Week 4 - Muscle Diseases/Soft Tissue Tumors Flashcards
Describe the genetic defect for spinal muscular atrophy.
- Autosomal Recessive
- mutations affecting survival motor neuron 1 (SMN1) on chromosome 5
Compare and contrast the pathogenesis of Duchenne Muscular Dystrophy and Becker Muscular Dystrophy.
- DMD
- little or no dystrophin
- BMD
- defective or decreased amounts of dystrophin
Compare and contrast the clinical outcome of Duchenne and Becker muscular dystrophy.
- DMD
- symptoms by age 5 (weak pelvic/shoulder girdle, “duck-like” gait, Gower’s maneuver, “pseudohypertrophy”)
- survival of approximately 35 yrs
- BMD
- later onset, milder symptoms
- survive well into the 40’s and beyond
Describe the genetic defect for myotonic dystrophy.
- Autosomal Dominant
- trinucleotide repeat disorder
- increased CTG trinucleotide repeat sequences on chromosome 19
- results in defects affecting transcription of proteins for a chloride channel (CLC1)
Describe the genetic defect and clinical presentation of malignant hyperpyrexia (malignant hyperthermia).
- several mutations that encode proteins that control levels of cystolic calcium
- upon exposure to an anesthetic, the abnormal calcium channels allow uncontrolled release of calcium from skeletal muscle cells
- acute medical emergency –> TETANY (involuntary muscle contraction)
- excessive heat production!
What are the three subgroups of inflammatory myopathies?
- Infectious
- ex. Clostridial gas gangrene
- Systemic Inflammatory Disease Associated
- ex. Systemic lupus erythematosis
- Noninfectious inflammatory Disease associated
- Dermatomyositis
Dermatomyositis
- pathogenesis
- clinical presentation
- pathologic findings
- Immunologic disease with immunologic injury and damage to small blood vessels and capillaries in the skeletal muscle.
- Symmetric muscle weakness (proximal first) & skin rash (Gottron papules of upper eyelids)
- Lymphocytic inflammation around small blood vessels & perimysial connective tissue, perifascicular myocyte atrophy
***Be aware of underlying malignancy(15-25%)!!!
Polymyositis
- pathogenesis
- clinical presentation
- pathologic findings
- autoantibodies directed against histidyl t-RNA synthetase (activated CD8+ cytotoxic Tcells injury muscle)
- Elevated creatine kinase, no skin involvement (no rash)
- Lymphocytic inflammation surrounding and invading muscle fibers, necrotic and regenerating muscle fibers throughout fascicle, no atrophy, no vascular injury
Inclusion Body Myositis
- pathogenesis
- clinical presentation
- pathologic findings
- uncertain (inflammatory vs. degenerative w/ 2° inflammation)
- distal muscle weakness, >50 years old, asymmetric, moderately elevated creatine kinase
- rimmed vacuoles, lymphocytic inflammatory infiltrate
**Myasthenia Gravis **
- pathogenesis
- key clinical associations
- autoimmune disease causeed by AChR autoantibodies –> lost of function of acetylcholine receptor
- thymic abnormalities (hyperplasia 30%, thymoma 10%), generalized muscle weakness/extraocular muscle weakness
Lambert-Eaton myasthenia syndrome
- pathogenesis
- key clinical associations
- immune disorder due to autoantibodies directed against presynaptic calcium channels (block ACh release)
- Extremity weakness, rapid repetitive stimulation of the affected muscle increases the muscle response
***Paraneoplastic syndrome, malignancy 60%, (often small cell lung carcinoma)
What are the causes of elevated Creatine Kinase?
- Acute MI or myocardial injury
- Skeletal muscle diseases (Rhabdo, muscular dystrophy, skeletal muscle trauma)
- Cerebrovascular accidents, head injury
What is the classification scheme for mesenchymal/soft tissue tumors?
- types of tissue that they recapitulate or differentiate to
- histogenetic categories
- divided into benign and malignant sarcoma
Describe the typical pattern of spread of sarcomas when they metastasize.
Metastasize via hematogenous routes (to lung and bone)
What is the type of cell that gives rise to soft tissue tumors.
Mesenchymal stem cells
