lecture 1

病理知识思维导图，包括：pathologist、pathology、nomenclature术语、技术四部分内容。

lecture 1

• pathologist
  • goal and duty
    • 通过对组织和细胞morphological studies的方法确定疾病的诊断与预后，预测疾病对治疗的反应
  • 识别normal and diseased states of the tissues (histology), the cells (cytology) and the sub-cellular material (genomics, proteomics, transcriptomics, metabolomics)
  • 也进行post-mortem examinations尸检
    • 尸检的changes
      • 1.在整个身体死亡后伴随着细胞死亡（somatic death)
      • post-mortem autolysis死后自溶:self-digestion by enzymes
      • post-mortem putrefaction死后腐败：在整个身体死亡后组织被细菌的酶降解
      • rigor mortis尸僵:在死后stiffening变硬 of all muscles
• pathology
  • is the study of disease
    • disease
      • developmental:genetic,congenital
      • inflammatory:trauma,infections,immune
      • neoplastic:tumors,cancers
      • degenerative:ageing
    • epidemiology,aetiology,pathogenesis,morphology,clinical significance,management,complications并发症，prevention
  • It involves the investigation of the causes of disease and the associated changes at the level of cells, tissues and organs, which in turn give rise to the presenting signs and symptoms of the patient
  • 临床意义：1.functional derangements and its clinical manifestations resulting from the morphological changes 2.signs and symptoms, course and prognosis of disease depend on the morphology
  • mission
    • Defining the aetiology and pathogenesisof diseases is essential for understanding a disease AND for developing rationale treatments
    • Pathology provides the scientific foundation for the practice of medicine
    • 是临床基础学科与临床医学的桥梁
    • 提供了一种逻辑手段将正常的结构和功能与异常的结构与功能联系起来
  • 分类
    • general pathology
      • 在大部分组织中由病理学刺激所造成的细胞和组织的alterations:common changes:发炎，cancer，ageing
    • systemic pathology
      • 不同的specialised的器官的反应和异常：器官特定的变化：肺炎，乳腺癌
    • 亚分类
  • 历史
    • animism万物有灵论<magic<humors<abiogenesis自然发生<environmental<genetic
    • 现代病理学之父：Rudolph Virchow魏尔啸
• nomenclature术语
  • Sign: A change in a body that can be measured or observed (by a doctor) as a result of a disease
  • Symptom: A change in body function that is felt by a patient as a result of a disease
  • Aetiology: the origin of a disease, including the underlying causes and modifying factors (genetic, environmental…)
    • Multifactorial aetiology
    • 遗传因素影响获得性疾病，环境对基因疾病有很大影响
    • Environmental agents:
      • physical
      • chemical
      • nutritional
      • infections
      • immunological
      • psychological
    • Genetic Factors：
      • ageing
      • genes
  • Pathogenesis: the steps in the development of a disease. It describes how aetiologic factors trigger cellular and molecular changes that characterise the disease
  • Aetiology refers to why a disease arises：Cause vs. risk factors pathogenesis describes how a disease develops：sequence of events from the initial stimulus to the ultimate expression of the disease
• 技术
  • morphology
    • gross
      • size,shape,weight,colour,consistency平滑度，surface,edge,section
    • microscopic
      • Most commonly tissues are formalin-fixed → H&E (haematoxylin and eosin) stained
        • Proteins and starch stain pink
        • Nucleic acids (DNA, RNA) stain blue
        • Air, water, sugar and lipids do not stain at all
        • Naturally coloured materials, black, brown, green
          • golden(黄，棕，绿）-Bile
          • brown:haemosiderin血铁黄素,lipofuscin(iron)脂褐质
          • black:carbon,melanin褪黑素
      • special stains
        • periodic acid-Schiff-PAS糖原染色>starch/sugar
        • Prussian blue>iron
        • Oil Red O>lipids
      • ultrastructural observation
        • TEM
        • SEM
    • radiologic
      • RX
      • Magnetic resonance
      • CT
    • molecular
      • Immunohistochemistry(IHC)
        • Immunohistochemistry (IHC) combines histological, immunological and biochemical techniques for the identification of specific tissue proteins by means of a specific antigen-antibody reaction tagged with a visible label
        • IHC makes it possible to visualise the distribution and localisation of specific proteins within a cell or tissue
        • Application
          • location analysis
            • cytokeratin>cell membrane
          • clinical diagnosis and distinguishing鉴别(肿瘤组织发生的诊断）
        • 作用
          • specific cells and tissue expression of an Ag
          • Major (but probably not minor)changes in the expression pattern of an Ag
          • IHC tells us not only whether a certain protein is expressed, but where it is expressed within the tissue
          • intracellular tyrosine kinase PTK6 is expressed in villus epithelial cells in 小肠
        • limitations
          • qualitative not quantitative,To quantify protein expression, other techniques must be applied (i.e. western blotting)
        • how怎么操作的
          • Preparation of tissue
            • fixation:Fresh unfixed, fixed, or formalin-fixation and paraffin-embedding
              • 缺陷:基于固定时间的结果的可变性
            • sectioning:Slides will be cut from the tissue
            • chenmical preparation:The series of reactions which prepare the tissue to react with the antibody
          • control
            • positive
              • 证明反应是有效的
            • negative
              • 证明抗体的特异性
      • In situ hybridisation
        • IHC and in situ hybridisation can be performed on the same slide, either simultaneously or in two different experiments
        • Method of localising either mRNA within the cytoplasm or DNA within the chromosomes, by hybridising the sequence of interest to a complementary strand of a nucleotide probe
        • 为什么要进行原位杂交
          • 因为蛋白质和RNA的分布是不同的--protein transport,extracellular
          • different temporal changes时间的 in protein and RNA
          • 整个组织的分析可能不够敏感-single cell sensitivity
          • RNA is not uniformly distributed in a cell-neurons:axon vs. soma
        • 子主题
      • PCR
      • DNA sequencing
      • flow cytometry
      • FISH
      • biochip technique
        • gene chip(DNAchip)
        • protein chip(pro microarray)
        • tissue chip(tissue microarray)
• 染色的强度与蛋白的表达不成正比
• 1.every living cell arises from a pre-existing living cell 2.Disease is caused by patterns of injuries (lesions) to cells, extra-cellular matrix, tissue, organ, person