27: Skeletal Muscle

Question 1

Describe DMD genetics and pathology.

Answer 1

Duchenne muscular dystrophy is a severe & progressive, x-linked, inherited condition characterized by degeneration of muscles, especially those of the pelvic and shoulder girdles.

Question 2

Describe 2 physical exam findings typical of DMD.

Answer 2

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.

Question 3

What are the 2 most common causes of death for DMD?

Answer 3

Complications of respiratory insufficiency due to muscular weakness or cardiac arrhythmia due to myocardial involvement.

Both are muscular causes of death.

Question 4

What is the molecular basis of DMD?

Answer 4

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.

Question 5

What is the role of dystrophin & what happens when it is defective?

Answer 5

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.

Question 6

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.

Answer 6

symmetric; increase; nonsuppurative

Question 7

What are the 4 most common morphologic charictaristics of the inflammatory myopathies?

Answer 7

1. inflammatory cells
2. necrosis and phagocytosis of muscle fibers
3. mixture of regenerating and atrophic fibers
4. fibrosis

Question 8

How is Dermatomyosities is distinguished from the other myopathies (i.e., polymyositis and inclusion body myositis)?

Answer 8

By the presence of a charicteristic heliotropic rash on the upper eyelids, face, and trunk.

Question 9

Patients with inflammatory myopathies have increased serum levels of ______ kinase and other muscle enzymes.

Answer 9

creatine

Question 10

Elevated _____ phosphatase is associated with liver and bone disease.

Answer 10

alkaline

Question 11

Alpha-fetoprotein and carcinoembryonic antigen are markers of ______.

Answer 11

neoplasia

Question 12

Elevated blood urea nitrogen is associated with _____ disease.

Answer 12

renal

Question 13

What are the symptoms and causes of Myesthenia gravis?

Answer 13

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).

Question 14

Antibodies to the ______ receptor can be demonstrated in the serum of most patients with myesthenia gravis and localized in muscle biopsies by _______.

Answer 14

acetylcholine; immunohistochemistry

Question 15

What 2 conditions are associated with myasthenia gravis? What organ is removed in many patients with MG?

Answer 15

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.

Question 16

What is Polymyositis caused by?

Answer 16

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.

Question 17

What can trigger polymyositis?

Answer 17

Although viral infections like influenza may trigger polymyositis, muscle tissue has not yeilded a virus on culture.

Question 18

An inflammatory myopathy indistringuishable from polymyositis occurs in many cases of _____ infection, but the role of the lentivirus is unclear.

Answer 18

HIV

Question 19

What is Dermatomyositis?

Answer 19

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).

Question 20

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.

Answer 20

lung

Question 21

Lambert-Eaton myasthenic syndome is seen in patients with lung cancer, but is ____ associated with a skin rash or muscle inflammation.

Answer 21

not

Question 22

What is Lambert-Eaton myasthenic syndome?

Answer 22

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.

Question 23

Describe the autoimmune basis of Lambert-Eaton myasthenic syndome. What do the autoantibodies target?

Answer 23

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.

Question 24

Myotonic dystrophy: genetics, cause, & other systems it affects.

Answer 24

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.

Question 25

Myotonic dystrophy can be separated into two clinical groups: adult onset and congenital. Most adult patients display _____ of type 1 fibers and _____ of type 2 fibers.

Answer 25

atrophy; hypertrophy

Note: there is never hypertrophy of the type 1 fibers

Question 26

Necrosis and regeneration of muscles occur in what 2 diseases?

Answer 26

DMD & myotonic dystrophy

Question 27

Exercise indiced myoglobinuria is due to what disease?

Answer 27

carnitine palmityl transferase deficiency

Question 28

What is carnitine palmityl transferase deficiency?

Answer 28

Patients with carnitine palmityl transferase deficiency cannot metabolize long chain fatty acids because of an inability to transport these lipids into the mitochondria, where they undergo B-oxidation. After prolonged exercise, these patients have muscular pain, which may progress to myoglobinuria.

After such an episode, fibers regenerate and restore muscle structure. Biopsies show no abnormalities and the dx depends on the biochemical assay for carnitine palmityl transferase activity.

Question 29

Glycogen storage diseases are autosomal _____, inherited, metabolic disorders characterized by an inability to degrade _____.

Answer 29

recessive; glycogen

Question 30

What is Pompe’s disease?

Answer 30

The acid maltase deficiency discovered by Pompe (Pompe’s disease) is the most severe form and occurs in the neonatal or early infantile stage. These patients have an enlarged tongue and cardiomegaly and die of cardiac failiure, usually with in the first 2 years of life. It is a glycogen storage disease.

Note: Glycogen storage diseases are autosomal recessive, inherited, metabolic disorders characterized by an inability to degrade glycogen.

Question 31

In Pompe disease, the most significant involement is in ____ and _____ muscle, the CNS, and the liver. Serum creatine kinase level is only slightly to moderatley _____ & glocogen accumulates.

Answer 31

skeletal; cardiac; increased

Question 32

Hurler syndrome is an inhereted _____ in mucopolysaccharide metabolism.

Answer 32

defect

Question 33

Discuss the the pathologic features of inclusion body myositis.

Answer 33

The pathologic features of inclusion body myositis resemble those of polymyositis and consist of single fiber necrosis and regeneration with predominantly enomysial CD8 cells.

Question 34

Discuss the histological details of inclusion body myositis.

Answer 34

The inclusions are stained by congo red and represent a form of intracellular amyloid that can be demonstrated by electron microscopy.

Question 35

The fibers in the electron micrograph for question 12 dealing with inclusion body myositis represent amyloid filaments. These filaments are immunoreactive for Beta-amyloid protein just like in ______. The pathogenic significance of the inclusions is not understood.

Answer 35

Beta; Alzheimers

Question 36

What is Rhabdomyolysis?

Answer 36

Rhabdomyolysis refers to the dissolution of skeletal muscle fibers and the release of myoglobin into the circulation, and event that may result in myoglobinuria and acute renal failiure.

The disorder may be acute, subacute, or chronic.

Question 37

What happens in acute Rhabdomyolysis?

Answer 37

During acute Rhabdo, the muscles are swollen, tender, and weak.

Question 38

Rhabdomyolisis may complicate ____ stroke or _____ hyperthermia after administration of an anesthetic such as halothane.

Answer 38

heat; malignant

Question 39

Pathologic changes in rhabdomyolisis correspond to an active, _____ myopathy, with scattered _____ of muscle fibers and varying degrees of regeneration and degeneration.

Answer 39

noninflammatory; necrosis

Question 40

A muscle biopsy is a highly sensitive test for detecting a lesion of the _____ motor neuron (denervation), but the pattern of denervation does not identfy the cause of the lesion.

When a skeletal muscle fiber becomes separated from contact with its lower motor neuron, it _____ due to loss of myofibrils. In the end stage, muscle fibers disappear and are replaced by _____ tissue.

Answer 40

lower; atrophies; adipiose

Question 41

On cross section biopsy, the atrophic muscle fiber has a charictaristic _______ configuration, seemingly compressed by surrounding normal muscle fibers.

If the fiber is not reinnervated, the atrophy proceeds to complete loss of _____, and the nuclei _____ into aggregates.

Answer 41

angular; myofibrils condense

Question 42

Bodybuilding hypertrophies type 1 or type 2 fibers?

Answer 42

Type 2

Question 43

Stimulation of type ___ fibers elicits a faster, shorter, and more powerful contraction than occurs in type ____. Type ____ muscle fibers are suitable for rapid contractions of breif duration and react to strength training with hypertrophy.

Answer 43

2; 1; 2

Question 44

Androgenic steroids also induce _____ of type 2 fibers, and disuse of the muscle results in their selective atrophy.

Answer 44

hypertrophy