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44 Cards in this Set
- Front
- Back
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What is myasthenia gravis?
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-a chronic autoimmune disease -varying degrees of weakness of the skeletal musculature
-hallmark of MG is muscle weakness that increases during activity and improves after rest |
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Myasthenia gravis
Pathogenesis |
-auto-Abs against the ACh nicotinic postsynaptic receptors in the motor endplates of skeletal m--> reduction in # w/ a reduction in efficiency of NM transmission
-activation of C and subsequent destruction of postysnaptic membranes, maybe CMI |
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Myasthenia gravis
Etiology |
-thymus plays an important role since 75% of pts have some degree of thymus abnL (85% thymic hyperplasia and 15% have thyoma)
-thymectomy results in the clinical improvement of many pts -epi myoid cells have ACh receptors, could be Ag source of Ab production |
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Second type of Myasthenia gravis
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-auto Abs are directed at muscle specific kinase (MuSK) a tyrosine kinase receptor
-genetic defects in MuSK are responsible for auto recessive congen MYASTHENIA SYNDROME |
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Myasthenia gravis
Associations |
-RA, SLE, small lung cancer, Hodgkin disease associations
-young women w/ HLA-DR3 -older men a/w thyoma -D-penacillamine may cause MG |
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Neonatal (Transient) MG
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-30% of infants born to mothers w/ the disease
-local or generalized weakness and respiratory depression -symptoms subside over to 4 weeks and disappear altogether w/in 2-3 months of birth |
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Myasthenia gravis
Frequency |
-3 peaks of onset:
1. neonates 2. 20-30 y/o (female predominance) 3. ppl over 50 (male predominance) -M:F ratio in kids and adults is 2:3 |
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Ophthalmic Manifestations of MG
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-75-90%
1. Ptosis (MC initial finding) -may be uni or bilat, and may shift from eye to eye 2. Dipolopia (due to eye muscle weakness) |
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Nonopthalmic manifestations of MG
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a. oropharyngeal (15%)- dysphagia and dysphonia
b. limb and trunk weakness c. Respiratory failure * this can also be the 1st presentation of the disease |
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Myasthenia crisis
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-pt is unable to maintain an airway or make sufficient resp movements
***-constitutes as a medical emergency requiring a respirator for assisted ventilation -w/in 3 years 12-16% have it |
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What are some possible triggers of Myasthenia crisis?
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1. Infections
2. Aspiration 3. Physical and emotional stress 4. Noncompliance of medication 5. Change in medication |
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Myasthenia gravis
Prognosis |
-majority of pts is good
-lead nL or lives -some cases pts go into remission, muscle weakness may disappear completely, medication stop -possible death from mya crisis |
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Duchenne Muscular Dystrophy
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-X-linked
-result of mutations in the dystrophin gene on the short arm of X (Xp21) which codes for dystrophin |
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Duchenne Muscular Dystrophy
Dystrophin |
-integral to the structral stability of the myofiber
-functional loss --> loss of other components of the transmem complex and breakdown of sarcolemma |
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What happens when there is a breakdown of the sarcolemma in pts w/ Duchenne Muscular Dystrophy?
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-Ca++ ion influx, phospholipase activation, oxidative cellular injury, and ultimately necrosis of the myofiber
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Duchenne Muscular Dystrophy
Genetics |
-X link = disease of young boys
-F are carriers and no or mild sx -ALTERNATELY disease can occur from a spontaneous somatic mutation which accounts for 30% of cases -F w/ Turner (XO) may manifest |
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Duchenne Muscular Dystrophy
Frequency |
-most common muscular dystrophy to occur in children in the US
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Duchenne Muscular Dystrophy
Manifestations |
-1-5 y/o
-marked serum increase in serum creatinine kinase levels -pelvic weakness, then shoulder girdle, later limb and resp muscles -calf muscle pseudohypertrophy |
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What is Gower Sign?
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-in Duchenne Muscular Dystrophy, because of lower back and extremity weakness, the child pushes on his knees in order to stand up
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Other manifestations of Duchenne Muscular Dystrophy
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-Cardiomyopahty may lead to CO failure and pulmonary congestion, a common cause of death in these pts
-low IQ score -GI motility is affected -Scoliotic deformity--> impairs pulmonary fxn--> PNA |
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Duchenne Muscular Dystrophy
Morphology |
-degen w/ phagocytosis and regen attempts along the muscle fibers (ringed by fibrous tissue)
-as necrosis predoms, fibers are replaced by fat and scar tissue -healthy fibers undergo hypertrophy--> variability in sizes of fibers |
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Duchenne Muscular Dystrophy
Prognosis |
-nearly all lose the ability to walk sometime btwn 7-12 y/o
-wheelchair bound by age 10, bedridden by 15 -MC cause of death are resp insufficiency or cardiac arrhythmias |
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Becker Muscular Dystrophy
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-rare and relatively benign form of muscular dystrophy of the pelvis-girdle type, manifests later in life
-weakness is milder than in Duchenne muscular dystrophy |
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Becker Muscular Dystrophy
Pathogenesis |
-also involves dystrophin gene in which it is prod but in less than nL amounts, and structural abnLity
-frame mutation hypothesis has been proposed to explain abnL translation of gene |
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Becker Muscular Dystrophy vs
Duchenne Muscular Dystrophy Dystrophin Protein |
Becker has abnL but functional dystrophin whereas Duchenne has mutations that lead to failure to produce dystrophin
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Becker Muscular Dystrophy
Manifestations |
-2-21 y/o mean onset age 11
-children are clumpsy -serum CK levels are only mod inc -some men need chairs by 30s, while others may manage for many years w/ canes |
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Becker Muscular Dystrophy
Other manifestations |
-calf muscle pseudohypertrophy
-toe walking -Gower sign -ambulatory status and age may differentiate Duchenne from Becker |
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Becker Muscular Dystrophy
Morphology |
-similar to Duchenne except changes are less including:
a. myofiber degen b. variability in fiber sizes c. necrosis of fibers and replacement of fat and scar tissue d. definition of fiber types |
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What does dystrophin Ab staining in Becker Muscular Dystrophy reveals?
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-the presence of dystrophin in variable amounts in muscle sections
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Becker Muscular Dystrophy
Prognosis |
-course of the disease is highly variable
-wheelchair mean age 27 (12-30) -death MC from resp or cardiac failure mean age 42 (23-63) |
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Myotonic Dystrophy
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-THE MC FORM OF ADULT ONSET MUSCULAR DYSTROPHY
-auto dom, mulstystemic disease -can manifest at any age from birth to old age but usually 20-30s -DM1 and DM2 |
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What is the most severe from of Myotonic Dystrophy?
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-congenital Myotonic Dystrophy and its onset is in infancy
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Myotonic Dystrophy
Pathogenesis |
-it is a trinucleotide disorder
-DM1 aka Steinert's disease -DM2 aka Proximal myotonic myopathy (PROMM) |
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Myotonic Dystrophy
Steinert's Disease Pathogenesis |
-the trinucleotide repeat is Cytosine-Thymine-Guanine (CTG)
-on gene DMPK that codes for myosin kinase (myotonin) on long arm of chromo 19 -once repeated triplet seq exceeds 50 the gene is unstable |
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What is the phenomenon of anticipation?
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-as each child of an affect inidividual will inherit an increased number of repeats and thus the illness becomes more severe w/ each successive generation
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Myotonic Dystrophy
DM2 - PROMM Pathogenesis |
-trinucleotide complex repeat motif consisting of (TG), (TCTG) and (CCTG) in a gene CNBP coding for a zinc finger RNA binding protein on chromosome 3
-the altered mRNA interacts w/ certain proteins--> clumps |
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Myotonic Dystrophy
Manifestations |
-DM2 is generally milder than DM1
-the severe congenital form that occurs in DM1 not found in DM2 -manifestations vary considerably and can be correlated to # of repeats in DM1 but not DM2 |
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Mild DM1
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-CTG repeat 50-150
-age of onset: 20-70 -age of death: 60 yrs to nL life span -Clinical signs: Cataracts and mild myotonia |
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Classical DM1
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-CTG repeat 100-~1000
-age of onset: 10-30 -age of death: 48-55 -Clinical signs: Cataracts and mild myotonia |
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Additional clinical signs of Classical DM1
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-Muscle weakeness: foot drop/gait disturbance
-cardiac abnL -frontal balding -testicular failure -insulin resistance -mild to moderate dementia |
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Congenital DM1
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-CTG repeat >2000
-age of onset: birth - 10 yrs -age of death: 45 (excluding neonatal deaths) -Clinical signs: infantile hypotonia, resp deficits, severe mental retardation |
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DM2 Manifestations
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-present initially w/ muscle weakness, pain and myotonia
-earliest affected: neck and finger flexors--> muscles of shoulders, hips, and upper legs (trunk) *DIFFERS FROM DM1 |
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What is one condition commonly seen in DM2 that is not seen in DM1?
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hypertophy of calf muscles
-other manifestations in DM2 are sim to DM1 but usually milder |
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Myotonic dystrophy
Morphology |
-can't distinguish between DM1 and DM2
-necrotic fibers, scattered severely atrophic fibers w/ pyknotic nuclei -increase in # of internal nuclei -RING FIBER (but not pathognomic for myotonic dystrophy) |
