Neuromuscular junction pathologies Flashcards
What are the synapses called which are formed between motor neurons and muscle?
The neuromuscular junction
Define a neuromuscular junction and define the motor end plate
- A neuromuscular junction is a synapse between a motor neuron and skeletal muscle
- The synapses formed between motor neurons and muscle are called the motor end plate
They both seem pretty similar
What is the main neurotransmitter involved in motor neuron synapses and what is its function?
Acetylcholine (ACh) - its function is to cause muscles to contract
Describe how acetylcholine causes muscles to contract
- AP moves along the axon of the motor neuron
- Voltage gated Ca2+ channels open allowing influx of Ca2+
- Vesicles of acetyl choline released into synaptic cleft
- Acetylcholine diffuses across the synaptic cleft
- The acetlcholine receptor opens and renders the membrane permeable to Na / K ions (mainly Na+)
- The depolarisation starts an AP at the motor end plate ==> muscule contraction
What are the 2 main pre-synaptic disorders affecting the neuromuscular junction?
- Botulism
- Lambert Eaton Myasthenic Syndrome
What is botulism caused by ?
- Caused by Clostridium botulinum bacteria which produce highly posinous toxins
- Can get it from food when someone eats food containing the toxins because it hasn’t been properly canned, preserved or cooked esp unregrigerated sausages
- Or from wounds when a wound becomes infected with the bacteria, usually as a result of IV drug use esp black tar heroin
Describe the pathological process behind botulism
Botulinum toxin cleave presynaptic proteins involved in vesicle formation and block vesicle docking with the presynaptic membrane
Describe the presentation of botulism
Results in rapid onset weakness without sensory loss
Causes paralysis that spreads down the body from the head to the legs.
- Drooping eyelids
- Blurred or double vision (diplopia)
- Facial muscle weakness
- Difficulty swallowing (dysphagia)
- Slurred speech (dysarthria)
- Breathing difficulties ==> resp failure
What is the treatment of botulism ?
Botulinum antitoxin
What is lambert eaton myasthenic syndrome (LEMS)?
A rare condition caused by antibodies to presynaptic Ca2+ channels leading to less ACh vesicles release
In what patients is LEMS most common in ?
- About half of the cases are triggered by alteration in the immune system with people with lung cancer (basically just look out for someone with LEMS symptoms that have lung cancer)
- The other cases are autoimmune cause
Describe the typical presentation of LEMS
The main symptoms are weakness in the legs, arms, neck and face, and autonomic involvement such as dry mouth, constipation and impotence
Weakness begins in the proximal legs (unlike in MG which begins in the face down) typically hip flexion and hip abduction, with variable progression, and subsequently usually affects the proximal arms. So think gait difficulties before eye signs
Symptoms:
- aching muscles
- difficulty walking and climbing stairs
- difficulty lifting objects or raising the arms
- drooping eyelids, dry eyes and blurred vision
- swallowing problems
- dizziness upon standing
- a dry mouth
- constipation
- erectile dysfunction in men
- strength that improves one exercising (due to build up of ACh in the synpatic cleft)
- hyporeflexia and weakness improve after exercise
What is the treatment of LEMS ?
Diaminopyridine or IV immunoglobulin
What is the main post-synpatic disorder of neuromuscular junctions and the most common neuromuscular junction disorder overall?
Myasthenia gravis
Descibe the pathogenesis of myasthenia gravis
- It is an autoimmune disease caused by antibodies to acetyl choline receptors (AChR) (anti-AChR antibodies)
- This results in a reduced number of functioning receptors leads to muscle weakness and fatiguability
- Antibodies block binding of ACh but also trigger inflammatory cascades that damage the folds of the postsynaptic membrane
- Thymus plays a role, 75% patients have hyperplasia or thymoma (tumour in the thymus)
- Both B and T cells are involved
What are the 2 peaks of incidence of myasthenia gravis (MG)?
- females in 3rd decade
- males in 6th or 7th decade
Note it may occur at any age though
Describe the typical presentation of MG
- Most common presentation with extraocular weakness, facial and bulbar weakness
- Limb weakness typically proximal
- Symptoms tend to affect the extraocular muscles, then bulbar (swallowing, chewing), then face, neck, then limb girdle and then trunk
Symptoms:
- droopy eyelids
- double vision
- difficulty making facial expressions
- problems with chewing and difficulty swallowing
- slurred speech
- weak arms, legs or neck
- SOB and occasionally serious breathing difficulties
- tendon reflexes are normal
The symptoms tend to get worse when you’re tired (unlike LEMS which is improved on exercise). Many people find they are worse towards the end of the day, and better the next morning after getting some sleep.
