Muscle Disease Flashcards
Type I myofibers
High in oxidative activity, low in glycolytic capacity, red grossly (from myoglobin and mitochondrial cytochromes), contracts slowly, capable of continuous and repeated contraction
Type II myofibers
Low in oxidative activity, high in glycolytic activity, white grossly, fast contracting, cannot maintain repeated contraction
Neurogenic atrophy clinical clues
Nerve damage often with associated sensory features
Neurogenic atrophy histopathological features
Fiber type grouping, group atrophy
Neurogenic atrophy etiology
Motor nerve damage
Disuse/steroid atrophy clinical clues
Bedridden/ICU, corticosteroids (long term use), hypothyroidism
Disuse/steroid atrophy histopathological features
Type II myofiber atrophy
Disuse/steroid atrophy etiology
Atrophy of fast twitch fibers
Dystrophin related myopathy clinical clues
Childhood onset
Dystrophin related myopathy histopathological features
Myofiber size variability, necrosis, regeneration, endomysial fibrosis, fatty replacement
Dystrophin related myopathy etiology
Hereditary abnormalities of dystrophin or related proteins
Inflammatory myopathy clinical clues
Adult onset, associated rheumatologist features
Inflammatory myopathy histopathological features
Inflammation (usually T-cells), necrosis and regeneration
Inflammatory myopathy etiology
Autoimmune
Congenital myopathy clinical clues
Onset at birth, floppy baby
Congenital myopathy histopathological features
Wide variety of specific changes, inclusions, etc. (nemaline rods, central cores)
Congenital myopathy etiology
Variable
Channelopathies clinical clues
Myotonia, intermittent symptoms
Channelopathies histopathological features
May be normal
Channelopathies etiology
Muscle sodium channel protein SCN4A defect
Myopathic patterns
Often associated with scattered myofiber necrosis and regeneration
Inflammatory myopathies pattern
Myopathic but also characterized by inflammatory infiltrates and/or intracellular inclusions
Neuropathic changes
Fiber type grouping or group atrophy
Type II myofiber atrophy from disuse
Due to any cause for prolonged immobilization, results in focal or generalized muscle atrophy, tends to affect type II more than type I
Type II myofiber atrophy glucocorticoids
History of exposure, either exogenous or endogenous (as in Cushing syndrome), can cause muscle atrophy
Dystrophinopathies
Duchenne and Becker muscular dystrophy
Broad definition of muscular dystrophies
Diseases associated with the dystrophin-glycoprotein complex
Dystrophin-glycoprotein complex function
Skeletal muscle membrane associated proteins involved in the mechanical stabilization and signaling interactions between the cytoskeleton, membrane, and extracellular matrix
Duchenne muscular dystrophy clinical course
Evident around 5 years, wheelchair-bound by teenagers, death in early adulthood
Clinical features of DMD
Gower’s sign in children, clumsiness, inability to keep up with peers, weakness begins in pelvic girdle and then shoulder, calf muscles enlarged (pseudohypertrophy), high serum creatine kinase levels early on but fall as muscle mass is lost
Clinical features of BMD
Appears later in childhood or adolescence, slower and more variable progression, live well into adulthood with nearly normal life span
Histologic changes in dystrophinpathologies
Ongoing myofiber necrosis and regeneration, progressive replacement of muscle tissue by fibrosis and fat, variation in myofiber size and abnormally placed internal nuclei (all of these in both BMD and DMD, but BMD is more mild), dystrophin sarcolemmal staining pattern negative (DMD) or reduced (BMD)
Pathogenesis of dystrophinopathies
Loss of function mutations in dystrophin gene on the short arm of the X chromosome (Xp21)
Congenital myopathy examples
Central core disease, nemaline myopathy, centronuclear myopathy
Congenital myopathy patterns
Perinatal or early childhood presentation and often result in relatively static deficits
Channelopathy patterns
Myotonia, relapsing episodes of hypotonic paralysis associated with abnormal serum potassium levels
Hyperkalemic periodic paralysis
Mutations in gene encoding skeletal muscle sodium channel protein SCN4A, which regulates sodium entry during contraction
Metabolic myopathy (glycogen synthesis abnormalities)
Detected with PAS and myophosphorylase
Metabolic myopathy (lipid abnormalities)
Detected with Oil Red O
Mitochondrial myopathies
Mutations in mitochondrial or nuclear genomes, usually manifest in early adulthood with proximal muscle weakness and sometimes severe involvement of ocular musculature, ragged red fibers on histology from aggregates of mitochondria
Inflammatory myopathy examples
Polymyositis, dermatomyositis, inclusion body myositis
Polymyositis
Autoimmune disorder associated with T-cells and increased expression of MHC class I on myofibers, endomysium damaged, responds to corticosteroids and immunosuppressive agents
Dermatomyositis
Autoimmune disorder, presents with malar rash, rash on upper eyelids, red papules on elbows, knuckles, knees, on histology there is myofiber damage in a paraseptal or perifascicular pattern
Inclusion body myositis
Typically in patients older than 60, morphologic hallmark is presence of rimmed vacuoles, might be a degenerative disorder of aging, myopathic changes, mononuclear cell infiltrates, endomysial fibrosis, fatty replacement, chronic and progressive course, does not respond well to immunosuppressive agents
Toxic myopathy (thyroxine)
Acute or chronic proximal muscle weakness, show myofiber necrosis and regeneration, associated with thyrotoxicosis
Toxic myopathy (ethanol)
After an episode of binge drinking, degree of rhabdomyolysis may be severe (can lead to acute renal failure secondary to myoglobinuria), patients present with acute muscle pain (generalized or localized to a group), myocyte swelling, necrosis, regeneration
Toxic myopathy (drug)
Most commonly drugs from the statin family, affected muscles show evidence of myopathic injury usually without an inflammatory component
