Skeletal Muscle Function & in Ageing

Question 1

What are the 3 basic motor unit types?

Answer 1

fast-fatiguable (FG, IIX), fast-resistant (FOG, IIA), slow (SO, I)

Question 2

Type I muscle fibres

Answer 2

slow oxidative; slow-twitch, small force, high resistance to fatigue

Question 3

Type IIA muscle fibres

Answer 3

fast oxidative/glycolytic; fast-twitch, medium force, high resistance to fatigue

Question 4

Type IIX muscle fibres

Answer 4

fast glycolytic; fast-twitch, large force, low resistance to fatigue

Question 5

Fast muscle fibres are ______ in size and fatigue _______

Answer 5

larger, more easily

Question 6

Slower muscle fibres are _______ in size and are fatigue ________

Answer 6

smaller, resistant

Question 7

What are ‘pure’ muscle fibres?

Answer 7

have one type of MyHC ie either fast or slow

Question 8

What are ‘hybrid’ muscle fibres?

Answer 8

contain multiple forms of MyHC ie combinations of fast and slow

Question 9

T/F Muscles are static units

Answer 9

False; muscle fibres are highly malleable and change their properties based on thes timulus they receive

Question 10

T/F Within our muscles there is either only pure fibres or hybrid fibres

Answer 10

False; there is a combination of pure and hybrid

Question 11

T/F Slow contracting muscle (eg soleus) do not contain any fast-twitch (IIA or IIX) fibres

Answer 11

False; they contain relatively smaller amounts but they are still present

Question 12

What is the role of myostatin?

Answer 12

Negative regulator of muscle mass; if it is inhibited it results in muscle hypertrophy

Question 13

What is the role of myostatin in muscle wasting?

Answer 13

In muscle wasting disorders eg inflammatory environments, myostatin levels rise contributing to atrophy of muscle

Question 14

What is spinal muscular atrophy (SMA)?

Answer 14

Loss of motor neurons and dendritic contracts to muscle results in atrophy and loss of function

Question 15

T/F Cachexic weight loss can directly cause death

Answer 15

True; >20% of cancer-related deaths are attributable to cachexia as loss of muscle mass over 40% is fatal

Question 16

T/F Cachexia impairs patient respons to chemo and radiotherapies

Answer 16

True

Question 17

T/F Muscle is an endocrine organ

Answer 17

True; it produces and releases different hormones into the circulation

Question 18

In cachexia and critical illness myopathy, muscle

Answer 18

atrophies and has disrupted architecture

Question 19

What is critical illness myopathy?

Answer 19

An inflammatory environment associated with infection sets of a cascade of signalling pathways leading to degradation of muscle protein and atrophy over a matter of days

Question 20

T/F Muscle fibres cannot switch types

Answer 20

False; eg stimulation of a fast twitch muscle like TA with low-freqeuency slow-twitch type innervation can change it from FF to SO

Question 21

What is sarcopenia?

Answer 21

Age-related muscle wasting with associated loss of muscle function

Question 22

What changes in ageing are associated with sarcopenia?

Answer 22

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

Question 23

T/F Cachexia is the same as sarcopenia

Answer 23

False; cachexia may be a component of sarcopenia, but sarcopenia is specifically age-related

Question 24

Diagnosis of sarcopenia should be considered in

Answer 24

older patients with observed declines in physical function, strength, or overall health

Question 25

Initial criteria for sarcopenia diagnosis are

Answer 25

bedridden, cannot independently rise from chair, gait speed less than 1m/s

Question 26

What changes accompany loss of muscle mass in ageing?

Answer 26

Increase in non-contractile material - connective tissue and fat; change in architecture of the muscle

Question 27

Which type of physical activity, running or weightlifting/explosive force events declines faster in ageing?

Answer 27

Weight lifting/quick contraction activities that are dynamic and require a lot of muscle power decline at an even greater rate

Question 28

What is muscle weakness?

Answer 28

Inability to develop initial force appropriate for the circumstances eg unable to rise from a chair

Question 29

Muscle strength declines steeply beyond age

Answer 29

50

Question 30

T/F Slow muscles are more susceptible to age related changes

Answer 30

False; fast muscles

Question 31

What are the mechanisms of age-related motor unit remodelling?

Answer 31

loss of fast type II motor unit innervation results in death of fast-twitch muscle fibres; expansion of type I motor units innervates fast fibres and converts them to slow fibres

Question 32

What is intrinsic weakness?

Answer 32

With ageing, force produced per CSA of muscle fibre is decreased

Question 33

What is fibre-type grouping?

Answer 33

selective loss of fast motor units leads to loss of checkerboard pattern of fast and slow fibre distribution

Question 34

Fibre-type grouping is seen in

Answer 34

neuromuscular disorders AND sarcopenia

Question 35

What is the cause of the slowing of contraction and relaxation of muscle with age?

Answer 35

impaired release and reuptake of Ca2+ by the SR

Question 36

T/F Age-related changes in speed of contraction occur concurrently with atrophy

Answer 36

False; these changes occur well before there is significant loss of muscle mass

Question 37

What happens to motor neurons with ageing?

Answer 37

MNs are lost, numbers and diameters of motor axons decrease; some fibres die, others survive due to sprouting from slow fibres

Question 38

What changes occur at the NMJ with age?

Answer 38

widening of the end-plate, longer nerve terminals, fewer side branches - futile remodelling

Question 39

What changes occur to nerves in ageing?

Answer 39

Increase in connective tissue between axons, aberrant small diameter axons, dysmyelination

Question 40

What is responsible for the stiffening of muscles with age?

Answer 40

Muscles lose their elasticity because connective tissue increases between muscle fibres

Question 41

Strength training in the elderly increases what type of fibres?

Answer 41

type II (fast)

Question 42

What contributes to the inability to combat sarcopenia even with optimal strength training?

Answer 42

Decreased circulating levels of anabolic hormones - GH, IGF-1, testosterone - compromises efficiency of muscle regeneration or repair of daily wear and tear

Question 43

What characterized DMD?

Answer 43

Generalized weakness and muscle wasting affecting limb and trunk muscles first; calves are often enlarged; elevated CK levels

Question 44

What is Gower's sign?

Answer 44

due to weakness of limb muscles, need to walk self off of floor up the thighs to stand, can't just stand using limb muscles

Question 45

What changes occur to the appearance of muscle in DMD?

Answer 45

loss of fibres, variable size of remaining fibres, significant fibrotic infiltration (fat and CT)

Question 46

DMD is caused by

Answer 46

multiple mutations on dystrophin gene (X-linked) causing deficiency in dystrophin expression, a ctyoskeletal protein

Question 47

What is the normal role of dystrophin?

Answer 47

Ctyoskeletal protein involved in shock absorption and force transmission by anchoring actin to transmembrane proteins, anabolic signalling blood flow signalling via connection to laminin

Question 48

What is the difference in dystrophin in Becker MD?

Answer 48

there are significant amounts of abnormal, smaller stable fragments that confer some stability to muscles

Question 49

Dystrophin is postulated to have a structural role in stabilizing the ________ during contraction via the ________

Answer 49

sarcolemma; dystrophin-glycoprotein complex (DGC)

Question 50

What are costameres?

Answer 50

Lattices of DGC on the cytoplasmic face of the sarcolemma that join sarcomeres to laminin in the EXM`

Question 51

What is the result of loss of costameres in DMD?

Answer 51

Membrane fragility and disruption causing instability in the muscle fibres - membranes tear on activation leading to fibrosis of ECM and leakage of calcium ions which can activate muscle destruction (proteases, phospholipases)

Question 52

What is the role of BPG-15 in DMD?

Answer 52

Increases HSP-72 (HSPs help fold misfolded proteins) to improve SERCA levels (takes up Ca into SR) to improve muscle function