patho2test 3: Peripheral Nervous System mppt

Peripheral Nervous System

• Direct extension of the central nervous system that monitors and reacts to external stimuli
• Two components: autonomic nervous system (ANS) and somatic nervous system
• Autonomic nervous system (ANS):
  • Not regulated by conscious control
  • Helps maintain homeostasis
  • Automatically adjusts the activity of the sympathetic and parasympathetic nervous systems to match the body's needs
• Somatic nervous system:
  • Afferent (sensory) nerves: primarily come from sensory receptors and travel into the central nervous system
  • Efferent (motor) nerves: travel from the CNS to primarily muscle for motor activation

Components of Peripheral Nervous System

• Cranial nerves
• Spinal nerves:
  • Provide movement and sensation to a specific region of the body
  • Carry sympathetic, parasympathetic, motor, and sensory information

Sensory Receptors

• General sensation: light touch and vibration
  • Carried by the dorsal columns in the spinal cord
  • We adapt to these sensations more rapidly than heat and pain because they are carried by faster fibers
• Pain:
  • Highly subjective
  • Carried by the spinothalamic tract in the spinal cord
  • "First pain" - sharp, immediate, a "good" thing that acts as a warning signal to respond to a harmful stimulus
  • "Second pain" - delayed, longer-lasting sensation, chronic "bad" pain that comes from damage or pathology that remains even after the stimulus is gone
• Temperature:
  • Carried by the spinothalamic tract in the spinal cord
  • Interestingly, both pain and temperature can be sensed by the same receptors
  • Extreme heat or extreme cold can trigger the sensation of pain

Diabetic Peripheral Neuropathy

• Most common complication of diabetes
• Duration and severity of hyperglycemia and metabolic syndrome are the 2 most important risk factors in patients with type 1 or type 2 diabetes
• Distal symmetric polyneuropathy:
  • Can involve sensory, motor, and autonomic neurons
  • Sensory neurons are more susceptible to damage than motor neurons because most sensory neurons are unmyelinated
• Pathophysiology:
  • Distal portions of long sensory axons degenerate
  • Ischemia due to microvascular damage from hyperglycemia
  • Buildup of advanced glycation end products (AGEs) contributes to oxidative stress and damages nerves
• Clinical manifestations:
  • Progressive loss of sensation
  • Negative symptoms (numbness, loss of balance)
  • Positive symptoms (tingling, pain)
  • Symptoms start distally in the toes and feet, and positive symptoms are usually worse at night

Guillain-Barré Syndrome

• Autoimmune destruction of the schwann cells surrounding peripheral nerves
• Post-infectious autoimmune neuropathy
• ~ 70% of patients have a preceding infection
• Campylobacter jejuni is a common organism that can trigger GBS
• Molecular mimicry:
  • One of the main mechanisms through which infectious (or chemical) agents produce an autoimmune response
  • Similarities between foreign peptides and "self" peptides cause activation of T/B cells
• Clinical manifestations:
  • Symmetric, ascending weakness is the hallmark, typically begins in the legs
  • Numbness
  • Tingling
  • Weakness that can progress to paralysis
  • Symptoms generally progress over a period of 2 weeks
• Diagnosis:
  • Typically, a clinical diagnosis (preceding infection with characteristic presentation, etc.)
  • EMG and nerve studies can be helpful if unclear
• Treatment:
  • Start with supportive care
  • Monitor for progression
  • Monitor respiratory status
  • Monitor blood pressure and heart rate
  • DVT prophylaxis
  • Pain control
  • Main medication for GBS is IVIG (Intravenous immunoglobulin)

Carpal Tunnel Syndrome

• Common condition causing numbness, tingling, and pain in the hand and forearm
• Really an anatomic issue, not a "physiologic" one
• Median nerve is compressed as it travels through the wrist (the carpal tunnel)
• Compression of the median nerve leads to ischemia and mechanical disruption
• Presents as pain, paresthesia, and less commonly, weakness in the median nerve distribution
• Traversing the carpal tunnel:
  • The carpal tunnel is formed by the transverse carpal ligament superiorly with the carpal bones inferiorly
  • As the median nerve crosses the wrist, it passes through the carpal tunnel along with nine flexor muscle tendons

Charcot-Marie-Tooth Disease (CMT)

• Group of hereditary disorders that cause peripheral neuropathy in both sensory and motor neurons
• Often abnormalities in the axons or production/maintenance of the myelin sheath
• The "demyelinating" disorder of the peripheral nervous system
• Over time, neurons degenerate leading to muscle weakness/atrophy
• Affects longer nerves first
• Symptoms typically begin in the feet/lower legs and then the fingers, hands, and arms
• High arched feet due to muscular imbalance (from atrophy)

Myasthenia Gravis

• Autoimmune disorder of the neuromuscular junction that manifests as progressive skeletal muscle weakness and fatigability
• Pathogenesis:
  • The body makes autoantibodies to the acetylcholine receptor
  • The antibodies bind to the receptor and interfere with neurotransmitter function
  • There are fewer acetylcholine receptor sites available when an action potential arrives
• Clinical manifestations:
  • Generalized proximal limb weakness and fatigability with repeated activities → this improves with rest
  • Drooping of eyelids (ptosis)
  • Double vision (diplopia)
  • Flattened smile
  • Difficulty chewing and/or swallowing
  • If severe: difficulty breathing
• Treatment:
  • Acetylcholinesterase inhibitors
  • Block the enzyme that's breaking down Ach = more Ach around to bind to receptors that are still functional
  • It is also used to diagnose MG by showing improvement of muscle weakness with use
  • Immunosuppressants like corticosteroids
  • Plasmapheresis to remove autoantibodies from the blood
  • IV immunoglobulin: give other antibodies that block the anti-AChR antibodies