Peripheral Nervous System and Skeletal Muscle ▪Perimysium: groups muscle fibers into primary

and secondary bundles (fasciculi)

▪Functional unit: motor unit ▪Epimysium:envelops single muscles or large
▪Motor unit consists of: groups of fibers
o Lower motor neuron: ant horn of spinal
cord/ cranial nerve motor nucleus in Pathology
brainstem
o Axon PNS
o Muscle fibers ▪Target of insult: Schwann cels or axon
▪Lower Motor Neurons: arranged somatotopically ▪Diseases thatGen Path – Dr. Yabut
affect Schwann cells:loss of
▪Muscles with highly refined movements (eg eye): myelination
PNS or segmental
and demyelination
Skeletal muscle
neuron-to-muscle fiber ratio = 1:10 ▪Primary involvement of neuron and its axon:
Feb 02, 2008
▪Muscles with coarse and stereotyped movements axonal degeneration  may be followed by axonal
(calf) = 1:1800 regeneration and reinnervation of muscle

Normal Peripheral Nerve Muscle

▪Principal structural component: nerve fiber
▪Nerve fiber = axon + Schwann cells + myelin
sheaths
▪Nodes of Ranvier: between Schwann cells
▪Myelin Protein Zero (MPZ): major protein of myelin
▪3 major connective tissue components of PN:
o Epineurium: encloses entire nerve
o Perineurium: encloses each fascicle
o Endometrium: surrounds indiv nerve
fibers
▪Perineurial barrier, blood-nerve barrier, nerve-
cerebrospinal fluid barrier: regulates nerve
microenvironment
Normal Skeletal Muscle
▪Muscle fibers, myocytes are syncitia derived from
the fusion of a contiguous column of indiv embryonic
cells  multinucleated
▪Satellite cells: stem cell population located adjacent
to sarcolemma; covered by basement membrane
▪Myofilaments: form the contractile apparatus of
myofibrils
▪Myofibrils: consist of sarcomeres
▪Sarcomeres:
o Actin: longitudinally directed thin
filaments, binds to dystrophin
o Myosin: thick filaments
o Z-bands (α-actinin): perpendicular to
sarcomere
▪T-tubule system: calcium release during excitation
▪2 major types of fibers:
o Type 1: “one slow fat red ox”
o Type 2: rich in glycolytic enzymes,
involved in rapid, phasic contractions
▪All fibers of a single unit are of the same type
▪Muscle spindles: fusiform structures that respond
to stretch in muscles  role in maintaining tone
▪Endomysium: surrounds indiv muscle fibers
▪Denervation atrophy: due to loss of axons
▪Primary abnormality of muscle fiber: myopathy
Segmental Demyelination
▪Occurs when there is dysfunction of the Schwann
cell
▪Guillain-Barre syndrome
o Damage to myeln sheath (hereditary
motor and sensory neuropathy)
o There is no primary abnormality of the
axon
o The denuded axon provides a stimulus
for remyelination
o Newly formed myelinated internodes
are shorter than normal and several
are required to bridge the
demyelinated region
o New myelin sheath is thin in proportion
to diameter of the axon
o Sequential episodes of demyelination
and remyelination  onion bulb
appearance
Axonal Degeneration and Muscle Fiber Atrophy
▪Axonal degeneration: result of primary destruction
of the axon with secondary disintegration of its
myelin sheath
▪Wallerian degeneration: axonal injury occurs as a
result of a focal lesion (trauma, ischemia)  axon
breaks down, Schwann cells catabolize myelin and
engulf axon fragments, formation of myelin ovoids
▪Neuronopathy and axonopathy: axonal
degeneration is scant  only few fibers actively
degenerate at any given time
▪When axonal degeneration occurs, muscle fibers
w/in the affected motor unit lose their neural input
and undergo denervation atrophy (cells remain
viable)
▪Type specific Atrophy: atrophy of disuse (common
in type 2 fibers)
Nerve Regeneration and Reinnervation of Muscle
▪Regenerating cluster: multiple closely aggregated,
thinly myelinated small caliber axons  evidence of
regeneration (a slow process)
▪Reinnervation: occurs when axons belonging to an
unaffected neighboring motor unit extend sprouts to
reinnervate the denervated myocytes and
incorporate them in to the healthy motor unit

Reactions of the Muscle Fiber

▪Segmental necrosis: destruction of a portion of the
length of a myocyte
▪Vacuolation, alterations in structural proteins or
organelles and accumulation of intracytoplasmic
deposits
▪Regeneration
▪Fiber hypertrophy: in response to increased load