Exam 2.3 Flashcards
Structure CNS
Organ=brain and SC
Org.=overall command center
Function=process/integrate into
Structure PNS
Organs=N. and gang.
Org.=receive/send to and from CNS
Function=Mediator some reflex
Function-motor
CNS/PNS=axon transmit N. impulses from CNS–>muscle/gland
Somatic=voluntary of sk. muscle
Automatic=involun. control of sm. muscle cardiac/glands
Function-SENSORY
CNS/PNS=both(axon transmit N. impulse from peripheral strucutre–>CNS)
-Eye and ears=PNS
Somatic=transmit input from skin, fascia, joint and sk. muscle
Automatic=transmit input from stomach and intestine (viscera)
light traveling and reflection
goes from axon layer–>retinal pigmented epith. and goes back up
Glaucoma-Pathogenesis
Incre. intraocular P.
-incre. production/decre. vitreous humor
Block blood flow through intraocular vessel in uvea(compress)
Decre. BF=depriving retinal from nutrients
-atrophy of retinal layer
Glaucoma-tx
reduce fluid prod. or drain
Glaucoma-damage and S/S
Retinal damage=blurred vision, impaired dark adaptation
Corneal damage=halos around lights
Optic N. atrophy
Glaucoma-retinal atrophy
Disrupt N. fiber layer -AKA axon layer Ganglion cell layer Damage to layers of rod/cons Thinning of retina
Middle ear dis.
Otosclerosis
Otosclerosis-symp or not
Genetic is usually asymp.
Other times symp.
Otosclerosis-oval window involvement
Bony growth around oval window (stapes dnt move window)
-no reabsoprt. b/c incre. bone= decre. stapes mov.
:no vibration transmitted (even if Incus moving)
Otosclerosis-path.
Uncoupling of resorption/deposition Fibrosisi and vascularization of temporal bone Dense new bone replace fibrotic tissue -anchor footplate of stapes -no vibration=deaf
Inner ear dis.
Tinnitus
Tinnitus
Ears ringing
-also hissing, whistling, humming and roaring
Transient not assoc. w/ dis.
-excessive stim. of hair cells
Persistent is assoc. w/ hearing loss
-assoc. w/ cochlear or CN VII dysfunction
Neuromuscular dis. vs. myelin sheath dis.
Neurmusc.=myasthenia gravis
Myelin sheath.=multiple sclerosis
Neuromuscular junction- synapse type on terminal motor axons synapse w/ sarcolemma
Chemical synapse -NT activate ion uptake in post. synp. memb. (dendrites/sk. muscle) Electrical synp. -ion travel through gap junction -common in cardiac, sm. muscle
NT
1st discovered=Ach and N.epi
Activate and inhib.
Usually amine, AA or small peptide
Degraded in synaptic clef or taken up by endocytosis
-stop prolong stim.
-post/pre syn. memb.
may act as paracrine horm. outside N. syst.
Myasthenia gravis-immune dis.
Autoimmune dis.-->antiBD med. -antBD to ach Recep. -induce aggregation and degradation of recep. Reduced ach Recep. -post-synp. memb. -decre. resp. to ach=muscle wk. AntiBD also interact w/ thymus -benign thymoma -thymic hyperplasia :B cell follicles in thymus (not just overgrow)
Myasthenia gravis-symp.
Fluctuating wk.
-incre. over the course of the day
-incre. upon exertion
-decre. muscle responsiveness upon repeated stim.
Involvement of extra-ocular muscles(unusual for myopathy)
-diplopia/ptosis
Myasthenia Gravis-Tx
Acetylcholinesterase inhib.
-ach persisits in synaptic cleft
Immunosuppressive thearpy (glucocorticoids) or plamapheresis
Thymectomy for pts. w/ thymoma
Myelin sheath.-chact.
Layers of memb. surround an axon CNS=white matter macroscopic Import. for sig. transmission Salutatory Conduction - signals jumps from node to node
Myelin sheath dis?
Multiple sclerosis
MS is autoimmune dis?
yes
MS-autoimmune dis.
Immune response to myelin sheath
Chronic immune cell (T cell/MAC) around myelin sheath plaque (lost myelin)
Complex multigene dis.
-link to MHC comp. DR2
-Also IL-2/IL-7 Recep.
Lesion w/in M. Sheath decr. N. transmission efficiency
Relapsing episode of N. Def.
-variable duration (wks or yrs)
-grad./partial recovery=each recovery (steady decline)
Freq. incre. w/ time while recovery=P. Restrict dis.
MS-immune response
T helper cell initiate immune response against
Cytokines release promote MAC and leuko. infiltration
MAC and leuko. release agents to damage invades
Agents myelin sheath instead
-since there r no invaders
MS-tissue damage
Consist w/ others immune dis. have studied
Immune response itself produce tissue damage
Lesion r firmer than surrounding tissue
-sclerosis b/c myline incre. lipid components
:usual fibrosis but ~ b/c tissue is lost
MS-S/S
Unilateral visual impair=b/c optic N. b4 optic chiams Brain stem -CN signs (no hear/taste) -Ataxia=impaired coordinate -Nystagmus=involv. Rhythmic eye mov. -Internuc. Ophthalmogplegia :eye goes one way and other drags behind it Spinal cord lesion -motor/sensory N. (muscle control) -Spascity and lost bladder control
CNS dis.
Ethanol toxicity Cerebrovascular dis. Prion dis. Motor N. dis. (degenerative) Degenerative dis. Dementia (degenerative)
Cerebrovascular dis.
Cerebral edema
Focal cerebral ischemia
Toxic CNS damage
ethanol toxicity
creutzfeldt-jakob dis.
prion dis.
ALS
motor n. dis.
Parkinson’s dis.
degenerative dis.
alzheimer dis.
dementia
Toxic N. Damage
Cellular and tissue loss due to toxicity
Unique Consideration in CNS
-isolation (BBB)=toxin in blood dnt affect and need to cross barrier
-incre. metabolic needs=ie gluc. need (more sensitivity)
-repair cap.=limited
:harder to recover from toxicity
Acute vs. chronic ethanol induced toxicity
Acute=abuse is gen. reversible
Chronic=alcohol abuse assoc. w/ metabolic disturbances
Ethanol toxicity-hepatic encephalopathy
Glial response w/in CNS (w/in cerebral cortex/basal gang.)
changes liver
Incre. Ammonia and pro-inflam. cytokines
Astrocyte changes=alzheimer type II cell
-enlarged nuclei
-minimal reactive cytop.
ethanol toxicity-thamine def.
Malnutrient or malabsorp.
Assoc. w/ chronic ethanol abuse
Acute=wernicke encephalopathy
Chronic=Korsakoff synd.
Wernicke Encephalopathy
Acute thiamine def.
Reversible (w/ thiamine supplement)
Ophthalmoplegia
Psychotic symp.
Korsakoff synd.
Chronic thiamine def. Irreversible Assoc. w/ lesion in the thalamus -short term memory prob. -Confabulation Pathology -Early=dilated cap. w/ prominent endoth. cell -hemorrhagic/necrotic foci in ventricular walls -eventual cyst formation
Ethanol toxicity in CNS
Direct/2dry to malnutrition
Cerebellar dysfunction in 1% of chronic alcoholics
-ant. vermis
Atrophy and loss of granules cell (interN. –>purkinje cells)
Atrophy/loss of granule cells
Excite sig. form res of N. syst.
Participate in processing visual and motor info
-learn and memory
Ethanol toxicity CNS-clinical
truncal ataxia
Unsteady gate
Nystagmus
Cerebral Edema
Sig.=accum excess fluid w/in brain parenchyma
-not w/in CSF but around N. cell
Cause=excess fluid leakage from BV or CNS cell damage
Caused by
-vasogenic=BBB disruption and incre. perm. allowing fluid to move from w/in vasculature to w/in parenchymal space
-cystotoxic=2ndry to cell memb. injury (N., glial, endoth.)
:generalized hypoxia/ischemia
:Metabolic disruption-ionic homeostasis
Cerebral edema-2 pathway
Vasogenic=BBB disruption and incre. perm.
-allowing fluid to move from w/in vasculature to w/in parenchymal space
Cytotoxic=2ndry to cell memb. injury (N., glial, endoth.)
-generalized hypoxia/ischemia
-Metabolic disruption-ionic homeostasis
Cerebral edema-BRAIN pathology/morphology
Gyri flattened/sulci narrow
Ventricles compressed
If untx=herniation
Cerebral edema-death
range from subtle neurolgical deficits to death
Focal Cerebral Ischemia
Sig.=Limited to no BF to specific area of brain Cause=Arterial occlusion/hyoperfusion Caused by -embolism -vascular inflam. -In-situ thrombosis (athersclerosis MC)
focal cerebral ischemia-response
N. stress=red N. b/c eosin MAC/reactive gliosis to clean up damage Repair -removal of tissue -loss of architecture -gliosis (incre. glial)
Cause rapidly progressive neurodegenerative disorders
Human -creutzfeldt-jakob dis. -fatal familial insomnia -Kuru Sheep/goat=scrapie Bovine spongiform encephalopathy=mad cow dis.
Kuru
Plaque w/in humans tissue Extracell aggregated PrPsc Detectable w/ PAS or congo red W/in cerebellum Also varients CJD(vCJD)
Bovine spongiform encephalopathy
vCJD=dnt change PrP gene
Ingest contaminated beef w/ prions or blood
Damage cerebral cortex
Conformational change of prions
Abnormal forms of cellular protein
-specific protein termed prion protein (PrP)
Alpha helix containing isoform(PrPc)–>abnorma. beta shee isoform(PrPsc)
Rapid progressive N. degen. disorder
-sporadic, familial or transmitted
spongiform changes Common pathology
Caused by intracellular vacuoles in N. and glia
Cerebral cortex
Progressive dis.=not rapidly noticed atrophy
-only seen in grow examine
Avg. survival is 7 mo.
spongiform symp.
Changes in memory/behavior
Dementia
Start myoclonus=abnormal jump instead of jerk
Amyotrophic lateral sclerosis(ALS) AND what does the name mean
Motor N. dis.
Amyotrophic
-muscle paralysisi w/ no atrophy
-hypertonia(rigid) and exaggerated deep muscle tendon reflexes
Lateral sclerosis
-corticospinal tract degen.
-produce upper/lower motor N. paralysis in extremities
Lou Gehrig’s dis.
ALS-motor N. dis.
ALS-motor N. loss
Loss of lower motor N. -Spinal cord and brain stem Loss of upper motor N. -projection into spinal cord -NOT brain stem
familial ALS
GOF of coper-zinc superoxide dismutase (SOD1)
-dnt eliminate ROS originally thought to kill N.
-UPR induced by misfold SOD1=new
-contribute to malfunction of glial cells
Other mutation
-dynactin(retrograd transport)
-VAMP-assoc. prot B (reg. of vesicle transport)
-Alsin=guanine exchange factor domaine
-reg. endosomal trafficking
ALS-pathogenesis
SOD1 mutation
Altered axonal transport
Neurofilament abnorm.
Glutamate toxicity=excited death(overstim. cell death)
-incre. intracell. Ca2+
Develop protein aggregation
-Bunina bodies(PAS-binding inclusion in cytop.)
ALS-S/S
Motor/N. loss -hand weakness -Arm and leg spascity/cramp Eventually -muscle strength/bulk decre. -fasciculation -Death=resp. muscles
Parkinson-degenerative dis.
Substantia Nigra degen. in basal ganglia
S/S=tremor, rigidity, bradykinesia
L-dopa response=damage cell
Parkinson like dis.
Assoc. w/ toxin or other cuase
Dopamine antagonist
Parkinson-degen. of N. has a lack of what
dopamine
Parkinson-substantia Nigra
Loss pigmented N.
Assoc. gliosis
Parkinson-lewy bodies
Eosinophilic cytoplasmic inclusion
alpha-synuclein fiber
Parkinson dis.- alpha synuclein
Lipid-binding prot. assoc. w/ synapses
Mutation assoc. incre. gene copy=gene dosage effect
Overexpression induce lewy body formation in mice
Inhib. melanin production in skin
-linked to melanoma incidence
-enzymes for dopamine’s reg. tyrosine hydroxlase
Activates melanin production in N.
-Neuromelanin linked ot incre oxidative stress susceptability in dopaminergic N.
Parkinson-molecular genetic
Familial PD not common BUT instructive Assoc. GOF -leucin rich repeat kinase 2(LRRK2) -alpha synuclein -DJ1 (redox stress response) -PINK1(kinase that regulates mitoch. function) LOF=parkin(assoc. w/ juvenile form)
Parkinson-Genetic Mech.
Stress reposne(UPR/ROS)=alpha synunclin, DJ1 Defective proteasome function=parkin Change mitoch. function=DJ1 and PINK1
Parkinsonian disorder name and mitoch. toxin
1-methyl-4-phenyl-1,2,3,5-tetrahydrophridine
Byproduct of synthetic opioid production
Mitochondrial toxin
-generate model syst. for PD research
-selectively injure dopaminergic N.
:unkown mech. for selectivity
:dopamine eposure can incre. ROS=cells may be more sensitive
MPTP MOA
MPTP–>MPP+(N-methyl-4-phenylpyridinium) in astrocyte
-takes up dopa
MPP+ inhib. complex of ETC
Decre. ATP production and oxygen metabolism
Incre. ROS generation
-oxidative damage to lipid, prot., NA
dementia
inhib. memory or other cortical function w/ alert
Alzheimer dis.
MC of dementia
First sign is impaired learning and recall of recent memories
Alzheimer-presence of specific amyloid plaq.
Extracell
W/in cerebral cortex and BV walls (meningeal and cerebral)
AKA neurtic plaques
Central amyloid Beta core w/ halo prot.
Surrounded by netwrk of misshapen N. process/nutrients
Microglial and reactive astrocyte periphery
-immune response
Alheimer dis. intracel. protein
Neurofibrillary tangels (NFT)
-not specific AD
-paired helical filaments contain hyperphos. tau
:aggregate b/c microtub. binding prot.
-Found in N. processes (neurities) surrounding plaques
type of N. in alzheimer dis.
N. and synaptic loss and presence of reactive astrocytosis and microglial prolif.
Alzhimers-reactive astrocytosis
Incre. size and number in response to traumatic injury
Synthesis and release cytokine
Induce migration of immune cells into CNS
Astrocytes also remove excess glutamate through specific transplates
-TX=glutamine cytoxicty
alzheimer assoc. prot.
Presenilin (GOF)
Apolipoprotein E4
Amyloid Beta(AB) N. damage
N. loss consequence
Presenilin
Subunit of gama-secretase(from amyloid beta)
Import for proper amyloid processing
-other substrate critical N. function
Apolipoprotein E4
Mediates LDL binding to recp.
Promote Ab formation and deposition (possibly through binding)
ApoE3 bind tau
amyloid B(AB) N. damage
Directly cytotoxic -plaque number no correlate to dis. Synaptic dysfusntion -block long-term potnetiation -other memb. change Inflammatory response -mediators induce localized damage -affect tauP -Cause oxidative damage
Alzheimer’s-atrophy in cerebral cortex
Frontal lobe -planning complex behavior/multitasking -controling impulses, emotions, thoughts Temporal lobe -speech(cnt find the right word) -reading/writing Parietal lobe -integrates visual and auditory info.
Alzheimers-memory issues
Limbic system network -hippocampus thalamus, hypothalamus -necessary for learning and memory storage Posterior cortical areas -language comprehension Cortical assoc. area -storage of remote memories
