PATHOPHYSIOLOGY OF NERVE

Dr. Ayisha Qureshi

Professor & HoD
MBBS, MPhil
 Objectives
By the end of the lecture, students should be able to:
• Explain the effects of cutting a mixed nerve.
• Describe the process of degeneration and
regeneration of nerve.
• Explain the pathophysiology and symptoms of
Multiple Sclerosis (MS).
EFFECTS OF CUTTING A MIXED
NERVE:
What happens when you cut a mixed nerve?
1. LOSS OF MOTOR ACTIVITY: (All the changes listed below are
observed in muscles with the affected motor nerve.)
• Muscle becomes paralyzed.
• Muscle becomes flaccid (NO TONE).
• Muscle shows rapid loss of mass (WASTING).
• Muscle starts showing the ERB’S REACTION OF DEGENERATION
(altered response of the muscles to electrical stimulation seen
after loss of motor supply)

2. LOSS OF SENSATIONS:
• Loss of sensation in the area supplied by the affected sensory
nerves.

3. LOSS OF AUTONOMIC NERVE ACTIVITY:

• Area becomes blue & cold.
• Activity of the sweat glands is lost.

4. LOSS OF TROPHIC ACTION: (growth-promoting action)

• Atrophy (loss of mass & wasting) of the muscles that were
supplied by the motor nerves.
Degeneration is the loss of functional activity and trophic action in an
injured/ damaged neuron.
The loss of one neuron from a pathway can have drastic consequences
for the entire pathway!!

DEGENERATION & REGENERATION

OF NERVE FIBRES
How can the nerve fibers be damaged?
Nerve fibers may be damaged by being severed or crushed (as
during a traumatic event, such as a vehicle wreck, a gunshot
wound, or a diving accident) or by being deprived of their blood
supply (as during a stroke).

What happens when the nerve fiber is damaged?

When damaged, the affected axon is unable to conduct action
potentials.
If the cell body dies when a neuron is injured, the entire neuron
dies. If the cell body is intact and only the axon is severed, most
of the neuron survives.
 DEGENERATION:

When a nerve fibre is cut or severely crushed,

degenerative changes take place at 3 levels:

1. NERVE CELL BODY

2. Central/ Proximal stump: It is called RETROGRADE
DEGENERATION:.
3. Distal stump: It is called WALLERIAN DEGENERATION (also
called Secondary Degeneration)
 1. Changes in the nerve cell body:

• Cell body swells.

• Nissl granules undergo dissolution. (CHROMATOLYSIS)
• Nucleus is pushed to one side.
• Mitochondria, Golgi apparatus, ribosomes &
lysosomes show structural changes.
• If the axon is cut quiet close to the cell body, the
neuron may die....
 2. RETROGRADE DEGENERATION
Retrograde Degeneration is the degeneration that occurs in
the central or proximal segment of an injured neuron.

• Degenerated area may extend upwards for one or more

nodes.
• The degenerating area swells as substances carried into the
axon by axonal transport accumulate.
• Chemical factors produced by Schwann cells near the injury
site move by retrograde transport to the cell body, carrying
the information that injury has occurred.
• Degeneration my be followed by regeneration (if this part is
still attached to the cell body).
• If the area of degeneration is extensive or very close to the
cell body, the cell may die.
 3. Wallerian Degeneration?

Wallerian degeneration is an active process

of degeneration that results when a nerve fiber is
cut or crushed and the part of the axon distal to
the injury (i.e. farther from the neuron's cell
body) degenerates.
 REGENERATION:
Regeneration of injured nerve fibres refers to the regrowth or repair of
nervous tissues, cells or cell products.
It will take place in 2 cases:
1. If the injury was slight and/ or away from the cell body.
2. If the injured nerve fibre was part of the PNS. Cut axons in the peripheral
nervous system (PNS) can regenerate, whereas those in the central
nervous system (CNS) cannot.

WHAT HAPPENS:
• The nissl granules reappear & the nucleus resumes its central position.
• Full recovery may take up to 3-6 months (myelination takes up to 1 year to
complete).
• The endoneural tube is formed by the Schwann cells themselves. This tube
guides the regenerating nerve fibre to its proper destination.
• At the beginning of the process, axon in the central end of the cut nerve
fibres elongate & give rise to large no. of fibrils that enter into the endo-
neural tube.
 NO REGENERATION IN CNS:
• Regeneration DOES NOT take place in optic nerve and in the
CNS due to the following reasons:
1. The endoneural tubes are absent in the CNS as there are no
Schwann cells present; so the regenerating axons cannot be
guided.
2. The oligodendrocytes cannot aid in regeneration as they
secrete growth inhibiting factors instead of the growth
promoting factors (unlike the Schwann cells).
3. The activity of the astrocytes results in the formation of scar
tissue.
Multiple Sclerosis (MS) is an auto-immune disease in which nerve
fibers in various locations throughout the nervous system lose
their myelin. This leads to disruption of nerve impulse conduction.

MULTIPLE SCLEROSIS
GOING, GOING, GONE…..
 Multiple Sclerosis:
Cause:
Exact cause is still unknown. It is suspected that a foreign agent such as a virus
alters the immune system so that the antibodies of the immune system mistakenly
attack and destroy Schwann cells, thus also destroying the myelin sheath. The
destroyed part is replaced with scar tissue. When myelin sheath is destroyed, the
nerve impulses travelling along the nerve fibers slows down. When more and more
nerves are affected, the person experiences interference with functions that are
controlled by the nervous system such as speech, memory, vision, walking etc.

Signs & symptoms:

Patchy destruction of myelin in the CNS→ slow & abnormal conduction of the nerve
impulses in the neurons
↓
1. Visual disturbances
2. Tingling & numbness
3. Muscle weakness & Fatigue
4. Gradual paralysis
5. Bladder & bowel problems
Myelin destruction in MS
 DIAGNOSIS & TREATMENT
DIAGNOSIS
Physicians take detailed history and
performs complete physical and
neurological examination.
• MRI
• Nerve Conduction Studies
• Cerebrospinal fluid exam (spinal tap,
lumbar puncture)
TREATMENT
• Debilitating disease but not fatal. The
quality of life is affected…. Death may
occur when the paralysis reaches the
respiratory muscles and the person
cannot breathe.
• No treatment as yet.
• Only symptomatic treatment.
1. Immunosuppressive therapy: as
autoimmune disease so you try to
suppress the immune system to
prevent further damage.
2. Corticosteroids
3. Alternative therapy: as homeopathy,
ayurvedic treatment etc.