Week 3 - E - Neuromuscular Junction and Muscle Flashcards
What are three clinical features of lower motor neurone disorders?
Weakness Hypotonia/hyporeflexia Fasciculations Atrophy
What are the synapses between motor neurons and muscle known as? These come after the neuromuscular junction at the actual point of contact
These are known as the motor end plate
Where do the spinal nerves that supply the skeletal muscles with motor innervation arise from in the spinal cord?
They arise from the ventral horns in the spinal cord to supply skeletal muscle with motor innervation (anterior horns give rise to anterior roots and rootlets - motor)
What is a motor unit?
A motor unit is a single alpha motor neuron and all the skeletal muscle fibres it innervates
Glutamate is the neurotrasmitter used in the vertebrate brain and spinal cord for excitatory functions Which ions do all glutamate receptor channels allow the influx of into a cell?
All glutamate receptor channels allow influx of sodium into the cell (non-NMDA glutamate channels allow the sodium influx and potassium efflux, NMDA channels allow the influx of sodium and calcium and potassium efflux)
NMDA receptors Have a high permeability to Ca2+,hence thought to promote neurotoxicity What drug can be given that act as NMDA glutamate receptor antagonists?
This would be memantine - given in the treatment of dementia (alzheimers and lewy body)
What is the neurotransmitter used at the neuromuscular junction?
The neurotransmitter used here is acetylcholine
To cause muscles to contract, action potenitals move along the nerve fibre causing the voltage gated calcium channel to open allowing for calcium influx (usually by excitatroy neurotransmitter glutamate) What does the influx of the calcium cause?
This causes vesicles containing acetylcholine to move towards the synaptic cleft allowing for the movement of sodium and potassium ions
How is the acetylcholine recycled?
The enzyme acteylcholinesterase breaks acetylcholine into acetate and choline where the choline is sequestered back into presynaptic vesicles
There are three different areas for problems to occur at the neuromuscular junction Pre-synaptically Synaptic cleft Post-synaptically Lambert-eaton myasthenic syndrome is a neuromuscular junction disorder, does this affect the presynaptic or postsynaptic channels? What is the antibody against?
Lambert Eaton Myasthenic Syndrome (LEMS) is an autoimmune condition characterised by antibodies against the presynaptic calcium channels leading to less vesicle release and therefore less muscle contraction
What other co-morbidity is LEMS associated with? Does it improve or worsen on exercise?
LEMS is associated with small cell carcinoma of the lung and it improves upon exercise
Botulinum toxin can cause similar problems with muscle contraction as Lambert Eaton Myasthenic syndrome How does botox work?
It cleaves presynaptic proteins involved in vesicle formation and therefore causes a rapid onset of muscle weakness without the sensory loss It prevents the release of the neurotransmitter acetylcholine from axon endings at the neuromuscular junction and thus causes flaccid paralysis. - prevents the vesicles containing ACh from binding with the synaptic membrane .
What causes botulinism?
The anaerobic bacterium clostridium botulinum
What is the most common neuromuscular junction disorder? What does it affect?
Myasthenia gravis This is an autoimmune disorder where antibodies attack the postsynaptic acetyl choline receptors
Myasthenia gravis is a rare long-term condition that causes muscle weakness that comes and goes. What are the typical age groups affected by myasthenia gravis? What is the hallmark feature of the condition?
Typical age groups affected at presentation are women under 40 and men above the age of 60 The hallmark feature of the condition is fatiguability - ie worsening with exercise or movement in general
It most commonly affects the muscles that control the eyes and eyelids, facial expressions, chewing, swallowing and speaking. But it can affect most parts of the body. In myasthenia gravis there is reduced number of ACh receptors and flattening of endplate folds What level of ACh receptors are usually reduced when symptoms begin?
Symtpoms usually begin when ACh receptors are at 30% of the norm
ACh antibodies are found in 80 - 90% patients with mysthenia gravis What gland in the body is found to have hyperplasia as well in myasthenia gravis?
in 75% of people there is abnromal growth of the thymus resulting in hyerplasia known as a thymoma
What is the function of the thymus gland?
The thymus serves a vital role in the training and development (maturation) of T-lymphocytes or T cells, an extremely important type of white blood cell and after puberty usually shrinks and becomes fat under the sternum
Where are the Tcells produced?
T cells are produced in the bone marrow and later move to the thymus where they mature.
What is the common presenting age of myasthenia gravis? What muscles are most commonly affected? Are males or females more predominantly affected?
3rd decade in females - women under 40 6th/7th decade in males - around the age of 70 Mostly the facial and eyelid muscles are affected in myasthenia gravis Females are affected more than males 3:2
Myasthenia gravis features Weakness typically fluctuating - worse through the day Most common presentation with extraocular weakness, facial and bulbar weakness What cranial nerves does bulbar weakness refer to? Where is the limb weakness typically?
Bulbar weakness refers to CN IX,X,XI,XII Limb weakness is typically proximal in myasthenia gravis
What is the acetylcholinesterase inhibitor that can be given in MG?
- You want to use AChE inhibitors that do not (in normal conditions) cross the blood brain barrier - for that reason donepzil, rivistigmine and galantamine are not used for myasthenia gravis (they are used to increase ACh levels in alzhiemers disease)
What is the drug that can be given to improve symtpoms in LEMS?
Pyridostigmine - inhibits the acteylcholinesterase and therefore more acetylcholine present in synaptic cleft to generate an action potential - muscle contraction
3,4 diaminopyridine is used in lambert eaton myasthenic syndrome - helps increase the action potential duration so more acetylcholine can flow through (doesnt work directly on increasing calcium channel levels)
Thymectomy is also advise in myasthenia gravis if there is a thymoma What is given for imunosuppression as treatment longer term in myasthenia gravis - usaly when pydridostigmine monotherapy does not work? What is given in a myasthenia gravis mergency? where there is weakness of respiratory muscles causing life threatening circumstance
Can combine prednisolone and azathioprine (both oral) IV immunoglobulin is given in myasthenic crisis - emergency where weakness of respiratory muscles occurs
Multinucleated, Striated, Voluntary What type of muscle is this? Striated, involuntary, single nucleus, branched What type of muscle is this? Involuntary, non striated, single nucleus, tapered What type of muscle is this?
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