病理生理学教学课件：03 inflammation1

1、Inflame 炎(-itis)Chapter . Inflammation炎 症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.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 . Definition of InflammationA defensive response of living tissue with a complex reaction in vascu

2、larized connective tissue and cell reaction intended to eliminate the initial cause as well as the necrotic cells and tissuesTwo main components: Vascular reaction Cellular reaction Protective response: Eliminate the initial causeDestroy harmful agents Intertwined with the process of repair Reconsti

3、tute damaged tissueInflammation is a double blade sword Basically a protective reactionDesdroy, dilute or isolate injurious agentsClear inflammationMake wound tissue healingHave Potential to cause harmThe basis of life-threatening allergic reaction to insect or drugsPericardial inflammation resultin

4、g in dense encasing scar that impair heart functionChronic inflammation often cause fibrosis of diseased organs2. Inflammatorycausesbacteria and toxinsTraumaMicrobialTissue necrosisForeign bodiesradiation PhysicalAcidsalkaliscoolingChemicalallergicburnsPM2.5Infection 感染Infective disease 感染性疾病 (Infec

5、tious 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，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

6、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Alteration(变质): degeneration and necros

7、is (Necrostic type)Exudation(渗出): vascular changes, (inflammatory hyperemia) extravasation of leukocyte and fluid (common cold, watery exudate on mucous membrane of nose)proliferation(增生): epithelium, connective tissue, and blood vessels (glanuloma, tonsillitis )II.炎症的基本病变 Basic Pathologic Changes o

8、f Inflammation(massive necrosis of liver in fulminant hepatitis )Normal structure of liverMassive necrosis of liver tissuephlegmonous appendicitis Normal slide of appendixLeukocyte Exudation(inflammatory infiltration炎性浸润)Leukocytes migrate from the vessel lumen to the inflammatory site of interstiti

9、al tissue.Leukocytes Neutrophile; B.Macropnage; C. Plasme cellD. Eosinophile; E. Lymphcyte; F. Mutilnucleated giant cell.Tonsillitis , enlargment of tonsillaNormal glomerular Acute glomerulonephritis Acute chronicOnset （发病） rapid slowDuration （病程） short longerPathology necrosis proliferation （病变） ed

10、ema fibrosis neutrophils lymphocyte A. Clinical classification according to the duration and severityIII. 炎症的分型 Classification of inflammation 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 变质为主的炎症临床分型 病理特点 病理分型. Morphologic types of acute inflammationDegenerative inflammation 变质性炎Serous in

11、flammation 浆液性炎Fibrinous inflammation 纤维蛋白性炎Purulent inflammation 化脓性炎Hemorrhagic inflammation 出血性炎Granulomatous inflammation 肉芽肿性炎1. Degenerative inflammation （变质性炎）The cell death is prominent in site of injury, usually occur in liver, heart, kidney and brain, Functions loss of organ or tissues ful

12、minating viral hepatitis. 炎症局部以组织细胞变性和坏死为主的炎症称为变质性炎Encephalitis B 1.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 thin fluid (plasma or the secretion of mesothelial cells)Outcomes：resorption (吸收) hydrops(积水)Skin blister resulting from a bur

13、n2.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 inflammatory 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，

14、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。Bacillary dysentery,菌痢3.Purulent Inflammation 化脓性炎Cause： pyogenic bacteria (化脓菌, staphylococci) terebinth (松节油)，coal tar(煤焦油)， die bone(死骨)， foreign body(异物

15、)Morphoogy： neutrophils infiltration purulent exudate (neutrophils, necrotic cells and 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)a localized area of pus accumulation within a tissuecentral region with a mass of necr

16、otic white cells and tissue cells, cavity formed there is usually a zone of preserved neutrophils around this necrotic focusAbscess (脓 肿)spleenbrainbonelung制脓膜Outcomes: repair(resolution, scarring)Ulcer(溃疡)， Sinus(脓窦)， fistula(瘘管)phlegmonous inflammation蜂 窝 织 炎Empyema, 积脓Orther types of inflammation

17、炎症的其他类型Haemorrhagic inflammation (出血性炎)Lung anthrax 肺炭疽interstitial inflammation（间质性炎）Viral myocarditis病毒性心肌炎Perivessel inflammation血管周围性炎 epidemic encephalitis B(乙脑) Syphilis(梅毒)Fibrinoid necrotic inflammation 纤维蛋白样坏死性炎Necrotic arteritis 坏死性动脉炎二. Chronic Inflammation慢性炎症Progress from acute inflam.P

18、ersistence of the injurious agentInterference in the process of healingBeginning as chronic inflam.Viral intracellular infectionsPersistent microbial infectionsNondegradable exogenous material Autoimmune diseases1. General chronic inflammation:Histologic characteristics: Chronic inflammatory cellsDe

19、struction of parenchymaReplacement by connective tissueTypes of chronic inflammationChronic inflammation of lung with Lymphcytes , Macrophages infiltration and interstitial fibrosis非特异性增生性炎慢性胆囊炎慢性活动性肝炎4. Granulomatous Inflammation (肉芽肿性炎症)Definition: A distinctive pattern of chronic inflammation cha

20、racterized by aggregates of activated macrophages that assume a squamous cell-like (epithelioid) apperance. 以肉芽肿形成为特点的炎症。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 形成的结节状病灶Granuloma (肉芽肿)A focus of aggregates of activated macrophages (epithelioid and Multi-nuclear giant cells) Types: Infective granuloma Foreig

21、n-body granulomagranuloma (肉芽肿)A focus of aggregates of activated macrophages (epithelioid and Multi-nucleate giant cells) Epithepioid cellsMultinucleate giant cellsExamples of granulomatous inflammationBacterial: tuberculosis, leprosy, syphilitic gumma, cat-scratch diseaseParasitic: schistosomiasis

22、Fungal: histoplasma capsulatum, blastomycosis, cryptococcus neoformans, Inorganic metals or dusts: silicosis, berylliosisForeign body: suture, breast prosthesis, vascular graftUnknown: sarcoidosistuberculosisleprosyTyphoid feverschistosomiasisinflammatory pseudotumor(炎性假瘤)inflammatory polyp(炎性息肉)3.

23、othersI. Acute Inflammation 急性炎症1.vascular changes: changes in vascular flow and caliber increased vascular permeability2.Cellular reaction: leukocyte extravasation phagocytosis 二.Inflammative pathgenesis1. Changes in Vascular Flow and Caliber （inflammatory hyperemia，炎性充血）Transient constriction of a

24、rteriolesVasodilation: arterioles - capillary bedsHyperemiaIncreased vascular permeabilityStasisNerve:quick, shortChemical Mediators: slow, permanenceHydrostatic pressureColloid osmotic pressure2. Increased Vascular Permeability（inflammatory exudation，炎性渗出）An immediate transient response (30)Histami

25、ne and leukotrienesA delayed response (2h-10h)Kinins, complement productsA prolonged responseDirect endothelial injuryGaps due to endothelial contractionVenulesVasoactive mediatorsMost comonFast and short-lived(minutes)Direct injuryArterioles,capillaries, and venulesToxins, burns, chemicalsFast and

26、may be long-lived(hours to days)Leukocyte-dependent injuryMostly venulesPulmonary capillariesLate responseLong-lived (hours)Increased transcytosisVenulesVascular endothelium-derived growth factorNew blood vessel formationSites of angiogenesisPersists until intercellular junction formIncrease of Vasc

27、ular LeakageExudate: plasma (protein) and WBC, RBC Intercomparsion 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 inf

28、ections Eosinophilia - parasitic infestations and asthma Shift to the left 核左移现象 Leukopenia （白细胞减少） - typhoid fecver 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）, somno

29、lence（嗜睡）, and malaise（不适） Question：Please summarize the pathological features of different inflammatory types.ABCDEFGHIG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，

30、纤维化）injured cells and tissue 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 cellsStable cells 稳定型细胞Parenchymal cells of liver, kidneys, and pancreasendothelial

31、 cells, lymphocytes, leukocytesPermanent cells 固定型细胞Neurons, skeletal muscle, cardiac muscleCell-cycle细胞周期Cyclins-CDKsABC、D、EGrowth 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 wound contractionbFG

32、F: 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 for PMNs, M, Lympho

33、cytes, 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 intercellular signaling自

34、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 stuctural proteins： collagen胶原蛋白(间质性I、III，基膜性IV、V） elastin弹性蛋白 2.adhesive glycoproteins： 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

35、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 MMP(膜型MMP) MT-MMP-MMP-2other (MMP11

36、、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- ECMMMP1和MMP-3的活化： Pro-uPA uPA PAI + - Plasminogen Plasmin TIMP-1 + - pro-MMP MMPMMP-2的活化： MT-MMP TIMP-2 + - Pro-MMP-2 MMP-2(1).granulation tissue肉芽组织 Newly formed

37、 capillariesProliferation of FibroblastInflammaroty cells. Repair by Healing with connective tissue结缔组织修复The formation of granulation tissue is the critical stape in healingNew small blood vessels(新生的小血管)Proliferation of Fb(成纤维细胞)Inflammaroty cells Healing processes:Induction of inflammation process

38、 (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 contractionAcquisition of wound strengthAngiogenesis from pre-existing vesselsAngiogenesis from endothelial precursor cellsGranulation tissue Scar 肉芽组织 - 纤维组织 - 瘢痕组织肉芽组织