病理学：3 inflammation

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1、Chapter III.Inflammation炎炎 症症隶书隶书 骨刻文骨刻文 Inflame 炎炎(-itis)炎炎病例讨论病例讨论n患者男性，患者男性，24岁，平时体健，今日午后开岁，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。检查发现体温适，急诊入院。检查发现体温39.5C，心率，心率90次次/分，率齐，两肺听诊正常，右下腹麦氏点处分，率齐，两肺听诊正常，右下腹麦氏点处明显压痛。实验室检查：白细胞计数明显压痛。实验室检查：白细胞计

2、数1.4万万/立方立方毫米，中性毫米，中性91%。n临床诊断？临床诊断？n病理改变？病理改变？正常阑尾正常阑尾 急性阑尾炎急性阑尾炎 I.Definition of InflammationA defensive response of living tissue with a complex reaction in vascularized connective tissue and cell reaction intended to eliminate the initial cause as well as the necrotic cells and tissues具有具有血管血管系统

3、系统的的活体组织活体组织对局部损伤所发生的对局部损伤所发生的防御反应防御反应。Two main components:Vascular reaction Cellular reaction Protective responses:Eliminate the initial causeDestroy harmful agents Intertwined with the process of repair Reconstitute damaged tissueInflammation is a double blade sword Basically a protective reaction

4、Clear infections (destroy,dilute or isolate injurious agents)Repair(make wound healing)Have potential to cause harmThe basis of life-threatening allergic reaction to insect or drugsPericardial inflammation resulting in dense encasing scar that impair heart functionChronic inflammation often cause fi

5、brosis of diseased organsII.Inflammatorycausesbacteria and toxinsTraumaMicrobialTissue necrosisForeign bodiesradiation PhysicalAcidsalkalisChemicalAllergicburnfrozenInfection 感染感染Infective disease 感染性疾病感染性疾病(Infectious disease,传染病传染病)proliferate and spread release toxin and enzymes induce immune rea

6、ction Primary(原发性原发性)Secondary(继发性继发性)炎症反应普遍存在，逐步进化炎症反应普遍存在，逐步进化致炎因子多，杂，变致炎因子多，杂，变炎症在医学中：重要、常见炎症在医学中：重要、常见 对炎症的研究、认识不断深入对炎症的研究、认识不断深入 现象：红、肿、热、痛、功能障碍现象：红、肿、热、痛、功能障碍 机制：组织机制：组织 细胞细胞 分子分子 传染病，感染性疾病传染病，感染性疾病 病理过程病理过程慢性胃炎胃溃疡的病因发现慢性胃炎胃溃疡的病因发现n 1979年，沃伦教授初年，沃伦教授初步发现幽门螺杆菌，之后步发现幽门螺杆菌，之后马歇尔与他合作开展研究。马歇尔与他合作开展

7、研究。“那时我们没有名气，国那时我们没有名气，国际学术界根本不认同我们际学术界根本不认同我们的发现。的发现。”参加澳大利亚参加澳大利亚的一次学术会议，他们提的一次学术会议，他们提交的论文被退回来交的论文被退回来“每个每个年轻科学家都会收到退稿年轻科学家都会收到退稿信，并因此感到羞愧、沮信，并因此感到羞愧、沮丧。我的建议是，把退稿丧。我的建议是，把退稿信保存在抽屉里。有一天，信保存在抽屉里。有一天，当你通过艰苦的努力证明当你通过艰苦的努力证明你是正确的，就可以拿出你是正确的，就可以拿出所有退稿信大声地说，是所有退稿信大声地说，是他们错了。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

8、法进行动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。试药，喝下自己培养的细菌。“我的助手说我疯了。连续我的助手说我疯了。连续5天，天，我呕吐不断，呼吸困难我呕吐不断，呼吸困难”，后来他用抗生素治愈了自己。马歇尔，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慢性胃炎胃溃疡的病因发现马歇尔获马歇尔获2005年诺贝尔医学奖年诺贝尔医学奖Ac

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

10、):epithelium,connective tissue,and blood vesselsVI.Pathological Features of Inflammation急性炎症急性炎症炎症炎症类型类型浆液性炎浆液性炎纤维蛋白性炎纤维蛋白性炎化脓性炎化脓性炎出血性炎、出血性炎、慢性炎症慢性炎症增增生生炎症炎症类型类型肉芽肿性炎肉芽肿性炎炎性息肉炎性息肉炎性假瘤炎性假瘤变变质质变质为主的炎症变质为主的炎症渗渗出出Acute Inflammation急性炎症急性炎症Vescular changes -vasodilation -increased vascular permeabilityC

11、ellular events -cellular recruitment and activationDefinition:The immediate and early response to injury designed to deliver leukocytes to sites of injury.即刻、早期、活动期即刻、早期、活动期 特点：短，快，显特点：短，快，显I.Morphologic types of acute inflammationDegenerative inflammation 变质性炎变质性炎Serous inflammation 浆液性炎浆液性炎Fibrino

12、us inflammation 纤维蛋白性炎纤维蛋白性炎Purulent inflammation 化脓性炎化脓性炎Hemorrhagic inflammation 出血性炎出血性炎1.Degenerative inflammation（变质性炎）（变质性炎）nThe cell death is prominent in site of injurynUsually occurs in liver,heart,kidney and brainnFunctions loss of organ or tissues fulminating viral hepatitisEncephalitis B

13、 2.Serous Inflammation (浆液性炎浆液性炎)Site：skin(皮肤皮肤)，mucosa(粘膜粘膜)，serosa(浆膜浆膜)，loose tissue(疏松组织疏松组织)Morphology：effusion of a thin fluid(plasma or the secretion of mesothelial cells)Outcomes：resorption(吸收吸收)hydrops(积水积水)Skin blister resulting from a burn大疱性炎大疱性炎3.Fibrinous Inflammation 纤维蛋白性炎纤维蛋白性炎 Site

14、：serosa(浆膜浆膜)，lung(肺肺)，mucosa(粘膜粘膜)-(seudomembrenous inflammation 假膜性炎假膜性炎)Morphology：more sever injuries(necrosis)exudation(fibrin with inflammatory cells)Outcomes：resolution(脱落、排出、吸收、消散脱落、排出、吸收、消散)organization and scarring(机化、粘连机化、粘连)Fibrinous pericarditis,Shaggy Heart 纤维蛋白性心包炎，绒毛心纤维蛋白性心包炎，绒毛心 Lob

15、ar pneumonia,gray hepatization大叶性肺炎肝变期大叶性肺炎肝变期Lobar pneumonia,gray hepatizationDiphtheria,白喉白喉pseudomembranous inflammation 假膜性炎假膜性炎 -发生在粘膜上的纤维蛋白性炎发生在粘膜上的纤维蛋白性炎。浮浮 膜膜Bacillary dysentery,菌痢菌痢纤维蛋白纤维蛋白+中性粒细胞中性粒细胞+坏死脱落的上皮坏死脱落的上皮+病原体病原体4.Purulent Inflammation 化脓性炎化脓性炎Definition：This is manifested by the

16、presence of large amounts of purulent exudate consisting of neutrophils,necrotic cells and edema fluid.Cause：pyogenic bacteria(化脓菌化脓菌,staphylococci)terebinth(松节油松节油)，coal tar(煤焦油煤焦油)，die bone(死骨死骨),foreign body(异物异物)4.Purulent Inflammation 化脓性炎化脓性炎Morphology：neutrophils infiltration(Purulent cell)PU

17、S necrotic cells edema fluid Types：abscess(脓肿脓肿)脓腔，脓壁，脓液脓腔，脓壁，脓液(pus)phlegmonous inflammation(蜂窝织炎蜂窝织炎)purulent catarrh(脓性卡他脓性卡他)，empyema(积脓积脓)Abscess(脓脓 肿肿)nDefinition:A focal collection of pus that may be caused by deep seeding of pyogenic organisms into a tissue or by secondary infections of necr

18、otic foci.ncentral region with a mass of necrotic white cells and tissue cells,cavity formednCause:staphylococci （蛋白溶解酶）（蛋白溶解酶）nPredilection site:Skin Parenchymal organs Abscess(脓脓 肿肿)spleenbrainbone转移性脓肿转移性脓肿（层连蛋白受体）（层连蛋白受体）There is usually a zone of preserved neutrophils around this necrotic focus

19、lung制脓膜制脓膜（血浆凝固酶）（血浆凝固酶）Outcomes:Repair(resolution,scarring)Ulcer(溃疡溃疡)，Sinus(脓窦脓窦)，Fistula(瘘管瘘管)Cavity(空洞空洞)phlegmonous inflammation蜂蜂 窝窝 织织 炎炎nDefinition:Diffused purulent inflammation in loose connective tissue.nCause:hemolytic streptococcus （透明质酸酶、链激酶）（透明质酸酶、链激酶）nPredilection site:subcutaneous t

20、issue muscle appendix phlegmonous inflammation蜂蜂 窝窝 织织 炎炎Appendicitis phlegmonous inflammation蜂蜂 窝窝 织织 炎炎肌组织蜂窝组织炎肌组织蜂窝组织炎 phlegmonous inflammation蜂蜂 窝窝 织织 炎炎Empyema,积脓积脓 表面化脓表面化脓5.Orther types of inflammation炎症的其他类型炎症的其他类型 Haemorrhagic inflammation (出血性炎出血性炎)blood vessel necrosis or brokenLung anthr

21、ax 肺炭疽肺炭疽并非独立炎症并非独立炎症血管严重受损血管严重受损 Haemorrhagic inflammation(出血性炎出血性炎)Interstitial inflammation(间质性炎间质性炎)Viral myocarditis病毒性心肌炎病毒性心肌炎 Perivessel inflammation血管周围性炎血管周围性炎Syphilis(梅毒梅毒)epidemic encephalitis B(乙脑乙脑)Fibrinoid necrotic inflammation 纤维蛋白样坏死性炎纤维蛋白样坏死性炎Necrotic arteritis 坏死性动脉炎坏死性动脉炎Chronic

22、 Inflammation慢性炎症慢性炎症Progress from acute inflammation.Persistence of the injurious agentInterference in the process of healingBeginning as chronic inflammation.Viral intracellular infectionsPersistent microbial infectionsNondegradable exogenous material Autoimmune diseases慢性炎症特点慢性炎症特点杂杂 慢慢，长，长温温，迁，迁

23、，跳，跳I.General chronic inflammation:Histologic characteristics:Infiltration with chronic inflammatory cells -mononuclear cells Tissue destruction of parenchyma -destruction of parenchyma Repair -replacement by connective tissue Chronic inflammation of lung with Lymphocytes,Macrophages infiltration,ti

24、ssue destruction and interstitial fibrosisII.Morphologic types of chronic inflammationNon-specific and proliferation inflammation 非特异性增生性炎非特异性增生性炎Granulomatous inflammation 肉芽肿性炎肉芽肿性炎1.Non-specific and proliferation inflammation 非特异性增生性炎非特异性增生性炎Proliferationfibroblast,endothelial cell,histocytechron

25、ic inflammatory cellslocal epithelial cellsScar1.Non-specific and proliferation inflammation 非特异性增生性炎非特异性增生性炎慢性胆囊炎慢性胆囊炎慢性活动性肝炎慢性活动性肝炎2.Granulomatous Inflammation (肉芽肿性炎症肉芽肿性炎症)以以肉芽肿肉芽肿形成为特点的慢性炎症。形成为特点的慢性炎症。肉芽肿：是以肉芽肿：是以巨噬细胞巨噬细胞及及其演化的细胞其演化的细胞 在炎症局部大量浸润和在炎症局部大量浸润和增生增生所所 形成的境界清楚的结节状病灶形成的境界清楚的结节状病灶Defini

26、tion:A distinctive pattern of chronic inflammation characterized by aggregates of activated macrophages that assume a squamous cell-like(epithelioid)appearance.Granuloma(肉芽肿肉芽肿)A focus of aggregates of activated macrophages(epithelioid and Multi-nuclear giant cells)Types:Infective granuloma Foreign-

27、body granulomaEpithepioid cellsMultinucleate giant cellsGranuloma(肉芽肿肉芽肿)Examples of granulomatous inflammationBacterial:tuberculosis,leprosy,syphilitic gumma,cat-scratch diseaseParasitic:schistosomiasisFungal:histoplasma capsulatum,blastomycosis,cryptococcus neoformans,Inorganic metals or dusts:sil

28、icosis,berylliosisForeign body:suture,breast prosthesis,vascular graftUnknown:sarcoidosisTuberculosisLeprosyTyphoid feverSchistosomiasisChronic granulomatous inflammationnA granuloma is an aggregate of epithelioid histiocytesn本书中的一些重要肉芽肿本书中的一些重要肉芽肿结核结节结核结节 树胶肿树胶肿风湿小体风湿小体 慢性虫卵结节慢性虫卵结节矽肺结节矽肺结节 伤寒小结伤寒小

29、结胶质小结胶质小结 异物性肉芽肿异物性肉芽肿n直径为直径为0.5至至2mm，单个肉眼难以看见，单个肉眼难以看见，多个溶合可呈灰白色，粟粒大小，多个溶合可呈灰白色，粟粒大小n由结节中心向外依次是：由结节中心向外依次是：Caseous NecrosisEpithelioid Histiocytes and Giant cellsLymphocytes and FibroblastsChronic granulomatous inflammationTubercleChronic granulomatous inflammationChronic granulomatous inflammation

30、TubercleLanghans Giant cellEpithelioid Histiocyte硅结节硅结节伤寒小结伤寒小结髓样肿胀期髓样肿胀期慢性虫卵肉芽肿慢性虫卵肉芽肿多核巨细胞多核巨细胞风湿小体风湿小体风湿细胞风湿细胞inflammatory pseudotumor(炎性假瘤炎性假瘤)inflammatory polyp(炎性息肉炎性息肉)3.Others chronic inflammationinflammatory polyp(炎性息肉炎性息肉)I.Acute Inflammation 急性炎症急性炎症1.Vascular changes:change in vascular f

31、low 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），炎性充血）Transient constriction of arteriolesVasodilation:arterioles-capillary bedsHyperemiaIncreased vasc

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

33、sA 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 injuryMostly venulesPu

34、lmonary 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 Intercomparsion of Exudate

35、and Transulate exudate渗出液渗出液transudate漏出液漏出液protein30g/L30g/Lspecific gravity 1.01815109-20109 cell/L IL-1 and TNF Bone marrow output of leukocytes Significance:Neutrophilia-most bacterial infections Lymphocytosis-viral infections Eosinophilia-parasitic infestations and asthma Shift to the left 核左移现

36、象核左移现象 Leukopenia（白细胞减少）（白细胞减少）-typhoid fever and some viruses infection 单核巨噬细胞系统增生单核巨噬细胞系统增生SpleenLiverLymph nodes MarrowImpaired function of multiple organs 实质脏器功能损害实质脏器功能损害 heart,liver,kidney,brain,全身炎性反应综合征全身炎性反应综合征 headache（头痛），（头痛），anorexia（厌食）（厌食）,somnolence（嗜睡）（嗜睡）,and malaise（不适）（不适）Questio

37、n：Please list and describe three protective effects and three harmful reactions of inflammation to the host.ABCDEFGHIGBD急性炎症急性炎症渗渗出出 炎症炎症类型类型浆液性炎浆液性炎纤维蛋白性炎纤维蛋白性炎化脓性炎化脓性炎出血性炎、出血性炎、慢性炎症慢性炎症增增生生炎症炎症类型类型肉芽肿性炎肉芽肿性炎炎性息肉炎性息肉炎性假瘤炎性假瘤变质变质为主的炎症 修修 复复Chapter.Repair修复修复 proliferation parenchyma实质实质 connective t

38、issue间质间质 regeneration healing(scar,fibrosis)（再生）（再生）（疤痕，纤维化）（疤痕，纤维化）injured cells and tissue repair.Control of normal cell proliferation and tissue growth细胞生长及其调节细胞生长及其调节Cells-proliferative activity(增生能力增生能力)Labile cells 不稳定型细胞不稳定型细胞Surface epithelia,cells of bone marrowhematopoietic tissuesStem ce

39、lls(self-renewing)Stable cells 稳定型细胞稳定型细胞Parenchymal cells of liver,kidneys,and pancreasendothelial cells,fibroblastPermanent cells 固定型细胞固定型细胞Neurons,cardiac muscleCell-cycle细胞周期细胞周期Cyclins-CDKsABC、D、EStem Cells 干细胞干细胞:lLabile cellsl具有自我复制能力的多潜能细胞，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具有无限分裂能力和非对称复制的特点。在特

40、定条件下分化成多种功能细胞在特定条件下分化成多种功能细胞。l Two types Embryonic stem cells,ES cells 胚胎干细胞胚胎干细胞 最为最为幼稚的幼稚的干细胞；干细胞；存在于胚囊内细胞团中；存在于胚囊内细胞团中；具有强大的自我更新能力。具有强大的自我更新能力。Adult stem cells 成体干细胞成体干细胞/组织干细胞组织干细胞 幼稚程度低于幼稚程度低于ES cells；存在于器官或组织的已分化细胞中；存在于器官或组织的已分化细胞中；分化潜能被限制于他们所在的组织分化潜能被限制于他们所在的组织/器官的部分器官的部分/全部细胞。全部细胞。lInduced p

41、luripotent stem cells,iPS cells 多能干细胞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，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 生长因子生长因子:1.EGF:mitogenic for keratinocytes and Fb2.PDGF:chemotactic for PMNs,M,Fb,SMC;stimulates production of MM

42、Ps,Fn,HA,angiogenesis and wound contraction3.bFGF:chemotactic for Fb,mitogenic for Fb and keratinocytes,stimulates keratinocyte migration,angiogenesis,matrix deposition4.HGF:stimulates proliferation of epithelial and endothelial cells5.KGF:stimulates keratinocyte migration,proliferation and differen

43、tiation6.TGF-:chemotactic for PMNs,M,Lymphocytes,Fb,SMC;stimulates TIMP synthesis,keratinocyte migration,angiogenesis and fibroplasia;inhibits production of MMPs and keratinocyte proliferation7.IL-1:chemotactic for PMNs;stimulation of MMP-1 synthesis8.TNF:activates M,regulates other cytokinesGeneral

44、 patterns of intercellular signaling自分泌自分泌旁分泌旁分泌内分泌内分泌PIP24，5二磷酸磷脂酰肌醇；二磷酸磷脂酰肌醇；DAG二乙酰基甘油；二乙酰基甘油；IP3三磷酸肌醇三磷酸肌醇.Extracellular matrix,ECM细胞外基质细胞外基质Major components of ECM：1.fibrous structural proteins 纤维结构蛋白：纤维结构蛋白：collagen胶原蛋白胶原蛋白(间质性间质性I、III，基膜性，基膜性IV、V）elastin弹性蛋白弹性蛋白 2.adhesive glycoproteins 粘连糖蛋白：

45、粘连糖蛋白：fibronectin纤连蛋白纤连蛋白 laminin层连蛋白层连蛋白 3.proteoglycans 蛋白聚糖：蛋白聚糖：氨基多糖氨基多糖GAG蛋白核心蛋白核心 GAG：透明质酸、硫酸软骨素和硫酸皮肤素、：透明质酸、硫酸软骨素和硫酸皮肤素、硫酸类肝素和肝素、硫酸角质素硫酸类肝素和肝素、硫酸角质素细胞外基质的代谢细胞外基质的代谢 合成合成：细胞内合成、分泌，细胞外组建细胞内合成、分泌，细胞外组建 降解降解：多种酶参与多种酶参与(MMP，TIMP)代谢的调节代谢的调节：细胞（生长）因子（：细胞（生长）因子（TGF-）ECM degradematrix metalloproteinas

46、e(MMPs,基质金属蛋白酶基质金属蛋白酶)。interstitial collagenase(间质胶原酶间质胶原酶)MMP-1,-5-Col和和Coltype collagenase(型胶原酶型胶原酶)MMP-2,-9 -Col和和Colstromelysin(基质溶解素基质溶解素)MMP-3,-10-蛋白多糖和连接糖蛋白蛋白多糖和连接糖蛋白membrane-type MMP(膜型膜型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金属蛋白酶抑制因子 -基质

47、降解的负反馈调节基质降解的负反馈调节TIMP-1 -MMP-1，-3，-13TIMP-2 -MMP-2，-9TIMP-3 -？慢性炎症慢性炎症-TIMP-ECM(1).granulation tissue肉芽组织肉芽组织 Newly formed capillariesProliferation of FibroblastInflammatory cellsIII.Repair by Healing with connective tissue结缔组织修复结缔组织修复/纤维性修复纤维性修复The formation of granulation tissue is the critical s

48、tage in healingNew small blood vessels(新生的小血管新生的小血管)Proliferation of Fb(成纤维细胞成纤维细胞)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 granulatio

49、n tissueSynthesis of ECM proteins and collagen depositionTissue remodelingWound contractionAcquisition of wound strengthAngiogenesis from pre-existing vesselsAngiogenesis from endothelial precursor cellsGranulation tissue Scar 肉芽组织肉芽组织 -纤维组织纤维组织 -瘢痕组织瘢痕组织肉芽组织的作用肉芽组织的作用 有利有利 1 抗感染及保护创面抗感染及保护创面 2 机化血凝

50、块，坏死组织和异物机化血凝块，坏死组织和异物 或包裹坏死组织或包裹坏死组织 3 填补组织缺损填补组织缺损 不利不利 1 组织器官功能损失（不全愈合）组织器官功能损失（不全愈合）2 张力减退张力减退（室壁瘤）（室壁瘤）3 疤痕收缩，功能障碍疤痕收缩，功能障碍.Wound Healing创伤愈合创伤愈合first intention：创面窄而齐，出血损伤少，无感染创面窄而齐，出血损伤少，无感染 一期愈合一期愈合 second intention：创面大，出血损伤多，常有感染创面大，出血损伤多，常有感染 二期愈合二期愈合CutaneousWoundInflammationGranulation Ti

51、ssue ReepithelializationHealingComplications in cutaneous wound healing（并发症）（并发症）：Deficient scar formation 瘢痕形成不足瘢痕形成不足Wound dehiscence(伤口裂开伤口裂开)Ulceration（溃疡）（溃疡）Excessive formation of the repair components 瘢痕形成瘢痕形成过度过度keloid（瘢痕疙瘩）（瘢痕疙瘩）aggressive fibromatoses（侵袭性纤维瘤病）（侵袭性纤维瘤病）Formation of contract

52、ures 挛缩挛缩Deformities of the wound and the surrounding tissuekeloid（瘢痕疙瘩）（瘢痕疙瘩）.Factors influencing wound healing 影响修复的因素影响修复的因素Systemic factors：nutrition(营养营养)Metabolic status(代谢状况代谢状况)Circulatory status(循环状况循环状况)Hormones(激素激素)Local factors：Infection(感染感染)Mechanical factors(机械磨擦机械磨擦)Foreign bodies(异

53、物异物)Size,location and type of wound(大小、部位、伤口类型）大小、部位、伤口类型）Fibrosis of organs 器官纤维化器官纤维化2.器官内某些细胞活化、增器官内某些细胞活化、增 生（生（Fb）如肝星状细胞，肾小球系膜细胞，如肝星状细胞，肾小球系膜细胞，肺原始间叶细胞肺原始间叶细胞 伴有伴有ECM沉积沉积1.慢性炎症持续存在、刺激慢性炎症持续存在、刺激 3.器官结构改变，功能异常器官结构改变，功能异常123 ECM慢性持续性损伤慢性持续性损伤（启动）（启动）上皮、内皮损伤，上皮、内皮损伤，间质水肿，间质水肿，组织支架结构损伤组织支架结构损伤 （氧自由

54、基、弹性蛋白酶、（氧自由基、弹性蛋白酶、MMP-2）间叶增生和细胞介质分泌间叶增生和细胞介质分泌(调节调节)上皮细胞增生，上皮细胞增生，间叶细胞增生间叶细胞增生 肾系膜细胞增生肾系膜细胞增生 功能活化（功能活化（TGF-，胶原，胶原，FN，），）（巨噬细胞（巨噬细胞TGF-，HGF、KGF、EGF）系膜细胞增生系膜细胞增生TGF-1表达增加表达增加系膜细胞增生和系膜细胞增生和ECM合成合成(效应效应)ECM合成增多、降解减少合成增多、降解减少PASC-IVFNECM沉积和分解沉积和分解(持续或消退持续或消退)器官结构改变，功能异常器官结构改变，功能异常 （病因持续、（病因持续、MMP-2、TIMP）Question:nPlease distinguish the definitions and morphological features between granulation tissue and granuloma.