PNS Flashcards
- PNS - Neuron
Structure - cell body, dendrites (receives/transmits message), axons
- Transmission -
a. action potential
b. unmyelinated and myelinated (saltatory conduction)
c. AP generated by potential on dendrite or cell body
d. Graded membrane potential types:
stimulatory (influx of na or ca) and inhibitory (influx of cl)
d. synaptic integration- sum of all gm potentials>AP initiated
e. nerve terminal - impulse reaches axon terminal>depolar>influx ca >neurotrans release by synaptic vesicles
- Axonal transport from cell body to synaptic ending, can be retrograde
- neural cleft
- Neurotransmitters - excitatory (acetylcholine and glutamate -brain) and inhibitory (GABA common, others, monoamines- norepi,seratonin, dopamin, histamine)
- !Support cells- Schwann cells wrap around axons to form myelin sheath. Gaps called nodes of Ranvier. Support unmyelinates axons.
- PNS neuron types
- Lower(somatic) motor neurons from spine to skeletal muscle.
a. alpha motor neurons (innervate)
b. gamma MN - innervate spindles - Neuromuscular junction
a. terminal portion of mn, synaptic cleft, and end plate muscle region.
b. no inhibitory synapses exist on skeletal muscle fibers.
- PNS Receptor types
- Cholinergic
a. nicotinic (skeletal muscles and postganglionic neurons)
b. muscarinic - cardiac, smooth muscles, glands - Adrenergic - alpha and beta adrenergic
- Normal skeletal muscle PNS
- Type I - slow twitch (red) - dependent on fat catabolism and tonic contractions wt bearing
- Type II fast twitch fibers (white) - high dependence on glycogen, rapid phase contractions
c. motor neuron determine fiber type - Muscle spindles respond to stretch and maintain muscle tone
- Neuronal Injury PNS
Injury to:
- myelin sheath>segmetnal demyelination - mylein engulfed by schwann cell and macrophages, inferior myelin replacement>further axonal injury
- Schwann cell - cell is repaired/replaced
- Axonal - destruction secondary to myelin sheath disintegration>axonal degeneration
a. Wallerian degernation - !deg of axon distal to injury - new terminal sprouts from proximal segment ans uses schwann cell sheath if possible
b. injury above hilium >axon death - Denervation atrophy
a. decrease in muscle cell content (atrophy or weakness)
b. receptors in denervated fibers spread across muscle membrane(spontaneous discharge fascicluation or spon contraction fibrillations) - Reinnervation - proximal axons extend sprouts to reinnervate denervated myocytes
a. may lose fine motor abilities
b. ! assume muscle fiber type of innervating neuron
- Neuronal Injury - Cranial nerves
Axonal injury
a. Wallerian degeneration followed by sprouting
b. sprouting guidance lacking
c. neuronal loss not replaced.
- Mononeuropathy
sensory s/s and deficits assoc with single peripheral nerve
- Polyneuropathy
- sensory s/s and deficits assoc with single peripheral nerves
- symmetric sesnory loss affects legs more than the arms
- Radiculopathy*
- sensory s/s along a dermatome
2. assoc with spinal nerve or nerve root diseases
- Shingles
Etio:
Reactivation of chicken px virus in sensory nerve ganglia of spinal cord d/t decreased immunity
Patho:
inflamm response to viurs > neuronal injury and loss
Clinic manif:
a. vesicular skin eruption via dermatomes
b. radiculr pain, burning, tingling
c. risk for post herpatic neruologia
- Guillian-Barre Syndrome
or Acute inflammotory neuropathy believed to be a immunologic reaction directed spinal nerve root and peripheral nerve myelin
a. incidence 2-3/100K
b/etio: viral influenza-like illness, CMV, epstein -bar
c. ! patho-
1. Tcellmediated autoimmune response vs myelin
2. lymphocyte and macrophage infiltration
3. segmental demyelination by macrophages
4. dcreased nerve conduction velocity or comltet loss
5. inflamm respose/cytoking releae damage
Clinical Mnaif-
a. ascending paralysis
2. parethesias and pain
3. !possible autonomic instability
5. !elevation of CSF protein level
6. prolonged recovery
- Botulism
Etio:
Toxins bind to peripheral nerve endings
Patho:
Block synaptic release of acetylcholine
Clinic manif;
a. weakness, blurred vision
b. diplopia
c. dyphasia (M p169)
d paralysis of respiratory and skeletal muscle
- Myasthenia Gravis
autoimmune d/o of NM transmission
Etio:
genetic predisp or thymic abnormalities
Patho: p160
- Ab IgG vs postsynaptic nicotinc ACh receptors(muscle) lead to loss of functional AChR
a. bind receptor on end plate and block activation
b. immune mediated destruction of ACh receptor (AChR) - Decreased muscle contraction
a. decremental response with repeated stimulation
b. small motor units most often affected (ocular)
Clinic manif:
a. weakness 1st noted in extraocular muscles (ptosis and diplopia
b. flucturating weakness and gatigability
c. improvement after rest and administration of acetyl-cholinesterae inhibitor or
acetylcholine
d. Dx based on response to Tensilon, Ab presence, and repetitive sing-fiber EMG.
e. Histology- !loss of post synaptic recept at motor end plate, circulating Ab to AChR, scattered lyphocytes at motor end plates
- Post polio syndrome
Etio: prev virl polio infection
Patho:
nueronal fatigue and new neuronal loss
a. orig disease causes nerve cell death
b. unaffected neurons innervate orphaned muscle
c. overuse of enlarged motor units fatigue neuronal function with ^ metabolic demands > slow deterioration of motor units> terminal malfunction and permanent weakness
Clinic Manif
a. new muscle weakening
b. muscle atrophy
c. pain and fatigue
d. s/s age related changes
- Duchenne muscular dystrophy- most common, most severe
Etio: 2/3 familiar x-linked
et 1/3 new mutation
Patho:
- Defect stops the formation of dystrophin
- !Dystrophin anchors sarcomere to sarcolemma cell membrane in myocytes (K, 802) > tearing apart during contraction.
- regenerated defective mescle fibers perpetuate the process
Clinic Manif
1. s/s begin age 2-5, wheelchair by 7-12, 25% live to age 21.
- !Muscle weakens postural muscles (pelvic and shoulde) et not sit or walk early with ^clumsiness and falling
- muscle atrophy,> severe wasting, contractures, heart failure
- Assoc iwth cognitive impairment
- *Lab- ^CK,
- !Western blot shows absence of dystrophin. hytology- deg/necrosis of muscle fibers replaced by fat and connective tissue
- Becker muscular dystrophy- less severe
Etio: genetic/familial x-linked
Patho:
a. !defect diminishes amount of dystrophin and molecular wt
b. allows anchorage of muscle to membrance but alterations impair long term function
Clinic Manif:
a. ! occurs late childhood or adolescence with slow progression
b. PROXIMAL muscle weakness, cardiac muscle disease
c. !western blot reveals altered dystrophin size
- Myotonic dystrophy
sustained involuntary contraction of a group of muscles with delayed relaxation
Etio:
genetic -autosomoal dominant
Patho:
a.! defect cause nucleotide (CTG) repeats on the gene
b. ! succeeding gnerations, # of repeats ^ and s/s appear at younger age.
c. dfect influences level of protein inmuscle altering fiber structure and function
Clinic Manif!:
a. invol contraction with delayed relaxation
b. weakness of DISTAL extensor muscles (hands/feet)
c. muscles of face atrophy
d. histology - fiber vary in size, degen, necrosis, phagocytosi of muscle fibers.
ONLY DYSTROPHY TO SHOW PATHO CHANGES IN MUSCLE SPINDLE AS WELL.
- Thyrotoxic Myopathy
- Acute or chronic PROXIMAL muscle weakness stemming from hyper or hypo thryroid disease.
- Protein catabolism and altered metab>aletered muscle function
- HIstology - myofiber necrosis, ^ # of nuclei, regeneration and intersittial lymphocytosis
- Ethanol Myopathy
- Heavy or binge drinking> muscle tissue breakdown>rhadomyolysis (striated muscle fiber dinsintegration with myoglobinuria
- sudden onset of muscle pain, swelling, and proximal muscle weakness
- Histology - myocyte swelling, necrosis, and cell phagocytosis, ner denervation
- Steroid myopathy
- From Cushing syndrom or therapeutic adm of steroids
- R/t decreased protein synthesis, ^ protein degradation, alteration in CHO met, and decreased sarcolemma excitability.
Corticosteroids are catabolic - PROXIMAL Muscle weakness and atrophy
- Spinal Cord
- 31 pairs of nerves
- contain both sensory and motor neurons which supply and receive info. Cell bodies located in plexus/ganglia near sc.
- relfex arc directly stimulates motor neuron within spinal segment
- Motor systems - upper motor neurons
Include cerebellar, pyramidal and extrapyramidal. m p149
- Pyramidal
a. corticospinal tract = cell bodies originate in cerebral cortex, down brain and cord w.o synasping in the basal ganglia (synapse with alphamotor neurons, responbile for voluntary FINE motor mvmt.
b. Corticobulbar - cell bodies origiante in cerebral cortex down brainstem where synapse with motor nuclei of cranial nervers (responsilbe for fine motor mvmt and control FACE and tongue. - Extrapyramidial - cell odies originate in different parts of brains and synapse at basal ganglia. Neurons descend down brain and spinaltract, regulates vol mvmt, INVOL Gross mvmt, maintains posture.
- Somatosensory Pathways
- Fibers conduct sensations of position/vibraton/fine touch thru dorsal column and also ascend>medulla>thalamus>cerebral cortex
- Fibers conduct sens of pain and temp to dorsal horn>synapse with secondary neuron in cord> cross opposit side>ascen in lateral spinothalamic tract>thalamus>cortex
- Fibers conduct sens of crude touch/pressure pass dorsal horn>synapse with secondary neuron> cross opposite side>asend anterior spinothalamic tract>thalamus>cortex
Fine distinctions made in cortex, only crude in thalamus.
- Pain - Physiology
Nociception (conscious pain)
- transduction
a. nociceptors (bare sensory nerve endings) respond to nocious, mechanical, thermal, and inflam mediators to elicit AP
b. Inflam mediators include bradykinin, PG, substand P, leukotrienes, serotonin - transmission
a. Pain travels from A and C peripheralnerve fibers (1st order) to dorsal horn in spinal cord
(A-delta fibers are myelinated>fast conducting. C fibers unmeylinated>slow)
b. Synsapse with secondary neuron in cord>corss oppos side
c. ascend lateral spinothalamic and spino reticular tract>reticular formation>thalamus
d. synpase with 3rd order neurons to carry info to other brains parts and cerebral cortex. - Pain perception occurs in brain
a. reticular system - sends info to limbic system and integrates autonomic response
b. thalamus - localizes pain
c. somatosenoryt cortex characterizees and interprets pain
d. limbic system -emotional and behaviroal response to pain - Pain modulation mp155
a. inhibiting pain transmission pathway by: cortex (descending pathway to thalamus and periaqueductal gray matter-located in mdbrain et sends signals to midline raphe nucleus in medulla)
Midline raphe nucleus inmedulla sends signals down cord and synapse in dorsal horn to inhibit excitatory pain neurotransmitters.
Dorsal horn - “gatekeeper” receives inhibitory signals from raphe nucleus, pain modulated by stimulation of large sensory afferents fro skin that lbokc impulse>block pain. - Pathway neurotransmitters- endorphins, enkephalins, dynorphins, seratonin, norepi, GABA