18. Muscle in health and disease - Robson Flashcards
What is the pattern of nuclei in a skeletal muscle cell?
Multinucleate cell
Where are the nuclei located in cells of skeletal muscle?
Nuclei are positioned peripherally
How long are skeletal muscle fibres?
10cm
What is the diameter of skeletal muscle fibres?
Vary between 10-100 micrometers
What is the significance of centrally located nuclei in skeletal muscle fibres?
Satellite cells have been activated to repair damaged muscle (nucleus moves back into the periphery once repaired)
What is the endomysium?
Aereolar connective tissue - covers each muscle fibre/muscle cell
What is the perimysium?
Connective tissue sheath - surrounds a bundle of muscle fibres from 10-100 - forms a muscle fascicle
What is the epimysium?
Fibroelastic tissue surrounding a muscle
How many muscle fibres are contained within a muscle fascicle?
Between 10-100
What is the centre of a skeletal muscle cell composed of?
Nuclei are peripheral so the centre is full of actin and myosin contractile proteins
Is skeletal muscle striated muscle? Why?
Yes - sometimes called striated muscle
This is because the actin and myosin form streaks - striated appearance
What is the shape of nuclei in the periphery of skeletal muscle cells?
Flattened
What is the shape of nuclei in the centre of skeletal muscle cells?
More rounded and bigger
What is skeletal muscle innervated by?
What does the innervation of the skeletal muscle lead to?
Innervated by motor neurones - initiate the contraction of the muscle
What chemical is involved in the innervation of skeletal muscle and where are these released from?
What are the receptors involved with this?
Ach
Ach released from the synapse terminal
Activation of nicotinic Ach receptor on the muscle fibre
Muscle contraction is initiated
How many muscle fibres are innervated by one motor neurone?
Between 5-200 muscle fibres
What is a motor unit?
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
What is the significance of the loss of a single motor neurone?
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
What is the effect on the shape of the skeletal muscle fibre if there is a loss of the innervating motor neurone?
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
What is the process of reinnervation?
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
Where are stress signals from deinnervated muscle fibres sent to?
Neuromuscular junction of neighbouring muscle fibres - want to signal to the motor neurone innervated neighbouring motor unit
What is the main consequence of reinnervation?
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
What is the phenotype of a muscle fibre dependent on?
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
How does reinnervtion result in a switch in the phenotype of muscle fibres?
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
What is the common name given to infantile hypotonia?
Floppy baby syndrome
What are the two different types of infantile hypotonia?
One affecting type 1 muscle fibres
One affecting type 2 muscle fibres
What type of metabolism is undergone by type 1 muscle fibres?
Mainly aerobic metabolism
What type of metabolism is undergone by type 2 muscle fibres?
Mix of aerobic and anaerobic metabolism
What are the two different types of infantile hypotonia and how do these present differently?
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
Are type 1 muscle fibres slow or fast contracting?
Slow contracting/slow twitch
Are type 2 muscle fibres slow or fast contracting?
Fast contracting/fast twitch
How can you distinguish between the two types of infantile hypotonia?
Using an ATP scan and looking at the ATP levels being used for contraction of the fibre
Can a H&E scan be used to distinguish between the two types of infantile hypotonia?
No
When does infantile hypotonia arise?
Congenital
What is the effect of infantile hypotonia on the individual in later life?
Individual can undertake normal daily activity and live normal lives but cannot do such intense sports and they get tired a lot faster
Does the hypotonia in infantile hypotonia improve in later life?
Why?
Fibres start to improve as the infant gets older - there is a lot of continued growth of the muscle postnatally
Do type 1 muscle fibres appear pale or dark?
Pale
Do type 2 muscle fibres appear pale or dark?
Dark
What is sarcopenia?
The loss of skeletal muscle strength and mass as a result of ageing
What conditions is sarcopenia closely associated with?
Osteoporosis
Do individuals experience weight loss when they have sarcopenia? Why?
No.
Because the muscle that is lost is replaced with fat
What is the difference in the onset in sarcopenia between men and women?
There is no difference
Give some potential cases for sarcopenia
Loss of motor neurones with age
Suboptimal nutrition
Mitochondrial dysfunction associated with ageing
Chachexia
What is chachexia?
Increase in the number of inflammatory conditions whilst we age - release of proinflammatory cytokines which cause damage to muscle
What are the three stages involved in diagnosing muscle disorders?
History
Muscle biopsy
Needly EMC
What is involved in taking a history to diagnose a muscle disorder?
Pain and weakness in the muscle Twitching and cramps Muscle atrophy and contractures Family history Any endocrine disorders?
What is the purpose of the needle EMC in diagnosing a muscle disorder?
Use this to differentiate between a neuropathy and a myopathy
What is a neuropathy?
Disease or dysfunction of one or more peripheral nerves
What is a myopathy?
Disease of muscle tissue/muscle membrane - spontaneously activated
What are the different types of myopathies?
Inflammatory
Degenerative
What are inflammatory myopathies commonly associated with?
Microbial infections
Which muscles are affected first in inflammatory myopathies?
Proximal muscles - big muscles of the shoulder and the hips, arms and thighs - symmetrical involvement
Give the name of two types of inflammatory myopathies
Polymyositis
Dermatomyositis
Are inflammatory myopathies autoimmune conditions?
Yes
Are inflammatory myopathies more prevalent in males or females?
Females
2:1 ratio
What is the common age of onset of inflammatory myopathies?
40-60 years
What is indicated by a raised serum creatinine kinase level?
Indicates that muscle fibres have been injured - these are releasing creatinine kinase into the blood
What will an EMG trace look like if there is no muscle movement?
Trace will be flat
What is the most definitive investigation for an inflammatory myopathy?
Biopsy
What can be looked for in a muscle biopsy?
Variation in fibre size
Central nuclei
Necrosis and regeneration
Infiltrate of inflammatory cells (lymphocytes)
What is the typical clinical presentation of dermatomyositis?
Purple coloured rash over the eyelids - the forehead is spared
May have a stripy appearance on the back
What is calcification at the dermis indicative of?
Involvement of the skin in an inflammatory myopathy - autoimmune condition
What autoimmune antibodies are prevalent in inflammatory myopathies?
ANA - antinuclear antigens e.g. anti-Jo1 in fibroblasts
What is the treatment for inflammatory myopathies?
Corticosteroids - high dose until creatinine kinase levels return to normal
Infliximab (t-cells) and rutuximab (b-cells)
What is the problem with stopping the corticosteroids too early when treating inflammatory myopathies?
If you stop too early - can end up with a flare of the disease which is even harder to control
What is the most common cause of death in individuals with inflammatory myopathies?
Pulmonary fibrosis - the connective tissue of the lungs becomes inflamed
What is inclusion body myositis?
This is a common muscle disease of the elderly
Only small muscle groups are involved
Is inclusion body myositis more common in males or females?
Males
Why is dysphagia common in inclusion body myositis (BM)?
The muscles in the oesophagus can be affected
How does inclusion body myositis appear on a biopsy?
Presence of inclusions and muscle damage
What are ‘inclusions’?
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
What protein is commonly involved in the formation of inclusions and vacuoles in IBM?
Beta-amyloid and hyperphophorylated Tau
What neurological condition is IBM very similar to?
Alzheimer’s disease - but in the muscle
What is a muscular dystrophy?
A hereditary condition marked by progressive weakening and wasting of the muscles
What is Duchenne muscular dystrophy?
Severe muscular dystrophy caused by genetic defect - severe weakening of the muscles
X-linked so seen in boys
What is Becker’s muscular dystrophy?
This is a milder form of Duchenne muscular dystrophy
Which muscles are mainly affected in muscular dystrophies?
The big, proximal muscles
Are the female carriers of Duchenne muscular dystrophy symptomless?
No - have a milder form
What are the creatine kinase levels like in an individual with Duchenne muscular dystrophy?
Elevated - muscle damage
What is the prognosis of Duchenne muscular dystrophy?
Continuous slow decline
Cannot walk by 7-12 years
Death in mid-late teens but now in late 20s to early 30s
What are the three characteristics seen in a biopsy in Duchenne muscular dystrophy?
Muscle fibres undergoing phagocytosis
Centrally located nuclei
Variation in the size of the muscle fibres
What happens in Duchenne muscular dystrophy?
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
Why do many individuals with Duchenne muscular dystrophy commonly die from cardiac complications?
Cardiac muscle does not have satellite cells and so it cannot repair itself
What type of myopathy can occur from corticosteroid intake?
Type 2 fibre atrophy
What type of myopathy can occur from alcohol intake?
Type 2 fibre atrophy
What is rhabdomyolosis?
The destruction of striated muscle cells
What is fibromyalgia?
Widespread muscle pain - problem of the connective tissue around the muscle
Is fibromyalgia more common in males or females?
80-90% of patients are female
In what age group is fibromyalgia common?
30-60 year olds
What is the common treatment for fibromyalgia?
Amitriptyline antidepressant - neuropathic pain analgesic
Also helps to reset the normal sleep cycle
Also SSRIs and exercise
Polymyositis and dermatomyositis are what type of muscular condition?
Inflammatory myopathy
Main cells involved in inflammatory myopathies are?
Lymphocytes
Dysphagia is a sign of what muscular condition?
Inclusion body myositis - damage to oesophagus
Muscle composition of the oesophagus is?
Upper 1/3 - striated/skeletal muscle
Lower 1/3 - smooth muscle
Middle - transitional
What reflex is lost in inclusion body myositis?
Quadriceps reflex - associated polyneuropathy
Is creatinine kinase raised in IBM?
Mildly
Duschenne muscular dystrophy occurs in males or females?
Males - x-linked
Rhambdomyelosis is caused by intake of what drug type?
Statins
