損傷的修復ppt課件(1)

1、損傷的修復損傷的修復Tissue Repair 病理學系病理學系李李 學學 農農 (Prof. MD, PhD) (Prof. MD, PhD)nfydlxn126nfydlxn126P23P23損傷損傷(injury)(injury)缺損缺損(defect)(defect)修復修復(repair)(repair)修復修復(repair)n機體對損傷所構成缺損進展修補恢復的過程。nRepair is a response to tissue injury and the process to restore integrity to an injured tissue by the organ

2、ism. 修復方式修復方式(Types of repair)(Types of repair)1.1.再生再生(regeneration):(regeneration): 同種組織完全再生同種組織完全再生 Repair by same Repair by same tissuetissue2.2.纖維性修復纖維性修復(fibrous (fibrous repair) repair) 纖維結締組織修復纖維結締組織修復 Replacement by Replacement by fibrous tissuefibrous tissue第一節(jié)第一節(jié) 再生性修復再生性修復Regenerationn定義

3、定義: :由損傷部周圍由損傷部周圍的同種細胞來修復，的同種細胞來修復，稱為再生稱為再生(regeneration)(regeneration)nRepair by cells Repair by cells of same typeof same typen特點特點: :完全恢復原組完全恢復原組織的構造及功能織的構造及功能 一一 組織的再生才干組織的再生才干 (Regenerative potentials of tissues)n低等動物低等動物 高等動物高等動物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才干強易受損傷和常更新組織再生才干強n取決于動物的種類和組織分化才干取決于動

4、物的種類和組織分化才干n生物進化生物進化(evolution)(evolution)細胞再生才干分類細胞再生才干分類(Types)n1.1.不穩(wěn)定細胞不穩(wěn)定細胞(labile cells) (labile cells) 強再生才強再生才干干; ; 表皮表皮, ,粘膜上皮粘膜上皮, ,間皮間皮, ,淋巴及造血細胞淋巴及造血細胞n2.2.穩(wěn)定細胞穩(wěn)定細胞(stable cells) (stable cells) 較強再生才較強再生才干干, , 肝肝, ,胰胰, ,腎腎, ,腺體腺體, ,平滑肌平滑肌, ,原始間葉細胞原始間葉細胞及其分化細胞及其分化細胞( (纖維母纖維母, ,軟骨軟骨, ,骨母骨母

5、) )n3.3.永久性細胞永久性細胞(permanent cells) (permanent cells) 微弱或微弱或無再生才干無再生才干; ; 神經元神經元, ,骨骼肌骨骼肌, ,心肌細胞心肌細胞 1. Labile cells: continuously dividing cells2. Stable cells: quiescent cells that divide only when needed3. Permanent cells: nondividing cells that permanently removed from cell cycle 二二 組織的再生過程組織的再生

6、過程(Regeneration of various (Regeneration of various tissues)tissues)1被覆上皮 (lining epithelium) 基內幕胞分裂增生2 2腺上皮腺上皮 (glandular (glandular epithelium)epithelium) BM BM未破壞未破壞完全再完全再生生 BM BM破壞破壞不完全再生不完全再生Regeneration of various tissues3.纖維結締組織 (fibrous connective tissue) 未分化間葉細胞 纖維母細胞(fibroblast) 分泌原膠原蛋白 膠原

7、纖維(collagen) 纖維細胞(fibrocyte)Regeneration of various tissues4.血管(blood vessel)小血管及毛細血管 內皮出芽-實性條索血流沖擊-構成管腔大血管 內皮:完全再生 肌層:疤痕修復Regeneration of various tissues5.肌組織(muscular tissue)(1)骨骼肌(skeletal muscle)肌膜存在-完全修復肌膜破壞-瘢痕修復 肌衛(wèi)星細胞增生分化(2)平滑肌(smooth muscle) 再生或纖維修復(3)心肌(myocardium) 纖維修復Regeneration of variou

8、s tissues6.神經組織 (nervous tissue)(1)腦及脊髓神經細胞(nerve cell) 膠質瘢痕 (glial scar) 可再生！6.神經組織(nervous tissue)(2)外周神經(peripheral nerve)可完全再生髓鞘及軸突崩解神經鞘細胞增生軸突延伸1mm/Day創(chuàng)傷性神經瘤創(chuàng)傷性神經瘤Traumatic neuroma三三 細胞再生與分化的分子機制細胞再生與分化的分子機制 1. 1.干細胞干細胞(stem cell)(stem cell)具有自我更新和分化潛能具有自我更新和分化潛能的未分化細胞的未分化細胞自我更新自我更新(Self-renewal

9、)(Self-renewal)分化潛能分化潛能(Differentiation)(Differentiation)前體細胞前體細胞/ /特化細胞特化細胞precursors/specializprecursors/specialized celled cell細胞再生與分化的分子機制細胞再生與分化的分子機制2.2.細胞外基質細胞外基質(ECM)(ECM) (Extracellular (Extracellular Matrix)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, ,基基質細胞蛋白質細胞蛋白3.3.信號轉導信號轉導(Signal

10、(Signal transduction)transduction)4.4.細胞因子細胞因子/ /生長因子生長因子 (Cytokine/growth (Cytokine/growth factor)factor)Growth factors & cytokinesnPDGF-platelet derived growth factornFGF-fibroblast growth factornEGF-epidermal growth factornTGF-transforming growth factornVEGF-vascular endothelial growth factor

11、nNGF- nerve growth factornHGF-hepatocyte growth factornTNF-tumor necrosis factornIL-1interleukin-1(白細胞介素白細胞介素-1)細胞再生與分化的分子機制細胞再生與分化的分子機制5.5.接觸抑制接觸抑制(contact (contact inhibition)inhibition)6.6.抑素抑素(chalone)(chalone)7.7.基因調控基因調控(gene regulation)(gene regulation) 原癌基因原癌基因(proto-oncogene)(proto-oncogene

12、) 細胞周期基因細胞周期基因(cell division (cell division cycle genes, CDC genes)cycle genes, CDC genes)第二節(jié)第二節(jié) 纖維性修復纖維性修復 (Fibrous (Fibrous repair)repair)P28P28n纖維性修復,瘢痕修復(Scar repair)n再生才干弱或缺乏再生才干的組織；n無原組織的構造及功能n不完全修復(incomplete repair)纖維性修復特點纖維性修復特點Features of fibrous Features of fibrous repair repair 肉芽組織肉芽組織g

13、ranulation tissue)granulation tissue)pink, soft, wet and granular一一 肉芽組織肉芽組織(granulation (granulation tissue)tissue)v由新生的毛細血管、增生的纖維母細胞和各種炎性細胞組成,呈鮮紅色,顆粒狀,柔軟潮濕,形似鮮嫩的肉芽vFibroblasts and new capillaries in a loose extracellular matrix. Granulation tissue: morphologyn新生毛細血管,垂直于創(chuàng)面nRichly capillary sprouts

14、n纖維母,肌纖維母細胞nReactive fibroblasts and myofibroblastsn炎細胞:中性粒,巨噬,淋巴細胞nVariable numbers of inflammatory cells Granulation tissue: functionn抗感染及維護創(chuàng)面；抗感染及維護創(chuàng)面；n填補傷口及組織缺損；填補傷口及組織缺損；n機化或包裹壞死、血栓、炎癥滲機化或包裹壞死、血栓、炎癥滲n 出物及異物出物及異物n 轉化轉化疤痕組織疤痕組織(scar) (scar) 二二 瘢痕組織瘢痕組織scar tissuescar tissuen瘢痕組織是肉芽組織逐漸成熟(纖維化)并老化玻

15、璃樣變的纖維結締組織。n 瘢痕組織形狀(morphology)n毛細血管退化、消逝n纖維母細胞/纖維細胞稀少n炎細胞消逝n膠原纖維大量平行交錯n間質致密玻璃樣變瘢痕組織的作用瘢痕組織的作用(function)n有利有利(advantages)n 填補創(chuàng)傷缺損填補創(chuàng)傷缺損,堅持組織器官完好堅持組織器官完好性性n 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,堅持組織的鞏固性。堅持組織的鞏固性。Complications of Scar -Excessive scar formation n不利不利(disadvantages)(disadvantages)n瘢痕收縮瘢痕收縮(Scar

16、 (Scar contractures):contractures):n 關節(jié)攣縮關節(jié)攣縮 瘢痕粘連瘢痕粘連(Adhesions): (Adhesions): 腸粘連腸粘連器官硬化器官硬化(Sclerosis): (Sclerosis): 肺纖維化肺纖維化 肥大性瘢痕肥大性瘢痕(Hypertrophic (Hypertrophic Scar): Scar): 瘢痕疙瘩瘢痕疙瘩keloid)keloid)蟹足腫蟹足腫(cheloid)(cheloid)v瘢痕體質瘢痕體質v(genetic (genetic predisposition)predisposition)vIIIIII型膠原型膠原(D

17、eposition of Type (Deposition of Type III collagen)III collagen)第四節(jié)第四節(jié) 創(chuàng)創(chuàng) 傷傷 愈愈 合合(Wound healing)P29P29n創(chuàng)傷愈合創(chuàng)傷愈合(wound (wound healing) healing) 是指機是指機體蒙受外力作用，體蒙受外力作用，皮膚等組織出現(xiàn)離皮膚等組織出現(xiàn)離斷或缺損后的愈復斷或缺損后的愈復過程。過程。 一一 創(chuàng)傷愈合的根本過程創(chuàng)傷愈合的根本過程(Basic courses of wound (Basic courses of wound healing)healing)1.1.傷口早期變化

18、傷口早期變化2.2.傷口收縮傷口收縮:2-3d:2-3d3.3.肉芽組織和瘢痕構成肉芽組織和瘢痕構成4.4.表皮等組織再生表皮等組織再生 3d: 3d:肉芽組織肉芽組織5-6d:5-6d:膠原纖維構成膠原纖維構成, , 3-4w:3-4w:瘢痕完全構成瘢痕完全構成1. 一期愈合一期愈合(Healing by first intention)There 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)1一期愈合Healing by first intentio

19、n條件: 組織缺損少,創(chuàng)緣整齊,對合好,無感染，特點: 血凝塊少,炎癥反響輕,表皮再生1-2d,肉芽組織3d,膠原纖維構成5-6d,完全愈合2-3w結局: 線狀瘢痕Summary2.2.二期愈合二期愈合(Healing by second (Healing by second intention)intention)Wound edges cannot Wound edges cannot be apposed, or be apposed, or following wound following wound infection, or infection, or large tissue

20、large tissue defect.defect.More granulation More granulation tissue.tissue.2.二期愈合Healing by second intention條件 組織缺損較大,創(chuàng)緣不整,對合不佳,伴有感染特點壞死組織多,炎癥反響明顯；傷口大,收縮明顯,多量肉芽組織;愈合時間較長,構成的瘢痕較大Summary三三 影響創(chuàng)傷愈合的要素影響創(chuàng)傷愈合的要素 Factors affecting wound healing1.1.全身要素全身要素(Systemic factors)(Systemic factors)(1)(1)年齡年齡(Age)

21、(Age)(2)(2)營養(yǎng)營養(yǎng)(Nutrition) (Nutrition) 蛋白質甲硫、胱蛋白質甲硫、胱 vitC vitC、B B、A A、D, D, 鋅鋅(3)(3)免疫形狀免疫形狀(Immune status) (Immune status) (4)(4)疾病疾病(Chronic diseases)(Chronic diseases)(5)(5)藥物藥物(Corticosteroids etc)(Corticosteroids etc) 影響創(chuàng)傷愈合的要素影響創(chuàng)傷愈合的要素(續(xù)續(xù))2.2.部分要素部分要素(Local (Local factors)factors)Type, size,

22、 and Type, size, and location of the location of the woundwoundInfectionInfectionForeign body Foreign body AppositionAppositionMobilityMobilityBlood supplyBlood supplyPoor wound healing in a patient being treated with corticosteroids.Key factors: 損傷損傷的性質、程度、的性質、程度、組織再生才干、組織再生才干、醫(yī)療處置醫(yī)療處置(清創(chuàng)清創(chuàng),對對合合,抗感

23、染抗感染,生長因生長因子治療子治療)四四 骨折愈合骨折愈合(Fracture healing)n修復過程修復過程: :n 四個階段四個階段外傷性外傷性 病理性病理性n骨折骨折1.1.血腫構成期血腫構成期 (Hematoma (Hematoma formation)formation)1-2d1-2dHematoma & Hematoma & Inflammation Inflammation PDGF, IL, PDGF, IL, TGFTGFn3d-2wn纖維性暫時骨痂纖維性暫時骨痂nGranulation tissue with osteoblasts and matrix

24、 (soft callus) 2. 2. 纖維骨痂構成期纖維骨痂構成期(Fibrous callus (Fibrous callus formation)formation)3.骨性骨痂構成期骨性骨痂構成期(Bony callus formation)3-8w3-8w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(osteoid (osteoid tissue)tissue)編織骨編織骨(woven bone)(woven bone)Deposition of Deposition of Calcium to form Calcium to form hard callus hard c

25、allus 軟骨性骨痂軟骨性骨痂 (cartilage callus)骨性骨痂骨性骨痂 (bony callus)Osteoblasts 4. 4. 骨痂改建期骨痂改建期Bony callus remodelling Bony callus remodelling v8w-monthsv生物應力作用生物應力作用v骨小梁陳列及構造骨小梁陳列及構造v板層骨板層骨vRemodelling removal of excess irregular bone 骨性骨痂改建骨性骨痂改建(Bony callus remodelling )Summary: Healing in Bone 1D - Hematoma formation & Inflammation 1W - Soft callus granulation, osteoid tissue 3W Hard Callus ossification, woven bone 8W - Re-modeling absorb/deposit, lam