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1、Pathology&PathophysiologyIntroductiontoChapter1.Pathology&Pathophysiology病因学：病因学：疾病发生的原因疾病发生的原因发病学：发病学：病因作用下疾病发生发展过程病因作用下疾病发生发展过程病理变化：病理变化：疾病过程中机体的功能、代谢和形态学变化疾病过程中机体的功能、代谢和形态学变化临床病理联系：临床病理联系： 病理变化引起的临床表现以及转归和结局等病理变化引起的临床表现以及转归和结局等 ThefouraspectsofadiseaseprocessthatformthecoreofpathologyEtiology：cau
2、sesofthediseasePathogenesis：themechanismsofitsdevelopmentPathologicalchange：thestructuralalterationinducedinthecellsandorgansofthebody.Clinicalpathologicalcorrelation：theclinicaleffectsofthepathologicalchanges.WhatispathologyInitsbroadestsense,itisthestudyofhowtheorgansandtissuesofahealthybodychange
3、tothoseofsickperson.Itunderpinseveryaspectofmedicine,fromdiagnostictestingandmonitoringofchronicdiseasestocutting-edgegeneticresearchandbloodtransfusiontechnologies.Pathologyisintegraltothediagnosisofeverycancer.“MedicineISPathology”Pathologyisabranchofmedicalsciencewhichstudiesthenature,causes,deve
4、lopments,processes,consequencesandeffectsofthediseases.WhatispathophysiologyPathophysiologyisthestudyoffunctionalchangesinthebodythat occur in response todiseaseorinjury.Therearetwoseparatemedicalfieldsinvolvedinpathophysiology.Thefirstisphysiology,thestudyofthebodyanditsfunctions.Thesecondispatholo
5、gy,thestudyofdiseaseanditsimpactonthebody.Whencombined,studentslookathowtheprogressofadiseasechangesthebody,andhowthechangescanbetreatedorreversed.病理学和病理生理学是研究疾病的病因、发病机制、形态结构、功能和代谢、基因及其表观调控等改变，揭示疾病的发生发展规律，从而阐明疾病本质的医学科学。Whatispathology&pathophysilogyMedicine Medicine developmendevelopmengenomic & epi
6、genomic General therapyMedicine Medicine developmendevelopmenstructural and functionalPatho & Patho & pathophypathophyPersonal therapyPatho & Patho & pathophypathophybridgingbridgingPatho-&PathophysiologyBasicMedicineClinicMedicineBridge病理知识和病理诊断是临床疾病诊断治疗的根本与依据病理知识和病理诊断是临床疾病诊断治疗的根本与依据 病理生理学是治疗疾病及预测疾
7、病转归的理论基础病理生理学是治疗疾病及预测疾病转归的理论基础BothBoth serves serves as as a a bridgebridgebridgebridge or or link link link link between between the the preclinical preclinical sciencessciences ( (anatomy, anatomy, anatomy, anatomy, physiology, physiology, physiology, physiology, etcetcetcetc.) and the courses in
8、clinical medicine.) and the courses in clinical medicine.EveryDiseaseHasAPathologicBasisPneumoniaPneumoniaNormallungAbridging disciplineinvolvingbothbasicscienceandclinicalpractice.Devotedtothestudyofthestructural and functional changes in cells, tissues and organs that underlie disease.Toexplainthe
9、whys and wherefores of the signs and symptomsofthepatients.Providingasoundfoundation for rational clinical care and therapy.(1)Pathologyisabridgingbetweenbasicscienceandclinicalmedicine(2)Pathologyisalsoapracticalclinicmedicine(DiagnosticPathologyorSurgicalPathology)(3)Pathophysiologyasabridgenotbet
10、weenthebasicscienceanddiseasesbutvariousbasicsciences.(4)Pathophysiologyenablingthestudents,cliniciansandotherpractitionerstounderstandwhyandhowdiseasesdevelopandvariousclinicalmanifestationsappear,andwhatarethefundamentalmechanisms.Position(1)HumanpathologyTheprincipalaimofhumanpathologyconsidersst
11、ructuralabnormalitiesofcellsandtissuesgrosslyandmicroscopicallyexaminedfrompatientstissues(2)ExperimentalpathologyExperimentalpathologyresearchescellularprocessesincorporateanimalexperimentandtissueandcellculturesClassificationClassification1.Humanpathology(1)Autopsy(means“seeforyourself”)Autopsyisa
12、specialoperation,performedbyspeciallytrainedphysician,onadeadbody尸体解剖尸体解剖(autopsy) (autopsy) 对死者的遗体进行病理剖验对死者的遗体进行病理剖验Thefunctionsofautopsy ClarifythecausesofdeathDiagnosisandtreatmentqualitycontrolRecognizingofnegligenceRecognitionofnewdiseasesandnewdiseasespatternsSourceofinformationProvidematerial
13、foreducationandscientificresearchRecognitionoftreatmenteffectiveness 意义：确定死因；提高医疗质量；发现特殊疾病；收集、积累各种疾病的病理资料等 Biopsyistheremovalofasampleoftissuefromthebodyforexaminationandthetissuewillbeexaminedunderamicroscopetoassistindiagnosis(2)Biopsy 活活组组织织检检查查(biopsy) (biopsy) 对对活活体体组组织织采采用用局局部部切切除除、钳钳取取、针针吸吸、搔
14、刮等方法，进行取材检查搔刮等方法，进行取材检查 意意义义：在在活活体体情情况况下下对对患患者者作作出出诊诊断断；术术中中诊诊断断，协协助助选选择择术术式式和和手手术术范范围围；随随诊诊观观察察病病情情，判判断断疗疗效效；组组织织化化学学和和细细胞胞化化学等方法进一步诊断学等方法进一步诊断(3)CytologyCytologyisresponsibleforpreparation,stainingandmicroscopicexamination.(smear,fineneedleaspiration)2.Experimentalpathology (1)Animalexperiment:Ani
15、malexperimentisapathologicalmethodusinganimalmodeltostudydiseaseswithinthebody. (2)TissueandcellcultureTissueandcellcultureisthatthetissueorcellsamplefromahumanoranimalisobtainedandmaintainedinvitroforexperimental,diagnosticortherapeuticpurposes(1)GrossappearanceThemorphologicalfeatureofalesion(such
16、assize,shape,weight,color,consistency,surfaceedge,section)isobservedbyeyesorassistedbyusingaruler,steelyard,magnifyingglass,orothertools.BasicexaminationmethodsBasicexaminationmethods(2)Histologicandcytologicobservation(2)HistologicandcytologicobservationThespecimensfrompatientsarepreparedasasection
17、orsmear,thenstainedandexaminedbyusingmicroscopy超微结构观察超微结构观察 Ultrastructural observation:用透射和用透射和扫描电镜对细胞内部或表面亚细胞水平超微结构进行观察扫描电镜对细胞内部或表面亚细胞水平超微结构进行观察形态计量和图像分析技术形态计量和图像分析技术 Morphometry and image analysis technology :对组织和细胞的形态因素和对组织和细胞的形态因素和 显色反应结果进行定量研究显色反应结果进行定量研究分子生物学技术分子生物学技术 Molecular biology techno
18、logyMolecular biology technology 包括包括PCRPCR、原位杂交、实现对、原位杂交、实现对DNADNA、RNARNA、蛋白质等大分子进行、蛋白质等大分子进行定性、定位和定量检查定性、定位和定量检查cytologic observationHistologic observationmost common: basic formalin fixed HE (hematoxylin and eosin) stained（3 3）HistochemistryandcytochemistryHistochemistryandcytochemistryHistochemi
19、stryandcytochemistryisalsocalledspecialstainmethod.Sometissuestructuresandsubstances(protein,enzyme,nucleicacid,glycogen,lipid)arecoloredwhenachemicalgroup(carboxyl,phosphoric,oraldehyde)reactswiththestainPAS (glycogen) BMSudan fatImmunohistochemistryImmunohistochemistry Ag-AbspecificreactionLocatio
20、nanalysis(cytokeratincellmembrane)Clinicaldiagnosisanddistinguishing(diagnosisoftumorhistogenesis)Western blot(4)immunoreaction(5)Electronmicroscope (6)Laserscanningconfocalmicroscope(LSCM)alivingcellobservationinsituordevelopmentorquantitative(7)Molecularbiologytechnique(7)Molecularbiologytechnique
21、 Polymerasechainreaction(PCR) DNAsequencing Biochiptechnique Genechip(DNAchip) Proteinchip(proteinmicroarray) Tissuechip(tissuemicroarray)Text of PathologyText of Pathology(1)Generalpathology:concernedwiththebasicreactionofcellsandtissuestoabnormalstimulithatunderliealldiseases.(2)Systemicpathology:
22、describethespecificresponsesofspecializedorgansandtissuestodefinedstimuli.BranchesofpathologyGeneralpathologycellinjurytissuerepairhemodynamicdisordersinflammationtumorSystemicpathologythebloodvesselsandthehearttherespiratorysystemthedigestivesystemtheurinarysystemthemaleandfemalegenitalsystemthener
23、voussystemtheendocrinesystemBranchesofPathologylGeneralPathologylSystemicPathologylGrossPathologylCellularPathologylSurgicalPathologylClinicalPathologylImmunopathologyChapter 2:Chapter 2: Conspectus of Conspectus of DiseaseDisease 1.Concepts of health and disease 2.Etiology 3.Pathogenesis Section 1:
24、Section 1: health and diseaseHealth: The definition of health from WHO, health indicates not only without any evidence of disease, but also a state of complete well-being physically, mentally and socially. Sub-healthSub-health/chronic fatigue syndrome (CFS): a situation, in which the person does not
25、 show specific symptoms and signs of disease, but lives a low-quality of life both physically and mentally.Criteria of Sub-health ConditionYouhavechronicfatiguecomplexasresultsofovertaxingphysicalandmentalworkorlongtermstress,suchasinsomnia,forgetfulness,somnolence,profusedreaming,dizziness,distenti
26、oninthehead,mentalfatigue,cumbersomelimbs,shoulderandbacksoreness,lackofconcentration,pronenesstofluandcold,etc.;Youhaveapoorappetite,dizzyheadandvision,depressionandfright,vexation,agitation,irascibility,tidalfever,vacuitysweating,congestion,shortofbreath,generalbodyweakness,irregularmenses,poorsex
27、ualperformancewhicharetheresultsofendocrinedisorders,menopausalcomplexandaging;andYouexperiencevacuitysweating,congestion,shortofbreath,palpitation,dizzyheadandvision,andgenerallackofstrength,whichoccurafteraseriousillnessorchronicdiseases.Afullevaluationofhealthconditionsisnecessaryfortheeffectivei
28、mplementationofpublichealthinterventions.However,termstoaddresstheintermediatestatebetweenhealthanddiseasearelacking,leadingthepublictooverlookthisstateandthusincreasingtherisksofdevelopingdisease.2013Disease: Disease: An abnormal life process which is induced by disorders of homeostasis under the a
29、ction of certain causes and conditions. A pathologic process with disturbances of function, metabolism, and structure in the body, which are manifested by a characteristic set of signs and symptoms.Section 2: EtiologyEtiology studies the contributing factors that cause diseases including causative,
30、predisposing, and precipitating factors.(1) Etiological factors / Causes of diseases (2)Conditions for / Precipitating factors of disease(3) Predisposing factors of diseasestable anginaClinical complain: chest painPredisposing factor :Concentric coronary stenosisCauseagitationPrecipitating factor(1)
31、Etiologicalfactors/CausesofdiseasesAetiologicalfactorcausesadiseaseanddeterminesitscharacteristics.ClassificationofetiologicalfactorsBiologicalfactorsPhysicalfactorsChemicalfactorsNutritionalfactorsImmunologicalfactorsHereditaryfactorsCongenitalfactorsSocialandpsychologicalfactorsBiological factorsB
32、iological agents: microorganisms (such as bacteria, virus, fungi, etc.), parasites, and their toxins and metabolic products.Physical factorsPhysical agents include mechanical injuries, extremes of temperature, electricity and radiation. Chemical factorsChemical agents: can damage cells by varies pat
33、hways. For instance, corrosive chemicals, such as strong acids and alkalis, can destroy cells at the site of contact. Other chemicals are selective in their sites of action, such as binding of carbon monoxide to hemoglobin.Nutritional imbalanceNutritional imbalanceEither Either excessesexcesses or o
34、r deficienciesdeficiencies of nutrients of nutrients predispose cells to injury. predispose cells to injury. For example, high lipids and carbohydrates For example, high lipids and carbohydrates diet predispose a person to obese disease, diet predispose a person to obese disease, atherosclerosis and
35、 diabetes. atherosclerosis and diabetes. The most common nutritional deficiency is the The most common nutritional deficiency is the lack in certain constituents, such as lack in certain constituents, such as vitamins, calcium, and trace elements.vitamins, calcium, and trace elements. Immunological
36、factorsAlthough the immune response is a normal protective mechanism, it may cause diseases when the response is inappropriately strong (allergy or hypersensitivity) misdirected (autoimmune disease)deficient (immunodeficiency disease)Genetic factorsGenetic aberrancies may be caused by single or poly
37、genic mutations. they are transmitted by defective genes, such as sickle cell anemia, and colorblindness. Gene mutationChromosomal aberration Congenital factors The disorders result from abnormal embryonic development, and most of them are nongenetic. For example, congenital birth defects, mental or
38、 physical, may be due to a developmental error during pregnancy. The fetus is usually susceptible to not only infectious diseases but also diet and drug-taking of the mother during intrauterine life; harelipanencephalusSocial and psychological factorsSocial and psychological factors Strong or persis
39、tent psychological Strong or persistent psychological stimulation or stress may lead to mental illness stimulation or stress may lead to mental illness and may be related to some diseases, such as and may be related to some diseases, such as hypertension, peptic ulcer, coronary heart disease, hypert
40、ension, peptic ulcer, coronary heart disease, and depression.and depression.(2) (2) Conditions for disease Precipitatingfactor:intensifytheeffectsofcausativefactorsandpromotetheonsetanddevelopmentofdiseases,includingnatural,physical,andsocialconditions.Riskfactor(3)PredisposingfactorsofdiseaseApredi
41、sposingfactorreferstothefactorthatinfluencesthesusceptibilityorresistancetocertaindisease.Itincludesthegeneticconstitution,physiologicalmakeup,aswellasvariouspsychologicalcharacteristics.GeneticpredispositionSummarySpecificcausesandpredisposingfactorstogetherdeterminesthediseaseoccurrence;precipitat
42、ingfactorsinfluencetheonsetanddevelopmentofillness.Somediseasesonlyhaveonecause.However,manydiseasesaremultifactorialinorigin,suchashypertension,atherosclerosisanddiabetes,etcEnvironmentalandgeneticfactors Section Section 3. Pathogenesis3. Pathogenesis The general rules and common mechanisms The gen
43、eral rules and common mechanisms underlying the development of diseases underlying the development of diseases (1) The basic mechanisms of disease(1) The basic mechanisms of disease(1) The basic mechanisms of disease(1) The basic mechanisms of disease (2) General rules of disease development (2) Gen
44、eral rules of disease development (2) General rules of disease development (2) General rules of disease development (3)Outcome of disease (3)Outcome of disease (3)Outcome of disease (3)Outcome of disease (1)ThebasicmechanismsofdiseaseAlthoughvariousspecificmechanismsmayunderliedifferentdisorders,the
45、yallgenerallyinvolvethefollowingfourlevelsofderegulations:neural,humoral,cellularandmolecularmechanisms.NeuralmechanismNeuralsystemplaysacentralroleinregulatingentirelifeactivities;thedisturbanceoccurredinneuralsystemandinperipheryorgansaremutuallyaffected.EncephalitisBviruscandamageneuralsystemdire
46、ctly;somepoisonsmayinterruptthemetabolismofneuralcellsandtheproductionandreleaseofneurotransmitters.Humoralmechanism(humoralfactors,cytokines)Humoralregulationiscrucialinmaintaininginternalhomeostasis.Humoraldysfunctiongenerallyindicatesthealterationsinnumberandinactivitiesofsomehumoralfactors(hormo
47、nes,chemicalmediators,cytokines).Theyfunctionthroughendocrine,paracrine,andautocrinetoregulatethemetabolismandactivitiesofthecells.CellularandmolecularmechanismCellularandmoleculardamagesoralterationsarefundamentalinthedevelopmentofdisease.Strongacidandalkalidestroythecellswithnoselection;hepatitisv
48、irusdamagesspecificallythehepatocytes.整体水平细胞水平分子水平研究疾病时功能代谢结构的变化及其发生机制器官水平Integratedmedicine,Systemsbiology(2)GeneralrulesofdiseasedevelopmentThegeneralrulesforadiseasetotakeplaceanddevelopDisruptionofhomeostasisbypathologicalinsultsBodysresponsestodamagesandanti-damageactivitiesReversalroleofcause-
49、consequenceinthediseaseprocessRelationshipbetweensystemicandlocalalterationsRegulationanddisruptionofhomeostasis Homeostasis:theprocesswherebytheinternalenvironmentofanorganismtendstoremainbalancedandstable,whichisrequiredforoptimumfunctioning.e.g.,maintenanceoftemperaturehomeostasis.Disruptionofhom
50、eostasisbyharmfulagentsmaycausediseases.e.g.,hyperthermiaResponsesofdamagesandanti-damagesDamagesinduceanti-damageresponses,andtheinteractionsgothroughthewholeprocessofdiseasesanddeterminesthedevelopmentofdiseasesOverdoofanti-damagescausenewinjurese.g.Burninginjury(damage)-constrictionofsmallbloodve
51、ssels:maintainingproperbloodpressure(anti-damage).However,sustainedvasoconstriction-hypoxia,cellularnecrosis,anddysfunction.AlternationofcauseandresultindiseaseprocessAcauseofadiseaseleadstoaresult,whichcanbeanewcauseforanotherresultsinthedevelopmentofthedisease,evenformingviciouscycle,e.g.hemorrhag
52、icshock.大失血时的因果交替示意图细胞缺氧微循环障碍休克死亡血管收缩机械力创伤大失血心输出量交感-肾上腺系统兴奋心率心收缩力维持动脉血压恢复viciouscyclevirtuouscycleCorrelationbetweensystemicandlocalregulations Localalterationsandthesystemicstatuescanaffecteachotheranddiseasedevelopment.e.g.,aseverefurunclewillnotonlycauselocalinflammation,butalsoleadtosystemicreac
53、tionsoffeverandelevatedleukocytes.Ontheotherhand,afurunclemaybecausedbydiabetesandcouldonlybecuredbypropercontrolofdiabetes.(3)Outcomeofdisease-completerecovery,incompleterecovery,deathTheoutcomeofadiseaseisdeterminedbythefightbetweentheevilforcesandthedefendingforces,correctdiagnosisandtreatment.Co
54、mpleterecoveryThebestoutcomeofadisease:theetiologicalfactorsdisappearthepathologicallyalteredmetabolism,structureandfunctionareperfectlyrestoredthesymptomsandsignsofthediseasedisappearentirelyhomeostasisisrecoveredIncompleterecoveryThe main symptoms and signs disappear butsome pathological changes a
55、re left behind, namelysequela.Sequela is generally brought about by thecompensatory response to maintain a relativelynormalactivity.For example, the permanent damage to theheartvalveafterrheumaticfever.BraindeathBraindeathisastateofprolongedirreversiblecessationofallbrainactivitywiththecompleteabsen
56、ceofconsciousandvoluntarymovements,responsestostimuli,brainstemreflexes,andspontaneousrespirations.Death Criteriaforbraindeath(WHO)IrreversiblecomacerebralunresponsibilityCessationofspontaneousrespirationAbsenceofcephalicreflexesanddilatedpupilsAbsenceofelectricalactivityofbrainCessationofcerebralci
57、rculationPrecisediagnosisofbraindeathisimportantforhavingproperdonorsinorganictransplantation!Braindeath(脑死亡)Vegetativestate（植物状态）定义自主呼吸意识脑干反射恢复的可能性全脑功能丧失无丧失无无脑的认知功能丧失有有睡眠醒觉周期，但无意识有有 AdaptationandinjuryofcellandtissueCellsoperateinaverynarrowrangeofphysiologicparameterstheymaintainhomeostasisHomeost
58、asisequilibriumofthemicroenvironmentofthecellChemicalelectrolytes,glucose,Chemicalelectrolytes,glucose,pH,etc.pH,etc.Physicaltemperature,etc.Physicaltemperature,etc.正常细胞正常细胞正常细胞正常细胞适应适应适应适应可逆性损伤（变性）可逆性损伤（变性）可逆性损伤（变性）可逆性损伤（变性） 不可逆性损伤不可逆性损伤不可逆性损伤不可逆性损伤（坏死和凋亡）（坏死和凋亡）（坏死和凋亡）（坏死和凋亡）外界持续性刺激（病因）外界持续性刺激（病因）
59、外界持续性刺激（病因）外界持续性刺激（病因）CellreactiontostressandinjuriousstimuliCellreactiontostressandinjuriousstimuliMyocardialcellreactiontostimuliAdaptations are Degrees of Normality Cells Adaptations are Degrees of Normality Cells adapt in many ways: adapt in many ways: increase in number above normal (hyperplasi
60、a)increase in size (hypertrophy)become smaller (atrophy)be replaced by different types of cells (metaplasia)Section 1Section 1： Cellular Cellular adaptationsadaptations Responses to stress that allow cells to modulate their structure and function and thus escape injuryDefinitionDefinition: Adaptatio
61、ns are reversible changes : Adaptations are reversible changes in the number, size, metabolic activity, and in the number, size, metabolic activity, and functions of cellsfunctions of cellsTypesTypes: Two basic types: Two basic typesPhysiologicPhysiologicCellular response to normal stimulationCellul
62、ar response to normal stimulatione.g. - hormonese.g. - hormonesPathologicPathologicModified cellular response to avoid injury Modified cellular response to avoid injury 一、Atrophy 1. Definition:Definition: Acquired loss of size due to reduction of cell size or number of parenchyma cells in an organ.萎
63、缩萎缩：是指发：是指发育正常的器官、育正常的器官、组织由于实质组织由于实质细胞体积的缩细胞体积的缩小或数目减少小或数目减少使其体积缩小使其体积缩小2. 2. Types:Types:lPhysiologic:Physiologic: i. e. Aging; shrinking mammary gland after lactation; the uterus after delivery or in old age. inadequate nutritioninadequate nutrition brain ischemiabrain ischemiabrain atrophybrain
64、atrophypressurepressure hydronephrosishydronephrosis Kidney Kidney atrophyatrophydecreased workloaddecreased workload long-term long-term bed bed muscle muscle atrophyatrophyloss of endocrine stimulationloss of endocrine stimulation Pituitary tumor adrenal adrenal atrophyatrophyloss of innervation)l
65、oss of innervation) poliomyelitispoliomyelitismuscular muscular paralysisparalysisl PathologicPathologicHere is a very small liver you can tell how small it is in comparison to the gall bladder! This is hepatic atrophy.GrossGross The fundamental cellular change is identical in all, representing a re
66、treat by the cell to a smaller size at which survival is still possible. Although atrophic cells may have diminished function, they are not dead. MicroscopicMicroscopicAtrophied cells are smaller with a reduced cytoplasm to nuclear ratio. In atrophied organs where cells have been lost, intercellular
67、 spaces may be replaced by adipose tissue or fibrous tissue.Here is some abdominal musculature from a dog with Cushings disease. Not so many muscle fibers left and most have been replaced with fat. This is skeletal muscle atrophy, common in this diseaseWhat is your observation? 3. Morphologic change
68、3. Morphologic changeAtrophy represents a reduction in the structural components of the cell. The cell contains fewer mitochondria, myofilaments, a lesser amount of endoplasmic reticulum, and increasing in the number of autophagy vacuoles. Muscle atrophy occurs by a change in the normal balance betw
69、een protein synthesis and protein degradation. During atrophy, there is a down-regulation of protein synthesis pathways, and an activation protein degradation.Some of the cell debris within the autophage vacuole may resist digestion and persist as membrane bound residual bodies that may remain as a
70、sarcophagus in the cytoplasm. When present in sufficient amounts, they impart a brown discoloration to the tissue (brown atrophy). Brown atrophy of the heartisatrophyoftheheartmuscle(ormyocardium)commonlyfoundintheelderly.Itisdescribedasbrownbecausefibersbecomepigmentedbyintracellularlipofuscindepos
71、its(mostlyaroundthecellnucleus)atypeoflipochromegranule.Ithasnoknowneffectonfunction,andisdescribedasbeingexpectedornormalinaging.lipofuscinhydrocephalus Compare the normal brain (left) with the abnormal section (right). What is this lesion called?KidneyatrophyBrain atrophyBrain atrophyBrain Brain a
72、trophyatrophykidneyPseudohypertrophyabnormalenlargementofanorganorbodystructurecausedbyanovergrowthoffattyandfibroustissues.Hypoplasiaisunderdevelopmentorincompletedevelopmentofatissueororgan.Althoughthetermisnotalwaysusedprecisely,itproperlyreferstoaninadequateorbelow-normalnumberofcellsAgenesis in
73、medicine,agenesisreferstothefailureofanorgantodevelopduringembryonicgrowthanddevelopmentduetotheabsenceofprimordialtissue.组织、器官的实质细胞萎缩时，常继发其间质组织、器官的实质细胞萎缩时，常继发其间质( (主要是脂肪组织主要是脂肪组织) )增生，有时使组织、器官的体积甚至比正常还大，称为增生，有时使组织、器官的体积甚至比正常还大，称为假性肥大假性肥大( (见于萎缩的胸腺、肌肉等见于萎缩的胸腺、肌肉等) )。器官先天地、部分性和完全性末发育所致的体积小，分别称为器官先天地、
74、部分性和完全性末发育所致的体积小，分别称为发发育不全育不全(hypoplasia)(hypoplasia)和不发育和不发育(agenesis)(agenesis)，并非萎缩。，并非萎缩。1. Definition: IncreaseinthesizeofcellsresultinginincreaseIncreaseinthesizeofcellsresultinginincreaseinthesizeoftheorganinthesizeoftheorgan Nonewcells,justbiggercellsNonewcells,justbiggercells Occursincellst
75、hatcannotdivideOccursincellsthatcannotdivide 二、二、hypertrophyNormalheart HypertrophiedheartHypertrophiedanddilatedheart2. Types:Types: Physiologic:Physiologic:Physiologic:Physiologic: i. e. the physiologic growth of the uterus during pregnancy involves both hypertrophy and hyperplasia. The cellular h
76、ypertrophy is stimulated by estrogenic hormones through smooth muscle estrogen receptors. Pathologic: Pathologic: causes: causes: Increased workload, hormonal stimulation and growth factors stimulation. i.e. hypertrophy of heart the most common stimulus is chronic hemodynamic overload, due either to
77、 hypertension or to faulty valves. Ventricular hypertrophyVentricular hypertrophyIn the case of chronic pressure overload (as through anaerobic exercise, which increases resistance to blood flow by compressing arteries), the chamber radius may not change; however, the wall thickness greatly increase
78、s as new sarcomeres are added in-parallel to existing sarcomeres. This is termed concentric concentric hypertrophy hypertrophy （compensatory hypertrophycompensatory hypertrophy） Normal Hypotrophy microscope:Physiologichypertrophyoftheuterusduringpregnancy.A,grossappearanceofanormaluterus(right)andag
79、raviduterus(left)thatwasremovedforpostpartumbleeding, 三、三、 Hyperplasia (增生）增生） 1.1. Definition:AnincreaseinthenumberofcellsinAnincreaseinthenumberofcellsinanorganortissue,whichmaythenhaveanorganortissue,whichmaythenhaveincreasedvolume.increasedvolume.2.2. Types: Physiologic:Physiologic: ResponseResp
80、onse toto need,need, e.e. g.g. hyperplasiahyperplasiaofof thethe femalefemale breastbreast epitheliumepithelium atat pubertypuberty oror ininpregnancy.pregnancy. Compensatory:Compensatory:Responsetodeficiency,e. g. Hyperplasia following surgicalremoval of part of liver or of onekidney;hyperplasiaoft
81、hebonemarrowinanemia. Excessive stimulation:Excessive stimulation:Pathologic:asinovariantumorproducingestrogenandstimulatingendometrialhyperplasia;pancreaticislethyperplasiaininfantsofadiabeticmother(stimulatedbyhighglucoselevel). Failure of regulation: Pathologic, asinhyperthyroidismorasinhyperpara
82、thyroidismresultingfromrenalfailureorvitaminDdeficiency. Neoplastic:Totallossofnormalcontrol mechanism. Should not betermedhyperplasia.3.Mechanisms:Mostformsofpathologichyperplasiaareinstancesofexcessivehormonalstimulationoraretheeffectsofgrowthfactorsontargetcells.四、四、Metaplasia 化化 生生 Reversiblecha
83、ngeinwhichoneadultcelltypeisreplacedbyanotheradultcelltypeCellssensitivetoacertainstressarereplacedbyanothercelltypecapableofbetterwithstandingthatstressItisagenetic“reprogramming”ofstemcellsandnotchangingofalreadydifferentiatedcellsFunctioncanbereducedIncreasedchanceofmalignanttransformationExample
84、s-Cigarettesmoking-GastricrefluxColumnar-squamous(cervix)Squamous-columnar(Barrettesophagitis)Stomach-intestinalepitheliumConnectivetissue-formationofcartilage,boneoradiposetissue支气管粘膜假复层纤毛柱状上皮化支气管粘膜假复层纤毛柱状上皮化生为复层鳞状上皮生为复层鳞状上皮 正常支气管上皮正常支气管上皮支气管上皮鳞状化生支气管上皮鳞状化生假复层柱状纤毛上皮 Squamous metaplasia in bronchiti
85、s 食道的胃上皮化生食道的胃上皮化生 Squamous-columnar宫颈正常的柱状上皮在慢性炎症刺激下演变为复层鳞状上皮。宫颈正常的柱状上皮在慢性炎症刺激下演变为复层鳞状上皮。（箭头（箭头1 1为正常的柱状上皮，箭头为正常的柱状上皮，箭头2 2为复层鳞状上皮）为复层鳞状上皮） 2MetaplasiaofcolumnartosquamousepitheliumSection 2: Cell injury OccurswhencellsareunabletoadapttostressOccurswhencellsareunabletoadapttostressorwhentheyareexpo
86、sedtodamagingagentsorwhentheyareexposedtodamagingagentsorsufferintrinsicabnormalitiesorsufferintrinsicabnormalities一、CauseslIatrogenic（医源性）-DoctorcauseddiseaseordisordermedicationreactionlFomite-Objectcapableoftransmittingadisease-improperlycleanedinstrumentlStressfactors-Hypoxia-oxygendeficiency-Is
87、chemia-decreasedbloodsupplylInadequateoxygenationofblood-pneumonialReductioninoxygen-carryingcapacityofbloodanemia,COpoisoninglChemicalagents-Altermembranepermeability,osmoticInfectiousagentsl-Viruses,bacteria,fungi,protozoans,etc.lStressfactors-Immunologicreactions-Defendagainstpathologicorganisms-
88、AutoimmunereactionsagainstonesowntissueslAllergicreactionslGeneticdefects-Cancausecellinjurybyinbornerrorsofmetabolism-AccumulationofdamagedDNA二、二、The mechanism of damageThe mechanism of damage三、三、Morphological changeMorphological change（一）DegenerationSomecelldamagecanbereversedoncethestressisremove
89、dorifcompensatorycellularchangesoccur.Fullfunctionmayreturntocellsbutinsomecasesadegreeofinjurywillremain cellularswellingorhydropicdegenerationfattychangeorsteatosishyalinedegenerationmucoiddegenerationamyloidosispathologicpigmentationReversibleReversible Cellular swellingCellular swelling 1.causes
90、 1.causes：infectiousinfectious、toxintoxin、hypoxiahypoxia、feverfever 2.mechanisms 2.mechanisms： （1 1）membrane damagemembrane damage increase permeability increase permeability （2 2）mitochondria damagemitochondria damage APT reductionAPT reduction Na Na+ + pump dysfunctionpump dysfunction cellular swe
91、llingcellular swelling Cellularswellingmayoccurduetocellularhypoxia,whichdamagesthesodium-potassiummembranepump;itisreversiblewhenthecauseiseliminated.Cellularswellingisthefirstmanifestationofalmostallformsofinjurytocells.3.Pathological change3.Pathological change： Gross：When it affects many cells i
92、n an organ, itcausessomepallor,increasedturgor,andincreaseinweightoftheorgan.肾肾体体积积增增大大，切切面面膨膨出出，边边缘缘外外翻翻，色色泽泽混混浊浊 Onmicroscopicexamination,smallclearvacuolesmaybeseenwithinthecytoplasm;theserepresentdistendedandpinched-offsegmentsoftheendoplasmicreticulum.Thispatternofnon-lethalinjuryissometimescal
93、ledhydropicchangeorvacuolardegeneration.气球样变气球样变(ballooning change)(ballooning change)。肾近端小管内部上皮细胞肿胀，胞质内布满红染的颗料状物质，管腔变狭窄 肝细胞高度水肿，胞质疏松透明，呈气球样改变 Theultrastructuralchangesofreversiblecellinjuryinclude:BlebbingBluntingdistortionofmicrovillilooseningofintercellularattachmentsmitochondrialchangesdilationo
94、ftheendoplasmicreticulum肾曲管浊肿肾曲管浊肿肾曲管上皮空泡变4 .Clinical significance：Cellularswellingisthefirstmanifestationofalmostallformsofinjurytocells.Whenitaffectsmanycellsinanorgan,itcausessomepallor,increasedturgor,andincreaseinweightoftheorgan.(1)Mildswelling，reversible(2)Severeswelling,resultinginfattychang
95、eCellhasbeendamagedandisunabletoadequatelymetabolizefat.Smallvacuolesoffataccumulateandbecomedispersedwithincytoplasm.Mildfattychangemayhavenoeffectoncellfunction;howevermoreseverefattychangecanimpaircellularfunction.Intheliver,theenlargementofhepatocytesduetofattychangemaycompressadjacentbilecanali
96、culi,leadingtocholestasis.Dependingonthecauseandseverityofthelipidaccumulation,fattychangeisgenerallyreversible.Fatty changeFatty change（脂肪变性）脂肪变性）Predilectionsite:liver,heart,kidneylDecreasedmitochondrialfattyacidbeta-oxidationlIncreasedendogenousfattyacidsynthesisorenhanceddeliveryoffattyacidstoth
97、eliverlDeficientincorporationorexportoftriglyceridesasverylow-densitylipoprotein(VLDL)2.Mechanism1.Causes:Infection,poisoning,hypoxia,malnutrition3. Pathological change3. Pathological change： Gross：increasedorgansize，turnyellow，greasy肝肝体体积积增增大大，表表面面光光滑滑，呈呈淡淡黄黄色色 Fatty changeMassonstrichrome&Verhoeff
98、stain.Theliverhasaprominent(centrilobular)macrovesicularsteatosis(white/clearround/ovalspaces)andmildfibrosis(green).Thehepatocytesstainred. liver fatty changeLiver fatty change fatty degeneration of liverfatty degeneration of liverMycardial fatty infiltrationmyocardialfattychange虎斑心虎斑心 tigroidheart
99、.由于机体慢性酒精中毒或缺氧等原因，导致心肌细胞发生脂肪变性，肌纤维弹性降低，心室扩展，肥大，呈局灶性或弥漫性黄褐色，切面浑浊，结构不清。在左心室内膜下和乳头肌周围，在红褐色（心肌纤维）的背景上出现灰黄色（心肌脂肪变性）条纹或斑块，状似虎斑，故称虎斑心。 4 . Clinical significance . Clinical significance：（1 1）Mild fatty changeMild fatty change：reversiblereversible；（2 2）Severe changeSevere change： Jaundiceandliverdysfunctionc
100、irrhosis decreasedcardiaccontractilityHFHyaline changeAn alteration within cells or in the extra-cellular space-homogenous,glassy,pinkappearanceIntracellular accumulations of proteins,Russellbodies,MallorybodyExtrcellular hyalineoldscar,extravasatedplasmaprotein,depositionofbasementmembranemateriala
101、myloidtypestypesCellular Cellular hyaline change changeFibrillar connective tissueFine arterial wallPersistent spasm Intima permeability increased Plasma protein exudation and coagulation basement membrane-like material 1.1.Finearterialwall:hypertension肾肾小小动动脉脉管管壁壁增增厚厚，管管腔腔狭狭窄窄 2.2.Fibrillarconnecti
102、vetissue： Morecommon in scar tissue, fibrous plaques ofatherosclerosis。Russellbodiesarepinkeosinophilicaccumulationswithinplasmacells.Todate,twohypotheseshaveattemptedtoelucidatethebiologicaleventsbehindtheformationofthesebodies.Onetheorysustainsthatsuchbodiesconstitutecytoplasmicaccumulationofimmun
103、oglobulinderivativescontainedintheperinuclearcisternofthesmoothendoplasmicreticulumbecauseofanincreasedsynthesisoralteredsecretion.Ontheotherhand,sinceitsinitialdescriptioninthemedicalliterature,severalauthorshaveattributedtheformationofsuchbodiestothepresenceofmicroorganismssuchasinthecaseofRussell
104、bodygastritisanditsassociationtoHelicobacterpyloriinfection.3.Cellular3.Cellularhyalinechangechange MalloryMalloryMalloryMallory bodybodybodybody Russell body Russell body Mallory bodyMallory body Mucoid degenerationMucoid degeneration Mucoid degeneration (MD) is a rare pathologicalaffectionoftheant
105、eriorcruciateligament(前交叉韧带，ACL).MucinousmaterialwithinthesubstanceofACLproducespainandlimitedmotionintheknee.BrHeartJ.1969May;31(3):343-51.Ballooning deformity (mucoid degeneration) of atrioventricular valves.Amyloidosisisararediseasethatresultsfromaccumulationofinappropriatelyfoldedproteins.Thesem
106、isfoldedproteinsarecalledamyloids.Whenproteinsthatarenormallysolubleinwaterfoldtobecomeamyloids,theybecomeinsolubleanddepositinorgansortissues,disruptingnormalfunctionAmyloidosisThepresentationofamyloidosisisbroadanddependsonthesiteofamyloidaccumulation.Thekidneyandheartarethemostcommonorgansinvolve
107、d.Skinfeaturesofamyloidosiscutisdyschromica.Hyperpigmentedandhypopigmentedmaculeson(A)lowerlegs,(B)backandwaist,(C)waist.(D)IndividualblistersonupperarmAmyloidosisDiagnosisofamyloidosisrequirestissuebiopsycalcificationamyloidosisPigmentsExogenous Carbonorcoale.g.anthracosisTatooingEndogenousLipofusi
108、n(lipidperoxidation)MelaninHemosiderinBilirubinHemosiderinimageofakidneyviewedunderamicroscope.Thebrownareasrepresenthemosiderinpathologic pigmentationpathologic pigmentationHemosiderinmaydepositindiseasesassociatedwithironoverload.Thesediseasesaretypicallydiseasesinwhichchronicbloodlossrequiresfreq
109、uentbloodtransfusions,suchassicklecellanemia.Hemosiderinismostcommonlyfoundinmacrophagesandisespeciallyabundantinsituationsfollowinghemorrhage,suggestingthatitsformationmayberelatedtophagocytosisofredbloodcellsandhemoglobin.Hemosiderincanaccumulateindifferentorgansinvariousdiseases.含铁血黄素含铁血黄素heart f
110、ailure cellsheart failure cells：左心衰竭肺淤血时，有些：左心衰竭肺淤血时，有些巨噬细胞巨噬细胞吞噬了吞噬了红细胞红细胞并将其并将其分解，胞浆内形成含铁血黄素，此时这种细胞称为心力衰竭细胞。如急性肺淤分解，胞浆内形成含铁血黄素，此时这种细胞称为心力衰竭细胞。如急性肺淤血时，肺泡腔中可见肺泡巨噬细胞吞噬红细胞形成的心衰细胞。但并不是所有血时，肺泡腔中可见肺泡巨噬细胞吞噬红细胞形成的心衰细胞。但并不是所有肺淤血都能见心衰细胞，只有左心衰引起的肺淤血才能见到。肺淤血都能见心衰细胞，只有左心衰引起的肺淤血才能见到。 lipofuscin:melanin:Pathologi
111、c calcificationDystrophiccalcificationMetastaticcalcificationDystrophic calcificationInareasofnecrosisasfinewhitegranulesorclumps.Intracellularorextracellular,orinboth.Heterotopic bonemaybeformed.Psammoma bodies.冠状动脉钙化主动脉粥样硬化，钙化淋巴结钙化、骨化，愈合之TBMetastatic calcificationHyercalcemiamay be in normal tissu
112、eIncreasedsecretionofparathyroidhormoneDestructionofbonetissueVitaminD-relateddisordersRenalfailure肺转移性钙化肺转移性钙化Irreversible cell injuryNecrosis EnzymaticdigestionofthecellsDenaturationofproteinsApoptosisMechanismsofirreversibleinjuryMitochondrialdysfunctionLossofmembranephospholipidsCytoskeletalabno
113、rmalitiesReactiveoxygenspeciesLipidbreakdownproductsLossofintracellularaminoacidsMorphology of necrosisIncreasedeosinophiliaMoreglassyhomogeneousappearanceVacuolatedcytoplasmaCalcificationNuclear changesPyknosis,karyo-rrhexis,karyolysistotallydisappearPyknosis,karyo-rrhexis,karyolysisPatterns of nec
114、rosisCoagulative necrosisLiquefactive necrosisGangrenous necrosisdrygangrenewetgangrenegasgangreneSpecial necrosisCaseousnecrosisFatnecrosisFibrinoidnecrosisCoagulative necrosisPreservation of the basic outlineofdiedtissueforsomedaysGrosslyfirm textureAcidophilic,coagulatedCharacteristicofhypoxic de
115、athofcellsinalltissueexcept the brainNormalmyocardiumMyocardiumwithcoagulationnecrosisIncreasedeosinophiliaMoreglassyhomogeneousappearancehepatitiswithscatteredfociofcoagulativenecrosis脾，凝固性坏死Patterns of necrosisCoagulative necrosisLiquefactive necrosisGangrenous necrosisdrygangrenewetgangrenegasgan
116、greneSpecial necrosisCaseousnecrosisFatnecrosisFibrinoidnecrosisLiquefactive necrosisOftenwithbacterialoroccasionallyfungalinfectionOftenwiththeaccumulationofinflammatory cells Completely digests the dead cellsTransformationoftissueintoaliquid viscous mass Liquefaction necrosis of a focus in the myo
117、cardium脑软化脑软化脑软化肝膿肿肝脓肿肝脓肿肺脓肿肠阿米巴，液化性坏死Patterns of necrosisCoagulative necrosisLiquefactive necrosisGangrenous necrosisdrygangrenewetgangrenegasgangreneSpecial necrosisCaseousnecrosisFatnecrosisFibrinoidnecrosisGangrenous necrosisNecrosis+superimposedbacterial infectionUsuallyappliedtoalimbDry gangre
118、ne:necrosiswithminimalputrefactivechange-mummificationWet gangrene:deadtissuesuperimposedputrefactivebacteria-black and foul-smellingGas gangrene:infectedwithsaccharolyticclostridia（梭状芽胞杆菌）andcontaminatedwithputrefactiveclostridia-swelling with gas三种坏疽的特点三种坏疽的特点三种坏疽的特点三种坏疽的特点干性坏疽干性坏疽动脉阻塞、静动脉阻塞、静脉回流脉
119、回流受阻受阻四肢、与外界四肢、与外界相通的地方相通的地方湿润肿胀，暗湿润肿胀，暗绿色、界限不绿色、界限不清清发展快，全身发展快，全身中毒症状明显，中毒症状明显，预后差预后差动脉受阻、静脉动脉受阻、静脉回流正常回流正常好发于四肢末端好发于四肢末端黑褐色、干燥皱黑褐色、干燥皱缩，与正常组织缩，与正常组织界限清楚界限清楚无明显全身症状，无明显全身症状，预后较好预后较好坏死伴产气腐败坏死伴产气腐败菌感染菌感染深部肌肉创伤，深部肌肉创伤，伤口较小伤口较小湿润肿胀湿润肿胀呈蜂窝呈蜂窝状，有捻发音状，有捻发音发展迅速、全身发展迅速、全身症状明显，中毒症状明显，中毒性休克。性休克。气性坏疽气性坏疽湿性坏疽湿性
120、坏疽Patterns of necrosisCoagulative necrosisLiquefactive necrosisGangrenous necrosisdrygangrenewetgangrenegasgangreneSpecial necrosisCaseousnecrosisFatnecrosisFibrinoidnecrosisCaseous necrosisAdistinctiveformofcoagulativenecrosisMostofteninfocioftuberculous infectionWhite and cheesyingrossappearanceTh
121、etissuearchitectureiscompletelyobliteratedAmorphous granular debrisenclosedwithinagranulomatousreactionTB，干酪样坏死TB，干酪样坏死TB，干酪样坏死TB，干酪样坏死Fat necrosisFat destructionasaresultofreleaseofactivatedpancreaticlipasesOftenseeninacute pancreatitisReleasedfattyacidcombinewithcalciumChalky white areas(fatsaponi
122、fication皂化)Fociofshadowy outlinesofnecroticfatcellsAcutepancreatitis:fatnecrosisandinflammatorycellsindamagedpancreaticparenchyma脂肪坏死脂肪坏死Fibrinoid necrosisThecombinationofcell deathanddepositionoffibrin-like materialfibrinimmunoglobinsotherplasmaproteins纤维素样坏死Apoptosis1972,“falling off”Aformofcellde
123、athAwaytoeliminate unwanted host cellsthroughactivationofacoordinated,internallyprogrammedseriesofeventsApoptosis in physiologic situationsTheprogrammeddestructionofcellsduringembryogenesisHormone-dependent involutionintheadultCelldeletioninproliferatingcellpopulationsDeath of neutrophilesduringanac
124、uteinflammatoryresponseDeathoflymphocytesattheendofanimmuneresponseCelldeathinducedbycytotoxicTcellsEliminationofpotentialharmfulself-reactivelymphocytesApoptosis in pathologic conditionsDNA damage (if insult is mild)Accumulation of misfolded proteins (ER stress)Pathologic atrophyinparenchymalorgans
125、afterductobstructionCellinjuryincertaininfections(e.g.Viralhepatitis,AIDS) Dysregulated apoptosisDisorders associated with inhibited apoptosis and increased cell survivalCancersAutoimmunedisordersDisorders associated with increased apoptosis and excessive cell deathNeurodegenerativediseaseIschemicin
126、juryVirus-inducedlymphocytedepletionMechanism of apoptosisSignalingpathwaysControlandintegrationAcommon-executionphaseRemovalofdeadcellsbyphagocytosisSpecific examples of apoptosisFas-Fas ligand-mediatedapoptosisTNF-inducedapoptosisCytotoxic T-lymphocyte-stimulatedapoptosisApoptosisaftergrowth facto
127、r deprivationDNA damage-mediatedapoptosisMorphology of apoptosisSinglecellsorsmallclustersofcellsRoundorovalmassofeosinophiliccytoplasmwithdensenuclearchromatinfragmentsNoinflammationCell shrinkageChromatin condensation nucleus fragmentsFormation of cytoplasmic blebs and apoptotic bodiesPhagocytosis
128、 of apoptotic cells or bodiesBiochemicalfeaturesofapoptosisProtein cleavageproteinhydrolysiscaspasecleavesthenuclearscaffoldandcytoskeletalproteins,triggerendonucleasesProtein cross-linkingintocovalentlylikedshrunkenshellsapoptoticbodiesDNA breakdowninto50-300kbpieces,theninto180-200bpbyCa2andMg2dependentendonucleasesPhagocytic recognition
