8.5 Skeletal Muscle Structure, Function and Disorders

Question 1

What are some biopsy hallmarks of normal skeletal muscle?

Answer 1

• No scarring
• No inflammatory markers
• Equal sized muscle fibres
• Normal connective tissue structures (epi/perimysium)

Question 2

Outline the key features of dermatomyositis

Answer 2

(muscle inflammation)

• Facial and hand rash
• Muscle Weakness
• Perifascicular atrophy/MHC 1 expression and inflammatory infiltrate

Question 3

Outline the key features of inclusion body myositis (IBM)

Answer 3

• Muscle weakness; classically finger flexors and knee extensors, but can cause dysphagia
• Inflammatory infiltrate; fibre size variability
• May eventually need help with ADLs

Question 4

What are key symptoms of Immune Mediated Necrotising Myopathy? What drug may cause it?

Answer 4

• Atrophy
• Loss of weight
• May be associated with statins

Question 5

What are the key histological features of Immune Mediated Necrotising Myopathy?

Answer 5

Diffuse necrotic fibres. Paucicellular inflammatory infiltrate.

Question 6

What does creatine kinase do? Thinking back to energy pathways, why is this useful?

Answer 6

• Forms phosphocreatine from creatine in muscle and phosphate from ATP hydrolysis
• Can be stored for rapid use in initiation of exercise

Question 7

What diagnostically useful molecule is produced during the purine nucleotide cycle? Why is it important?

Answer 7

• Ammonia (NH3)
• May be comorbid with oxidative dysfunction

Question 8

What are three blood tests that should be performed in the setting of suspected muscle metabolic disorders? Why?

Answer 8

• Creatine kinase (could explain second wind phenomena)
• TSH (hypothyroidism)
• Vitamin D (calcium is required for muscle contraction, after all)

Question 9

What is rhabdomyolysis?

Answer 9

“Rod muscle loosening”
- Necrosis of muscle with leakage of intracellular components into bloodstream.

Question 10

Outline glycogen storage diseases, including the different symptoms of different types.

Answer 10

Glycogen-based abnormalities:

Types 1/3: inability to properly break down glucose; weakness, hepatomegaly, hypoglycaemia

Type 4: Abnormal glycogen triggers autoimmune response; liver cirrhosis

Question 11

What are some symptoms of fatty acid oxidation disorders? Why does this make sense?

Answer 11

Fatty acids are the fuel used by muscles at rest:

• Lethargy
• Hypotonia

Can arise from dysfunction

Question 12

Outline the classical presentation of mitochondrial disorders

Answer 12

• External opthalmoplegia (extraocular weakness)
• Lactic acidosis (krebs cycle interrupted)

Question 13

In one go, describe the structural organisation of muscles

Answer 13

• Sarcomeres make fibrils
• Fibrils make fibres
• Fibres make fascicles
• Fascicles make muscle
• Endomysium surrounds fibres
• Perimysium surrounds fascicles
• Epimysium surrounds muscle

Question 14

Describe skeletal muscle contraction in one go

Answer 14

• Presynaptic impulse -> calcium influx
• ACh release
• If big enough, sarcolemma (and therefore T tubules) are depolarised
• Voltage gated Ca2+ release
• Binds to tropomyosin
• Myosin binds to actin = contraction

Question 15

What is a motor unit?

Answer 15

All the muscle fibres innervated by a single motor neuron.

Question 16

How does motor unit recruitment influence muscle force?

Answer 16

• More motor units recruited for bigger force
• More rapid stimulation of muscle fibres to increase their individual force

Question 17

What is a motor neuron pool?

Answer 17

All the motor neurons innervating a given muscle

Question 18

In terms of stimulation, how can we alter the force produced by each motor unit? (this is called ____ coding)

Answer 18

• Faster impulses = more force
• This is called rate coding

Question 19

What are H, I, and A bands in terms of sarcomere structure?

Answer 19

H: Between light chain (actin)
I: Between myosin
A: Within myosin

(H chain is between the H-shaped actin, I chain is between the I-shaped myosin, A chain is within myosin, which is the best = A)

Question 20

What is the pathogenesis of adult polymyositis?

Answer 20

Autoimmune rxn of CD8 T cells and macrophages against skeletal muscle cells that abnormally express MHC 1.

(The “P” and “O” Combine to form an “8”, signifying CD8 T cell rxn against MHC class 1)

Question 21

What is the pathogenesis of adult dermatomyositis?

Answer 21

• Binding of autoantibodies to capillary vasculature -> complement activation.
• Reduction in number of capillaries in fascicles, perivascular inflammation

Question 22

Inclusion body myositis pathogenesis

Answer 22

• Autoreactive T and B cells on muscle
• Misfolded proteins drive the T cell response
• Mitochondrial abnormalities

(Inclusion = inclusive = both T and B cells are involved; heck, mitochondrial disorders are even included)

Question 23

How MAY IvIg help in inflammatory muscle disorders?

Answer 23

• MAY inhibit T cell activation
• MAY reduce cytokine production

Question 24

Rituximab is a form of immunosuppressive therapy. Which kind of cells does it target?

Answer 24

B Cells (CD20 protein)

Question 25

Describe the skeletal-muscle based features of inflammatory muscle disorders

Answer 25

• Insidious, bilateral
• Proximal > distal
• Dysphagia
• LL: trouble getting up from chair
• UL: trouble with overhead activities

Question 26

Which muscles are classically affected in inclusion body myositis?

Answer 26

• Quadriceps
• Forearm finger flexors
• Ankle dorsiflexors

Question 27

Outline the basic pathogenesis of necrotising myopathy/immune mediated necrotising myopathy

Answer 27

• Predominantly muscle fibre necrosis with min/no inflammation
• IMNM: immunological mechanisms are thought to be important

Question 28

What is the effect of resistance training on the catabolic/anabolic balance? Does it promote/reduce inflammation in patients with inflammatory muscle disorders?

Answer 28

• Increases anabolism; helping to counteract effects of atrophy
• Reduces inflammation