损伤的修复ppt课件(1)

1、损伤的修复损伤的修复Tissue Repair 病理学系病理学系李李 学学 农农 (Prof. MD, PhD) (Prof. MD, PhD)nfydlxn126nfydlxn126P23P23损伤损伤(injury)(injury)缺损缺损(defect)(defect)修复修复(repair)(repair)修复修复(repair)n机体对损伤所构成缺损进展修补恢复的过程。nRepair is a response to tissue injury and the process to restore integrity to an injured tissue by the organ

2、ism. 修复方式修复方式(Types of repair)(Types of repair)1.1.再生再生(regeneration):(regeneration): 同种组织完全再生同种组织完全再生 Repair by same Repair by same tissuetissue2.2.纤维性修复纤维性修复(fibrous (fibrous repair) repair) 纤维结缔组织修复纤维结缔组织修复 Replacement by Replacement by fibrous tissuefibrous tissue第一节第一节 再生性修复再生性修复Regenerationn定义

3、定义: :由损伤部周围由损伤部周围的同种细胞来修复，的同种细胞来修复，称为再生称为再生(regeneration)(regeneration)nRepair by cells Repair by cells of same typeof same typen特点特点: :完全恢复原组完全恢复原组织的构造及功能织的构造及功能 一一 组织的再生才干组织的再生才干 (Regenerative potentials of tissues)n低等动物低等动物 高等动物高等动物n分化低分化低 分化高分化高n易受损伤和常更新组织再生才干强易受损伤和常更新组织再生才干强n取决于动物的种类和组织分化才干取决于动

4、物的种类和组织分化才干n生物进化生物进化(evolution)(evolution)细胞再生才干分类细胞再生才干分类(Types)n1.1.不稳定细胞不稳定细胞(labile cells) (labile cells) 强再生才强再生才干干; ; 表皮表皮, ,粘膜上皮粘膜上皮, ,间皮间皮, ,淋巴及造血细胞淋巴及造血细胞n2.2.稳定细胞稳定细胞(stable cells) (stable cells) 较强再生才较强再生才干干, , 肝肝, ,胰胰, ,肾肾, ,腺体腺体, ,平滑肌平滑肌, ,原始间叶细胞原始间叶细胞及其分化细胞及其分化细胞( (纤维母纤维母, ,软骨软骨, ,骨母骨母

5、) )n3.3.永久性细胞永久性细胞(permanent cells) (permanent cells) 微弱或微弱或无再生才干无再生才干; ; 神经元神经元, ,骨骼肌骨骼肌, ,心肌细胞心肌细胞 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 组织的再生过程组织的再生

6、过程(Regeneration of various (Regeneration of various tissues)tissues)1被覆上皮 (lining epithelium) 基内幕胞分裂增生2 2腺上皮腺上皮 (glandular (glandular epithelium)epithelium) BM BM未破坏未破坏完全再完全再生生 BM BM破坏破坏不完全再生不完全再生Regeneration of various tissues3.纤维结缔组织 (fibrous connective tissue) 未分化间叶细胞 纤维母细胞(fibroblast) 分泌原胶原蛋白 胶原

7、纤维(collagen) 纤维细胞(fibrocyte)Regeneration of various tissues4.血管(blood vessel)小血管及毛细血管 内皮出芽-实性条索血流冲击-构成管腔大血管 内皮:完全再生 肌层:疤痕修复Regeneration of various tissues5.肌组织(muscular tissue)(1)骨骼肌(skeletal muscle)肌膜存在-完全修复肌膜破坏-瘢痕修复 肌卫星细胞增生分化(2)平滑肌(smooth muscle) 再生或纤维修复(3)心肌(myocardium) 纤维修复Regeneration of variou

8、s tissues6.神经组织 (nervous tissue)(1)脑及脊髓神经细胞(nerve cell) 胶质瘢痕 (glial scar) 可再生！6.神经组织(nervous tissue)(2)外周神经(peripheral nerve)可完全再生髓鞘及轴突崩解神经鞘细胞增生轴突延伸1mm/Day创伤性神经瘤创伤性神经瘤Traumatic neuroma三三 细胞再生与分化的分子机制细胞再生与分化的分子机制 1. 1.干细胞干细胞(stem cell)(stem cell)具有自我更新和分化潜能具有自我更新和分化潜能的未分化细胞的未分化细胞自我更新自我更新(Self-renewal

9、)(Self-renewal)分化潜能分化潜能(Differentiation)(Differentiation)前体细胞前体细胞/ /特化细胞特化细胞precursors/specializprecursors/specialized celled cell细胞再生与分化的分子机制细胞再生与分化的分子机制2.2.细胞外基质细胞外基质(ECM)(ECM) (Extracellular (Extracellular Matrix)Matrix) 胶原纤维胶原纤维, ,弹力纤维弹力纤维, ,粘附蛋白粘附蛋白, ,蛋白多糖蛋白多糖, ,基基质细胞蛋白质细胞蛋白3.3.信号转导信号转导(Signal

10、(Signal transduction)transduction)4.4.细胞因子细胞因子/ /生长因子生长因子 (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(白细胞介素白细胞介素-1)细胞再生与分化的分子机制细胞再生与分化的分子机制5.5.接触抑制接触抑制(contact (contact inhibition)inhibition)6.6.抑素抑素(chalone)(chalone)7.7.基因调控基因调控(gene regulation)(gene regulation) 原癌基因原癌基因(proto-oncogene)(proto-oncogene

12、) 细胞周期基因细胞周期基因(cell division (cell division cycle genes, CDC genes)cycle genes, CDC genes)第二节第二节 纤维性修复纤维性修复 (Fibrous (Fibrous repair)repair)P28P28n纤维性修复,瘢痕修复(Scar repair)n再生才干弱或缺乏再生才干的组织；n无原组织的构造及功能n不完全修复(incomplete repair)纤维性修复特点纤维性修复特点Features of fibrous Features of fibrous repair repair 肉芽组织肉芽组织g

13、ranulation tissue)granulation tissue)pink, soft, wet and granular一一 肉芽组织肉芽组织(granulation (granulation tissue)tissue)v由新生的毛细血管、增生的纤维母细胞和各种炎性细胞组成,呈鲜红色,颗粒状,柔软潮湿,形似鲜嫩的肉芽vFibroblasts and new capillaries in a loose extracellular matrix. Granulation tissue: morphologyn新生毛细血管,垂直于创面nRichly capillary sprouts

14、n纤维母,肌纤维母细胞nReactive fibroblasts and myofibroblastsn炎细胞:中性粒,巨噬,淋巴细胞nVariable numbers of inflammatory cells Granulation tissue: functionn抗感染及维护创面；抗感染及维护创面；n填补伤口及组织缺损；填补伤口及组织缺损；n机化或包裹坏死、血栓、炎症渗机化或包裹坏死、血栓、炎症渗n 出物及异物出物及异物n 转化转化疤痕组织疤痕组织(scar) (scar) 二二 瘢痕组织瘢痕组织scar tissuescar tissuen瘢痕组织是肉芽组织逐渐成熟(纤维化)并老化玻

15、璃样变的纤维结缔组织。n 瘢痕组织形状(morphology)n毛细血管退化、消逝n纤维母细胞/纤维细胞稀少n炎细胞消逝n胶原纤维大量平行交错n间质致密玻璃样变瘢痕组织的作用瘢痕组织的作用(function)n有利有利(advantages)n 填补创伤缺损填补创伤缺损,坚持组织器官完好坚持组织器官完好性性n 瘢痕中胶原纤维具有一定抗拉力瘢痕中胶原纤维具有一定抗拉力,坚持组织的巩固性。坚持组织的巩固性。Complications of Scar -Excessive scar formation n不利不利(disadvantages)(disadvantages)n瘢痕收缩瘢痕收缩(Scar

16、 (Scar contractures):contractures):n 关节挛缩关节挛缩 瘢痕粘连瘢痕粘连(Adhesions): (Adhesions): 肠粘连肠粘连器官硬化器官硬化(Sclerosis): (Sclerosis): 肺纤维化肺纤维化 肥大性瘢痕肥大性瘢痕(Hypertrophic (Hypertrophic Scar): Scar): 瘢痕疙瘩瘢痕疙瘩keloid)keloid)蟹足肿蟹足肿(cheloid)(cheloid)v瘢痕体质瘢痕体质v(genetic (genetic predisposition)predisposition)vIIIIII型胶原型胶原(D

17、eposition of Type (Deposition of Type III collagen)III collagen)第四节第四节 创创 伤伤 愈愈 合合(Wound healing)P29P29n创伤愈合创伤愈合(wound (wound healing) healing) 是指机是指机体蒙受外力作用，体蒙受外力作用，皮肤等组织出现离皮肤等组织出现离断或缺损后的愈复断或缺损后的愈复过程。过程。 一一 创伤愈合的根本过程创伤愈合的根本过程(Basic courses of wound (Basic courses of wound healing)healing)1.1.伤口早期变化

18、伤口早期变化2.2.伤口收缩伤口收缩:2-3d:2-3d3.3.肉芽组织和瘢痕构成肉芽组织和瘢痕构成4.4.表皮等组织再生表皮等组织再生 3d: 3d:肉芽组织肉芽组织5-6d:5-6d:胶原纤维构成胶原纤维构成, , 3-4w:3-4w:瘢痕完全构成瘢痕完全构成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 创伤愈合的类型创伤愈合的类型(Types)1一期愈合Healing by first intentio

19、n条件: 组织缺损少,创缘整齐,对合好,无感染，特点: 血凝块少,炎症反响轻,表皮再生1-2d,肉芽组织3d,胶原纤维构成5-6d,完全愈合2-3w结局: 线状瘢痕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条件 组织缺损较大,创缘不整,对合不佳,伴有感染特点坏死组织多,炎症反响明显；伤口大,收缩明显,多量肉芽组织;愈合时间较长,构成的瘢痕较大Summary三三 影响创伤愈合的要素影响创伤愈合的要素 Factors affecting wound healing1.1.全身要素全身要素(Systemic factors)(Systemic factors)(1)(1)年龄年龄(Age)

21、(Age)(2)(2)营养营养(Nutrition) (Nutrition) 蛋白质甲硫、胱蛋白质甲硫、胱 vitC vitC、B B、A A、D, D, 锌锌(3)(3)免疫形状免疫形状(Immune status) (Immune status) (4)(4)疾病疾病(Chronic diseases)(Chronic diseases)(5)(5)药物药物(Corticosteroids etc)(Corticosteroids etc) 影响创伤愈合的要素影响创伤愈合的要素(续续)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: 损伤损伤的性质、程度、的性质、程度、组织再生才干、组织再生才干、医疗处置医疗处置(清创清创,对对合合,抗感

23、染抗感染,生长因生长因子治疗子治疗)四四 骨折愈合骨折愈合(Fracture healing)n修复过程修复过程: :n 四个阶段四个阶段外伤性外伤性 病理性病理性n骨折骨折1.1.血肿构成期血肿构成期 (Hematoma (Hematoma formation)formation)1-2d1-2dHematoma & Hematoma & Inflammation Inflammation PDGF, IL, PDGF, IL, TGFTGFn3d-2wn纤维性暂时骨痂纤维性暂时骨痂nGranulation tissue with osteoblasts and matrix

24、 (soft callus) 2. 2. 纤维骨痂构成期纤维骨痂构成期(Fibrous callus (Fibrous callus formation)formation)3.骨性骨痂构成期骨性骨痂构成期(Bony callus formation)3-8w3-8w骨性骨痂骨性骨痂软骨性骨痂软骨性骨痂骨样组织骨样组织(osteoid (osteoid tissue)tissue)编织骨编织骨(woven bone)(woven bone)Deposition of Deposition of Calcium to form Calcium to form hard callus hard c

25、allus 软骨性骨痂软骨性骨痂 (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生物应力作用生物应力作用v骨小梁陈列及构造骨小梁陈列及构造v板层骨板层骨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