Skeletal & PNS Pathology - Lawlor Flashcards Preview

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Flashcards in Skeletal & PNS Pathology - Lawlor Deck (40):


What are the two varieties of drug-induced myopathies?




Steroid myopathy

Statin-induced myopathy



What fibers are affected in steroid myopathy?


What muscle groups does it affect?


Type 2b fibers 


It affects muscles in the proximal limb



What tissue makes up the peripheral nervous system?


What is the biggest difference between the PNS and the CNS?


Anything that is not the brain or the spinal cord


The CNS can not regenerate, while the PNS can


Define the following terms

Motor Unit


Schwann cell



Motor Unit-one neuron and all the muscle fibers it innervates

Axon- the long connector between the neuron cell body and the dendrites

Schwann cell- the cell that myelinates the axon in PNS




What patterns of myelination should you see as nerve fibers increase in size?


What can clusters of small, poorly myelinated axons indicate?


As the axon increases in size, the myelin sheath should be thicker


Axonal regrowth



Explain the difference between Wallerian degeneration, Neuronopathy, and axonopathy.


Which of these syndromes have digestion chambers on histology?


Wallerian degeneration- degeneration of a distal neuron after an injury cuts it off from the cell body

Neuronopathy- a generalized disorder that affects the cell body 

Axonopathy- a generalized disorder that attacks the axon, resulting in "dying back"


Wallerian degeneration and axonopathy have digestion chambers (they are the only disorders where the axon is dying and being digested)



What are the three inflammatory neuropathies?


What are the differences seen between them? 


Guillain Barre- rapidly ascending weakness, that clears quickly; immune system target the muscle fibers

Chronic Inflammatory Demyelinating Polyradiculopathy- slowly progressing weakness moving from proximal to distal; immune system targets the muscle fibers

Vasculitis- death of perivesicular muscle fibers; immune system targets the vessels, but muscle gets caught in the fray.  Typically affects ONE nerve as opposed to many



What is seen on histology in Chronic Inflammatory Demyelinating Polyradiculopathy?



On cross-section, axons of similar size may have drastically reduced levels of myelin


Also, inflammatory infiltrate



What two infectious diseases might cause neuropathy?


What might help distinguish these two?





Leprosy will typically have travel outside of the US, can affect any age, and tends to attack cooler area of the body.  On histology, there will be granulomas (pathognomonic)


Shingles typically affects only the immunocompromised and the elderly.  It tends to follow a single dermatome, usually on the trunk.  



What is Charcot Marie Tooth type 1?


What is the genetic defect and how is it inherited?



A demyelinating disorder that affects long nerves, causing atrophy of distal limbs.


It is caused by a duplication or deletion (so any frame shift I guess?) in PMP22.  This is autosomal dominant inheritance.



What is seen on histology in Charcot Marie Tooth?


What symptoms are seen?


Onion skin formation around nerves from failed myelination attempts


Gait disorders, stork legs, foot drop, hammer toes, pes cavus



What type of neuropathy is diabetic neuropathy?


What distribution of nerve problems is seen?


It is an axonal degeneration


loss of motor and sensation are seen in the hands and feet



What is carpal tunnel syndrome?


How is it treated?


Impingement of the median nerve at the wrist causing pain/tingling in the thumb and first three digits.


Brhavior modification, wrist splinting, surgical fascia release



What are neuromas?


What "harmless" procedure can they result from?


intraneural scarring/overgrowth of peripheral nerves, causing intense pain, tingling


A nerve biopsy, so be judicious

Can also be cause by compression, fracture, or surgical lesion 


Abnormal grouping of muscle fiber types is indicative of what process?

Denervation with reinnervation


Describe each of the following pathologic reactions of muscle:

  • hypertrophy
  • degeneration/necrosis
  • regeneration

  • Hypertrophy: reaction to increased load due to exercise or pathologic condition
  • Degeneration/necrosis: destruction of all or part of a myofiber; stimulates infiltration by macrophages
  • Regeneration: satellite cells around degenerated fibers proliferation. Regenerating fibers have a bluish (basophilic) color


Describe the fiber type grouping reaction in the context of reinnervation

After denervation, neighboring axons sprout and reinnervate denervated myocytes. The reinnervated fiber assumes the same fiber type as those innervated by the new axon


Describe the histologic appearance of neurogenic degradation. Is there necrosis?

Describe the histologic appearance of myopathic degradation. Is there necrosis?

  • Neurogenic -> no necrosis, fibrosis, or inflammation
    • Bimodal size distribution
    • Angulated fibers
    • Apparent increase in nuclei (nuclear clumps)
  • Myopathic -> necrosis with regeneration, fibrosis (+/-), and inflammation
    • centralization of nuclei
    • round fibers
    • random size variation



What is the main distinction between ALS and SMA?

ALS: UMNs and LMNs



What age group is most affected by ALS?

What age group is most affected by SMA?

50-60 years old

children >>> adults


What is the genetic inheritance pattern of spinal muscular atrophy?

What is the genetic defect?

Are patients with SMA intellectually normal?

Compare the deep tendon reflex findings of SMA to ALS

autosomal recessive

SMN1 (survival motor neuron gene 1)

normal intellect

SMA: areflexia; ALS: hyperreflexia


Describe the histologic pattern seen in Werdnig Hoffmann disease

Large groups of atrophic fibers (panfascicular) with scattered hypertrophic fibers


What is the function of dystrophin?

Defects of dystrophin are associated with which two diseases?

What is the genetic inheritance pattern of these two diseases?

Plays a major role in connecting the myoblast cytoskeleton to the extracellular collagen matrix in muscle tissue

Duchenne MD and Becker MD



Dystrophin: which is more important: quality or quantity?

How is this related to the severity/presentation of DMD and BMD?


DMD patients do not produce any dystropin (or nearly none), so the disease is more severe. BMD patients produce less (or lower quality) dystrophin, leading to less severe disease and (possibly) later presentation.


Gower's maneuver is characteristically seen with what disease?

Give one major serum lab finding that is associated with this disease.


CK greatly increased (>10,000)


Describe the physical findings in DMD

  • proximal muscle weakness
  • slower movement -> wheelchair-bound by age 11-12y
  • Large calves (squishy, filled with fibro-fatty tissue rather than muscle)
  • Waddling
  • Gower's maneuver
  • Scapular winging
  • Contractures
  • Sparing of the eyes and face
  • Dilated cardiomyopathy
  • Mild intellectual impairment and developmental delay (IQ ~85)


Describe (3) major immunohistologic stain findings in DMD

Dystrophin(-): some dystrophin may appear in isolated islands where (for some reason) there was spontaneous 'read-through' of the defective gene.

Spectrin(+): marked increase over normal tissue

Utrophin(+): normally found in capillaries/vessels only. Seen throughout muscle tissue in DMD.


Modern genetic testing makes western blots unnecessary for diagnosis of DMD and BMD (but still useful for treating doctor-wallet dystrophy). Descibe the findings for:

  • BMD
  • DMD

BMD: reduced size and amount (lighter bands than control, bands further down the gel = smaller)

DMD: essentially no dystrophin present (blank gel)


What is the most common muscular dystrophy in adults?

What is the genetic inheritance pattern? What is the defective gene? How many repeats must be present for disease?

Myotonic dystrophy

Autosomal dominant. CTG repeats in DMPK gene on chromosome 19 (DM1)

Disease requires at least 80 repeats. Shows genetic anticipation.


Describe the major physical exam finding of myotonic dystrophy. Why does this happen?

Describe other clinical findings

Difficulty releasing grip

Due to impaired Cl- conduction -> slower repolarization -> impaired relaxation

Other clinical findings:

  • elongated face (myopathic facies)
  • temporal wasting
  • weakness in distal hands and feet (grip and foot drop)
  • premature cataracts
  • cardiac arrhythmias
  • decreased intellect (more severe with increasing repeats)
  • ptosis, receding hairline, testicular atrophy


What accounts for the dramatic variation in severity/presentation of mitochondrial myopathies?

Mitochondia segregate independently, so different proportions of 'good' and 'bad' mitochondria can end up in different tissues. More severe disease depends on (1) greater proportion of defective mitochondria and (2) segregation of more defective mitochondria into especially-sensitive tissues (CNS, liver, nerves -> i.e. metabolically demanding tissues). Skin is relatively unaffected.


What is the defect in MELAS?

Describe the clinical features

What's 'weird' about the distribution of affected muscles?

MtDNA mutation (tRNA_Leu)

Clinical features:

  • Stroke-like episodes before age 40 (metabolic, not vascular)
  • Encephalopathy
  • Lactic acidosis with ragged red fibers

Muscle distribution:

  • Opthalmoparesis: myopathy of the motor muscles of the eyes with relative sparing of the face and head
  • 'cape-like' proximal upper weakness
  • Thigh


Which glycogen storage disease features generalized (multi-organ) glycogen storage dysfunction with particular prominence in the heart?

Which enzyme is deficient?

Pompe's disease

Acid maltase (glucosidase)


Which enzyme is deficient in McArdle's disease?

Which tissue does this primarily affect?

Phosphorylase a

Muscle (myopathic disease)


Does polymyositis feature a rash? What about dermatomyositis?

Which sex is more affected by polymyositis? Inflammation is mediated primarily by what cell type? Where are the immune cells found?

Which is more affiliated with malignancy?

Poly: no rash; Dermato: rash

F > M; CD8+ T-cell mediated, endomysial (intermingled among muscle fibers)

Dematomyositis (poly has no malignancy association)


Describe the skin findings of dermatomyositis


Shawl sign (skin redness over upper/lateral face - like a shawl)

Heliotropic rash (violaceous)

Nail bed thrombi with hemorrhages

painful subQ calcifications (more common in juvenile variant)

Gottron's papules (erythematous lesions over knuckles)


Which immune cell is predominant in the pathogenesis of dermatomyositis?

How does this contibute to the histological appearance of dermatomyositis?

B cells predominate

The humoral reaction attacks the microvasculature, leading to perifascular atrophy and necrosis (not endofascicular like polymyositis)


Describe the clinical exam findings of Inclusion Body Myositis (IBM)

Which age group is primarily affected?

Describe the histologic findings

Describe another histologic finding (hint: amyloid)

Describe the EM findings

Medial forearm atrophy (deep finger flexors), Severe quadriceps atrophy (early effect)

Older adults >50 y.o.

Large basophilic vacuoles in regenerating cells

Amyloid deposits noted with Congo Red Stain (apple-green birefringence)

Cytoplasmic inclusions of tuberofilaments (tangle of yarn)


Which of the following diseases responds to immunosuppressive therapy?

  • Dermatomyositis
  • Polymyositis
  • Inclusion Body Myositis

  • Yes
  • Yes
  • No