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CNSpathologyThirdyearmedicalstudents
DrHeyamAwad2018
Lecture1:anintroduction
CNScourse
• Thisisa7hourcourseandthetopicscoveredareimportantforyourclinicalyearsandyourworkasadoctorinanyspecialityyouchoose.Pleasegiveittheimportanceitdeserves.• Wesynchronisedthelectures’topicsbetweenalldisciplines(mainlyanatomy,physiologyandpathology)soyoucanunderstandsubjectsfullyandeasilyandweminimisedrepetitionoftopicsbetweendisciplines.• Isentthecoursesyllabus,ILOSandlecturedistribution.Pleasehavealookatthesetofamiliariseyourselfwiththecourse.• Pleasenotethefacultyisbeingverystrictwithattendancepolicy,makesureyoudon'tputyourselfintotrouble;wewillnotbeabletohelpyouwiththis.
Pathologylectures
• Asusualwewillhavetwosetsofslides;oneasapresentation,andadetailedslideforthecontentofthelectures.• Thedetailedslideswillcontainalltheinformationyouneedfortheexam.• AtthebeginningofeachslideIwilllistthelearningoutcomesofthelecture,attheendIwillputasummaryofthemainpointsyouneedtoconcentrateonaswellaspracticequestionstocheckyourunderstandingandtoknowwhattoexpectintheexam.• Theslideswillbeavailableonyourwebsiteandthetheelearningbeforethelectureday.
Lecture1:introductionILOS• AquickrevisionoftheCNSstructureincludingbrainlobesandsomeoftheirfunctions• Tounderstandtheasymmetrybetweentherightandlefthemispheres,withexamples.• Toknowthestructureandfunctionofneuronsandglialcells• Tounderstandhowneuronsandglialcellsrespondtoinjury.• Toapplytheaboveknowledgeinunderstandingbraindiseases
CNS
• TheCNSiscomposedofthebrainandthespinalcord.• Itsmainfunctionistoreceiveinformation,coordinateitandsendappropriatecommandstotherestofthebody.• CNSiscomposedofwhiteandgreymatter.• Thewhitematteriscomposedofmyelinatedaxons(myelincomposedofcellmembranesofoligodendrocytes).• Thegreymatteriscomposedoftheneuronesofthecortexandcertainnuclei.
Brainlobesthebrainiscomposedoffouranatomicallobes:frontal,occipital,temporalandparietallobes.
Cerebralcortex1.frontallobe• Containstheprimarymotorcortex:performsfinalcorticalmotorprocessing• Broca’sareaintheleftfrontallobecontrolsmotor patternofspeech,ifdamaged=expressivedysphasia=thepersonknowswhathewantstosaybutcannotexpressthem.
2.Temporallobe
• Importantforcomplexprocessingofsensoryinput• ContainsWernicke'sarea:auditory,visualandsomaticassociationscoalesceinthisarea.• Ifdamaged:inabilitytounderstandspokenorwrittenlanguage.(receptivedysphasia)
ThereareassociationsbetweenBroca’sandWernicke’sareas
3.Parietallobe
• Containshighordersensoryareas• Containsareafornamingobjects• Containsareaforprocessingofvisuallanguage=reading
4.Occipitallobe:Containsthevisualcortex
Brainasymmetry
Whyunderstandingbrainasymmetryisimportant?• Samediseaseprocessescanhavedifferentconsequencesaccordingtothesideaffected• Example:astrokeaffectingtheBroca’sareaintheleftfrontallobecanresultinexpressivedysphasia.Similarlesioninthemirrorimageareaintherightsidemightresultinnosymptomsatall.
BRAINCELLS
• TheCNScontains100billionneurons.• Italsocontains10-50timesthisnumberofglialcells.• 40%ofourgenesparticipateintheformationoftheCNS.
neuron
• IstheprincipalfunctionalunitoftheCNS.• Theyreceiveandtransmitinformation• Matureneuronscannotdivide:theyarepermanentcells• However,neuralprogenitorsarefoundinthebrainandcandivide…..???ExpansionofthesecanhelppatientswithCNSdiseases(thisisanareaofactiveresearch)
Neuralprogenitors
• Neuralprogenitorsarecellsthatarecapableofdividingalimitednumberoftimesandhavethecapacitytodifferentiateintoarestrictednumberofneuronalandglialcelltypes.• Zikavirusinfectionisassociatedwithmicrocephaly,probablythroughinfectingneuralprogenitorscausingtheirdeathandresultingindecreasedbraingrowthinembryos.
ZIKAVIRUS
• Basedonasystematicreviewoftheliteratureupto30May2016,WHOhasconcludedthatZikavirusinfectionduringpregnancyisacauseofcongenitalbrainabnormalities,includingmicrocephaly.itisthoughtthatthevirusdoessobyinfectingprogenitorcells.
Basicstructureofneurons.
Neuronscomeinseveralshapes!
GLIALcells= ةیقبدایالخ
• Aresupportivecells4types:1. Astrocytes2. Oligodendrocytes3. Microglialcells4. Ependymalcells
Astrocytes= ةیمجنایالخ
• givestructuralsupporttoneurons• controlneuralbiochemicalenvironment.• Astrocyteprocessesareassociatedwiththebloodvesselstoformthebloodbrainbarrier
Astrocytes
Oligodendrocytes= نصغتلاةلیلقةیقبد
• Oligodendrocytesformthemyelinsheathwhichsurroundsaxonsandisimportantforfasttransmissionofactionpotentialbysalutatoryconduction
Microglialcells= ةریغصلاةیقبدلاایالخلا
• Microglia:bloodderivedmacrophages
Ependymalcells ةیبصعلاةناطبلاایالخ =
• Theylinetheventricleandthespinalcord.
ReactionofneuronstoACUTE injury
• Acute neuronalinjuryformsredneurons• redneutronsresultusuallyduetoacuteinjuryduetohypoxiaorischemia.• redneuronistheearliestmorphologicmanifestationofneuronalcelldeath• Appearafter12-24hoursofirreversible injury• Characterisedmicroscopicallybyshrinkageofcellbody,pyknosis,disappearanceofthenucleolusandLossofNisslsubstance(seenextslidefordefinition)• lossofNisslsubstanceresultsinintensecytoplasmiceosinophilia
• Nisslsubstance:largegranularsubstancefoundinneurons.Thesegranules areofroughendoplasmicreticulum(RER)withrosettesoffreeribosomes,andarethesiteofproteinsynthesis.
Redneurons
Redneurons
Subacuteandchronicneuronalinjury
• =degeneration• Neuronaldeathduetoprogressivedisease• Example:inAlzheimer• Celllossaffectingfunctionally relatedneurons(notnecessarilystructurallyrelated)
-Neuronaldeathusuallyisapoptoticdeathandisassociatedwithreactivegliosis.
GLIOSIS
• Gliosis isanonspecific reactivechangeofglialcellsinresponsetodamagetoCNS.Inmostcases,gliosis involvestheproliferation&/orhypertrophyofseveraldifferenttypesofglialcells,includingastrocytes,microglia,andoligodendrocytes.
• SO:GLIALCELLSCANPROLIFERATEANDDIVIDEINRESPONSETOINJURY.
Gliosissimplymeansincreasedglialcellsthinkofitascounterpartoffibrosisintherestofthebody
Reactionofastrocytestoinjury
• Astrocytesaretheprinciplecellsresponsibleforrepairandscarformation=gliosis• Reactiveastrocytesduringrepairundergochanges=gemistocyticastrocyte.
repair
• Astrocytesarethemaincellsresponsibleforrepairandscarformation(gliosis).• Injurycausesthefollowingchangesinastrocytes:• 1.hypertrophyandhyperplasiainastrocytes.• 2.enlargednuclei• 3.prominentnucleoli.• 4.increasedpinkcytoplasm.• 5.increased,ramifyingprocessesThesechangesinastrocytes:gemistocyticastrocyte.
gemistocytes
Gemistocytes
ReactionsofMicrogliatoInjury
• Microgliaaremesoderm-derivedphagocyticcellsthatserveastheresidentmacrophagesoftheCNS.• Theyrespondtoinjuryby(1)proliferating;(2)developingelongatednuclei(rodcells) (3)formingaggregatesaroundsmallfocioftissuenecrosis(microglialnodules);or(4)congregatingaroundcellbodiesofdyingneurons(neuronophagia).• Inadditiontoresidentmicroglia,blood-derivedmacrophagesmayalsobepresentininflammatoryfoci.
Microglialnodules..youcanthinkoftheseasgranulomas=aggregatesofmicrogliawhicharebasicallymacrophages.
Rodcells
ExamquestionAllofthefollowingstatementsarecorrectaboutthecellsseeninthispictureexcept:
A.originatefromastrocytes
B.indicatethestartofarepairprocessafterinjury
C.canbeseenaroundareasofdemyelination.
D.cellsoforiginarepermanentcells
E.canbeseeninthevicinityofresolvedinfarction.
Answertopreviousquestion
• D..becausegemistocytesoriginatefromastrocyteswhichareglialcellsandunlikeneurones,glialcellsdodivide;theyaren'tpermanent• therestofthechoicesareobviouslycorrect.Notethegemistocytescanbearesponsetoanyformofinjurysothechoicesaboutdemyelinationandoldinfarctarecorrect.
Examstylequestion
• A27yearoldfemaleunderwentacaesariansectionduringwhichshehadmassivebleeding.Hersystolicbloodpressuredroppedto45.Thebleedingcontinuedandshedied13hoursaftertheoperation.Ifyouweretodotheautopsyexamyouwouldexpecttoseewhichofthefollowingchangesinherneurons• A.cytoplasmicbasophilia• B.Prominentnucleoli• C.cellswelling• D.pyknosis• E.Gliosis
Explanationofthequestion
• Thescenariohereisaboutacuteischemicdamage.the13hourperiodmeanthatthemorphologicchangeshavedeveloped.Rememberthatredneuronesarethefirstmorphologicmanifestationofischemicdamageandtheyneed12hourstodevelop.• ObviouslytheonlycorrectchoiceisD,therestarewrongandglossiswrongbecauseit’snotaneuronaldamageandisnotanacutechange.
Afinalnote
• theexamquestionswillbesimilartothequestionsintheexamplesabove,andsomewillbeclinicallyoriented..soyouknowwhattoexpect.
• Foryourinformation:thewordneuroneiswrittenwithane attheend(British)orwithoutane (Americanstyle)
SUMMARY1/3• CNScellsareoftwotypes:neuronesthatarethefunctionalunitsandglialcellswhicharesupportive.glialcellsaremuchmoreabundant.• Glialarefourtypes:• 1.astrocytesthataresupportive,controlthemicroenvironment,formpartofthebloodbrainbarrierandareresponsibleforgloss(fibrosisandscarringofCNS).• 2.Oligodendrocytes:theircellmembranesformmyelinsheathimportantforinsulatingnerveimpulsesthusmakingtransmissionquicker• 3.Ependymalcells,linetheventriclesandspinalcordcavity.SpecialisedependymalformchoroidplexusthatsecretesCSF• 4.MicrogliaarespecialisedresidentmacrophagesimportantforinflammatoryandimmunologicreactionofCNS.
SUMMARY2/3
• Neuronesrespondtoacute injurybychangingtored neutrons.theyappear12hoursafterirreversibleinsultandcharacterisedbycytoplasmicshrinkageandincreasedeosinophilia(duetolossofNisslsubstance),pyknosis,lossofnucleolusandincreasedramifyingprocesses.• subacuteorchronicneuronalinjurycausesdegenerationanddeathofneurones,usuallybyapoptosis(todecreaseriskofdamaginginflammation).• chronicneuronalinjuryusuallyaffectsfunctionallyrelated neurones
SUMMARY3/3
• glialcellsarelessvulnerabletoacuteinjuryandrespondduringrepairprocessandgliosisformation.• Astrocytesarethemaincellsinvolvedinrepairandrespondbyforminggemistocytes:hypertophiccellswithlargeeosinophiliccytoplasm,largenucleiandprominentnucleoli• glialcellscanproliferatewhileneuronescannot(althoughneuronalprogenitorshavealimitedcapacitytodivide)• Microgliarespondtoinjuryby:hyperplasia,rodcells,neurophagiaandmicroglialnoduleformations.