病理学教学课件：Disease of Central Nervous System

Disease of Central Nervous SystemThe nervous system（神经系统）神经系统）central nervous system(CNS)brain spinal cordperipheral nervous system(PNS)2Disease of CNS nIntroductionnBasic pathological changes Neurodegenerative disease:AD;PD.nCommon complicationsnHemodynamic Derangement&Cerebral Vascular DisordersnTumornInfection disease31.Delicate structure,more than 50%human genes are neuronal related：structure or metabolism;complex or arcaneIntroduction:Disease of CNS42.Lesions may have location indication (selective dysfunction)signal to and from different regions of the body are controlled by very specific areas within the nervous system nervous system vulnerable to focal lesions Introduction:Disease of CNS53.Dual influences of some structures such as skull and dura,protection of brain and may facilitate increased intra-cranial pressure.6Introduction:Disease of CNS4.Special disease:Degenerative disease Demyelination disease Psychiatric diseases less understandingCongenital anomalies:high incidence7Cells in CNS Neuron glia cells astrocyte oligodendrocyte microglial cellsBasic pathological changes of cells in CNSNeuropil:process of the cells in the CNS to form a delicate fibrillary background Basic Changes of Cells Neuron（神经元）神经元）9Basic Changes of Cells Neuron（神经元）神经元）1.Central Chromatolysis(中央性尼氏小体溶解中央性尼氏小体溶解)Cause：axonal injury,Viral infection,deficiency of Vit.B,anoxia.Morphology:Sequalae:In early stage,increased dissociated ribosome from RER may facilitate protein synthesis.The change would be reversible,if cause abolished.Insistent change may lead to neuronal death.Normal Neuron Central Chromatolysis101.1.尼氏体尼氏体(Nissl bodies)Nissl bodies)rough endoplasmic reticulum(RER)Basic Changes of Cells Neuron（神经元）神经元）11Basic Changes of Cells Neuron（神经元）神经元）1.Central Chromatolysis(中央性尼氏小体溶解中央性尼氏小体溶解)Cause：axonal injury,Viral infection,deficiency of Vit.B,anoxia.Morphology:Sequalae:In early stage,increased dissociated ribosome from RER may facilitate protein synthesis.The change would be reversible,if cause abolished.Insistent change may lead to neuronal death.Normal Neuron Central Chromatolysis102.Ischemic Changes（Acute Necrosis）Cause：ischemia,anoxia,hypoglucemia,lower blood pressure,epilepsy Morphology：vacuolation,red neuron,ghost cell Basic Changes of Cells Neuron VacuolationRed Neuron12Basic Changes of Cells Neuron 3.Neurophagia(嗜神经元现象）嗜神经元现象）dead neuron engulfed and phagocytosed by M.134.Inclusion Bodies(包涵体包涵体)viral infections;neurodegenerative disease (1)Rabies:Negri body diagnostic hallmark of rabies HSV;Encephalitis B Jap.virus;Poliovirus Basic Changes of Cells Neuron Negri Body144.Inclusion Bodies(包涵体包涵体)Parkinson Dis.：Lewy bodyMuhammao Ali Substantia nigraBasic Changes of Cells Neuron 15Neurodegenerative changes:SP,NFTsvSenile Plaque(SP,老年斑老年斑)：the core composed with-amyloid protein,surrounded by a halo and swollen degenerative axons Basic Changes of Cells Neuron 4.Inclusion Bodies(包涵体包涵体)16神经原纤维（神经原纤维（neurofibrilneurofibril）17vNeurofibrillary Tangle(NFTs,神经原纤维缠结神经原纤维缠结):a.the tangle composed by double spiral strands of neurofibils with abnormal phosphorylated tau proteinb.marker of dying neuronc.seen in Alzheimers Dis.,boxer brain,post-encephalitis,ParkinsonismBasic Changes of Cells Neuron 4.Inclusion Bodies(包涵体包涵体)18Senile PlaqueNeurofibrillary Tangle Alzheimers disease ADHigh density and widespread distribution of plaques and tangles in the neocortical areas in the setting of dementia that allows one to make a diagnosis of AD195.Wallerian Degeneration(华勒变性）华勒变性）usually occur in traumatic transfection of a nerveBasic Changes of Cells Neuron 20 Neuron Immunofluorescence Anti glial fibrillary acid protein(GFAP)Astrocyte are the major supporting cells in the brainBasic Changes of Cells astrocyte HE staining naked nucleiSliver impregnation21Basic Changes of Cells Astrocyte（星形胶质细胞）星形胶质细胞）vHypertrophy：The cytoplasm is shown with HE stain.The processes elongate The cell and its nuclear are enlarged with binuclei,multinuclei or bizarre nucleivProliferation：reactive astrogliosis:repair process after insults forming glial scar.Seen in local anoxia,edema,infarct and at the periphery of abscess or tumor.22Basic Changes of Cells Astrocyte（星形胶质细胞）星形胶质细胞）-Rosenthal fibernHE:a thick,elongated,worm-like or corkscrew eosinophilic(pink)bundle that is found on H&E staining of the brain nThe fibers are found in astrocytic processes and are thought to be clumped intermediate filament proteins(GFAP).nlong standing gliosis,occasional tumors(pilocytic astrocytoma),and some metabolic disorders(Alexanders disease).pilocytic astrocytomavCorpora amylacea(淀粉样小体）淀粉样小体）:increased with aging glycoprotein-rich material located at the end process of astrocytes,especially in the subpil and perivascular zonesBasic Changes of Cells Astrocyte（星形胶质细胞）星形胶质细胞）23Basic Changes of Cells Oligodendrocyte (少突胶质细胞少突胶质细胞)Myelin formation cells in CNS(in PNS:Schwann cellsHE staining:in size and shape like lymphocytevLeucodystrophy(白质营养不良白质营养不良)myelin sheath formation disturbance different congenital enzyme deficiencyvDemyelination(脱髓鞘病变脱髓鞘病变)formed myelin sheath destroyed due to allergy,anoxia or toxificationPerivascular demyelination(Luxol fast blue staining)24nProgressive multifocal leukocephalopathy(PML)-Demyelinating diseasenThe cause of PML is a type of polyomavirus called the JC virus(JCV)nSevere immune deficiency,such as transplant patients on immunosuppressive medications,patients receiving certain kinds of chemotherapy or AIDS patients(5%)Basic Changes of Cells Oligodendrocyte (少突胶质细胞少突胶质细胞)-intranuclear inclusionsn PML destroys oligodendrocytes;produces intranuclear inclusionsMicroglia (小胶质细胞）小胶质细胞）Resting microglia may activated and turn into M (1)Focal proliferation forming microglial nodule (2)Rodlike microglia seen in advanced syphilis25Gitter cell/foam cells26Microglial nodule -rod cells27 normally line the ventricular cavities and the central canal of the spinal cord Silence,Oncogenesis,Deficiency after injury may repaired by astrocyte,forming so called granular ependymitis (颗粒性室管膜炎颗粒性室管膜炎)Basic Changes of Cells Ependymal cells(室管膜细胞室管膜细胞)28Common Complicationsn脑水肿脑水肿 （Brain Edema)n脑积水（脑积水（hydroceplus)n颅内压升高及脑疝（颅内压升高及脑疝（herniation)20Common Complications脑水肿脑水肿 （Brain Edema)Increased water contents within brain parenchymaCause:anoxia,infarction,inflammation,injury,toxification and tumor.Mechanism:1.Vasogenic:disrupted normal BBB interstitial edema white mattergray matter 2.Cytotoxic:cytomembranous pump(ATPase)intracellular edema white matter=gray matter usually mixed typeComponentsComponentsnEndothelial cellsEndothelial cellsnBasal membraneBasal membranenpericytepericytenAstrocytic feet Astrocytic feet 血脑屏障（血脑屏障（Blood-Brain Barrier,BBBBlood-Brain Barrier,BBB）Functions protection EdemaEdemaMorphology:brain volume,weight,narrow sulci,widened gyri,cutting surface showed small ventricle,increased reflection.Herniation may ensure.Common complications Hydrocephalus（脑积水脑积水)Accumulation of excessive CSF with ventricular dilatation as a result of a disturbance of its secretion,circulation and absorption CSF:cerebrospinal fluidThree layers of the meningesvdura mater leptomeningesvthe arachnoid mater(arachnoid villi)the subarachnoid space(CSF)v the pia Circulation of CSF Choroids plexus-ventricular system-arachnoid villiThe rate of formation and absorption of CSF remain in balanceFunction:act as the lymphocytic drainage in the brain1.Over-secretion of CSF(tumor of choroid plexus)2.Absorption disturbances of CSF1)Noncomunicating(obstructive)：tumor,inflammatory,adhesion,hemorrhage,or deformity in III ventricle.2)Communicating:meningitis,subarachnoid hemorrhage,with subsequent organization,or causing scarring of arachnoid granulation or Villi.Cause&PathogenesisMorphology:Dilation of ventricles with atrophy of parenchyma of brain,due to compression of CSF.CPC:headache,vomiting,papilloedema of optic N.Common complications Hydrocephalus（脑积水脑积水)Common complicationHypertension of intracranial pressure(ICP)and Herniation (颅内压升高和脑疝形成）颅内压升高和脑疝形成）The CSF pressure more than 2kPa(normally 0.6-1.8 kPa)with lateral recumbent position Cause：（1）cerebral edema,hydrocephalus（2）occupying lesion:tumor,hemorrhage,hematoma（3）inflammation:meningitis,cerebral abscess,encephalitis（4）brain infarctionThe factors influence the results:（1）the size of the lesion and its development rapidity.（2）existed cranial cavity situationsenile atrophy or unclosure of fontanelle allowing more space for expending of brainHypertension of ICP&HerniationSequalae：（1）headache,vomiting,papilloedema,coma,death Hypertension of ICP&HerniationSequalae：(2）herniation1)Subfalcine(cingulate gyrus)herniation：v local tissue hemorrhagic and necrotic,v weakness and sensory dysfunction of legCommon complicationsHypertension of ICP&HerniationAnterior cerebral arteryHerniation:displacement of brain tissue from one intracranial component into another,or into the spinal canal 1.Subfalcine(cingulate gyrus)herniation 2.Transtentorial(uncinate gyrus)herniation 3.Tonsillar herniation 4.External cerebral herniation2)Transtentorial(uncinate gyrus)herniation：v ipsilateral III N compressed leading to pupils constricted dilatedv Kernohan incisionv paralysis of ipsilateral extremities (false localization sign)v periaquaductal hemorrhagethe cerebral pedunclethe corticospinal tractIII oculomotor nerve海马钩回疝海马钩回疝Transtentorial(uncinate gyrus)herniation：Transtentorial(uncinate gyrus)herniation：vipsilateral III N compressed leading to pupils constricted dilated “blown pupil”vparalysis of ipsilateral extremities (false localization sign)foramen magnumHypertension of ICP&Herniation3)Tonsillar herniation,life-threatening press respiration centers in medulla oblongata sudden death virtal respiratory and cardic centers in the medullaforamen magnumHemodynamic Derangement&Cerebral Vascular DisordersHemodynamic Derangement&Cerebral Vascular DisordersCirculation disturbances:ischemic encephalopathy infarction(thrombotic or embolitic)hemorrhageVascular disorders:arteriolosclerosis,atherosclerosis,arteritis,aneurysm,ateriovenous malformation(AVM)widespread ischemia/hypoxia injury occurs due to a generalized reduction of cerebral perfusion caused by hypertension,cardiac arrest,hemorrhage and shock.the brain:1%2%of body weight oxygen consumption about 20%systolic pressure less than 50mmHg will cause severe brain injuryHemodynamic Derangement&Cerebral Vascular Disorders global cerebral ischemia/ischemic EncephalopathyPredisposing factors：vhigher metabolic rate：more susceptible NeuronAsOligoEndo Gray MatterWhite Matter 3rd、5th、6th layers of cortex are most vulnerable vPersistence and severity of ischemia mild ischemia:no remarkable change severe ischemia,survive few hours before death:not remarkable moderate ischemia,survive more than 12 hours：typical changesvArchitecture of cerebral arteries the location at the border zone of cerebral arteries is much more vulnerable.Border zone of cortex C shape Architecture of Cerebral ArteriesChanges:vlaminar cortical necrosis:neurons in 3rd,5th,6th layers of cortex involvedvhippocampus sclerosis：pyramidal neuron deathvborder zone infarction：early stage：“C”shaped infarct later stage:astrogliosis(granular atrophy)cardiopetal developmentglobal necrosis(respirator brain)Hemodynamic Derangement&Cerebral Vascular DisordersIschemic EncephalopathyLaminar Cortical NecrosisHemodynamic Derangement&Cerebral Vascular DisordersIschemic EncephalopathyFresh border zone infarctGranular atrophy(gliosis)Cutting surface of granular atrophyRespirator brainHemodynamic Derangement&Cerebral Vascular DisordersIschemic EncephalopathyCPC：weakness sensation abnormalities coma,persistent vegetative state death clinical criteria for brain death respirator brain:autolytic process brown discoloration and unfixed brainperson in a vegetative state/vegetable can wake up?Hemodynamic Derangement&Cerebral Vascular DisordersFocal Cerebral IschemiaCause：thrombosis,embolism,space occupying lesion,local vessels compressed by herniationTypes:thrombotic:on the sites of atherosclerosis inner carotid A,basilar A,cerebral arteries,The symptoms:insidious and gradual development from weakness of muscles to semiplegia or comaembolic:the emboli often are cardiogenic,or from atherosclerotic plaque,with sudden onset and poor prognosis.Hemodynamic Derangement&Cerebral Vascular DisordersCerebral InfarctionThe most common form of cerebrovascular disease,accounting for 70%80%of all cerebral vascular accidents“stroke”Changes:extent of ischemia:vOcclusion in inner carotid artery:circle willis may compensate completely,no infarctionvOcclusion in mid-size artery:as middle cerebral A,the infarct smaller than its supply area due to partial anastomosis.vOcclusion in terminal arteries:leading to supplied area infraction.Hemodynamic Derangement&Cerebral Vascular DisordersCerebral InfarctionTypes:vwhite infarctvred infarct:incomplete occlusion or frangible emboli going further to small vessels,resulting in blood escape from injured vascular wall.Morphology changes:v first 412h:normalv then:ischemic neuronal changesv 36-48h:swollen and soft;demarcation between gray and white matter becomes blurred due to edemav the third day:macrophage,progressive marked demarcation of the lesionv 1 month:liquefaction,irregular cavitiesv 6 month:completely liquefied with gliosis(scar)Pathological changes ischemic neuronal changesliquefaction,irregular cavitiesreactive gliosisTwo important terms of Brain infarction vLacunae(腔隙性梗死）腔隙性梗死）:sharply defined necrosis less than 1.5cm in diameter,corresponding to the territory of a single perforating artery,the main cause of lacunae was considered to be hypertensionTwo important terms of Brain infarction vLacunae(腔隙性梗死）腔隙性梗死）:sharply defined necrosis less than 1.5cm in diameter,corresponding to the territory of a single perforating artery,the main cause of lacunae was considered to be hypertensionvTIAs(transient ischemic attacks 一过性脑缺血一过性脑缺血)transient episode of neurologic dysfunction lasting several minutes24 hours an important predictor of subsequent infarcts 1/3 patients with TIA developing clinically significant infarcts within 5 years Infarction area supplied by middle cerebral A.Hemodynamic Derangement&Cerebral Vascular DisordersBrain HemorrhageIntracerebral HemorrhageCause:hypertension*congenital saccular aneurysms,tumors,hemorrhagic diathesis,vasculitis,AVM,trauma Hypertension accounts for about half of Spontaneous brain hemorrhage Pathogenesis:anoxia of vascular wallanoxia of perivascular tissue Charcot Bouchard microaneurysmsmicro-softening focivessels rupturedspasm of vessels B.P hemorrhagenOccur in small blood vessels(less than 300 micrometre diameter)nOften located in the lenticulostriate vessels of the basal ganglia and are associated with chronic hypertensionn A common cause of stroke Charcot Bouchard microaneurysmsCommon locations:the putamen,caudate,thalamus,pons,and cerebellum.Changes:In the center of foci,normal structure is destroyed and filled with RBC，at periphery multifoci of hemorrhage The old hemorrhage foci becomes cavitated&with hemosiderin.Hemodynamic Derangement&Cerebral Vascular DisordersBrain HemorrhageHypertensive HemorrhagesCPC：vB.G hemorrhage:directed to insular contralateral semiplegia directed to ventricle,thalamus deathvPons hemorrhage:pin-like pupils,persistent high fever or sudden deathvCerebellar hemorrhage:severe occipital headache,frequent vomitingHemodynamic Derangement&Cerebral Vascular DisordersBrain HemorrhageCerebral HemorrhageSubarachnoid hemorrhagenThe most common cause of spontaneous(nontraumatic)nRupture of a saccular(berry)aneurysm approximately 1%of the general population different from the fusiform dialtion in atheroslcerosis or infectious(mycotic)aneurysm 80%arise at the arterial bifurcations in the territory of the internal carotid artery:MCA,ACMnDeveloped the infarct of brain parenchymaCPC:Abrupt,severe headache,vomitting,loss of consciousness Meningeal signs Bloody CSF 50%died in several days acute hydrocephalus herniation brain infarction chronic:hydrocephalusVascular malformationnAbnormalities in angiogenesis in the developing brainn AVM:the most common caused vessels of variable caliber including A,V Hemorrhagic,calcification,reactive gliosisTumors of CNSAstrocytoma（星形胶质细胞瘤星形胶质细胞瘤)The most common categories of brain tumors in CNS Gliomas shares 40%of brain tumors，astrocytoma shares 70%of gliomasMost astrocytomas are of diffuse infiltrativeAstrocytomas in Children and Adults Location differentiation demarcation often in brain stemcerebellum beneathtentoriumwell,gelatinousin gross appearanceChildrenpoormost often above tentorium in hemispheresrelatively poor granular in gross appearancewellAdultsPage 417Morphology:npilocytic astrocytoma:common in children,elongated processes extend from two poplars(grade I)nfibrillary astrocytoma and cytoplasmic astrocytoma:mimic their original astrocytes(grade II)ngemistocytic astrocytoma:(grade IIIII)nanaplastic astrocytoma:(grade III)nglioblastoma multiform:(grade IV)GFAP(+)Tumors of CNSAstrocytoma（星形胶质细胞瘤星形胶质细胞瘤)Gross inspection of astrocytomaAstrocytoma(WHO Grade II)Cytoplasmic astrocytomaAnaplastic astrocytoma WHO Grade IIIAnaplastic astrocytoma WHO Grade IIIglioblastoma multiform(GBM)WHO Grade IVglioblastoma multiform(GBM)WHO Grade IVGlioblastoma Multiform(GBM)The tumor originates from menigoepithelium of arachoid granules villa or fibroblasts.Its grows outside the brain,pressing the brain parenchyma and may be resected complete.Grossly:tumor shows spherical or lobulated,expanding in growthHistology:Menigothelial or syncytial type Fibroblastic variants Transitional type OthersPrognosis:most benign,a few(15%)recurs after resection,few undergoes malignant transformation EMA(+)Vimentin(+)Tumors of CNS Meningioma（脑膜瘤脑膜瘤)Meningioma（脑膜瘤脑膜瘤)Gross inspectionMicroscopic appearance psammoma bodyvEmbryogenic tumor,malignant,mostly seen in children under ten with poor prognosisvThe tumor originates from primitive neuroecdermal cells of vermis or out layers of granular cells of cerebellum.vThe tumor shows whitish pink or gray in color,located at IV ventricle or cerebellar hemisphere.vThe cells are small,primitive with scanty cytoplasm.The nuclei are round or carrot-shaped with frequent mitoses.Sometimes,may surround a fibrillary core having rosette formationvMutual differentiation:GFAP（+）NF（+）Tumors of CNS Meduloblastoma（髓母细胞瘤髓母细胞瘤)Medulloblastoma（髓母细胞瘤髓母细胞瘤)Gross inspectionMicroscopic appearancevThe benign tumor originates from schwann cell,often located at 8th nerve(acoustic neurilermmoma 听神经瘤）听神经瘤）or trunk of peripheral N.v Slow growth,very rare malignant transformationv Spherical,or lobulated mass,white-gray in color on cut surface,or shows light yellow color when mucinous degeneration occur.quite often cavitation vSpindle shaped cells,in whirl or tight arrangement (Antoni A type)or in reticular arrangement（Atoni B型）型）Tumors of CNS Schwannoma（神经鞘瘤神经鞘瘤,施万氏瘤施万氏瘤)Schwannoma（神经鞘瘤神经鞘瘤,施万氏瘤施万氏瘤)Microscopic appearanceGross inspection1.Etiology:the disease cause by living pathogens,which are infective,endemic in certain geographic areas and in certain seasons (传染性，流行性，地方性，季节性）传染性，流行性，地方性，季节性）2.Unique route of invasion,a given pathogen has:vunique entrance of invasionvunique mode of spreading among hostvunique affinity for special tissue or organs,causing special pathological changes3.Pathogenesis v bacteria:endotoxin and/or exotoxinv viruses:cellular and/or humoral immunityInfectious DiseaseCommon Features(共同特性）共同特性）4.Basic pathologic changes:inflammation(acute/chronic)depending on host pathogen host:immunity pathogen:invasion ability,toxins,metabolic substance evocation of allergic reaction of host5.Clinical coursev Incubation period:v Pre drome period:non specific symptoms and signsv Dominant period:diagnostic symptoms and signs peakv Recovery period:the disease subsides typical/atypical/subclinical courseInfectious DiseaseCommon Features(共同特性）共同特性）免疫性免疫性6.ConsequencesvComplete recovery