病理生理學教學課件：03 inflammation1

1、Inflame 炎(-itis)Chapter . Inflammation炎 癥炎病例討論患者男性，24歲，平時體健，今日午后開始發(fā)熱，乏力，中上腹不適，自服感冒片。至晚體溫升高，食欲不振，右下腹隱約疼痛，全身不適，急診入院。檢查發(fā)現(xiàn)體溫39.5C，心率90次/分，率齊，兩肺聽診正常，右下腹麥氏點處明顯壓痛。實驗室檢查：白細胞計數(shù).4萬/立方毫米，中性91。臨床診斷？病理改變？正常闌尾 急性闌尾炎 . 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,傳染病） proliferate and spread release toxin and enzymes induce immune reaction Primary(原發(fā)性) secondary(繼發(fā)性)炎癥反應普遍存在，逐步進化致炎因子多，雜，變炎癥在醫(yī)學中：重要、常見對炎癥的研究、認識不斷深入 現(xiàn)象：紅、腫、熱、痛、功能障礙 機制：組織 細胞 分子 傳染病，感染性疾病 病理過程慢性胃炎胃潰瘍的病因發(fā)現(xiàn) 1979年，沃倫教授初步發(fā)現(xiàn)幽門螺桿菌，之后馬歇爾與他合作開展研究?！澳菚r我們沒有名氣，國際學術界根本不認同我們的發(fā)現(xiàn)?！眳⒓影拇罄麃喌囊淮螌W術會議，他們提交

6、的論文被退回來 “每個年輕科學家都會收到退稿信，并因此感到羞愧、沮喪。我的建議是，把退稿信保存在抽屜里。有一天，當你通過艱苦的努力證明你是正確的，就可以拿出所有退稿信大聲地說，是他們錯了?！?如何證明幽門螺桿菌是導致胃潰瘍等疾病的元兇？無法進行動物模型實驗，因為動物與人體的胃差異很大。馬歇爾勇敢地以身試藥，喝下自己培養(yǎng)的細菌?！拔业闹终f我瘋了。連續(xù)5天，我嘔吐不斷，呼吸困難”，后來他用抗生素治愈了自己。馬歇爾說，自己是幸運的，因為抗生素對胃潰瘍的治愈率僅為70。慢性胃炎胃潰瘍的病因發(fā)現(xiàn)馬歇爾獲2005年諾貝爾醫(yī)學獎Alteration(變質): degeneration and necros

7、is (Necrostic type)Exudation(滲出): 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.炎癥的基本病變 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炎性浸潤)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 （發(fā)?。?rapid slowDuration （病程） short longerPathology necrosis proliferation （病變） ed

10、ema fibrosis neutrophils lymphocyte A. Clinical classification according to the duration and severityIII. 炎癥的分型 Classification of inflammation 急性炎癥滲出 炎癥類型漿液性炎纖維蛋白性炎化膿性炎出血性炎、慢性炎癥增生炎癥類型肉芽腫性炎炎性息肉炎性假瘤變質 變質為主的炎癥臨床分型 病理特點 病理分型. Morphologic types of acute inflammationDegenerative inflammation 變質性炎Serous in

11、flammation 漿液性炎Fibrinous inflammation 纖維蛋白性炎Purulent inflammation 化膿性炎Hemorrhagic inflammation 出血性炎Granulomatous inflammation 肉芽腫性炎1. Degenerative inflammation （變質性炎）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. 炎癥局部以組織細胞變性和壞死為主的炎癥稱為變質性炎Encephalitis B 1.Serous Inflammation (漿液性炎)Site：skin(皮膚)，mucosa(粘膜)，serosa(漿膜)，loose tissue(疏松組織)Morphology： effusion of a thin fluid (plasma or the secretion of mesothelial cells)Outcomes：resorption (吸收) hydrops(積水)Skin blister resulting from a bur

13、n2.Fibrinous Inflammation 纖維蛋白性炎 Site：serosa(漿膜)，lung(肺)， mucosa(粘膜）-（seudomembrenous inflammation 假膜性炎）Morphology：more sever injuries (necrosis)exudation (fibrin with inflammatory cells)Outcomes：resolution (脫落、排出、吸收、消散) organization and scarring (機化、粘連)Fibrinous pericarditis, Shaggy Heart 纖維蛋白性心包炎，

14、絨毛心 Lobar pneumonia, gray hepatization大葉性肺炎肝變期Lobar pneumonia, gray hepatizationDiphtheria, 白喉pseudomembranous inflammation 假膜性炎 -發(fā)生在粘膜上的纖維蛋白性炎。Bacillary dysentery,菌痢3.Purulent Inflammation 化膿性炎Cause： pyogenic bacteria (化膿菌, staphylococci) terebinth (松節(jié)油)，coal tar(煤焦油)， die bone(死骨)， foreign body(異物

15、)Morphoogy： neutrophils infiltration purulent exudate (neutrophils, necrotic cells and edema fluid) Types： abscess (膿腫) 膿腔，膿壁， 膿液(pus) phlegmonous inflammation (蜂窩織炎) purulent catarrh(膿性卡他)，empyema(積膿)Abscess (膿 腫)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 (膿 腫)spleenbrainbonelung制膿膜Outcomes: repair(resolution, scarring)Ulcer(潰瘍)， Sinus(膿竇)， fistula(瘺管)phlegmonous inflammation蜂 窩 織 炎Empyema, 積膿Orther types of inflammation

17、炎癥的其他類型Haemorrhagic inflammation (出血性炎)Lung anthrax 肺炭疽interstitial inflammation（間質性炎）Viral myocarditis病毒性心肌炎Perivessel inflammation血管周圍性炎 epidemic encephalitis B(乙腦) Syphilis(梅毒)Fibrinoid necrotic inflammation 纖維蛋白樣壞死性炎Necrotic arteritis 壞死性動脈炎二. Chronic Inflammation慢性炎癥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非特異性增生性炎慢性膽囊炎慢性活動性肝炎4. Granulomatous Inflammation (肉芽腫性炎癥)Definition: A distinctive pattern of chronic inflammation cha

20、racterized by aggregates of activated macrophages that assume a squamous cell-like (epithelioid) apperance. 以肉芽腫形成為特點的炎癥。肉芽腫：是以巨噬細胞及其演化的細胞 在炎癥局部大量浸潤和增生所 形成的結節(jié)狀病灶Granuloma (肉芽腫)A focus of aggregates of activated macrophages (epithelioid and Multi-nuclear giant cells) Types: Infective granuloma Foreig

21、n-body granulomagranuloma (肉芽腫)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 急性炎癥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，炎性滲出）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滲出液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 核左移現(xiàn)象 Leukopenia （白細胞減少） - typhoid fecver and some viruses infection 單核巨噬細胞系統(tǒng)增生SpleenLiverLymph nodes MarrowImpaired function of multiple organs 實質臟器功能損害 heart, liver, kidney, brain,全身炎性反應綜合征 headache （頭痛），anorexia（厭食）, somno

29、lence（嗜睡）, and malaise（不適） Question：Please summarize the pathological features of different inflammatory types.ABCDEFGHIG急性炎癥滲出 炎癥類型漿液性炎纖維蛋白性炎化膿性炎出血性炎、慢性炎癥增生炎癥類型肉芽腫性炎炎性息肉炎性假瘤變質變質為主的炎癥 修 復Chapter . Repair修復 proliferation parenchyma實質 connective tissue間質 regeneration healing (scar, fibrosis) （再生） （疤痕，

30、纖維化）injured cells and tissue repair. Control of normal cell proliferation and tissue growth細胞生長及其調節(jié)Cells-proliferative activity(增生能力)Labile cells 不穩(wěn)定型細胞Surface epithelia, cells of bone marrowhematopoietic tissuesStem cellsStable cells 穩(wěn)定型細胞Parenchymal cells of liver, kidneys, and pancreasendothelial

31、 cells, lymphocytes, leukocytesPermanent cells 固定型細胞Neurons, skeletal muscle, cardiac muscleCell-cycle細胞周期Cyclins-CDKsABC、D、EGrowth factors 生長因子: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、分泌旁分泌內分泌PIP24，5二磷酸磷脂酰肌醇；DAG二乙?；视?；IP3三磷酸肌醇. Extracellular matrix, ECM細胞外基質Major components of ECM： 1.fibrous stuctural proteins： collagen膠原蛋白(間質性I、III，基膜性IV、V） elastin彈性蛋白 2.adhesive glycoproteins： fibronectin纖連蛋白 laminin層連蛋白 3.proteoglycans 蛋白聚糖： 氨基多糖GAG蛋白核心 GAG：透明質酸、硫酸軟骨素和硫酸皮膚素、 硫酸類肝素和肝素、硫酸角質素細胞外基

35、質的代謝 合成： 細胞內合成、分泌，細胞外組建 降解： 多種酶參與（MMP，TIMP) 代謝的調節(jié)：細胞（生長）因子（TGF-）ECM degradematrix metalloproteinase (MMPs, 基質金屬蛋白酶)。interstitial collagenase(間質膠原酶) MMP-1, -5 - Col和Coltype collagenase (型膠原酶) MMP-2, -9 - Col和Colstromelysin(基質溶解素) MMP-3, -10 -蛋白多糖和連接糖蛋白membrane-type MMP(膜型MMP) MT-MMP-MMP-2other (MMP11

36、、MMP12)Tissue inhibitor of matrix metalloproteinase 基質金屬蛋白酶抑制因子 - 基質降解的負反饋調節(jié)TIMP-1 - MMP-1，-3， -13TIMP-2 - MMP-2， -9TIMP-3 - ？慢性炎癥- 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肉芽組織 Newly formed

37、 capillariesProliferation of FibroblastInflammaroty cells. Repair by Healing with connective tissue結締組織修復The formation of granulation tissue is the critical stape in healingNew small blood vessels(新生的小血管)Proliferation of Fb(成纖維細胞)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 肉芽組織 - 纖維組織 - 瘢痕組織肉芽組織