1、炎炎 症症InflammationNANJING MEDICAL UNIVERSITYlyq_ a protective response involving host cells,blood vessels,and proteins and other mediators that is intended to eliminate the initial cause of cell injury,as well as the necrotic cells and tissues resulting from the original insult,and to initiate the pr
2、ocess of repair.What is Inflammation?F机体的机体的保护性保护性反应反应F目的：目的：清除引起损伤的因素清除引起损伤的因素 清除坏死组织清除坏死组织F参与者：血管，血液，白细胞参与者：血管，血液，白细胞炎症的概念炎症的概念 什么时候会有炎症反应？什么时候会有炎症反应？机体为什么要清除损伤因素和坏死组织？机体为什么要清除损伤因素和坏死组织？如果炎症反应：如果炎症反应：异常发生异常发生inappropriate 过于强烈过于强烈too strong 持续时间过长持续时间过长prolonged 为啥要吃消炎药？为啥要吃消炎药？炎症过程伴随正常细胞损伤炎症过程伴随正
3、常细胞损伤与慢性病和癌症有关与慢性病和癌症有关致炎因子致炎因子F感染感染 Infection F坏死坏死Tissue necrosis F异物异物 Foreign bodies(ex&en)F免疫反应免疫反应 Immune reactions IschemiaTrauma Chemical injuryPhysical injury炎症的步骤炎症的步骤1.识别致炎因子和识别致炎因子和坏死组织坏死组织2.招募白细胞招募白细胞 3.清除致炎因子和清除致炎因子和坏死组织坏死组织4.修复修复5.调控发生于过程调控发生于过程炎症的基本病理变化炎症的基本病理变化 变质变质 渗出渗出 增生增生exudati
4、on渗出液成分渗出液成分Leukocytes:FNeutrophils(PMNs)FMonocytes(macrophages,M)FLymphocytesFPlasma cellsFEosinophils Plasma proteins:FAlbuminsFGlobulinsFComplementFFibrinogen Fibrins 细菌屏障细菌屏障 修复支架修复支架exudates炎症的局部表现炎症的局部表现红、肿、热、痛、功能障碍红、肿、热、痛、功能障碍Aeromonas hydrophila infection following puncture with fishing hook
5、皮肤蜂窝织炎皮肤蜂窝织炎cellulites慢性肾小球肾炎慢性肾小球肾炎炎症类型：急性与慢性炎症类型：急性与慢性F急性炎症急性炎症Acute inflammation持续时间短持续时间短中性粒细胞中性粒细胞浸润浸润 渗出明显渗出明显F慢性炎症慢性炎症Chronic inflammation持续时间长持续时间长单个核细胞浸润（巨噬单个核细胞浸润（巨噬C，淋巴，淋巴C，浆，浆C）组织增生修复明显组织增生修复明显急性炎症与慢性炎症比较急性炎症与慢性炎症比较 Feature AcuteChronicOnsetFast:minutes or hoursSlow:daysCellular infiltra
6、teMainly neutrophilsMonocytes/macrophages and lymphocytesTissue injury,fibrosisUsually mild and self-limitedOften severe and progressiveLocal and systemic signsProminentLess prominent;may be subtle急性肺炎急性肺炎慢性肺炎慢性肺炎 血流增加血流增加蛋白渗出蛋白渗出PMNsPMNs游出游出 把蛋白和白细胞送至损伤处把蛋白和白细胞送至损伤处 急性炎症急性炎症急性炎症过程分解急性炎症过程分解血管变化血管变化
7、 Vascular changes u血流动力学改变血流动力学改变 hyperemia u通透性增加通透性增加 leakage 白细胞事件白细胞事件Cellular events u白细胞招募白细胞招募 recruitment u白细胞杀伤和清除白细胞杀伤和清除 activation inflammatory mediators Dilation of arterioles Opening up of capillaries 充血充血细动脉短暂收缩细动脉短暂收缩Gaps漏出液漏出液Transudate 渗出液渗出液Exudate1Proteins 充血和通透性增加导致：充血和通透性增加导致：水
8、肿水肿edema/积液积液effusion血流停滞血流停滞satsis 白细胞边集白细胞边集marginationTransudates Crosses intact membraneMost clear(acellular)Caused by hydrostatic imbalance or osmotic gradientsExudatesCrosses through gaps in capillaryMost cloudy(cellular)Caused by inflammationEdema can be caused by exudates or transudatesPeric
9、ardial Effusion:Exudate Versus Transudate ExudateTransudateEtiologyMalignancyInfectious Postpericardiotomy syndromeCollagen vascular diseasesRadiationUremiaHypothyroidismTraumaSpecific gravity(g/mL)1.0153.00.50.60.6Fluid/serum glucose ratio1.0LDH=lactate dehydrogenaseRetraction of endotheliumEndothe
10、lial injury血管通透性增加的机制血管通透性增加的机制血管通透性增加的机制血管通透性增加的机制F内皮收缩内皮收缩F内皮损伤内皮损伤 FIncreased transcytosis of proteins FLeakage from new blood vessels Immediate transient responsedelayed prolonged leakage Immediate sustained leakage 渗出液？漏出液？渗出液？漏出液？渗出液？漏出液？渗出液？漏出液？肝硬化病人伴肝硬化病人伴腹水腹水渗出液？漏出液？渗出液？漏出液？淋巴系统在炎症中的作用淋巴系统在
11、炎症中的作用Helps drain edema fluid,leukocytes,and cell debris May transport the offending agent(especially microbes)ulymphangitis ulymphadenitis lymphangitis due to Trypanosomiasistsetse flylymphadenitis due to tularemiau Groin u Armpit u Neck u Under the jaw and chin u Behind the ears u On the back of t
12、he head Common areas where the lymph nodes can be felt include:细胞事件：招募与激活细胞事件：招募与激活 通常只发生在需要的时间和地点通常只发生在需要的时间和地点 白细胞：白细胞：得到通知得到通知停下停下出血管出血管向正确的方向行走向正确的方向行走 白细胞招募白细胞招募 recruitment滚动滚动 rolling 粘附粘附 adhesion 游出游出 transmigration 趋化作用趋化作用 chemotaxis 血管内血管内跨血管跨血管血管外血管外The journey of leukocytes is mediated
13、 and controlled by adhesion molecules and chemokines.粘附分子粘附分子趋化因子趋化因子Endothelial MoleculeLeukocyte MoleculeMajor RoleP-selectinSialyl-Lewis X-modified proteinsRolling(neutrophils,monocytes,lymphocytes)E-selectinSialyl-Lewis X-modified proteinsRolling and adhesion(neutrophils,monocytes,T lymphocytes)
14、GlyCam-1,CD34L-selectinRolling(neutrophils,monocytes)*ICAM-1(immunoglobulin family)CD11/CD18 integrins(LFA-1,Mac-1)Adhesion,arrest,transmigration(neutrophils,monocytes,lymphocytes)VCAM-1(immunoglobulin family)VLA-4 integrinAdhesion(eosinophils,monocytes,lymphocytes)CD31CD31Transmigration(all leukocy
15、tes)趋化因子趋化因子chemoattractants趋化作用趋化作用Chemotaxis locomotion along a chemical gradient趋化因子趋化因子（best identified）1.Soluble bacterial products2.Complement components C5a3.Chemokines(IL-8,MCP-1)4.LTB4(AA metabolite)白细胞游出白细胞游出Transmigrationdiapedesis白细胞血管外阿米巴样运动白细胞血管外阿米巴样运动 不同场合聚集的白细胞种类不同不同场合聚集的白细胞种类不同 与炎症反
16、应的阶段有关与炎症反应的阶段有关 （the age of the inflammatory response）中性粒细胞中性粒细胞PMNs单核单核/巨噬细胞巨噬细胞Monocytes/macrophges6 6hrhr2424hrhr48hr7272hrhr不同场合聚集的白细胞种类不同不同场合聚集的白细胞种类不同 与致炎因子种类有关（与致炎因子种类有关（the type of stimulus）萄球菌、链球菌萄球菌、链球菌 嗜中性粒细胞嗜中性粒细胞 病毒病毒 淋巴细胞淋巴细胞 过敏性反应过敏性反应 嗜酸性粒细胞嗜酸性粒细胞 蠕虫感染蠕虫感染 嗜酸性粒细胞嗜酸性粒细胞Myocardium inf
17、arctDay 1Day 3病毒性脑炎病毒性脑炎哮喘哮喘 Asthma白细胞激活白细胞激活SenseSense到死细胞和到死细胞和微生物的存在微生物的存在吞噬吞噬 phagocytosis细胞内杀伤和降解细胞内杀伤和降解细胞外捕捉细胞外捕捉“traps”生产炎症介质生产炎症介质TLRsinflammasome调理素受体调理素受体吞噬吞噬 PhagocytosisReactive Oxygen Species(ROS)Nitric Oxide溶酶体中的酶和蛋白溶酶体中的酶和蛋白 细胞内杀伤及降解机制细胞内杀伤及降解机制oxidative burstdefensinslysozymelactofe
18、rrincathelicidinsMajor basic proteinNeutral proteaseAcid proteaselysosomal granulesDegrade&killingphagocyteA long fibre Leaked enzymes 杀菌物质被释放到细胞外杀菌物质被释放到细胞外 Emphysema肺气肿肺气肿 due to 1-antitrypsin deficiencyNeutrophil extracellular traps(NETs)Healthy neutrophils被困之链球菌被困之链球菌细胞外杀伤机制细胞外杀伤机制白细胞介导的组织损伤白细胞介
19、导的组织损伤 Fbystander tissues FAutoimmune diseasesFAllergies FIschemia reperfusionrelease of lysosomalgranule contents巨噬细胞激活后的功能巨噬细胞激活后的功能Phagocytose pathogens and dying cells Produce cytokines to amplify or limit inflammatory reactions Produce growth factors endothelial cells fibroblasts collagen synth
20、esis Presenting antigen Defects in leukocyte adhesionuLAD-1uLAD-2Defects in microbicidal activity uChronic granulomatous disease Defects in phagolysosome formation uChdiak-Higashi syndrome 先天性白细胞功能缺陷先天性白细胞功能缺陷CGD获得性白细胞功能缺陷获得性白细胞功能缺陷放射性治疗放射性治疗 Radiation injury癌症治疗癌症治疗 Cancer therapy 糖皮质激素糖皮质激素 Glucoc
21、orticoid administration 糖尿病糖尿病 Diabetes酗酒酗酒 Alcoholism感染的扩散和蔓延感染的扩散和蔓延局部蔓延局部蔓延淋巴道蔓延淋巴道蔓延血行蔓延血行蔓延菌血症菌血症 toxemia毒血症毒血症 septicemia败血症败血症 septicemia脓毒血症脓毒血症 pyemiaSummary:Acute inflammationFrapidly delivers and to sites of injury Fthe main vascular reactions are andFthe resulting fluid accumulation is c
22、alled Fafter the endothelial cells get the signal from,they and leukocytes upregulate the expression of to facilitate the movements of leukocytes that include and Fpredominate in the early inflammatory infiltrate and are later replaced by.Fthe main jobs of leukocytes at site are andFthe most powerfu
23、l weapons to kill is called owned by Facute inflammation often cause unwanted damage becauseFthe out comes may be,orSummary:Acute inflammation炎症介质炎症介质 Mediators The most important mediators of acute inflammation are:Vasoactive amines(histamine)Lipid products(prostaglandins&leukotrienes)Cytokines(inc
24、luding chemokines)Complement productsthe substances that initiate and regulateinflammatory reactions来源来源Sources:细胞细胞释放释放 血浆蛋白中前体激活血浆蛋白中前体激活Majorly by the sentinelsOthers:PMNs,Plts,endothelium,epithelium 炎症介质炎症介质 Mediators 有活性的炎症介质只在相应的刺激下生成有活性的炎症介质只在相应的刺激下生成 大部分短命大部分短命 一种介质可刺激其他介质释放一种介质可刺激其他介质释放 扩张细
25、动脉，增加细静脉通透性扩张细动脉，增加细静脉通透性 Histamine 储存在肥大细胞颗粒中，储存在肥大细胞颗粒中，受刺激迅速释放受刺激迅速释放 引起引起Histamine释放的释放的stimuli：血管活性胺血管活性胺:Histamine组胺组胺 and Serotonina)physical injury b)binding of Ab to mast cells(allergies)c)anaphylatoxins(C3a and C5a)细胞来源的炎症介质细胞来源的炎症介质 花生四烯酸花生四烯酸AA代谢产物代谢产物 eicosanoids前列腺素前列腺素 prostaglandins，
26、PG白细胞三烯白细胞三烯 leukotriene，LT脂质素脂质素 lipoxins，LXuAAAA主要存在于细胞磷脂膜中主要存在于细胞磷脂膜中（糖皮质激素抑制磷脂酶活性使糖皮质激素抑制磷脂酶活性使AAAA不能解离不能解离）u主要来源主要来源:白细胞白细胞/肥大细胞肥大细胞/内皮细胞内皮细胞/血小板血小板u参与介导炎症的每一步参与介导炎症的每一步 AA代谢途径代谢途径Cyclooxygenases produces PGFPGI2,PGD2,PGE2 mediated vasodilation and increased vascular permeabilityFPGE2 also medi
27、ates fever and pain前列腺素前列腺素 Lipoxygenases produces LTFLTB4 attracts and activates neutrophils 趋化中性粒细胞趋化中性粒细胞FLTC4,LTD4,LTE4 mediate vasoconstriction,bronchospasm,and increased permeability 白三烯白三烯 Pharmacologic Inhibitors of PG<FCyclooxygenase inhibitorsNonsteroidal anti-inflammatory drugs(NSAIDs)a
28、spirin,ibuprofenSelective COX2 inhibitors(increase the risk of cardiovascular and cerebrovascular events)FCorticosteroids(reduce the transcription of genes encoding COX-2,phospholipase A2,IL-1,TNF and iNOS)非甾体类抗炎药非甾体类抗炎药 糖皮质激素糖皮质激素 补体类介质补体类介质FPositive vascular effects(C3a and C5a)FLeukocyte chemotax
29、is(C5a)FOpsonization and phagocytosis(C3b)FCell lysis(MAC,membrane attack complex)凝血系统和激肽系统凝血系统和激肽系统 FCoagulation proteins:uncertain Hageman factor is important in DIC FKinin system cleaves HMWK to bradykinin which mediates vasodilation,increased vascular permeability,and pain 血浆中的血浆中的炎症介质炎症介质激肽系统激肽
30、系统补体系统补体系统凝血系统凝血系统纤溶系统纤溶系统急性炎症的病理学类型急性炎症的病理学类型 浆液性炎浆液性炎 Serous 纤维素性炎纤维素性炎 Fibrinous 化脓性炎化脓性炎 Suppurative(purulent)出血性炎出血性炎 hemorrhagic浆液性炎浆液性炎 A skin blister 口唇疱疹口唇疱疹 皮肤水疱皮肤水疱皮肤水疱皮肤水疱Skin blisters 胸腔积液胸腔积液 pleural effusion 纤维素性炎纤维素性炎.绒毛心绒毛心绒毛心绒毛心“Bread and butter”Pericarditis 纤维素性炎纤维素性炎.绒毛心绒毛心 Early
31、 organization of the fibrinous exudate粘连性心包炎粘连性心包炎adhesive pericarditis 限制性心包炎限制性心包炎constrictive Pericarditis 假膜性炎假膜性炎 粘膜发生的纤维素性炎粘膜发生的纤维素性炎A PSEUDOMEMBRANE(假膜假膜)results when the upper portion of a mucosal surface undergoes necrosis,freeing fibrinogen from vessels that then clots along the surface 白喉
32、白喉Diphtheria白喉白喉Diphtheria支气管内纤维素性渗出形成假膜支气管内纤维素性渗出形成假膜 病人，女，病人，女，87岁，肠镜图片岁，肠镜图片（黑色箭头：假膜；白色箭头：肠粘膜红肿）（黑色箭头：假膜；白色箭头：肠粘膜红肿）镜下示镜下示 假膜形成假膜形成 病病 史史 病人（女，病人（女，87岁）因右下肺肺炎岁）因右下肺肺炎在他院治疗，在他院治疗，10天前出院。出院后遵天前出院。出院后遵医嘱每日口服莫西沙星医嘱每日口服莫西沙星moxifloxacin，强力霉素强力霉素doxycycline。出院后渐感虚。出院后渐感虚弱，气短。便秘，间中排数次稀便。弱，气短。便秘，间中排数次稀便。假
33、膜性肠炎假膜性肠炎47 year old patient who recently finished a course of antibiotics,now has watery diarrhea and abdominal pain.Clostridium difficile infection u Recent history of antibiotic useu Sudden leukocytosisu Age and frail condition如何诊断如何诊断?如何治疗如何治疗?急性大叶性肺炎急性大叶性肺炎 正常正常 急性大叶性肺炎急性大叶性肺炎 Pulmonary fibrosi
34、s(complication)化脓性炎化脓性炎 渗出液渗出液 exudates中含大量中性粒细胞，中含大量中性粒细胞，坏死组织和水肿液，称脓液坏死组织和水肿液，称脓液 pus。坏死的中性粒细胞称脓细胞。坏死的中性粒细胞称脓细胞。u表面化脓表面化脓粘膜和浆膜表面粘膜和浆膜表面u积脓积脓积于体腔积于体腔u蜂窝织炎蜂窝织炎弥散弥散 u脓肿脓肿 abscess局限局限化脓性脑膜炎化脓性脑膜炎Purulent meningitis Gyrus Sulus 化脓性脑膜炎化脓性脑膜炎 化脓性脑膜炎化脓性脑膜炎 化脓性阑尾炎化脓性阑尾炎化脓性阑尾炎化脓性阑尾炎 appendicitis正常阑尾正常阑尾化脓性阑
35、尾炎化脓性阑尾炎 阑尾腔阑尾腔阑尾腔中的脓液阑尾腔中的脓液 化脓性阑尾炎化脓性阑尾炎正常阑尾正常阑尾（示肌层）（示肌层）化脓性阑尾炎化脓性阑尾炎讨讨 论论 When treated promptly,most patients with purulent appendicitis recover without difficulty.If treatment is delayed,the appendix can burst,causing peritoneal infection and even death.要点：要点：蜂窝织炎蜂窝织炎 阑尾壁结构特点阑尾壁结构特点Why?咽喉蜂窝织炎咽喉
36、蜂窝织炎咽喉蜂窝织炎咽喉蜂窝织炎脓脓 肿肿 Abscess组织内局限性化脓性炎症组织内局限性化脓性炎症u化脓菌化脓菌seedingu坏死灶继发感染坏死灶继发感染 形态形态:中心坏死形成脓液（脓腔）中心坏死形成脓液（脓腔）周边肉芽组织包裹（脓肿膜）周边肉芽组织包裹（脓肿膜）疤痕修复疤痕修复小叶性肺炎小叶性肺炎/支气管肺炎支气管肺炎肺炎伴脓肿形成肺炎伴脓肿形成肾脓肿肾脓肿肝脓肿肝脓肿疖疖疖、痈疖、痈痈痈Tooth abscess臀部深部脓肿伴肛周瘘管形成臀部深部脓肿伴肛周瘘管形成 Cavity due to pulmonary abscessacute pyelonephritis急性炎症的结局急
37、性炎症的结局offending agentstissue destruction repairclearedpersistentstopcontinue SARS SARS suviving patientDifusse interstitial pulmonary fibrosis慢性炎症慢性炎症F持续时间长持续时间长(weeks to years)F可由急性炎症发展而来，也可隐可由急性炎症发展而来，也可隐匿起病，病人没有急性表现匿起病，病人没有急性表现 F炎症，组织损伤和修复同时进行炎症，组织损伤和修复同时进行inflammation,tissue injury and attempts
38、at repair coexist慢性炎症病因慢性炎症病因F持续感染持续感染(most common)FAutoimmune and allergic reactionsF Prolonged exposure to potentially toxic agents(silicosis,Atherosclerosis)FAlzheimer disease,metabolic syndrome,type 2 diabetes,and certain cancers mycobacteria parasitesfungivirus慢性炎症的病变特点慢性炎症的病变特点F单个核细胞浸润单个核细胞浸润
39、Infiltration with M,lymphocytes,and plasma cellsF组织损伤组织损伤 Tissue destruction by offending agents or inflammatory cellsF瘢痕修复瘢痕修复 Attempts at healing angiogenesis and fibrosisChronicinflammationinthelungA wound at the ankle of a Japanese man who has a history of canine bite 25 years ago.足分支菌病足分支菌病足分支菌
40、病足分支菌病Mycetoma(madura foot)严重病例严重病例 慢性胆囊炎慢性胆囊炎Normal gall bladder炎性息肉炎性息肉inflammatory polyps炎性息肉炎性息肉/炎性假瘤炎性假瘤 pseudotumorColon polypColorectal PolypsRectal polypCervical polypNasal polypBladder polypIntestinal polypUterine polypEndometrial polyp 肉芽肿性炎肉芽肿性炎以以肉芽肿肉芽肿形成为特征的炎症形成为特征的炎症 Limited conditions
41、to cause it:u certain infections(Tuberculosis)u immune-mediated(Crohn disease)u inert foreign bodies u unknown etiology(sarcoidosis)巨噬细胞及其衍生细胞聚集形成结节状病灶巨噬细胞及其衍生细胞聚集形成结节状病灶granulomasGranuloma is a cellular attempt to contain something hard to eradicate.肉芽肿的类型肉芽肿的类型1.异物性异物性lTalclSuturelfiber2.免疫性免疫性lpe
42、rsistent microbelself antigen 坏死型和无坏死型坏死型和无坏死型1.Caseatingl结核病结核病TuberculosislFungal infection2.Noncaseatingl异物反应异物反应lSarcoidosislBeryllium exposerlCrohn diseaselCat scratch disease肺结核肺结核肺结核肺结核Tuberclosis结核性肉芽肿：结核性肉芽肿：中央干酪样坏死中央干酪样坏死Caseating area 类上皮细胞类上皮细胞Epithelioid cells 朗汉斯巨细胞朗汉斯巨细胞Langhansgiantc
43、ells 淋巴细胞淋巴细胞Lymphocytes 成纤维细胞成纤维细胞Fibroblasts类上皮细胞类上皮细胞类上皮细胞、类上皮细胞、Langhans巨细胞巨细胞异物巨细胞异物巨细胞梅毒树胶肿梅毒树胶肿Effectively“walls off”the offending agent(not always eradicates)Tissue distructionSerious tissue fibrosis 肉芽肿的意义肉芽肿的意义梅毒树胶肿梅毒树胶肿梅毒树胶肿梅毒树胶肿炎症的全身反应炎症的全身反应 the acute-phase reaction u发热发热Fever(pyrogens)u外周血白细胞计算数增加外周血白细胞计算数增加 Leukocytosis u Elevated plasma levels of acute-phase proteins C-reactive protein(CRP),fibrinogen,and serum amyloid A(SAA)protein erythrocyte sedimentation rate(ESR)Mediated by TNF,IL-1,and IL-6
