Muscle in Health and Disease Flashcards
How many % of total body mass is muscle?
How many % of the total body water is in muscle?
40%
80%
What does muscle store? (4)
Intracellular ions such as potassium
Water
Calcium
Glucose
What is another role of muscle?
Important for heat production
Describe a muscle cell.
Multi-nucleate, 10cm long and 10-100mm in diameter.
Peripheral nuclei
What is a muscle fibre formed of?
Formed by the fusion of many individual cells (up to 200) together into a muscle fibre.
When might a muscle cell nucleus be central (rather than peripheral)?
When it has undergone damage that required repair, so it is regenerating. It will move to the periphery once it is repaired.
What two contractile proteins are muscle fibres made up of?
Actin and myosin
What is the endomysium?
Surrounds each individual myocyte
What is the perimysium?
Surrounds a bundle of muscle fibres, grouping them together
What is the epimysium?
Surrounds the entire muscle.
Motor neurons initiate contraction of muscle - how?
They cause the release of Ach from synapse terminal which activates the nicotinic Ach receptors on fibre and initiates contraction.
What is a muscle unit?
A single motor neuron innervates 5-200 muscle fibres - this is a muscle unit.
What happens if you lose a single motor neuron?
All the muscle fibres/whole unit innervated by that motor neuron are affected and they atrophy as they are no longer innervated. They become small, angulated muscle fibres.
Why are all the fibres in a motor unit the same fibre type?
Because the fibre type is determined by the primary motor neuron that innervates the unit.
How does loss of a motor neuron cause grouping and enlargement?
The loss of a motor neuron puts out stress signals to the NMJ on neighbouring fibres, causing remaining motor axons to sprout to innervate de-innervated fibres. This means that the motor units are enlarged (made up of more fibres) and the fibres become grouped (when it should be a haphazard arrangement of fast/slow fibres and scattered). The re-innervated fibres may switch from their old phenotype to a new one determined by this new motor neuron.
What is infantile hypotonia often called?
What is it?
Floppy baby syndrome
Decreased muscle tone due to congenital fibre type disproportion.
What do the fibres look like on biopsy (in infantile hypotonia)?
Most fibres are small and round with a few massively hypertrophic fibres
Why do type 2 fibres stain dark with ATPase stain?
Type 2 fibres are (small) fast-contracting fibres, that use mixed aerobic and anaerobic metabolism. The more ATP you have, the quicker you can contract the muscle (i.e. fast fibres have lots of ATP) and this stain demarks fibres with lots of ATPase versus those with less, so they appear dark.
Why do type 1 fibres stain pale with ATPase stain?
Type 1 fibres are (large) slow-contracting fibres, that use mainly aerobic metabolism. The more ATP you have, the quicker you can contract the muscle (i.e. slow fibres don’t have a lot of ATP) and as this stain demarks fibres with lots of ATPase versus those with less, they appear pale.
There are two types of infantile hypotonia. How are these differentiated?
Need ATPase stain to tell the difference
One type - type 1 fibres are normal/larger than normal and type 2 are small.
Other type – type 2 fibres are normal/larger than normal, type 1 are small
Sarcopenia - what is this?
Loss of muscle
What is the rate of muscle loss after age of 50?
What about if you are physically inactive?
0.5 – 1%
3% - 5%
What is the difference in muscle loss between men and women?
No difference
Why don’t people with sarcopenia lose weight?
The muscle is replaced with fat.
What are the endocrine causes of sarcopenia? (5)
Corticosteroids GH IGF-1 Abnormal thyroid function, Insulin resistance
What are the age-related/primary causes of sarcopenia? (3)
Sex hormones
Apoptosis
Mitochondrial dysfunction
What are other causes of sarcopenia? (4)
Cachexia
Disuse (immobility, physical inactivity)
Sub-optimal nutrition and malabsorption
Neurodegenerative disease – motor neuron loss
What should be asked about when taking a history for diagnosing muscle disorders? (7)
Any history of endocrine disorders? Muscle atrophy or contractures? Which muscles affected? Family history? Drug exposure? Pain and weakness? Twitching and cramps?
How are muscle disorders diagnosed?
Muscle biopsy (taken from quadriceps) Needle EMG
How does the EMG of a patient with a myopathy look?
Low grade, low amplitude, constant irritated muscle EMG.
Name three inflammatory myopathies.
Polymyositis
Dermatomyositis
Inclusion body myositis
Dermatomyositis - what is it associated with?
What type of disorder is it?
Associated with microbial infection
Autoimmune
What does dermatomyositis cause to the muscle?
Proximal muscle weakness
How many people get dermatomyositis per year?
5-10 million
What age group does dermatomyositis mainly affect?
40-60 years
Is dermatomyositis more common in men or women?
2:1 prevalence in females
What are the clinical features of dermatomyositis?
What is most definitive?
Symmetrical involvement of large proximal muscles of shoulders, arms and thigh
Serum creatine kinase elevated (released by injured muscle fibres)
EMG (typical irritability in 90%)
Biopsy most definitive
What is seen on biopsy for dermatomyositis?
Variation in fibre size
Central nuclei
Necrosis and regeneration
Infiltrate of inflammatory cells (lymphocytes)
How do lymphocytes damage the muscle in dermatomyositis?
Infiltrating CD8+ T lymphocytic cells surround and invade individual histologically healthy muscles fibres expressing MHC class I antigens, with macrophages to remove necrotic fibres. They attack outer edges/fibres of muscle first. This damages muscle fibres and results in splits.
Describe the rash in dermatomyositis.
Rash on face and back, involvement of hands with psoriasis plaques. There is also heliotrope rash over eyelids with oedema.
The rash is typically purplish in colour and often
has a streaky pattern.
What is a complication of dermatomyositis?
Subcutaneous calcifications (forms at epidermal-dermal junction) in muscles and skin
Dermatomyositis is an autoimmune connective tissue disease. What is the relevance of this?
This means that 90% of patients are positive for the autoimmune antibody ‘anti-nuclear antigen’. The most prevalent one is anti-Jo1 (positive in 20-40% of cases).
How is dermatomyositis treated?
Corticosteroids (high dose of 1mg/kg prednisone per day) until 1-2 weeks after creatine kinase returns to normal
Azathioprine and methotrexate (for immunosuppression)
What happens if corticosteroid treatment for dermatomyositis is stopped early?
There can be flares/rebound, which are difficult to control
What is the 5 year survival for dermatomyositis?
80%
What is the 8 year survival for dermatomyositis?
73%
When is death in dermatomyositis more likely?
If anti-Jo 1 positive
What do patients with dermatomyositis often die from?
Malignancy or infection (due to immunosuppressive treatment) Pulmonary involvement (pulmonary fibrosis)
What is the most common muscle disease of elderly?
What is the prognosis?
Inclusion body myositis
Poor prognosis
Is inclusion body myositis more common in men or women?
Men
Which muscles are most affected in inclusion body myositis?
Finger and wrist flexors Knee extensors (quadriceps)
What does inclusion body myositis cause? (5)
Muscle weakness Mild elevation in creatine kinase Loss of quadriceps reflex Dysphagia Associated polyneuropathy (motor neurons have inclusions as well)
What is seen on biopsy of inclusion body myositis?
Fibres contain empty vacuoles and clumps of cellular material that contain amyloid-like material.
Variation in muscle fibre size
Centrally located nuclei
What do the inclusions of IBM contain? (5)
Beta amyloid Hyperphosphorylated tau Apolipoprotein E Presenillin 1 Prion protein
What inheritance patterns are there for progressive genetically linked degenerative myopathies?
X-linked
Autosomal recessive
Autosomal dominant
How is Duchenne MD inherited?
X-linked
How is Emery-Dreifuss MD inherited?
X-linked, autosomal recessive or autosomal dominant
How is oculo-pharyngeal MD inherited?
Autosomal dominant
Which is the largest category of dystrophies?
Duchenne (23%)
How many males per 100,000 are affected by Duchenne per year?
20-30 per 100,000 (1 in 3,500 male babies)
How does Duchenne present?
How does the disease progress?
Proximal muscle weakness during first 2 years
Elevated creatine kinase
Continuous slow decline - unable to walk by 7-12 years
Death usually late 20s/early 30s (usually from resp failure or cardiomyopathies)
What causes DMD?
An absence of dystrophin, a protein that helps keep muscle cells intact.
How does DMD appear on biopsy? (4)
Fibre size variability
Centrally located nuclei
Endomysial fibrosis
Degenerating muscle fibres undergoing myophagocytosis
What is muscle replaced with in DMD?
What does this cause?
Fibrotic material and fat, causes weakness
Drug induced myopathies lead to atrophy of what type of fibres?
Type 2
Give three examples of drugs that can cause myopathies.
Corticosteroids (fluorinated steroids)
Statins
Alcohol
How many % of patients on statins get rhabdomyolysis?
10%
Acute heavy alcohol intake causes…?
Chronic causes…?
Rhabdomyolysis
Slow progressive proximal weakness, loss of type 2 fibres
What is the major symptom of fibromyalgia?
Widespread muscle pain on both sides of the body, above and below waist, in axial skeleton.
What tissue is affected in fibromyalgia?
Connective tissue around the muscle
Fibromyalgia is autoimmune. What antibodies are found in 50% of patients?
Antipolymer antibodies
How many specific tender points are needed for diagnosis?
11 out of 18
How many % of patients with fibromyalgia are female? What age group does it mainly affect?
80-90%
30-60 year age group
Why is sleep important for fibromyalgia patients?
Deep, non-REM sleep is restorative and without it, there is muscular pain, tenderness, fatigue and functional disturbance. This then causes further sleep disturbance.
How is fibromyalgia treated? (4)
Tricyclic antidepressants - amitriptyline to help sleep
SSRIs - fluoxetine
Exercise
Complementary therapy
What causes angular fibres?
Denervation
What causes split fibres?
Dystrophy
What causes ring fibres?
Myotonic dystrophy
What causes target fibres?
Reinnervation
