《病理学》教学课件：9 CNS疾病

1、Disease of Central Nervous System,The nervous system（神经系统） central nervous system(CNS) brain spinal cord peripheral nervous system(PNS),2,Disease of CNS,Introduction Basic pathological changes Neurodegenerative disease : AD ; PD. Common complications Hemodynamic Derangement complex or arcane,Introdu

2、ction : Disease of CNS,4,2. 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 CNS,5,3.Dual influences of s

3、ome structures such as skull and dura, protection of brain and may facilitate increased intra-cranial pressure.,6,Introduction : Disease of CNS,4. Special disease : degenerative disease demyelination disease psychiatric diseases less understanding Congenital anomalies: high incidence,7,Cells in CNS

4、Neuron glia cells astrocyte oligodendrocyte microglial cells,Basic pathological changes of cells in CNS,Neuropil: process of the cells in the CNS to form a delicate fibrillary background,Basic Changes of Cells Neuron（神经元）,9,Basic Changes of Cells Neuron（神经元）,1.Central Chromatolysis (中央性尼氏小体溶解) Cause

5、： 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 Chroma

6、tolysis,10,1. 尼氏体 (Nissl bodies),rough endoplasmic reticulum (RER),Basic Changes of Cells Neuron（神经元）,11,2.Ischemic Changes （Acute Necrosis） Cause：ischemia, anoxia, hypoglucemia, lower blood pressure, epilepsy Morphology：vacuolation, red neuron, ghost cell,Basic Changes of Cells Neuron,Vacuolation,R

7、ed Neuron,12,Basic Changes of Cells Neuron,3. Neurophagia(嗜神经元现象） dead neuron engulfed and phagocytosed by M.,13,4. Inclusion Bodies (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

8、 Neuron,Negri Body,14,4. Inclusion Bodies (包涵体) Parkinson Dis.： Lewy body,Muhammao Ali,Substantia nigra,Basic Changes of Cells Neuron,15,Neurodegenerative changes : SP, NFTs Senile Plaque (SP , 老年斑)： the core composed with -amyloid protein, surrounded by a halo and swollen degenerative axons,Basic C

9、hanges of Cells Neuron,4. Inclusion Bodies (包涵体),16,神经原纤维（neurofibril）,Normal structure,17,Neurofibrillary Tangle (NFTs, 神经原纤维缠结): the tangle composed by double spiral strands of neurofibils with abnormal phosphorylated tau protein marker of dying neuron seen in Alzheimers Dis., boxer brain, post-en

10、cephalitis, Parkinsonism,Basic Changes of Cells Neuron,4. Inclusion Bodies (包涵体),HE,Sliver impregnation,18,Senile Plaque,Neurofibrillary Tangle,Alzheimers disease AD,High density and widespread distribution of plaques and tangles in the neocortical areas in the setting of dementia that allows one to

11、 make a diagnosis of AD,19,5. Wallerian Degeneration (华勒变性） usually occur in traumatic transfection of a nerve,Basic Changes of Cells Neuron,20,Immunofluorescence Anti glial fibrillary acid protein (GFAP),Astrocyte are the major supporting cells in the brain,Basic Changes of Cells astrocyte,HE stain

12、ing: naked nuclei,Sliver impregnation,21,Basic Changes of Cells Astrocyte,Hypertrophy： The cytoplasm is shown with HE stain. The processes elongate The cell and its nuclear are enlarged with binuclei, multinuclei or bizarre nuclei Proliferation ： reactive astrogliosis: repair process after insults f

13、orming glial scar. Seen in local area of anoxia, edema, infarct and at the periphery of abscess or tumor.,22,Basic Changes of Cells AstrocyteRosenthal fiber,HE: a thick, elongated, worm-like or corkscrew eosinophilic (pink) bundle that is found on H produces intranuclear inclusions,Microglia (小胶质细胞）

14、 Resting microglia may activated and turn into M (1) Focal proliferation forming microglial nodule (2) Rodlike microglia seen in advanced syphilis,25,Gitter cell/foam cells,26,Microglial nodule - rod cells,27,normally line the ventricular cavities and the central canal of the spinal cord Oncogenesis

15、, Deficiency after injury may repaired by astrocyte, forming so called granular ependymitis (颗粒性室管膜炎),Basic Changes of Cells Ependymal cells (室管膜细胞),28,Common Complications,脑水肿 （Brain Edema) 脑积水（ hydroceplus) 颅内压升高及脑疝（ herniation),20,Common Complications脑水肿 （Brain Edema),Increased water contents wit

16、hin brain parenchyma Cause: 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 type,Edema,Mor

17、phology: brain volume, weight, narrow sulci, widened gyri, cutting surface showed small ventricle, increased reflection. Herniation may ensure.,Common complications Hydrocephalus （脑积水),Accumulation of excessive CSF with ventricular dilatation as a result of a disturbance of its secretion, circulatio

18、n and absorption CSF: cerebrospinal fluid,Three layers of the meninges dura mater leptomeninges the arachnoid mater(arachnoid villi) the subarachnoid space(CSF) the pia Circulation of CSF Choroids plexus-ventricular system-arachnoid villi The rate of formation and absorption of CSF remain in balance

19、,Function: act as the lymphocytic drainage in the brain,Over-secretion of CSF(tumor of choroid plexus) Absorption disturbances of CSF Noncomunicating (obstructive)： tumor, inflammatory, adhesion, hemorrhage, or deformity in III ventricle. 2) Communicating : meningitis, subarachnoid hemorrhage, with

20、subsequent organization, or causing scarring of arachnoid granulation or Villi.,Cause demarcation between gray and white matter becomes blurred due to edema the third day: macrophage, progressive marked demarcation of the lesion 1 month: liquefaction, irregular cavities 6 month: completely liquefied

21、 with gliosis( scar),Pathological changes,ischemic neuronal changes,liquefaction, irregular cavities,reactive gliosis,Two important terms of Brain infarction,Lacunae(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

22、cause of lacunae was considered to be hypertension,Two important terms of Brain infarction,Lacunae(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 hypertension TIAs( transient

23、ischemic attacks 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 &

24、Cerebral Vascular DisordersBrain Hemorrhage,Intracerebral Hemorrhage Cause: hypertension * congenital saccular aneurysms, tumors, hemorrhagic diathesis, vasculitis, AVM, trauma Hypertension accounts for about half of Spontaneous brain hemorrhage Pathogenesis:,anoxia of vascular wall,anoxia of periva

25、scular tissue,Charcot Bouchard microaneurysms,micro-softening foci,vessels ruptured,spasm of vessels B.P,hemorrhage,Occur in small blood vessels (less than 300 micrometre diameter) Often located in the lenticulostriate vessels of the basal ganglia and are associated with chronic hypertension A commo

26、n cause of stroke,Charcot Bouchard microaneurysms,Common 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 hemosideri

27、n.,Hemodynamic Derangement & Cerebral Vascular DisordersBrain Hemorrhage,Hypertensive Hemorrhages,Cerebral Hemorrhage,CPC： B.G hemorrhage:directed to insular contralateral semiplegia directed to ventricle , thalamus death Pons hemorrhage: pin-like pupils, persistent high fever or sudden death Cerebe

28、llar hemorrhage: severe occipital headache, frequent vomiting,Hemodynamic Derangement & Cerebral Vascular DisordersBrain Hemorrhage,Subarachnoid hemorrhage,The most common cause of spontaneous(nontraumatic) Rupture of a saccular(berry) aneurysm approximately 1% of the general population different fr

29、om the fusiform dialtion in atheroslcerosis or infectious (mycotic) aneurysm 80% arise at the arterial bifurcations in the territory of the internal carotid artery: MCA, ACM Developed the infarct of brain parenchyma,CPC: Abrupt, severe headache, vomitting, loss of consciousness Meningeal signs Blood

30、y CSF 50% died in several days acute hydrocephalus herniation brain infarction chronic: hydrocephalus,Vascular malformation,Abnormalities in angiogenesis in the developing brain AVM: the most common caused vessels of variable caliber including A,V Hemorrhagic, calcification, reactive gliosis,Etiolog

31、y: 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） Unique route of invasion, a given pathogen has : unique entrance of invasion unique mode of spreading among host unique affinity for special tissue or organs ,

32、 causing special pathological changes Pathogenesis bacteria: endotoxin and /or exotoxin viruses: cellular and /or humoral immunity,Infectious DiseaseCommon Features(共同特性）,Basic pathologic changes: inflammation( acute/chronic) depending on host pathogen host: immunity pathogen: invasion ability, toxi

33、ns, metabolic substance evocation of allergic reaction of host Clinical course Incubation period: Pre drome period: non specific symptoms and signs Dominant period: diagnostic symptoms and signs peak Recovery period: the disease subsides typical/atypical/subclinical course,Infectious DiseaseCommon F

34、eatures(共同特性）,免疫性,Consequences Complete recovery the host gains temporary or permanent immunity Chronic course Recurrence of disease Death,Infectious DiseaseCommon Features(共同特性）,Infectious DiseaseCommon Features in CNS(共同特性）,Skull Meninges dura 硬脑膜 arachnoid 蛛网膜 pia 软脑膜 BBB effectively protected CN

35、S from the infective agents Pre-existing immunodeficiency conditions Special virulence factors of pathogens Host defense mechanism are suboptimal to control pathogen infection in CNS,leptomenige （软脑膜）,Page 410,Route of infection Hematogenic: septicema, viremia Local disseminated: opened skull fractu

36、re, sinusitis, mastoiditis Direct infected: trauma, iatrogenic interference (lumbar puncture) Through peripheral nervous system: rabies, HSV,Infectious DiseaseCommon Features in CNS(共同特性）,Inflammation feature,Stereotyped Reaction neurons: degeneration, necrosis secondary demyelination limited exudat

37、ion with perivascular cuffing formation Presence of BBB (blood brain barrier) and V-R space limits the spread of inflammation Absence of intrinsic lymphatic and lymphoid tissue T/B cells are blood born(exogenic) glia nodule formation microglial nodule in early stage. astrocytic nodule in later stage

38、, repair,Components Endothelial cells Basal membrane pericyte Astrocytic feet,血脑屏障（Blood-Brain Barrier, BBB）,Functions protection,Pathogens: Pyogenic meningitis: meningococci, H influenza, Pneumococci, Streptococci, Staphylococci, E Coli Granulomatous meningitis: T.B.mycobacterium, Fungi Lymphocytic

39、 meningitis: viruses, spirochetes,Meningitis,Epidemic Meningococcic Meningitis(流行性脑膜炎双球菌性脑膜炎),Anton Weichselbaum in 1887 Pathogen: meningococcus Spherical, 0.61.0m in diameter, gram negative only infect human often carried in the nose and throat without symptoms Spread by droplet cough or sneezed ou

40、t Epidemic seasons : Winter & Spring,Bacteria spread by air (sneeze and spray), located at nasopharynx, most are bacteria carrier (15% population, in epidemic season:7080%) Victims are children, most younger than 10yrs old Basic changes：acute purulent inflammation (Leptomeninge & CSF ) Clinical symp

41、toms & signs: fever, headache, vomiting, petechia & ecchymosis on the skin & mucosa, meningeal irrigative signs, shock in severe cases Temporary immunity after recovery,Epidemic Meningococcic Meningitis(流行性脑膜炎双球菌性脑膜炎),Meningitis,Pathogen: meningococci, endotoxin and capsule are pathogenic Route of i

42、nfection:,Spray from carrier,Mucosa of nasopharyx,Blood (septicemia or bacteremia),leptomeniges,meningitis,Usually 5%30%, 7080% in epidemic period,URI, catarrh (sore throat red and edematous mucosa, mucous discharge),Petechia ecchymosis,Bacterial emboli,Vascular paralysis, dilation, thrombosis,shock

43、,bilateral severe hemorrhage of adrenal cortex ( Waterhouse- Friderichsen syndrome),(+),Meningitis,Pathological Changes: Vassels: bacterial thrombi, thrombosis, focal hemorrhage Meninge: acute purulent inflammation,Gross: dura: tense, hyperemic Subarachnoid space filled with grayish yellow pus espec

44、ially at convex of hemisphere at the base in cisternae along circle Willis, roots of cranial & spinal Nerves,Purulent Meningitis,LM： Strikingly enlarged subarachnoid space with large amount of purulent exudation , mainly polys. Vascular congestion Adjacent brain parenchyma be edematous,MeningitisCli

45、nical Pathological Correlation(CPC),Meningeal irritation signs,inflammation,Swelling of roots of cranial & spinal N,Compression at ostiole or intervertebral holes,Preventive muscular spasm at back in order to fix the position of nerve root at holes,Kernigs Sign(+),Brudzinski Sign(+),neck stiffness o

46、r opisthotonus (角弓反张）,Opisthotonos from Greek roots, opistho meaning behind and tonos meaning tension, an individuals head, neck and spinal column enter into a complete bridging or arching position. This abnormal posturing is an effect and is caused by spasm of the axial muscles along the spinal col

47、umn.,Brudzinski Sign(+) An involuntary flexion of the hip and knee when the neck is passively flexed. It can occur in patients with meningitis. Kernigs sign(+) Inability to completely extend the leg when sitting or lying with the thigh flexed upon the abdomen,Meningitis CPC,Hypertention of ICP,Infla

48、mmatory exude,adhesion of arachnoid granules,decreasing absorption of CSF,vascular congestion,cerebral edema,Projectile vomiting,headache,coma,CSF changes,MeningitisCPC,CSF Changes Increasing pressure Turbid, protein ，cell count Pus(+), bacteria(+) Sugar,MeningitisCPC,Waterhouse-Friderichsen syndrom

49、e(华佛氏综合症),severe septicemia,large amount of endotoxin released,DIC,shock,bilateral hemorrhage of adrenal cortex,Extensive ecchymosis purpura,Mild or no meningeal changes,Prognosis: quite good. The usage of antibiotics makes more than 90% patients recovered . Complications: quite few focal adhesive a

50、rachnoiditis hydrocephalus: due to inflammatory adhesion, decreasing absorption of CSF cranial nerve injury: palsy, blindness, deafness strabismus (III、IV、V、VII ) cerebral infarction: inflammation vessels inflammatory injury and occluded,Meningitis Consequence and prognosis,Suspicion of meningitis i

51、s a medical emergency and immediate medical assessment is recommended. Current guidance in the United Kingdom is that any doctor who suspects a case of meningococcal meningitis or septicaemia (infection of the blood) should give intravenous antibiotics (benzylpenicillin or Cefotaxime) and admit the

52、ill person to the hospital. This means that laboratory tests may be less likely to confirm the presence of Neisseria meningitidis as the antibiotics will dramatically lower the number of bacteria in the body. The UK guidance is based on the idea that the reduced ability to identify the bacteria is o

53、utweighed by reduced chance of death.,vaccine,Remarks on viral infection,Absolute parasitism in host cells, selective vulnerability of different group of neuron. Invades neuron: cytolysis, inclusion body formation Glia cell proliferation, multinuclear giant cell(HIV) T/B cell immunity,Inflammation f

54、eature,Stereotyped Reaction neurons: degeneration, necrosis secondary demyelination limited exudation with perivascular cuffing formation Presence of BBB (blood brain barrier) and V-R space limits the spread of inflammation Absence of intrinsic lymphatic and lymphoid tissue T/B cells are blood born(

55、exogenic) glia nodule formation microglial nodule in early stage. astrocytic nodule in later stage, repair,Epidemic Japanese B Encephalitis(流行性乙型脑炎)Concept,1934 Japan Japanese B Encephalitis (RNA) virus Global incidence, high morbidity and mortality China: more than 10 000 cases annually Arboviral e

56、ncephalitis most cases show acute clinical course, tropical region: epidemic through the year temperate region: summer and autumn.,Victims are children, teenagers, with drowsiness, higher fever, severe headache, convulsion, vomiting, deep coma. Basic pathological change is neuronal degeneration Perm

57、anent immunity after suffering of disease Mortality : 70% before to 10% now,Epidemic Japanese B Encephalitis(流行性乙型脑炎)Concept,Encephalitis B Jap.,Pathogen：Encephalitis B Jap. Virus (RNA) Route of Infection,bite of mosquito,virus,Endothelium of local blood vessels,M further multiplication,viremia,norm

58、al immunity & BBB,incompetent BBB,subclinical infection,neuron,encephalitis,Encephalitis B Jap.Pathology,Gray matter involved. mainly Cerebral CortexB.G. Thalamus Gross Inspection: Congestion of Meninges Brain Edema Microscopic findings: Sieve-like softening foci, well demarcated Necrosis of neurons Congestion and perivascular cuffing Proliferation of glial cells Microglia proliferation(acute stage) with foamy cell formation Astrocyte proliferation(chronic stage),Sieve like softening