病理学教学课件：绪论

PathologyIntroduction

绪论DefinitionofPathologyClassicdefinitionofpathologyStudyofsufferring(path)

Modern(definitionof)pathologyBothascienceandaclinicalpractice

PathologyStudiesEtiology(病因学)Pathogenesis(发病机制)Pathologicalchanges(diagnosis)

(病理改变)Consequence(prognosisandtherapeuticguidance)

(结局)病理学----研究疾病的发生原因,发病机制,

及组织细胞的病理改变肝炎病毒癌基因突变肝癌肝癌大体和镜下细胞改变CategoryofPathologyClinicalPathologySurgicalpathology(biopsyandorganresection)AutopsycytologyMolecularpathologyBasicPathologyLaboratoryexperimentAnimalexperimentResourcesResourcesKumar,Cotran&RobinsBasicPathology7thedition8theditionContentsofPathologyGeneralPathology

StudyofMechanismsofDiseaseSystemic(specialorgansystem)Pathology

StudyofDiseasesbyOrganSystemBriefhistory3stages:

一.Organpathology(器官病理学）

Morgagni(1688~1771)700cases《thesitesandcausesofdisease》(1761)

Rokitansky(1800~1878)30thousandscasesofautopsiesperformed二.

Cellularpathology(细胞病理学)

19世纪30年代microscopy--cell

Virchow(1821~1902)《cellularpathology》(1859)Virchow’soffice--BerlinMedicine-HistoryMuseum三.Ultrastructuralandmolecularpathology

(超微结构和分子病理学)

30thage－electronmicroscope(电镜)50thage－ultrathinsection(超薄切片)70thage－molecularbiology(分子生物学)PathologydevelopmentofChina20世纪初中国开办医学院第一代病理学家北京协和医学院1915年胡正祥广州中山大学医学院1926年梁伯强国立上海医学院1927年谷镜汧

1922德国海岱山大学,柏林大学

1925北京协和

1927上海医学院

1929中华医学会第七次大会胡正祥心的先天性畸形一例报告谷镜汧中国人动脉之病理的研究

1951主编<病理学总论><实用病理学提纲>

1954年12月中华医学会病理学会成立

RoleinMedicine

(QueenofMedicine

orasdoctors’doctor)BridgebetweenbasicbiomedicalresearchandclinicalsciencesProvidediagnosisofthediseasesServeasoneofthegoldencriteriaformedicalservicequalitiesProvidemostdefinitiveevidenceofthediseaseprocessHowtostudywell?PutahighvalueofpathologicalpracticeMakeconnectionsbetweengeneralandsystemicpathologyLinkpathologicchangeswithclinicalmanifestationsAlwaysthinkpatientfirst急性肝炎—肝细胞水样变性----肝肿大ExamandGradingPolicies50%

Writtentestincludingmultiplechoices,pathologyterminologydefinitionandexplanation,questions,etc.30%

Experimentaloraltest

10%

Performanceinlaboratorycourse10%

Mid-termexamEnglish(orgeneralperformanceinpathologycourse)ChapterI.

Celladaptation,InjuryandDeath

(细胞适应、损伤和死亡）Adverseagents:

Intrisical:metabolicproductsischemiaEnviromental:Physical(radiation,violetlight,etc.)Chemical(CO,CCl4,etc.)Biologic(bacteria,virus,etc.)Affectingfactors:

Nature,severityanddurationofthestressCharactersofthecell

(vulnerability,differentiation,bloodsupply,andnutritionalstatus)Hypoxia(缺O2)Normalcardiomyocyte(正常心肌细胞）Adaptation（适应）Reversibleinjury

（可复性损伤）Irreversibleinjury

（不可复性损伤）Celladaptation

（细胞适应）Definition机体组织、细胞对内、外环境的变化所发生的形态结构和功能代谢的改变Classification

Physiologic:erythocytosisinhealthypeoplelivedinplateau

Pathologic:Atrophy—decreaseincellsizeHypertrophy—increaseincellsizeHyperplasia—increaseincellnumberMetaplasia—changeincelltypeA.Atrophy（萎缩）

Definition

发育正常的器官、组织或细胞体积的缩小

Shrinkageinthesizeofthecellbythelossofcellsubstance

Classifications&causes

Physiologic:AtrophicthymusinadultAtrophicuterusinoldwoman

Pathologic:

Inadequatenutrition(营养不良)Lossofinnervation(丧失神经营养)Decreasedworkload(废用性)

Pressurefromsurroundingtissue,fluid,masses(压迫性)Lossofendocrinestimulation(内分泌减少)Aging(老年性)

Biochemicalmechanism

Affectedbalancebetweensynthesisanddegradation

Degradationpredominance

Morphologicchanges

Gross:Smallerandbrown(brownatrophy)

LM:Smallercells(细胞变小）

Increasedlipofuscin(脂褐素增多)

EM:Decreasedorganelles(细胞器减少)Increasedautophagicvacuoles(自噬泡增多)ConsequenceReversiblechange(可复性改变)Diminishedfunction(功能降低)

－Atrophicbrain-Alzheimerdisease(老年性痴呆症)

－Atrophicpancreaticislet-diabetesmellitus(糖尿病)B.Hypertrophy（肥大）

Definition实质细胞体积增大引起器官体积变大

Anincreaseinthesizeofcellsandconsequentlyanincreaseinthesizeoftheorgan

Nonewcells（非新生细胞）

Nocellularswelling（非细胞肿胀）Classification

Physiologic:uterusduringpregnancy(妊娠子宫)

Pathologic:

－Compensatoryoradaptive:hypertensiveheart

－Substitutive:enlargedkidneyMorphologicalchanges

Gross:EnlargedorganLeftventricularhypertrophy

LM:biggercellLargeranddarkerstainofnucleiEnlargedmyocardialfiber

EM:IncreasedorganellesIncreasedmyofilamentConsequenceAadaptivechangeAlimitedcompensationC.Hyperplasia(增生）

Definition器官或组织中细胞数量增加

AnincreaseinthenumberofcellsinanorganortissueClassificationPhysiologic:

—Hormonal:

glandularepitheliumofthefemalebreastduringpregnancy

—Compensatory:

remaininglivercellafterresectingaportionofliverPathologic:

—Hormonal（激素依赖性）

—Woundhealing（创伤愈合）

—Skinwart（皮肤疣）Morphologicalchange

—Increasednumberofcell—Increasedmitosisofnuclei乳腺小叶增生前列腺结节性增生ConsequenceAdaptivechange:proliferationofconnectivetissuecellinwoundhealingAdverseeffect:cancerousproliferation(endometricalcancer,cervicalcancer,etc)D.metaplasia(化生）Definition一种分化成熟的细胞类型（上皮或间质细胞)被另外一种成熟的细胞所代替

Oneadultcelltype(epithelialormesenchymal)isreplacedbyanotheradultcelltype

化生通常见于具有极强再生能力的组织，如上皮组织和结缔组织。

通常是由上述组织中具有潜在分化和增殖能力的细胞如基底细胞、储备细胞、原始间充质细胞等增生转化所致。Classification

Epithelial(上皮化生）

Squamous:

(e.g.squamousmetaplasiaofrespiratoryepithelium)

鳞状细胞化生

Glandular:

(erstinalmetaplasiaofgastricmucosa)

肠上皮化生

Mesenchymal(间叶细胞）

Metaplasiainconnectivetissue

（骨化生、软骨化生、脂肪化生、粘液化生）ConsequenceAdaptivechange:proliferationofconnectivetissuecellinwoundhealingAdverseeffect:cancerousproliferation(endometricalcancer,cervicalcancer,etc)Cellulardegeneration

(细胞变性）

Reversibleinjury

（可复性损伤）A.CellularSwelling（细胞肿胀）

Mild,reversible,commonlesioninparenchymalcells(e.g.liver,kidney,heart,brain)

Granularorvacuolarandhydropicdegeneration

轻者：颗粒变性，重者：空泡变性或水样变性Pathologicchanges

Gross:

Pallor,increasedturgor,andincreasedweight

LM:

Cytoplasmicvisiblegranule-granulardegenerationCytoplasmicclearvacuole-vacuolarorhydropic,degeneration肾小管上皮肿胀肝细胞肿胀

EM:

－Blebbing,bluntingordistortionofmicrovilliandlooseningofintercellularattachment

－Mitochondrialswellingwithformationofamorphousdensities

－DilationofEndoplasmicReticulumwithdetachmentofribosomesanddissociationofpolysome

－DisaggregationofgranularandfibrillarelementsofnucleiMechanism

DepletionofATP

Na+-K+ATPaseinjuriedMembranepermeability↑B.Fattydegeneration(脂肪变性）又名：fattychange(steatosis)Definition

Anyabnormalaccumulationoftriglycerideswithinparenchymalcell

ReversiblesevereinjuryMostofteninliver,alsoinheart,kidney,skeletalmuscleVariouscauses(toxin,proteinmalnutrition,diabetesmellitus,obesity,anoxia,especiallyalcoholabuse)

Pathologicchanges

Fattychangeoftheliver

Gross:EnlargementandprogressivelyyellowcolorIncreasedweight,andbecometuftandgreasy

苏丹III呈橘红色LM:

Cytoplasmicfatvacuole,roundandclearinroutingtissuesectionOrangeredintissuesectionwithsudanIVoroilredO

胞质内圆形空泡，大小不等，核可偏位苏丹III呈橘红色，锇酸呈黑色部位可分:小叶中央型——淤血、四氯化碳中毒

小叶周边型——酒精、感染、磷中毒

全小叶型——严重感染、中毒

Fattychangeoftheheart

Gross:Tigeredheart

虎斑心(e.g.anemia)Uniformlyaffectedmyocytes(e.g.diphthelia)

FattychangeofthekidneyGross:LipidstreakinrenalcortexEM:roundvacuolewithlowerelectrondensity

Mechanism

Fattyacidaccumulation—Increasedmobilizationoffattyacid(e.g.starvation)—Inhibitedoxidationoffattyacid(e.g.anoxia)—Decreasedthesynthesisoflipoproteins(teinmalnutrition)

FreeofstructuredlipidIII.Celldeath

(细胞死亡）

又名：Irreversibleinjury（不可复性损伤）

Twopatterns:Necrosis（坏死）

Apoptosis(凋亡）A.Necrosis（坏死）Definition

Localdeathofthecellorthetissueinalivingorganism

有生命机体（活体）局部组织或细胞的死亡Biologicalprocesses

Self-digestionorenzymaticdigestionAutolysis（自溶）

Heterolysis（异溶）

DenaturationoftheproteinsMorphologicchanges

Nuclearchanges（核改变）

Pyknosis（核固缩）,karyorrhexis(核碎裂）Kalyolysis（核溶解）

Cytoplasmicchanges（胞质改变）

Granulardegenerationorfattychange

（颗粒变或脂肪变）

Eosinophilicstainincreased（嗜酸性增强）

Interstitialchanges（间质改变）

Collagendegradation&stromadeaggreation

（胶原降解&基质解聚）

Inflammatoryreaction（炎症反应）

Necroticpatterns（坏死类型）

a.Coagulativenecrosis（凝固性坏死）

PredominantdenaturationofproteinStructurednecrosisCommoninheart,kidney,liver,spleen,etc.b.Liquefactivenecrosis（液化性坏死）

Predominantself-digestionLiquefactivelesionCommoninbrain,spinalcord,orabscessetc.c.Specificpatternofnecrosis（特殊类型坏死）

Caseousnecrosis(干酪样坏死）

－MostofteninT.B.infection

－Dryandyellowcheesyfocigrossly

－Structureless,amorphousgranulardebris

Fatnecrosis（脂肪坏死）

－

Typicallyoccuringafterpancreaticinjury

－Chalkywhiteareasgrossly

－Necroticfatcellswithbasophiliccalciumdeposit

－Inflamatoryinfiltration

Fibrinoidnecrosis

（纤维蛋白样坏死）

－

Mostlyoccurringinhypersensitivityreaction

－Smudgyeosinophilicandhomogeneousmasses(Fibrin,Ig,andplasmaproteins)Gangrene（坏疽）

又名：gangrenousnecrosis（坏疽性坏死）－Attachedbybacterialinfectionininfarctedorgansortissues(ofteninopenedorgans)组织坏死后，再合并腐败菌感染，使组织变黑的一种坏死－Presentedwithdarkorblackcolorinnecroticareas(Fe2++H2SFeS)

－Dividedinto3categories(dry,wetandgas)

类型及特点：

干性湿性气性原因A阻塞A、V均阻塞深部组织创伤+厌氧菌感染形态干燥黑褐色分界清湿润污黑色分界不清湿润污黑或污绿色肢体肿胀、捻发音

后果局部肢体切除局部肢体切除伴全身中毒症状Consequence

Resolutionandabsorption（溶解吸收）Detachmentanddischarge（分离排出）－Ulcer

（溃疡）－Cavity（空洞）－

Encapsulation（包裹化）

Organization（机化）Calcification（钙化）B.Apoptosis（凋亡）又名：Programmedcelldeath（程序性细胞死亡）Definition

DeterminedbyintrinsicgeneApathwayofcell“suicide”Mainlybephysiologic

由机体局部组织内在遗传或基因决定的、自身破坏机制所引起的细胞死亡。

刺激因素---信号传导---特异调节分子---胱冬肽酶家族---细胞死亡

---凋亡小体---被噬清除·病变：

生物化学改变：胱冬肽酶参与，裂解支架和激活内核苷酶活化转谷氨酰胺酶——蛋白质交联，形成凋亡小体

DNA被内核苷酶裂解成碎片和寡核苷酸特异性电泳带细胞或小体表面分别有磷脂酰丝氨酸或血小板反应蛋白表达——为吞噬细胞所识别Morphologicchanges

Roundorovalmasseswithintenselyeosinophiliccytoplasminsinglecellorclustersofcell

CondensednuclearchromatinwithkaryorrhexisandformationofapoptoticbodiesApoptoticcell,theirfragmentscouldbephagocytosedordegradedNoinflammationEM：核膜下核染色质积聚、团块状或碎片状

Tab2.ComparisonbetweenapoptosisandcoagulationnecrosisCoagulationNecrosisApoptosisStimuliHistologicappearanceDNAbreakdownMechanismTissuereactionHypoxia,toxinsCellularswellingCoagulationnecrosisDisruptionoforganellesRandom,diffuseATPdepletionMembraneinjuryFreeradicaldamageInflammationPhysiologicandpathologicfactorsSinglecellsChromatincondensationApoptoticbodiesInternucleosomalGeneactivationEndonucleasesProteasesNoinflammationPhagocytosisofapoptoticbodiesIV.Hyalinedegeneration

（玻璃样变性，简称玻变）

又名：Hyalinosis（透明变性或玻璃样变性）Conception

细胞内、间质内或血管壁呈现一种均匀一致、嗜酸性物，状如毛玻璃样形态的病变

Amorphologicalterm

PresentingeosinophilicandhomogenousdepositsinHEstainedsection

Occurringincell,interstitiumandvascularwallCategory

Intracellularhyalinedegeneration

（细胞内玻璃样变）

－Virusorviralgranule

Negribody–hydrophobia（狂犬病）

CMVinclusion–CMVinfection（巨细胞病毒感染）

－

Proteinsabsorbedorsynthesized

Absorbedprotein

－Nephritis（肾炎）

－

Russselbody

－Igsynthesizedinplasmacell（浆细胞合成Ig）－Accumulatedcytokeratinintermediatedfilments

Mallorybody–alcoholichepatitis（酒精性肝炎）－Apoptosisorcoagulativenecrosis

Councilmanbody–viralhepatitis（病毒性肝炎）

Hyalinedegenerationofcardiomyocyte–diphtheria（白喉）

Hyalinosisofvascularwall（血管壁玻变）

Hyalinosisofconnectivetissue（结缔组织玻变）

－Scar（疤痕）－Atheroma（粥样斑块）－Scleroticglomerulus（硬化性肾小球）Consequence

Dependingontheircauses,mechanismandbiochemicalconstituentV.Amyloidosis（淀粉样变）

Conception

Proteinaceousmaterial(amyloid)depositedintissueinterstitiumorvascularwall

PresentingbrowncolorafterreactingtoiodineChemicalnature

Amyloidlightchain(AL)protein（免疫球蛋白轻链）

－producedbyplasmacell

－associatedwithsomeformofmonoclonalB-cellproliferation

Amyloidassociated(AA)protein（淀粉样相关蛋白）

－Aproteinof8.5kDmolecularmass（76aminoacidresidue)

－Derivedfrom12kDSAA(serumamyloid-associated)synthesizedintheliver

－DepositedinthesettingofchronicinflammatorystatesMorphologicchanges

Amorphous,eosinophilic,hyalineextracellularsubstancewithHEstainPink-reddepositswithCongo-redstainYellow-greenbirefringencebypolarizingmicroscopeAmyloidfibril(7~10nm)onEMexaminationConsequencePressureatrophyofdepositedorgans(kidney,heart,etc.)VI.Pathologiccalcification

（病理性钙化）Conception

Abnormaldepositionofcalciumsalts,togetherwithsmallamountsofiron,magnesiumandothermineralsClassification

A.Dystrophiccalcification（营养不良性钙化）

Depositionofcalciumsaltsindeadordyingtissues(necroticfoci,thrombus,atheroma,tumor,etc.)AbsenceofcalciummetabolicderangementFormationofcrystallinecalciumphosphatedduetolocallyincreasedCa2+,PO42-locally

沉积于病变组织，如坏死灶、血栓、粥样斑块、肿瘤、虫卵等

ATP酶有机磷酸脂PO2-4+Ca2+=Ca（PO4）2pH↓B.Metastaticcalcification（转移性钙化）

Depositionofcalciumsaltsinnormaltissue(vessel,lung,gastricmucosa,kidney)

Somederangementincalciummetabolism(hypercalciemia)dueto:

－Increasedsecretionofparathyroidhormone

－Destructionofbone

－VitDrelateddisorders

－Renalfailure沉积于骨外正常组织，尤其是酸性环境的胃粘膜、肾小管、肺等组织.MorphologicfeaturesFine,whitegranulesorclumps,grosslyBasophilicdepositshistologicallyHeterotopicboneformation,sometimes

ConsequenceAcauseoforgandysfunction

－Compromisedvalvemotion(cuspalcalcification)

－Respiratorydeficits(extensivecalcificationofthelung)

－Renaldamage(nephrocalcinosis)VI.Pathologiccalcification

（病理性钙化）Conception

Abnormaldepositionofcalciumsalts,togetherwithsmallamountsofiron,magnesiumandothermineralsClassification

A.Dystrophiccalcification（营养不良性钙化）

Depositionofcalciumsaltsindeadordyingtissues(necroticfoci,thrombus,atheroma,tumor,etc.)AbsenceofcalciummetabolicderangementFormationofcrystallineca