteristics of lower motor neurone disorders?

Answer 1

weak
low tone
fasiculations

Question 2

where do the cell bodies of motor neurones which innervate skeletal muscle arise?

Answer 2

ventral horn of spinal cord

Question 3

what does the terminal portion of motor neurones give rise to?

Answer 3

very fine projections that run along muscle cell

Question 4

what name is given to the synapses formed between motor neurones and muscle?

Answer 4

motor end plate

Question 5

how many motor neurones can one muscle cell respond to?

Answer 5

one

Question 6

how many muscle cells may a single motor neurone control?

Answer 6

many

Question 7

what is the presynaptic process of NMJ?

Answer 7

action potential moves along nerve

voltage gated calcium channels open allowing influx of calcium

vesicles of acetyl choline released into synaptic cleft

Question 8

what is the post synaptic process of NMJ?

Answer 8

acetyl choline diffuses across synaptic cleft

the acetyl choline receptor opens and renders membrane permeable to Na / K ions

the depolarisation starts an action potential at motor end plate

Question 9

what is the role of acetylcholinesterase?

Answer 9

breaks down acetyl choline into acetate and choline

Question 10

what happens to choline after it being formed from breakdown of acetylcholine?

Answer 10

sequestered into presynaptic vesicles

Question 11

what is name given to substance which occupies same position on ACh receptor but does not open ion channel?

Answer 11

curare (d tubocurarine)

Question 12

what is the fatal consequence of curare?

Answer 12

no muscle contraction so no respiration

Question 13

in what circumstances is curare toxic?

Answer 13

when given IV / IM (1-15 mins)

Question 14

how does novichok work?

Answer 14

inhibits cholinesterase

Question 15

what is clostridium botulinum?

Answer 15

organism present in soil

food and wounds can become infected

IVDU - black tar heroin

Question 16

how does botulinum toxin work?

Answer 16

cleaves presynaptic proteins involved in vesicle formation and blocks vesicle docking with presynaptic membrane

rapid onset weakness without sensory loss

Question 17

what is lambert eaton myasthenic syndrome (LEMS)?

Answer 17

antibodies to presynaptic calcium channels leads to less vesicle release

Question 18

what cancer is strongly associated to LEMS?

Answer 18

small cell carcinoma

Question 19

how is LEMS treated?

Answer 19

3-4 diaminopyridine

Question 20

what is myasthenia gravis?

Answer 20

autoimmune disorder where antibodies produced to acetyl choline receptors (AChR)

this causes reduced number of functioning receptors which leads to muscle weakness and fatiguability

Question 21

what is the pathophysiology of MG?

Answer 21

reduced number of ACh receptors and flattening of endplate folds

even with normal ACh the transmission becomes inefficient

Question 22

when do symptoms of MG begin?

Answer 22

when ACh receptors are reduced to 30% of normal

Question 23

in what percentage of patients with MG are ACh antibodies found?

Answer 23

80-90%

Question 24

as well as blocking binding of ACh, what else to the antibodies do in MG?

Answer 24

trigger inflammatory cascades that damage the folds of postsynaptic membrane

Question 25

as thymus plays a role in MG, 75% patients also have what other conditions?

Answer 25

hyperplasia or thymoma

Question 26

MG may occur at any age but what are the two peaks of incidence?

Answer 26

females in 3rd decade | males in 6th or 7th decade

Question 27

what is the clinical feature of MG?

Answer 27

weakness fluctuating - worse through day

Question 28

what is most common presentation of MG?

Answer 28

extraocular weakness facial weakness bulbar weakness

Question 29

limb weakness is typically proximal or distal?

Answer 29

proximal

Question 30

what is the acute treatment of MG?

Answer 30

acetylcholinesterase inhibitor - pyridostigmine IV immunoglobulin thymectomy

Question 31

what is long term treatment of MG?

Answer 31

immunomodulating steroids steroid sparing agents - azathioprine / mycophenolate

Question 32

what is the emergency treatment of MG?

Answer 32

plasma exchange or immunoglobulin

Question 33

what is biggest drug to avoid in MG?

Answer 33

gentamicin

Question 34

what is mortality of MG?

Answer 34

3-4%

Question 35

what is most common cause of death in MG?

Answer 35

respiratory failure and aspiration pneumonia

Question 36

what is the smallest contractile unit of skeletal muscle?

Answer 36

muscle fibre

Question 37

what is characteristics of muscle fibre?

Answer 37

long, cylindrical structure containing nucleii, mitochondria and sacromeres

Question 38

what surrounds each muscle fibre?

Answer 38

thin layer endomysium

Question 39

20-80 muscle fibres are grouped to form what? what encapsulates these groups?

Answer 39

fascicle encapsulated by perimysium

Question 40

what surrounds skeletal muscle as a whole?

Answer 40

epimysium

Question 41

what is type I muscle fibre also known as?

Answer 41

slow oxidative

Question 42

what is characteristics of type I muscle fibres?

Answer 42

dense capillary network myoglobin resist fatigue

Question 43

what is type IIa muscle fibres also known as?

Answer 43

fast oxidative

Question 44

what is characteristic of type IIa muscle fibres?

Answer 44

aerobic metabolism

Question 45

what is type IIb muscle fibres also known as?

Answer 45

fast glycolytic

Question 46

what is characteristic of type IIb muscle fibres?

Answer 46

easily fatigued

Question 47

what is fasciculations?

Answer 47

visible, fast, fine, spontaneous twitch

Question 48

can fasciculations occur in healthy muscle?

Answer 48

yes - precipitated by stress, caffeine and fatigue

Question 49

in which abnormal muscle can fasciculations occur?

Answer 49

denervated muscle which become hyperexcitable

Question 50

fasciculations are usually a sign of disease where?

Answer 50

motor neurone, not muscle

Question 51

what is myotonia?

Answer 51

failure of muscle relaxation after use

Question 52

what channel is involved in myotonia?

Answer 52

chloride channel

Question 53

what are the 4 main signs / symptoms of muscle disease?

Answer 53

myalgia muscle weakness wasting hyporeflexia

Question 54

what are examples of immune mediated muscle disease?

Answer 54

dermatomyositis | polymyositis

Question 55

what are examples of inherited muscle disease?

Answer 55

muscular dystrophies dystrophinopathies limb girdle muscular dystrophies myotonic dystrophy

Question 56

what are examples of congenital muscle disease?

Answer 56

congenital myasthenic syndromes | congenital myopathies

Question 57

what is the clinical feature of polymyositis?

Answer 57

symmetrical, progressive proximal weakness developing over weeks to months

Question 58

how is polymyositis treated?

Answer 58

responds to steroids

Question 59

what is the clinical feature of dermatomyositis?

Answer 59

similar to polymyositis but also has skin lesions - heliotrope rash on face

Question 60

up to 50% of patients with dermatomyositis have underlying what?

Answer 60

malignancy

Question 61

what is clinical sign of degenerative muscle disease?

Answer 61

typically slowly progressive weakness in 6th decade with characteristic thumb sparing

Question 62

what is the most common muscular dystrophy?

Answer 62

myotonic dystrophy

Question 63

what pattern of inheritance is myotonic dystrophy?

Answer 63

autosomal dominant

Question 64

what is symptoms of myotonic dystrophy?

Answer 64

``` myotonia weakness cataracts ptosis frontal balding cardiac defects ```

Question 65

what type of disorder is myotonic dystrophy?

Answer 65

trinucleotide repeat disorder with anticipation

Question 66

what are other 2 common muscular dystrophies?

Answer 66

duchenne and becker

Question 67

what are infective causes of muscle disease?

Answer 67

viral - coxsacchie trypanosomiasis cistercercosis - undercooked pork borrelia

Question 68

what are toxic causes of muscle disease?

Answer 68

drugs | venoms

Question 69

what causes rhabdomyolysis?

Answer 69

many things eg crush injuries, toxins, post convulsions and extreme exercise

Question 70

what is the triad of clinical features of rhabdomyolysis?

Answer 70

myalgia muscle weakness myoglobinuria

Question 71

what are 2 complications of rhabdomyolysis?

Answer 71

acute renal failure | disseminated intravascular coagulation

Question 72

what are the 5 grades of MRC muscle power?

Answer 72

0 = no movement 1 = flicker of movement when attempting to contract muscle 2 = some 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

Question 73

what is rhabdomylosis?

Answer 73

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