Musculoskeletal 1 Flashcards
What are the two types of muscle fibers?
1 (slow, red) - depends on oxidative metabolism (fat)
2 (fast, white) - more powerful, depends on anaerobic glycolysis
How does each muscle fiber type stain for myosin ATPase at high pH?
Type 1 (slow, red) fibers don’t stain, Type 2 (fast, white) fibers stain darkly.
Is each human muscle composed of either type 1 or type 2 muscles, or are they mixed?
They are mixed
What is the determinant for the development of a type 1 or 2 muscle fiber?
The nerve that supplies it (fiber type can switch if the nerve type is changed)
What is a motor unit?
A nerve and all the muscle fibers that it innervates.
Muscular atrophy is characterized by abnormally _______ myofibers.
small
Can denervation atrophy affect both fiber types? What do fibers that have undergone denervation atrophy look like microscopically?
It can affect both fiber types. Fibers become small and angular on cross section.
What is fiber-type grouping? What is group atrophy and what is it a hallmark of?
When adjacent nerves make new connections to muscles that have been affected by dernervation atrophy, the fibers switch to the fiber type of the new nerve (checkerboard pattern). If this new nerve dies, then large groups of fibers atrophy - a hallmark of recurrent neurogenic atrophy.
What does disuse atrophy look like microscopically?
Small, angular fibers, primarily type 2, random distribution.
What muscles are primarily affected by steroid-induced (exogenous or endogenous glucocorticoid) atrophy?
Proximal muscles, type 2 fibers.
In advanced cases of muscular dystophy, muscle fibers are replaced by ______ tissue, and labs will show elevated serum ______ ______.
fibrofatty tissue replaces muscle
elevated serum creatine kinase from degenerating muscle
Name two X-linked muscular dystrophy diseases. Which one is more severe? Which one is more common?
Duchenne (more severe, more common) and Becker
Name the disease: begins with weakness in the proximal muscles of extremities at about 1 year of age. Clinically evident by age 5, progressing to immobilization and wheelchair dependence by ages 10-12, wasting, contracture and death by the early 20s.
Duchenne muscular dystrophy
What is the etiology (genetic and protein product) for both Duchenne and Becker muscular dystrophy?
Mutation on short arm of X chromosome –> decreased (Becker) or absence (Duchenne) of dystrophin, a protein that connects the contractile elements to the plasma membrane of the muscle cell.
Duchenne and Becker muscular dystrophy are characterized by relentless _______ of muscle fibers, followed by regeneration and progressive ________.
relentless necrosis –> repair, regeneration –> fibrosis
What type of inflammatory cells are often found in muscles of patients with Duchenne/Becker?
Macrophages - scavenging
Does Duchenne/Becker affect cardiac muscle?
Yeah
How is Duchenne/Becker muscular dystrophy diagnosed (other than clinical features)?
Abnormal staining for dystrophin or western blot.
What is the main difference between the immunohistological staining of muscle of a patient with Duchenne vs. a patient with Becker?
In Duchenne, there is NO dystrophin staining. In Becker, there is diminished dystrophin staining (reflects the relative severities of the diseases)
What are seven clinical features of the x-linked muscular dystrophies (Duchenne, Becker)?
- Boys with DMD are normal at birth.
- Elevated serum creatine kinase.
- Walking is delayed.
- Weakness begins in pelvic girdle, then goes to the shoulder girdle.
- PSEUDOHYPERTROPHY of the calves.
- Immobilization by age 10-12, bedridden by age 15.
- Death from resp. insufficiency or cardiac arrhythmias.
Aside from staining for dystrophin, what other microscopic changes can be seen in DMD/BMD (5)?
- Over-contracted segments of sarcoplasm between degenerated segments.
- Macrophages.
- Some fibers are small with a granular sarcoplasm.
- Enlarged, vesicular nuclei with prominent nucleoli (degenerating fibers).
- Collagen deposition.
What is the pattern of inheritance of myotonic dystrophy?
Autosomal dominant
At what age do symptoms of myotonic dystrophy usually manifest?
Age of onset and severity are variable, but onset usually occurs in adult years
What is the incidence of myotonic dystrophy?
14 per 100,000
What is the genetic mutation involved in myotonic dystrophy? What does the gene encode?
CTG trinucleotide repeat expansion of the gene for dystrophia myotonica protein kinase (DMPK), located on the long arm of chromosome 19. It encodes a novel serine-threonine protein kinase.
Myotonic dystrophy is characterized by impaired muscle _______, along with weakness associated with ________ and muscle wasting.
impaired muscle relaxation; weakness associated with myotonia (delayed muscle relaxation)
Describe early symptoms of myotonic dystrophy (2).
- Early childhood - gait abnormalities due to weak foot dorsiflexors.
- Progression to weakness of intrinsic hand muscles and wrist extensors, followed by facial muscle atrophy and ptosis (eyelid drop).
Name three seemingly random other clinical features that myotonic dystrophy is associated with.
- Cataracts
- Testicular atrophy
- Baldness
Myotonic dystrophy worsens with each passing generation due to trinucleotide repeat expansion. What is this characteristic called?
Anticipation.
What microscopic changes are seen in a muscle of a person affected with myotonic dystrophy (3)?
- Central nuclei
- Variation in fiber size
- Fibrosis
What are the two types of myopathies?
- Congenital
2. Toxic
Are most mitochondrial genes in nuclear DNA, or mtDNA? Where are the mutated genes located involved in mitochondrial myopathy?
Most are in nuclear DNA. Mitochondrial myopathy is inherited from mom in the mtDNA.
Clinical expression of mitochondrial myopathy depends on the ______ of the mitochondrial genes that are mutated.
proportion
True or false: the fraction of mutant mtDNA must exceed a critical threshold for a mitochondrial disease to be symptomatic (dose effect).
Tru dat
What are the microscopic morphological changes seen in mitochondrial myopathy (2)?
- Accumulation of a excessive mitochondria –> aggregation of reddish granular material in the sarcoplasm (“RAGGED RED FIBERS”).
- EM shows too many mt, with abnormalities including funky size and shape, and para-crystalline “PARKING LOT INCLUSIONS” or alterations in the structure of cristae.
What are the clinical features of mitochondrial myopathy (5)?
Begins in childhood with (1) proximal muscle weakness and (2) sometimes severe ocular muscle involvement.
There can also be (3) neuro symptoms, (4) lactic acidosis, and (5) cardiomyopathy.
Myasthenia gravis is an autoimmune disorder of the ______ _______ characterized by muscle weakness.
neuromuscular junction
What is the incidence of myasthenia gravis? When does it present? What is the male:female ratio?
3 in 100,000
can present at any age
1:3 male:female
What cellular mechanism causes myasthenia gravis?
Abnormal Abs bind Ach receptors at the neuromuscular junction and block them (Type II rxn w/ antibody-mediated cellular dysfunction)
_______ _______ is found in 65% of myasthenia gravis patients and a _______ is found in 15% of patients. Therefore, ________ can be an effective treatment in these cases.
Thymic hyperplasia in 65%, thymoma in 15%
Tx is thymectomy
In the case of myasthenia gravis, most muscle endplates appear normal under EM, but there may be _______ of type II muscle fibers and focal collection of ________ within the fascicles.
there may be atrophy of type II fibers and a focal collection of lymphocytes within the fascicles
What are the clinical features of myasthenia gravis (5)?
- Muscle weakness that is worsened with intense use; recovery after rest.
- Severe weakness of extraocular muscles –> ptosis (eyelid drop) and diplopia (double vision).
- Weakness progresses to muscles involved with chewing, swallowing, breathing, speaking, and to the extremities.
- Sensory and autonomic functions are NOT affected.
- Respiratory failure.
What are four treatments for myasthenia gravis?
- Anticholinesterases
- Thymectomy
- Corticosteroids
- Methotrexate
What is Lambert-Eaton syndrome?
A disease that causes myasthenia gravis-like symptoms due to paraneoplastic syndrome (from a neoplasm - small cell lung ca or thymoma) or from autoimmune diseases (hypothyroidism, DM type 1).
Describe the cellular defect involved in Lambert-Eaton syndrome.
IgG Abs target voltage-sensitive Ca2+ channels (the ones at the end of the motor neuron that let Ca2+ in so that it can release nt vesicles) –> no Ach release.
Do anticholinesterases help patients with Lambert-Eaton syndrome?
Nope
What are two main differences between clinical features of myasthenia gravis and Lambert-Eaton syndrome?
- Lambert-Eaton syndrome DOES affect autonomic function.
2. Anticholinesterases do NOT help patients with Lambery-Eaton syndrome.
What are the treatments for Lambert-Eaton syndrome (3)?
Immunosuppression or treat the neoplasm (if applicable); repeated electric stimulation increases muscle strength.
Are skeletal muscle neoplasms almost all malignant?
Yeah
What is the most common soft tissue sarcoma of childhood and adolescence?
Rhabdomyosarcoma
Where in the body do rhabdomyosarcomas usually manifest (3)?
Head, neck, or GI tract
What genetic change is often seen in rhabdomyosarcomas? What do these genes do?
PAX3 from chromosome 2 fuses with FKHR gene on chromosome 13.
PAX3 normally controls skeletal muscle differentiation; the fusion causes dysregulation of differentiation.
Are rhabdomyosarcomas aggressive? How are they treated? What influences the prognosis?
They are aggressive.
Treated with combo of surgery, chemo, radiation.
Prognosis is influenced by location, variant, and age (adults do worse - curable in 2/3 of children).
What are the three histologic classes of rhabdomyosarcoma? What feature is diagnostic of all cases? Describe it.
- Embryonal
- Alveolar
- Pleomorphic
Rhabdomyoblast is the diagnostic cell in all types. They have a granular eosinophilic cytoplasm rich in thick and thin filaments, and they stain with anti-myosin. They can look like TADPOLES or STRAP CELLS with cross striations.
Leiomyosarcomas comprise ___ to ___ of soft tissue sarcomas, occur most commonly in females, and commonly present as firm, painless masses, however _______ tumors can be large, bulky, and cause abdominal discomfort.
10-20%
retroperitoneal tumors can be large, bulky, and cause abdominal discomfort
What is a leiomyoma?
Benign smooth muscle tumor, well-circumscribed, most common in the uterus.
True or false: superficial cutaneous leiomyosarcomas are usually small and have a good prognosis.
True or false: retroperitoneal tumors are large, cannot be entirely excises, and cause death by both local extension and metastatic spread.
tru dat
tru dat
What microscopic changes are seen in a leiomyosarcoma?
Spindle cells with cigar-shaped nuclei arranged in interweaving fascicles, pleomorphism, and hyperchromatism.
