Skeletal Muscle & PNS Pathology Flashcards Preview

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Flashcards in Skeletal Muscle & PNS Pathology Deck (24):
1

Normal Muscle

Beehive is normal

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Normal Muscle

Checkerboard is normal

  • Grouping is abnormal ⇒ indicates denervation with reinnervation

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2

What are the pathologic reactions of muscle (3)?

  • Hypertrophy
    • Occurs secondary 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 fiber proliferate. Regenerating fiber has bluish color

3

Describe denervation atrophy (neurogenic atrophy)

  • Clusters of fibers (of one type) become smaller and develop angular contours (group atrophy)
  • Lack of neural input results in:
    • Breakdown of myosin and actin
    • Resorptionof myofibrils
    • Decrease in cell size
  • Both type 1 and type 2 fiber clusters are found

4

Describe reinnervation: 

  • Neighboring axons sprout and reinnervate denervated myocytes 
  • Fiber assumes fiber type conferred by the neighboring axon
  • This causes fiber type grouping

5

Neurogenic vs. Myopathic

Neurogenic

  • bimodal size distribution
  • angulated fibers
  • apparent increase in nuclei (nuclear clumps)
  • no necrosis, regeneration, fibrosis, or inflammation

Myopathic

  • random size variation
  • round fibers
  • centralization of nuclei
  • necrosis, regeneration, +/-fibrosis, inflammation

6

List the motor neuron diseases:

  • Amyotrophic Lateral Sclerosis (ALS)
    • Aka Lou Gehrig’s disease
    • Motor Neuron Disease
  • Spinal Muscular Atrophy (SMA)

7

ALS

  • Definition: 
  • Pathogenesis: 
  • Onset: 

  • Progressive, neurodegenerative d/o
  • UMN + LMN degeneration;
    • normal sensation
  • Onset: 50-60y of age (avg)

8

What are the clinical s/s of ALS?

  1. Weakness
    • Muscle atrophy of affected body part
    • Dysphagia, dysarthria
  2. Fasciculations
    • Affected body part, tongue
  3. Hyperreflexia
  4. Positive Babinski
  5. Spasticity
  6. Pseudobulbar palsy
    • Emotional lability
  7. Executive dysfunction

9

Spinal Muscular Atrophy (SMA)

  • Definition: 
  • Incidence: 
  • Demographics: 
  • Etiology: 

  • Degenerative LMN d/o of childhood>>adulthood
  • 2nd most common autosomal recessive disorder
  • Panethnic
  • Homozygous deletion of exon 7 of SMN1 (survival motor neuron) gene

10

What are the clincal s/s of SMA?

  • Proximal muscle weakness >>> distal
  • Dysphagia ⇒ GT
  • Respiratory weakness ⇒ hypercapnia ⇒ death
    • Diaphragm failure
    • Intercostal weakness
  • Normal intellect
  • Areflexic on exam
  • Different subtypes—infantile, older infant, childhood, adult onset

11

Werdnig Hoffmann Disease

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  • Large groups of rounded atrophic fibers (panfascicular atrophy)
  • Sparse scattered markedly hypertrophic fibers 
  • Differs from typical pattern of neurogenic atrophy seen in adults

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12

List the muscular dystrophies:

  • X-linked muscular dystrophies
    • Duchenne MD (DMD)
    • Becker MD (BMD)
  • Autosomal Muscular dystrophies
    • Myotonic MD (DM)

13

Why is dystrophin important to the pathogenesis of muscular dystrophies? 

  • Mutation in Xp21
    • Deletion of ≥1 exons in DMD; duplications; stop codons
  • LARGEST gene in humans
  • Reason that 1/3rd of cases are new mutations
  • Size of dystrophin does NOT matter as much as quantity of dystrophin does 

14

DMD vs BMD

  • DMD ⇒ 99% have none/nearly no dystrophin
  • BMD ⇒ 85% have abnormal dystrophin in reduced quantity
    • 15% have normal dystrophin in reduced quantity

15

What are the clinical s/s of DMD?

  1. Proximal muscle weakness
  2. Intact milestones or slightly delayed
  3. Gower’s maneuver
  4. Face/Eyes SPARED
  5. CK ↑↑↑ > 10,000
  6. Slower movement than peers ⇒ wheelchair bound by 11-12y
  7. Large calves
  8. Waddling
  9. Scapular winging
  10. Contractures
  11. Dilated cardiomyopathy
  12. Intellectual impairment (average IQ 85)

16

What is the clinical course of BMD?

  • Later onset
  • Near normal lifespan—mid 60’s
  • Still have weakness

17

Which lane represents DMD?

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Lane 4: DuchenneMD: essentially no dystrophin protein present

18

What is the most common muscular dystrophy in adults?

Myotonic dystrophy (DM)

19

What is the etiology of DM?

  • Autosomal dominant
  • DM1 = dystrophia myotonica type 1
  • CTG repeat expansion in DMPK gene on Ch 19
    • Normal 5-37 repeats
    • Full mutation is >80 repeats
  • Genetic anticipation

20

What is the major clinical sign in myotonic dystrophy?

Difficulty releasing grip ⇒ myotonia

  • Impaired Cl- conduction ⇒ slower repolarization ⇒ impaired relaxation
  • Also will see foot drop

21

What are other clinical s/s of DM?

  • Weakness
    • Proximal muscles
    • Face—hatchet face
  • Elongated face ⇒ “myopathic” face
  • Temporal wasting
  • Endocrine abnormalities
    • Testicular atrophy ⇒ balding
    • Diabetes (insulin resistance)
  • Premature cataracts
  • Cardiac arrhythmias—90% of pts
  • ↓ Intelligence (higher repeat #)

22

What are the metabolic myopathies (2)?

  • Mitochondrial myopathies
    • Mutations in nuclear or mitochondrial DNA involved in oxid phosphorylation cause mito myopathies
  • Glycogen storage diseases
    • Hereditary deficiency of enzyme involved in synthesis or degradation of glycogen

23

What is MELAS and causes it?

  • Mitochondrial myopathy, encephalopathy, lactic acidosis, & stroke-like episodes
  • MtDNA mutation
    • Mutation codes for tRNA(Leu)
    • Most common mutation m.3243A>G

24

What are the 3 criteria for MELAS?

  • Stroke-like episodes < 40y
    • Not vascular
    • Progressive cognitive impairment ⇒ dementia
  • Encephalopathy
    • Seizures, stroke-like episodes
    • Neurodegenerative component
  • Lactic acidosis, ragged-red fibers or both
    • Myopathy—proximal, eyes