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
- Pain Pathophysiology
Abnormal pain processing
- Peripheral
a. nociceptor sensitization by enchanced response to noxious stim or newly acquired responsiveness to wider range of stim
b. damaged or diseased nerves (neuropathic paon produces abn painful sensations (dysesthiesias)
c. growth of axonal spouts
d. formation of ectopic foci which fire spontaneiously
f. upregulation of receptors - Central (at dorsal horn
a. sensitization of second order neurons are triggered by less timuli, augmented strength of stimulus(summation/windup) , prolonged discharge, spontaneous implulse activity
b. activation of additional neurons to conduct pain impulse
c. loss of inhibitory interneuron activity - Central (brain)
a. sensitization of 3rd order neurons,reorganization of neural connections, altered perception of pain.
Nociception is sustained in chronic pain
a. spontaneous self-sustaining neuronal activity
b. may also be secondary to neural inflamm, chronic nerve compression, lesions, down regulation or loss of modulation pathway
- Spinal Cord Trauma
Occurs from hyperextension, hyperflexion, vertical compression or rotation of spine
Patho:
a. central gray matter microscopic hemorrhages
b. whitematte axonal edema>impairs microcirculation
c. decreased perfusion>ischemia>myelin disruption>axon degeneration (maximal at injury site and two cord segments above and below)
d. inflamm response>cause futher ischemia and vasc damage
e. necrosis and scar tissue formation
Clinical manif:
a. spinal shock - normal activity of spinal cord ceases at and below level of injury et coplete loss of reflex function (skletal, bladder, bowel, sex fucn, thermal and autonomic control)
b. paraplegia or quadraplegia
c. autonomic dysreflexia - hyperactivation of SNS in response to noxious stimulation of sensory receptors below level of cord lesion.
- Herniated Intervertebral disc
Patho:
a. weakness and degeneration of annulus fibrosus and post longitudinal ligament cause bulging or protrusion
b. most herniations occur posterolaterally compromising spinal nerve root >pain (irritation/inflamm of dural membranes also cause pain)
c. Occurs commonly at L4-5 adn L5-S1
Clinical manif (depend on location)
a. pain radiates along dermatome with sudden onset or chronic pain
b. loss of sensation (pain,temp, touch) m p154 as laeral spinothalamic fibers
c. at risk for possible motor weakness from compression of lateral corticospinal tract
- Brown-Sequard Syndrom
- Occurs with traums or lesions that involve 1/2 of cord, usually cervical region.
b. loss of proprioception on same side as lesion
c. loss of pain, temp sensation on opposite side
d. loss of vol motor function from corticospinal tract on same side as lesion
- Syringomyelia (central cord syndrome)
a. cyst, tumor, or trauma which inuures the central gray matter of cord
b. loss of motor power and sensation at level of lesion (cervical cord lesions - across shoulders and upper arms)
- Protective structures of CNS
- ! Cranium
- Meninges
a. dura mater
b. arachnoid membrane and subarachnoid space
c. pia mater - ! CSF and ventricular system
a. produced by ependymal cell in choroid plexuses
b. CSF reabsorbed into the venous circulation through arachnoid villi - CNS blood supply - CO2 regulates blood flow in CNS
- BBB
a. tight junctions between the cap endo cell
b. encircling astrocyte feet
c. ependymal cell in choroid plexus control entry of substances from blood into CNS.
31 Neuroglia
Support cells of the CNS
- Astrocytes
a. provide nutitional support
b. regulate blood flow to provide O2 to neurons in need.
c. ! provide structural support to neurons
d. maintains bbb
e. responds to CNS injury by releasing cytokines, multiply in number, repairs tissue and forms scar tissue.
f. regulates EC concentrations of neurotransmitters and helps terminate neuronal responses to glutamate - Oligodendrocytes - wrap around axons to form myelin sheath
- Microglia -phagocytic cells of the brain, act as immune cells
- ICP
Etio:
- edema-^brain tissue vol
- Tumor - same
- hydrocephalus - ^CSF in ventricular system from impaired flow, reabsorp, or overprod of CSF
- HTN
- hemorrhage, vasodilation
Clinical Manif
- retinal edema
- decreased perfusion>ischemia>cell death
- tissue atrophy d/t compression and lack of circulation
- reflex ^ in BP to maintain perfusion
- Change in LOC d/t ischemia, altered neuronal conduction, compression of cortical structure or compresssion of ascending reticular activating system or other cognition pathyway
- herniation
- Vascular traumatic injury - hematomas
- Epidural - collection of arterial blood between dura mater and cranium et expands rapidly
- subdural hematoma - collection of blood between dura and arachnoid, venous blood et slower bleed.
- subarachnoid hemorrhage/intraparenchymal - blood escape into subarach space>meningeal irritation>disruption of CSF circulation/absorp>^rise in ICP.
Intraparencymal hemorrhage >tissue compression
- TIA
- Brief, reversible impairment of neurologic function d/t blood flow interruption
- s/s last seconds to hours
- neuronal cell death d/t ischemia or hypoxia (5-10 min or cortical neurons and 30 min for brain stem neurons)
- ^risk for reoccurrence( 30% at 3 mons, 60% at 6, 80% at year)
- Ischemic stroke
Definition- sudden onset of focal neurologic deficit that lasts at least 2 hrs d/t abn cerebral circulation.
Types:
A. Thrombotic
1. generally large arteries like internal carotid, mid cerebral artery, post. cerebral artery, basilar artery
a. atherosclerosis common cause
b. size, location, shape of infarct determined by modifying variable, esp adequate collateral flow.
B. Lacunar
a. microinfarcts involving small arteries
b. assoc with HTN, SM, atherosclerosis
c. clinically silent or produce significant motor or sensory defiticts
C. Embolic (large and small arteries)
a. emboli traveling heart, aorta, carotids>occlude middle cerebral artery (it carries 80% blood flow to hemispheres)
b. emboli traveling vertebral and basilar arteries>occlude basilar arteri, posterior cerebral arteries
Patho:
1. Nerve cells are damaged or killed by energy deprivation d/t ischemia
- At ischemic region edges, neurons die from excessive stim of glutamate receptors(also called neuronal excitotoxicity or glutamate toxicity m p179 !!KNOW)
a. Ischemia depletes brain tissue energy supplies > inhibits Na+K+ATPase>loss of normal ion gradient
b. ^ IC Na and ^EC K
c. ^ K deploarized nerve termianl>glutamate release from terminals
d. ^ EC glutamate >excessive stim of glutamate receptors (>^Ca influx causing sustained activation of enzymes>protein breakdown, free radical formation, lipid peroxidation, DNA fragmentation, nuclear breakdown in neuron et stimulates NO production).
e. sustained activation leads to cell death - receptor antagonists administered to reduce size of ischemic lesions. - Neuronal injury in brain
a. cell body shrinkage, disappearnce of nucleolus, loss of Nissl substance
b. injured axons undergo swelling and axonal transport disrupted (Wallerian degeneration followed by sprouting, guidance for sprouts lacking, neuronal loss not replaced)
c. inflamm response>vasodilation^ICP - Astrocyte activation -
a. undergo hypertrophy and hyperplasia
b. responsible for repair and scar formation> can become seizure focus - Micorglia activation -proliferation et function as phagocytes of CNS
- Hemorrhagic CVA
Etio:
- HTN (Charcot-Bouchard)
a. rupture of small intraparenchymal vessels
b. small vessels all common wihch supply basal ganglia, thalamus, pns, cerebellum - Aneurysm rupture or AV malformation or weak vessel
a. aneurysm - congenital (berry) most common
b. ! AV malformation - tangle of fragile, tortuous misshapen vessels
c. spontaneous from plt or coag d/o
d. cocaine and amphetamine use > rapid elevation BP or drug induced vasculitis
Patho:
a. hemorrhage>^ICP
b. inflam and edema>^ICP
c. secondary vasospasm from blood toxicity>ischemia
d. compresssion ischemia/neuronal cell death
- Consciousness and Cognition disorders
Structure/Func:
a. arousal - state of wakefulness in RAS
b. cognition - mediated by functional cerebral cortex
Etio of pathology:
- Destructive mechanisms
a. lesions in RAS
b. hemorrhages, ischemic infarctions, abscesses or tumors in cerebral hemisphere
c. deposition of neuritic plaques/neurofibrillary tangles, amyloid deposits, etc in brain tissue - Compressive mechanisms
- Metabolic-toxic mechanisms - substrate depletion, hypoxia, toxins, fluid and lyte imbalance.
- Psychogenic arousal alterations
- Seizures
Def: intermittent disturbance in cerebral function caused by abn synchronous dc of cortical neurons
Epilepsy - recurrent seizures
Patho:
- Epileptogenic focus - abn excitable area of brain
a. popn of pathologically excitable neurons (possible lower threshold for depolariz, ^permeability, or chronical state of partial depolar)
b. ^excitatory glutamate transmisson
c. diruption in the inhibitory system (GABA) - Spread of local dc
a. enhancement of excitatory stimuli- EC K accumulates around epileptogenic focus, ^ dc frequency in EF ^ CA influx > ^neurotransmitter release at excitatory synapses, in seconary epilepsy - sprouting of fibers from exc neurons
b. reduction in inhibitory stim - desensitization of GABA receptors with ^freq stim, in secondary epilepsy, loss of inhibitory circuits
3. synchronous dc - seizure (cx’d by sudden brief attacks of altered consciousness, motor activity, or sensory phenomena
40 MS
Def- autoimmune demyelinating d/o charac by episodes of neurologic deficits, attributable to diffuse demyelinating white matter lesions
Patho:
a. CD4T cell autoreactivity to single myelin basic protein (MBP)>protein in myein sheath membrane
b. Th1 secretion of cytokins and inflamm response
c. macrophage (microglia), CD8 Tcell and B cell activation vs MBP
d. demyelinated patches or plaques (axons preserved)
e. remyelination with inferior thinned myelin sheath
f. repeated exacerbation os autoimmune activity and oligodendrocyte injury
g. gliosis (glial scarring) - permanent plaques> defined areas of gray discoloration of white matter kp833, perm disruption in conduction
Clinical manif:
episodes of neuro defecits>gradual, partial remission. As disease progresses>less improvement between exacerbations and ^neuro dysfunction
- Sensory
a. plaque in optic nerve
b. plaque in spinal cord and brain stem - paresthesias, numbness, decreased proprioception, thermal sense, pain - Motor.
a. plaque in brain stem - ataxia, nystagmus, paralysis, hyperreflexia, decreased corordination
b. plaque in spinal cord - motor impairment of trunk and limbs - Autonomic - bladder incontinence, impotence
- Alzheimer’s Disease
Patho:
- Neuritic plaques
a. collection of neuritic processes around a central amyloid AB peptide core
b. interfere with synaptic transmission os ACh
c. tend to occur in hippocampus, amygdala, cortex - Ayloid eta peptid production (major protein in neuritic plaques)
a. formed from abn breakdown of amyloid precursosr protein (APP) which is normally syntheszied by neuronal membrance and expressed on cell surface an is used to support neurite growth. breakdown products do not produce AB peptide, and if so,its cleared from brain..
b. More AB peptide is produced than can be cleared>aggregate.
c. AB peptide is neurotoxic>loss on neurons
d. triggers release of glutamate from glial cells - Neurofibrillary tangles
a. microtubular proteins in neuron become distorted and twisted
b. displace or encircle nucleus>interfere with function>neuronal loss
c. insoluble and persist in nervous tissue after cell death - Loss of neurons and interference with normal transmission
- Inflamm response to AB deposits
a. oxidative damage
b. alterations in calcium homeostasis
Clinical Manif:
- Progressive dementia from progressive neuronal loss and reduction in brain ACh and other neurotransmitters
a. early - impairment of higher intellectual function and alteration in mood and behavior
b. progressive disorientation, memory loss, aphasia and functional decline
c. profoundly disabled, mute, and immobile - Histology
presence of plaques and neurofibrillary tangles with brain tissue atrophy
- Parkinson’s Disease
Damage to or degeneration of dopaminergic neurons of substantial nigra or nigrostriatal pathway
Etio:
a. idiopathic
b. gene mutations
c. exposure to toxins/heavy metal poisoning, herbicides>cause free radical damage to dopamine secreting neurons
d. drugs - antipsychotic which deplete dopamine or designer drugs MPTP>free radical damage to dopaminergic neurons
e. secondary from trauma or other diseases
Patho:
a. !loss of dopaminergic neurons in substantia nigra and nigrostriatal pathyway
b.! decreased dopamine
c. !loss of normal dopamine and ACh balace in striatum
Net effect- increased inhibitory output from striatum
Clinica Manif:
- Histology -pale substantia nigra et lewy bodies (neuronal filaments around protein core)
- ^ striatal inhibitory output manifested by:
a. diminished facial expression
b. akinesia/bradykinesia
c. rigidity
d. pill rolling tremor
d. postural instability d/t loss of speed of normal postural reflexes
e. depression, slowness of thinking
- Huntington’s Disease
Herediatry disease charac by progressive movement disorder, dementia, neuronal degeneration in corpus striatum and frontal cerebral cortex
Etio:
Genetic - autosomal dominant mutation to chromosome 4
a. encode a protein - huntington
b.! mutation ^ # of CAG repeats
c. CAG repeats inversely r/t age of onset (^repeats>progressively earlier presentation)
Patho: mutant protein damages brain neurons
- causes func abn in mitochondria
a. insuff supply of energy for cell func
b. interferes with manuf and packaging of neurotransmitters
c. interferes with manuf of antioxidants >ROS damage - Mutant protein degraded and forms aggregate >interfere with normal neuronal func
- Mutant protein fails to fold properly and accumulation of misfolded protein triggers apoptosis
- ! Loss of neuronsof the corpus striatum (caudate nucleus and putamen) and atrophy Kp840. Net effect of decreased striatal inhibitory output and decreased modulation of movement
Clinical manif
- invol rapid, jerky movements (corea), slow writherin mvmt of limbs and trunk (athetosis)
- cognitive impairment/dmentia, depression
- dopamine antagonists reduce invol mvment - block inhibition of remaining striatal neurons.
- Amyothrophic Lateral Sclerosis (ALS)
a progressive neuromuscular d/o caused by degeneration of upper and lower motor neurons
Etio:
- familial/inherited genetic defect (10%)
a. superoxide dismutase SOD1
b. TAR DNA binding protien
c. FUS (fused in sarcome/TLS (translocated in liposarcoma
d. ubiquilin 2 gene - viral and autoimmune or other environmental factors
Patho:
- SOD1 (an antioxidant) defect interferes with enzymes that produce it> free radical damage to upper and lower motor neuron and neuronal degeneration and loss.
Genetic mutation >misfolding of protein>apoptosis - Ubiquilin 2 recycles damaged or misfolded protein in motor and cortical neurons. Genetic mutation causes problem with disposal of misfolded or damaged proteins
- Glutamate toxicity contribute to neuronal loss - ALS pts have ^ glutamate levels in fluid bathing brain and spinal cord.
- Degeneration and loss of upper motor neuron including corticobulbar tracts.
- Degeneration and loss of lower motor neurons - corticospinal tracts in lateral portion of spinal cord and loss of anterior horn cells.
- Skeletal muscle denervation and atrophy
Clinic Manif
- Muscle weakness, atrophy, eventual loss of use - early manif are asymmetric weakness of hand and difficulty with fine motor tasks
- hyperreflexia ann spasticity of arms and legs - degeneration of corticospinal tract neurons>release of reflexes from inhibition>hyperreflexia and spasticity
- cramping and fasciculations
- Involvement with bulbar muscles cause difficulty with speech, swallowing, breathing, coughing. - no involvement of CN III, IV or VI
- preservation of intellect
- fatal within 3-5 d/t respiratory muscle failure and pulmonary infection
44.Bacterial meningitis
Major charac: infection of arachnoid and pia membranes and CSF withing subarachnoid space with inflam response.
Etio:
a. neonate - B strep and E coli
b. infants and above - H. influenza, neisseria meningitides (meningococcal meningitis), and strep pneumonia
Patho:
- Entry into CNS via choroid plexus or altered areas of BBB
- Bacteria multiply in subarachnoid space - host defenses are inadequate to control infection in subarach space.
- Inflam response
a. cytokine release - TNF-alpha, IL-1, other proinflam molecules>neuronal injury
b. ^ permeability of BBB>edema
c. vasodilation>ruptures small vessels>bleeding
d. stimulates clotting cascade>thrombosis
e. neutrophil migration into subarachnoid space>thick exudate production>interferes with normal CSF drainage>hydrocephalus - Scar tissue formation and neuron loss
Clinical manif
a. meningeal irritation and ^ICP - HA, photophobia, nuchal rigidity, altered mentation, irritability, fever
b. CSF - cloudy, WBD, ^protein concentration, Decreased sugar content
c. meningococcal meningitis - petechial rash
d. complications - septicemia, secondary infection of brain issue>abscess formation, herniation
- Common visual field defects
- prechiasmal lesions
a. complete lesions of the optic nerve>total blindness of affected eye
b. partial lesion of the optic nerve>hemianopia(impaired vision in the ipsilateral eye - same side - Lesions that compress the central portion of the chiasm like pituitary tumors- Bitemporal hemianopia - loss of the temporal half of each eye
- retrochiasmal lesions (behind chiasm)
a. lesions across optic tract and optic radiation - cause visual loss in the contralateral field of both eyes, homonyous hemaniopia - partial lesions across the optic tract or optic radiation
- superior or inferrior quadrantanopia
- Glaucoma
- ormal flow of aqueous humor
- Open angle glaucoma (most common)
a. abn trabecular mesh work/blockage which slows drainage of aq humor>^Intraocular pressure (trab mesh control flow into canal of schlemm
b. angle-closue glaucoma- angle formed by cornea and iris narrows preventing the aw humor from draining out of the eye. -with age lensgrows larger decreasing ability of aq humor to pass between iris and lens onits way to ant chamber>fluid pressure build up>furthering narrowing of angle.
Clinical Manif
- ^ IOP
- Changes in visual field/optic nerve damage
- Macular Degeneration
Lossof central vision and is most common cause of reduced vision and leading cause of blindness >age 75.
risk: HTN, smoking, DM, genetic.
Two forms:
a. Dry type (90%) -
a. waste products from photoreceptors accumulate under retinal pigment epithelium=called drusen
b. atrophy and degeneration of the rod and cone photorecpt/retinal pigment epithelium
- Wet form - subretinal neovascularization, bleeding, and scar tissue formation
- Hearing loss types
- conductive - d/t external or middle ear problems
- sensorineural - hearing loss d/t disease of cochlea and CNVIII
- Central - d/t diseases affecting the cochlear nuclei or auditory pathways in the CNS
- Meniere’s Disease
Patho
- fluctuating endolymph pressure of inner ear
- dilation of membranous labyrinth (hydrops) from ^ endolymph pressure - ^ presure mayb e from decreased absorption of endolymph, blockage of endo pathways, or ^ endo production.
- Migraine HA
Patho
- trigger phase
- aura with slow expanding area of reduced cortical electrical activity
- ! activation of brain stem area responsible for physiological response to stress and panic (locus ceruleus) and excitation of the trigeminal nuclei.
- release of pro-inflamm peptide in meninges and vessels, plt release of 5-HT, and degranulation of mast cell>”neurogenic inflamm”
a. vasodilation, plasma protein extravasation, swelling of meninges and dura
b. distrubances in BBB cause N/V
Clinic Manif:
- preceded by aura in1/5 cases
- Pain - from activation of the trigeminal nerve anteriorly and upper cervical nerves (C2/C3) posteriorly.
a. explains neck pain, neck muscle tenderness, and spasm
b. alterations in periaqueductal grey matter (PAG) and brain stem nuclei>loss of natural anti-nociceptive function - N/V, photophobia, irritability, malaise
- nasal congestion, rhinorrhea, lacrimation
Depression
Patho:
- Monoamine hypothesis - deficit in brain norepi, dopamine, or serotonin.
a. decreased levels in synaptic cleft d/t decreased presynaptic release or dec postsynaptic sensitivity
b. decrease in serotonin receptor binding in serotonin system - raphe-serotonin modulates homeostasis, emotionality, tolerance to adverse experiences - Classic stress pathway hypothesis - disturbances in the function of the HPA axis
a. impaired feedback inhibition of CRH by endogenous glucocorticoids (hypersecretion of CRH in depressed pts, ^cortisol levels in am/pm et spike erratically over 24 hrs)
b. decreased glucocorticoid function in the CNS
a. possible downregulation of glucocortiocoid receptors>decreased glucose metabolism
b. prolonged elevation in CRH secretion may downregulate CRH receptors in pituitary in brain
c. prolonged elevation in CRH may alter DNA expression>change the functional capacity of neurons - Antidepressants upregulate glucocorticoid receptor function
- Other mechanisms:
a. decreased frontal and temporal lobe volumes
b. decreased blood flow to frontal cortex
c. increased blood flow and O2 consumption to cortical areas interconnected with amygdala - positively r/t negative affect in depressed pts. Amygdala helps person relate to surrounding environment>pattern appropriate behavior, emotions, regulation, and modulation.
