5炎症与组织细胞损伤的修复医学PPT课件.ppt

HEALTH&DISEASEPEACE&WAR炎症与损伤的修复炎症与损伤的修复InflammationandRepairBy Dr.S.J.YANGDepartment of Patholgy,4th Military Medical University学习内容学习内容1.炎症的概念(Conception of Inflammation)2.病因(Etiologic Agents)3.局部表现和全身反应(Local and Systemic Manifestations Signs&Symptoms)4.炎症的基本病理变化(Morphologic Patterns of Inflammation)5.急性性炎症类型及特点、发病机制(Acute Inflammation and Pathogenesis)6.损伤的修复(Repair)7.慢性炎症及其类型和特点(Chronic Inflammation)8.炎症的结局(Prognosis of Inflammation)AulusCorneliusCelsusJohnHunterRudolfVirchowElieMetchnikoffPaulEhrlichThomas,LewisHISTORICAL HIGHLIGHTS:Big Robbins lists,or might have listed.Cornelius Celsus(ancient Rome)described rubor(redness),calor(heat-this applies only to the skin),dolor(pain),and tumor(which then simply meant swelling)as the cardinal signs of inflammation.John Hunter(the great early surgeon,*1793,*parodied by William Blake as Jack Tearguts)first characterized inflammation as a nonspecific body response.Rudolf Virchow added functio laesa(loss of function)as the fifth cardinal sign of inflammation,and his student,Julius Cohnheim,provided the basic studies of the pathologic microanatomy of inflammation.Elie Metchnikoff(*1892)was the first to observe and study phagocytosis.(*This is the same Metchnikoff who popularized yogurt as a health and longevity food.He died at age 70.)Paul Ehrlich developed the idea of humoral immunity early in this century.(This is the same Ehrlich who developed the magic bullet for syphilis,and most of the stains we still use.)Thomas Lewis demonstrated that inflammation is brought about by chemical mediators,most of which act locally.Someone may still ask you about the triple response of Lewis to a superficial scratch:(1)an immediate red scratch mark;(2)a red flare around the scratch mark;(3)a red swollen area(wheal)around the flare.(Try it!)Dr.Lewis found that he could eliminate the flare,but not the others,by cutting the autonomic nerve supply(i.e.,preventing the axon reflex).This experiment led to the discovery of histamine,which mediates events 1 and 3.Inflammation Definition各种致炎因子引起机体的组织损伤所诱发的以防御为主的局部组织反应。(第一版）具有血管系统的活体组织对损伤因子所发生的防御反应。（第四版）Inflammation and repair-Defensive reaction.Defensive?Defective?Definition by Big Robbins“Inflammation is the reaction of living tissues to all form of injury.It involves vascular,neurologic,humoral and cellular response at the site of injury”（Basic Pathology）Etiologic Agents of Inflammation“All the factors that can injury the tissues and cells can also cause inflammation of the body.They include the physical,chemical biological,and Immunological agents et al.”炎症的致病原因炎症的致病原因Local and systemic manifestationsAcute InflammationCardinal Signs(Celsus,1 AD)Redness(rubor)Swelling(tumor)Heat(calor)Pain(dolor)Loss of function(functio laesa)(the fifth cardinal sign supposedly added by Virchow)Acute InflammationCardinal Signs-Redness Acute InflammationCardinal Signs-Swelling Acute InflammationCardinal Signs-Pain InflammationSystemic Manifestations of InflammationFever-clinical hallmark of inflammationEndogenous pyrogens:IL-1 and TNF-aLeukocytosis-may be neutrophils,eosinophils,or lymphocytesLeukopenia-rareAcute Phase Reactants-non-specific elevation of many serum proteins-will markedly increase the“sed rate”LeukocytosisLines of DefenseInflammationSystemic Manifestations of InflammationShock most common in gram-negative septicemia(bacteria in the bloodstream),although it can occur with gram-positive bacteremiaLipopolysaccharide(endotoxin)of gram-negatives can produce symptoms of shock when injected into animalsTNF-a can produce a similar syndrome 三、炎症的基本病理变化三、炎症的基本病理变化基本病变基本病变变质：变质：Alteration渗出：渗出：Exudation增生：增生：Proliferation变质和渗出出现于早期，而增生出现于晚期变质和渗出出现于早期，而增生出现于晚期变质（变质（Alteration）1、概念：、概念：炎症局部组织发生的炎症局部组织发生的变性和坏死变性和坏死2、原因：、原因：致病因子直接作用致病因子直接作用 局部血液循环障碍局部血液循环障碍 免疫介导免疫介导 炎症反应产物的间接作用炎症反应产物的间接作用3、变质的细胞的类型和形态变化、变质的细胞的类型和形态变化实质细胞实质细胞变性：细胞水肿、脂肪变性变性：细胞水肿、脂肪变性坏死：凝固性和液化性坏死坏死：凝固性和液化性坏死间质细胞间质细胞变性：黏液变性、玻璃样变性变性：黏液变性、玻璃样变性坏死：纤维素样坏死坏死：纤维素样坏死渗出渗出(Exudation)1、概念：、概念：炎症局部组织血管内的液体成分、蛋白质炎症局部组织血管内的液体成分、蛋白质和各种白细胞通过血管壁进入和各种白细胞通过血管壁进入 组织、体腔、组织、体腔、体表和粘膜表面的过程，称为体表和粘膜表面的过程，称为渗出渗出渗出是炎症最重要特征性变化渗出是炎症最重要特征性变化增生增生(Proliferation)1、实质细胞增生：、实质细胞增生：肝炎时，肝细胞的再生肝炎时，肝细胞的再生 慢性胆囊炎时粘膜上皮和腺体增生慢性胆囊炎时粘膜上皮和腺体增生2、间质细胞增生：、间质细胞增生：包括巨噬细胞、血管内包括巨噬细胞、血管内 皮细胞和成纤维细胞皮细胞和成纤维细胞炎症的类型炎症的类型 Classification of inflammation临床类型临床类型急性炎症：病程短，几天急性炎症：病程短，几天1月，以变质渗出为主月，以变质渗出为主慢性炎症：病程长，慢性炎症：病程长，数月数年，以增生为主数月数年，以增生为主OUTCOMES OF INFLAMMATIONInciting StimulusAcuteInflammation Chronic-active InflammationChronicInflammationResolutionAbscessResolution with scarring*The longer the stimulus persists,the greater the scarring will be.A dynamic continuum of changeSpreadingBacteremiaToxemiaSepticemiaPyemiaStory of miceAcute Inflammation1.PathogenesisofAcuteInflammation2.TypeofAcuteInflammation急性炎症急性炎症 PHASES OF INFLAMMATIONInitiationAmplificationTermination 急性炎症的类型急性炎症的类型病理分类病理分类浆液性炎浆液性炎纤维素性炎纤维素性炎化脓性炎化脓性炎出血性炎出血性炎 InflammationPhases of Acute InflammationInitiation(开始或启动开始或启动)血管反应为中心血管反应为中心Stimulation(injury)with changes in microvasculatureStructural changes leading to extravasationEmigration of WBCs to the site of injuryAmplification(扩大或进展扩大或进展)*-炎症介质和炎细炎症介质和炎细胞的作用胞的作用Both soluble mediators and cellular inflammatory systems are activated and amplifiedTermination(终止终止)*-再生、修复和愈合再生、修复和愈合-accomplished by specific inhibition or dissipation of the mediators 急性炎症的早期反应急性炎症的早期反应Phases of Acute Inflammation-InitiationInitial vasoconstriction(seconds to minutes),followed by a longer period of vasodilationLeakage of fluid and plasma from the intravascular compartment(increased permeability)Stasis,with transmigration of leukocytes and erythrocytes into extravascular tissueThe Triple Response-Sir Thomas Lewis(1927)Normal regulation of fluid transport Extravascular fluid (little protein or pressure)HydrostaticHydrostaticpressurepressureOncoticOncoticpressurepressureEDEMA-TRANSUDATE (protein content low-specific gravity 1.012)HydrostaticHydrostaticpressurepressureOncoticOncoticpressurepressureNon-Inflammatory Edema Increased Hydrostatic PressureEDEMA-TRANSUDATE (protein content low:specific gravity 1.020)HydrostaticHydrostaticpressurepressureOncoticOncoticpressurepressureInflammatory Edema Increased Vascular PermeabilityDiapedesis血球渗出 Acute InflammationPathogenesis of EdemaNon-inflammatory edema,e.g.:Pulmonary edema due to heart failure(increased hydrostatic pressure)Nephrotic syndrome(decreased oncotic pressure)Inflammatory edema,either:Direct,irreversible injury-all vessels(burns)Transient increase in vascular permeability,i.e.,the effect of mediators on post-capillary venules浆液性炎浆液性炎SerousexudationSerousinflammationSerousexudationSerousinflammation浆液性炎浆液性炎Fibrinousexudation白喉白喉纤维素性炎纤维素性炎Fibrinousexudattion白喉白喉Fibrinousexudattion绒毛心绒毛心Pseudomembranousenterocolitis假膜性炎假膜性炎Pseudomembranousenterocolitis假膜性炎假膜性炎HemorrhagicInflammationHemorrhagic Fever with Renal Syndrome出血性炎出血性炎炎症灶的血管损伤严重，渗出物中含有大量红炎症灶的血管损伤严重，渗出物中含有大量红炎症灶的血管损伤严重，渗出物中含有大量红炎症灶的血管损伤严重，渗出物中含有大量红细胞。细胞。细胞。细胞。不是独立的类型，常与其他类型合并存在，如不是独立的类型，常与其他类型合并存在，如不是独立的类型，常与其他类型合并存在，如不是独立的类型，常与其他类型合并存在，如纤维素性出血性炎纤维素性出血性炎纤维素性出血性炎纤维素性出血性炎常见于流行性出血热、钩端螺旋体和鼠疫等急常见于流行性出血热、钩端螺旋体和鼠疫等急常见于流行性出血热、钩端螺旋体和鼠疫等急常见于流行性出血热、钩端螺旋体和鼠疫等急性传染病。性传染病。性传染病。性传染病。急性炎症扩展急性炎症扩展PhasesofInflammation-AmplificationPMNs and macrophages are recruited to the site of injury from peripheral blood by chemokines,principally IL-8,plus c5a,TGF-b,and Platelet-derived Growth FactorIL-1 and TNF cause the release of post-mitotic reserve granulocytes from the marrow,plus induce the production of Colony Stimulating Factors(CSF)ExudationofbloodcellsInflammationNeutrophilInflammationNeutrophilGranulesPrimary-contain serine proteases,lysozyme and phospholipase A2Secondary-similar to primary,but also contain lactoferrin and collagenaseTertiary-present at the leading edge of migrating PMNs,contain gelatinases that are capable of degrading basement membraneInflammationEosinophil InflammationMONONUCLEARPHAGOCYTES InflammationLymphocyteInflammationPlasmacell白细胞游出白细胞游出Leukocyte ExtravasationMargination,rolling,and adhesionTransmigration(diapedesis)Migration toward the site of injury along a chemokine gradientSequential involvement of adhesion moleculesCentralAxialStreamRolling Adhesion TransmigrationSELECTINS(E&P)INTEGRINS&Ig-LIKE MOLECULES(ICAM,VCAM)QualitativeandQuantitativeEndothelialandPMNChangesInflammation Adhesion Molecule ModulationP-selectin is redistributed to the cell surface from the Weibel-Palade bodies due to stimulation by thrombin,histamine,and Platelet Activating Factor(PAF)Induction of E-selectin on endothelium by IL-1 and TNFIncreased avidity of binding of integrins(conformational change)InflammationMargination and PavementingInflammationTransmigration趋化作用趋化作用 ChemotaxisExogenous mediators,e.g.:N-formyl methionine terminal amino acids from bacteria Lipids from destroyed or damaged membranes(including LPS)Endogenous mediators,e.g.:Complement proteins(C5a)Chemokines,particularly IL-8Products of lipoxygenase(LTB4)炎细胞的作用炎细胞的作用 Inflammatory Cell FunctionPhagocytosis opsonized by IgG(subtypes 1 or 3)or C3bLocal immune response by monocytes and lumphocytes as well as cytokinesTissue injury by inflammatory cells though the proteinase and inflammatory mediators吞噬作用、免疫作用、引起组织损伤吞噬作用、免疫作用、引起组织损伤 InflammationMononuclear PhagocytesNeutrophil ingestion of bacteria,gram stain炎症介质炎症介质Chemical Mediators of InflammationVasoactive aminesComplement systemKinin systemCoagulation pathwayFibrinolytic pathwayArachodonic acid metabolitesPlatelet activating factorCytokinesNitric oxide-以中性粒细胞渗出为主，并伴有不同程度的组织坏死和脓以中性粒细胞渗出为主，并伴有不同程度的组织坏死和脓以中性粒细胞渗出为主，并伴有不同程度的组织坏死和脓以中性粒细胞渗出为主，并伴有不同程度的组织坏死和脓液形成。液形成。液形成。液形成。脓液脓液脓液脓液：为脓性渗出物，外观呈浑浊的凝乳状液体，灰黄色：为脓性渗出物，外观呈浑浊的凝乳状液体，灰黄色：为脓性渗出物，外观呈浑浊的凝乳状液体，灰黄色：为脓性渗出物，外观呈浑浊的凝乳状液体，灰黄色或灰白色，稀薄或粘稠或灰白色，稀薄或粘稠或灰白色，稀薄或粘稠或灰白色，稀薄或粘稠脓液的成分脓液的成分脓液的成分脓液的成分：脓细胞、细菌、坏死组织、浆液：脓细胞、细菌、坏死组织、浆液：脓细胞、细菌、坏死组织、浆液：脓细胞、细菌、坏死组织、浆液脓细胞脓细胞脓细胞脓细胞：为变性坏死的中性粒细胞。：为变性坏死的中性粒细胞。：为变性坏死的中性粒细胞。：为变性坏死的中性粒细胞。化脓性炎化脓性炎中性白细胞渗出中性白细胞渗出 Purulent inflammation-Exudation of Neutrophil(1 1 1 1).).).).表面化脓和积脓表面化脓和积脓表面化脓和积脓表面化脓和积脓表面化脓表面化脓表面化脓表面化脓-指发生于粘膜或浆膜的化脓性炎指发生于粘膜或浆膜的化脓性炎指发生于粘膜或浆膜的化脓性炎指发生于粘膜或浆膜的化脓性炎,黏膜的化脓性炎黏膜的化脓性炎黏膜的化脓性炎黏膜的化脓性炎又呈脓性卡他性炎如化脓性尿道炎，中性白细胞向黏又呈脓性卡他性炎如化脓性尿道炎，中性白细胞向黏又呈脓性卡他性炎如化脓性尿道炎，中性白细胞向黏又呈脓性卡他性炎如化脓性尿道炎，中性白细胞向黏 膜表面渗出，膜表面渗出，膜表面渗出，膜表面渗出，深部组织不明显深部组织不明显深部组织不明显深部组织不明显.积脓积脓积脓积脓 -当化脓性炎发生于粘膜或浆膜时，脓液积聚于浆膜腔、胆当化脓性炎发生于粘膜或浆膜时，脓液积聚于浆膜腔、胆当化脓性炎发生于粘膜或浆膜时，脓液积聚于浆膜腔、胆当化脓性炎发生于粘膜或浆膜时，脓液积聚于浆膜腔、胆囊和输卵管腔内囊和输卵管腔内囊和输卵管腔内囊和输卵管腔内.(2).(2).(2).(2).脓肿脓肿脓肿脓肿(3).(3).(3).(3).蜂窝织炎（蜂窝织炎（蜂窝织炎（蜂窝织炎（phegmonousphegmonous inflammation inflammation）疏松结缔组织的弥漫性化脓性炎，常发生于皮肤、肌疏松结缔组织的弥漫性化脓性炎，常发生于皮肤、肌疏松结缔组织的弥漫性化脓性炎，常发生于皮肤、肌疏松结缔组织的弥漫性化脓性炎，常发生于皮肤、肌 肉和阑尾。肉和阑尾。肉和阑尾。肉和阑尾。溶血性链球菌溶血性链球菌溶血性链球菌溶血性链球菌透明质酸酶透明质酸酶透明质酸酶透明质酸酶降解结降解结降解结降解结缔组织基质中的透明质酸缔组织基质中的透明质酸缔组织基质中的透明质酸缔组织基质中的透明质酸链激酶链激酶链激酶链激酶溶解纤维素溶解纤维素溶解纤维素溶解纤维素Acute meningitis-Purulent exudate 表面化脓表面化脓Acute salpingitis-Purulent exudate 积脓积脓Acute salpingitis -Purulent exudate Abscesss脓肿脓肿InflammationTissue Injury by Inflammatory Cells脓肿脓肿InflammationAcute Inflammatory cell infiltration弥漫性化脓弥漫性化脓Activated oxygen speciesCan migrate through intact plasma membranesInitiate lipid peroxidationReact with DNAOxidize sulfhydryl groups of proteinsDegrade extracellular matrix components炎症引起组织损伤炎症引起组织损伤Tissue Injury by Inflammatory Cells炎症引起组织损伤炎症引起组织损伤Tissue Injury by Inflammatory CellsLysosomal enzymesSince these enzymes are used to degrade microorganisms in lysosomes,obviously they could damage tissue in the extracellular environmentUsually protease activity is controlled by a variety of anti-proteases present in plasma(a1-anti-trypsin,a2-macroglobulin,etc.)炎症引起组织损伤炎症引起组织损伤Tissue Injury by Inflammatory CellsPhagocytic cell adherenceAdherence to basement membranes,other components of the extracellular matrix and other cells by phagocytes enhances the damage caused by reactive oxygen species and lysozyme,because normal inhibitors present in plasma cannot gain access to that space by virtue of the phagocytic cell adherence炎症引起组织损伤炎症引起组织损伤Tissue Injury by Inflammatory CellsThe relatively primitive and non-specific immune effects of polymorphonuclear leukocytes and macrophages upon invading microorganisms are also capable of damaging the host by the extracellular release of enzymes and activated oxygen speciesInflammationTissue Injury by Inflammatory CellsInflammation Typhoidal ulcersInflammationTissue Injury by Inflammatory Cells损伤的修复损伤的修复Tissue Repair损伤的修复与愈合损伤的修复与愈合Regeneration,Repair and Healing修修复复（repair）：损损伤伤造造成成机机体体部部分分细细胞胞和和组组织织丧丧失失后后，机机体体对对所所形形成成缺缺损损进进行行修修补恢复的过程，称为修复。补恢复的过程，称为修复。方式方式再生性修复再生性修复再生性修复再生性修复,由周围同种细胞增生修复由周围同种细胞增生修复由周围同种细胞增生修复由周围同种细胞增生修复纤维性修复纤维性修复纤维性修复纤维性修复,由肉芽组织填补由肉芽组织填补由肉芽组织填补由肉芽组织填补再再生生（Regeneration）：是是指指由由同同种种细细胞胞分分裂裂增增生生来来补补充充机体老化、消耗或坏死的细胞的过程。可分为：机体老化、消耗或坏死的细胞的过程。可分为：生生理理性性再再生生：也也称称为为完完全全性性再再生生。是是指指生生理理过过程程中中老老化化、消消耗耗的的细细胞胞由由同同种种细细胞胞分分裂裂增增生生补补充充，如如表表皮皮角角化化层层经经常脱落，由表皮基底细胞增生、分化，予以补充。常脱落，由表皮基底细胞增生、分化，予以补充。病病理理性性再再生生：也也称称不不完完全全再再生生。是是指指病病理理状状态态下下，组组织织细细胞损伤后发生的再生，一般由纤维组织增生代替。胞损伤后发生的再生，一般由纤维组织增生代替。再生修复再生修复Repair by RegenerationDefinition-RegenerationRegeneration is a type of repair.The best example of healing by regeneration in humans occurs in the liver,which has incredible regenerative properties.It is possible to resect virtually an entire lobe of liver,and the organ will repair itself over a period of months to completely recapitulate its previous structure.（1）不稳定细胞（不稳定细胞（Labilecells）再生能力最强，如全身的上皮细胞、淋巴造血细胞等。再生能力最强，如全身的上皮细胞、淋巴造血细胞等。（2）稳定细胞（稳定细胞（Stablecells）损伤后，有较强再生能力。如肝、胰、内分泌腺等腺上损伤后，有较强再生能力。如肝、胰、内分泌腺等腺上皮，成纤维细胞、血管内皮细胞、骨细胞和原始间叶细皮，成纤维细胞、血管内皮细胞、骨细胞和原始间叶细胞等，平滑肌细胞也属稳定细胞，但再生能力弱。胞等，平滑肌细胞也属稳定细胞，但再生能力弱。（3）永久性细胞（）永久性细胞（Permanentcells）几乎没有再生能力，受损伤后由结缔组织增生修补，如几乎没有再生能力，受损伤后由结缔组织增生修补，如神经细胞、心肌细胞及骨骼肌等。神经细胞、心肌细胞及骨骼肌等。细胞的再生能力细胞的再生能力Classification of cells by their proliferative potentialCell classificationLabile cells:This sub-population of cells is constantly turned over.The best examples are found in the epithelial cell population of the skin or gut,and the hematopoetic cells of the bone marrow.These cells have a short,finite life span,die via apoptosis,and are rapidly replaced.Cell classificationStable cells:Stable cells are a sub-population of cells that are normally replaced very slowly,but are capable of rapid renewal after tissue loss.Hepatocytes and the proximal convoluted tubule cells of the kidney are good examples.Cell classificationPermanent cells:Permanent cells are found in the central nervous system and heart.Once they are destroyed,they cannot regenerate.Peripheral nerve cells are capable of limited regeneration has been demonstrated,but,for all practical purposes,those of the CNS are permanent cells.损伤的修复损伤的修复 Wound Healing-ChickenpoxREGENERATION再生 ATN,regenerative(polyuric)phase.Hyperplasia增生Chronic ulcerative colitis with crypt abscessesSquamous Metaplasia 化生 Uterine CervixDysplasia,cervix 不典型增生损伤的纤维性修复损伤的纤维性修复Repair by connective tissue Wound HealingRepair Granulation tissue is the initial response to an injury,and consists of richly vascular connective tissue which contains capillaries,young fibroblasts,and a variable infil