Muscle/Nerve Flashcards
What are the three groups of peripheral nerve pathology?
Wallerian Degeneration
Distal Axonopathy
Segmental demyelination/remyelination
What can skeletal muscle disease fall into?
Neurogenic: Primary problem is the motor neuron/axon
Myopathic: Primary problem is with the muscle
What are major types of myopathic disease?
Muscular dystrophy
Inflammatory myopahties
Metabolic myopathies
Congenital myopathies
How are muscle fibers distributed in a normal individual?
THe different motor units are intermixed with each other
How many muscle fibers are innervated by a single axon?
10-2000
What is the muscle findings in an individual who has demyelination and remyelination?
The motor units are multipled from a single motor unit
What are types of axonal degeneration
Peripheral neuropathy
- Classic Wallerian Degeneration: Injury of vascular disease
- Distal axonopathy: Systemic meta disease, toxins, some genetic disease
Starts distal because of how metabolic toxics hit the periphery first
Demyelination/Remyelination
-Inflammation, toxins, some genetic diseases
What are some Ischemic neuropathies?
Cause axonal degeneration
Vasculitis (PAN)
Collagen Vascular diseases
Paraneoplastic Microvasculitis
Diabetic symmetrical sensorimotor neuropathy
What are the steps of axonal degeneration in a crush injury?
Schwann cells distal to injury dye and demylinate
Macrophages come and clean up the debris
Proliferation of schwann cells back in to myelinate the axon
Regenerated axon
What is seen in vasculitis?
Fibrinoid necrosis of the vessel wall
In vasculitic neuropathy what occurs to the axons?
They are preferentially hit, due to the blood supply some of the neurons may be spared
-Fascile to Fascicle variation in degree of axon loss
What is diabetic neuropathy?
A axonal degeneration due to acquired metabolic/toxic neuropathy
Predominated by axonal degen with some regen
Often has ischemic componenet
Endoneural microvascular thickening: ischemia
How can you tell a loss of axon density?
The axonal loss is seen as less dark areas in an LFB stain
What is a demyelinating neuropathy?
Pattern is segmental demyelination
What is the etiology of demyelinating neuropathy?
Inflammatory (immune-mediated)
- Guillain-Barre Syndrome or Acute inflammatory demyelinating polyradiculoneuropathy
Toxins
Some genetic diseases, CHARCOT TOOTH DISEASE
What is the clinical presentation of GBS?
Ascending paralysis
Involve resp muscles sometimes
Slowed conduction velocity
Elevated CSF protein
What type of inflammation is seen in GBS?
Endoneurial and perineurial
Lymphs, Macros»»> plasmas
Segmental demyelination
Some dmg to axons, in severe disease
Remyelination is seen: THINNER SHEATH
How do you see segmental demyelination?
Teased fiber preparation
Variation in myelin sheath thickness and internodal length
What is seen around a naked neuron?
Myelin Debris surrounding a naked axon
What is Charcot-Marie-Tooth Disease
Most common hereditary periphearl neuropathy
Progressive muscular atrophy of CALVES; weak
Genetically heterogeneous
Demyelinating neuropathy: Repetitive demyelination and remyelination
Pathy:
Thin myelinated axons
Hypertrophic ONION BULB neuropathy
What causes onion bulb neuropathy?
Chronic demyelination and remyelination
Concentric rings of Schwann cell processes
What is seen in normal muscle biopsy?
Frozen section shows peripheral nuclei
What is seen in normal muscle biopsy?
Frozen section shows peripheral nuclei
What is the content of a type 1 muscle fiber?
Sustained force, SLOW TWITCH
Color: Red
Lipids: Abundant
Glycogen: Scant
Enzyme content: NADH Dark, ATPase light (ph 9.4)
What is the content of a type 2 muscle fiber?
Action: sudden movement, purposeful
Enzymes: NADH (light), ATPase (Dark) different stain than type 1, how to distinguish
Lipids: Scant
Glycogen: Abundant
Physiology: Fast-twitch
Color: White
What color are type two muscle fibers in ATPase stain (9.4)
Dark
What color are type 1 muscle fibers in ATPase stain (9.4)
Light
What are neurogic muscle diseases?
Motor neuron disease:
- ALS
- Spinal muscular atrophy
Peripheral neuropathy
NMJ
-Myasthenia gravis
What are myopathic muscle diseases?
Dystrophy
-Duchennes
Inflammatory
-Polymyositis
Metabolic
-Storage diseases
Congenital
-Centronuclear myopathy
What are clinical features of a neurogenic muscle disease?
Site: DISTAL
Pain/tender: NONE
Fasciculations: Present
Serum Enzymes: Normal
EMG: Fibrillations potential
Nerve conduction: Variable
What are clinical features of myogenic muscle disease?
Site: Proximal
Pain/tender: Variable
Fasciculations: Absent
Serum Enzymes: Elevated (CK)
EMG: Polyphasic potential
Nerve conduction: NOrmal
What are the histological differences between neuropathy and myopathy?
Atrophy
- Neuropathy: Angular fibers, Grouped
- Myopathy: Rounded fibers, scattered
Neuropathy: Target fibers
Myopathy: Fiber necrosis, inflammation, internal nuclei, endomysial fibrosis
Where are angulated fibers seen in neuopathy?
Grouped
What happens after regeneration in neuropathy?
The muscle fibers are in large groups
What causes duchennes muscular dystrophy?
A mutation in the dystrophin gene
Cytoplasmic protein that anchors to the extracellular action
What is seen in early muscular dystrophy?
Myocyte necrosis
Atrophy and hypertrophy of next muscle fiber
What happens in late muscular dystrophy?
There is endomysial fiboris and fatty replacement
Atrophy and hypertrophy still seen
What is seen in myotonic dystrophy?
Autosomal Dominatn disease
Trinucleotide repeat disease
Path: Myopathic features with INTERNAL NUCLEI, occasional ring fibers
NEED GENETIC TESTING
What are some inflammatory myopathies?
Primary
- Polymyositis
- Inclusion body myositis
- Dermatomyositis
Secondary
-Other CT diseases,, immune processes, or infections
What are some inflammatory myopathies?
Primary
- Polymyositis
- Inclusion body myositis
- Dermatomyositis
Secondary
-Other CT diseases,, immune processes, or infections
What is seen in early polymyositis?
Inflammation (endomysial) and muscle fiber necrosis
What is seen in late polymyositis?
Regnerating muscle
Scarring fibrosis
Inflammation
What is seen in inclusion body myositis?
Gradual onset/progression
Male predominance
Proximal and distal weakness
Dysphagia in some
Lymphocytic inflammation, angular annd round atrophy
Autophagic “rimmed” vacuoles
What is the main histo feature to look for inclusion bodymyositis?
Rimmed Vacuoles
Abnormal filaments
What are some metabolic myopathies?
Glycogen storage diseases
- Type II (pompe disease): Def a1,4-glucosidase (acid maltase)
-Type V (McArdle disease): Def myophosphorylase (not lysosomal)
Lipid storage myopathy: (carnitine def)
MIto myopathy: Ragged Red fibers
What is seen on PAS of Pompe disease?
Lots of glycogen seen in vacuoles
What are some characteristics of mitochondrial DNA?
Maternally inherited
Circular
Heteroplasmy
What is mitochondrial heteroplasmy?
Each cell has hundreds of mitos
Each mitochondrion has 2-10 copies of mtDNA
Each cell has thousands of mtDNA
MItosis, mitos are randomly distributed
If abnormal mtDNA it will be different in each cell
What is the hallmark of mito myopathy?
Ragged red fibers
Paracrystalline inclusions
