Skeletal Muscle Flashcards
What is the pathology of spinal muscular atrophy?
Progressive destruction of anterior horn cells and cranial nerve motor neurons
What is the mutation and inheritance that causes spinal muscular atrophy?
Autosomal recessive
Survival Motor Neuron 1 (SMN1)
What is the cause of Duchenne Muscular Dystrophy?
Dystrophin protein defect from abnormal gene
Most common type of MD
X-linked
What is the clinical presentation of DMD?
Normal at birth, followed by delayed walking and clumsiness
Pseudohypertrophy of the calves
Impaired cognition
Death occurs from respiratory failure, cardiac decompensation, or lung infection
What is Becker Muscular Dystrophy?
Defect in dystrophin quality/quantity of protein
Less common, less severe, later onset than DMD
How does limb girdle muscular dystrophy present?
Begin to walk with a waddling gait because of weak hip and leg muscles
Trouble getting out of chairs or climbing stairs
Many types related to dystrophin glycoprotein complex
What is facioscapulohumeral MD?
Facial weakness and wasting of the upper arm and shoulder muscles
Winged scapula
What is the triad of Emery’Dreifuss MD?
early on humeroperoneal weakness
Prominent contractures, especially in the elbows and ankles
Cardiomyopathy
What is the cause of myotonic dystrophy?
Autosomal dominant of expansion mutations in Dystrophila myotonia-protein kinase (DMPK)
Displays anticipation: onset at a younger age in succeeding generations
How does myotonic dystrophy present?
Stiffness and difficulty releasing grip
Onset in childhood
Abnormal gait, weakness of intrinsic hand and wrist extension
Facial muscle atrophy and ptosis
What is the most common channelopathy?
Hypokalemic periodic paralysis
What is hypokalemic periodic paralysis?
Most common is Ca channel mutations
Patient suffers attacckes of flaccid weakness provoked by carb meals, exercise, heat, cold, stress, meds
What is malignant hyperpyrexia?
Sudden hypermetabolic state with tachypnea and general muscle contraction
Triggered by anesthesia: Halogen containing gases or succinycholine
What is the cause and treatment of malignant hyperpyrexia?
Ryanodine receptor RyR1 mutation
Release of Ca from SR causes ATP depletion and anaerobic metabolism
Causes hyperthermia, Rhabdomyolysis, Hyperkalemia, Renal failure
Treatment: Dantrolene
What is Central core disease?
Autosomal dominant hypotonic myopathy caused by RYR1 gene defect
Risk for malginant hyperthermia
Centrally light area in type 1 fibers seen on microscopic examination
What is Nemaline myopathy?
Nonprogressive hypotonia, weakness that involve sproximal limb muscle
Causes developmental delays in kids
What is centronuclear myopathy?
Myopathy characterized by central nuclei usually confined to type 1 fibers
What are lipid myopathies caused by?
Defects in carnitine transport system or mitochondrial dehydrogenase enzyme system that results in the accumulation of lipid in myocytes
What are mitochondrial myopathies and what is found on microscopic examination?
Oxidative phosphorylation diseases caused by defects in mtDNA or nuclear DNA
Ragged red fibers from aggregated mitochondria and mitchondria “parking lot” paracrystalline inclusions
What is dermatomyositis?
Skin rash precedes or bigeins with myositis
Causes scaling erythematous eruption or dusky red patches over knuckles, elbows, knees (Grotten lesions)
Slow and symmetrical muscle weakness with or without myalgias
What additional symptoms occur in Juvenile dermatomyositis?
GI vasculopathy leads to ulceration, hemorrhage and perforation
What is the pathology of dermatomyositis?
Microvasculature attacked by antibodies and compliment creating ischemia
Perifascicular atrophy
Inflammation in perimysial connective tissue NOT muscle
Mediated by CD4 T cells and B cells
What is the pathology of Polymyositis?
Autoantibodies against tRNA synthetases
Can be +/- ANA positive
Cytotoxic CD8+ T cells in endomysium destroy muscle
How does Polymyositis present?
Systemic inflammatory myopathy
Muscle weakness +/-myalgias
Lung disease, vasculitis, myocarditis
What is the pathology of inclusion body myositis?
Intracellular depsoits of B-amyloid protein, B-pleated sheet fibrils, Hyperphosphorylated Tau protein
CD8 T cells
How does inclusion body myositis present?
> 50 years begins insidiously
Distal muscles, quads, wrist and finger flexors
May be asymmetric
What is thyrotoxic myopathy?
Acute or chronic proximal muscle weakness tha tmay precede signs of thyroid dysfunction
Exophthalmic ophthalmoplegia - protrusion of the eyeballs and diplopia due to orbital edema and contracture of ocular muscles
How does hypothyroidism myopathy present?
Cramping/aching muscle; slow movement
Slow reflexes
Proximal weakness e.g. posterior neck
Elevated CK
Fiber atrophy
What is ethanol myopathy?
Acute rhabdomyolysis after a drinking binge
Painful, myoglobinuria can lead to renal failure
What drugs can induce myopathy?
Steroid
Chlororquine
Statins
What is ICU myopathy?
Myosin deficient myopathy
Associated with corticosteroid therapy
Degraded myosin thick filaments
What is the pathology of Myasthenia gravis?
Neuromuscular junction disease caused by an immune-mediated loss of acetylcholine receptors
How does myasthenia gravis present?
Often begins with extraocular muscle weakness - drooping eyelids, diplopia
May present with generalized weakness that is variable from minute-to-minute
What is the treatment for MG?
Thymectomy
Acetylcholinesterase
Prednisone
Plasmapherises
What is Lambert-Eaton Myasthenic Syndrome?
Neuromuscular junction disorder caused by antibodies that inhibit presynaptic calcium channel and block acetylcholine release
Usually paraneoplastic from small cell carcinoma
Enhanced neurotransmission with repetitive stimulation
