18. Muscle in health and disease - Robson

Question 1

What is the pattern of nuclei in a skeletal muscle cell?

Answer 1

Multinucleate cell

Question 2

Where are the nuclei located in cells of skeletal muscle?

Answer 2

Nuclei are positioned peripherally

Question 3

How long are skeletal muscle fibres?

Answer 3

10cm

Question 4

What is the diameter of skeletal muscle fibres?

Answer 4

Vary between 10-100 micrometers

Question 5

What is the significance of centrally located nuclei in skeletal muscle fibres?

Answer 5

Satellite cells have been activated to repair damaged muscle (nucleus moves back into the periphery once repaired)

Question 6

What is the endomysium?

Answer 6

Aereolar connective tissue - covers each muscle fibre/muscle cell

Question 7

What is the perimysium?

Answer 7

Connective tissue sheath - surrounds a bundle of muscle fibres from 10-100 - forms a muscle fascicle

Question 8

What is the epimysium?

Answer 8

Fibroelastic tissue surrounding a muscle

Question 9

How many muscle fibres are contained within a muscle fascicle?

Answer 9

Between 10-100

Question 10

What is the centre of a skeletal muscle cell composed of?

Answer 10

Nuclei are peripheral so the centre is full of actin and myosin contractile proteins

Question 11

Is skeletal muscle striated muscle? Why?

Answer 11

Yes - sometimes called striated muscle

This is because the actin and myosin form streaks - striated appearance

Question 12

What is the shape of nuclei in the periphery of skeletal muscle cells?

Answer 12

Flattened

Question 13

What is the shape of nuclei in the centre of skeletal muscle cells?

Answer 13

More rounded and bigger

Question 14

What is skeletal muscle innervated by?

What does the innervation of the skeletal muscle lead to?

Answer 14

Innervated by motor neurones - initiate the contraction of the muscle

Question 15

What chemical is involved in the innervation of skeletal muscle and where are these released from?

What are the receptors involved with this?

Answer 15

Ach

Ach released from the synapse terminal
Activation of nicotinic Ach receptor on the muscle fibre
Muscle contraction is initiated

Question 16

How many muscle fibres are innervated by one motor neurone?

Answer 16

Between 5-200 muscle fibres

Question 17

What is a motor unit?

Answer 17

These are the 5-200 muscle fibres that are all innervated by the same action potential from the same motor neurone - these fibres all contract at the same time

Question 18

What is the significance of the loss of a single motor neurone?

Answer 18

Then all the muscle fibres that are innervated by this motor neurone will cease to function - i.e. the whole motor unit will cease to function

Question 19

What is the effect on the shape of the skeletal muscle fibre if there is a loss of the innervating motor neurone?

Answer 19

Loss of innervating motor neurone
Muscle fibres are no longer innervated - become deinnervated and are no longer used
These muscle fibres undergo atrophy and become angulated in shape

Question 20

What is the process of reinnervation?

Answer 20

Deinnervated muscle fibres - start to atrophy and releases stress signals to neighbouring muscle fibres (at the neuromuscular junction)
Causes neighbouring motor neurones to sprout extra ends to innervated these deinnervated muscle fibres

Question 21

Where are stress signals from deinnervated muscle fibres sent to?

Answer 21

Neuromuscular junction of neighbouring muscle fibres - want to signal to the motor neurone innervated neighbouring motor unit

Question 22

What is the main consequence of reinnervation?

Answer 22

More muscle fibres are being innervated by the same motor neurone - the size of the motor unit is increasing
Fibres are now more grouped together
Results in switch in the phenotype of the neighbouring muscle fibres and hence alters proper functioning of the muscle

Question 23

What is the phenotype of a muscle fibre dependent on?

Answer 23

Dependent on the frequency of stimulation of the motor unit by the motor neurone
The frequency influences whether you have fast or slow twitch fibres

Question 24

How does reinnervtion result in a switch in the phenotype of muscle fibres?

Answer 24

If fibres from slow frequency motor neurones die and are now innervated by fibres from high frequency motor neurones - these fibres will switch in the phenotype

Question 25

What is the common name given to infantile hypotonia?

Answer 25

Floppy baby syndrome

Question 26

What are the two different types of infantile hypotonia?

Answer 26

One affecting type 1 muscle fibres | One affecting type 2 muscle fibres

Question 27

What type of metabolism is undergone by type 1 muscle fibres?

Answer 27

Mainly aerobic metabolism

Question 28

What type of metabolism is undergone by type 2 muscle fibres?

Answer 28

Mix of aerobic and anaerobic metabolism

Question 29

What are the two different types of infantile hypotonia and how do these present differently?

Answer 29

One - hypertrophy of the type 1 muscle fibres and disproportion between the size of the muscle fibres Two - hypertrophy of the type 2 muscle fibres and disproportion between the size of the muscle fibres The phenotype between these two is actually the same

Question 30

Are type 1 muscle fibres slow or fast contracting?

Answer 30

Slow contracting/slow twitch

Question 31

Are type 2 muscle fibres slow or fast contracting?

Answer 31

Fast contracting/fast twitch

Question 32

How can you distinguish between the two types of infantile hypotonia?

Answer 32

Using an ATP scan and looking at the ATP levels being used for contraction of the fibre

Question 33

Can a H&E scan be used to distinguish between the two types of infantile hypotonia?

Answer 33

No

Question 34

When does infantile hypotonia arise?

Answer 34

Congenital

Question 35

What is the effect of infantile hypotonia on the individual in later life?

Answer 35

Individual can undertake normal daily activity and live normal lives but cannot do such intense sports and they get tired a lot faster

Question 36

Does the hypotonia in infantile hypotonia improve in later life? Why?

Answer 36

Fibres start to improve as the infant gets older - there is a lot of continued growth of the muscle postnatally

Question 37

Do type 1 muscle fibres appear pale or dark?

Answer 37

Pale

Question 38

Do type 2 muscle fibres appear pale or dark?

Answer 38

Dark

Question 39

What is sarcopenia?

Answer 39

The loss of skeletal muscle strength and mass as a result of ageing

Question 40

What conditions is sarcopenia closely associated with?

Answer 40

Osteoporosis

Question 41

Do individuals experience weight loss when they have sarcopenia? Why?

Answer 41

No. | Because the muscle that is lost is replaced with fat

Question 42

What is the difference in the onset in sarcopenia between men and women?

Answer 42

There is no difference

Question 43

Give some potential cases for sarcopenia

Answer 43

Loss of motor neurones with age Suboptimal nutrition Mitochondrial dysfunction associated with ageing Chachexia

Question 44

What is chachexia?

Answer 44

Increase in the number of inflammatory conditions whilst we age - release of proinflammatory cytokines which cause damage to muscle

Question 45

What are the three stages involved in diagnosing muscle disorders?

Answer 45

History Muscle biopsy Needly EMC

Question 46

What is involved in taking a history to diagnose a muscle disorder?

Answer 46

``` Pain and weakness in the muscle Twitching and cramps Muscle atrophy and contractures Family history Any endocrine disorders? ```

Question 47

What is the purpose of the needle EMC in diagnosing a muscle disorder?

Answer 47

Use this to differentiate between a neuropathy and a myopathy

Question 48

What is a neuropathy?

Answer 48

Disease or dysfunction of one or more peripheral nerves

Question 49

What is a myopathy?

Answer 49

Disease of muscle tissue/muscle membrane - spontaneously activated

Question 50

What are the different types of myopathies?

Answer 50

Inflammatory | Degenerative

Question 51

What are inflammatory myopathies commonly associated with?

Answer 51

Microbial infections

Question 52

Which muscles are affected first in inflammatory myopathies?

Answer 52

Proximal muscles - big muscles of the shoulder and the hips, arms and thighs - symmetrical involvement

Question 53

Give the name of two types of inflammatory myopathies

Answer 53

Polymyositis | Dermatomyositis

Question 54

Are inflammatory myopathies autoimmune conditions?

Answer 54

Yes

Question 55

Are inflammatory myopathies more prevalent in males or females?

Answer 55

Females | 2:1 ratio

Question 56

What is the common age of onset of inflammatory myopathies?

Answer 56

40-60 years

Question 57

What is indicated by a raised serum creatinine kinase level?

Answer 57

Indicates that muscle fibres have been injured - these are releasing creatinine kinase into the blood

Question 58

What will an EMG trace look like if there is no muscle movement?

Answer 58

Trace will be flat

Question 59

What is the most definitive investigation for an inflammatory myopathy?

Answer 59

Biopsy

Question 60

What can be looked for in a muscle biopsy?

Answer 60

Variation in fibre size Central nuclei Necrosis and regeneration Infiltrate of inflammatory cells (lymphocytes)

Question 61

What is the typical clinical presentation of dermatomyositis?

Answer 61

Purple coloured rash over the eyelids - the forehead is spared May have a stripy appearance on the back

Question 62

What is calcification at the dermis indicative of?

Answer 62

Involvement of the skin in an inflammatory myopathy - autoimmune condition

Question 63

What autoimmune antibodies are prevalent in inflammatory myopathies?

Answer 63

ANA - antinuclear antigens e.g. anti-Jo1 in fibroblasts

Question 64

What is the treatment for inflammatory myopathies?

Answer 64

Corticosteroids - high dose until creatinine kinase levels return to normal Infliximab (t-cells) and rutuximab (b-cells)

Question 65

What is the problem with stopping the corticosteroids too early when treating inflammatory myopathies?

Answer 65

If you stop too early - can end up with a flare of the disease which is even harder to control

Question 66

What is the most common cause of death in individuals with inflammatory myopathies?

Answer 66

Pulmonary fibrosis - the connective tissue of the lungs becomes inflamed

Question 67

What is inclusion body myositis?

Answer 67

This is a common muscle disease of the elderly | Only small muscle groups are involved

Question 68

Is inclusion body myositis more common in males or females?

Answer 68

Males

Question 69

Why is dysphagia common in inclusion body myositis (BM)?

Answer 69

The muscles in the oesophagus can be affected

Question 70

How does inclusion body myositis appear on a biopsy?

Answer 70

Presence of inclusions and muscle damage

Question 71

What are 'inclusions'?

Answer 71

These are proteins that are abnormally folded | These form complexes known as vacuoles - these should not be present in muscle as they can cause damage

Question 72

What protein is commonly involved in the formation of inclusions and vacuoles in IBM?

Answer 72

Beta-amyloid and hyperphophorylated Tau

Question 73

What neurological condition is IBM very similar to?

Answer 73

Alzheimer's disease - but in the muscle

Question 74

What is a muscular dystrophy?

Answer 74

A hereditary condition marked by progressive weakening and wasting of the muscles

Question 75

What is Duchenne muscular dystrophy?

Answer 75

Severe muscular dystrophy caused by genetic defect - severe weakening of the muscles X-linked so seen in boys

Question 76

What is Becker's muscular dystrophy?

Answer 76

This is a milder form of Duchenne muscular dystrophy

Question 77

Which muscles are mainly affected in muscular dystrophies?

Answer 77

The big, proximal muscles

Question 78

Are the female carriers of Duchenne muscular dystrophy symptomless?

Answer 78

No - have a milder form

Question 79

What are the creatine kinase levels like in an individual with Duchenne muscular dystrophy?

Answer 79

Elevated - muscle damage

Question 80

What is the prognosis of Duchenne muscular dystrophy?

Answer 80

Continuous slow decline Cannot walk by 7-12 years Death in mid-late teens but now in late 20s to early 30s

Question 81

What are the three characteristics seen in a biopsy in Duchenne muscular dystrophy?

Answer 81

Muscle fibres undergoing phagocytosis Centrally located nuclei Variation in the size of the muscle fibres

Question 82

What happens in Duchenne muscular dystrophy?

Answer 82

There is a loss of muscle - muscle fibres undergo phagocytosis and are damaged - centrally located nuclei appear Muscle is then replaced by fibrous tissue - either connective tissue or fat Muscles are weakened

Question 83

Why do many individuals with Duchenne muscular dystrophy commonly die from cardiac complications?

Answer 83

Cardiac muscle does not have satellite cells and so it cannot repair itself

Question 84

What type of myopathy can occur from corticosteroid intake?

Answer 84

Type 2 fibre atrophy

Question 85

What type of myopathy can occur from alcohol intake?

Answer 85

Type 2 fibre atrophy

Question 86

What is rhabdomyolosis?

Answer 86

The destruction of striated muscle cells

Question 87

What is fibromyalgia?

Answer 87

Widespread muscle pain - problem of the connective tissue around the muscle

Question 88

Is fibromyalgia more common in males or females?

Answer 88

80-90% of patients are female

Question 89

In what age group is fibromyalgia common?

Answer 89

30-60 year olds

Question 90

What is the common treatment for fibromyalgia?

Answer 90

Amitriptyline antidepressant - neuropathic pain analgesic Also helps to reset the normal sleep cycle Also SSRIs and exercise

Question 91

Polymyositis and dermatomyositis are what type of muscular condition?

Answer 91

Inflammatory myopathy

Question 92

Main cells involved in inflammatory myopathies are?

Answer 92

Lymphocytes

Question 93

Dysphagia is a sign of what muscular condition?

Answer 93

Inclusion body myositis - damage to oesophagus

Question 94

Muscle composition of the oesophagus is?

Answer 94

Upper 1/3 - striated/skeletal muscle Lower 1/3 - smooth muscle Middle - transitional

Question 95

What reflex is lost in inclusion body myositis?

Answer 95

Quadriceps reflex - associated polyneuropathy

Question 96

Is creatinine kinase raised in IBM?

Answer 96

Mildly

Question 97

Duschenne muscular dystrophy occurs in males or females?

Answer 97

Males - x-linked

Question 98

Rhambdomyelosis is caused by intake of what drug type?

Answer 98

Statins