What are the two principal pathologic processes seen in skeletal muscle?
pathology of muscle fiber itself = myopathy
WHen would you do a muscle biopsy?
WHen you have a patient that has a suspected skeletal muscle disease that cannot be explained through clinical examination alone
it's used to detect a morphological abnormality
Where would yo uwant to take a muscle biopsy from?
You'd want to biopsy an area that is only moderately affected - if you do something that's highly involved you'll only see what happens in end-stage
WHat are the two types of muscle fibers? What will this look like under an ATPase histochemical stain?
THere are type 1 (slow twitch) and type 2 (fast twitch)
under stain the muscle will look like a checkerboard pattern with type 1 fibers being light and type 2 fibers being dark
WHy would you lose the checkerboard pattern of skeletal muscle under ATPase histochemical stain?
If there's axonal degeneration of 1 type of muscle fiber followed by reinnervation by a neuron of a type 2 muscle fiber, makeing the original type 1 fibers become type 2
What is spinal muscular atrophy?
it's an autosomal recessive motor neuron disease that presents in childhood or adolescence
it's associated with mutations affecting survival motor neurons 1, a gene on chromosomes 5 that is required for motor neuron survival
it causes neurogenic muscle atrophy
What is the most common form of spinal muscular atrophy?
What are the most common forms of childhood muscular dystrophy?
Duchenne muscular dystrophy
Becker muscular dystrophy
DUchene's and Becker's are both mutations in what gene, for what protein?
the X-linked gene Xp21, which encodes for dystrophin
it's a protein on the cytoplasm adjacent to the sarcolemmal membrane which forms an interface between the itnracellular contractile apparatus and the ECM, transferring the contractil force to the CT tissue
What is the difference between Duchene's and Becker's?
In Duchene's they have no dystrophin. In Becker's they have decreased amounts of dystrophin or defective dystrophin
How will DMD present?
symptoms by age 5
weakness in pelvic girdle first, followed by shoulder girdle.
pseudohypertrophy of the calf muscles
wheel chair dependent by age 12
respiratory insufficiency and infections
mean survival = 35 years
creatine kinase will be elevated
How is the presentation different for Becker's?
later onset with milder symptoms
What will muscle biopsy show in both DMD and BDM?
variation in muscle fiber size
icnreased endomysial CT
degeneration and necrosis of muscle fibers
some muscle fiber regeneration
eventually muscles are almost completely replaced by fat and CT
What is the treatment fo muscular dystrophies as of now?
immunosuppressives, but stem cells are in the works
Besides doing a muscle biopsy, what lab test could you do to test for DMD or BMD?
A western blot looking for dystrophin
it would be absent in DMD and reduced in BMD
What would you be able to see on IH staining of a female carrier for DMD?
Some muscle fibers won't have dystrophin
WHat is the most common form of ADULT dystrophy?
Describe myotonic dystrophy
Autosomal dominant disorder with increased CTG trinucleotide repeat sequences on chromosome 19
affects the mRNA for the dystrophia myotonia protein kinase (DMPK)
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, and open mouth; other abnormalities include cataracts, frontal balding, gonadal atrophy, abnormal glucose tolerance, and cardiomyopathy
What will muscle biopsy show in myotonic dystrophy?
selective atrophy of the type 1 fibers as well as ring fibers (althouh not specific)
also elevated creatine kinase
What are two examples of ion channel myopathies?
1. period paralysis: hyperkalemic, hypokalemis or normokalemic
2. Malignant hyperpyrexia (inhalational anesthetics trigger uncontrolled release of caclium from skeletal muscle sarcoreticuli)
What will biopsy show in nemaline myopathy?
rod-shaped intracyctoplasmic inclusions called hemaline bodies
What are the three subgroups of inflammatory myopathies?
2. associated with systemic inflammatory disease -autoimmune
3. noninfectious inflammatory disease
What is dermatomyositis?
inflammatory disorder of skin and skeletal muscle
causes a violaceous discoloration of upper eyelids with periorbital edema and scaling erythematous eruption over knuckles elbows and knees
muscle weakness (proximal first)
20-25% have an underlying malignancy!!!! So check!!!!
pathogenesis probably due to immunologic injury to small blood vessels in skeletal muscle
you get perifascicular myocyte atrophy on biopsy.
How is polymyositis different from dermatomyositis?
It doesn't involve the skin
pathogenesis may be caused by T-cell mediated injury of myocyts. Muscle biopsy shows lymphocytic inflammation surrounding and invading muscle fibers without th eperifascicular atrophy seen in dermatomyositis
What would you see in inclusino body myositis?
you'll have a muscle biopsy that shows rimmed vacuoles in the muscle fibers with lymphocytic inflammatory infiltrates
it begins with distal muscles and can be asymmetric
How is thyroid hormone related fo muscle health?
hyperthyroidism is associated with muscle degeneration and necrosis with regeneration
In hypothyroidism patients may get muscle fiber atrophy
What acute muscle syndrome can binge drinking cause?
ethanol myopathy - an acute toxic syndrome of rhabdomyolysis with rapid breakdown of skeletal muscle
What are some drugs that can cause myopathies?
steroids (muscle type 2 fiber atrophy)
chloroquine (proximal myopathy)
Usually myasthenia gravis is an autoimmune disease with antibodies against eh acetylcholine receptor, but sometimes it's actually antibodies against what?
the muscle specific tyrosine kinase receptor (MuSK)
What associated disorder should you check for in someone with myasthenia gravis?
thmic problems: thymic hyperplasia or thymoma
What is a muscle disorder that is commonly seen as a paraneoplastic syndrome in small cell lung carcinoma?
Lambert-Eaton myasthenia syndrome
it's antibodies against the calcium channels so you don't get enough NT released and they have muscle weakness
What does creatine kinase do? WHat is it a marker of?
It converts creatine to phosphocreatine
\it has three isoenzymes CK-BB, CK-MB, CK-MM
skeletal muscle primarily expresses the MM and some MB.
as skeletal muscle is damaged and regeneration occurs, there is often increase MB expression
It's a marker for muscle cell damage
What is the primary issue with the myoglobin levels in rhabdomyolysis?
Myoglobin levels will be elevated, which can cause acute tubular necrosis with acute renal failure (myoglobinuria)