病理學(xué)課件 2014本科修復(fù)3

第三節(jié)損傷的修復(fù)(RepairofInjury)P25損傷(injury)缺損(defect)修復(fù)(repair)修復(fù)(repair)機(jī)體對損傷所形成缺損進(jìn)行修補恢復(fù)的過程。Repairisaresponsetotissueinjuryandtheprocesstorestoreintegritytoaninjuredtissuebytheorganism.

修復(fù)形式(Typesofrepair)1.再生(regeneration)

同種組織完全再生Repairbysametissue2.纖維性修復(fù)(fibrousrepair)

纖維結(jié)締組織修復(fù)

Replacementbyfibroustissue

第一節(jié)

再生

（Regeneration）P25定義

由損傷部周圍同種細(xì)胞來修復(fù)，稱為再生(regeneration)Repairbycellsofsametype特點

完全恢復(fù)原組織結(jié)構(gòu)及功能再生的條件(Conditions)①Theabilityofregenerationofparenchymaltissueisstrong.②Damageareaissmallandthestromalframeworkoftheinjuredtissueispreservativewell.

CompleteregenerationIncompleteregeneration

一、再生的種類

(Typesof

Regeneration)生理性PhysiologicalRegeneration

病理性PathologicalRegeneration

二、再生潛能

(Regenerativepotentialsoftissues)低等動物>高等動物(higheranimal)幼稚組織>成熟組織(differentiation)易受損傷和常更新組織(turnover)動物的種類和組織分化能力(species)生物進(jìn)化(organicevolution)細(xì)胞再生能力分類(Types)1.不穩(wěn)定細(xì)胞(labilecells)

持續(xù)分裂細(xì)胞

再生能力強

表皮,粘膜上皮,間皮,淋巴及造血細(xì)胞ContinuouslydividinganddyingCoveringepithelia

Hematopoieticcells(thebonemarrowcellsandthelymphoidcells)2.穩(wěn)定細(xì)胞(stablecells)靜止細(xì)胞

再生能力較強

肝,胰,腎,腺體,平滑肌,原始間葉細(xì)胞及其分化細(xì)胞(纖維母,軟骨,骨母)QuiescentbutcanrapidlydivideinresponsetoinjuryParenchymalofsolidglandulartissues:liver,kidney,pancreas,glandsEndothelialcellsConnectivetissue(fibroblast,osteoblasts)

Smoothmuscle

3.永久性細(xì)胞(permanentcells)非分裂細(xì)胞

微弱或無再生能力;

神經(jīng)元（節(jié)）、骨骼及心肌細(xì)胞BeterminallydifferentiatedandnonproliferativeafterthegrowthearlyinlifeNervecells(neuron),striatedandcardiacmusclecellsLabilecells

Continuouslydividingcells2.Stablecells

quiescentcells

thatdivideonlywhenneeded3.Permanentcells

nondividingcells

thatpermanentlyremovedfromcellcycle小結(jié)(Summary)

三、再生過程(Regenerationofvarioustissues)（一）上皮組織（epithelia

tissue）1．被覆上皮

(coveringepithelia)基底細(xì)胞分裂增生2．腺上皮

(glandularepithelia)

BM未破壞—完全再生

BM破壞—不完全再生

(reticulinscaffold)Regenerationofvarioustissues(二)

血管(bloodvessel)小血管及毛細(xì)血管

內(nèi)皮出芽(sprout)

--實性條索血流沖擊--形成管腔(canalization)大血管

內(nèi)皮(endothelialcells)--完全再生肌層(smoothmuscle)--纖維修復(fù)

Regenerationofvarioustissues(三)纖維結(jié)締組織

(Fibrousconnectivetissue)未分化間葉細(xì)胞

(primitivecells)纖維母細(xì)胞(fibroblast)

分泌原膠原蛋白

(secretionoftropocollagen)

膠原纖維(collagen)

纖維細(xì)胞(fibrocyte)Regenerationofvarioustissues（四）神經(jīng)組織

(nervoustissue)1.腦及脊髓神經(jīng)細(xì)胞(nervecell)—膠質(zhì)瘢痕

(glialscar)

可再生！2.外周神經(jīng)(peripheralnerve)可完全再生髓鞘及軸突崩解神經(jīng)鞘細(xì)胞增生軸突延長1-2mm/Day正常NF斷離，髓鞘神經(jīng)鞘細(xì)胞增生軸突延伸末梢及軸突崩解basiccondition相應(yīng)神經(jīng)元仍然存活裂端距離＜25mm斷處不能有纖維疤痕創(chuàng)傷性神經(jīng)瘤Traumaticneuroma

裂端太遠(yuǎn)纖維組織增生阻隔軸突長不到遠(yuǎn)端截肢后神經(jīng)瘤Amputationtumor

Osteoblasts

Regenerationofvarioustissues（五）軟骨和骨組織(

boneand

cartilage

tissue)(1)軟骨(cartilage)弱軟骨膜-軟骨母－軟骨細(xì)胞纖維結(jié)締組織修復(fù)(2)骨(bone)

強

骨祖、間充質(zhì)和成纖維細(xì)胞－

骨母細(xì)胞－骨組織Regenerationofvarioustissues(六)肌組織(musculartissue)1.骨骼肌(skeletalmuscle)肌膜存在-完全修復(fù)肌膜破壞-瘢痕修復(fù)

肌衛(wèi)星細(xì)胞增生分化2.平滑肌(smoothmuscle)

再生或纖維修復(fù)3.心肌(myocardium)

纖維修復(fù)三、細(xì)胞再生與分化的分子機(jī)制

1.干細(xì)胞(stemcell)具有自我更新和分化潛能的未分化細(xì)胞自我更新(Self-renewal)分化潛能(Differentiation)不對稱復(fù)制(asymmetricreplication)前體細(xì)胞/特化細(xì)胞precursors/specializedcell新概念:再生醫(yī)學(xué)

RegenerativeMedicine

胚胎干細(xì)胞(EmbryonicStemcells):PluripotentcellsTherapeuticCloning成體干細(xì)胞(AdultStemcells):MorerestricteddifferentiationcapacityBoneMarrowHaematopoieticstemcells新概念:再生醫(yī)學(xué)細(xì)胞再生與分化的分子機(jī)制2.細(xì)胞外基質(zhì)(ECM)(ExtracellularMatrix)膠原纖維,彈力纖維,粘附蛋白,蛋白多糖,基質(zhì)細(xì)胞蛋白-細(xì)胞連接一起3.信號轉(zhuǎn)導(dǎo)

(Signaltransduction)4.細(xì)胞因子/生長因子

(Cytokine/growthfactor)Growthfactors&cytokinesPDGF---plateletderivedgrowthfactorFGF---fibroblastgrowthfactorEGF---epidermalgrowthfactorTGF---transforminggrowthfactorVEGF---vascularendothelialgrowthfactorNGF---nervegrowthfactorHGF---hepatocytegrowthfactorTNF---tumornecrosisfactorIL-1—interleukin-1細(xì)胞再生與分化的分子機(jī)制5.接觸抑制(contactinhibition)6.抑素(chalone)7.基因調(diào)控(generegulation)原癌基因(proto-oncogene)細(xì)胞周期基因(celldivisioncyclegenes,CDCgenes)

第二節(jié)

纖維性修復(fù)

(Fibrousrepair)P28纖維性修復(fù),瘢痕修復(fù)(Scarrepair)再生能力弱或缺乏再生能力組織；無原組織的結(jié)構(gòu)及功能不完全修復(fù)(incompleterepair)纖維性修復(fù)特點

Featuresoffibrousrepair

肉芽組織（granulationtissue)pink,soft,wetandgranular一、肉芽組織(granulationtissue)由新生的毛細(xì)血管、

增生的纖維母細(xì)胞和各種炎性細(xì)胞組成

呈鮮紅色,顆粒狀,

柔軟濕潤,

形似鮮嫩的肉芽。Fibroblastsandnewcapillariesinalooseextracellularmatrix.

Granulationtissue:morphology新生毛細(xì)血管,

垂直于創(chuàng)面

Richlycapillarysprouts

纖維母,肌纖維母細(xì)胞

Reactivefibroblastsandmyofibroblasts炎細(xì)胞:中性粒,巨噬,淋巴細(xì)胞Variablenumbersofinflammatorycellsgranulationtissue

Granulationtissue:function①抗感染及保護(hù)創(chuàng)面Anti-infectionandprotectthewoundsurface②填補傷口及組織缺損Tomakeupthedeficiencyandrepairtheinjuredtissue③機(jī)化或包裹壞死、血栓、炎癥滲出物及異物Toorganizebloodclotting,necrotictissuesorabnormalsubstances轉(zhuǎn)化疤痕組織(scar)

二、瘢痕組織（scartissue）瘢痕組織肉芽組織漸成熟(纖維化)

并老化（玻璃樣變）的纖維結(jié)締組織。Fibrosis/maturationandretrogradationofgranulationtissuePale-gray,hard,lackofelasticity,tissueshrinkage瘢痕組織形態(tài)(morphology)毛細(xì)血管退化消失(avascular)纖維母細(xì)胞/纖維細(xì)胞稀少(fibroblasts)炎細(xì)胞消失(inflammatorycells)膠原纖維大量平行交錯(collagensynthesis)間質(zhì)致密玻璃樣變(hyalinechange)瘢痕組織的作用(function)有利(advantages)

①填補創(chuàng)傷缺損,保持組織器官完整性

Integrality:fillthedefectandrepairthetissue

②瘢痕中膠原纖維具有一定抗拉力,保持組織的堅固性。

Firmness:moretensilestrengthComplicationsofScar

---Excessivescarformation

不利(disadvantages)①瘢痕收縮(Scarcontractures):關(guān)節(jié)攣縮

(jointcontracture)

②瘢痕粘連(Adhesions):

腸粘連③器官硬化(Sclerosis):

肺纖維化

④肥大性瘢痕(HypertrophicScar):

瘢痕疙瘩（keloid)蟹足腫(cheloid)瘢痕體質(zhì)(geneticpredisposition)III型膠原(DepositionofTypeIIIcollagen)Keloid疤痕疙瘩，瘢痕組織過度增生，形成突出皮膚表面并向周圍不規(guī)則擴(kuò)展，臨床稱為“蟹足腫”Hyalinizedcollageninakeloid第三節(jié)

創(chuàng)傷愈合

(Woundhealing)P29創(chuàng)傷愈合(woundhealing)

是指機(jī)體遭受外力作用，皮膚等組織出現(xiàn)離斷或缺損后的愈復(fù)過程。Acomplexbutorderlyprocess,involvingbothparenchymalcellsregenerationandtheformationofconnectivetissuescar.

一、

皮膚創(chuàng)傷愈合

(woundhealingofskin)

（一）創(chuàng)傷愈合的基本過程

(Basiccoursesofwoundhealing)1.傷口早期變化(exudate)2.傷口收縮

(contractionofthewound)3.肉芽組織和瘢痕形成

(granulation&mature)4.表皮等組織再生(regeneration)

3d:肉芽組織5-6d:膠原纖維形成3-4w:瘢痕完全形成1.一期愈合(Healingbyfirstintention)Thereisacleanwoundwithwell-apposededges,andminimalclotformation.（二）創(chuàng)傷愈合的類型(Types)1．一期愈合（Healingbyfirstintention）條件:組織缺損少,創(chuàng)緣整齊,對合好,無感染(regulardefects,uninfected,clean,well-apposededges)，特點:血凝塊少,炎癥反應(yīng)輕,表皮再生1-2d,肉芽組織3d,膠原纖維形成5-6d,完全愈合2-3w(mildinflammationreaction)結(jié)局:線狀瘢痕(linearscar)Summary2.二期愈合(Healingbysecondintention)Woundedgescannotbeapposed,orfollowingwoundinfection,orlargetissuedefect.Moregranulationtissue.2.二期愈合（Healingbysecondintention）條件

組織缺損較大,創(chuàng)緣不整,對合不佳,伴有感染(largeirregulartissuedefect,infection)特點①壞死組織多,炎癥反應(yīng)明顯(morenecrosis,extensiveinflammation,moregranulation)②傷口大,收縮明顯,多量肉芽組織(contraction)③愈合時間較長,形成的瘢痕較大(largerscar)Summary3.痂下愈合(Healingunderscar)血液、滲出物及壞死組織干燥后形成硬痂痂下進(jìn)行二期愈合二、骨折愈合(Fracturehealing)修復(fù)過程:四個階段外傷性(Traumatic)

病理性(Pathologic)骨折1.血腫形成期

(Hematomaformation)

1-2d

Hematoma&Inflammation–PDGF,IL,TGF

3d-2w纖維性暫時骨痂Softcallus:granulationtissuewithosteoblastsandmatrix2.纖維骨痂形成期(Fibrouscallusformation)3.骨性骨痂形成期

(Bonycallusformation)3-8w骨性骨痂軟骨性骨痂骨樣組織(osteoidtissue)編織骨(wovenbone)Hardcallus:depositionofcalcium軟骨性骨痂(cartilagecallus)骨性骨痂(bonycallus)Osteoblasts

4.

骨痂改建期

Bonycallusremodelling

8w-months生物應(yīng)力作用骨小梁排列及結(jié)構(gòu)板層骨(lamellarbone)Remodelling–removalofexcessirregularbone

骨性骨痂改建

(Bonycallusremodelling)Summary:HealinginBone

1D-Hematomaformation&Inflammation1W-Softcallus–granulation,osteoidtissue3W–HardCallus–ossification,wovenbone8W-Re-modeling–absorb/deposit,lamellate1.全身因素(Systemicfactors)(1)年齡(Age)(2)營養(yǎng)(Nutrition)

蛋白質(zhì)（甲硫、胱）

vitC、B、A、D,

鋅(3)免疫狀態(tài)(Immunestatus)

(4)疾病(Chronicdiseases)(5)藥物(Corticosteroids

etc)三、影響創(chuàng)傷愈合的因素

影響創(chuàng)傷愈合的因素(續(xù))2.局部因素(Localfactors)Type,size,andlocationofthewoundInfectionForeignbodyAppositionMobilityBloodsupplyPoorwoundhealinginapatientbeingtreatedwithcorticosteroids.Keyfactors:

損傷的性質(zhì)、程度、組織再生能力、醫(yī)療處理(清創(chuàng),對合,抗感染,生長因子治療)影響骨折愈合因素骨愈合畸形Deformityofbonehealing及時正確復(fù)位

Properreduction及時牢固固定Immobilization適時功能鍛煉Functionalexercise骨愈合畸形(Deformityofbonehealing):假關(guān)節(jié)(Pseudoarthrosis)小結(jié)(Summary)修復(fù)再生(regeneration)纖維性修復(fù)(Fibrousrepair)再生分類不穩(wěn)定細(xì)胞(labilecells)穩(wěn)定細(xì)胞(stablecells)永久性細(xì)胞(permanentcells)肉芽組織瘢痕組織新生毛細(xì)血管(capillary)纖維母細(xì)胞(fibroblast)多量炎細(xì)胞(inflammatorycells)

一期

二期

組織破壞

少

大

創(chuàng)緣

齊

不齊

感染

無

有

傷口對合

好

差

愈合時間

一周內(nèi)

長

瘢痕

少

多

功能影響

很小

較大創(chuàng)傷愈合骨折愈合過程骨性肉芽毛細(xì)血管纖維母細(xì)胞骨母細(xì)胞軟骨母細(xì)胞纖維性骨痂骨性骨痂血腫形成骨痂改建+鈣鹽骨性骨痂軟骨性骨痂骨樣組織編織骨板層骨granulationtissueKeloidHyalinizedcollageninakeloid

形成性練習(xí)

一、名詞解釋

●不完全性再生

●肉芽組織

●蟹足腫

●stablecells

●纖維骨痂

●二期愈合二、是非判斷題1.毛細(xì)血管的再生過程是以出芽方式來完成的。2.細(xì)胞損傷后能否重新構(gòu)建為正常結(jié)構(gòu)依賴于細(xì)胞外基質(zhì)。

3.纖維性修復(fù)必須通過肉芽組織的增生才能完成。4.平滑肌細(xì)胞是永久性細(xì)胞。5.不論損傷程度，骨折后