病理學：3 inflammation

1、Chapter III. Inflammation炎 癥隸書 骨刻文 Inflame 炎(-itis)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)1.4萬/立方毫米，中性91%。臨床診斷？病理改變？正常闌尾 急性闌尾炎 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具有血管系統(tǒng)的活體組織對局部損傷所發(fā)生的防御反應(yīng)。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,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(yīng)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。“那時我們沒有名氣

6、，國際學術(shù)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(shù)會議，他們提交的論文被退回來 “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Ac

7、ute ChronicOnsetrapid slow（發(fā)病）Durationshorter longer（病程） (days) (months)Pathology edema proliferation（病變） neutrophil lymphocyteIII. Classification of InflammationAlteration(變質(zhì)): degeneration and necrosisExudation(滲出): vascular changes, extravasations of leukocyte and fluidProliferation(增生): epitheli

8、um, connective tissue, and blood vesselsVI. Pathological Features of Inflammation急性炎癥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(zhì)變質(zhì)為主的炎癥滲出Acute Inflammation急性炎癥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、活動期 特點：短，快，顯I. Morphologic types of acute inflammationDegenerative inflammation 變質(zhì)性炎Serous inflammation 漿液性炎Fibrinous inflammation 纖維蛋白性炎Purulent inflammation 化膿性炎Hemorrhagic inflammation 出血性炎1. Degenerative

10、 inflammation （變質(zhì)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 (漿液性炎)Site：skin(皮膚)，mucosa(粘膜)，serosa(漿膜)，loose tissue(疏松組織)Morphology： effusion of a th

11、in fluid (plasma or the secretion of mesothelial cells)Outcomes：resorption (吸收) hydrops(積水)Skin blister resulting from a burn大皰性炎3.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 infl

12、ammatory 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，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。浮 膜Bacillary dysentery,菌痢纖維蛋

13、白+中性粒細胞+壞死脫落的上皮+病原體4.Purulent Inflammation 化膿性炎Definition： This is manifested by the presence of large amounts of purulent exudate consisting of neutrophils, necrotic cells and edema fluid.Cause： pyogenic bacteria (化膿菌, staphylococci) terebinth (松節(jié)油)，coal tar(煤焦油)， die bone(死骨), foreign body(異物)4.Pu

14、rulent Inflammation 化膿性炎Morphology： neutrophils infiltration (Purulent cell) PUS necrotic cells 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)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 (膿 腫)spleenbrainbone轉(zhuǎn)移性膿腫（層連蛋白受體）There is usually a zone of preser

16、ved neutrophils around this necrotic focuslung制膿膜（血漿凝固酶）Outcomes: Repair (resolution, scarring)Ulcer (潰瘍)， Sinus (膿竇)， Fistula (瘺管) Cavity (空洞) phlegmonous inflammation蜂 窩 織 炎Definition: Diffused purulent inflammation in loose connective tissue.Cause: hemolytic streptococcus （透明質(zhì)酸酶、鏈激酶）Predilection

17、site: subcutaneous tissue muscle appendix phlegmonous inflammation蜂 窩 織 炎Appendicitis phlegmonous inflammation蜂 窩 織 炎肌組織蜂窩組織炎 phlegmonous inflammation蜂 窩 織 炎Empyema, 積膿表面化膿5. Orther types of inflammation炎癥的其他類型Haemorrhagic inflammation (出血性炎) blood vessel necrosis or brokenLung anthrax 肺炭疽并非獨立炎癥血管嚴重

18、受損Haemorrhagic inflammation (出血性炎)Interstitial inflammation(間質(zhì)性炎)Viral myocarditis病毒性心肌炎Perivessel inflammation血管周圍性炎Syphilis(梅毒)epidemic encephalitis B (乙腦)Fibrinoid necrotic inflammation 纖維蛋白樣壞死性炎Necrotic arteritis 壞死性動脈炎Chronic Inflammation慢性炎癥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慢性炎癥特點雜 慢 ，長溫 ，遷 ，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 非特異性增生性炎Granulomatous inflammation 肉芽腫性炎1.Non-specific and proliferation inflammation 非特異性增生性炎Proliferationfibroblast, endothelial cell, histocytechronic inflammatory cellslocal epithelial cellsScar1.Non-specific and proliferation inflammation 非特異性增

22、生性炎慢性膽囊炎慢性活動性肝炎2. Granulomatous Inflammation (肉芽腫性炎癥) 以肉芽腫形成為特點的慢性炎癥。 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 形成的境界清楚的結(jié)節(jié)狀病灶Definition: A distinctive pattern of chronic inflammation characterized by aggregates of activated macrophages that assume a squamous cell-like (epithelioid) appearance.Granuloma (肉芽腫)A

23、 focus of aggregates of activated macrophages (epithelioid and Multi-nuclear giant cells) Types: Infective granuloma Foreign-body granulomaEpithepioid cellsMultinucleate giant cellsGranuloma (肉芽腫)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本書中的一些重要肉芽腫結(jié)核結(jié)節(jié) 樹膠腫風濕小體 慢性蟲卵結(jié)節(jié)矽肺結(jié)節(jié) 傷寒小結(jié)膠質(zhì)小結(jié) 異物性肉芽腫直徑為0.5至2mm，單個肉眼難以看見，多個溶合可呈灰白色，粟粒大小由結(jié)節(jié)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硅結(jié)節(jié)傷寒小結(jié)髓樣腫脹期慢性蟲卵肉芽腫多核巨細胞風濕小體風濕細胞inflammatory pseudotumor(炎性假瘤)inflammatory polyp(炎性息肉)3. Others chronic inflammationinflammatory polyp(炎性息肉)I. Acute Inflammation 急性炎癥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，炎性滲出）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 infections Eosinophilia - parasitic infestations and asthma Shif

32、t to the left 核左移現(xiàn)象 Leukopenia （白細胞減少） - typhoid fever and some viruses infection 單核巨噬細胞系統(tǒng)增生SpleenLiverLymph nodes MarrowImpaired function of multiple organs 實質(zhì)臟器功能損害 heart, liver, kidney, brain,全身炎性反應(yīng)綜合征 headache （頭痛），anorexia（厭食）, somnolence（嗜睡）, and malaise（不適） Question：Please list and describe t

33、hree protective effects and three harmful reactions of inflammation to the host.ABCDEFGHIGBD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(zhì)變質(zhì)為主的炎癥 修 復Chapter . Repair修復 proliferation parenchyma實質(zhì) connective tissue間質(zhì) regeneration healing (scar, fibrosis) （再生） （疤痕，纖維化）injured cells and tissue

34、repair. Control of normal cell proliferation and tissue growth細胞生長及其調(diào)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 cells (self-renewing)Stable cells 穩(wěn)定型細胞Parenchymal cells of liver, kidneys, and pancreasendothelial cells, fibro

35、blastPermanent cells 固定型細胞Neurons, cardiac muscleCell-cycle細胞周期Cyclins-CDKsABC、D、EStem Cells 干細胞:Labile cells具有自我復制能力的多潛能細胞，具有無限分裂能力和非對稱復制的特點。在特定條件下分化成多種功能細胞。Two typesEmbryonic stem cells, ES cells 胚胎干細胞 最為幼稚的干細胞； 存在于胚囊內(nèi)細胞團中； 具有強大的自我更新能力。Adult stem cells 成體干細胞/組織干細胞 幼稚程度低于ES cells； 存在于器官或組織的已分化細胞中；

36、分化潛能被限制于他們所在的組織/器官的部分/全部細胞。Induced pluripotent stem cells, iPS cells 多能干細胞在完全分化的細胞中導入一系列對維持干細胞去分化具有關(guān)鍵作用的基因，并導致體細胞核重編碼。這些獲得許多干細胞特性的細胞即為iPS cells。Growth 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 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自分泌旁分泌內(nèi)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細胞外基質(zhì)Major components of ECM： 1.fibrous structural proteins 纖維結(jié)構(gòu)蛋白： collagen膠原蛋白(間質(zhì)性I、III，基膜性IV、V） elastin彈性蛋白 2.adhesive glycoproteins 粘連糖蛋白： 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(zhì)

40、酸、硫酸軟骨素和硫酸皮膚素、 硫酸類肝素和肝素、硫酸角質(zhì)素細胞外基質(zhì)的代謝 合成： 細胞內(nèi)合成、分泌，細胞外組建 降解： 多種酶參與 (MMP，TIMP) 代謝的調(diào)節(jié)：細胞（生長）因子（TGF-）ECM degradematrix metalloproteinase (MMPs, 基質(zhì)金屬蛋白酶)。interstitial collagenase(間質(zhì)膠原酶) MMP-1, -5 - Col和Coltype collagenase (型膠原酶) MMP-2, -9 - Col和Colstromelysin(基質(zhì)溶解素) MMP-3, -10 -蛋白多糖和連接糖蛋白membrane-type M

41、MP(膜型MMP) MT-MMP-MMP-2other (MMP11、MMP12)Tissue inhibitor of matrix metalloproteinase 基質(zhì)金屬蛋白酶抑制因子 - 基質(zhì)降解的負反饋調(diào)節(jié)TIMP-1 - MMP-1，-3， -13TIMP-2 - MMP-2， -9TIMP-3 - ？慢性炎癥- TIMP- ECM(1).granulation tissue肉芽組織 Newly formed capillariesProliferation of FibroblastInflammatory cellsIII. Repair by Healing with c

42、onnective tissue結(jié)締組織修復/纖維性修復The formation of granulation tissue is the critical stage in healingNew small blood vessels(新生的小血管)Proliferation of Fb(成纖維細胞)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