27: Skeletal Muscle Flashcards
(44 cards)
Describe DMD genetics and pathology.
Duchenne muscular dystrophy is a severe & progressive, x-linked, inherited condition characterized by degeneration of muscles, especially those of the pelvic and shoulder girdles.
Describe 2 physical exam findings typical of DMD.
The weakness is thus noted around the pelvic and shoulder girdles via proximal muscle weakness and is progressive.
Pseudohypertrophy enlargement of the calf muscles develops. It is pseudo because it is enlargement of the muscle due to abundant replacement of muscle fibers by fibroadipose tissue. Wheelchair bound by age 10 & bedridden by 15.
What are the 2 most common causes of death for DMD?
Complications of respiratory insufficiency due to muscular weakness or cardiac arrhythmia due to myocardial involvement.
Both are muscular causes of death.
What is the molecular basis of DMD?
DMD is caused by mustations of a large gene on the short arm of the X chromosome. This gene codes for dystrophin, a protein localized to the inner surface of the sarcolemma.
What is the role of dystrophin & what happens when it is defective?
Dystrophin links the subsarcolemman cytoskeleton to the exterior of the cell through a transmembrane complex of proteins and glycoproteins that binds to laminin.
Dystrophin-deficient muscle fibers this lack the normal interaction between the sarcolemma and the extracellular matrix. This causes osmotic fragility of the dystrophic muscle, the excessive influx of calcium ions, and the release of soluble muscle enzymes like creatine kinase into the serum.
The inflammatory myopathies represent a heterogeneous group of acquired disorders, all of which feature _____ proximal muscle weakness, _____ serum levels of muscle-derived enzymes (creatine kinase), and ______ inflammation of skeletal muscle. They are thought to have an autoimmune origin.
symmetric; increase; nonsuppurative
What are the 4 most common morphologic charictaristics of the inflammatory myopathies?
- inflammatory cells
- necrosis and phagocytosis of muscle fibers
- mixture of regenerating and atrophic fibers
- fibrosis
How is Dermatomyosities is distinguished from the other myopathies (i.e., polymyositis and inclusion body myositis)?
By the presence of a charicteristic heliotropic rash on the upper eyelids, face, and trunk.
Patients with inflammatory myopathies have increased serum levels of ______ kinase and other muscle enzymes.
creatine
Elevated _____ phosphatase is associated with liver and bone disease.
alkaline
Alpha-fetoprotein and carcinoembryonic antigen are markers of ______.
neoplasia
Elevated blood urea nitrogen is associated with _____ disease.
renal
What are the symptoms and causes of Myesthenia gravis?
Myesthenia gravis is an acquired autoimmune disease characterized by abnormal muscular fatigability. It is caused by circulating antibodies to the acetylcholine receptor at the myoneural junction (motor endplate).
Antibodies to the ______ receptor can be demonstrated in the serum of most patients with myesthenia gravis and localized in muscle biopsies by _______.
acetylcholine; immunohistochemistry
What 2 conditions are associated with myasthenia gravis? What organ is removed in many patients with MG?
The thymus plays an important role in the pathogenisis of myasthenia gravis. Many patients with thyoma develop myathenia gravis, and surgical removal of the tumor is often curative.
Other patients with myasthenia gravis have thymic hyperplasia, and in such cases, thymectomy is oftan an effective treatment.
Acetylcholine receptors have been demonstrated on the surface of some thymic cells in both thyoma and thymic hyperplasia.
What is Polymyositis caused by?
Polymyositis is related to direct muscle cell damage produced by CD8 cells. Healthy muscle fibers are initially surrounded by CD8 cells and macrophages after which muscle fibers degenerate. There is a frequent association between polymyositis and anti-Jo-1, an antibody against histidyl-tRNA synthetase, with the concomitant presence of intersitial lung disease, Raynaud’s, & nonerosive arthritis.
What can trigger polymyositis?
Although viral infections like influenza may trigger polymyositis, muscle tissue has not yeilded a virus on culture.
An inflammatory myopathy indistringuishable from polymyositis occurs in many cases of _____ infection, but the role of the lentivirus is unclear.
HIV
What is Dermatomyositis?
Dermatomyositis is an immune-mediated microangiopathy that leads to obliteration of capillaries, ischemic injury, and muscle damage. Immunofluourescence demonstrates that the walls of many capillaries contain C5b-9 proteins (membrane attack complex).
When dermatomyositis occurs in a middle-aged man, it is associated with an increased risk of epithelial cancer, most commonly carcinoma of the _____. By contrast, polymyositis and inclusion body myositis have only a chance association with malignancy.
lung
Lambert-Eaton myasthenic syndome is seen in patients with lung cancer, but is ____ associated with a skin rash or muscle inflammation.
not
What is Lambert-Eaton myasthenic syndome?
Lambert-Eaton myasthenic syndome is a paraneoplastic disorder that manifests as muscular weakness, wasting, and fatigability of the proximal limbs and trunk. It is usually associated with small cell carcinoma of the lung, and may occur in other malignancies.
Describe the autoimmune basis of Lambert-Eaton myasthenic syndome. What do the autoantibodies target?
Lambert-Eaton myasthenic syndome seems to have an autoimmune basis because it can be transferred to mice by IgG from patients and it responds to treatment with corticosteroids.
The pathogenic IgG autoantibodies recognize voltage-sensitive calcium channels that are expressed both in the motor end terminals and in the cells of the lung cancer. The calcium channels, which are necessary for release of acetylcholine, are greatly reduced in the presynaptic membrane in these patients, thereby interfering with neuromuscular transmission.
Myotonic dystrophy: genetics, cause, & other systems it affects.
Myotonic dystrophy is the most common form of adult muscular dystrophy. It is an autosomal dominant disorder characterized by slowing muscle relaxation (myotonia) and progressicve muscle weakness and wasting.
In addition to skeletal muscle, myotonic dystrophy affects the heart, smooth muscle, CNS, endocrine glands, and eye.
