8.5 Skeletal Muscle Structure, Function and Disorders Flashcards
What are some biopsy hallmarks of normal skeletal muscle?
- No scarring
- No inflammatory markers
- Equal sized muscle fibres
- Normal connective tissue structures (epi/perimysium)
Outline the key features of dermatomyositis
(muscle inflammation)
- Facial and hand rash
- Muscle Weakness
- Perifascicular atrophy/MHC 1 expression and inflammatory infiltrate
Outline the key features of inclusion body myositis (IBM)
- Muscle weakness; classically finger flexors and knee extensors, but can cause dysphagia
- Inflammatory infiltrate; fibre size variability
- May eventually need help with ADLs
What are key symptoms of Immune Mediated Necrotising Myopathy? What drug may cause it?
- Atrophy
- Loss of weight
- May be associated with statins
What are the key histological features of Immune Mediated Necrotising Myopathy?
Diffuse necrotic fibres. Paucicellular inflammatory infiltrate.
What does creatine kinase do? Thinking back to energy pathways, why is this useful?
- Forms phosphocreatine from creatine in muscle and phosphate from ATP hydrolysis
- Can be stored for rapid use in initiation of exercise
What diagnostically useful molecule is produced during the purine nucleotide cycle? Why is it important?
- Ammonia (NH3)
- May be comorbid with oxidative dysfunction
What are three blood tests that should be performed in the setting of suspected muscle metabolic disorders? Why?
- Creatine kinase (could explain second wind phenomena)
- TSH (hypothyroidism)
- Vitamin D (calcium is required for muscle contraction, after all)
What is rhabdomyolysis?
“Rod muscle loosening”
- Necrosis of muscle with leakage of intracellular components into bloodstream.
Outline glycogen storage diseases, including the different symptoms of different types.
Glycogen-based abnormalities:
Types 1/3: inability to properly break down glucose; weakness, hepatomegaly, hypoglycaemia
Type 4: Abnormal glycogen triggers autoimmune response; liver cirrhosis
What are some symptoms of fatty acid oxidation disorders? Why does this make sense?
Fatty acids are the fuel used by muscles at rest:
- Lethargy
- Hypotonia
Can arise from dysfunction
Outline the classical presentation of mitochondrial disorders
- External opthalmoplegia (extraocular weakness)
- Lactic acidosis (krebs cycle interrupted)
In one go, describe the structural organisation of muscles
- Sarcomeres make fibrils
- Fibrils make fibres
- Fibres make fascicles
- Fascicles make muscle
- Endomysium surrounds fibres
- Perimysium surrounds fascicles
- Epimysium surrounds muscle
Describe skeletal muscle contraction in one go
- 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
What is a motor unit?
All the muscle fibres innervated by a single motor neuron.
How does motor unit recruitment influence muscle force?
- More motor units recruited for bigger force
- More rapid stimulation of muscle fibres to increase their individual force
What is a motor neuron pool?
All the motor neurons innervating a given muscle
In terms of stimulation, how can we alter the force produced by each motor unit? (this is called ____ coding)
- Faster impulses = more force
- This is called rate coding
What are H, I, and A bands in terms of sarcomere structure?
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)
What is the pathogenesis of adult polymyositis?
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)
What is the pathogenesis of adult dermatomyositis?
- Binding of autoantibodies to capillary vasculature -> complement activation.
- Reduction in number of capillaries in fascicles, perivascular inflammation
Inclusion body myositis pathogenesis
- 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)
How MAY IvIg help in inflammatory muscle disorders?
- MAY inhibit T cell activation
- MAY reduce cytokine production
Rituximab is a form of immunosuppressive therapy. Which kind of cells does it target?
B Cells (CD20 protein)
Describe the skeletal-muscle based features of inflammatory muscle disorders
- Insidious, bilateral
- Proximal > distal
- Dysphagia
- LL: trouble getting up from chair
- UL: trouble with overhead activities
Which muscles are classically affected in inclusion body myositis?
- Quadriceps
- Forearm finger flexors
- Ankle dorsiflexors
Outline the basic pathogenesis of necrotising myopathy/immune mediated necrotising myopathy
- Predominantly muscle fibre necrosis with min/no inflammation
- IMNM: immunological mechanisms are thought to be important
What is the effect of resistance training on the catabolic/anabolic balance? Does it promote/reduce inflammation in patients with inflammatory muscle disorders?
- Increases anabolism; helping to counteract effects of atrophy
- Reduces inflammation
