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Skin MS: Week 5 > Pathology: Muscle Diseases > Flashcards

Pathology: Muscle Diseases Flashcards

1
Q

The two principal pathologic processes seen in skeletal muscle

A

Denervation atrophy and primary pathologic abnormalities of the skeletal muscle fiber itself (myopathy)

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2
Q

Indications for muscle biopsy

A

suspected skeletal muscle disease w/ unexplained weakness, cramps or pain, or unexplained enzymatic evidence of skeletal muscle injury (CK)

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3
Q

Spinal Muscular Atrophy

A

Group of mainly autosomal recessive motor neuron diseases that present in childhood or adolescence. NEUROGENIC ATROPHY
loss of motor neurons –> muscle atrophy and weakness

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4
Q

Genetic defect –> Spinal muscular atrophy

A

Most forms of SMA are associated with mutations affecting survival motor neuron 1 (SMN1), a gene on chromosome 5 that is required for motor neuron survival

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5
Q

Most common form of SMA

A

Werdnig-Hoffman Disease

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6
Q

Muscular dystrophy

A

heterogeneous group of inherited disorders which result in muscle weakness and eventually muscle atrophy and wasting, with muscle replaced by fibrofatty tissue

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7
Q

Two most common forms of childhood muscular dystrophy

A

X-linked disorders Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD)

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8
Q

DMD and BMD are caused by mutations of an X-linked gene (Xp21 region) that encodes for ____________

A

a protein named dystrophin

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9
Q

Dystrophin is located _______________, and dystrophin and the dystrophin associated protein complex form an interface between the _________________, transferring contractile force to the connective tissue.

A

in the cytoplasm adjacent to the sarcolemmal membrane

intracellular contractile apparatus (actin) and the extracellular connective tissue matrix

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10
Q

Patients w/ DMD have ____ dystrophin, whereas BMD have _______ dystrophin

A

Patients with DMD have little or no dystrophin; patients with BMD have decreased amounts of dystrophin or a defective, abnormal form of dystrophin

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11
Q

DMD and BMD are sometimes referred to as ____________

A

dystrophinopathies

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12
Q

Sxs (observable) of DMD

A

symptoms by age 5
weakness in the pelvic girdle, followed by the shoulder girdle.
Waddling “duck-like” gait and place hands on knees to assist in standing (Gower’s maneuver).
“pseudohypertrophy” of the calf muscles (enlargement due to atrophic muscle being replaced by adipose tissue).

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13
Q

Clinical outcomes DMD

A

Patients are often wheel chair dependant by 10-12 years. Complications include respiratory insufficiency with infections and cardiomyopathy, with median survival approximately age 35 years.

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14
Q

DMD: Creatine kinase is ______ early in the disease, even before symptoms appear; electromyogram shows a ______ pattern

A

increased, myopathic (versus neurogenic)

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15
Q

Electromyogram

A

test that measures the electrical activity of skeletal muscle

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16
Q

Testing for DMD

A

Genetic tests are often used to establish the diagnosis (peripheral blood). Muscle biopsy can also be used to establish the diagnosis (western (protein) immunoblot for dystrophin).

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17
Q

Clinical Outcomes BMD

A

Patients with BMD have a later onset with milder symptoms, and can survive well into the 40’s and beyond.

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18
Q

Muscle biopsy in DMD and BMD show variation in _________, increased ____________, _____ and ________ of muscle fibers (it is believed that defects in the protein complex lead to membrane tears with influx of calcium), and muscle fiber _________. Eventually, the muscles become almost completely replaced by____________ and __________

A

Muscle biopsy in both conditions show variation in muscle fiber size, increased endomysial connective tissue, degeneration and necrosis of muscle fibers (it is believed that defects in the protein complex lead to membrane tears with influx of calcium), and muscle fiber regeneration. Eventually, the muscles become almost completely replaced by fat and connective tissue.

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19
Q

Tx muscular dystrophy (DMD, BMD)

A

There is no cure, and in some cases patients are treated with immunosuppression. Definitive therapy would involve restoration of dystrophin levels in skeletal muscle and cardiac muscle.

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20
Q

Female carriers of DMD,BMD

A

Female carriers can demonstrate increased creatine kinase levels, and can be at risk for cardiomyopathy.

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21
Q

Myotonia

A

sustained involuntary contraction of a group of muscles

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22
Q

Genetic basis for myotonic dystrophy

A

Autosomal dominant disorder - increased CTG trinucleotide repeat sequences on chromosome 19 (trinucelotide repeat disorder), which affects the mRNA for dystrophia myotonia protein kinase (DMPK). This results in defects affecting transcription of proteins for a chloride channel called CLC1, resulting in myotonia.

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23
Q

Sxs of myotonic dystrophy

A

Patients often present in late childhood with abnormalities of gait, which eventually progresses to weakness of the hand and wrist; facial muscle atrophy leads to a typical facial appearance with a sagging face, ptosis (drooping upper eyelid), and open mouth. Other abnormalities include cataracts, frontal balding, gonadal atrophy, abnormal glucose tolerance, and cardiomyopathy.

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24
Q

Testing for myotonic dystrophy

A

Muscle biopsy can show selective atrophy of type 1 fibers as well as ring fibers (both not specific); patients will also have elevated creatine kinase. Genetic test is available (peripheral blood).

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25
Q

Ion channel myopathies

A

Group of inherited diseases caused by mutations affecting function of ion channel proteins. Depending on channel affected, clinical manifestations may include epilepsy, migraine, movement disorders with cerebellar dysfunction, peripheral nerve disease, and muscle disease.
Mutations can affect potassium, sodium, calcium, and chloride channels, resulting in either hypotonia (decreased muscle tone) or hypertonia (increased muscle tone).

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26
Q

Malignant hyperthermia - characterized by what, triggered by what

A

Malignant hyperpyrexia (malignant hyperthermia) is a rare clinical syndrome characterized by a marked hypermetabolic state (tachycardia, tachypnea, muscle spasms, and later hyperpyrexia) triggered by certain inhalational anesthetics.

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27
Q

Malignant hyperthermia triggered by what

A

This condition is associated with several mutations that encode proteins that control levels of cytosolic calcium.

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28
Q

Malignant hyperthermia process

A

Upon exposure to an anesthetic, the abnormal calcium channels allow uncontrolled release of calcium from skeletal muscle cells. This acute medical emergency leads to tetany, increased muscle metabolism, and excessive heat production.

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29
Q

Congenital myopathies

A

Group of inherited myopathies defined largely on basis of pathologic findings in skeletal muscle biopsy - typically manifest at infancy (vs MD, after infancy)

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30
Q

Myopathies associated w/ inborn errors of metabolism

A

Many types exist, including:
Disorders of glycogen metabolism
Disorders of lipid metabolism
Mitochondrial myopathies, associated with mutations of mitochondrial enzymes (typically these disorders impair mitochondrial ATP generation, and thus affect tissues rich in cell types with high ATP requirements, such as cardiac cells and neurons).

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31
Q

3 Subgroups of inflammatory myopathies

A

Infectious
Associated w/ systemic inflammatory disease
Noninfectious inflammatory disease

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32
Q

Infectious inflammatory myopathy examples

A

trichinosis, necrotizing fasciitis and myositis due to group A streptococcus, clostridial gas gangrene

33
Q

Inflammatory myopathy associated w/ systemic inflammatory disease examples

A

systemic lupus erythematosis (SLE), polyarteritis nodosa, rheumatoid arthritis, sarcoidosis

34
Q

Noninfectious inflammatory myopathies examples

A

Dermatomyositis
Polymyositis
Inclusion Body Myositis

35
Q

autoimmune disease with immunologic injury and damage to small blood vessels and capillaries in the skeletal muscle, along with skin involvement and characteristic skin rash.

A

dermatomyositis

36
Q

dermatomyositis

A

autoimmune disease with immunologic injury and damage to small blood vessels and capillaries in the skeletal muscle, along with skin involvement and characteristic skin rash.

37
Q

dermatomyositis muscle biopsy

A

lymphocytic inflammation around small blood vessels and in the perimysial connective tissue, along with perifascicular myocyte atrophy secondary to ischemia. Necrotic muscle fibers with regeneration can also be seen.

38
Q

_________________ are involved in capillary damage in dermatomyositis

A

Activated B and T cells and antibodies with complement activation are involved in the capillary damage

Dermatomyositis

39
Q

Clinical manifestations of dermatomyositis

A

muscle weakness and skin rash

possible extramuscular manifestations (interstitial lung disease, dysphagia, myocarditis)

40
Q

classic rash of dermatomyositis

A

a violaceous discoloration of upper eyelids associated with periorbital edema, accompanied by a scaling erythematous eruption or dusky red patches over the knuckles, elbows, and knees (Gottron papules).

41
Q

muscle weakness pattern of dermatomyositis

A

Muscle weakness typically affects proximal muscles first and is symmetric, often accompanied by myalgias (muscle pain).

42
Q

15-25% of patients with dermatomyositis have _______________.

A

an underlying malignancy (screen newly diagnosed patients for malignancy!)

43
Q

Dermatomyositis - juvenille

A

Juvenile form of the disease exists, more often is accompanied by abdominal pain and involvement of the gastrointestinal tract.

44
Q

Dermatomyositis testing/lab and treatment

A

Patients will have elevated creatine kinase; treat with immunosuppressive agents.

45
Q

Muscle and systemic involvement is similar to that seen in dermatomyositis, except for the lack of skin involvement.

A

polymyositis

46
Q

Polymyositis - lab and treatment

A

Patients will have elevated creatine kinase; treat with immunosuppressive agents.

47
Q

Polymyositis pathogenesis

A

Pathogenesis is believed to be caused by immunologic injury to muscle by activated CD8+ cytotoxic T cells. Autoantibodies similar to that seen in dermatomyositis may be present, such as anti-Jo1, which is directed against histidyl t-RNA synthetase.

48
Q

polymyositis pathology

A

Muscle biopsy shows lymphocytic inflammation surrounding and invading muscle fibers, without the perifascicular atrophy seen in dermatomyositis. Necrotic and regenerating muscle fibers are found throughout the fascicle. No vascular injury is seen.

49
Q

polymyositis vs dermatomyositis

A

Muscle and systemic involvement is similar to that seen in dermatomyositis, except for the lack of skin involvement.

50
Q

Polymyositis mostly seen in _______

A

adults

51
Q

Inclusion body myositis pathogenesis

A

uncertain, as it is not known whether this is an inflammatory condition or a degenerative process with secondary inflammation

52
Q

Inclusion body myositis clinical presentation

A

Often begins with the involvement of distal muscles, in contrast to dermatomyositis and polymyositis.

Muscle involvement may be asymmetric.
Older people

53
Q

Inclusion body myositis muscle biopsy

A

Muscle biopsy shows rimmed vacuoles (not specific), along with lymphocytic inflammatory infiltrate.

54
Q

Inclusion body myositis lab/treatment

A

Modest elevations of creatine kinase are present.

There is often no beneficial effect with immunosuppressive agents.

55
Q

Toxic myopathies examples

A

Thyrotoxic, ethanol, drug-induced

56
Q

Thyrotoxic myopathy

A

hyperthyroidism is associated with increased levels of thyroid hormone, which can cause muscle degeneration/necrosis with regeneration. Patients can get exophthalmic opthalmoplegia with swelling and enlargement of the ocular muscles. In hypothyroidism, patients may get muscle fiber atrophy.

57
Q

Ethanol myopathy

A

binge drinking can produce an acute toxic syndrome of rhabdomyolysis, with rapid breakdown of skeletal muscle. Also, if pass out - on hard surface - pressure necrosis

58
Q

Drug-induced myopathy

A

steroids, whether associated with Cushings syndrome or therapeutic use, can produce muscle fiber atrophy, predominately of type 2 fibers. Choroquine, used for treatment of malaria, can produce a proximal myopathy. Satins, used to reduce cholesterol, can also produce myopathy. Statin use is one of the most common causes of prescription drug-induced myopathy!

59
Q

_________ use is one of the most common causes of prescription drug-induced myopathy!

A

Statin

60
Q

autoimmune disease caused by immune mediated loss of function of the acetylcholine receptor (AChR).

A

Myasthenia Gravis

61
Q

Autoantibodies in Myasthenia Gravis

A

AChR autoantibodies can be detected in most patients (85%). Some patients have antibodies directed against a sarcolemmal protein, muscle specific receptor tyrosine kinase. AChR autoantibodies lead to degradation of the receptors; muscle specific tyrosine kinase autoantibodies interfere with the function of the receptor.

62
Q

Myasthenia gravis associated with ___ abnormalities

A

Myasthenia gravis is often associated with thymic abnormalities, with thymic hyperplasia in 30% and thymoma (tumor of the thymus) in 10%.

63
Q

Clinical presentation Myasthenia gravis

A

Muscle weakness may be generalized, or localized to the extraocular muscles (ptosis).

64
Q

Diagnosis Myasthenia gravis

A

Detection of the above autoantibodies in the appropriate clinical setting; electrophysiologic studies can also be helpful, as well as bed-side tests in those patients with ptosis (ice pack test, edrophonium test).

65
Q

Tx MG

A

Treatment is with anticholinesterase drugs, immunosuppressive agents, plasmapheresis in acute cases, and thymectomy in those with thymic tumors.

66
Q

Lambert-Eaton Myasthenia pathogenesis

A

autoantibodies directed against presynaptic calcium channels, which block acetylcholine release. In contrast to myasthenia gravis, rapid repetitive stimulation of the affected muscle increases the muscle response.

67
Q

Lambert-Eaton Myasthenia often seen as a ________________ syndrome, with ____________ present in 60% of cases (often _____________).

A

This condition is often seen as a paraneoplastic syndrome, with malignancy present in 60% of cases (often small cell lung carcinoma).

68
Q

Lambert-Eaton Myasthenia Dx

A

Patients may have detectable “voltage gated calcium channel autoantibodies” and show no improvement with anticholinesterase agents; electrophysiologic studies are quite helpful in distinquishing this entity from myasthenia gravis, along with the presence of non-thymic malignancies.

69
Q

Creatine Kinase

A

cytosolic enzyme which converts creatine to phosphocreatine; in the process ATP is converted to ADP

70
Q

Creatine kinase exists as three isoenzymes:

A

CK-BB, CK-MB, and CK-MM (B = brain, M = muscle) .

71
Q

Skeletal muscle primarily expresses _____(98%) with very low levels of______; however, as skeletal muscle is damaged and regeneration occurs, skeletal muscle can exhibit increased _______ expression.

A

Skeletal muscle primarily expresses CK-MM (98%) with very low levels of CK-MB; however, as skeletal muscle is damaged and regeneration occurs, skeletal muscle can exhibit increased CK-MB expression.

72
Q

Cardiac muscle expresses______ (70%) and ______ (20-25%). ______ is expressed at low levels in many tissues.

A

Cardiac muscle expresses CK-MM (70%) and CK-MB (20-25%). CK-BB is expressed at low levels in many tissues.

73
Q

________ is released into the interstitial space and blood when cells are damaged.

A

Creatine kinase is released into the interstitial space and blood when cells are damaged.

74
Q

Elevations of creatine kinase are seen in a variety of conditions

A

Acute myocardial infarct or other myocardial injury (e.g. myocarditis)
Skeletal muscle diseases such as inflammatory myopathies, muscular dystrophies, rhabdomyolysis, skeletal muscle trauma
Cerebrovascular accidents, head injury

75
Q

__________ isoenzyme was once used primarily for the diagnosis of acute myocardial infarct, along with cardiac troponin I. Why not?

A

CK-MB
While cardiac troponin I is specific for cardiac muscle, CK-MB is not. As such, cardiac troponin I is the preferred enzyme to measure for detection of myocardial injury.

76
Q

______ is helpful in the assessment of skeletal muscle injury, in the absence of cardiac disease or other conditions that may cause increased CK.

A

Total CK

77
Q

Protein found in skeletal muscle and cardiac muscle.

As with creatine kinase, elevations occur when cardiac muscle or skeletal muscle is damaged.

A

Myoglobin

78
Q

In rhabdomyolysis, elevated levels of myoglobin can cause ________________

A

acute tubular necrosis with acute renal failure (myoglobinuria).

Skin MS: Week 5 (6 decks)

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