病理学英文版教学课件：Disease of Central Nervous System

DiseaseofCentralNervousSystemThenervoussystem（神经系统）centralnervoussystem(CNS)

brain

spinalcordperipheralnervoussystem(PNS)1.UniqueStructuralandCellularCharacters

2.Lesionsmayhavelocationindication(selectivedysfunction)signaltoandfromdifferentregionsofthebodyarecontrolledbyveryspecificareaswithinthenervoussystemCharacters

ofCNS3.Dualinfluencesofsomestructures

skullanddura:protectionofbrainfacilitateincreasedintra-cranialpressureCharacters

ofCNS4.Specialdisease:

Degenerativedisease:

ParkinsonDis.AlzheimerDis.Demyelinationdisease:

multiplesclerosis

Psychiatricdiseaseslessunderstanding

Congenitalanomalies:highincidence3%newborns7Characters

ofCNSDiseaseofCNSBasicpathologicchangesofcellsCommoncomplicationsHemodynamicDerangement&CerebralVascularDisordersTumorPartIBasicpathologicchangesofcellsinCNSCellsinCNSNeuronglialcells

(astrocyteoligodendrocyteependyma)bloodvesselsmicrogliaNeuropil

神经毡processofthecellsintheCNStoformadelicatefibrillarybackground1.CentralChromatolysis(中央性尼氏小体溶解)dispersionofNisslsubstanceandswellingofneuroncellbodyMorphology:

Neuron（神经元）

NormalNeuronCentralChromatolysisCause：axonalinjury,Viralinfection,

deficiencyofVit.B,anoxia.reversiblechange尼氏体(Nisslbodies)

roughendoplasmicreticulum(RER)2.

CoagulationNecrosisCause:ischemia,anoxia,hypoglucemia,lowerbloodpressure,epilepsyMorphology：redneuron

(cytoplasmicacidophilic,nuclearpyknosisandkaryolysis)

Neuron（神经元）RedNeuron

ghostcelldissolveredneuronghostcell

Neuron（神经元）3.InclusionBodies(包涵体)viralinfectionsHSV;EncephalitisBJap.virus;PoliovirusRabies:NegribodyNegriBodyNeuron（神经元）3.InclusionBodies(包涵体)neurodegenerativediseaseAli

LewybodyParkinsonDis.Neuron（神经元）Substantianigra黑质PigmentednervecelldopamineParkinsonDis.normalP.D.4

NeurofibrillaryTangle(NFTs,神经原纤维缠结)markerofdyingneuroncomposedbydoublespiralstrandsofneurofibilswithabnormalphosphorylatedtauproteinseeninAlzheimer’sDis,boxerbrain,post-encephalitis,ParkinsonismSliverstainNeuron（神经元）Alzheimer’sdis.

SenilePlaque(老年斑)thecorecomposedwithβ-amyloidprotein,surroundedbyahaloandswollendegenerativeaxons

cerebralatrophyImmunofluorescenceAnti–glialfibrillaryacidprotein(GFAP)ThemajorsupportingglialcellsinthebrainAstrocyte（星形胶质细胞）SliverimpregnationBBBblood–brainbarrierreactiveastrogliosis:repairprocessafterinsults

formingglialscarSeeninlocalanoxia,edema,infarctandattheperipheryofabscessortumor.

FibroblastAstrocyteTheprincipalcellsresponsibleforrepairandscarformationintheCNSgliosisAstrocyteHypertrophyandhyperplasia：homogeneouseosinophiliccytoplasm

multiplestout,ramifyingprocessesenlargednuclearwithbinuclei,multinucleiorbizarrenuclei(closetocytoplasmicmembrane)gemistocyticastrocytesGFAPnoextracellularmatrixCorporaamylacea(淀粉样小体）:round,faintlybasophilic,concentricallylamellatedstructurestheendprocessofastrocytes,esp.subpialandperivascularzonesdegenerativechange

increasewithaging

AstrocyteOligodendrocyte

(少突胶质细胞)MyelinformationcellsinCNS(inPNS:Schwanncells)HE:insizeandshapelikelymphocyte

scantyperinuclearcytoplasmwithmultiplefineprocess

Ingreymatter:

Satellitephenomenon

卫星现象

>5oligodendrocytessurroundingoneneuronuncertainsignificanceOligodendrocyte

Oligodendrocyte

Demyelination(脱髓鞘病变)

formedmyelinsheathdestroyedduetoallergy,anoxiaortoxificationLeucodystrophy(白质营养不良)

myelinsheathformationdisturbancedifferentcongenitalenzymedeficiencyPerivasculardemyelination(Luxolfastbluestaining

)Oligodendrocyte

Microglia(小胶质细胞）monocytelineage

restingmicroglia

MΦantigen-presentingcellsininflammatoryconditionsFocalproliferationformingmicroglialnodule

MicrogliaRodlikemicrogliaseeninadvancedsyphilisrodcellsMicrogliaNeuronophagia(嗜神经元现象）Deadneuronengulfedandphagocytosedbymicroglialcells.Microgliagittercells

foam/cellsMicrogliaFoamymacrophagesPartIICommonComplications

CommonComplicationsCerebral

edema

(脑水肿)Hydrocephalus(脑积水)Herniation(脑疝)skullandspinalcanallittleroomforbrainexpansionedema,hydrocephalus,masslesionCerebralEdema

（脑水肿)theaccumulationofexcessfluidwithinthebrainparenchyma.Cause:anoxia,infarction,inflammation,injury,toxificationandtumor.Page423Mechanism:1.Vasogenic:disruptedBBBinterstitialedema

2.Cytotoxic:cytomembranouspump↓(ATPase)intracellularedema

usuallymixedtype

CerebralEdemaMorphology:brainvolume↑,weight↑,narrowsulci,widenedgyri,smallventricleCerebralEdemaMultiplesmallmetastasesCerebralEdemawidenedgyrinarrowedsulciCerebralEdemaLoosebrainparenchymawidenedV-Rspace(Virchow-Robinspace)Hydrocephalus

（脑积水)

AccumulationofexcessiveCSFwithintheventricularsystemCSF—cerebrospinalfluidPage424CirculationofCSFChoroidsplexus

ventricularsystem

arachnoidvilliformation=absorptionFunction--actasthelymphocyticdrainageinthebrainOver-secretionofCSF(tumorofchoroidplexus)

AbsorptiondisturbancesofCSFNoncomunicating(obstructive)：

portionofventriclestumor,inflammatory,adhesion,hemorrhage,ordeformityinIIIventricle.2)Communicating

entireventricularsystem↓CSFresorption.

meningitis,subarachnoidhemorrhage,withsubsequentorganization,orcausingscarringofarachnoidgranulationorVilli.Cause&PathogenesisHydrocephalusoverproductionimpairedflowresorption

Morphology:

headenlarged(beforeclosureofcranialsutures)dilationofventricles+atrophybrain

Page424HydrocephalusCPC:increasedintracranialpressure→headache,vomiting,papilloedemaofopticN.,coma,death

HydrocephalusHerniation脑疝Page425Thecranialvaultissubdividedbyrigidduralfolds--falxandtentoriumdisplacementofbraintissuefromoneintracranialcomponentintoanother,orintothespinalcanal

1.Subfalcine(cingulate)herniation2.Transtentorial(uncinate)

herniation3.Tonsillarherniation4.ExternalcerebralherniationHerniationSubfalcine(cingulate)herniation

cingulategyrusundertheedgeoffalxlocaltissuehemorrhagicandnecrotic,weaknessandsensorydysfunctionoflegAnteriorcerebralarteryTranstentorial(uncinate)herniationthemedialaspectofthetemporallobeiscompressedagainstthefreemarginofthetentoriumuncusofthehippocampusipsilateralIIINcompressed

pupilsconstricted,dilated

“blownpupil”IIIoculomotornerveTranstentorial(uncinate)herniationKernohan’snotchhemiparesisofipsilateralextremities(falselocalizationsign)thecerebralpeduncle大脑脚Kernohan’snotchTranstentorial(uncinate)herniationDurethemorrhagetearingofpenetratingV.A.DurethemorrhagegrimprognosisTranstentorial(uncinate)herniationTonsillarherniationcerebellartonsilsintotheforamenmagnumlife-threatening virtalrespiratory/cardiccentersinthemedulla

→suddendeath

foramenmagnumTonsillarherniationPartIII

HemodynamicDerangement&

CerebralVascularDisordersStroke中风3mechanisms:thromboticocclusionembolicocclusionvascularrupturehemorrhagedirecttissuedamagesecondaryischemicinjurylossofoxygen&metabolicsubstratesinfarction/ischemicinjurycompletelossofperfusionseverehypoxemiaprofoundhypoglycemiaHypoxia,ischemia,andinfarctionGlobalcerebralischemiaFocalcerebralischemiaIntracranialhemorrhage

PrimarybrainparenchymahemorrhageSubarachnoidhemorrhageandsaccularaneurysmsVascularmalformationsCerebralamyloidangiopathyOthervasculardiseasesHypertensivecerebrovascularDis.Vasculitisbrain:1%~2%ofbodyweight15%cardiacoutput

20%O2consumptionfunctionalhypoxialowO2(highaltitude)↓O2-carryingcapacity(severeanemia,CO),↓O2use(cyanidepoisoning)IschemiahypotensionvascularobstructionHypoxia,ischemia,andinfarctionwidespreadischemia/hypoxiainjuryoccursduetoageneralizedreductionofcerebralperfusioncausedbyhypotension,cardiacarrest,hemorrhageandshock.

GlobalcerebralischemiaHypoxia,ischemia,andinfarctionsystolicpressures<50mmHgNeuronsarefarmorevulnerabletoischemicinjurythanglialcells.

Hypoxia,ischemia,andinfarctionGlobalcerebralischemiaPurkinjecellsincerebellumHypoxia,ischemia,andinfarctionGlobalcerebralischemiathepyramidalcellsinthehippocampusthePurkinjecellsofthecerebellumneuronswithintheglobuspallidusofthebasalganglia

DifferentlayersofthecortexMolecularlayerExternalgranularlayerExternalpyramidallayerInternalgranularlayerInternalpyramidallayerFusiformlayer(notshown)Hypoxia,ischemia,andinfarctionGlobalcerebralischemiaLaminarCorticalNecrosis3rd、5th、6thlayersofcortexarevulnerable

thelocationattheborderzoneofcerebralarteriesismuchmorevulnerable.

Hypoxia,ischemia,andinfarctionGlobalcerebralischemiaBorderzoneofcortex‘Cshape‘watershedzoneInfarctioninthewatershedzonebetweenanteriorandmiddlecerebralarterialcirculations.Hypoxia,ischemia,andinfarctionGlobalcerebralischemiaFreshborderzoneinfarctGranularatrophy(gliosis)Hypoxia,ischemia,andinfarctionGlobalcerebralischemiaHypoxia,ischemia,andinfarctionHistopathologicchanges:Earlychanges(12-24h)

acuteneuronalcellchange,thenglialcells

infiltrationbyneutrophilsSubacutechanges(24h-2w)

necrosisoftissue,influxofmacrophage,vascularproliferation,reactivegliosisRepair(after2w)removalofnecrotictissue,lossoforganizedCNSstructure,gliosis

GlobalcerebralischemiaCPC：transientpostischemicconfusionalstatepersistentvegetativestatebraindeath--diffusecorticalinjury,brainstemdamage, absentofreflexes/respiratorydrive

respiratorbrain:

autolyticprocessbrowndiscolorationandunfixedbrainHypoxia,ischemia,andinfarctionGlobalcerebralischemiaCerebralarterialocclusion

focalischemiainfarctionHypoxia,ischemia,andinfarctionFocalcerebralischemiaCause:

※embolic: Cardiacmuralthrombi thromboemboliarisinginarteries atheromatousplaqueswithinthecarotidarteries.

themiddlecerebralartery

※thrombotic:

atherosclerosiscarotidbifurcationmiddlecerebralarteryateitherendofthebasilarartery

Hypoxia,ischemia,andinfarctionFocalcerebralischemiaTypes:

nonhemorragicinfarctshemorrhagicinfarctsreperfusioncollateraldissolutionofintravascularocclusionsHypoxia,ischemia,andinfarctionFocalcerebralischemiaGross:first6h--little48h--pale,soft,andswollen,andthecorticomedullaryjunctionbecomesindistinct.2dto10d--gelatinousandfriable,andthepreviouslyill-definedboundarybetweennormalandabnormaltissuebecomesmoredistinctasedemaresolvesintheadjacenttissuethathassurvived.Hypoxia,ischemia,andinfarctionFocalcerebralischemiaMicroscopy:first12H--redneurons,edema48H--neutrophilicemigration2-3W--Phagocyticcellsactivatedmicroglia

Gross:10dto3w—liquefies,afluid-filledcavitylinedbydarkgraytissue,Hypoxia,ischemia,andinfarctionFocalcerebralischemiaMicroscopy:1W--Reactiveastrocytesseveralmonths-wallofthecavityhemorrhagicinfarctionparallelischemicinfarction,withtheadditionofbloodextravasationandresorption.pathologicalchangesHypoxia,ischemia,andinfarctionFocalcerebralischemiaInfarctionareasuppliedbymiddlecerebralA.Hypoxia,ischemia,andinfarctionFocalcerebralischemiapathologicalchangesResolutionofliquefactivenecrosis

cysticspaceHypoxia,ischemia,andinfarctionFocalcerebralischemiaischemicneuronalchangesliquefaction,irregularcavitiesreactivegliosisHypoxia,ischemia,andinfarctionFocalcerebralischemiagemistocyticastrocytesareasofanacuteinfarctionRedneuronsneutrophilattheedgeAfter10Dmacrophagesgliosistissuelosswithasmallamountofresidualgliosis.

Intracranialhemorrhage

Subarachnoidhemorrhagesrupturedaneurysms

Subduralorepiduralhemorrhagestrauma.Hemorrhagewithinthebrain:hypertension,othervascularwallinjurystructurallesion(arteriovenous/cavernousmalformations)tumorsPrimarybrainparenchymahemorrhageIntracranialhemorrhagemid-tolateadultlife,peak60yruptureofasmallintraprenchymalvesselshypertension15%deathinchronichypertensionlargeportionorventricularsystemdevastatingsmallregionsclinicallysilentArchitectureofCerebralArteriesIntracranialhemorrhageHypertensiontypicallyinbasalganglia,thalamus,pons,andcerebellumPrimarybrainparenchymahemorrhagesmallpenetratingarteriesChanges:CenternormalstructuredestroyedfilledwithRBCPeripherymultifociofhemorrhageOldhemorrhagefocicavitated withhemosiderinPrimarybrainparenchymahemorrhageIntracranialhemorrhageSubarachnoidhemorrhageruptureofasaccular(berry)aneurysm(mostcommon)IntracranialhemorrhageSaccular(berry)aneurysmSaccularaneurysmflowerMangnoliaSubarachnoidhemorrhageIntracranialhemorrhagecongenitalaneurysmdevelopruptureyoungtomiddleage50%diedinseveraldays acutehydrocephalus herniation braininfarctionchronic:hydrocephalusCPC:Abrupt,severeheadache,vomitting,lossofconsciousnessMeningealsignsBloodyCSFSubarachnoidhemorrhageIntracranialhemorrhageVascularmalformationAbnormalitiesinangiogenesisinthedevelopingbrainarteriovenousmalformations(AVM),cavernousangiomas,capillarytelangiectasiasvenousangiomas.IntracranialhemorrhageVascularmalformationIntracranialhemorrhagearteriovenousmalformation(AVM)VascularmalformationIntracranialhemorrhagePartIVTumorofCNS½to3/4--primarytumorstherest--metastatic20%ofallcancersofchildhoodChild--posteriorfossaAdultscerebralhemispheresPage417CharacteristicsofCNStumors:DistinctionbetweenbenignandmalignantlesionsislessevidentanatomicsiteoftheneoplasmcanhavelethalconsequencesirrespectiveofhistologicclassificationthepatternofspreadPage417Astrocytoma（星形胶质细胞瘤)

Meningioma（脑膜瘤)

Medulloblastoma（髓母细胞瘤)

Schwannoma（神经鞘瘤,施万氏瘤)Astrocytoma（星形胶质细胞瘤)Gliomas--40%ofbraintumorsAstrocytoma--70%ofgliomasMostastrocytomasareofdiffuseinfiltrativePage417gliomaAstrocytoma（星形胶质细胞瘤)Locationdiff.demarcationofteninbrainstemcerebellu