Muscle pathology

Question 1

What are the 3 layers of muscle

Answer 1

Epimyisum
Perimysium - surrounds fasicles, fibrovascular septa project from the sheath dividing the muscle into fascicles
Endomysium- surrounds individual muscle fibres

Question 2

In muscular dystrophies what replaces muscle tissue?

Answer 2

Fat and adipose tissue

Question 3

What are the 3 types of muscle fibre?

Answer 3

Type 1 ( dark): Rich in oxidative enzymes, myoglobin, mitochondria 
Type 2 a ( light): Rich in glycolytic enzymes + glycogen 
Type 2 b ( intermediate): Mixed function

Question 4

What changes occur to the muscles from LMN lesions causing muscle denervation?

Answer 4

Atrophy 
Motor unit enlargement - growth of active myofibrils to reinnervate the denervated areas 
Target fibres produced 
Atrophy of isolated myofibers
loss of myofilaments

Question 5

What type of influence do LMN have on the muscle?

Answer 5

Trophic influence

Stimulate protein synthesis and contraction due to release of trophic factors at the synapse

Question 6

What are histological features of denervation?

Answer 6

• atrophy of isolated myofibers
• loss of myofilaments
• Chronic illness: Fibre type grouping + axonal sprouting of healthy fibres to innervate denervated fibres. This combined denervation + innervation leads to enlargement of the motor unit

Question 7

What are target fibres?

Answer 7

Lose oxidative enzyme in centre with more intense activity on the periphery

Question 8

What are the symptoms of neuromuscular disorders?

Answer 8

Muscle weakness
Droppy eyelid 
Paralysis 
Muscle loss
Pseudohypertrophy ( DMD)
Atrophy + hypotonia 
trouble swallowing and breath

Question 9

What type of disorder is spinal muscular atrophy?

Answer 9

Autosomal recessive caused by a deletion mutation in SMN1 on chromosome 5qB

Question 10

What is survival motor protein?

How is it produced?

Answer 10

For lower motor neurones to be healthy enough SNM protein must be produced by SMN1 genes

Functional survival motor protein is produced by SNM1
Non functional survival motor protein is produced by SNM2

Question 11

What do deficiencies in survival motor protein cause?

Answer 11

• Defective splicing of mRNA sequences in spinal motor neurones

Question 12

What is the key difference between SNM1 + SNM2 and how does this affect the condition?

Answer 12

SNM1 +SNM2 are mostly identical apart from a single base difference at exon 7

SNM1 = C
SNM2 = T 

SNM1 mRNA keeps exon 7 but SNM2 does not keep exon 7
Exon 7 is critical for healthy survival motor protein which is functional + stable

Question 13

What is the most common type of SMA ?

What are other types of SMA?

Answer 13

5qSMA

Deletion on one chromosome and point mutation on the other. Both cause loss of exon 7 -> non functional survival motor protein

Question 14

What are the 4 types of 5qSMA and what are their typical features?

Answer 14

Type 1: Onset before 6 months, baby unable to sit up independently. Most likely to require respiratory support

Type 2: Develop between 7-8 months: Able and sit up and notable to walk. Weak respiratory muscles

Type 3: Onset between 3-18 years. Not life threatening can stand and walk but often lose ability with time

Type 4: Least severe, mild muscle weakness unlikely to use a wheel chair