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1、第二章第二章 損傷的修復(fù)損傷的修復(fù)(Tissues Repair)P27損傷損傷(injury)缺損缺損(defect)修復(fù)修復(fù)(repair)修復(fù)修復(fù)(repair)n機(jī)體對(duì)損傷所形成機(jī)體對(duì)損傷所形成缺損進(jìn)行修補(bǔ)恢復(fù)缺損進(jìn)行修補(bǔ)恢復(fù)的過(guò)程。的過(guò)程。nRepair is a response to tissue injury and the process to restore integrity to an injured tissue by the organism. 問(wèn)題與啟迪問(wèn)題與啟迪(questions)n什么是瘢痕？什么是瘢痕？n瘢痕是怎樣形成的？瘢痕是怎樣形成的？n能不能不形成瘢
2、痕？能不能不形成瘢痕？n瘢痕形成有正面意義嗎？瘢痕形成有正面意義嗎？n能否加速傷口愈合？能否加速傷口愈合？n傷口愈合不佳的原因傷口愈合不佳的原因 有哪些？有哪些？修復(fù)形式修復(fù)形式(Types of repair)1.1.再生再生(regeneration): : 同種組織完全再生同種組織完全再生 Repair by same tissue2.2.纖維性修復(fù)纖維性修復(fù)(fibrous repair) 纖維結(jié)締組織修復(fù)纖維結(jié)締組織修復(fù) Replacement by fibrous tissue 第一節(jié)第一節(jié) 再生再生（Regeneration）P27P27n定義定義: :由損傷部周圍由損傷部周圍的
3、同種細(xì)胞來(lái)修復(fù)，的同種細(xì)胞來(lái)修復(fù)，稱為再生稱為再生(regeneration)nRepair by cells of same typen特點(diǎn)特點(diǎn): :完全恢復(fù)原組完全恢復(fù)原組織的結(jié)構(gòu)及功能織的結(jié)構(gòu)及功能Whats regeneration? 一一 組織的再生能力組織的再生能力 (Regenerative potentials of tissues)n低等動(dòng)物低等動(dòng)物 高等動(dòng)物高等動(dòng)物n分化低分化低 分化高分化高n易受損傷和常更新組織再生能力強(qiáng)易受損傷和常更新組織再生能力強(qiáng)n取決于動(dòng)物的種類和組織分化能力取決于動(dòng)物的種類和組織分化能力n生物進(jìn)化生物進(jìn)化(evolution)一一 細(xì)胞再生能力分
4、類細(xì)胞再生能力分類(Types)n1.1.不穩(wěn)定細(xì)胞不穩(wěn)定細(xì)胞(labile cells) 強(qiáng)再生能力強(qiáng)再生能力; ;表皮表皮, ,粘膜粘膜上皮上皮, ,間皮間皮, ,淋巴及造血淋巴及造血細(xì)胞細(xì)胞nContinuously dividing and dyingnCovering epithelia nHematopoietic cells(the bone marrow cells and the lymphoid cells)2.2.穩(wěn)定細(xì)胞穩(wěn)定細(xì)胞( (stable cells)stable cells)n較強(qiáng)再生能力較強(qiáng)再生能力, , 肝肝, ,胰胰, ,腎腎, ,腺體腺體, ,平滑肌平
5、滑肌, ,原始間葉細(xì)原始間葉細(xì)胞及其分化細(xì)胞胞及其分化細(xì)胞( (纖維母纖維母, ,軟骨軟骨, ,骨母骨母) )nQuiescent but can rapidly divide in response to injurynParenchymal of solid glandular tissues: liver, kidney, pancreas, glandnEndothelial cellsnConnective tissue (fibroblast, osteoblasts) nSmooth muscle 3.3.永久性細(xì)胞永久性細(xì)胞(permanent cells)n微弱或無(wú)再生能力微
6、弱或無(wú)再生能力; ; 神神經(jīng)元經(jīng)元, ,骨骼肌骨骼肌, ,心肌細(xì)胞心肌細(xì)胞 nBe terminally differentiated and nonproliferative after the growth early in lifenNerve cells(neuron), striated and cardiac muscle cells1. Labile cells: continuously dividing cells2. Stable cells: quiescent cells that divide only when needed3. Permanent cells: n
7、ondividing cells that permanently removed from cell cycle小結(jié)小結(jié)(Summary):(Summary):細(xì)胞再生力分類細(xì)胞再生力分類 二二 組織的再生過(guò)程組織的再生過(guò)程(Regeneration of various tissues)1 1被覆上皮被覆上皮 ( (covering epithelia) 基底細(xì)胞分裂增生基底細(xì)胞分裂增生2 2腺上皮腺上皮 (glandular epithelia) BMBM未破壞未破壞完全再生完全再生 BMBM破壞破壞不完全再生不完全再生 (reticulin scaffold ) )Regenerati
8、on of various tissues3.3.血管血管(blood vessel)n小血管及毛細(xì)血管小血管及毛細(xì)血管 內(nèi)皮出芽?jī)?nèi)皮出芽( (sprout) - - -實(shí)性條索實(shí)性條索 血流沖擊血流沖擊-形成管腔形成管腔(canalization)n大血管大血管 內(nèi)皮內(nèi)皮(endothelial cells )-完全再生完全再生 肌層肌層(smooth muscles):-疤痕修復(fù)疤痕修復(fù)Regeneration of various tissues4.4.神經(jīng)組織神經(jīng)組織 (nervous tissue)(1)(1)腦及脊髓神經(jīng)細(xì)胞腦及脊髓神經(jīng)細(xì)胞(nerve cell) 膠質(zhì)瘢痕膠質(zhì)瘢痕
9、 (glial scar) 新知識(shí)點(diǎn)：可再生！新知識(shí)點(diǎn)：可再生！4.神經(jīng)組織(nervous tissue)(2)(2)外周神經(jīng)外周神經(jīng)(peripheral nerve)n可完全再生可完全再生n髓鞘及軸突崩解髓鞘及軸突崩解n神經(jīng)鞘細(xì)胞增生神經(jīng)鞘細(xì)胞增生n軸突延長(zhǎng)軸突延長(zhǎng)n1 1mm/Daymm/Day創(chuàng)傷性神經(jīng)瘤創(chuàng)傷性神經(jīng)瘤Traumatic neuroma三三 細(xì)胞再生的分子機(jī)制細(xì)胞再生的分子機(jī)制 1. 1.干細(xì)胞干細(xì)胞(stem cell)n具有自我更新和分化潛具有自我更新和分化潛能的能的未分化未分化細(xì)胞細(xì)胞n自我更新自我更新(Self-renewal)n分化潛能分化潛能(Differe
10、ntiation)n不對(duì)稱復(fù)制不對(duì)稱復(fù)制(asymmetric replication)n前體細(xì)胞前體細(xì)胞/特化細(xì)胞特化細(xì)胞precursors/specialized cell新概念新概念: 再生醫(yī)學(xué)再生醫(yī)學(xué)nRegenerative Medicine n胚胎干細(xì)胞胚胎干細(xì)胞(Embryonic stem cells, ESC) : pluripotent cells nTherapeutic cloningn成體干細(xì)胞成體干細(xì)胞(Adult Stem cells, ASC) :More restricted differentiation capacity nBone Marrow Hae
11、matopoietic stem cells 新概念新概念: 再生醫(yī)學(xué)再生醫(yī)學(xué)新概念新概念: 再生醫(yī)學(xué)再生醫(yī)學(xué)n誘導(dǎo)性多能干細(xì)胞（誘導(dǎo)性多能干細(xì)胞（iPSC）(induced pluripotent stem cells) :已分化成體細(xì)胞的重新已分化成體細(xì)胞的重新編程編程細(xì)胞再生與分化的分子機(jī)制細(xì)胞再生與分化的分子機(jī)制2.2.細(xì)胞細(xì)胞外基質(zhì)外基質(zhì)(ECM) (Extracellular Matrix) 膠原纖維膠原纖維,彈力纖維彈力纖維, 粘附蛋白粘附蛋白,蛋白多糖蛋白多糖,3.3.信號(hào)信號(hào)轉(zhuǎn)導(dǎo)轉(zhuǎn)導(dǎo)(Signal transduction)4.4.細(xì)胞細(xì)胞因子因子/生長(zhǎng)因子生長(zhǎng)因子 (Cyt
12、okine/growth factor)Growth factors & cytokinesnPDGF-platelet derived growth factornFGF-fibroblast growth factornEGF-epidermal growth factornTGF-transforming growth factornVEGF-vascular endothelial growth factornNGF- nerve growth factornHGF-hepatocyte growth factornTNF-tumor necrosis factornIL-1inter
13、leukin-1(白細(xì)胞介素白細(xì)胞介素-1)細(xì)胞再生與分化的分子機(jī)制細(xì)胞再生與分化的分子機(jī)制5.5.接觸抑制接觸抑制(contact inhibition)6.6.抑素抑素(chalone)7.7.基因調(diào)控基因調(diào)控(gene regulation) 原癌基因原癌基因(proto-oncogene) 細(xì)胞周期基因細(xì)胞周期基因(cell division cycle genes, CDC genes)第二節(jié)第二節(jié) 纖維性修復(fù)纖維性修復(fù) (Fibrous repair)P36P36n纖維性修復(fù)纖維性修復(fù), ,瘢痕修復(fù)瘢痕修復(fù)(Scar repair)n再生能力弱或缺乏再生能再生能力弱或缺乏再生能力的
14、組織力的組織(less regeneration capacity)；n無(wú)原組織的結(jié)構(gòu)及功能無(wú)原組織的結(jié)構(gòu)及功能n不完全修復(fù)不完全修復(fù)(incomplete repair)纖維性修復(fù)特點(diǎn)纖維性修復(fù)特點(diǎn)Features of fibrous repair 肉芽組織肉芽組織（granulation tissue)pink, soft, wet and granular一一 肉芽組織肉芽組織(granulation tissue)v由新生的毛細(xì)血管、由新生的毛細(xì)血管、增生的纖維母細(xì)胞增生的纖維母細(xì)胞和各種炎性細(xì)胞組和各種炎性細(xì)胞組成成, ,呈鮮紅色呈鮮紅色, ,顆粒顆粒狀狀, ,柔軟濕潤(rùn)柔軟濕潤(rùn),
15、,形似形似鮮嫩的肉芽鮮嫩的肉芽vFibroblasts and new capillaries in a loose extracellular matrix. Granulation tissue: morphologymorphologyn新生毛細(xì)血管新生毛細(xì)血管, ,垂直于創(chuàng)垂直于創(chuàng)面面nRichly capillary sprouts n纖維母纖維母, ,肌纖維母細(xì)胞肌纖維母細(xì)胞nReactive fibroblasts and myofibroblastsn炎細(xì)胞炎細(xì)胞: :中性粒中性粒, ,巨噬巨噬, ,淋淋巴細(xì)胞巴細(xì)胞nVariable numbers of inflammato
16、ry cells Granulation tissue: functionn抗感染及保護(hù)創(chuàng)面抗感染及保護(hù)創(chuàng)面 Anti-infection and protect the wound surfacen填補(bǔ)傷口及組織缺損填補(bǔ)傷口及組織缺損 To make up the deficiency and repair the injured tissuen機(jī)化或包裹壞死、血栓、炎癥滲出物及異物機(jī)化或包裹壞死、血栓、炎癥滲出物及異物 To organize blood clotting, necrotic tissues or abnormal substancesn 轉(zhuǎn)化轉(zhuǎn)化 疤痕組織疤痕組織(sca
17、r) 二二 瘢痕組織瘢痕組織(scar tissue)n瘢痕組織是肉芽組瘢痕組織是肉芽組織逐漸成熟織逐漸成熟( (纖維化纖維化) )并老化（玻璃樣變）并老化（玻璃樣變）的纖維結(jié)締組織。的纖維結(jié)締組織。nFibrosis/maturation and retrogradation of granulation tissuenPale-gray, hard, lack of elasticity, tissue shrinkage瘢痕組織形態(tài)瘢痕組織形態(tài)(morphology)n毛細(xì)血管退化消失毛細(xì)血管退化消失(blood capillary)n纖維母細(xì)胞纖維母細(xì)胞/ /纖維細(xì)胞纖維細(xì)胞稀少稀少(
18、fibroblasts)n炎細(xì)胞消失炎細(xì)胞消失(inflammatory cells)n膠原纖維大量平行交錯(cuò)膠原纖維大量平行交錯(cuò) (collagen synthesis)n間質(zhì)致密玻璃樣變間質(zhì)致密玻璃樣變(hyaline change)瘢痕組織的作用瘢痕組織的作用(function)n有利有利(advantages) 填補(bǔ)創(chuàng)傷缺損填補(bǔ)創(chuàng)傷缺損,保持組織器官完整性保持組織器官完整性 Integrity: fill the defect and repair the tissue 瘢痕中膠原纖維具有一定抗拉力瘢痕中膠原纖維具有一定抗拉力,保持組保持組織的堅(jiān)固性?？椀膱?jiān)固性。 Firmness: m
19、ore tensile strengthComplications of Scar -Excessive scar formation n不利不利(disadvantages)瘢痕收縮瘢痕收縮 關(guān)節(jié)攣縮關(guān)節(jié)攣縮 瘢痕粘連瘢痕粘連( (: : 腸粘連腸粘連器官硬化器官硬化 肺纖維化肺纖維化 Complications of Scar 肥大性瘢痕肥大性瘢痕(Hypertrophic Scar): 瘢痕疙瘩瘢痕疙瘩（keloid)蟹足腫蟹足腫(cheloid)v瘢痕體質(zhì)瘢痕體質(zhì)(genetic predisposition)vIII型膠原型膠原(Deposition of Type III coll
20、agen) Complications of Scar 第三節(jié)第三節(jié) 創(chuàng)創(chuàng) 傷傷 愈愈 合合(Wound healing)P40P40n創(chuàng)傷愈合創(chuàng)傷愈合(wound healing) 是指機(jī)體遭是指機(jī)體遭受外力作用，皮膚等受外力作用，皮膚等組織出現(xiàn)離斷或缺損組織出現(xiàn)離斷或缺損后的愈復(fù)過(guò)程。后的愈復(fù)過(guò)程。nA complex but orderly process, involving both parenchymal cells regeneration and the formation of connective tissue scar.Whats wound healing? 一一 創(chuàng)傷
21、愈合的基本過(guò)程創(chuàng)傷愈合的基本過(guò)程(Basic process of wound healing)1 1. .傷口早期變化傷口早期變化(exudate)2 2. .傷口收縮傷口收縮(contraction of the wound):2-3d2-3d3 3. .肉芽組織和瘢痕形成肉芽組織和瘢痕形成(granulation & mature)4.4.表皮等組織再生表皮等組織再生(regeneration) n3 3d:d:肉芽組織肉芽組織n5-65-6d:d:膠原纖維形成膠原纖維形成 n3-43-4w:w:瘢痕完全形成瘢痕完全形成1. 一期愈合一期愈合(Healing by first inten
22、tion)nThere is a clean wound with well-apposed edges, and minimal clot formation.二二 創(chuàng)傷愈合的類型創(chuàng)傷愈合的類型(Types)1 1一期愈合一期愈合（Healing by first intention）n條件條件: : 組織缺損少組織缺損少, ,創(chuàng)緣整齊創(chuàng)緣整齊, ,對(duì)合好對(duì)合好, ,無(wú)無(wú)感染感染( (regular defects, uninfected, clean, well-apposed edges)，n特點(diǎn)特點(diǎn): : 血凝塊少血凝塊少, ,炎癥反應(yīng)輕炎癥反應(yīng)輕, ,表皮再生表皮再生1- 1-2 2
23、d,d,肉芽組織肉芽組織3 3d,d,膠原纖維形成膠原纖維形成5-65-6d,d,完全完全愈合愈合2-32-3ww (mild inflammation reaction)n結(jié)局結(jié)局: : 線狀瘢痕線狀瘢痕(linear scar)小結(jié)：Summary2.2.二期愈合二期愈合(Healing by second intention)v Wound edges cannot be apposed, or following wound infection, or large tissue defect.v More granulation tissue.2.2.二期愈合二期愈合（Healing
24、by second intention）n條件條件 組織缺損較大組織缺損較大, ,創(chuàng)緣不整創(chuàng)緣不整, ,對(duì)合不佳對(duì)合不佳, ,伴有伴有感染感染( (large irregular tissue defect/infection) )n特點(diǎn)特點(diǎn)壞死組織多壞死組織多, ,炎癥反應(yīng)明顯炎癥反應(yīng)明顯(more necrosis, extensive inflammation, more granulation )傷口大傷口大, ,收縮明顯收縮明顯, ,多量肉芽組織多量肉芽組織(contraction)愈合時(shí)間較長(zhǎng)愈合時(shí)間較長(zhǎng), ,形成的瘢痕較大形成的瘢痕較大(larger scar)小結(jié)：Summar
25、y三三 影響創(chuàng)傷愈合的因素影響創(chuàng)傷愈合的因素 Factors affecting wound healing1.1.全身因素全身因素(factors)(1)(1)年齡年齡( (2)(2)營(yíng)養(yǎng)營(yíng)養(yǎng)( ( 蛋白質(zhì)（甲硫、胱）蛋白質(zhì)（甲硫、胱） vitC vitC、B B、A A、D, D, 鋅鋅(3)(3)免疫狀態(tài)免疫狀態(tài) (4)(4)疾病疾病( (5)(5)藥物藥物(Corticosteroids 影響創(chuàng)傷愈合的因素影響創(chuàng)傷愈合的因素( (續(xù)續(xù)) )2.2.局部因素局部因素nType, size, and location of the woundnInfectionnForeign body
26、nAppositionnMobilitynBlood supplyPoor wound healing in a patient being treated with corticosteroids.Key factors: 損損傷的性質(zhì)、程度傷的性質(zhì)、程度、組織再生能力、組織再生能力、醫(yī)療處理、醫(yī)療處理( (清創(chuàng)清創(chuàng), ,對(duì)合對(duì)合, ,抗感染抗感染, ,生生長(zhǎng)因子治療長(zhǎng)因子治療) ) 影響創(chuàng)傷愈合的因素影響創(chuàng)傷愈合的因素( (續(xù)續(xù)) )四四 骨折愈合骨折愈合(Fracture healing)n修復(fù)過(guò)程修復(fù)過(guò)程: : 四個(gè)階段四個(gè)階段(Four repair process)外傷性外傷性(T
27、raumatic) 病理性病理性(Pathologic)n 骨折骨折1.1.血腫形成期血腫形成期 (Hematoma formation) 1-2d Hematoma: inflammation, PDGF, IL, TGFn3d-2wn纖維性暫時(shí)骨痂纖維性暫時(shí)骨痂nSoft callus: granulation tissue with osteoblasts and matrix2. 2. 纖維骨痂形成期纖維骨痂形成期(Fibrous callus formation)3. 骨性骨痂形成期骨性骨痂形成期(Bony callus formation)3-8w3-8w骨性骨痂骨性骨痂(bony
28、 callus)軟骨骨痂軟骨骨痂(cartilage callus)骨樣組織骨樣組織(osteoid tissue)編織骨編織骨(woven bone)Hard callus: deposition of calcium軟骨性骨痂軟骨性骨痂 (cartilage callus)Osteoblasts 骨性骨痂骨性骨痂 (bony callus)4.4.骨痂改建期骨痂改建期Bony remodelling v8w-monthsv生物應(yīng)力作用生物應(yīng)力作用v骨小梁排列及結(jié)構(gòu)骨小梁排列及結(jié)構(gòu)v板層骨板層骨(lamellar bone)v重塑重塑(Remodelling): removal of exc
29、ess irregular bone 骨性骨痂改建骨性骨痂改建(Bony callus remodelling )影響骨折愈合因素影響骨折愈合因素n骨愈合畸形骨愈合畸形n及時(shí)正確復(fù)位及時(shí)正確復(fù)位Proper reduction n及時(shí)牢固固定及時(shí)牢固固定Immobilization n適時(shí)功能鍛煉適時(shí)功能鍛煉Functional exercise小小 結(jié)結(jié)(Summary)n修復(fù)修復(fù)再生再生(regeneration)纖維性修復(fù)纖維性修復(fù)(Fibrous repair)n再生力分類再生力分類不穩(wěn)定細(xì)胞不穩(wěn)定細(xì)胞(labile cells)穩(wěn)定細(xì)胞穩(wěn)定細(xì)胞(stable cells)永久性細(xì)胞永
30、久性細(xì)胞(permanent cells)n肉芽組織肉芽組織(granulation)n瘢痕組織瘢痕組織(scar tissue)新生毛細(xì)血管新生毛細(xì)血管(capillary)纖維母細(xì)胞纖維母細(xì)胞(fibroblast)多量炎細(xì)胞多量炎細(xì)胞(inflammatory cells)小小 結(jié)結(jié)(Summary) 一期一期 二期二期組織破壞組織破壞 少少 大大 創(chuàng)緣創(chuàng)緣 齊齊 不齊不齊感染感染 無(wú)無(wú) 有有傷口對(duì)合傷口對(duì)合 好好 差差愈合時(shí)間愈合時(shí)間 一周內(nèi)一周內(nèi) 長(zhǎng)長(zhǎng)瘢痕瘢痕 少少 多多 功能影響功能影響 很小很小 較大較大骨折愈合過(guò)程骨折愈合過(guò)程骨性肉芽骨性肉芽毛細(xì)血管毛細(xì)血管 纖維母細(xì)胞纖維母細(xì)
31、胞 骨母細(xì)胞骨母細(xì)胞軟骨母細(xì)胞軟骨母細(xì)胞+鈣鹽鈣鹽 骨性骨痂骨性骨痂 軟骨性骨痂軟骨性骨痂 骨樣組織骨樣組織編織骨編織骨板層骨板層骨形成性練習(xí)形成性練習(xí)granulation tissueKeloidHyalinized collagen in a keloid復(fù)習(xí)思考題復(fù)習(xí)思考題1 解釋下列名詞：不完全性再生，解釋下列名詞：不完全性再生，肉芽組織；蟹足腫；瘢痕修復(fù)，肉芽組織；蟹足腫；瘢痕修復(fù)，stable cells，纖維骨痂纖維骨痂 ，二期愈，二期愈合合2簡(jiǎn)述肉芽組織的形態(tài)特點(diǎn)及其簡(jiǎn)述肉芽組織的形態(tài)特點(diǎn)及其在修復(fù)過(guò)程中的意義？在修復(fù)過(guò)程中的意義？復(fù)習(xí)思考題復(fù)習(xí)思考題3 廣州某印刷廠切紙工不
32、慎將食廣州某印刷廠切紙工不慎將食指切斷，指切斷，2小時(shí)后在南方醫(yī)院創(chuàng)小時(shí)后在南方醫(yī)院創(chuàng)骨科行斷指再植術(shù)，術(shù)后斷指骨科行斷指再植術(shù)，術(shù)后斷指存活，請(qǐng)問(wèn)有幾種組織參與損存活，請(qǐng)問(wèn)有幾種組織參與損傷修復(fù)？并簡(jiǎn)述各組織修復(fù)及傷修復(fù)？并簡(jiǎn)述各組織修復(fù)及愈合的特點(diǎn)及過(guò)程？愈合的特點(diǎn)及過(guò)程？課外參考資料課外參考資料n本校病理學(xué)國(guó)家精品課程網(wǎng)站本校病理學(xué)國(guó)家精品課程網(wǎng)站(http:/ of Pathology, University of Cambridge（http:/www.path.cam.ac.uk/）nFlorida State University College of Medicine WebPath（http:/medlib.med.utah.edu/WebPath/webpath.html#GUIDE）nThe Urbana Atlas of Pathology（http:/www.med.uiuc.edu/PathAtlasf/titlepage.html）nKumar V, Cotran RS, Robbins SL.Basic Pathology.8th edtion, Elsevier 2010n李青主編李青主編. 病理學(xué)復(fù)習(xí)指導(dǎo)病理學(xué)復(fù)習(xí)指導(dǎo). 中國(guó)協(xié)和醫(yī)科大學(xué)出中國(guó)協(xié)和醫(yī)科大學(xué)出版社版社. 2013
病理學(xué)：第二章?lián)p傷的修復(fù)
