Musculoskeletal

Question 1

Osteogenesis imperfecta (OI), (aka brittle bone disease) is a group of hereditary conditions characterized by

Answer 1

abnormal development of type I collagen, a major component of bone matrix but also present in many tissues including skin, joints, and eyes.

Question 2

Four major variants of this disorder are known and associated with .

Answer 2

variable severity.

Question 3

Osteogenesis imperfecta

Autosomal dominant (most common) and autosomal recessive forms are seen with

Answer 3

multiple bone fractures being the primary associated pathosis.

Question 4

Osteogenesis imperfecta

In the severe forms, extreme bone fragility leads to

Answer 4

death in utero or shortly after passage through the birth canal

Question 5

Osteogenesis imperfecta

. In milder forms, the fractures don’t appear until

Answer 5

childhood (may be confused with child abuse) and don’t shorten life significantly.

Question 6

Osteogenesis imperfecta

Intermediate forms also are

Answer 6

present.

Question 7

Osteogenesis imperfecta

Other interesting but inconsistent findings include

Answer 7

blue sclera and opalescent teeth which resemble dentinogenesis imperfecta.

Question 8

Osteogenesis imperfecta

Management includes

Answer 8

minimizing factors that cause fractures.

Question 9

Osteogenesis imperfecta

Prognosis depends on the

Answer 9

type of OI and expression of the gene.

Question 10

Osteopetrosis (marble bone disease) is a group of rare hereditary disorders characterized by

Answer 10

deficient osteoclastic activity with resultant defective bone remodeling.

Question 11

Osteopetrosis

Both autosomal dominant and autosomal recessive forms are seen with an associated

Answer 11

variable presentation and severity.

Question 12

Osteopetrosis

Affected patients present with

Answer 12

significantly thickened, heavily mineralized and abnormally brittle bone, prone to fractures.

Question 13

Osteopetrosis

Since the marrow space is replaced with

Answer 13

dense bone, pancytopenia is common leading to anemia, thrombocytopenia, leukopenia, and an increased prevalence of infections such as osteomyelitis.

Question 14

Osteopetrosis

Compression on the cranial foramina and nerve roots creates

Answer 14

nerve palsies (blindness, deafness) in many patients.

Question 15

Osteopetrosis

Because osteoclasts are derived from marrow monocyte precursors, bone marrow transplantation can

Answer 15

provide recipients with fully functional osteoclasts.

Question 16

Osteopetrosis

May be complicated by .

Answer 16

GVHD

Question 17

Osteoporosis refers to an increased porosity of the .

Answer 17

skeleton resulting from reduced bone mass with an associated increased bone fragility and increased prevalence of fractures.

Question 18

Osteoporosis

The process may be

Answer 18

localized (such as cases of disuse in an immobilized extremity) or generalized.

Question 19

Osteoporosis

Generalized osteoporosis can arise

Answer 19

secondarily to a wide variety of pathoses.

Question 20

Osteoporosis

When primary, the process most commonly is associated with

Answer 20

aging and is distinctly common in postmenopausal females with associated reduced estrogen (2-3X more frequent).

Question 21

Osteoporosis

About 25% of women sustain fractures by

Answer 21

age 65 and 50% by age 90.

Question 22

Osteoporosis

It is the most common form of

Answer 22

acquired, metabolic bone disease (10 million in US, 44 million osteopenia).

Question 23

Osteoporosis

Osteoporotic fractures affect more women than

Answer 23

heart attack, stroke and breast cancer combined

Question 24

Osteoporosis

Over 95% of the cases are

Answer 24

primary and appear to be related to reduced estrogen in females and lower androgens in males which develop with age.

Question 25

Osteoporosis

Because mechanical forces are known to stimulate bone remodeling, reduced physical activity also is associated with

Answer 25

increased bone losses.

Question 26

Osteoporosis

Other factors thought to be important in osteoporosis are

Answer 26

genetic factors, calcium nutritional state, and secondary causes such as corticosteroid therapy.

Question 27

Osteoporosis

Bone remodeling occurs throughout life; and normally, there is a balance between

Answer 27

bone resorption and apposition.

Question 28

Osteoporosis

It appears there is an age-related decrease in

Answer 28

osteoblastic activity as well as an increase in osteoclastic activity.

Question 29

Osteoporosis

In health, bone formation outpaces resorption until about age

Answer 29

25-30 (time of peak bone mass); followed by a plateau from ages 35-40, with no net gain or loss of bone.

Question 30

Osteoporosis

After age 40, new bone formation does not quite compensate for

Answer 30

bone loss, resulting in a gradual attrition of bones.

Question 31

Osteoporosis

A few years prior to and following menopause, the

Answer 31

imbalance worsens; and although the rate of loss slows the bone density continues to decrease.

Question 32

Osteoporosis

As peak bone mass is generally less in

Answer 32

females, they are typically more vulnerable than men to the impacts of osteopenia/osteoporosis.

Question 33

Osteoporosis:

Although all bones are affected, those containing abundant cancellous bone such as the spine and femoral head demonstrate the

Answer 33

most severe involvement.

Question 34

Osteoporosis

The most common complaint is

Answer 34

bone pain, especially backache, secondary to microfractures and collapse.

Common sites of involvement include the vertebral bodies, pelvis, femoral neck, and other weight-bearing bones.

Question 35

Osteoporosis

Osteoporosis may lead to

Answer 35

kyphoscoliosis and subsequent reduced respiratory function.

Question 36

Osteoporosis

Fracture often follows

Answer 36

trivial trauma.

Question 37

Osteoporosis

Hip fractures result in increased

Answer 37

morbidity and mortality.

Pulmonary embolism and pneumoniae are common complications of

Question 38

Osteoporosis

Pulmonary embolism and pneumoniae are common complications of

Answer 38

fractures, and result in up to 50K deaths annually.

Question 39

Osteoporosis:

In the early stages,

Answer 39

standard radiographs are not sufficiently sensitive, but the process can be confirmed by a DEXA (dual-energy x-ray absorptiometry) scan.

Question 40

Osteoporosis:

The primary therapy to slow bone loss includes

Answer 40

adequate dietary calcium intake, vitamin D supplementation, and regular weight-bearing exercise.

Question 41

Osteoporosis:

This approach works best when initiated prior to age

Answer 41

30 to maximize the peak bone mass.

Question 42

Osteoporosis:

The first line of medical therapy for affected patients is the use of

Answer 42

bisphosphonates (E.g. Actonel, Boniva, and Fosamax) due to their ability to reduce osteoclastic activity.

Question 43

Osteoporosis:

Unfortunately, bisphosphonates have been associated with a predisposition to

Answer 43

gnathic osteonecrosis.

Question 44

Osteoporosis:

Other approaches include

Answer 44

estrogen receptor agonists and several newer hormone based drug therapies (E.g. Forteo, Evista) that do not increase the risk for breast and ovarian cancer.

Question 45

Osteoporosis:

New treatment modalities also include

Answer 45

monoclonal antibodies such as Denosumab (Prolia) which acts as a Rank-ligand inhibitor.

Question 46

Paget disease (osteitis deformans) is a fairly common bone disorder characterized by

Answer 46

repetitive episodes of frenzied, regional osteoclastic activity and bone resorption (osteolytic stage), followed by exuberant osteoblastic activity and bone formation (mixed osteoclastic-osteoblastic stage), and finally by an apparent exhaustion of cellular activity (osteosclerotic stage).

Question 47

Paget disease

The net effect is a gain in

Answer 47

bone mass; but the newly formed dense bone is disordered, structurally weak and prone to fracture.

Question 48

Paget disease

These processes produce

Answer 48

skeletal deformation caused by accumulation of excessive amounts of abnormal, unstable bone.

Question 49

Paget disease

The abnormality is rare before the age of

Answer 49

40 and exhibits a slightly increased prevalence in males.

Question 50

Paget disease

There is a marked variation in prevalence in different populations with the pathosis being

Answer 50

rare in individuals from China, Japan, and Africa while affecting up to 10% of the white adult population in many western countries.

Question 51

Paget disease

The lesions may be confined to a

Answer 51

single bone (monostotic, represent ~15%), involve numerous bones (polyostotic, represents ~85%) or rarely the entire skeleton.

Question 52

Paget disease

The etiology is unknown, but

Answer 52

paramyxovirus is suspected.

Question 53

Paget disease

As mentioned, the process evolves through

Answer 53

three stages.

Question 54

Paget disease

Initially, there is a period of

Answer 54

osteoclastic activity, hypervascularity and bone loss that is followed by a phase of mixed osteoclastic and osteoblastic proliferation which gradually evolves into a late osteosclerotic phase.

Question 55

Paget disease

The typical microscopic features of the disease show

Answer 55

active osteoclastic and osteoblastic activity, many times on the same trabecula of bone.

Question 56

Paget disease

The interstitial tissue is

Answer 56

loosely arranged and highly vascular.

Question 57

Paget disease

The histopathologic features form a

Answer 57

mosaic pattern of bone.

Question 58

Paget disease

Radiographically, the bone shows a mixture of

Answer 58

radiolucent-radiopaque areas referred to as a cotton-wool pattern.

Question 59

Paget disease:

Any bone may be affected. About 80-90% are

Answer 59

asymptomatic, and most are discovered on routine radiographs or blood studies. =

Question 60

Paget disease:

When present, the clinical manifestations and symptoms are

Answer 60

variable and include bone enlargement, bone pain, deformity, cranial nerve compression, hearing loss and visual disturbances, bowing of bones and fractures.

Question 61

Paget disease:

Other possible complications include

Answer 61

leontiasis ossea (lion face, characterized by an overgrowth of the facial and cranial bones) and a slight increased risk (1 % lifetime) for development of sarcomas (particularly osteosarcoma).

Question 62

Paget disease:

The diagnosis is made

Answer 62

secondary to the radiographic and microscopic appearances combined with demonstration of elevated levels of urinary hydroxyproline (⇑bone resorption) and serum alkaline phosphatase (⇑bone apposition).

Question 63

Paget disease:

Most patients have

Answer 63

mild symptoms which can be controlled by calcitonin or bisphosphonates and analgesics.

Question 64

Hyperparathyroidism is characterized by

Answer 64

inappropriate secretion of PTH (parathyroid hormone).

Question 65

Hyperparathyroidism

PTH plays a central role in

Answer 65

calcium homeostasis via its effects on: osteoclast activation, increased calcium resorption by the kidneys, and increased synthesis of vitamin D (kidneys) resulting in increased calcium absorption from the gut.

Question 66

Hyperparathyroidism

The net result is an elevation in

Answer 66

serum calcium.

Question 67

Hyperparathyroidism

Patients often develop

Answer 67

skeletal changes (bone appears ground glass and osteoporotic) due to activation of osteoclasts.

Question 68

Hyperparathyroidism

Osteitis Fibrosa Cystica (cyst-like brown tumors of bone) can also be observed in patients with

Answer 68

hyperparathyroidism. These lesions are histopathologically identical to central giant cell granuloma of the jaws.

Question 69

Primary hyperparathyroidism is one of the most common

Answer 69

endocrine disorders, and it is an important cause of hypercalcemia.

Question 70

Primary hyperparathyroidism

In more than 95% of cases, primary hyperparathyroidism is caused by

Answer 70

parathyroid adenomas or hyperplasia (less commonly by parathyroid carcinoma, but more severe).

Question 71

Primary hyperparathyroidism

Primary hyperparathyroidism is usually a disease of

Answer 71

adults and is more common in women.

Question 72

Primary hyperparathyroidism

The most common manifestation of primary hyperparathyroidism is an increase in

Answer 72

serum calcium due to an increased level of PTH.

Question 73

Primary hyperparathyroidism

Primary hyperparathyroidism has been traditionally associated with a constellation of symptoms that included

Answer 73

“painful bones, renal stones, abdominal groans, and psychic moans”.

Question 74

Primary hyperparathyroidism

Pain, secondary to fractures of bones weakened by osteoporosis and resulting from renal stones, with obstructive uropathy, was at one time a

Answer 74

prominent manifestation of primary hyperparathyroidism.

Question 75

Primary hyperparathyroidism

Because serum calcium is now routinely assessed in the

Answer 75

work-up of most patients who need blood tests for unrelated conditions, clinically silent hyperparathyroidism is detected early.

Question 76

Primary hyperparathyroidism

Hence, many of the classic clinical manifestations, particularly those

Answer 76

referable to bone and renal disease are seen much less frequently.

Question 77

Primary hyperparathyroidism

Treatment involves removal of the

Answer 77

affected gland/tumor.

Question 78

Secondary Hyperparathyroidism is caused by any condition associated with a

Answer 78

chronic depression in the serum calcium level, because low serum calcium leads to compensatory over activity of the parathyroids.

Question 79

Secondary Hyperparathyroidism

Chronic renal insufficiency is associated with

Answer 79

decreased phosphate excretion, which in turn results in hyperphosphatemia.

Question 80

Secondary Hyperparathyroidism

Renal failure is by far the most common cause of

Answer 80

secondary hyperparathyroidism.

Question 81

Secondary Hyperparathyroidism

The elevated serum phosphate levels directly

Answer 81

depress serum calcium levels and thereby stimulate parathyroid gland activity.

Question 82

Secondary Hyperparathyroidism

In addition, loss of renal substances reduces the synthesis of the active form of

Answer 82

vitamin D, which in turn reduces intestinal absorption of calcium.

Question 83

Secondary Hyperparathyroidism

The clinical manifestations of secondary hyperparathyroidism are generally less severe than the

Answer 83

primary form.

Question 84

Secondary Hyperparathyroidism

The associated renal failure is the

Answer 84

most clinically significant aspect.

Question 85

Secondary hyperparathyroidism:

The treatment of the underlying cause (e.g. renal transplant, Vitamin D supplementation)

Answer 85

will resolve the secondary hyperparathyroidism.

Question 86

Osteomyelitis refers to an

Answer 86

infection spreading through the medullary spaces of a bone.

Question 87

Osteomyelitis

Bacteria can colonize the spaces within bone, normally through one of three pathways.

Answer 87

1. Hematogenous spread
2. Contiguous infection (i.e. odontogenic infections)
3. Direct traumatic introduction (i.e. compound fractures, surgical procedures)

Question 88

Osteomyelitis

Hematogenous osteomyelitis is caused most frequently by

Answer 88

Staphylococcus aureus; while mixed infections, often with anaerobes, are seen in those secondary to trauma or dental problems.

Question 89

Osteomyelitis

Pain and tenderness will be present in the affected area with subsequent development of

Answer 89

redness and swelling in the area.

Question 90

Osteomyelitis

Fever is seen

Answer 90

frequently.

Question 91

Osteomyelitis

Early in the course, radiographic alterations are difficult to ascertain until

Answer 91

significant bone necrosis occurs.

Question 92

Osteomyelitis

With progression,

Answer 92

ill-defined areas of radiolucency develop and may be intermixed with radiopaque sequestra.

Question 93

Osteomyelitis

Treatment may include

Answer 93

drainage and appropriate antibiotics, with or without surgical debridement.

Question 94

Fibrous Dysplasia is characterized by progressive

Answer 94

replacement of normal bone by fibrous tissue intermixed with unorganized, woven bone. This may reflect disordered bone maturation with arrest at an immature stage of woven bone due to a specific mutation.

Question 95

1. Monostotic fibrous dysplasia (single bone):

Answer 95

70% of all cases. It usually manifests in childhood and often becomes stationary at puberty. The most common sites of involvement in descending order of frequency are the ribs, femur, tibia, jaws, calvarium, and humerus.

Question 96

2. Polyostotic fibrous dysplasia without endocrine involvement (Jaffe-Lichtenstein Syndrome):

Answer 96

Multiple bones are affected, and the involvement often tends to be unilateral. This pattern accounts for about 25% of the cases, often arises at an earlier age, and can continue to cause problems during adulthood. Frequently affected bones are craniofacial bones (including jaws), femur, tibia, humerus, and pelvis. Café-au-lait pigmentations are variable but not rare; related endocrine abnormalities are absent.

Question 97

3. Polyostotic fibrous dysplasia in association with endocrinopathies (McCune-Albright syndrome):

Answer 97

This pattern is the least common, represents around 3% of all cases, and typically is accompanied by melanin pigmentation of the skin (café-au-lait spots) and endocrine abnormalities. Although precocious sexual development is the most common endocrine abnormality, other disorders such as hyperthyroidism, excess growth hormone, and primary adrenal hyperplasia may be seen. Females are affected much more than males. The process often is unilateral and affects the majority of the bones on the altered side.

Question 98

Fibrous Dysplasia:

Histopathologic examination of early lesions reveals a mixture of

Answer 98

cellular fibrous connective tissue intermixed with elongated trabeculae of immature woven bone and this pattern has been termed Chinese characters. When radiographically examined with film capable of high detail (dental films), the affected area will appear as an ill-defined area of increased radiopacity described as ground glass. Less detailed radiographs often depict an ill-defined radiolucency.

Question 99

Fibrous Dysplasia
The clinical manifestations and potential of this disease are variable. Swelling and destruction of bone with considerable deformity

Answer 99

can occur. Many cases will stabilize at puberty. Others will progress slowly. Treatment involves surgery and/or close observation. Treatment may vary from observation (May stabilize at puberty), anti-resorptive therapy to surgical reduction (usually delayed until skeletal maturity).

Question 100

A wide variety of benign and malignant tumors of bone can occur. These develop from

Answer 100

bone-producing cells, cartilage-producing cells and interstitial tissue. Bone is also a common site for metastasis of other malignancies. This discussion with focus on one primary bone tumor, osteosarcoma.

Question 101

Osteosarcoma is a bone and osteoid producing

Answer 101

malignancy.

Question 102

Osteosarcoma

Outside of lymphoproliferative diseases, osteosarcoma is the most common

Answer 102

primary malignant tumor of bone.

Question 103

Osteosarcoma

Osteosarcomas occur in all age groups, but most patients are

Answer 103

younger than age 20 (mean age 18yrs).

Question 104

Osteosarcoma

Any bone can be affected, however the

Answer 104

metaphyseal region of long bones in the extremities is the most frequent site (60% occurring in the knee vs 8 % in the jaws).

Question 105

Osteosarcoma

A painful enlarging mass is the

Answer 105

most frequent clinical presentation; however pathologic fracture can also be the first sign of disease.

Question 106

Osteosarcoma

The radiographic appearance is generally that of a

Answer 106

large, destructive, mixed radiolucent-radiopaque lesion that may present with a “sunburst” appearance.

Question 107

Osteosarcoma

A characteristic feature is the formation of an

Answer 107

acute angle between the neoplastic bone and the cortex (Codman’s triangle).

Question 108

OSteosarcoma

Diagnosis requires

Answer 108

histologic evidence of direct production of osteoid by malignant mesenchymal cells.

Question 109

Osteosarcoma

Aggressive surgery and chemotherapy is the standard

Answer 109

treatment and results in a 5 yr survival of 60-70%.

Question 110

Osteosarcoma

This disease must be treated adequately the

Answer 110

first time because once the patient has a recurrence, survival drops significantly.

Question 111

Osteoarthritis (degenerative joint disease) is the most common disorder of the joints and is a very frequent, if not inevitable, part of aging. The fundamental feature of osteoarthritis is

Answer 111

degeneration of the articular cartilage. The changes that follow in the underlying bone are secondary.

Question 112

Osteoarthritis

The process may be primary ——— or secondary ———-

Answer 112

(arises without obvious predisposing factors)

(arises in a previously deformed joint).

Question 113

Osteoarthritis

In contrast to rheumatoid arthritis, osteoarthritis is not

Answer 113

primarily an inflammation of the joints but may become secondarily inflamed as the process progresses.

Question 114

Osteoarthritis

Although the pathogenesis is unknown, perhaps the most important factors appear to be

Answer 114

aging and mechanical effects. Although osteoarthritis is not exclusively a wear-and-tear process, there is little doubt that mechanical stresses on the joints play a major role in its development.

Question 115

Osteoarthritis

The fundamental feature of osteoarthritis is degeneration of the

Answer 115

articular cartilage; any structural changes in the underlying bone are secondary. Normal articular cartilage is bathed in synovial fluid and ensures a friction-free joint surface.

In addition, the cartilage spreads the load across the joint surface, helping the bone absorb shock and weight without being crushed.

Question 116

Osteoarthritis

In the early stages, the cartilage cap develops

Answer 116

vertical fissures. With time, these fissures extend through the full thickness to the subchondral bone. Eventually, portions of the cartilage are eroded completely with exposure of the underlying bone. Fragments of dislodged bone and cartilage often float free in the joint space and form “joint mice”. Eventually, the entire surface of the bone becomes exposed, thickened and polished to an ivory-like appearance.

Question 117

Osteoarthritis

At the margins of the joint, small bony outgrowths termed

Answer 117

osteophytes arise and help to further inflame the surrounding synovial membrane.

Question 118

Osteoarthritis

The initial symptoms typically develop after the age of

Answer 118

50 and include crepitus (grating or popping sensation), joint stiffness and deep, aching pain, especially in the morning.

Question 119

Osteoarthritis

Repeated use of the joint tends to

Answer 119

aggravate the pain.

Question 120

Osteoarthritis

The signs and symptoms develop slowly and usually affect only

Answer 120

one or a few joints.

Question 121

Osteoarthritis

As the disease progresses,

Answer 121

pain, deformity and limitations of motion become apparent.

Question 122

Osteoarthritis

In contrast to rheumatoid arthritis, fusion of the joint does not occur. Fortunately, most people are without severe disability. Aside from complete inactivity, there is no way to prevent or halt the progression. Although the process can stabilize, it generally is slowly progressive. Treatment includes

Answer 122

NSAIDs, intrajoint hyaluronic acid, cortisone shots, physical therapy, braces to wear, and joint replacement.

Question 123

Gout is a disorder caused by

Answer 123

tissue accumulation of excessive amounts of uric acid.

Question 124

Gout

High levels of uric acid in these patients can cause

Answer 124

supersaturation of the blood, crystallization of the uric acid and production of recurrent bouts of arthritis.

Question 125

Gout

Elevation of the serum uric acid may result from

Answer 125

overproduction or reduced excretion of uric acid or from both. In most cases, the process is due to an idiopathic overproduction of uric acid.

Question 126

Gout

Whatever the cause, the high uric acid in body fluids leads to

Answer 126

precipitation of urate crystals that trigger a chain of events that culminate in joint injury.

Question 127

Gout

The released crystals activate

Answer 127

complement and cause chemotaxis of neutrophils.

Question 128

Gout

Dying neutrophils and reacting macrophages release

Answer 128

destructive lysosomal enzymes and inflammatory mediators.

Question 129

Acute gouty arthritis arises upon

Answer 129

precipitation of urate crystals in the synovial fluid and membranes. These crystals elicit an acute inflammatory response until the crystals resolubilize. osteoarthritis.

Question 130

Acute gout

Although any joint may be affected, the

Answer 130

great toe is affected in close to 90%.

Question 131

Acute gout

Peripheral joints like the hands and feet are affected more frequently, most likely

Answer 131

secondary to reduced solubility of urate in these cooler joints.

Question 132

Chronic gouty arthritis arises

Answer 132

secondary to repeated episodes of acute attacks.

Question 133

Chronic gouty arthritis;

Crystals become

Answer 133

encrusted on the articular surface and even penetrate deeply into surrounding bone and soft tissue. Each deposit is known as a tophus and is diagnostic of gout. Erosion and progressive destruction of the joint occurs secondary to tophi and resembles advanced

Question 134

Gout

After the joints, the ——– is the most frequently affected organ.

Answer 134

kidney

Question 135

Gout

Renal conditions such as pyelonephritis, nephrosclerosis, tubular deposition of crystals, intertubular deposition of crystals and uric acid renal stones are seen

Answer 135

secondary to gout.

Question 136

Gout

Advanced arteriosclerosis, hypertension and obesity also are

Answer 136

positively associated with gout.

Question 137

Gout

Gout exhibits a

Answer 137

male predominance and rarely produces symptoms prior to 30 years of age.

Question 138

Gout

In most cases, the onset of symptoms is

Answer 138

abrupt and followed by asymptomatic intervals and recurrent episodes of arthritis.

Question 139

Gout

With time, increased numbers of joints are

Answer 139

involved with eventual development of permanent joint deformity.

Question 140

Gout

Drugs (NSAIDs, corticosteroids, colchicine, allopurinol) are available to

Answer 140

abort or prevent gout attacks. Diet modification can also aid in management of gout.

Question 141

Duchenne muscular dystrophy

Answer 141

x-linked recessive

Question 142

Duchenne muscular dystrophy:

caused by the absence of a

Answer 142

structuraprotein termed dystrophin and is seen in about 1/3500 live male births.

Question 143

Duchenne muscular dystrophy

Dystrophin attaches portions of the muscle fibers to the

Answer 143

cell membrane, thus playing an important role in the structural and functional integrity of the myocyte.

Question 144

Duchenne muscular dystrophy

Absence or abnormality of dystrophin is associated with

Answer 144

impaired contractile activity and a variety of other derangements in both skeletal and cardiac muscle.

Question 145

Duchenne muscular dystrophy

As would be expected, the disorder is seen predominantly in the

Answer 145

male offspring of carrier females.

Question 146

Duchenne muscular dystrophy

Rare cases occur from

Answer 146

mutations de novo or in females.

Question 147

Duchenne muscular dystrophy

The affected muscles undergo

Answer 147

progressive degeneration, and the process begins in the pelvis and shoulder girdles with eventual spread to the extremities.

Question 148

Duchenne muscular dystrophy

Despite musculature weakness, the leg muscles are

Answer 148

often enlarged secondary to pseudohypertrophy (replacement of lost muscle with fibrofatty tissue).

Question 149

Duchenne muscular dystrophy

The initial signs appear in

Answer 149

childhood and present as difficulty in standing, walking, and getting out of a chair.

Question 150

Duchenne muscular dystrophy

Signs and symptoms typically begin around

Answer 150

three to five years of age. By their teens, most patients are confined to wheel chairs; and death usually ensues before age 30 due to cardiac involvement, weakness of muscles necessary for respiration, or from pneumonia secondary to aspiration of food associated with difficulties in swallowing.

Question 151

Duchenne muscular dystrophy

The diagnosis is confirmed from the

Answer 151

family history, clinical presentation, elevated serum muscle enzymes, by electromyography, and biopsy.

Question 152

Myasthenia gravis is an

Answer 152

autoimmune disease which results in destruction of acetylcholine receptors in the neuromuscular junction and is manifested by weakness and prominent fatigability of voluntary muscles.

Question 153

Myasthenia gravis

The most active muscles generally are the most

Answer 153

severely affected, such as the muscles involved in eye movement, facial expression, chewing, swallowing and respiration.

Question 154

Myasthenia gravis

The disease can arise at any

Answer 154

age and exhibits a female predominance.

Question 155

Myasthenia gravis

Patients with myasthenia gravis exhibit an

Answer 155

increased prevalence of other autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, and Sjögren syndrome.

Question 156

Myasthenia gravis

In addition, there is a strong association with

Answer 156

thymus abnormalities.

Question 157

Myasthenia gravis

Approximately 65% will demonstrate

Answer 157

thymic hyperplasia, while another 15% will exhibit a thymoma.

Question 158

Myasthenia gravis

In both instances, the altered thymus tissue demonstrates

Answer 158

myoid cells which antigenically resemble acetylcholine receptors.

Question 159

Myasthenia gravis

Although the interaction with the thymus is not understood completely, many believe these altered thymus cells stimulate the

Answer 159

development of autoimmunity.

Question 160

Myasthenia gravis

Muscle contraction depends upon a critical number of interactions between acetylcholine and receptors. Myasthenic muscles have about a

Answer 160

70-90% reduction in the number of acetylcholine receptors per neuromuscular junction as compared to controls.

Question 161

Myasthenia gravis

The course and severity of the disease are extremely ——–.

Answer 161

variable

Question 162

Myasthenia gravis

The muscle weakness becomes evident with use and typically involves

Answer 162

small, frequently utilized muscles.

Question 163

Myasthenia gravis

The most common sites of initial involvement are the muscles of the

Answer 163

eyelids (ptosis: drooping of eyelids) and the muscles controlling eye movement (diplopia: double vision).

Question 164

Myasthenia gravis

In addition, involvement of the muscles of facial expression, speech and mastication is not

Answer 164

rare. Difficulty in chewing food or holding the head upright is not rare.

Question 165

Myasthenia gravis

The signs and symptoms are first seen as a

Answer 165

failure of contraction after sustained effort; however, this progresses to loss of contractility even after extensive rest.

Question 166

Myasthenia gravis

Weakness worsens with

Answer 166

repeated contractions, and symptoms are worse later in day.

Question 167

Myasthenia gravis

In some patients, the muscular weakness may be confined to a limited number of groups, and the disease is not

Answer 167

progressive and relatively benign. In others, the disorder may be a major threat to life secondary to respiratory compromise and increased susceptibility to pulmonary infections.

Question 168

Myasthenia gravis

The natural course of the condition is improved by

Answer 168

thymectomy in cases of thymus hyperplasia and removal of the tumor in those with a thymoma.

Question 169

Myasthenia gravis

In addition, medications such as

Answer 169

cholinesterase inhibitors and corticosteroids have been proven to be beneficial in many cases.

Question 170

Myasthenia gravis

Some cases of spontaneous remission have been

Answer 170

reported.

Question 171

Myasthenia gravis

In the past, ———- was a major cause of death; due to improved therapies, the current 5-year survival is ——

Answer 171

respiratory compromise

95%.