1、Zhigang Zhang Ph.DDepartment of Pathology, Shanghai Medical College,Chapter . Inflammation炎 症,“ inflammation is a spine of pathology ”,erysipelas,burn,炎,. Overview of inflammation,Definition: Inflammation is the reaction of living tissues to all forms of injury.A defensive response of living tissue
2、with a complex reaction in vascularized connective tissue and cellular reaction intended to eliminate the initial cause as well as the necrotic cells and tissues,Two main components: Vascular reaction Cellular reaction Protective response: Eliminate the initial causeDestroy harmful agents Intertwine
3、d with the process of repair Reconstitute damaged tissue,inflammation,Inflammation is a double blade sword,Basically a protective reactionDesdroy, dilute or isolate injurious agentsClear inflammationMake wound tissue healing,Have Potential to cause harmThe basis of life-threatening allergic reaction
4、 to insect or drugsPericardial inflammation resulting in dense encasing scar that impair heart functionChronic inflammation often cause fibrosis of diseased organs,Inflammatorycauses,bacteria and toxins,Trauma,Microbial,Tissue necrosisForeign bodies,radiation,Physical,Acidsalkalis,cooling,Chemical,a
5、llergic,burns,others,Infection 感染Caused by microbial agents (Infectious disease,传染病） proliferate and spread people to people release toxin and enzymes induce immune reaction AIDS, Tuberculosis,Alteration(变质): degeneration and necrosis (Necrostic type)Exudation(渗出): vascular changes, (inflammatory hy
6、peremia) 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. Basic Pathologic Changes of Inflammation,(massive necrosis of liver in fulminant hepatitis ),Normal
7、structure of liver,Massive necrosis of liver tissue,phlegmonous appendicitis,Normal slide of appendix,Leukocyte Exudation(inflammatory infiltration炎性浸润),Leukocytes migrate from the vessel lumen to the inflammatory site of interstitial tissue.,Leukocytes,Neutrophile; B.Macropnage; C. Plasme cellD. Eo
8、sinophile; E. Lymphcyte; F. Mutilnucleated giant cell.,Tonsillitis , enlargment of tonsilla,Normal glomerular Acute glomerulonephritis,Alteration(变质): degeneration and necrosis (Necrostic type)Exudation(渗出): vascular changes, (inflammatory hyperemia) extravasation of leukocyte and fluid (common cold
9、, watery exudate on mucous membrane of nose)proliferation(增生): epithelium, connective tissue, and blood vessels (glanuloma, tonsillitis ),II. Basic Pathologic Changes of Inflammation,(massive necrosis of liver in fulminant hepatitis ),Acute chronicOnset rapid slow（发病）Durationshort longer（病程） Patholo
10、gy necrosis proliferation （病变） edema fibrosis neutrophils lymphocyte,A. Clinical classification according to the duration and severity,III. Classification of inflammation,acute,chronic,Alteration,Exudation,Proliferation,Serous inflammation,Fibrinous inflammation,Purulent inflammation,Granulomatous i
11、nflammation,Alterative inflammation,Hemorrageic inflammation,Pathological types,B. Pathological classification of inflammation,Morphologic types of acute inflammation,Alterative inflammation 变质性炎Serous inflammation 浆液性炎Fibrinous inflammation 纤维蛋白性炎Purulent inflammation 化脓性炎Hemorrhagic inflammation 出
12、血性炎,1. Alterative inflammation （变质性炎）,The cell death is prominent in site of injury, Functions loss of organ or tissues Usually occur in liver, heart, kidney and brain,fulminating viral hepatitis.,Encephalitis B,Liquefactive necrosis of brain tissue Neurologicalsymptoms of patient,2.Serous Inflammat
13、ion (浆液性炎),Cause: II degree burn, snakebite, viral infection, common coldMorphology： Effusion or accumulation of a thin fluid in the site of inflammation Outcomes：resorption (吸收) hydrops(积水) （pleural effusion-hydrothorax ）,The inflammation with large watery exudationUsually occur in skin(皮肤)，mucosa(
14、粘膜)，serosa(浆膜)，loose tissue(疏松组织),Skin blister resulting from a burn of skin,3.Fibrinous Inflammation纤维蛋白性炎,Morphology：Exudation (fibrin with inflammatory cells) can be seen in site of inflammation. or the formation of pseudomembranous membrane on the surface of mucosa,Inflammatory exudation contain
15、s lof of fibrin Site：surface of serous membrane (浆膜) ( lung，heart, articular cavity and mucosa(粘膜）of bronchus or intestines Fibrinous inflammation in mucosa also called pseudomembrenous inflammation More severe injuries (necrosis),Fibrinous pericarditis, Shaggy Heart 纤维蛋白性心包炎，绒毛心,Lobar pneumonia, gr
16、ay hepatization大叶性肺炎肝变期,Lobar pneumonia, gray hepatization,pseudomembranous inflammation.,The fibrinous exudates occur on surfaces of mucous membrane in respiratory or intestinal tract, which is usually caused by a powerful necrotizing agent, such as diphtheria toxin or dysenteric bacili , it is cha
17、racterized by formation of a superficial membrane layer on mucous membrane,Bacillary dysentery,菌痢,Diphtheria, 白喉,Outcomes：resolution (脱落、排出、吸收、消散)organization and scarring (机化、粘连),4. Purulent Inflammation化脓性炎,Morphoogy： neutrophiles infiltration in site of inflammation purulent exudate (necrosis, ne
18、utrophils) pus(脓液) neutrophils, necrotic cells and edema fluidTypes： abscess (脓肿) phlegmonous inflammation (蜂窝织炎) empyema(积脓) on organ surface,Characterized by plenty of neutrophiles infiltration and pus formation.Cause：pyogenic bacteria (化脓菌, staphylococci), terebinth (松节油)， coal tar(煤焦油)， die bone
19、(死骨)， foreign body,Abscess (脓 肿),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 vascularized tissue with neutrophils around this necrotic focus-limited membrane of abscess,Abscess (脓 肿)
20、,spleen,brain,bone,lung,Limited membrane,Outcomes of abscess: repair (resolution, scarring)Ulcer(溃疡)， Sinus(脓窦)， fistula(瘘管),phlegmonous inflammation蜂 窝 织 炎,an inflammation characterized by a diffuse spread through tissue spaces and along tissue planes caused by the streptococci, infections tends to
21、 trek rapidly through large areas of tissue Characteristic of such infection is heavy edema and hyperemia of the inflammatory area,erysipelas,phlegmonous appendicitis, Empyema on organ surface,purulent meningitis,Purulent peritonitis,5.Granulomatous Inflammation(肉芽肿性炎症)Definition: A distinctive patt
22、ern of inflammation with granuloma formation which characterized by aggregates of activated macrophages and multinuclears giant cell.,Granuloma (肉芽肿)A focus of aggregates of activated macrophages (epithelioid and Multi-nuclear giant cells) Types: Infective granuloma Foreign-body granuloma,Examples o
23、f granulomatous inflammationBacterial: tuberculosis, leprosy, syphilitic gumma, cat-scratch disease, typhoid feverParasitic: schistosomiasisFungal: histoplasma capsulatum, blastomycosis, cryptococcus neoformans, coccidioides immitisInorganic metals or dusts: silicosis, berylliosisForeign body: sutur
24、e, breast prosthesis, vascular graftUnknown: sarcoidosis,Infective,Foreigen body,tuberculosis,Typhoid fever,schistosomiasis,Rheumatic Myocarditis,6. Orther rare types of inflammation炎症的其他类型,Hemorrhagic inflammation (出血性炎),Lung anthrax 肺炭疽,interstitial inflammation（间质性炎）,Viral myocarditis病毒性心肌炎,Periv
25、essel 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,IV. Pathogenesis of exudation in acute Inflammation 急性炎症,1.vascular changes:changes in vascular flow and caliberincreased vascular permeability2.Cellular events:leukoc
26、yte extravasationphagocytosis,Transient constriction of arteriolesVasodilation: arterioles - capillary beds,1. Changes in Vascular Flow and Caliber （inflammatory hyperemia，炎性充血）,HyperemiaIncreased vascular permeabilityStasis,Nerve:quick, shortChemical Mediators: slow, permanence,2. Increased Vascula
27、r Permeability（inflammatory exudation，炎性渗出）,Gaps due to endothelial contractionVenulesVasoactive mediatorsMost comonFast and short-lived(minutes),Direct injuryArterioles,capillaries, and venulesToxins, burns, chemicalsFast and may be long-lived(hours to days),Leukocyte-dependent injuryMostly venules
28、Pulmonary capillariesLate responseLong-lived (hours),Increased transcytosisVenulesVascular endothelium-derived growth factor,New blood vessel formationSites of angiogenesisPersists until intercellular junction form,Increase of Vascular Leakage,Exudate: plasma (protein) and WBC, RBC Intercomparsion o
29、f Exudate and Transulate exudate渗出液transudate漏出液protein30g/L30g/Lspecific gravity1.0181.018Cells1000X106L300X106LRivaltapositivenegativecoagulationpositivenegativeType of fluidturbidpellucid,Significances: H2O, dilution of toxinantibody, complements, and fibrin opsonizationWBC, phagocytosis andimmun
30、oreactionpush, organization and conglutination,3. Leukocyte Exudation(inflammatory infiltration炎性浸润),Definition: The sequence of events in the journey of leukocytes from the vessel lumen to the interstitial tissue.,Neutrophils(中性粒细胞)Small MicrophagesLobulated cell with rich neutrophil granules-Prote
31、inase, oxygen intermediatesEarly stageSuppurative inflammation,Types of Leukocytes in inflammation (炎症细胞),EosinophilsPhagocytosis of Ag-AB, Chronic inflammation,Allergies, parasitic infections,Monocytes, macrophagePhagocytosisSecretion (cytokins)Acute/chronic inflam.Granulomatous inflam.Epithelioid
32、and giant cells,Epithelioid cells,Multinucleated giant cells,Langhans foreign bodygiant cells giant cels,Lymphocytes and plasma cellsSecretion: lymphkins, interferon, antibodyImmune reactionChronic inflam. and immune disorders,Steps of Leukocytes ExudationIn the lumen: margination，rolling，and adhesi
33、on to endothelium Pavement（附壁） 2. Transmigration across the endothelium Emigration（游出）3. Migration in interstitial tissues toward a chemotactic stimulationChemotaxis（趋化）,Pavement（附壁）,Endothelial/Leukocyte Adhesion Molecules,Regulation of endothelial and leukocyte adhesion molecules,Redistribution of
34、 P-selectinB. Cytokine activation of endotheliumC. Increased binding avidity of intetrins,Emigration,Leukocyte Chemotaxis and Active,Chemotaxis (趋化作用)chemoattractant (趋化因子)exogenous:bacterial productsendogenous: complement system,C5aproducts of the lipoxygenase pathway systemLTB4cytokinesIL-8,4. Pha
35、gocytosis & Degradation吞噬和降解,1.Recognition and attachment (识别、粘着)opsonins(调理素) IgGC3b receptorsCollectins(集结素),2.Engulfment (吞入)pseudopods(伪足)phagosome(吞噬体), Lysosome (溶酶体)phagolysosome(吞噬溶酶体),3.Killing and degradation (杀灭、降解)O2 dependent mechanism(依赖氧机制)Oxygen Free Radicals，OFR(氧自由基)O2., OH-, H2O2,
36、 HOClO2 independent mechanism(不依赖氧机制 )Lysozyme(溶菌酶) bactericidal permeability-increasing protein major basic protein, defensins(防御素),myeloperoxidase,hydrogen peroxide,halide,. Inflammatory Mediator(炎性介质)Chemical mediators can directly regulate the vascular and cellular events in inflammationProducti
37、on of mediators is triggered by microbial products or by host proteins such as complement, kinin, coagulation systems,Most mediators induce their effects by binding to specific receptors on target cells (通过受体)Mediators may stimulate target cells to release secondary mediators (放大或拮抗)Mediators may ac
38、t on only one target or have widespread activity (一个或多种靶细胞)Mediators are short-lived (作用短暂, 灭活、降解或抑制)Most mediators have the potential to cause harmful effects (潜在损伤作用),General principles,Originate: (来源) Plasma-derived mediators: circulate as inactive precursorsCell-derived mediators: secreted upon
39、activationsynthesized in response to a stimulus,Plasma protein-derived mediatorsVasoactive amines: histamine （组织胺） 血管活性胺 serotonin（5-羟色胺，5-HT）Plasma proteins: complement system（补体） 血浆蛋白 kinin system（激肽） clotting system(凝血系统)Arachidonic acid metabolites(花生四烯酸代谢产物) prostaglandins（前列腺素，PG） leukotrienes
40、（白三烯，LT） lipoxins（脂质素，LX）Platelet-activating factor (血小板激活因子，PAF),Major cell-derived mediatorsCytokines and chemokines: 细胞因子和趋化细胞因子tumor necrosis factor（肿瘤坏死因子，TNF）interleukin-1（白介素-1， IL-1）C-X-C，C-C，C, and CX3CNitric oxide(一氧化氮，NO)Lysosomal constituents of leukocytes(溶酶体成分)Oxygen-derived free radic
41、als（氧自由基，OFR）Neuropeptides: substance P（P物质） 神经多肽 neurokinin A（神经激肽A）,Role of mediators in different reactions of inflammation,. Chronic Inflammation慢性炎症,Progress from acute inflam.Persistence of the injurious agentinterference the process of healingBegin as chronic inflam.Viral intracellular infect
42、ionsPersistent microbial infectionsNondegradable exogenous material Autoimmune diseases,1. General chronic inflammation:Histologic characteristics: infiltration of Chronic inflammatory cellsDestruction of parenchymaReplacement by connective tissue,Types of chronic inflammation,Chronic inflammation o
43、f lung with Lymphcytes , Macrophages infiltration and interstitial fibrosis,Chronic active hepatitis with periportal necrosis of liver cells,2.Granulomatous Inflammation(肉芽肿性炎症)Definition: A distinctive pattern of chronic inflammation with granuloma formation which characterized by aggregates of activated macrophages and multinuclears giant cell.,inflammatory pseudotumor(炎性假瘤),inflammatory polyp(炎性息肉),3. others,. Consequences of inflammation炎症的结局,Influences 影响因素local:tissue structure组织结构特性 blood circulation血液循环状态 System: nutrition 营养(Vit C） immune reaction免疫反应 medical treatment治疗措施 others,
