Muscle Remodelling & Skeletal Muscle Myopathies

Question 1

Describe the changes that can occur in muscle fibres following prolonged exercise

Answer 1

• METABOLIC ADAPTATION
• SR swells
• Increased volume of mitochondria
• Increased ATPase
• Increase in number of contractile proteins
• Increase in Z band width

Question 2

Explain the effect of high resistance training on skeletal muscle

Answer 2

• Stimulates cellular HYPERTROPHY
• Stimulates contractile protein synthesis
• Myosatellite cells fuse with existing muscle
• Increase in muscle mass
• Can increase resistance over time as more cross bridges can form

Question 3

Explain the effect of endurance training on skeletal muscle

Answer 3

• Increases metabolic activity of muscle
• NO HYPERTROPHY
• Stimulates synthesis of mitochondrial proteins
• Changes in vascularisation to allow greater oxygen utilisation
• Shift to oxidative metabolism (LIPIDS)

Question 4

Explain why muscle weakness is common in the elderly

Answer 4

• DISUSE ATROPHY e.g. immobilisation, bed rest, sedentary behaviour
• Decrease of muscle mass increases with age (loss of protein > reduced fibre diameter > loss of power)

Question 5

What are the signs of DENERVATION ATROPHY?

Answer 5

• Muscle atrophy
• Muscle weakness
• Flaccidity of muscle

Question 6

Explain how neurogenic muscular atrophy can occur

Answer 6

• Death of motor neurone at motor end plate
• Muscle cells cannot be stimulated
• Muscle cells degenerate and shrink (ATROPHY) resulting in a reduced fibre diameter
• Loss of power of muscle (muscle weakness)

Question 7

State how you could increase the length of muscle fibres

Answer 7

Sustained stretching

Question 8

Explain the difference between ATROPHY and HYPERTROPHY

Answer 8

• ATROPHY destruction > replacement, decrease in muscle mass

- HYPERTROPHY destruction

Question 9

Explain the causes of MYASTHENIA GRAVIS

Answer 9

• Autoimmune destruction of motor end plate contains ACh receptors
• Immunoglobulin G antibodies attach to ACh receptors
• Loss of junctional folds at end plate and widening of synaptic cleft

Question 10

Describe the symptoms of myasthenia gravis and explain why they occur

Answer 10

• Fatiguability or sudden falling
• Drooping eyelids (ptosis)
• Double vision
• Reduced ACh binding so harder to sustain contraction of muscles

Question 11

How could you treat someone with myasthenia gravis?

Answer 11

• ACETYLCHOLINESTERASE INHIBITORS (ACh remains in cleft for longer so more chance of binding)
• IMMUNOSUPPRESSANTS
• PLASMAPHERESIS (remove harmful antibodies from patient’s serum)
• THYMECTOMY

Question 12

What is meant by a ‘muscular dystrophy’?

Answer 12

• GENETIC condition

- Progressive weakening and wasting away of muscles

Question 13

What is Duchenne Muscular Dystrophy characterised by?

Answer 13

• Complete loss of DYSTROPHIN protein (connects cytoskeleton to muscle fibre)
• Shrinkage of cells (dying)

Question 14

What are the consequences of a lack of dystrophin in muscle?

Answer 14

• Muscle fibres tear themselves apart on contraction
• Damage to cell membranes so Ca2+ enters causing cellular NECROSIS
• Enzymes such as creatine kinase can leak out of cell
• PSEUDOHYPERTROPHY

Question 15

What is PSEUDOHYPERTROPHY and when does it occur?

Answer 15

• ‘Swelling’ of muscle before replacement of muscle cells with adipose and connective tissue
• Gives illusion that muscle is not wasting
• Occurs during DMD

Question 16

Describe how DMD can be identified and treated

Answer 16

• Early onset
• Can be detected using GOWER’S SIGN (ask patient to push against quad muscles)
• CONTRACTURES (imbalance between agonist and antagonist muscles)
• Rigid contractions due to growth of connective tissue
• Treated using antiinflammatory steroids such as PREDNISOLONE
• Genetic research into causes (stem cells)

Question 17

Name 3 myopathies other than muscular dystrophy that can occur in the body

Answer 17

• INFLAMMATORY (polymyositis, myalgia -> influenza - inflammation of joints and muscle ache)
• THYROTOXICOSIS (increase in BMR and protein catabolism so breaks down muscle)
• HYPOPARATHYROIDISM (hypocalcaemia leading to sustained contraction of muscle - tetany)

Question 18

Explain the pathophysiology of malignant hyperthermia

Answer 18

• AUTOSOMAL DOMINANT - TRIGGERS INCREASED OXIDATIVE METABOLISM OF SKELETAL MUSCLE IN RESPONSE TO ANAESTHETICS
• Uncontrolled heat production and increased metabolism of muscle cells
• Body cannot supply O2 and remove CO2 fast enough, leading to death
• Treated with DANTROLENE which relaxes muscle by inhibiting Ca2+ release

Question 19

How does succinylcholine work?

Answer 19

• Non-competitive inhibitor of ACh for nicotinic receptors

- Broken down by BUTYRLCHOLINESTERASE which breaks it down much more slowly than acetylcholinesterase does to ACh