Muscle Diseases

Question 1

What are the two principal pathologic processes seen in skeletal muscle?

Answer 1

denervation atrophy

pathology of muscle fiber itself = myopathy

Question 2

WHen would you do a muscle biopsy?

Answer 2

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

Question 3

Where would yo uwant to take a muscle biopsy from?

Answer 3

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

Question 4

WHat are the two types of muscle fibers? What will this look like under an ATPase histochemical stain?

Answer 4

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

Question 5

WHy would you lose the checkerboard pattern of skeletal muscle under ATPase histochemical stain?

Answer 5

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

Question 6

What is spinal muscular atrophy?

Answer 6

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

Question 7

What is the most common form of spinal muscular atrophy?

Answer 7

Werdnig-Hoffmann disease

Question 8

What are the most common forms of childhood muscular dystrophy?

Answer 8

Duchenne muscular dystrophy

Becker muscular dystrophy

Question 9

DUchene’s and Becker’s are both mutations in what gene, for what protein?

Answer 9

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

Question 10

What is the difference between Duchene’s and Becker’s?

Answer 10

In Duchene’s they have no dystrophin. In Becker’s they have decreased amounts of dystrophin or defective dystrophin

Question 11

How will DMD present?

Answer 11

symptoms by age 5

weakness in pelvic girdle first, followed by shoulder girdle.

Waddling gate

Gower’s maneuver

pseudohypertrophy of the calf muscles

wheel chair dependent by age 12

respiratory insufficiency and infections

cardiomyopathy

mean survival = 35 years

creatine kinase will be elevated

Question 12

How is the presentation different for Becker’s?

Answer 12

later onset with milder symptoms

Question 13

What will muscle biopsy show in both DMD and BDM?

Answer 13

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

Question 14

What is the treatment fo muscular dystrophies as of now?

Answer 14

immunosuppressives, but stem cells are in the works

Question 15

Besides doing a muscle biopsy, what lab test could you do to test for DMD or BMD?

Answer 15

A western blot looking for dystrophin

it would be absent in DMD and reduced in BMD

Question 16

What would you be able to see on IH staining of a female carrier for DMD?

Answer 16

Some muscle fibers won’t have dystrophin

Question 17

WHat is the most common form of ADULT dystrophy?

Answer 17

myotonic dystrophy

Question 18

Describe myotonic dystrophy

Answer 18

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

Question 19

What will muscle biopsy show in myotonic dystrophy?

Answer 19

selective atrophy of the type 1 fibers as well as ring fibers (althouh not specific)

also elevated creatine kinase

Question 20

What are two examples of ion channel myopathies?

Answer 20

1. period paralysis: hyperkalemic, hypokalemis or normokalemic
2. Malignant hyperpyrexia (inhalational anesthetics trigger uncontrolled release of caclium from skeletal muscle sarcoreticuli)

Question 21

What will biopsy show in nemaline myopathy?

Answer 21

rod-shaped intracyctoplasmic inclusions called hemaline bodies

Question 22

What are the three subgroups of inflammatory myopathies?

Answer 22

1. infectious
2. associated with systemic inflammatory disease -autoimmune
3. noninfectious inflammatory disease

Question 23

What is dermatomyositis?

Answer 23

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.

Question 24

How is polymyositis different from dermatomyositis?

Pathogenesis?

Answer 24

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

Question 25

What would you see in inclusino body myositis?

Answer 25

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

Question 26

How is thyroid hormone related fo muscle health?

Answer 26

hyperthyroidism is associated with muscle degeneration and necrosis with regeneration

In hypothyroidism patients may get muscle fiber atrophy

Question 27

What acute muscle syndrome can binge drinking cause?

Answer 27

ethanol myopathy - an acute toxic syndrome of rhabdomyolysis with rapid breakdown of skeletal muscle

Question 28

What are some drugs that can cause myopathies?

Answer 28

steroids (muscle type 2 fiber atrophy)

chloroquine (proximal myopathy)

statins (myopathy)

Question 29

Usually myasthenia gravis is an autoimmune disease with antibodies against eh acetylcholine receptor, but sometimes it’s actually antibodies against what?

Answer 29

the muscle specific tyrosine kinase receptor (MuSK)

Question 30

What associated disorder should you check for in someone with myasthenia gravis?

Answer 30

thmic problems: thymic hyperplasia or thymoma

Question 31

What is a muscle disorder that is commonly seen as a paraneoplastic syndrome in small cell lung carcinoma?

Answer 31

Lambert-Eaton myasthenia syndrome

it’s antibodies against the calcium channels so you don’t get enough NT released and they have muscle weakness

Question 32

What does creatine kinase do? WHat is it a marker of?

Answer 32

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

Question 33

What is the primary issue with the myoglobin levels in rhabdomyolysis?

Answer 33

Myoglobin levels will be elevated, which can cause acute tubular necrosis with acute renal failure (myoglobinuria)