Muscle & Neuromuscular junctions

Question 1

features go LMN disorder?

Answer 1

Weakness
hypotonia
fasciculations

Question 2

What is the VERY basic pathway that allows muscle contraction?

• Where do the motor neurones that supply the skeletal muscle arise from?
• What is the motor end plate?
• What is a motor unit?
• what NT is involved?

Answer 2

-Motor neurone -> Neuromuscular junction
Muscle

• their cell bodies are located in the ventral horn of the spinal cord
• the synapses formed between in motor neurones and muscle are called the motor end plates

-a motor neuron and the skeletal muscle fibers innervated by that motor neuron’s axonal terminals
Each muscle cell responds to only 1 motor neurone

-acetylcoline

Question 3

Describe what happens in order for the muscle to contract?

Answer 3

-AP moves along the nerve and reaches the presynaptic bulbs
causes voltage gaited Ca channels to open and vesicles of ACh are released into the synaptic cleft
It then diffuses across the synaptic cleft and the acetylcholine receptor opens and renders the membrane permeable to Na/K ions
the depolarisation starts an AP at the motor end plate
Acetylcholine is then broken down by acetylcholine esterase to acetate and choline

Question 4

Presynaptic disorders

-give 2 and why they occur?

Answer 4

Botulism
food and wounds can be infected
the toxin cleaves presynaptic proteins involved in vesicle formation and block vesicle soaking with PS membrane get rapid onset of weakness without sensory loss

-Lambert Eaton Myasthenic Syndrome
antibodies to presynaptic Ca channels causes less vesicles to be released

Question 5

Post synaptic Disorders

-give an example

Answer 5

Myasthenia gravis

Question 6

Myasthenia graves

• mechanism & pathophysiology? (5)
• what organ might have a role in causing?
• overal features? (1)
• clinical features? (3)
• treatment? (4) in an emergency?
• complications?

Answer 6

-autoimmune- antibodies to the AChR (acetylcholine receptors)
get a reduced no. of ACh receptors and flattening of endplate folds
symptoms when ACh receptors are reduced to 30% of normal
They trigger an inflammatory cascade that leads to the damaged folds

• Thymus
• reduced no. receptors so muscle weakness and fatiguability

-weakness typically fluctuating- worse through the day
extra ocular weakness, facial and bulbar weakness
proximal limb weakness

-Acetylcholinesterase inhibitor pyridostigmine
thymectomy
Immunomodulating: steroids/azathioprine

plasma exchange/immunoglobulin

-resp failure and aspiration pneumonia

Question 7

Name the 3 muscle types?

Answer 7

skeletal

Smooth cardiac

Question 8

Skeletal muscle

• structure?
• smallast contraire unit an components?
• surrounded by what?

Answer 8

highly organised

-muscle fibre: long, cylindrical with nuclei, mitochondria, sarcomeres

-thin layer of endomysium
20-80 grouped to form fascicle encapsulated by perimysium, these are then grouped together and surrounded by epimysium

Question 9

Smooth muscle

• structure? (4)
• what is not present?

Answer 9

-cells not striated, single central nucleus
gap junctions between cells and surrounded by connective tissue

-No sarcomeres

Question 10

Fasciculations

• what are they?
• why do they occur?
• sign of what?

Answer 10

• visible, fast, fine spontaneous twitch
• in healthy muscle due to stress, in denervated muscle which becomes hyper excitable
• Usually a sign of disease in the motor neurone

Question 11

Myotonia

• what is it?
• due to?

Answer 11

failure of muscle relaxation after use

Chloride channel dysfunction?

Question 12

What are the signs of muscle disease?

Answer 12

-Myalgia
Muscle weakness
Wasting
hyporeflexia

Question 13

Give examples of muscle diseases of the following types:
inflammatory (2)
Inherited (4)
Congenital (2)

Answer 13

-Dermatomyositis
Polymyositis

Muscular Dystrophies
Dystrophinopathies
limb girdle muscular dystrophies
Myotonic dystrophy

Congenital myasthenic syndromes
Congenital myopathies

Question 14

inflammatory muscle disease
-Polymyositis 
what is it? investigations? treatment?
-dermatomyositis 
associated with what?

Answer 14

-symmetrical, progressive proximal weakness developing over weeks to months
raised CK
responds to steroids

-clinically similar
assoc with skin lesions
heliotrope rash on face
up to 50% have underlying malignancy

Question 15

Degenerative 
-Inclusion body myositis 
features?
-Myotonic dystrophy 
inheritance? presentation? 
-Muscular dystrophies
inheritance? most common?

Answer 15

• muscle disease characterized by slowly progressive weakness and wasting of both distal and proximal muscles, most apparent in the muscles of the arms and legs.
  slow progressive weakness in 6th decade with thumb sparing

-commonest, autosmal dominant, trinucleotide repeat disorder
multisystem
Myotonia, Weakness, cataracts, ptosis, frontal balding, Cardiac defects

-there is a genetic component so these are inherited conditions
progressive with no central or peripheral nerve abnormality
Duchess and Becker

Question 16

What drugs can cause myopathy? (4)

Answer 16

Statins, fibrates, nicotinic acid

dexamethasone, many more

Question 17

Rhabdomyolysis

• what is it?
• causes?
• Triad?
• complications?

Answer 17

-dissolution of muscle
image to skeletal muscle causes leakage of large quantities of toxic intracellular contents into plasma

• Many potential causes- crush injuries, toxins, post convulsions
• myalgia, muscle weakness, myoglobinuria (dark urine)
• acute renal failure and DIC