病理學(xué)之炎癥

1、Zhigang Zhang Ph.DDepartment of Pathology, Shanghai Medical College,Chapter Ⅲ. Inflammation炎 癥,,,“ inflammation is a spine of pathology ”,erysipelas,burn,,,炎,Ⅰ. Overview of inflammation,Definition: Inflammation is

2、the reaction of living tissues to all forms of injury.A defensive response of living tissue with a complex reaction in vascularized connective tissue and cellular reaction intended to eliminate the initial cause a

3、s well as the necrotic cells and tissues,,Two main components: Vascular reaction Cellular reaction Protective response: Eliminate the initial causeDestroy harmful agents Intertwined with the

4、 process of repair Reconstitute damaged tissue,inflammation,Inflammation is a double blade sword,,Basically a protective reactionDesdroy, dilute or isolate injurious agentsClear inflammationMake wound tiss

5、ue 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 of

6、ten cause fibrosis of diseased organs,Inflammatorycauses,bacteria and toxins,Trauma,Microbial,Tissue necrosisForeign bodies,radiation,Physical,Acidsalkalis,cooling,Chemical,allergic,,,,,,burns,others,,Infection 感染Ca

7、used by microbial agents (Infectious disease,傳染?。?proliferate and spread

8、 people to people release toxin and enzymes induce immune reaction

9、 AIDS, Tuberculosis,Alteration(變質(zhì)): degeneration and necrosis (Necrostic type)Exudation(滲出): vascular changes, (inflammatory hyperemia) extravasation of

10、 leukocyte and fluid (common cold, watery exudate on mucous membrane of nose)proliferation(增生): epithelium, connective tissue, and blood vessels

11、 (glanuloma, tonsillitis ),II. Basic Pathologic Changes of Inflammation,(massive necrosis of liver in fulminant hepatitis ),,,,Normal structure of liver,Massive necrosis of liver tissue,,phlegmonous appendici

12、tis,Normal slide of appendix,Leukocyte Exudation(inflammatory infiltration炎性浸潤),Leukocytes migrate from the vessel lumen to the inflammatory site of interstitial tissue.,Leukocytes,Neutrophile; B.Macropnage; C. Plasme

13、cellD. Eosinophile; E. Lymphcyte; F. Mutilnucleated giant cell.,,Tonsillitis , enlargment of tonsilla,,Normal glomerular Acute glomerulonephritis,Alteration(變質(zhì)): degeneration and necrosis (Necro

14、stic type)Exudation(滲出): vascular changes, (inflammatory hyperemia) extravasation of leukocyte and fluid (common cold, watery exudate on

15、mucous membrane of nose)proliferation(增生): epithelium, connective tissue, and blood vessels (glanuloma, tonsillitis ),II. Basic Pathologic Changes of Inf

16、lammation,(massive necrosis of liver in fulminant hepatitis ),Acute chronicOnset rapid slow（發(fā)?。〥urationshort longer（病程） Pathology necrosis

17、 proliferation （病變） edema fibrosis neutrophils lymphocyte,A. Clinical classification according to the

18、 duration and severity,III. Classification of inflammation,acute,chronic,Alteration,Exudation,Proliferation,Serous inflammation,Fibrinous inflammation,Purulent inflammation,Granulomatous inflammation,Alterative inflamma

19、tion,Hemorrageic inflammation,,,,,,,,,,,Pathological types,B. Pathological classification of inflammation,Morphologic types of acute inflammation,Alterative inflammation 變質(zhì)性炎Serous inflammation 漿液性炎Fibri

20、nous inflammation 纖維蛋白性炎Purulent inflammation 化膿性炎Hemorrhagic inflammation 出血性炎,1. Alterative inflammation （變質(zhì)性炎）,The cell death is prominent in site of injury, Functions loss of organ or tissues Usually occur in liv

21、er, heart, kidney and brain,,fulminating viral hepatitis.,Encephalitis B,Liquefactive necrosis of brain tissue Neurological symptoms of patient,2.Serous Inflammation (漿液性炎),Cause: II degree burn, snakebite

22、, viral infection, common coldMorphology： Effusion or accumulation of a thin fluid in the site of inflammation Outcomes：resorption (吸收) hydrops(積水) （pleural effusion-hyd

23、rothorax ）,The inflammation with large watery exudationUsually occur in skin(皮膚)，mucosa(粘膜)，serosa(漿膜)，loose tissue(疏松組織),Skin blister resulting from a burn of skin,3.Fibrinous Inflammation纖維蛋白性炎,Morphology：Exudation

24、 (fibrin with inflammatory cells) can be seen in site of inflammation. or the formation of pseudomembranous membrane on the surface of mucosa,Inflammatory exudation contains lof of fibrin Site：surface of ser

25、ous membrane (漿膜) ( lung，heart, articular cavity and mucosa(粘膜）of bronchus or intestines Fibrinous inflammation in mucosa also called pseudomembrenous inflammation More severe injuries (necr

26、osis),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 hepatization,pseudomembranous inflammation.,The fibrinous exudates occur on surfaces of mucous

27、 membrane in respiratory or intestinal tract, which is usually caused by a powerful necrotizing agent, such as diphtheria toxin or dysenteric bacili , it is characterized by formation of a superficial membrane layer on m

28、ucous membrane,,,Bacillary dysentery,菌痢,Diphtheria, 白喉,Outcomes：resolution (脫落、排出、吸收、消散)organization and scarring (機化、粘連),4. Purulent Inflammation化膿性炎,Morphoogy： neutrophiles infiltration in site of inflammation

29、 purulent exudate (necrosis, neutrophils) pus(膿液) neutrophils, necrotic cells and edema fluidTypes： abscess (膿腫) phlegmonous inflammatio

30、n (蜂窩織炎) empyema(積膿) on organ surface,Characterized by plenty of neutrophiles infiltration and pus formation.Cause：pyogenic bacteria (化膿菌, staphylococci), terebinth (松節(jié)油)， coal tar(煤焦

31、油)， die bone(死骨)， foreign body,①Abscess (膿 腫),a localized area of pus accumulation within a tissuecentral region with a mass of necrotic white cells and tissue cells, cavity formed,there is usually a zone of vascularize

32、d tissue with neutrophils around this necrotic focus-----limited membrane of abscess,,①Abscess (膿 腫),spleen,brain,bone,lung,,Limited membrane,,Outcomes of abscess: repair (resolution, scarring)Ulcer(潰瘍)， Sinus(膿竇

33、)， fistula(瘺管),②phlegmonous inflammation蜂 窩 織 炎,an inflammation characterized by a diffuse spread through tissue spaces and along tissue planes caused by the streptococci, infections tends to trek rapidly through larg

34、e areas of tissue Characteristic of such infection is heavy edema and hyperemia of the inflammatory area,erysipelas,phlegmonous appendicitis,,③ Empyema on organ surface,purulent meningitis,Purulent peritonitis,5.Granu

35、lomatous Inflammation(肉芽腫性炎癥)Definition: A distinctive pattern of inflammation with granuloma formation which characterized by aggregates of activated macrophages and multinuclears giant cell.,Granuloma (肉芽腫)A focu

36、s of aggregates of activated macrophages (epithelioid and Multi-nuclear giant cells) Types: Infective granuloma Foreign-body granuloma,Examples of granulomatous inflammationBacterial: t

37、uberculosis, leprosy, syphilitic gumma, cat-scratch disease, typhoid feverParasitic: schistosomiasisFungal: histoplasma capsulatum, blastomycosis, cryptococcus neoformans, coccidioides immitisInorganic metals or dust

38、s: silicosis, berylliosisForeign body: suture, breast prosthesis, vascular graftUnknown: sarcoidosis,Infective,Foreigen body,tuberculosis,Typhoid fever,schistosomiasis,Rheumatic Myocarditis,6. Orther rare types of inf

39、lammation炎癥的其他類型,Hemorrhagic inflammation (出血性炎),Lung anthrax 肺炭疽,interstitial inflammation（間質(zhì)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

40、 inflammation 纖維蛋白樣壞死性炎,Necrotic arteritis 壞死性動脈炎,IV. Pathogenesis of exudation in acute Inflammation 急性炎癥,,1.vascular changes:changes in vascular flow and caliberincreased vascular permeability2.Cellular e

41、vents:leukocyte extravasationphagocytosis,Transient constriction of arteriolesVasodilation: arterioles ---- capillary beds,,1. Changes in Vascular Flow and Caliber （inflammatory hyperemia，炎性充血）,,Hyperemia

42、↓Increased vascular permeability↓Stasis,Nerve:quick, shortChemical Mediators: slow, permanence,,2. Increased Vascular Permeability（inflammatory exudation，炎性滲出）,,Gaps due to endothelial contractionVenulesVasoactiv

43、e mediatorsMost comonFast and short-lived(minutes),Direct injuryArterioles,capillaries, and venulesToxins, burns, chemicalsFast and may be long-lived(hours to days),Leukocyte-dependent injuryMostly venulesPulmonar

44、y capillariesLate responseLong-lived (hours),Increased transcytosisVenulesVascular endothelium-derived growth factor,New blood vessel formationSites of angiogenesisPersists until intercellular junction form,Increas

45、e of Vascular Leakage,,Exudate: plasma (protein) and WBC, RBC Intercomparsion of Exudate and Transulate exudate滲出液transudate漏出液protein＞30g/L<30g/Lspecific gravity＞1.018<1.018Cells＞1000X1

46、06／L＜300X106／LRivaltapositivenegativecoagulationpositivenegativeType of fluidturbidpellucid,,,,Significances: H2O, dilution of toxinantibody, complements, and fibrin opsonizationWBC, phagocytosis

47、 andimmunoreactionpush, organization and conglutination,3. Leukocyte Exudation(inflammatory infiltration炎性浸潤),Definition: The sequence of events in the journey of leukocytes from the vessel lumen to the intersti

48、tial tissue.,,Neutrophils(中性粒細(xì)胞)Small MicrophagesLobulated cell with rich neutrophil granules-Proteinase, oxygen intermediatesEarly stageSuppurative inflammation,Types of Leukocytes in inflammation

49、 (炎癥細(xì)胞),EosinophilsPhagocytosis of Ag-AB, Chronic inflammation,Allergies, parasitic infections,Monocytes, macrophagePhagocytosisSecretion (cytokins)Acute/chronic inflam.Granulomatous inflam.Epithelioid and

50、 giant cells,,,Epithelioid cells,Multinucleated giant cells,Langhan’s foreign bodygiant cells giant cels,Lymphocytes and plasma cellsSecretion: lymphkins, interferon, antibodyImmune reactionChronic infl

51、am. and immune disorders,Steps of Leukocytes ExudationIn the lumen: margination，rolling，and adhesion to endothelium Pavement（附壁） 2. Transmigration across the endothelium Emigration（游出）3. Migration in intersti

52、tial tissues toward a chemotactic stimulationChemotaxis（趨化）,,Pavement（附壁）,Endothelial/Leukocyte Adhesion Molecules,Regulation of endothelial and leukocyte adhesion molecules,Redistribution of P-selectinB. Cytokine a

53、ctivation of endotheliumC. Increased binding avidity of intetrins,Emigration,Leukocyte Chemotaxis and Active,Chemotaxis (趨化作用)chemoattractant (趨化因子)exogenous:bacterial productsendogenous: complement system,C5

54、aproducts of the lipoxygenase pathway systemLTB4cytokinesIL-8,4. Phagocytosis & Degradation吞噬和降解,1.Recognition and attachment (識別、粘著)opsonins(調(diào)理素) IgGC3b receptorsCollectins(集結(jié)素),,2.Engulfmen

55、t (吞入)pseudopods(偽足)phagosome(吞噬體), Lysosome (溶酶體)phagolysosome(吞噬溶酶體),,,3.Killing and degradation (殺滅、降解)O2 dependent mechanism(依賴氧機制)Oxygen Free Radicals，OFR(氧自由基)O2., OH-, H2O2, HOCl–O2 ind

56、ependent mechanism(不依賴氧機制 )Lysozyme(溶菌酶) bactericidal permeability-increasing protein major basic protein, defensins(防御素),myeloperoxidase,hydrogen peroxide,,halide,,,,Ⅳ. Inflammatory Mediator(炎性介質(zhì))Chemical media

57、tors can directly regulate the vascular and cellular events in inflammationProduction of mediators is triggered by microbial products or by host proteins such as complement, kinin, coagulation systems,Most mediators in

58、duce their effects by binding to specific receptors on target cells (通過受體)Mediators may stimulate target cells to release secondary mediators (放大或拮抗)Mediators may act on only one target or have widespread activity

59、(一個或多種靶細(xì)胞)Mediators are short-lived (作用短暫, 滅活、降解或抑制)Most mediators have the potential to cause harmful effects (潛在損傷作用),General principles,Originate: (來源) Plasma-derived mediators: circulate as inactive precursorsC

60、ell-derived mediators: secreted upon activationsynthesized in response to a stimulus,,Plasma protein-derived mediatorsVasoactive amines: histamine （組織胺） 血管活性胺 serotonin（5-羥色胺，5-HT）Plasma protei

61、ns: complement system（補體） 血漿蛋白 kinin system（激肽） clotting system(凝血系統(tǒng))Arachidonic acid metabolites(花生四烯酸代謝產(chǎn)物) prostaglandins（前列腺素，PG） leukotrienes（白三烯

62、，LT） lipoxins（脂質(zhì)素，LX）Platelet-activating factor (血小板激活因子，PAF),Major cell-derived mediatorsCytokines and chemokines: 細(xì)胞因子和趨化細(xì)胞因子tumor necrosis factor（腫瘤壞死因子，TNF）interleukin-1（白介素-1， IL-1）C-X-C，C-C，

63、C, and CX3CNitric oxide(一氧化氮，NO)Lysosomal constituents of leukocytes(溶酶體成分)Oxygen-derived free radicals（氧自由基，OFR）Neuropeptides: substance P（P物質(zhì)） 神經(jīng)多肽 neurokinin A（神經(jīng)激肽A）,Role of mediators in different

64、 reactions of inflammation,Ⅶ. Chronic Inflammation慢性炎癥,,Progress from acute inflam.Persistence of the injurious agentinterference the process of healingBegin as chronic inflam.Viral intracellular infectionsPers

65、istent microbial infectionsNondegradable exogenous material Autoimmune diseases,1. General chronic inflammation:Histologic characteristics: infiltration of Chronic inflammatory cellsDestruction of parenchymaRe

66、placement by connective tissue,Types of chronic inflammation,Chronic inflammation of lung with Lymphcytes , Macrophages infiltration and interstitial fibrosis,Chronic active hepatitis with periportal necrosis of liver

67、cells,2.Granulomatous Inflammation(肉芽腫性炎癥)Definition: A distinctive pattern of chronic inflammation with granuloma formation which characterized by aggregates of activated macrophages and multinuclears giant cell.,i

68、nflammatory pseudotumor(炎性假瘤),inflammatory polyp(炎性息肉),3. others,Ⅷ. Consequences of inflammation炎癥的結(jié)局,,Influences 影響因素local:tissue structure組織結(jié)構(gòu)特性 blood circulation血液循環(huán)狀態(tài) System: nutrition 營養(yǎng)(Vit