Page 312 - Color Atlas Of Pathophysiology (S Silbernagl Et Al, Thieme 2000)

Demyelination
In myelinated nerves, the axon between two action potentials and low temperature favor
nodes of Ranvier (internodal segment) is sur- interruption of conduction because of decreas-
rounded by a myelin sheath (→ A). This is a ing sensitivity of the node R 2 (→ A1). Minor le-
precondition for saltatory conduction of the sions of the internodal segment can lead to
action potentials, i.e., the “jumping” propaga- slowing of conduction, because it can no lon-
Systems tion of excitation from one nodal constriction ger jump across nodes and the next node has
to be depolarized to its threshold before the
(R 1 ) to the next (R 2 ). The internodal segment it-
excitation is passed to the afternext nodes
self cannot generate an action potential, i.e.,
(→ A2). The resulting slowing may not be the
depolarization of the second node (R 2 ) is com-
Neuromuscular and Sensory node (R 1 ). However, the current is usually so persion of the signal may occur. Lastly, the
same in different fibers, so that temporal dis-
pletely dependent on the current from the first
strong that it can even jump across the nodes.
damaged site may itself trigger action poten-
Nevertheless, on the way along the inter-
tials, especially when the axon has concomi-
nodal segment the amplitude of the current
tantly suffered spontaneous damage or is un-
will diminish. First of all, the membrane in
der mechanical pressure (→ A3); excitation
can jump across two neighboring damaged
the internodal segment must change its polar-
ity, i.e., the membrane capacitance must be
nerve fibers (ephaptic transmission; → A4), or
Genetic defects of the myelin-sheath pro-
(→ A, green arrow). Secondly, current can also
tein (e.g., protein O [P 0 , of peripheral myelin
escape through individual ionic channels in
10 discharged, for which a current is needed conduction may run retrogradely (→ A5).
the axonal membrane (orange arrow). How-
protein 22 (PMP 22)]) or of gap junctions in
ever, myelination of the internodal segment the Schwann cells (connexin 22) lead to cer-
causes the membrane resistance (R m ) to be tain hereditary peripheral neuropathies (Char-
elevated and the capacity (C m ) of the mem- cot–Marie–Tooth syndrome, Dejerine–Sottas
brane condensor to be reduced (→ A, left). syndrome, Pelizaeus–Merzbacher disease).
The resistance of the axonal membrane of The most important demyelinating disease
the internodal segment is very high because is multiple sclerosis (→ B). It is more common
of the low density of ionic channels there. Fur- in women than men, familial aggregation
thermore, the perimembranous space is insu- sometimes occurs, and it has a higher inci-
lated by a layer of fat from the free extracellu- dence among carriers of HLA3 and HLA7. It is
lar space. The low capacitance of the conden- an autoimmune disease that may be triggered
sor is due to the large distance between the in- by a viral infection and is characterized by de-
terior of the axon and the free extracellular myelinating inflammatory foci (→ B1). The
space as well as the low polarity of the fatty typical feature of multiple sclerosis is the tem-
material in the space between them. porally unrelated occurrence of completely
Demyelination (→ A, right) can be caused by different neuronal deficits, caused by lesions
degenerative, toxic, or inflammatory damage in different parts of the brain. Some of the le-
sions may partly regress when the local in-
to the nerves, or by a deficiency of vitamins B 6
or B 12 . If this happens, R m will be reduced and flammatory process has subsided and the
C m raised in the internodal segment. As a re- nerves (in the case of intact axons) have been
sult, more current will be required to change remyelinated. The example in B2 illustrates
the polarity of the internodal segment (green that at first there is a fully reversible loss of vi-
arrow) and, through opening up the ionic sion due to a damaged optic nerve (→ p. 326),
channels, large losses of current may occur (or- followed by a partly reversible sensory loss
ange arrow). when the sensory tracts of the spinal cord are
If, after the losses in the internodal seg- affected (→ p. 318). Finally, ataxia sets in when
ment, the current generated at R 1 is not ade- the cerebellum becomes involved (→ p. 316).
quate to depolarize R 2 to the threshold level,
302 excitation is interrupted, even though the
axon is completely intact. High frequency of
Silbernagl/Lang, Color Atlas of Pathophysiology © 2000 Thieme
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