神经系统病理生理理

Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,2020/11/3,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,2020/11/3,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,2020/11/3,*,神经系统病理生理理,神经系统病理生理理神经系统病理生理理,Outline,I: General conception about human brain,II: Cognitive disorder,III: Consciousness disorder,IV: Summary,2020/11/3,2,1.Structural Characteristics,It 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 vertebral arteries and carotis interna,（颈内动脉）,The,brain blood barrier,protects brain from invasion of toxic insults,2020/11/3,3,Human Brain,To understand the dysfunction of the brain, its important to know a bit about the brain,The Brains Vital Statistics,Adult weight:,about 3 pounds,Adult size:,a medium cauliflower,Number of neurons:,100 billion,Number of synapses:,100 trillion,2020/11/3,4,Inside the Human Brain,2020/11/3,5,Cell Types of the Brain,Neurons,Glia,2020/11/3,6,Structure of Neuron,2020/11/3,7,Neurons,Specialized Regions of Neurons Carry out Different Functions,Structure of typical mammalian neurons,H,ippocampus,（海马）,2020/11/3,8,Glia,2020/11/3,9,Cellular Functions,Neuron is in charge of different functions,Glia nourishes and protects the neurons,2020/11/3,10,How are neurons connected?,Synapses!,Spine,2020/11/3,11,How does the Synapse carry the signal?,1.Electrical current travels down the axon,Vesicles with chemicals move toward the membrane,Chemicals are released and diffuse toward the next cells plasma membrane,4.The chemicals open up the transport proteins and allow the signal to pass to the next cell,2020/11/3,12,2. Characteristics of Metabolism,The most active organ in energy metabolism,Glucose is almost the only source of brain energy,The storage of glucose in the brain is very limited,2020/11/3,13,3. Characteristics of Brain Disease,Region-dependent consequences to injuries,Limited capacity for self repair,Acute brain damages will cause disturbance in consciousness whereas chronic lesions usually lead to cognitive dysfunction,2020/11/3,14,Brain responses to Injuries,Cellular responses:,Neuron death (necrosis, apoptosis),Degeneration (axon/dendrites retraction, atrophy ),Inflammation (microglia, astrocytes),Demyelination (oligodentrocytes),Functional responses:,Cognitive disorder,Consciousness disorder,2020/11/3,15,Outline,I: General conception about human brain,II: Cognitive disorder,III: Consciousness disorder,IV: Summary,2020/11/3,16,1.Cognition,The ability of the brain to process and store information in order to solve problems.,It involves a series of voluntary psychological and social behaviors, such as study, memory, language, thinking, emotion etc.,2020/11/3,17,Structural Basis of Cognition,Brodmann Mapping (52 areas),Cerebral cortex,2020/11/3,18,Function of cerebral cortex,Frontal cortex:,voluntary movements, complex intellectual activities such as writing, memory, creativity, judgment, vision and social responsibility.,Lesions in this area will result in contralateral,hemiplegia (,偏瘫,),agraphia,（失写症）,and frontal,dementia,（痴呆）,.,Damage in Brocas area (44 and 45) result in motor aphasia (,Brocas aphasia,失语症,),2020/11/3,19,Function of cerebral cortex,Parietal 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 (,失读症,),.,Lesions in the supamarginal gyrus (,缘上回,),result in,astereognosis (,实体感觉缺失,),.,2020/11/3,20,Function of cerebral cortex,Temporal cortex:,sensory receiving area for auditory impluses.,Lesions in area 22 (auditory association cortex) can lead to,Wernickes aphasia,（感觉性失语）,Lesions in temporal hippocampus can produce spatial or emotional memory impairment,2020/11/3,21,Function of cerebral cortex,Occipital cortex:,vision,Lesions 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).,2020/11/3,22,2. Cognitive Disorder,The disturbance of the mental process related to learning and memory, reasoning and judgment, accompanied by,aphasia(,失语,),apraxia (,失用,),agonasia (,失认,),or disturbance in executive functioning,2020/11/3,23,Major Manifestations,Learning and memory disorders,Aphasia,Agonosia,Apraxia,Dementia,2020/11/3,24,Learning and memory deficits:,Patient HM: MRI,HMs lesion includes medial temporal lope structures in addition to hippocampus,(amygdala, entorhinal cortex),2020/11/3,25,HMs good news and bad news,The surgery had a profound effect on declarative memory,Severe anterograde amnesia,Mild retrograde amnesia,Disability to transfer new short-term memory into long-term memory,But there was no effect on:,Personality,Attention,Intelligence,Many forms of memory were spared (short-term memory, motor, implicit memory, etc).,2020/11/3,26,3. Etiology and Pathogenesis,Chronic brain damage,Chronic systemic diseases,Mental and psychic disorder,Other factors,2020/11/3,27,Chronic Brain Damage,Imbalance of regulating molecules in the brain,Protein aggregation in the brain,Chronic cerebral ischemic injury,Environmental and metabolic toxins,Cerebral trauma,Brain aging,2020/11/3,28,(1) Imbalance of Regulating Molecules,Dopamine,Norepinephrine,Acetylcholine (Ach),Glutamate,Aberrant neuropeptide,Lack of neurotrophic factors,2020/11/3,29,Dopamine Pathway,Dopamine,2020/11/3,30,Dopamine Synthesis and Storage,Tyrosine, L-DOPA DA,2020/11/3,31,Distribution,：,Dopamine pathway,2020/11/3,32,Parkinson Disease,2020/11/3,33,Norepinephrine,2020/11/3,34,Glutamate,2020/11/3,35,(2) Protein Aggregation in the Brain,Gene mutations,Abnormal post-translational modification,Infection of slow virus in the brain,2020/11/3,36,Cleaved to generate N-terminal polyQ fragments,Aggregates form in cytoplasm and in nucleus-amyloid-like conformation,Controversy over whether aggregates are toxic or protective,Gain of toxic function and/or loss of protective function,Q,Q,Q,Q,Q,Q,Q,Q,Q,Mutant Huntingtin,in Huntingtons disease,2020/11/3,37,Mutant,a,-synuclein,in Parkinsons disease,2020/11/3,38,Alzheimer Disease,2020/11/3,39,Alzheimers Disease,Gradual memory loss,Decline in the ability to perform routine tasks,Disorientation,Difficulty in learning,Loss of language skills,Impairment of judgment and planning,Personality changes,2020/11/3,40,Senile plaques,Neurofibrillary tangles,2020/11/3,41,2020/11/3,42,2020/11/3,43,(3) Chronic Cerebral Ischemic Injury,Energy exhaustion and acidosis,Intracellular calcium overload,Free radical injury,Excitatory toxicity,Inflammatory reaction by cytokine,2020/11/3,44,Excitatory toxicity,A 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 extracellular 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.,2020/11/3,45,Pathogenesis of Cognitive Disorder,2020/11/3,46,4. Principles for Treatment of Cognitive Disorders,General neuroprotective treatments,Maintenance of normal neurotransmitter level,Surgery,2020/11/3,47,Outline,I: General conception about human brain,II: Cognitive disorder,III: Consciousness disorder,IV: Summary,2020/11/3,48,1. Consciousness,The sense of awareness of self and the environment.,It consists of two aspects:,State of arousal and content of consciousness.,2020/11/3,49,2. Consciousness Disorder,Parenchymal mental disorders in which there is impairment of the ability to maintain awareness of self and environment and to respond to environmental stimuli.,2020/11/3,50,Structural Basis for Consciousness,2020/11/3,51,Structural Basis for Consciousness disorders,Dysfunction of brain stem reticular formation,Dysfunction of thalamus,Dysfunction of cerebral cortex,2020/11/3,52,Major Manifestations,Delirium,Confusion,Drowsiness,Coma,谵妄,精神错乱,昏睡,昏迷,2020/11/3,53,3. Etiology and Pathogenesis,Acute brain injury,eg. Diffuse encephalic infection, diffuse brain trauma, subarachnoid hemorrhage, etc.,Acute brain intoxication,Intracranial extrusion and destructive lesion,2020/11/3,54,Acute Brain Intoxication,Endogeneous toxins injury,Alteration in neurotransmitter,Aberrant energy metabolism,Nerve cell membrane injury,Exogenous toxins injury,2020/11/3,55,Etiology and Pathogenesis of Consciousness Disturbance,2020/11/3,56,4. Principles of Prevention and Therapy,Urgent management,Making a definite diagnosis as soon as possible,Monitoring vital signs and consciousness state,Brain protections,2020/11/3,57,Outline,I: General conception about human brain,II: Cognitive disorder,III: Consciousness disorder,IV: Summary,2020/11/3,58,1. Glossary,cognition, cognitive disorder, Brocas aphasia, Wernickes aphasia, dementia, consciousness disorder, delirium, excitatory toxicity,2020/11/3,59,2. Questions,1. What is the characteristics of brain disease?,2. What is the pathogenesis of cognitive disorder?,3. What is the pathogenesis of consciousness disorder?,2020/11/3,60,谢谢观赏,