What is pathophysiology?

Size: px

Start display at page:

Download "What is pathophysiology?"

硫姚
5 years ago
Views:

1 Introduction to Pathophysiology 病理生理学简介 Jimin Shao ( 邵吉民 ) shaojimin@zju.edu.cn 1

2 Disciplines in Medical Sciences Basic Medical Sciences Clinical Medical Sciences Public Health Biochemistry Genetics Cell Biology Molecular Biology Anatomy Histology and Embryology Physiology Neuroscience Immunology Microbiology and Parasitology Pathology Pathophysiology Pharmacology

3 What is Pathophysiology? Pathophysiology is a science to study the etiology and pathogenesis of human diseases,more concerning functional and metabolic alterations and related mechanisms in diseases, which is the basis for diagnosis, treatment, and prevention of diseases. Why Is Pathophysiology Important? A bridge between basic medical sciences and diseases. Why and how diseases develop and various clinical manifestations appear. What are the underlying mechanisms. Basis for prevention, diagnosis, treatment, rational therapeutics. 3

4 Relationship with other disciplines Relationship with Physiology Pathologic physiology Clinical Physiology Physiological changes under diseased situation 4 Relationship with Pathology Pathology emphasizes the structural changes and the mechanisms. Pathophysiology deals with functional and metabolic alterations and the mechanisms.

5 How Pathophysiology is Arranged? 1. Conspectus of Disease: What disease is. The causes of diseases The basic laws and mechanisms those underlie all diseases 绪论疾病的病因与发病学 2. Cellular and molecular pathophysiology: Cell proliferation, differentiation, death and diseases Signal transduction and diseases Genetic and epigenetic changes in diseases 细胞功能异常与疾病 ( 细胞增殖分化死亡异常与疾病 ) 细胞信号转导异常与疾病基因结构与表达异常与疾病

6 3. Fundamental pathological processes: Common and whole set alterations in metabolism, function and structure, which may occur in different diseases. 水电解质代谢紊乱酸碱平衡紊乱应激发热缺氧自由基与组织损伤凝血与抗凝血平衡紊乱与 DIC 缺血 - 再灌注损伤休克多器官功能障碍肿瘤病因学与发病学 4. Organic & systemic pathophysiology: Specific responses and mechanisms of the critical systems and organs in diseased body. 心血管系统功能障碍呼吸系统功能障碍消化道与肝功能障碍肾功能障碍内分泌系统与代谢紊乱脑功能不全

7 Conspectus of Disease 疾病概论 Concept of Disease( 疾病的概念 ) Etiology ( 病因学 ) Pathogenesis( 发病学 ) 7

8 Cellular and molecular pathophysiology Genetic and Epigenetic Abnormalities and Diseases ( 基因结构和表达异常与疾病 ) Signal transduction and the Related Disorders ( 信号转导异常与疾病 ) Cell proliferation, differentiation, death and the Related Disorders ( 细胞增殖分化死亡异常与疾病 ) Introduction of Disease Databanks ( 疾病大数据库资源和应用 ) 8

9 Genetic and Epigenetic Abnormalities and Diseases 99

10 Signal transduction and diseases 10

11 Cell fate control and related diseases ( 细胞命运活动调控异常与疾病 ) Cell proliferation( 增殖 ), Cell growth( 生长 ); Cell survival( 生存 ); Quiescence( 静止 ): quiescent cells in Go or G1. Cell differentiation ( 分化 ); Cell dormancy( 休眠 ) ; Cell senescence( 衰老 ): irreversible entrance into a nonproliferative but viable state. Cell death ( 细胞死亡 ): necrotic cell death/cell necrosis( 细胞坏死 : 被动细胞死亡 ) ; programmed cell death(pcd, 程序性细胞死亡 : 主动细胞死亡 ); apoptosis( 细胞凋亡 )/apoptotic cell death; necroptosis ( 程序性细胞坏死 ) Autophagy( 自噬 ) 11

12 Apoptosis and Diseases Diseases Mechanism Apoptosis Heart failure AIDS AD, PD Cancer Autoimune diseases Atherosclerosis Ischemia, inflammation, etc. HIV infection of T 4 cell Ischemia, inflammation, etc P53, Bcl-2 Autoreactive T cells or B cells Endothelial cell, muscle cell

13 Fundamental pathological processes 水电解质代谢紊乱 (Water and Electrolytes Imbalance) 酸碱平衡紊乱 (Acid-Base Balance and Imbalance) 应激 (Stress and the Related Disorders) 发热 (Fever) 缺氧 (Hypoxia) 自由基与组织损伤 (Free Radical Injury) 凝血与抗凝血平衡紊乱与 DIC (Coagulation-Anticoagulation Disorders and DIC) 缺血 - 再灌注损伤 (Ischemia-Reperfusion Injury) 休克多器官功能障碍 (Shock and MODS) 肿瘤 (Tumor) 13

14 Fever

15 15

16 Pathogenesis of fever

17 Tumor 17 17

18 Organic & systemic pathophysiology 心血管系统功能障碍 (Heart Failure) 呼吸系统功能障碍 (Respiratory Failure) 消化道和肝功能障碍 (Hepatic Encephalopathy) 肾功能障碍 (Renal Failure) 内分泌系统功能紊乱 (Endocrine disorders) 代谢综合征 (Metabolic Syndrome) 脑功能不全 (Brain disfunction) 18

19 Hepatic Encephalopathy Liver disease neuropsychiatric syndrome 肝性脑病是继发于严重肝疾病的以代谢紊乱为基础的中枢神经系统功能失调综合症, 其主要临床表现是意识障碍行为失常和昏迷等

20 Clinical presentation: 肝性昏迷 (hepatic coma) 昏睡精神错乱睡眠障碍行为失常扑翼样震颤 Flapping tremor (asterixis) 轻微性格行为改变

21 Pathogenesis: Multifarious toxins Dysfunction of CNS (No obvious morphological change) Several hypotheses: 氨中毒学说 Ammonia intoxication 假性神经递质学说 False neurotransmitter 血浆氨基酸失衡学说 Amino acid imbalance γ- 氨基丁酸学说 GABA (γ-amino butyric acid ) & HE Integrative mechanism

22 Methodologies Molecular biology, omics,big data Cell, tissue, and organ levels Integrated medicine/systems biology Animal experiments Clinical research Epidemiological analysis Comprehensive, multi-disciplines Translational research

23 Column particle α- Flag Bait % 0 R y 1 y 2 y 3 y 4 y 5 y m/z y 7 y 8 y 9 A L S E I E G S N y 1 0

25 表观转录组学 (RNA 修饰 )

26 系统生物学的技术平台经典分子生物学 (Molecular biology) 基因组学 (Genomics) 转录组学 (Transcriptomics) 蛋白质组学 (Proteomics) 代谢组学 (Metabonomics) 相互作用组学 (Interactomics) 表型组学 (Phenomics) 计算生物学 (Computational Biology)

27 Tumor related signaling pathways

28 Intracellular Signaling Networks Regulate the Operations of the Cancer Cell. An integrated circuit operates within normal cells and is reprogrammed to regulate hallmark capabilities within cancer cells. Separate subcircuits (in differently colored fields) orchestrate the various capabilities. There is considerable crosstalk between subcircuits. Each of these subcircuits is connected with signals originating from other cells in the tumor microenvironment.

32 Non-stimulation St96h St96h+Rel 2h hrrm2 p53r2 hrrm1 CY MIT CY MIT CY MIT RR subunits hrrm1 p53r2 Mitochondria hrrm2 merge α-tubulin

33 Microdissection of Tumor from Normal Tissue Biopsy Phase I Triapine and Gemcitabine CT scan Comparison pre- and post- Treatment Tumor Sampling Phase II GTI 2040/Capecitabine in Breast Cancer Protocol

34 肿瘤治疗和药物开发步入精准时代例 : 近年来, 肺癌靶向治疗不断突破, 目前主要的靶点包括 : 34

35 精准诊疗模式已经写入 NCCN 肺癌治疗指南非小细胞肺癌指南 EGFR 突变型 NCCN 指南 ( 美国国立综合癌症网络 ) ESMO 指南 (European Society for Medical Oncology, 欧洲肿瘤内科学会 )

36 精准诊疗模式已经写入 NCCN 肺癌治疗指南非小细胞肺癌指南 ALK 阳性型 36

38 重要的国际癌症基因组大数据癌症基因组图谱 The Cancer Genome Atlas (TCGA) 国际癌症基因组联盟 International Cancer Genome Consortium (ICGC) 儿童癌症基因组计划 Pediatric Cancer Genome Project (PCGP) 38

39 Major Points in Learning Pathophysiology The general concepts The etiology and pathogenesis The alterations of metabolism and function The principles for prevention, diagnosis and therapies Review related knowledge in basic medical and clinical disciplines Pay attention to clinical practices Update your knowledge frequently 39

untitled

untitled 2013 II 12 II II 12 20 20 8 8 20 6