病理生理学教学课件：01 Introduction

1、Pathology Introduction 绪 论Definition of PathologyClassic definition of pathologyStudy of sufferring ( path) Modern (definition of) pathologyBoth a science and a clinical practice Pathology StudiesEtiology(病因学)Pathogenesis(发病机制)Pathological changes (diagnosis) (病理改变)Consequence (prognosis and therape

2、utic guidance) (结局)病理学-研究疾病的发生原因, 发病机制, 及组织细胞的 病理改变 肝炎病毒 癌基因突变 肝癌 肝癌大体和镜下细胞改变Category of PathologyClinical Pathology Surgical pathology (biopsy and organ resection) Autopsy cytology Molecular pathologyBasic Pathology Laboratory experimentAnimal experimentResourcesResourcesKumar, Cotran & RobinsBasic

3、 Pathology 7th edition8th editionContents of PathologyGeneral PathologyStudy of Mechanisms of DiseaseSystemic (special organ system) PathologyStudy of Diseases by Organ SystemBrief history 3 stages: 一. Organ pathology (器官病理学） Morgagni (16881771) 700 cases the sites and causes of disease(1761) Rokita

4、nsky (18001878) 30 thousands cases of autopsies performed二. Cellular pathology (细胞病理学) 19世纪30年代 microscopy - cell Virchow (18211902) cellular pathology(1859)Virchows office - Berlin Medicine - History Museum三. Ultrastructural and molecular pathology (超微结构和分子病理学) 30th age electron microscope (电镜) 50t

5、h age ultrathin section (超薄切片) 70th age molecular biology (分子生物学)Pathology development of China20世纪初 中国开办医学院 第一代病理学家 北京协和医学院 1915年 胡正祥 广州中山大学医学院 1926年 梁伯强 国立上海医学院 1927年 谷镜汧 1922 德国海岱山大学,柏林大学 1925 北京协和 1927 上海医学院 1929 中华医学会第七次大会 胡正祥 心的先天性畸形一例报告 谷镜汧 中国人动脉之病理的研究 1951 主编 1954年12月 中华医学会病理学会成立 Role in Med

6、icine(Queen of Medicine or as doctors doctor)Bridge between basic biomedical research and clinical sciencesProvide diagnosis of the diseasesServe as one of the golden criteria for medical service qualitiesProvide most definitive evidence of the disease processHow to study well?Put a high value of pa

7、thological practiceMake connections between general and systemic pathologyLink pathologic changes with clinical manifestationsAlways think patient first急性肝炎肝细胞水样变性-肝肿大Exam and Grading Policies50% Written test including multiple choices, pathology terminology definition and explanation, questions, et

8、c. 30% Experimental oral test 10% Performance in laboratory course10% Mid-term exam English (or general performance in pathology course )Chapter I. Cell adaptation, Injury and Death(细胞适应、损伤和死亡） Adverse agents: Intrisical: metabolic products ischemia Enviromental: Physical (radiation, violet light, e

9、tc.) Chemical (CO, CCl4, etc.) Biologic (bacteria, virus, etc.)Affecting factors: Nature, severity and duration of the stress Characters of the cell (vulnerability, differentiation, blood supply, and nutritional status)Hypoxia (缺O2)Normal cardiomyocyte (正常心肌细胞）Adaptation（适应） Reversible injury （可复性损伤

10、） Irreversible injury （不可复性损伤）Cell adaptation（细胞适应） Definition 机体组织、细胞对内、外环境的变化所发生的形态结构和功能代谢的改变Classification Physiologic: erythocytosis in healthy people lived in plateau 高原缺氧情况下的红细胞增多 失血情况下的皮肤、内脏血管收缩 Pathologic: Atrophy 萎缩 decrease in cell size Hypertrophy 肥大 increase in cell size Hyperplasia 增生 i

11、ncrease in cell number Metaplasia 化生 change in cell typeA. Atrophy（萎缩） Definition 发育正常的器官、组织或细胞体积的缩小 Shrinkage in the size of the cell by the loss of cell substance Classifications & causes Physiologic: Atrophic thymus in adult Atrophic uterus in old woman Pathologic: Inadequate nutrition (营养不良) 脑萎缩

12、 Loss of innervation (丧失神经营养) 脊髓灰质炎腿肌肉萎缩 Decreased workload (废用性) 骨折腿肌肉萎缩 Pressure from surrounding tissue, fluid, masses (压迫性) 肾积水皮质萎缩 Loss of endocrine stimulation (内分泌减少) 乳腺萎缩、肾上腺皮质萎缩 Aging (老年性) Biochemical mechanism Affected balance between synthesis and degradation Degradation predominance Mor

13、phologic changes Gross: Smaller and brown (brown atrophy) LM: Smaller cells (细胞变小） Increased lipofuscin (脂褐素增多) EM: Decreased organelles (细胞器减少) Increased autophagic vacuoles(自噬泡增多) Consequence Reversible change (可复性改变) Diminished function (功能降低) Atrophic brain - Alzheimer disease (老年性痴呆症) Atrophic

14、pancreatic islet - diabetes mellitus (糖尿病)B. Hypertrophy （肥大） Definition 实质细胞体积增大引起器官体积变大 An increase in the size of cells and consequently an increase in the size of the organ No new cells （非新生细胞） No cellular swelling （非细胞肿胀） Classification Physiologic: uterus during pregnancy (妊娠子宫) Pathologic: Co

15、mpensatory or adaptive: hypertensive heart Substitutive: enlarged kidney Morphological changes Gross: Enlarged organ Left ventricular hypertrophy LM: bigger cell Larger and darker stain of nuclei Enlarged myocardial fiber EM: Increased organelles Increased myofilament Consequence A adaptive change A

16、 limited compensationC. Hyperplasia (增生） Definition 器官或组织中细胞数量增加 An increase in the number of cells in an organ or tissue Classification Physiologic: Hormonal: glandular epithelium of the female breast during pregnancy Compensatory: remaining liver cell after resecting a portion of liver Pathologic:

17、 Hormonal （激素依赖性）如子宫内膜增生、 乳腺增生 Wound healing （创伤愈合） Skin wart （皮肤疣） Morphological change Increased number of cell Increased mitosis of nuclei乳腺小叶增生前列腺结节性增生Consequence Adaptive change: proliferation of connective tissue cell in wound healing Adverse effect: cancerous proliferation (endometrical cance

18、r, cervical cancer, etc) D. metaplasia (化生） Definition 一种分化成熟的细胞类型（上皮或间 质细胞)被另外一种成熟的细胞所代替 One adult cell type (epithelial or mesenchymal) is replaced by another adult cell type 化生通常见于具有极强再生能力的组织，如上皮组织和结缔组织。 通常是由上述组织中具有潜在分化和增殖能力的细胞如基底细胞、储备细胞、原始间充质细胞等增生转化所致。 Classification Epithelial (上皮化生） Squamous:

19、(e.g. squamous metaplasia of respiratory epithelium) 鳞状细胞化生 Glandular: (e.g. interstinal metaplasia of gastric mucosa) 肠上皮化生 Mesenchymal (间叶细胞） Metaplasia in connective tissue （骨化生、软骨化生、脂肪化生、粘液化生） Consequence An adaptive response （适应性改变）to a adverse enviroment Adverse effect: （不利影响） cancer transform

20、ation in the metaplastic epitheliumReversible injury （可复性损伤）Cellular degeneration (细胞变性）细胞水肿变性脂肪变性A. Cellular Swelling （细胞肿胀） Mild, reversible, common lesion in parenchymal cells (e.g. liver, kidney, heart, brain) Granular or vacuolar and hydropic degeneration Pathologic changes Gross: Pallor, incre

21、ased turgor, and increased weight LM: Cytoplasmic visible granule-granular degeneration Cytoplasmic clear vacuole-vacuolar or hydropic, degeneration 肾小管上皮肿胀肝细胞肿胀 EM: Blebbing, blunting or distortion of microvilli and loosening of intercellular attachment Mitochondrial swelling with formation of amor

22、phous densities Dilation of Endoplasmic Reticulum with detachment of ribosomes and dissociation of polysome Disaggregation of granular and fibrillar elements of nuclei Mechanism Depletion of ATP Na+-K+ ATPase injuried Membrane permeability B. Fatty degeneration (脂肪变性）又名：fatty change (steatosis) Defi

23、nition Any abnormal accumulation of triglycerides within parenchymal cell Reversible severe injury Most often in liver, also in heart, kidney, skeletal muscle Various causes (toxin, protein malnutrition, diabetes mellitus, obesity, anoxia, especially alcohol abuse) Pathologic changes Fatty change of

24、 the liver Gross: Enlargement and progressively yellow color Increased weight,and become tuft and greasy 苏丹III呈橘红色 LM: Cytoplasmic fat vacuole, round and clear in routing tissue section Orange red in tissue section with sudan IV or oil red O 胞质内圆形空泡，大小不等， 核可偏位 苏丹III呈橘红色，锇酸呈黑色部位可分: 小叶中央型淤血、四 氯化碳中毒小叶周

25、边型酒精、 感染、磷中毒 全小叶型严重感染、 中毒 Fatty change of the heart Gross: Tigered heart 虎斑心(e.g. anemia) Uniformly affected myocytes (e.g. diphthelia) Fatty change of the kidney Gross: Lipid streak in renal cortex EM: round vacuole with lower electron density Mechanism Fatty acid accumulation Increased mobilizatio

26、n of fatty acid (e.g. starvation) Inhibited oxidation of fatty acid (e.g. anoxia) Decreased the synthesis of lipoproteins (e.g. protein malnutrition) Free of structured lipid III. Cell death(细胞死亡） 又名：Irreversible injury （不可复性损伤） Two patterns: Necrosis （坏死） Apoptosis (凋亡）A. Necrosis （坏死） Definition L

27、ocal death of the cell or the tissue in a living organism Biological processes Self-digestion or enzymatic digestion Autolysis （自溶） Heterolysis （异溶） Denaturation of the proteins Morphologic changes Nuclear changes （核改变） Pyknosis Karyorrhexis Kalyolysis （核固缩） (核碎裂） （核溶解） Cytoplasmic changes （胞质改变） Gr

28、anular degeneration or fatty change （颗粒变或脂肪变） Eosinophilic stain increased （嗜酸性增强） Interstitial changes （间质改变） Collagen degradation & stroma deaggreation （胶原降解&基质 解聚） Inflammatory reaction （炎症反应） Necrotic patterns （坏死类型） a. Coagulative necrosis （凝固性坏死） Predominant denaturation of protein Structured

29、necrosis Common in heart, kidney, liver, spleen, etc.b. Liquefactive necrosis （液化性坏死） Predominant self-digestion Liquefactive lesion Common in brain, spinal cord, etc.c. Specific pattern of necrosis （特殊类型坏死） Caseous necrosis (干酪样坏死） Most often in T.B. infection Dry and yellow cheesy foci grossly Str

30、uctureless, amorphous granular debris Fat necrosis （脂肪坏死） Typically occuring after pancreatic injury Chalky white areas grossly Necrotic fat cells with basophilic calcium deposit Inflamatory infiltration Fibrinoid necrosis （纤维蛋白样坏死） Mostly occuring in hypersensitivity reaction Smuday eosinophilic an

31、d homogeneous masses (Fibrin, Ig, and plasma proteins) Gangrene （坏疽） 又名：gangrenous necrosis （坏疽性坏死） Attached by bacterial infection in infarcted organs or tissues (often in opened organs) Presented with dark or black color in necrotic areas (Fe2+ + H2S FeS) Divided into 3 categories (dry, wet and ga

32、s) Dry Wet GasCausesA occlusion A+V occlusionDeep wound + aerogen infectionMorphologic feature of lesion ConsequenceDry, demarcatedMild, localWet, poorly demarcated Severe, systemicWet, poorly demarcated, bubble formation Tab 1. Comparison of 3 Types of Gangrene Consequence (结局) Resolution and absor

33、ption （溶解吸收） Detachment and discharge （分离排出） Ulcer （溃疡） Cavity （空洞） Encapsulation （包裹化） Organization （机化） Calcification （钙化）B. Apoptosis （凋亡）又名：Programmed cell death （程序性细胞死亡） Definition Mainly be physiologic Determined by intrinsic gene A pathway of cell “suicide” 机体局部组织内在遗传或基因决定的、自身破坏机制所引起的细胞死亡。 凋

34、亡细胞常可被视为宿主不需要的细胞。病变机制： 生物化学改变： 胱冬肽酶参与，裂解支架和激活内核苷酶 活化转谷氨酰胺酶蛋白质交联，形成 凋 亡小体 DNA被内核苷酶裂解成碎片和寡核苷酸 特异性电泳带 细胞或小体表面分别有磷脂酰丝氨酸或血 小板反应蛋白表达为吞噬细胞所识别 Morphologic changes Round or oval masses with intensely eosinophilic cytoplasm in single cell or clusters of cell Condensed nuclear chromatin with karyorrhexis and f

35、ormation of apoptotic bodies Apoptotic cell, their fragments could be phagocytosed or degraded No inflammation Tab2. Comparison between apoptosis and coagulation necrosis Coagulation NecrosisApoptosisStimuliHistologic appearanceDNA breakdownMechanismTissue reactionHypoxia, toxinsCellular swelling Co

36、agulation necrosisDisruption of organellesRandom,diffuseATP depletionMembrane injuryFree radical damageInflammationPhysiologic and pathologic factorsSingle cells Chromatin condensationApoptotic bodiesInternucleosomalGene activationEndonucleasesProteasesNo inflammationPhagocytosis of apoptotic bodies

37、IV. Hyaline degeneration（玻璃样变性， 简称玻变） 又名：Hyalinosis （透明变性或玻璃样变性） Conception A morphological term Presenting eosinophilic and homogenous deposits in HE stained section Occuring in cell, interstitium and vascular wall Category Intracellular hyaline droplet （细胞内玻璃样小滴） Virus or viral granule Negri body

38、hydrophobia （狂犬病） CMV inclusion CMV infection （巨细胞病毒感染） Proteins absorbed or synthesized Absorbed protein Nephritis （肾炎） Russsel body Ig synthesized in plasma cell （浆细胞合成Ig） Accumulated cytokeratin intermediated filments Mallory body alcoholic hepatitis （酒精性肝炎） Apoptosis or coagulative necrosis Coun

39、cilman body viral hepatitis （病毒性肝炎） Hyaline degeneration of cardiomyocyte diphthelia （白喉） Hyalinosis of vascular wall （血管壁玻变） Hyalinosis of connective tissue （结缔组织玻变） Scar （疤痕） Atheroma （粥样斑块） Sclerotic glomerulus （硬化性肾小球） Consequence Depending on their causes, mechanism and biochemical constituentV

40、. Amyloidosis （淀粉样变） Conception Proteinaceous material (amyloid) deposited in tissue interstitium or vascular wall Presenting brown color after reacting to iodine Chemical nature Amyloid light chain (AL) protein （免疫球蛋白轻链） produced by plasma cell associated with some form of monoclonal B-cell prolife

41、ration Amyloid associated (AA) protein （淀粉样相关蛋白） A protein of 8.5 kD molecular mass （76 amino acid residue) Derived from 12kD SAA (serum amyloid-associated) synthesized in the liver Deposited in the setting of chronic inflammatory states Morphologic changes Amorphous, eosinophilic, hyaline extracell

42、ular substance with HE stain Pink-red deposits with Congo-red stain Yellow-green birefringence by polarizing microscope Amyloid fibril (710 nm) on EM examination Consequence Pressure atrophy of deposited organs (kidney, heart, etc.)VI. Pathologic calcification （病理性钙化） Conception Abnormal deposition

43、of calcium salts, together with small amounts of iron, magnesium and other minerals Classification A. Dystrophic calcification （营养不良性钙化） Deposition of calcium salts in dead or dying tissues (necrotic foci, thrombus, atheroma, tumor, etc.) Absence of calcium metabolic derangement Formation of crystal

44、line calcium phosphated due to locally increased Ca2+, PO42- locally 沉积于病变组织，如坏死灶、血栓、粥样斑块、 肿瘤、虫卵等 ATP 酶 有机磷酸脂 PO2-4+Ca2+ = Ca（PO4）2 pH B. Metastatic calcification （转移性钙化） Deposition of calcium salts in normal tissue(vessel, lung, gastric mucosa, kidney) Some derangement in calcium metabolism (hyperc

45、alciemia) due to: Increased secretion of parathyroid hormone Destruction of bone Vit D related disorders Renal failure沉积于骨外正常组织，尤其是酸性环境的胃粘膜、肾小管、肺等组织. Morphologic features Fine, white granules or clumps, grossly Basophilic deposits histologically Heterotopic bone formation, sometimes Consequence A cause of organ dysfunction Compromised valve mo