病理学：3 inflammation

1、Chapter III. Inflammation炎 症隶书 骨刻文 Inflame 炎(-itis)炎病例讨论患者男性，24岁，平时体健，今日午后开始发热，乏力，中上腹不适，自服感冒片。至晚体温升高，食欲不振，右下腹隐约疼痛，全身不适，急诊入院。检查发现体温39.5C，心率90次/分，率齐，两肺听诊正常，右下腹麦氏点处明显压痛。实验室检查：白细胞计数1.4万/立方毫米，中性91%。临床诊断？病理改变？正常阑尾 急性阑尾炎 I. Definition of InflammationA defensive response of living tissue with a complex reac

2、tion in vascularized connective tissue and cell reaction intended to eliminate the initial cause as well as the necrotic cells and tissues具有血管系统的活体组织对局部损伤所发生的防御反应。Two main components: Vascular reaction Cellular reaction Protective responses: Eliminate the initial causeDestroy harmful agents Intertwi

3、ned with the process of repair Reconstitute damaged tissueInflammation is a double blade sword Basically a protective reactionClear infections (destroy, dilute or isolate injurious agents)Repair(make wound healing)Have potential to cause harmThe basis of life-threatening allergic reaction to insect

4、or drugsPericardial inflammation resulting in dense encasing scar that impair heart functionChronic inflammation often cause fibrosis of diseased organsII. Inflammatorycausesbacteria and toxinsTraumaMicrobialTissue necrosisForeign bodiesradiation PhysicalAcidsalkalisChemicalAllergicburnfrozenInfecti

5、on 感染Infective disease 感染性疾病 (Infectious disease,传染病) proliferate and spread release toxin and enzymes induce immune reaction Primary(原发性) Secondary(继发性)炎症反应普遍存在，逐步进化致炎因子多，杂，变炎症在医学中：重要、常见 对炎症的研究、认识不断深入 现象：红、肿、热、痛、功能障碍 机制：组织 细胞 分子 传染病，感染性疾病 病理过程慢性胃炎胃溃疡的病因发现 1979年，沃伦教授初步发现幽门螺杆菌，之后马歇尔与他合作开展研究。“那时我们没有名气

6、，国际学术界根本不认同我们的发现。”参加澳大利亚的一次学术会议，他们提交的论文被退回来 “每个年轻科学家都会收到退稿信，并因此感到羞愧、沮丧。我的建议是，把退稿信保存在抽屉里。有一天，当你通过艰苦的努力证明你是正确的，就可以拿出所有退稿信大声地说，是他们错了。” 如何证明幽门螺杆菌是导致胃溃疡等疾病的元凶？无法进行动物模型实验，因为动物与人体的胃差异很大。马歇尔勇敢地以身试药，喝下自己培养的细菌。“我的助手说我疯了。连续5天，我呕吐不断，呼吸困难”，后来他用抗生素治愈了自己。马歇尔说，自己是幸运的，因为抗生素对胃溃疡的治愈率仅为70%。慢性胃炎胃溃疡的病因发现马歇尔获2005年诺贝尔医学奖Ac

7、ute ChronicOnsetrapid slow（发病）Durationshorter longer（病程） (days) (months)Pathology edema proliferation（病变） neutrophil lymphocyteIII. Classification of InflammationAlteration(变质): degeneration and necrosisExudation(渗出): vascular changes, extravasations of leukocyte and fluidProliferation(增生): epitheli

8、um, connective tissue, and blood vesselsVI. Pathological Features of Inflammation急性炎症炎症类型浆液性炎纤维蛋白性炎化脓性炎出血性炎、慢性炎症增生炎症类型肉芽肿性炎炎性息肉炎性假瘤变质变质为主的炎症渗出Acute Inflammation急性炎症Vescular changes - vasodilation - increased vascular permeabilityCellular events - cellular recruitment and activationDefinition: The im

9、mediate and early response to injury designed to deliver leukocytes to sites of injury.即刻、早期、活动期 特点：短，快，显I. Morphologic types of acute inflammationDegenerative inflammation 变质性炎Serous inflammation 浆液性炎Fibrinous inflammation 纤维蛋白性炎Purulent inflammation 化脓性炎Hemorrhagic inflammation 出血性炎1. Degenerative

10、 inflammation （变质性炎）The cell death is prominent in site of injuryUsually occurs in liver, heart, kidney and brainFunctions loss of organ or tissues fulminating viral hepatitisEncephalitis B 2.Serous Inflammation (浆液性炎)Site：skin(皮肤)，mucosa(粘膜)，serosa(浆膜)，loose tissue(疏松组织)Morphology： effusion of a th

11、in fluid (plasma or the secretion of mesothelial cells)Outcomes：resorption (吸收) hydrops(积水)Skin blister resulting from a burn大疱性炎3.Fibrinous Inflammation 纤维蛋白性炎 Site：serosa(浆膜)，lung(肺)， mucosa(粘膜)-(seudomembrenous inflammation 假膜性炎)Morphology：more sever injuries (necrosis)exudation (fibrin with infl

12、ammatory cells)Outcomes：resolution (脱落、排出、吸收、消散) organization and scarring (机化、粘连)Fibrinous pericarditis, Shaggy Heart 纤维蛋白性心包炎，绒毛心 Lobar pneumonia, gray hepatization大叶性肺炎肝变期Lobar pneumonia, gray hepatizationDiphtheria, 白喉pseudomembranous inflammation 假膜性炎 -发生在粘膜上的纤维蛋白性炎。浮 膜Bacillary dysentery,菌痢纤维蛋

13、白+中性粒细胞+坏死脱落的上皮+病原体4.Purulent Inflammation 化脓性炎Definition： This is manifested by the presence of large amounts of purulent exudate consisting of neutrophils, necrotic cells and edema fluid.Cause： pyogenic bacteria (化脓菌, staphylococci) terebinth (松节油)，coal tar(煤焦油)， die bone(死骨), foreign body(异物)4.Pu

14、rulent Inflammation 化脓性炎Morphology： neutrophils infiltration (Purulent cell) PUS necrotic cells edema fluid Types：abscess (脓肿) 脓腔，脓壁，脓液(pus) phlegmonous inflammation (蜂窝织炎) purulent catarrh(脓性卡他)，empyema(积脓)Abscess (脓 肿)Definition: A focal collection of pus that may be caused by deep seeding of pyog

15、enic organisms into a tissue or by secondary infections of necrotic foci.central region with a mass of necrotic white cells and tissue cells, cavity formedCause: staphylococci （蛋白溶解酶）Predilection site: Skin Parenchymal organs Abscess (脓 肿)spleenbrainbone转移性脓肿（层连蛋白受体）There is usually a zone of preser

16、ved neutrophils around this necrotic focuslung制脓膜（血浆凝固酶）Outcomes: Repair (resolution, scarring)Ulcer (溃疡)， Sinus (脓窦)， Fistula (瘘管) Cavity (空洞) phlegmonous inflammation蜂 窝 织 炎Definition: Diffused purulent inflammation in loose connective tissue.Cause: hemolytic streptococcus （透明质酸酶、链激酶）Predilection

17、site: subcutaneous tissue muscle appendix phlegmonous inflammation蜂 窝 织 炎Appendicitis phlegmonous inflammation蜂 窝 织 炎肌组织蜂窝组织炎 phlegmonous inflammation蜂 窝 织 炎Empyema, 积脓表面化脓5. Orther types of inflammation炎症的其他类型Haemorrhagic inflammation (出血性炎) blood vessel necrosis or brokenLung anthrax 肺炭疽并非独立炎症血管严重

18、受损Haemorrhagic inflammation (出血性炎)Interstitial inflammation(间质性炎)Viral myocarditis病毒性心肌炎Perivessel inflammation血管周围性炎Syphilis(梅毒)epidemic encephalitis B (乙脑)Fibrinoid necrotic inflammation 纤维蛋白样坏死性炎Necrotic arteritis 坏死性动脉炎Chronic Inflammation慢性炎症Progress from acute inflammation.Persistence of the i

19、njurious agentInterference in the process of healingBeginning as chronic inflammation.Viral intracellular infectionsPersistent microbial infectionsNondegradable exogenous material Autoimmune diseases慢性炎症特点杂 慢 ，长温 ，迁 ，跳I. General chronic inflammation:Histologic characteristics: Infiltration with chro

20、nic inflammatory cells - mononuclear cellsTissue destruction of parenchyma - destruction of parenchymaRepair - replacement by connective tissue Chronic inflammation of lung with Lymphocytes , Macrophages infiltration, tissue destruction and interstitial fibrosisII. Morphologic types of chronic infla

21、mmationNon-specific and proliferation inflammation 非特异性增生性炎Granulomatous inflammation 肉芽肿性炎1.Non-specific and proliferation inflammation 非特异性增生性炎Proliferationfibroblast, endothelial cell, histocytechronic inflammatory cellslocal epithelial cellsScar1.Non-specific and proliferation inflammation 非特异性增

22、生性炎慢性胆囊炎慢性活动性肝炎2. Granulomatous Inflammation (肉芽肿性炎症) 以肉芽肿形成为特点的慢性炎症。 肉芽肿：是以巨噬细胞及其演化的细胞 在炎症局部大量浸润和增生所 形成的境界清楚的结节状病灶Definition: A distinctive pattern of chronic inflammation characterized by aggregates of activated macrophages that assume a squamous cell-like (epithelioid) appearance.Granuloma (肉芽肿)A

23、 focus of aggregates of activated macrophages (epithelioid and Multi-nuclear giant cells) Types: Infective granuloma Foreign-body granulomaEpithepioid cellsMultinucleate giant cellsGranuloma (肉芽肿)Examples of granulomatous inflammationBacterial: tuberculosis, leprosy, syphilitic gumma, cat-scratch di

24、seaseParasitic: schistosomiasisFungal: histoplasma capsulatum, blastomycosis, cryptococcus neoformans, Inorganic metals or dusts: silicosis, berylliosisForeign body: suture, breast prosthesis, vascular graftUnknown: sarcoidosisTuberculosisLeprosyTyphoid feverSchistosomiasisChronic granulomatous infl

25、ammationA granuloma is an aggregate of epithelioid histiocytes本书中的一些重要肉芽肿结核结节 树胶肿风湿小体 慢性虫卵结节矽肺结节 伤寒小结胶质小结 异物性肉芽肿直径为0.5至2mm，单个肉眼难以看见，多个溶合可呈灰白色，粟粒大小由结节中心向外依次是：Caseous NecrosisEpithelioid Histiocytes and Giant cellsLymphocytes and FibroblastsChronic granulomatous inflammationTubercleChronic granulomato

26、us inflammationChronic granulomatous inflammationTubercleLanghans Giant cellEpithelioid Histiocyte硅结节伤寒小结髓样肿胀期慢性虫卵肉芽肿多核巨细胞风湿小体风湿细胞inflammatory pseudotumor(炎性假瘤)inflammatory polyp(炎性息肉)3. Others chronic inflammationinflammatory polyp(炎性息肉)I. Acute Inflammation 急性炎症1.Vascular changes: change in vascul

27、ar flow and caliber increased vascular permeability2.Cellular reaction: leukocyte extravasation phagocytosis VII. Inflammative Pathgenesis1.1 Changes in Vascular Flow & Caliber （inflammatory hyperemia，炎性充血）Transient constriction of arteriolesVasodilation: arterioles - capillary bedsHyperemiaIncrease

28、d vascular permeabilityStasisNerve: quick, shortChemical Mediators: slow, permanenceHydrostatic pressureColloid osmotic pressure1.2 Increased Vascular Permeability（inflammatory exudation，炎性渗出）An immediate transient response (30)Histamine and leukotrienesA delayed response (2h-10h)Kinins, complement

29、productsA prolonged responseDirect endothelial injuryGaps due to endothelial contractionVenulesVasoactive mediatorsMost commonFast and short-lived (minutes)Direct injuryArterioles,capillaries, and venulesToxins, burns, chemicalsFast and may be long-lived (hours to days)Leukocyte-dependent injuryMost

30、ly venulesPulmonary capillariesLate responseLong-lived (hours)Increased transcytosisVenulesVascular endothelium-derived growth factorNew blood vessel formationSites of angiogenesisPersists until intercellular junction form Increase of Vascular LeakageExudate: plasma (protein) and WBC, RBC Intercompa

31、rsion of Exudate and Transulate exudate渗出液transudate漏出液protein30g/L30g/Lspecific gravity1.01815109- 20109 cell/L IL-1 and TNF Bone marrow output of leukocytes Significance: Neutrophilia - most bacterial infections Lymphocytosis - viral infections Eosinophilia - parasitic infestations and asthma Shif

32、t to the left 核左移现象 Leukopenia （白细胞减少） - typhoid fever and some viruses infection 单核巨噬细胞系统增生SpleenLiverLymph nodes MarrowImpaired function of multiple organs 实质脏器功能损害 heart, liver, kidney, brain,全身炎性反应综合征 headache （头痛），anorexia（厌食）, somnolence（嗜睡）, and malaise（不适） Question：Please list and describe t

33、hree protective effects and three harmful reactions of inflammation to the host.ABCDEFGHIGBD急性炎症渗出 炎症类型浆液性炎纤维蛋白性炎化脓性炎出血性炎、慢性炎症增生炎症类型肉芽肿性炎炎性息肉炎性假瘤变质变质为主的炎症 修 复Chapter . Repair修复 proliferation parenchyma实质 connective tissue间质 regeneration healing (scar, fibrosis) （再生） （疤痕，纤维化）injured cells and tissue

34、repair. Control of normal cell proliferation and tissue growth细胞生长及其调节Cells-proliferative activity(增生能力)Labile cells 不稳定型细胞Surface epithelia, cells of bone marrowhematopoietic tissuesStem cells (self-renewing)Stable cells 稳定型细胞Parenchymal cells of liver, kidneys, and pancreasendothelial cells, fibro

35、blastPermanent cells 固定型细胞Neurons, cardiac muscleCell-cycle细胞周期Cyclins-CDKsABC、D、EStem Cells 干细胞:Labile cells具有自我复制能力的多潜能细胞，具有无限分裂能力和非对称复制的特点。在特定条件下分化成多种功能细胞。Two typesEmbryonic stem cells, ES cells 胚胎干细胞 最为幼稚的干细胞； 存在于胚囊内细胞团中； 具有强大的自我更新能力。Adult stem cells 成体干细胞/组织干细胞 幼稚程度低于ES cells； 存在于器官或组织的已分化细胞中；

36、分化潜能被限制于他们所在的组织/器官的部分/全部细胞。Induced pluripotent stem cells, iPS cells 多能干细胞在完全分化的细胞中导入一系列对维持干细胞去分化具有关键作用的基因，并导致体细胞核重编码。这些获得许多干细胞特性的细胞即为iPS cells。Growth factors 生长因子:EGF: mitogenic for keratinocytes and FbPDGF: chemotactic for PMNs, M, Fb, SMC; stimulates production of MMPs, Fn, HA, angiogenesis and w

37、ound contractionbFGF: chemotactic for Fb, mitogenic for Fb and keratinocytes, stimulates keratinocyte migration, angiogenesis, matrix depositionHGF: stimulates proliferation of epithelial and endothelial cellsKGF: stimulates keratinocyte migration, proliferation and differentiationTGF-: chemotactic

38、for PMNs, M, Lymphocytes, Fb, SMC; stimulates TIMP synthesis, keratinocyte migration, angiogenesis and fibroplasia; inhibits production of MMPs and keratinocyte proliferationIL-1: chemotactic for PMNs; stimulation of MMP-1 synthesisTNF: activates M, regulates other cytokinesGeneral patterns of inter

39、cellular signaling自分泌旁分泌内分泌PIP24，5二磷酸磷脂酰肌醇；DAG二乙酰基甘油；IP3三磷酸肌醇. Extracellular matrix, ECM细胞外基质Major components of ECM： 1.fibrous structural proteins 纤维结构蛋白： collagen胶原蛋白(间质性I、III，基膜性IV、V） elastin弹性蛋白 2.adhesive glycoproteins 粘连糖蛋白： fibronectin纤连蛋白 laminin层连蛋白 3.proteoglycans 蛋白聚糖： 氨基多糖GAG蛋白核心 GAG：透明质

40、酸、硫酸软骨素和硫酸皮肤素、 硫酸类肝素和肝素、硫酸角质素细胞外基质的代谢 合成： 细胞内合成、分泌，细胞外组建 降解： 多种酶参与 (MMP，TIMP) 代谢的调节：细胞（生长）因子（TGF-）ECM degradematrix metalloproteinase (MMPs, 基质金属蛋白酶)。interstitial collagenase(间质胶原酶) MMP-1, -5 - Col和Coltype collagenase (型胶原酶) MMP-2, -9 - Col和Colstromelysin(基质溶解素) MMP-3, -10 -蛋白多糖和连接糖蛋白membrane-type M

41、MP(膜型MMP) MT-MMP-MMP-2other (MMP11、MMP12)Tissue inhibitor of matrix metalloproteinase 基质金属蛋白酶抑制因子 - 基质降解的负反馈调节TIMP-1 - MMP-1，-3， -13TIMP-2 - MMP-2， -9TIMP-3 - ？慢性炎症- TIMP- ECM(1).granulation tissue肉芽组织 Newly formed capillariesProliferation of FibroblastInflammatory cellsIII. Repair by Healing with c

42、onnective tissue结缔组织修复/纤维性修复The formation of granulation tissue is the critical stage in healingNew small blood vessels(新生的小血管)Proliferation of Fb(成纤维细胞)Inflammatory cells Healing processes:Induction of inflammation process (remove damaged and dead tissue)Proliferation and migration of parenchymal and connective tissue cellsFormation of new blood vessels and granulation tissueSynthesis of ECM proteins and collagen depositionTissue remodelingWound contraction