PTH-03-Disease of Muscle Flashcards
Diagnosis of Muscle Disorder
History, exclude systemic disorder, EMG, Blood test, biopsy
Normal Motor Unit Consist
Motor neuron in brain stem or spinal cord.
Peripheral axon.
Neuromuscular junction.
Skeletal muscle fiber.
Muscle Disorders
Muscular Dystrophies Neurogenic disorders Inflammatory Myopathy Myotonic Syndromes Congenital Myopathies Metabolic e.g. glycogen storage diseases Endocrinopathies e.g. Cushing’s Syndrome Drug induced Neuromuscular junction disorders
Muscular Dystrophy
Primary disease of muscle
Several types, various inheritance
Start in childhood or adolescents, some late
Progressive degeneration of muscle fibers
Similar clinical & histological features, but differ in location & rate of progression
MD-Types
Duchenne muscle dystrophy Becker muscle dystrophy Limb Girdle dystrophy Myotonic Dystrophy Others
Duchenne Muscular Dystrophy (DMD)
Boys are affected.
Mostly X-linked inherited disease, female carrier
Rare sporadic mutations
Commonest & most severe
Starts at as 1 yr.- 5y., delayed walking, proximal weakness, death by age 20y
DMD-Pathogenesis
Loss of function mutation (deletion) of Dystrophin gene on short arm of Xp21
-Dystrophin stabilizes muscle during contraction
-Without dystrophin, sarcolemma are weak, tear & muscle shows splitting…etc
In DMD , Dystrophin is totally absent
DMD-Morphology
Marked variation in muscle fiber size
Degenerative changes in scattered fibers : fiber splitting,loss of striations, necrosis
Regenerative changes : basophilia, nuclear enlargement, prominent nucleoli
Increase in intermuscular connective tissue, few inflammatory cells
Later fiber loss & infiltration by fat
Abnormal dystrophin staining
DMD-CP
Boy born normal, but progressive muscle weakness
Starts proximally, first in the pelvis, later shoulder
Characteristic ‘Pseudohypertrophy’ of leg muscles
High serum creatine kinase which later returns to normal
Cardiomyopathy
Death from respiratory insufficiency & infection, cardiac failure
BMD
Starts later
Milder
Less common
Same gene defect but Dystrophin is decreased in amount & has abnormal molecular weight
Cardiac disease may be present
Outcome is variable with a nearly normal life span.
Muscle Atrophy
Muscular shrinkage secondary to deprivation of normal innervations
Initially all the muscle fibers in a motor neuron are affected
Later collateral sprouting , taken over by one nerve
Single type fiber→loss of normal mixture of Type 1 and Type 2
Called “GROUP ATROPHY “
Small angulated muscle fibers
MA-Cause
Motor neuron disease(ALS), Polio… Peripheral neuropathy Trauma Patients with disuse atrophy when immobilized Patients who receive glucocorticoids Patients with hypercortisolism
Inflammatory Myopathies
Infection (myositis)
- Bacterial
- Viral:- Influenza, coxsackie, HIV
- Parasitic: Trichinella spiralis, Cysticercosis
Noninfectious immune mediated myopathies
- Polymyositis
- Dermatomyositis
- Inclusion body myositis
Polymyositis & Dermatomyositis
Group of immunologically mediated muscle injury characterized by inflammation
May be associated with other disease of autoimmune nature
Polymyositis & Dermatomyositis-Pathogenesis:
Antibody mediated tissue injury in dermatomyositis and cytotoxic T- cell injury in polymyositis.
