Musculoskeletal

Question 1

Compare muscle fibers with myofibrils and fast muscle fibers with slow fibers.

Answer 1

Fast = white fibers for rapid, short movements

Slow = red fibers, maintain protracted contraction

In humans . . . intermixed.

Question 2

How are nerves connected with striated muscle cells?

Answer 2

Each muscle fiber is innervated by a motor neuron axon. Site of contact = neuromuscular junction

Question 3

Classify muscle diseases.

Answer 3

Neuromuscular disorders

Neurogenic muscle cell atrophy

Myasthenia gravis

Muscular dystrophy

Duchenne’s dystrophy

Limb-girdle dystrophy

Myotonic dystrophy

Congenital myopathy

Carnitine deficiency

Nemaline myopathy

Mitochondrial myopathy

Endocrine and metabolic myopathy

Thyroitoxicosis

Diabetes

Paraneoplastic myopathy

Dermatomyositis

Autoimmune and infectious myositis

Polymyositis and dermatomyositis

Infectious myositis

Trichinosis

Mechanical trauma

Crush injury

Muscle sprain

Rhabdomyolysis

Tumor

Rhabdomyosarcoma

Question 4

What are the most important causes of neurogenic muscle atrophy?

Answer 4

Can be upper or lower motor neuron.

Lower motor neuron injury

Spinal nerve disease

Nerve root compression

Axonal injury

Axonal branch injury

Upper motor neuron injury

Cortical neuron injury

Cortical tract injury

Spinal tract injury

Question 5

Compare neurogenic atrophy caused by upper and lower motor neuron disease.

Answer 5

Upper: strokes are the most important cause of upper motor neuron injury >> paralysis, hemiplegia. Located in the central cortex, connect the cortical neurons with the spinal cord.

Lower are in the anterior horn of the spinal cord, assembled into fascicles, and form peripheral nerves extending from the SC to muscles.

Question 6

Compare paraplegia and hemiplegia.

Answer 6

Paraplegia = loss of ability to move both legs

Hemiplegia = loss of ability to move muscle on one side of the body

Question 7

Compare the histologic features of single-cell and fascicular atrophy of muscle.

Answer 7

Loss of branches of axons, as is commonly seen in diabetic neuropathy or various toxic neuropathies, is accompanied by single muscle atrophy.

Transection of the entire nerve or its parts causes atrophy of larger groups of muscle fibers or the entire fascicle.

Question 8

Explain wallerian degeneration.

Answer 8

Wallerian degeneration progresses toward the nucleus of the nerve but stops at the first node of Ranvier proximal to injury. Schwann cells regenerate and form a new sheath through which the axon will find its way to reinnervate the muscle.

Question 9

What is myasthenia gravis?

Answer 9

An autoimmune disease involving the neuromuscular junction. Impaired neural impulse transmission.

*Note: many have enlargement of the thymus. Will show hyperplasia or neoplasia.

Question 10

What is the role of antibodies in the pathogenesis of myasthenia gravis?

Answer 10

Almost all patients with MG have antibodies to ACh receptors. The antibodies bind tot he receptor on the neuromuscular plate, preventing the binding of neurotransmitters.

Question 11

Which diseases are classified as muscular dystrophies and how do they differ?

Answer 11

They are a group of diseases, that have genetic defects (mendelian), primary muscle cell pathology, progressive course and symptoms related to muscle wasting.

Differ:

• Mode of inheritence
• Age of onset
• Muscle groups initially affected
• Severity
• associated findings

Question 12

How are Duchenne-type dystophy and Becker’s dystrophy related to the gene encoding dystrophin?

Answer 12

Dystrophin = an integral plasma membrane protein that holds together structural proteins, linking them to the cell membrane. It binds on one side with actin fibers (F-actin) and on the other side with cell membrane glycoproteins. The gene encoding dystrophin is on the X chromosome.

**Duchenne type = **most common

Beckers = 10x less common, milder

Question 13

What are the differences between Duchenne-type dystrophy and Becker’s dystrophy?

Answer 13

Duchenne: involve girdle muscles initially

• onset 3-5
• severe symptoms
• death by 25

Becker’s: involved girdle muscles initially

• onset 5-10
• mild but progressive
• death at 40

Question 14

Correlate the pathologic and clinical features of Duchenne-type dystrophy.

Answer 14

Early: individual muscle cell degeneration

Progression: muscle weakness, accompanied by compensatory hypertrophy of viable fibers and an ingrowth of fibrous tissue and fat cells

**Late: **muscle fascicles are gradually lost and replaced by fibrous tissue and fat cells

Question 15

What are the clinical features of myotonic dystrophy?

Answer 15

2nd most common genetic muscle disease

Caused by expansion of the CTG trinucleotide repeat on chromosome 19 encoding a protein kinase (DMPK)

Characterized by myotonia. Myotonic muscles can contract, but they remain contracted.

• eyelids droop
• hatchet face appearance
• multisystemic: diabetes, testicular atrophy, frontal baldness
• premature death

Question 16

What are the possible causes of congenital myopathies?

Answer 16

1. Inborn errors of lipid metabolism
2. Inborn errors of glycogen metabolism
3. Mitochondrial myopathies
4. Channelopathies

Question 17

What is cerebral palsy?

Answer 17

Most common form of muscle weakness in children.

Muscular atrophy, which varies in extent, is related to developmental defects of the motor cortex in the CNS.

Likely intrauterine brain injury.

Question 18

Give examples of acquired myopathies.

Answer 18

Diabetic myopathy

causes chronic hypoperfusion of muscles

affects peripheral nerves and causes neurogenic muscle atrophy and weakness

histology = focal atrophy, BV with thickened walls, loss of axons

Cancer myopathy

common paraneoplastic syndrome

antibodies may incite an immune-mediated inflammation

Question 19

What is myositis?

Answer 19

Describes inflammatory muscle diseases: infectious and immune

If more than one muscle involved = polymyositis

Question 20

Compare infectious myositis with immune myositis.

Answer 20

**Infectious: **caused by bacteria, virus, worms, protozoa

Immune: polymyositis, dermatomyositis, SLE, sarcoidosis

Question 21

Correlate the pathologic features of polymyositis with the clinical and laboratory findings in this disease.

Answer 21

Symptoms: pain, muscle weakness, difficulty moving, proximal parts of the extremities usually more involved

**Labs: **elevated CK levels, ANA

Histology: necrotic muscle cells are surrounded by an inflammatory infiltrate of macrophages and lymphocytes

Question 22

List the most important malignant tumors of the soft tissues.

Answer 22

**Rhabdomyosarcoma: **striated muscle cell, various sites

**Synovial sarcoma: **mesenchymal stem cell, leg

**Polymorphous cell sarcoma: **mesenchymal stem cell, leg, arm, retroperitoneum

**Liposarcoma: **fat cell, leg, retroperitoneum

**Leiomyosarcoma: **smooth muscle cell, retroperitoneum

Angiosarcoma: BV endothelial cells, head and neck