bios e-162b undergraduate review: neuropathophysiology ii and iii october 4, 2010
TRANSCRIPT
BIOS E-162B Undergraduate Review:
Neuropathophysiology II and III
October 4, 2010
HOT!
HOT!
Afferent pathway (sensory)
The CNS: interneurons, convergence, and divergence
HOT!
HOT!
Via association cortex
Efferent Pathway (motor)MOVE!
SLOW AND STEADY!
REFINE!MOVE!
How movement occurs:The neruomuscular junction
1. Action potential reaches motor neuron terminal 2. Ca2+ enters
3. Vessicles of acetylcholine bind to synaptic cleft
4. Acetylcholine binds to nicotinic receptors on motor end plate
5. Signal to muscle to contract
6. Acetylcholinesterase breaks down acetylcholine, reuptake of acetylcholine into presynaptic neuron
Drugs/Toxins
Curare
• Acts as an antagonist for Ach binding
Botulinum toxin
• Cleaves docking proteins off of the Ach-containing vessicles
Organophosphates
• Inhibit acetylcholinesterase
Strychnine
• Antagonist of the inhibitory neurotransmitter glycine
Tetanus
• Inhibits release of inhibitory transmitter GABA from pre-synaptic nerve terminals in CNS
Diseases
Genetics Injury/ Toxicity
Infection Immune
Myathenia gravis
Parkinson’s
MS
ALS
Guillain-Barre
Myathenia gravis
• B-cells make antibodies that bind to and block Ach nicotinic receptors
• Progressive muscle weakness, usually first at eyes
• Respiratory failure most life-threatening
• Treatment: mechanical ventilation, neostigmine, thymectomy
Parkinson’s Disease
• Loss of dopamine-producing neurons in a region of the basal ganglia
• Side effect of treatment drugs: schizoid behavior
Multiple sclerosis
• Demyelinization of CNS neurons
• Initially present with blurred or double vision
• Muscle weakness, loss of coordination/balance, spasticity, fatigue, paresthesias
• Tysabri appears to be an effective treatment, but with “black box” warning
Amotrophic lateral sclerosis (ALS)
• Loss of upper and lower motor neurons
• Muscle weakness, cramping, atrophy• Respiratory failure, choking• “Charcot ALS” (lower motor neurons first)
vs. “bulbar onset ALS” (upper motor neurons first)
• Riluzole slows progression of ALS, Baclofen relieves muscle spasticity
Guillain-Barre syndrome
• Demyelination of peripheral nerves
• Weakness of respiratory muscles, paresthesia
• Most people recover within one year
Other CNS injuries
Traumatic brain injury
• Damage to nerve axons, leads to loss of axon terminals
• Excitotoxicity and oxidative stress from release of neurotransmitters from damaged cells (esp glutamate)
• Hemorrhages, bruising, pressure from swelling
• Permanent damage, usually
Spinal cord injury
• From trauma, but also from release of neurotrasmitters (esp glutamate)
• Damage depends on site of injury:
SCI II
• Consequences– Loss of temperature control– Brown-Sequard’s syndrome– Pressure wounds– Autonomic dysreflexia
Stroke
• Protection– Circle of Willis– Myogenic autoregulation
• Ischemic (~85% of strokes)– Portion of blood flow to brain is blocked (by
thrombus or embolus)– Ischemic penumbra
• Hemorrhagic (~15% of strokes)– Blood vessel ruptures