What is muscular dystrophy?
A group of inherited disorders of muscle that begin in childhood, that lead to progressive weakness and muscle wasting. Muscle fibres undergo degeneration are are replaced with fibrofatty tissue and collagen.
disease of voluntary muscle
Name four pathological processes that can affect muscle fibres
Acute inflammation and fibre necrosis
Inherited metabolic failure (genetic disease)
Hypertrophy and regeneration
Ion channel disorders
What investigations could you do to determine if there has been muscle damage?
Blood test: serum creatine phosphokinase (CPK) is elevated in many dystrophies
Muscle biopsy: Histology of fibre types indicates denervation, inflammation and dystrophic changes. EM of muscle fibres for inflammation, necrosis or hypertrophy
Describe the 3 types of primary inflammatory myopathies
Polymyositis: Inflammatory myopathy of the proximal muscle. Facial weakness and dysphagia. No muscle pain. Inflammatory cells are found in the endomysium, necrotic and regenerating fibres are found throughout the fascicle.
Dermatomyositis is when the skin is involved, and there is a characteristic rash on the eyelids and fingers. Inflammatory infiltrates are found around the small blood vessels and there is atrophy and necrosis of fibres surrounding the fascicles.
Inclusion body myositis is where the distal muscles are involved e.g. quadriceps and flexors of the wrist and fingers. Inflammation causes formation of vacuoles in the myocytes.
Describe the pathology of Duchenne muscular dystrophy
X-linked recessive disorder due to a mutation in the dystrophin gene (deletion/ frameshift mutations).
Dystrophin is essential for cell membrane stability. It forms a complex with laminin within the sarcolemma and cytoplasmic actin (interface between the intracellular contractile filaments and extracellular tissue matrix).
Dysfunctional protein causes myocyte weakness and degeneration. Fibres tear with repeated contractions.
What is the histological appearance of muscle in DMD?
Variation in fibre size
Degeneration, necrosis and phagocytosis of muscle fibres
Regeneration of muscle fibres
Enlarged connective tissue in the endomysium
In later stages of the disease, the muscles become replaced by fat and connective tissue.
What are the for pathalogical responses to injury in skeletal muscle?
Change in fibre type distribution
Describe the features of axonal degeneration
Result of primary destruction of the axon due to trauma or ischemia, with secondary disintegration of the myelin sheath.
The axon degenerates and Schwann cells begin to breakdown myelin and engulf axon fragments. Macrophages are recruited and remove axonal and myelin debris.
The proximal stumps of the degenerated axons sprout and elongate during the process of regeneration.
What is the effect of degeneration/damage to nerves on muscle?
When nerve degeneration or damage occurs, the muscle fibres within the affected motor unit lose neural input.
Denervation leads to breakdown of actin and myosin, and decrease in cell size (denervation atrophy).
What are the changes histological that occur in reinnervation of muscle?
Reinnervation of skeletal muscle changes its composition, because the distribution of type 1 and type 2 fibres is altered.
Fibre types are determined by the motor neuron innervating it. All muscle fibres in a single motor unit are the same type. In normal tissue fibres of a single motor unit are distributed alternately across the muscle. (checkerboard pattern with histochem)
Atrophic muscle fibres are reiinervated by the axons of unaffected neighbouring motor units sprouting in innervate the myocytes. Therefore the reinnervated fibres assume the properties of the neighbouring motor unit. (loss of checkerboard).
When does type-specific atrophy occur in muscle?
(Type 2 - fast)
Type specific atrophy normally occurs in disease.
Type 2 fibre atrophy is common iwith inactivity or dissuse. This may occur following immobilisation of a fractured lumb, neurodegenerative diseases, or in therapy with glucocorticoids.
What investigations could you carry out using a muscle biopsy sample?
Compare the changes that occur in neurogenic disease vs. dystrophes and myopathies
Atrophy in groups of fibres
Dystrophies and myopathies:
Hypertrophy and atrophy possible
Single fibre degeneration
State 4 features of muscular dystrophies
Individual fibre loss
Result in abnormalities in contractile proteins and molecules connetinve muscle cells to the ECM
What is myotonic dystrophy?
Sustained, involuntary contraction of a group of muscles.
Patiients complain of stiffness and have difficulty releasing their grip.
Can be elicited by percussion of the thenar eminence
What is the clinical presentation of Duchenne Muscular dystrophy?
Difficulty running and rising to feet. Uses hands to climb up legs (Gower's sign).
Proximal limb weakness.