Skeletal Muscle

Question 1

What factors control muscle mass?

Answer 1

nutritional status, hormones, genetics, innervation, inflammation, oxidative stress, blood flow, exercise, disease

Question 2

What are the different muscle fibre types

Answer 2

Type I - slow twitch and Type IIa and IIx - fast twitch

Question 3

What is a pure muscle fibre?

Answer 3

one that contains only one type of heavy chain myosin vs hybrids which contain multiple forms

Question 4

What are the goals of interventions for muscle wasting disorders?

Answer 4

attenuate muscle atrophy, increase muscle strength without increasing muscle fatigue

Question 5

What is myostatin?

Answer 5

a negative regulator of muscle mass

Question 6

What are the different types of muscle atrophy?

Answer 6

disuse atrophy, denervation atrophy, disease states e.g. cancer cachexia

Question 7

What percentage of cancer related deaths are attributed to cachexia?

Answer 7

20%

Question 8

What is sarcopenia?

Answer 8

age related muscle wasting associated with loss of mass and function

Question 9

What are the causes of sarcopenia?

Answer 9

disuse, changing endocrine function, chronic diseases, inflammation, insulin resistance, nutritional deficiencies

Question 10

How is sarcopenia diagnosed?

Answer 10

gait speed of less than 1m/s and a lean to fat ratio of less than 2 SD of the average young adult - or a loss of muscle mass combined with low muscle strength and or low physical performance

Question 11

Can sarcopenia be stopped with healthy behaviours?

Answer 11

no

Question 12

What is weakness?

Answer 12

an inability to develop an initial force appropriate for the circumstance

Question 13

Are fast or slow muscles more affected by ageing?

Answer 13

fast muscles

Question 14

What is age related motor unit remodelling?

Answer 14

denervation of type II motor units and reinnervation with type I motor units - leads to slowed contraction

Question 15

What happens to motor neurons with age?

Answer 15

demyelination, small diameter axons, increase in connective tissue in nerves

Question 16

What happens to the NMJ with age?

Answer 16

longer nerve terminals, fewer side branches, widening of end plate

Question 17

Can the effects of ageing on muscle be attenuated?

Answer 17

yes - through strength training before 50 years of age

Question 18

Decreased circulating levels of what hormones contribute to changes in muscle size and strength?

Answer 18

testosterone, GH, IGF-1

Question 19

What is the age of onset of duchenne muscular dystrophy?

Answer 19

2-6 years old

Question 20

What are the symptoms of duchenne muscular dystrophy?

Answer 20

generalised weakness and muscle wasting affecting limb and trunk muscles first - calves often enlarged

Question 21

What is the progression of duchenne muscular dystrophy?

Answer 21

disease progresses slowly - affects all voluntary muscles - rarely survive beyond late twenties

Question 22

What is the inheritance of duchenne muscular dystrophy?

Answer 22

X-linked recessive

Question 23

How many newborn males are affected by DMD?

Answer 23

1 in 3500-6000

Question 24

How many cases of DMD are a result of a new mutation?

Answer 24

1 in 3

Question 25

What gene is mutated in DMD?

Answer 25

dystrophin

Question 26

What is the dystrophin associated protein complex?

Answer 26

a series of transmembrane proteins associated with dystrophin which maintain the architecture of the muscle fibre as well as being involved in cell signalling

Question 27

How is dystrophin bound to the cytoskeleton?

Answer 27

via binding with F-actin

Question 28

What happens to muscles in the absence of dystrophin?

Answer 28

muscle membranes will be highly fragile and there will be decreased muscle signalling

Question 29

What is the age of onset of becker muscular dystrophy?

Answer 29

adolescence or adulthood

Question 30

What are the symptoms of becker muscular dystrophy?

Answer 30

same as DMD but less severe

Question 31

What is the progression of BMD?

Answer 31

disease progresses slowly but will affect all voluntary muscle - survive into mid to late adulthood

Question 32

What is the inheritance of BMD?

Answer 32

X-linked recessive

Question 33

What gene is affected in BMD?

Answer 33

dystrophin

Question 34

What is the difference between DMD and BMD?

Answer 34

in DMD there is a deletion in the gene which causes a frame shift so there is only synthesis of very small fragments - in BMD the reading frame is preserved so larger more useful portions of dystrophin are synthesised

Question 35

Why does a lack of dystrophin lead to degeneration of skeletal muscle?

Answer 35

a loss of dystrophin will lead to disorganised costameres, membrane leak, increased oedema, inappropriate cytosolic calcium and ROS generation and increased extracellular matrix deposition around myofibres

Question 36

What are the different ways to treat muscular dystrophy?

Answer 36

gene therapy, stem cell therapy or pharmacological intervention

Question 37

What drugs are available for muscular dystrophy?

Answer 37

corticosteroids, anabolic steroids, beta 2 agonists, IGF-1, myostatin inhibitors, proteasome inhibitors, membrane sealants, vitamin E, calcium channel blockers, heat shock protein induction