Muscle disorders Flashcards
Describe and draw the structure of a skeletal muscle?
Muscle is made of fascicles
Fascicles made up of muscle fibres (the muscle cells)
Muscle fibres made of myofibrils
Myofibrils made of actin (thin) and myosin (thick) filaments
What are the names of the membranes that make up skeletal muscle?
Epimysium surrounds muscle
Perimysium surrounds fascicle
Endomysium surrounds muscle fibres
Sarcolemma is found just under the endomysium, surrounding the muscle fibres (cells)
What is the sarcolemma?
The cell membrane of the muscle fibre (cell)
Which is thick and which is thin?
Actin or myosin?
Myosin is thick
Actin is thin
What is a neuromuscular junction?
Where a nerve synapses with the muscle and an impulse from the brain activates the muscle to contract
Name some muscle disorders?
Myasthenia Gravis
Muscular dystrophy:
- Duchenne’s / Becker’s
Myopathy
Myositis
Myotonia
What is myopathy?
A general name for a disease of muscle tissue
What is myositis?
Inflammation of muscle
What is myotonia?
A disorder of muscle tone
Characterised by an inability to relax voluntary muscle after excercise
Name the enzyme that is linked with muscle and is raised in muscular dystrophy and inflammatory conditions but not for M. gravis or others?
Creatinine Kinase
What is myasthenia gravis?
An acquired autoimmune disease affecting the acetylcholine receptor
Causing weakness in muscles
Which muscles are most commonly affected in MG?
Ocular
Bulbar
Proximal skeletal: shoulders, thighs
Axial skeletal: neck and trunk, muscles of respiration
What are bulbar muscles?
Muscles of the mouth and throat that control swallowing and speaking
What is the progression pattern of MG?
Fluctuating pattern of remission and crises
Who gets MG?
Young women (20-35) Older men (60-75)
What causes MG?
We don’t really know but it is thought to have a genetic component
There are links with thymus too: thyoma is present in 75% of MG patients
Pathophysiology of MG?
Autoantibodies are created which attach the postsynaptic acetylcholine receptors at the neuromuscular junction
Motor impulses are struggle to get from the nerves to the muscles to make them contract = weakness
Clinical features of MG?
Variable between patients
Fatigability of muscle after exercise, that improves on rest
Often ocular muscles are affected: ptosis
The weakness moves down: difficulty chewing, talking, swallowing, respiratory difficulties
What is ptosis, and what features of ptosis would indicate to you the person may have MG?
Ptosis = drooping of eyelid
Unilateral
If it is improved by sleep or an ice pack
Investigations of MG?
Blood:
- won’t have creatinine kinase
- autoantibodies against Ach receptors
(TENSILON test - not used so much any more)
Electromyography: measure how fatigable muscle is
CT / MRI to look for thymus hyperplasia
What is the TENSILON test?
Test for muscle fatigability
Patients are given two drugs:
- edrophionium: prevents breakdown of ACh
- atropine prevents damage to heart while doing this test
This rapidly improves the symptoms of MG, but only for a few minutes
Management of MG?
Oral acetylcholinesterase inhibitor
Immunosupression: steroids
DMARDS: methotrexate
Monitoring of thymus
Thymectomy
Why are oral actelycholinesterase inhibitors used in MG?
List one.
Prevent destruction of acetylcholine by acetylcholinesterase in the synaptic space
Pyridostigmine
How would you manage MG in a crisis phase?
IV immunoglobluins
Plasmapheresis
What is the prognosis of MG?
Near normal life expectancy, can occasionally be fatal due to respiratory failure, but this rare
What is thyoma? Which muscle disorder is it linked with?
Hyperplasia of thymus
It is benign but can become cancerous
It is seen in 75% of people with myasthenia gravis
What is muscular dystrophy?
What are the features?
An umbrella term for a number of inherited diseases
Causing progressive weakness and wasting of muscles
Replacement of muscle tissue with fibrous connective tissue
Cardiac and resp involvement
Name the 2 main types of muscular dystrophy?
Duchenne’s
Becker’s
Describe Duchenne’s muscular dystrophy?
Very severe form of muscular dystrophy
Progressive wasting of muscles
Most do not survive past adolescence
Who gets Duchenne’s MD?
Boys only, it is an X linked condition
What is an X linked condition?
A condition caused by a mutation on the X chromosome inherited by a boy from his mother
Why are girls not affected by muscular dystrophy?
It is X-linked
A girl inherits one X chromosome from her mother and one for her father, so if she inherits an X chromosome with the mutation on it, she’ll have another X chromosome to back it up, so no disease is seen
Boys only have 1 X chromosome so if it is mutated, there is not another one to back it up?
What is the mutation in Duchenne’s?
The gene that codes for the molecule dystrophin is severely mutated so dystrophin is produced at all
What is dystrophin and what does it do?
Dystrophin is the molecule that is not produced in some boys, causing Duchenne’s
Without it, there is excessive calcium entry into the cell
This causes excess stress within the cell, damaging the sarcolemma and resulting in cell death
Clinical features of Duchenne’s?
Abnormal gait, tummy sticks forward
Gower’s sign
Difficulty with standing up, walking, motor skills
Pseudohypertrophy of calfs, due to replacement of muscle with fat
Usually unable to walk at age 10
Death during teens or early 20s
What is Gower’s sign?
A boy affected by muscular dystrophy, when he tries to stand up he will use his hands to ‘walk up’ his legs to stand upright
When is Duchenne’s typically diagnosed?
Between 5 and 5 1/2
When do boys with Duchenne’s usually:
- become wheelchair bound
- pass away?
By age 10 they are usually unable to walk
They usually die during teenage years or early 20s
Investigations of Duchenne’s?
Blood:
- creatinine kinase raised
Positive Gower’s test
Genetic tests, family history
Muscle biopsy shows absence of dystrophin
Treatment of Duchenne’s?
Corticosteroids: are aggressively used before the age of 10, this can dramatically reduce the aggressiveness of Duchenne’s to more of a Becker’s picture
Physiotherapy: can prolong life of muscle
Mechanical ventilation
What is the inheritance pattern of Duchenne’s and Becker’s?
Recessive X-linked
What is the difference between Becker’s and Duchenne’s?
In Becker’s there is insufficient dystrophin produced
In Duchenne’s there is no dystrophin produced
Duchenne’s is more severe
What is the life expectancy of people with Becker’s muscular dystrophy?
Around 40, onwards
Some live a nearly normal lifespan
Becker’s is in general a much less severe condition that Duchenne’s, what is more severe in Beckers?
Cardiac involvement tends to be worse in Becker’s
