神經(jīng)系統(tǒng)病理生理理

1、神經(jīng)系統(tǒng)病理生理理OutlineI: General conception about human brainII: Cognitive disorderIII: Consciousness disorderIV: Summary1.Structural CharacteristicsIt is located inside the skull, protects brain from injury, confines the brain It is composed of neurons and glial cells The blood supply is from twin verteb

2、ral arteries and carotis interna （頸內(nèi)動(dòng)脈）The brain blood barrier protects brain from invasion of toxic insultsHuman BrainTo understand the dysfunction of the brain, its important to know a bit about the brainThe Brains Vital StatisticsAdult weight: about 3 poundsAdult size: a medium cauliflowerNumber

3、of neurons: 100 billionNumber of synapses: 100 trillionInside the Human BrainCell Types of the BrainNeuronsGliaStructure of NeuronNeuronsSpecialized Regions of Neurons Carry out Different Functions Structure of typical mammalian neuronsHippocampus（海馬）GliaCellular FunctionsNeuron is in charge of diff

4、erent functions Glia nourishes and protects the neuronsHow are neurons connected?Synapses!SpineHow does the Synapse carry the signal?1.Electrical current travels down the axonVesicles with chemicals move toward the membrane Chemicals are released and diffuse toward the next cells plasma membrane4.Th

5、e chemicals open up the transport proteins and allow the signal to pass to the next cell2. Characteristics of MetabolismThe most active organ in energy metabolismGlucose is almost the only source of brain energyThe storage of glucose in the brain is very limited3. Characteristics of Brain DiseaseReg

6、ion-dependent consequences to injuriesLimited capacity for self repairAcute brain damages will cause disturbance in consciousness whereas chronic lesions usually lead to cognitive dysfunctionBrain responses to Injuries Cellular responses:Neuron death (necrosis, apoptosis)Degeneration (axon/dendrites

7、 retraction, atrophy )Inflammation (microglia, astrocytes)Demyelination (oligodentrocytes)Functional responses:Cognitive disorderConsciousness disorderOutlineI: General conception about human brainII: Cognitive disorderIII: Consciousness disorderIV: SummaryThe ability of the brain to process and sto

8、re information in order to solve problems.It involves a series of voluntary psychological and social behaviors, such as study, memory, language, thinking, emotion etc.Structural Basis of Cognition Brodmann Mapping (52 areas)Cerebral cortexFunction of cerebral cortexFrontal cortex: voluntary movement

9、s, complex intellectual activities such as writing, memory, creativity, judgment, vision and social responsibility.Lesions in this area will result in contralateral hemiplegia (偏癱), agraphia （失寫(xiě)癥） and frontal dementia （癡呆）.Damage in Brocas area (44 and 45) result in motor aphasia (Brocas aphasia 失語(yǔ)癥

10、)Function of cerebral cortexParietal cortex: plays major role in high level process and integration of sensory information.Lesions in this area produce controlateral sensory deficits.Lesions in the angular gyrus (角回) result in alexia (失讀癥) .Lesions in the supamarginal gyrus (緣上回) result in astereogn

11、osis (實(shí)體感覺(jué)缺失).Function of cerebral cortexTemporal cortex: sensory receiving area for auditory impluses.Lesions in area 22 (auditory association cortex) can lead to Wernickes aphasia （感覺(jué)性失語(yǔ)）Lesions in temporal hippocampus can produce spatial or emotional memory impairment Function of cerebral cortexO

12、ccipital cortex: visionLesions in the primary visual cortex result in visual fields defects. Lesions in the visual association cortex result in a lack of recognition of objects and in distinguishing the difference of animals (cat vs. dog).2. Cognitive DisorderThe disturbance of the mental process re

13、lated to learning and memory, reasoning and judgment, accompanied by aphasia(失語(yǔ)), apraxia (失用), agonasia (失認(rèn)) or disturbance in executive functioningMajor ManifestationsLearning and memory disordersAphasia Agonosia Apraxia Dementia Learning and memory deficits:Patient HM: MRIHMs lesion includes medi

14、al temporal lope structures in addition to hippocampus(amygdala, entorhinal cortex)HMs good news and bad newsThe surgery had a profound effect on declarative memory Severe anterograde amnesia Mild retrograde amnesia Disability to transfer new short-term memory into long-term memoryBut there was no e

15、ffect on:PersonalityAttentionIntelligenceMany forms of memory were spared (short-term memory, motor, implicit memory, etc).3. Etiology and PathogenesisChronic brain damageChronic systemic diseasesMental and psychic disorderOther factorsChronic Brain DamageImbalance of regulating molecules in the bra

16、inProtein aggregation in the brain Chronic cerebral ischemic injuryEnvironmental and metabolic toxins Cerebral traumaBrain aging(1) Imbalance of Regulating MoleculesDopamineNorepinephrineAcetylcholine (Ach)GlutamateAberrant neuropeptideLack of neurotrophic factorsDopamine PathwayDopamineDopamine Syn

17、thesis and StorageTyrosine L-DOPA DADistribution：Dopamine pathwayParkinson Disease NorepinephrineGlutamate(2) Protein Aggregation in the BrainGene mutationsAbnormal post-translational modificationInfection of slow virus in the brainCleaved to generate N-terminal polyQ fragments Aggregates form in cy

18、toplasm and in nucleus-amyloid-like conformationControversy over whether aggregates are toxic or protectiveGain of toxic function and/or loss of protective functionQQQQQQQQQMutant Huntingtin in Huntingtons diseaseMutant a-synuclein in Parkinsons diseaseAlzheimer DiseaseAlzheimers Disease Gradual mem

19、ory lossDecline in the ability to perform routine tasksDisorientationDifficulty in learningLoss of language skillsImpairment of judgment and planning Personality changesSenile plaquesNeurofibrillary tangles(3) Chronic Cerebral Ischemic InjuryEnergy exhaustion and acidosisIntracellular calcium overlo

20、adFree radical injuryExcitatory toxicityInflammatory reaction by cytokineExcitatory toxicityA general pathologic process beginning with the energy and metabolic dysfunction caused by cerebral ischemia and anoxia, which then result in inhibition of Na+-K+-ATPase in plasma membrane, elevation of extra

21、cellular K+ and depolarization of neurons. These changes then cause overdosed release of EAA (excitatory amino acids) into the synaptic cleft and overacitvation of EAA receptor, ultimately over excitement and death of neurons.Pathogenesis of Cognitive Disorder4. Principles for Treatment of Cognitive

22、 Disorders General neuroprotective treatmentsMaintenance of normal neurotransmitter level Surgery OutlineI: General conception about human brainII: Cognitive disorderIII: Consciousness disorderIV: Summary1. ConsciousnessThe sense of awareness of self and the environment.It consists of two aspects:St

23、ate of arousal and content of consciousness.2. Consciousness DisorderParenchymal mental disorders in which there is impairment of the ability to maintain awareness of self and environment and to respond to environmental stimuli.Structural Basis for ConsciousnessStructural Basis for Consciousness dis

24、ordersDysfunction of brain stem reticular formationDysfunction of thalamusDysfunction of cerebral cortex Major ManifestationsDeliriumConfusionDrowsinessComa譫妄精神錯(cuò)亂昏睡昏迷3. Etiology and PathogenesisAcute brain injuryeg. Diffuse encephalic infection, diffuse brain trauma, subarachnoid hemorrhage, etc.Acute brain intoxicationIntracranial extrusion and destructive lesionAcute Brain IntoxicationEndogeneous toxins injuryAlteration in neurotransmitterAberrant energy metabolismNerve cell membrane injuryExogenous toxins injuryEtio