MSCT Week 3: Skeletal Muscle Pathology Flashcards
Satellite Cells
Myofiber associated stem cells called satellite cells that can contribute to regeneration following injury
ONE SLOW RED OX
- Type 1
- Dark meat red legs these are high in oxidative activity, low in glycolytic capacity and red grossly because of high myoglobin and mitochondrial content
- they contract slowly but are capable of continuous and repeated contraction
Two Fast White Sugar
- Type II
- White meat
- low in oxidative activity
- high in glycolytic capacity
- fast contracting
- cannot maintain repeated contraction
Neurogenic Atrophy
Clinical Clues
Nerve Damage (often associated with sensory features)
Neurogenic Atrophy
Histopathologic Features
2 Listed
- Fiber Type Grouping
- Group Atrophy
Neurogenic Atrophy
Etiology
Motor Nerve Damage
Disuse/Steroid Atrophy
Clinical Clues
3 Listed
- Bedridden/ICU
- Corticosteroids
- Hyperthyroidism
Disuse/Steroid Atrophy
Histopathologic Features
Type II myofiber atrophy
Disuse/Steroid Atrophy
Etiology
Atrophy of Fast Twitch Fibers
Dystrophin Related Myopathy
Clinical Clues
Childhood onset
Dystrophin Related Myopathy
Histopathologic Features
5 Listed
- Myofiber size variability
- Necrosis
- Regeneration
- Endomysial fibrosis
- Fatty Replacement
Dystrophin Related Myopathy
Etiology
- Hereditary abnormalities of dystrophin or related proteins
- DMD gene
Inflammatory Myopathy
Clinical Clues
2 listed
- Adult-onset
- associated rheumatologic features
Inflammatory Myopathy
Histopathologic Features
3 listed
- Inflammation (usually T-cells)
- Necrosis
- Regeneration
Inflammatory Myopathy
Etiology
Autoimmune
Congenital Myopathy
Clinical Clues
2 Listed
- Onset at birth
- Floppy Infant
Congenital Myopathy
Histopathological Features
Wide variety of specific changes or inclusions etc (nemaline rods, central cores)
Congenital Myopathy
Etiology
Variable
Channelopathies
Clinical Clues
2 listed
- Myotonia
- intermittent symptoms
Channelopathies
Histopathologic Features
May be normal
Channelopathies
Etiology
Muscle Sodium channel protein SCN4A defect
Patterns of myopathic conditions
often associated with scattered myofiber necrosis and regeneration
Patterns of Inflammatory myopathic conditions
Are myopathic but are also characterized by inflammatory infiltrates and/or intracellular inclusions
Patterns of Fiber type Grouping and Grouped Atrophy, target Fibers conditions
Neuropathic changes
Patterns of Type II Myofiber Atrophy conditions
- Disuse atrophy due to any cause (prolonged bed rest in the sick, casting of a bone, can cause focal or generalized muscle atrophy, which tends to affect type II fibers more than type I
- Glucocorticoid exposure, whether exogenous or endogenous (Cushing’s Syndrome) can also cause muscle atrophy
- Hyperthyroidism can also result in Type II myofiber atrophy
Muscular Dystrophies
include a variety of diseases associated with the dystrophin-glycoprotein complex
dystrophin-glycoprotein complex
consists of skeletal muscle membrane-associated proteins involved in the mechanical stabilization and signalling interactions between the cytoskeleton, membrane, and extracellular matrix
Histology of DMD and BMD
2 listed
- progressive replacement of muscle tissue by fibrosis and fat is the result of degeneration outpacing repair (fibrosis and fatty replacement)
- As a result of ongoing repair muscles typically show marked variation in myofiber size and abnormal internally placed nuclei
DMD and BMD in cardiac muscles
BMD and DMD also affect cardiac muscles
BMD and DMD pathogenesis
- loss-of-function mutations in the dystrophin gene located on the short arm of the X chromosome (Xp21)
- Severity of the disease correlates with the degree of the dystrophin deficiency
Clinical features of DMD
- Clumsiness and inability to keep up with peers due to muscle weakness
- weakness usually begins in the pelvic girdle and moves to the shoulder girdle
- enlargement of calf muscles (pseudohypertrophy)
- owing to ongoing muscle degeneration, high serum creatine kinase levels at birth but slowly decrease as muscle mass is lost
Clinical Features of BMD
- symptomatic later in childhood or adolescence
- nearly normal life-span
- cardiac involvement can be the dominant feature and may result in death even in the absence of muscle weakness
Other X linked and Autosomal muscular dystrophies
- Myotonic Dystrophy
- Limb-girdle Muscular Dystrophy
- Emery-Dreifuss Muscular Dystrophy
- Fascioscapulohumeral Dystrophy
Congenital myopathies examples
- Central Core Disease
- Nemaline Myopathy
- Centronuclear Myopathy
Channelopathies, Metabolic Myopathies, Mitochondrial Myopathies
due to defects in ion channels characterized by myotonmia, relapsing episodes of hypotonic paralysis assocated with abnormal serum potassium levels or both
Muscle Sodium Channel Protein and chromosome
SCN4A
Chromosome 7
Malignant Hyperthermia
a rare syndrome that can result in death from anesthetic agents or succinylcholine during surgery
Mitochondrial Myopathies
stem from mutations in either the mitochondrial or nuclear genomes, usually manifest in early adulthood with proximal muscle weakness and sometimes severe involvement of the ocular musculature
some show aggregates of abnormal mitochondria (ragged red fibers)
Glycogen synthesis abnormalities are detected with
PAS and myophosphorylase
Lipid abnormalities are detected with
Oil Red O
Inflammatory myopathies
Myotonia
inability to relax voluntary muscle after vigorous effort.
