Skeletal muscle: ageing and disease Flashcards Preview

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Flashcards in Skeletal muscle: ageing and disease Deck (47):
1

List the factors that control muscle mass?

Nutritional status

Hormones

Genetics

Innervation

Inflammation

Oxidative stress

Blood flow

Exercise 

Disease

Protein synthesis and degradation

2

What are the three fibre types present in muscle?

Fast fatiguable

Fast resistant

Slow

3

Describe the difference in twitch responses between FF, FR and S muscle fibres?

FF: fast twitch

FR: fast twitch

S: slow twitch

4

Describe the difference in fatiguability between FF, FR and S muscle fibres?

FF: fatigue rapidly

FR: fatigue slowly

S: do not fatigue

5

Describe the concept of muscle fibre malleability?

Fibres exist as either pure (one type of MHC) or hybrids (multiple forms of MHC)

6

What determines the composition of MHC in a muscle fibre?

Varies according to stimuli

Composition reflects function 

7

What are the goals of intervention to attenuate muscle wasting?

Attenuate muscle atrophy

Promote muscle strength

NOT: increase muscle fatigue

8

Give an example of a genetic influence on muscle mass?

Myostatin: negative regulator of muscle mass

Knockout > increase muscle mass

9

Describe the situtations which may lead to disuse muscle atrophy?

Hindlimb underweighting

Immobilisation

Limb casting

Prolonged bed rest

Spaceflight

10

Describe the effect of denervation on muscle mass?

Denervation atrophy

11

Describe cancer cachexia?

Severe wasting and weakness in many cancer patients

Disruption of muscle architecture 

Affects up to 80% lung, pancreatic and GIT cancer patients 

Reduces QoL

Impairs response to chemo and radiotherapy 

12

Loss of how much muscle mass is fatal?

40%

13

Describe why muscle wasting is thought to occur so rapidly in the ICU?

How is this being combatted?

Inflammatory environment > cascade of signalling pathways > favour protein degradation 

Occurs over days

Treatment with electrical stimulation and exercise in the ICU

14

Describe the outcome of loss of muscle mass in disease states and old age?

Compromises QoL and survival

15

Describe sarcopenia?

Age-associated loss of skeletal muscle mass and function

16

Describe the cause of sarcopenia?

Multifactorial: disuse, endocrine changes, chronic diseases, inflammation, insulin resistance, nutritional deficiencies

17

In which patients should a diagnosis of sarcopenia be considered?

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

Bedridden, cannot rise from a chair or measured gait speed <1 m/s

18

Describe the functional effects of sarcopenia?

Descreased running performance

Descreased performace in explosive events 

Eventually impacts upon personal care, feeding and domestic duties 

19

Describe the changes that occur in muscle during sarcopenia?

Decreased muscle mass

Increased connectove tissue and fat

20

Define weakness?

Inability to develop an initial force appropriate for the circumstances 

21

At what age does loss of muscle strength usually onset?

50

22

Which muscle types are most affected by sarcopenia?

Fast muscles more affected than slow 

23

Describe the effect muscle fibre denervation and reinnervation with a new fibre type?

Muscle fibre changes to match new innervation 

24

Describe the chnages in speed of contraction that occur with ageing?

When do these changes occur?

Changes in Ca handling (impaired release and reuptake) > speed of contraction affected

Occurs before severe muscle wasting 

25

Describe how motoneuron losses in ageing are handled?

Type IIB fibres most susceptible > may be renervated by axonal sprouting from slow fibres, or may cease functioning 

26

Describe the changes that are thought to occur in motoneurons with ageing?

Demyelination

Remodelling of motor end plates 

Increased connective tissue

Smaller diameter axons

27

Are the changes that occur in sarcopenia reversilbe?

Can they be attenuated?

Generally not reversible 

Can be attenuated with strength training 

28

Describe the effects of strength training in the elderly?

Significant increase in muscle strength

Significant hypertrophy 

Increase lean total body mass

Increase in muscle fibre area

29

What are the adaptations that occur in strength training in the elderly thought to be an effect of?

Combination of neural adaptations and muscle hypertrophy

30

Describe the hormonal changes that occur with ageing that may have an effect on muscle mass and strength?

Decreased circulating levels of anabolic hormones: GH, IGF-1, testosterone

Compromises efficiency of muscle regeneration and repair 

31

Describe the age of onset of DMD?

2-6 years

32

Describe the inheritance of DMD?

X-linked recessive

33

Describe the pattern of onset of DMD?

Generalised weakness and muscle wasting affecting limb and trunk muscles first

Calves often enlarged

Progresses to affect all voluntary muscles 

34

Why are the calves enlarged in the initial stages of DMD?

During early stages, muscles are breaking down and repairing well

Fewer fibres are present, but they are hypertrophied

35

Describe the clinical features of DMD?

Lordotic and waddling gait

Gower's sign 

36

Describe the changes in the muscle that occur during DMD?

Loss of fibres

Variable fibre size

Infiltration of fibrosis

37

What is the cause of DMD?

Mutation in dystrophin gene on Xp21 > deficiency in dystrophin expression 

38

Describe the dystrophin-glycoprotein complex?

39

Describe the physiological role of dystrophin?

Structural role in stabilising sarcolema during muscle contraction 

Also a receiver and transducer of signals

40

Describe the age of onset of BMD?

Adolescence or adulthood

41

How do the symptoms and presentation of BMD differ from DMD?

Almost identical, but less severe

Significant heart involvements 

42

Describe how the cause of BMD differs to DMD?

X linked recessive mutation in dystrophin gene, but some dystrophin still produced 

Many abnormal, smaller molecules

Also some larger, useful proteins 

43

Describe the effect of loss of dystrophin on myofibre function and organisation?

Disorganised costameres > enhanced membrane leak 

Increased oedema

Inappropriate cystolic Ca and ROS generation 

Increased ECM deposition 

44

Describe the effect of costamere dysfunction on force transmission?

Muscle contraction > no force transmission 

45

Are dystrophic muscles more susceptible to contraction induced injury?

Why/why not?

There is support for this hypothesis

Membrane disruption allows influx of Ca, leads to hypercontraction and necrosis

High incidence of branching

46

Describe the biochemical signs of DMD and BMD?

Elevated serum CK (marker of muscle damage)

Increased Evans blue dye uptake (membrane disruption)

47

Describe the treatment targets of muscular dystrophy?

Correct genetic defect (gene therapy)

Cell therapy (myoblast transfer, stem cells)

Prevention of secondary consequences (corticosteroids)