Compare muscle fibers with myofibrils and fast muscle fibers with slow fibers.
Fast = white fibers for rapid, short movements
Slow = red fibers, maintain protracted contraction
In humans . . . intermixed.
How are nerves connected with striated muscle cells?
Each muscle fiber is innervated by a motor neuron axon. Site of contact = neuromuscular junction
Classify muscle diseases.
Neurogenic muscle cell atrophy
Endocrine and metabolic myopathy
Autoimmune and infectious myositis
Polymyositis and dermatomyositis
What are the most important causes of neurogenic muscle atrophy?
Can be upper or lower motor neuron.
Lower motor neuron injury
Spinal nerve disease
Nerve root compression
Axonal branch injury
Upper motor neuron injury
Cortical neuron injury
Cortical tract injury
Spinal tract injury
Compare neurogenic atrophy caused by upper and lower motor neuron disease.
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.
Compare paraplegia and hemiplegia.
Paraplegia = loss of ability to move both legs
Hemiplegia = loss of ability to move muscle on one side of the body
Compare the histologic features of single-cell and fascicular atrophy of muscle.
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.
Explain wallerian degeneration.
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.
What is myasthenia gravis?
An autoimmune disease involving the neuromuscular junction. Impaired neural impulse transmission.
*Note: many have enlargement of the thymus. Will show hyperplasia or neoplasia.
What is the role of antibodies in the pathogenesis of myasthenia gravis?
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.
Which diseases are classified as muscular dystrophies and how do they differ?
They are a group of diseases, that have genetic defects (mendelian), primary muscle cell pathology, progressive course and symptoms related to muscle wasting.
- Mode of inheritence
- Age of onset
- Muscle groups initially affected
- associated findings
How are Duchenne-type dystophy and Becker's dystrophy related to the gene encoding dystrophin?
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
What are the differences between Duchenne-type dystrophy and Becker's dystrophy?
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
Correlate the pathologic and clinical features of Duchenne-type dystrophy.
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
What are the clinical features of myotonic dystrophy?
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
What are the possible causes of congenital myopathies?
1. Inborn errors of lipid metabolism
2. Inborn errors of glycogen metabolism
3. Mitochondrial myopathies
What is cerebral palsy?
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.
Give examples of acquired myopathies.
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
common paraneoplastic syndrome
antibodies may incite an immune-mediated inflammation
What is myositis?
Describes inflammatory muscle diseases: infectious and immune
If more than one muscle involved = polymyositis
Compare infectious myositis with immune myositis.
Infectious: caused by bacteria, virus, worms, protozoa
Immune: polymyositis, dermatomyositis, SLE, sarcoidosis
Correlate the pathologic features of polymyositis with the clinical and laboratory findings in this disease.
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
List the most important malignant tumors of the soft tissues.
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