Week 3 - E - Neuromuscular Junction and Muscle

Question 1

What are three clinical features of lower motor neurone disorders?

Answer 1

Weakness Hypotonia/hyporeflexia Fasciculations Atrophy

Question 2

What are the synapses between motor neurons and muscle known as? These come after the neuromuscular junction at the actual point of contact

Answer 2

These are known as the motor end plate

Question 3

Where do the spinal nerves that supply the skeletal muscles with motor innervation arise from in the spinal cord?

Answer 3

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)

Question 4

What is a motor unit?

Answer 4

A motor unit is a single alpha motor neuron and all the skeletal muscle fibres it innervates

Question 5

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?

Answer 5

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)

Question 6

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?

Answer 6

This would be memantine - given in the treatment of dementia (alzheimers and lewy body)

Question 7

What is the neurotransmitter used at the neuromuscular junction?

Answer 7

The neurotransmitter used here is acetylcholine

Question 8

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?

Answer 8

This causes vesicles containing acetylcholine to move towards the synaptic cleft allowing for the movement of sodium and potassium ions

Question 9

How is the acetylcholine recycled?

Answer 9

The enzyme acteylcholinesterase breaks acetylcholine into acetate and choline where the choline is sequestered back into presynaptic vesicles

Question 10

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?

Answer 10

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

Question 11

What other co-morbidity is LEMS associated with? Does it improve or worsen on exercise?

Answer 11

LEMS is associated with small cell carcinoma of the lung and it improves upon exercise

Question 12

Botulinum toxin can cause similar problems with muscle contraction as Lambert Eaton Myasthenic syndrome How does botox work?

Answer 12

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 .

Question 13

What causes botulinism?

Answer 13

The anaerobic bacterium clostridium botulinum

Question 14

What is the most common neuromuscular junction disorder? What does it affect?

Answer 14

Myasthenia gravis This is an autoimmune disorder where antibodies attack the postsynaptic acetyl choline receptors

Question 15

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?

Answer 15

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

Question 16

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?

Answer 16

Symtpoms usually begin when ACh receptors are at 30% of the norm

Question 17

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?

Answer 17

in 75% of people there is abnromal growth of the thymus resulting in hyerplasia known as a thymoma

Question 18

What is the function of the thymus gland?

Answer 18

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

Question 19

Where are the Tcells produced?

Answer 19

T cells are produced in the bone marrow and later move to the thymus where they mature.

Question 20

What is the common presenting age of myasthenia gravis? What muscles are most commonly affected? Are males or females more predominantly affected?

Answer 20

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

Question 21

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?

Answer 21

Bulbar weakness refers to CN IX,X,XI,XII Limb weakness is typically proximal in myasthenia gravis

Question 22

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?

Answer 22

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)

Question 23

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

Answer 23

Can combine prednisolone and azathioprine (both oral) IV immunoglobulin is given in myasthenic crisis - emergency where weakness of respiratory muscles occurs

Question 24

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?

Answer 24

https://s3.amazonaws.com/classconnection/403/flashcards/11907403/jpg/pjpgpng-15F26779C2E789C1C07.jpg

Question 25

In skeletal muscle, what is the thin layer of connective tissue surrounding each muscle fibre? What are a group of muscle fibres?

Answer 25

Endomysium - thin layer of connective tissue surrounding each muscle fibre Group of muscle fibres are known as a fascicle

Question 26

What is the layer of connective tissue surrounding the fascicle known as? What is the layer of connective tissue surrounding the muscle known as?

Answer 26

Surrounding the fascicle is the perimysium Surrounding the muscle is the epimysium

Question 27

What is the functional unit of skeletal muscle?

Answer 27

Sarcomere is the functional unit of skeletal muscle

Question 28

There are three different types of skeletal muscle Type 1 Type IIa Type IIb(x) What are each of these?

Answer 28

Type I - Slow oxidative - ATP via oxidative phosphorylation Type IIa - Fast oxidative - ATP via oxidative phosphorylation Type IIb - Fast glycolytic - ATP via glycolysis

Question 29

Which type of skeletal muscle fibre type is easily fatiguable?

Answer 29

Type IIb is easily fatiguable Type I is well vasuclarised and therefore red muscle Type II is poorly vasuclarised and is white

Question 30

What is a fasciculation? When may it occur in a healthy person?

Answer 30

This is a fast spontaneous twitch due to small number of motor units firing - usually sign of disease in the motor neuron, not the muscle May occur in healthy muscle if stressed, fatigued or caffeinated

Question 31

What is the failure of muscle relaxation after use known as? What ion channel abnromalities is usually accountable for this? Which neurotransmitter usually opens these channels?

Answer 31

Failure to relax after use is myotonia Usually chloride channel abnormalities GABA - gamma amino butryic acid is what causes these channels to open

Question 32

Muscle disease can be inflammatory (immune mediated), inherited or congenital usually Name two inflammatory muscle disease? Name two inherited muscle diseases?

Answer 32

Inflammatory - Polymyositis, dermatomyositis Inherited muscle disease - Duchenne muscular dystrophy, limb girdle muscular dystrophies

Question 33

Describe polymositis and dermatomyositis What antibodies are raised?

Answer 33

Polymysoitis is characterized by proximal muscle weakness in the arms and legs - difficulty brushing hair and climbing stairs Dermatomysoitis is the same but with cutaneous manifestations eg heliotrope rash, gottron’s papues Anti-Jo1 antibody is raised

Question 34

What is the treatment of Poly/dermatomysoitis?

Answer 34

Prednisolone + Azathioprine or Methortrexate

Question 35

What is often misdiagnosed as polymyositis? Often see when polymyositis is treated with steroids and there is no improvement in the patients muscle weakness

Answer 35

This is inlcusion body myositis - occurs progressively over months to years

Question 36

Muscle power is graded using the MRC (medical research council) muscle power grading The score is 0-5, what does each score represent for muscle power?

Answer 36

0 - no muscle movement at all - complete paralysis 1 - flicker of contraction 2 - Movement possible if gravity eliminated 3 - Movment possible against gravity but not against resitance 4 - Movmeent against resitance but not full strength 5 - normal strength