Quiz6Review

Kris.neKra1s,M.D.

CNSOutline

•  Introduc.on

Grossanatomyofbrain

CellsoftheCNS

•  Neurons–transmitimpulses•  Astrocytes–partofbloodbrainbarrier•  Oligodendrocytes–producemyelin•  Microglia–phagocytoseintruders•  Ependymalcells–lineventricles

Neurons

Astrocytesandoligodendrocytes

Microglialcells

Ependymalcells

Reac.onsofCellstoInjury

•  Neurons:become“red”anddegenerate•  Astrocytes:undergohypertrophy,hyperplasia•  Microglia:proliferate•  Oligodendrocytesandependymalcellsdon’t

reactmuch

CNSOutline

•  Introduc.on•  Increasedintracranialpressure

CausesofIncreasedICP

•  Cerebraledema•  Generalized(diffuseinsult,likehypoxia,toxinexposure,encephali.s,trauma)

•  Focal(aroundfocallesions,likeacuteinfarcts,contusions,penetra.nginjuries,masslesions)

•  IncreasedCSFvolume(hydrocephalus)•  Expandingmasslesions

Hydrocephalus

•  Defini.on:accumula.onofexcessiveCSFwithintheventricularsystem

•  Usuallyduetoimpairedflowandresorp.onofCSF(rarelyduetooverproduc.onofCSF)

•  Ifoccursininfancy,headenlarges•  Ifa1erinfancy,ventriclesexpand,ICPincreases

CSFcircula.on

CNSOutline

•  Introduc.on•  Increasedintracranialpressure•  Vasculardisorders(“strokes”)

FocalCerebralIschemia

•  Duetoobstruc.onofbloodflow•  Hemorrhagic(red)infarcts

•  duetoemboli+reperfusion•  o1enarisefromheart

•  Ischemic(pale)infarcts•  duetothrombi•  o1enarisefromatherosclero.cplaques

•  Transientischemica_acks(TIAs)areo1enharbingers

Hemorrhagic(L)vs.ischemic(R)infarc.on

Thrombus

CNSOutline

•  Introduc.on•  Increasedintracranialpressure•  Vasculardisorders(“strokes”)•  Trauma

Coupvs.contrecoupinjury

Axonalshearing

Trauma.cVascularInjury

Epiduralhemorrhage•  Bloodabovedura•  Tearinmiddlemeningealartery•  Neurosurgicalemergency

Subduralhemorrhage•  Bloodbetweenduraandarachnoid•  Shearingofbridgingveins•  Acute(hours)orchronic(months)

Subarachnoidhemorrhage•  Bloodinsubarachnoidspace•  Contusions,rupturedberryaneurysms•  Neurosurgicalemergency

CNSOutline

•  Introduc.on•  Increasedintracranialpressure•  Vasculardisorders(“strokes”)•  Trauma•  Infec.ons

Meningi.s

•  Inflamma.onofthemeninges•  Symptoms:Fever,headache,s.ffneck.•  Withouttreatment:Lossofconsciousness,coma,death.•  Infec.ouscauses:

•  Bacteria(newborns:E.coli,S.agalac.ae;youngadults:N.meningi.dis;elderly:S.pneumoniae)

•  Viruses(Coxsackie,ECHO,mumps)•  Tuberculosis,rarely

CNSOutline

•  Introduc.on•  Increasedintracranialpressure•  Vasculardisorders(“strokes”)•  Trauma•  Infec.ons•  Tumors

Gliomas

•  Arisefromastrocytes,oligodendrocytes,ependymalcells

•  O1enfatal(loca.onandinfiltra.veborderspreventcompleteexcision)

•  Glioblastoma(highest-gradeastrocytoma)ismostmalignant

Glioblastomamul.forme(high-gradeastrocytoma)

Medulloblastoma

•  Tumorofprimi.veneurons•  Cerebellum•  Children•  Veryradiosensi.ve!

Medulloblastoma

Meningioma

•  Encapsulated,benigntumor•  Surfaceofbrain(noinvasion)•  Symptomscausedbycompression•  Curedbyresec.on

Meningioma

NerveSheathTumors

•  Arisefromcranial(esp.VIII)andspinalnerveroots,andperipheralnerves

•  Derivedfromsupportcellsofnerve•  Benignbutmaycompressnerve•  Schwannoma(“acous.cneuroma”ifinvolving

VIII),neurofibroma

“Acous.cneuroma”(schwannoma)

CNSOutline

•  Introduc.on•  Increasedintracranialpressure•  Vasculardisorders(“strokes”)•  Trauma•  Infec.ons•  Tumors•  Demyelina.ngdiseases

Mul.pleSclerosis

•  Mostcommondemyelina.ngdisorder•  E.ologyunknown;relatedtoautoimmunity•  Varietyofmotorandsensorysymptoms•  Relapsing-remifngcourse•  Plaques(areasofdemyelina.on)inbrain,cord

CNSOutline

•  Introduc.on•  Increasedintracranialpressure•  Vasculardisorders(“strokes”)•  Trauma•  Infec.ons•  Tumors•  Demyelina.ngdiseases•  Degenera.vediseases

AlzheimerDisease

•  Mostcommoncauseofdemen.aintheelderly•  Symptoms:

•  Earlyon:forgegulness,memorydisturbances•  Languagedeficits,lossoflearnedmotorskills,altera.onsinmood/behavior,disorienta.on

•  Finally,pa.entbecomesprofoundlydisabled,mute,immobile

•  Gross:Cor.calatrophy,neuronalloss•  Microscopic:neurofibrillarytangles,neuri.cplaques

Alzheimerdisease:brainatrophy

Alzheimerdisease:progression

Alzheimerdisease:plaques(L)andtangles(R)

ParkinsonDisease

•  Degenera.onofpigmentedneurons(containingdopamine)inthesubstan.anigra

•  Causeunknown•  Earlysymptoms:tremor,rigidity,slowmovement•  Later:cogni.veproblems,demen.a,dyskinesia•  Gross:atrophyofsubstan.anigra•  Microscopic:Lewybodies(inclusionsinneurons)

Parkinsondisease(R):atrophyofsubstan.anigra

Hun.ngtonDisease

•  Degenera.onofbasalgangliaandcerebralcortex•  Earlysymptoms:lackofcoordina.on,unsteadygait•  Later:chorea(involuntarywrithing),psychiatric

symptoms,demen.a•  Autosomaldominantmuta.on•  Beginsin30s-40s;slowprogressionover10-20years

AmyotrophicLateralSclerosis

•  Degenera.onofneuronsinvolvedinmotorcontrol•  Rapidlyprogressiveweakness,muscleatrophy,

spas.city,dysphagia•  Earlysymptoms:muscleweaknessinanarmorleg,

twitching,slurredspeech•  Deathwithin2-3yearsduetorespiratorycompromise•  Sensoryandcogni.vefunc.onareunaffected

ClinicalFeaturesofTes.cularCancer

•  Commoninmenbetween15-35

•  Firm,painlessenlargementofthetes.s

•  Somepresentwithmetastases

•  Treatable–curable!-ifdetectedearly

Tes.cularCancerClassifica.on

•  Seminoma

•  Non-seminoma•  Embryonalcarcinoma•  Yolksactumor•  Choriocarcinoma•  Teratoma

NodularHyperplasia

•  Verycommon!90%ofmenhaveitbytheir70s.

•  Bigprostate•  Usuallyaffectscentralzoneoftheprostate

•  Symptoms(in10%ofpa.ents):hesitancy,urgency,nocturia,poorurinarystream.

•  Cause:excessiveandrogens.mula.on

ClinicalFeaturesofProstateCancer

•  Mostcommon,2nddeadliestcancerinmen

•  Peakincidence:65-75•  Cause:androgens+gene.cs+?environment

•  Symptoms:asymptoma.c,thenpalpablenodule,thenlocalpain/obstruc.on

FemaleReproduc.veSystemOutline

•  Cervix

•  Uterus

•  Ovaries

•  Breast

CervicalIntraepithelialNeoplasia(CIN)

•  Precursortocarcinoma

•  AlmostallcarcinomasariseinCIN;butnotallcasesofCINprogresstocarcinoma!

•  Threegrades:•  CINI:milddysplasia(halfregress,20%progress)•  CINII:moderatedysplasia•  CINIII:severedysplasia(30%regress,70%progress)

•  Thehigherthegrade,themorelikelythelesionwillprogresstocarcinoma

CervicalCarcinomaRiskFactors

•  Earlyageatfirstintercourse•  Mul.plesexualpartners

•  Amalepartnerwithmul.plepreviouspartners

•  Persistentinfec.onwith“high-risk”HPV•  Smoking

•  Immunodeficiency

CervicalCarcinomaandHPV

•  HPVisdetectableinalmostallCINandcancer.

•  “High-risk”types:•  16,18,45,31•  Foundincarcinomas•  Integrateintogenome,inac.vatep53,RB

•  “Low-risk” types:•  6,11•  Foundincondylomas(benignlesions)•  Donotintegrateintogenome

InvasiveCervicalCarcinoma

•  Mostcasesaresquamous,arisingfromCIN

•  Smallnumberareadenocarcinomas

•  Peakage:45(10-15yearsa1erCINdevelops!)•  Spreadsslowly•  Mostcasesarediagnosedearly

•  Mortalityisrelatedtostage•  Stage0(preinvasive):100%5yearsurvival•  Stage4:10%5yearsurvival

FemaleReproduc.veSystemOutline

•  Cervix

•  Uterus•  Endometriosis•  Endometrialhyperplasia•  Tumors

Endometriosis

•  Loca.onofendometrialglandsoutsideuterus

•  Usuallyperitoneum,rarelylymphnodes

•  Endometriumundergoescyclicbleeding

•  Causesscarring,pain,some.messterility

•  Howdoesendometriumgetout?

Endometriosisinovary(“chocolatecyst”)

Endometrialhyperplasia

Simple Complex Atypical

Leiomyoma

•  “Fibroid”

•  Benigntumorofsmoothmuscle

•  Common!

•  S.mulatedbyestrogen

•  Menorrhagia,metrorrhagia,orasymptoma.c

Leiomyosarcoma

•  Malignanttumorofsmoothmuscle

•  Necro.c,withatypicalcellsandlotsofmitoses

•  O1enrecura1ersurgery

•  Manymetastasize,especiallytolungs

•  5yearsurvival=40%

Leiomyoma Leiomyosarcoma

EndometrialCarcinoma

•  Peakage:55-65(notbefore40)•  Frequentlyarisesinendometrialhyperplasia

•  Riskfactors:obesity,nulliparity,estrogenreplacement

•  Symptoms:leukorrhea,irregularbleeding

•  Metastasizeslate

FemaleReproduc.veSystemOutline

•  Cervix

•  Uterus

•  Ovaries•  Tumors

Surfaceepithelialtumors• Cystadenoma• Cystadenocarcinoma

Germcelltumors• Teratoma• Dysgerminoma• Yolksactumor• Choriocarcinoma

• Granulosa-thecacelltumor• Sertoli-Leydigcelltumor

Sexcord-stromaltumors

OriginofOvarianTumors

Teratoma

•  Benigntumorwithdifferen.a.onalongallthreegermcelllayers(ectoderm,endoderm,mesoderm)

•  Usuallycys.c,withskininside(“dermoidcyst”)

•  Sebaceousmaterial,ma_edhair,teeth,bone…

•  Malignantvarianthasimmature.ssues

Teratoma

OvarianCancer

•  22,000newcases/14,000deathsin2014•  5thcommonest,5thmostdeadlycancerinwomen

•  Danger:nodefini.vesignsun.ladvanced

•  Peakage:50•  Mostarecystadenocarcinomas

FemaleReproduc.veSystemOutline

•  Cervix

•  Uterus

•  Ovaries

•  Breast•  Fibrocys.cchange•  Tumors

Fibrocys.cChange

•  Twokinds:nonprolifera.veandprolifera.vechange•  Cause:exaggera.onofnormalbreastcycles

•  Rarelyassociatedwithincreasedcancerrisk

•  Verycommon(presentinmostwomenatautopsy)

•  Calledfibrocys.cchange,notfibrocys.cdisease

Fibrocys.cchange

Fibroadenoma

•  Mostcommonbenignbreasttumor

•  S.mulatedbyestrogen

•  Peakincidencein20s

•  Solitary,discrete,moveablemass

•  Fibrous.ssuewithcompressedductsandlobules

Fibroadenoma

BreastCarcinoma

•  233,000newcases/40,000deathsin2014•  Mostcommon,2nddeadliestcancerinwomen

•  Life.merisk:1in8

•  75%ofpa.entsare>50•  Ratewasincreasingbutnowstable

BreastCarcinomaRiskFactors

•  Age•  Familyhistory

•  Increasedestrogenexposure

•  Obesity•  Alcoholconsump.on

•  High-fatdiet

BreastCarcinomaHistologicTypes

Non-invasive•  Ductalcarcinomainsitu(DCIS)•  Lobularcarcinomainsitu(LCIS)

Invasive•  Ductal•  Lobular•  Inflammatory•  Others

Invasivebreastcarcinoma