损伤的修复_

第二章 损伤的修复(Tissues Repair),P27,病理学系李 学 农 (Prof. MD, PhD),损伤(injury)缺损(defect)修复(repair),修复(repair),机体对损伤所形成缺损进行修补恢复的过程。Repair is a response to tissue injury and the process to restore integrity to an injured tissue by the organism.,问题与启迪(questions),什么是瘢痕？瘢痕是怎样形成的？能不能不形成瘢痕？瘢痕形成有正面意义吗？能否加速伤口愈合？伤口愈合不佳的原因 有哪些？,修复形式(Types of repair),1.再生(regeneration): 同种组织完全再生 Repair by same tissue2.纤维性修复(fibrous repair) 纤维结缔组织修复 Replacement by fibrous tissue,第一节 再生（Regeneration）,P27,定义:由损伤部周围的同种细胞来修复，称为再生(regeneration)Repair by cells of same type特点:完全恢复原组织的结构及功能,Whats regeneration?,一 组织的再生能力 (Regenerative potentials of tissues),低等动物 高等动物分化低 分化高易受损伤和常更新组织再生能力强取决于动物的种类和组织分化能力生物进化(evolution),一 细胞再生能力分类(Types),1.不稳定细胞(labile cells) 强再生能力;表皮,粘膜上皮,间皮,淋巴及造血细胞Continuously dividing and dyingCovering epithelia Hematopoietic cells(the bone marrow cells and the lymphoid cells),2.稳定细胞(stable cells),较强再生能力, 肝,胰,肾,腺体,平滑肌,原始间叶细胞及其分化细胞(纤维母,软骨,骨母)Quiescent but can rapidly divide in response to injuryParenchymal of solid glandular tissues: liver, kidney, pancreas, glandEndothelial cellsConnective tissue (fibroblast, osteoblasts) Smooth muscle,3.永久性细胞(permanent cells),微弱或无再生能力; 神经元,骨骼肌,心肌细胞 Be terminally differentiated and nonproliferative after the growth early in lifeNerve cells(neuron), striated and cardiac muscle cells,1. Labile cells: continuously dividing cells,2. Stable cells: quiescent cells that divide only when needed,3. Permanent cells: nondividing cells that permanently removed from cell cycle,小结(Summary):细胞再生力分类,二 组织的再生过程(Regeneration of various tissues),1被覆上皮 (covering epithelia) 基底细胞分裂增生,2腺上皮 (glandular epithelia) BM未破坏完全再生 BM破坏不完全再生 (reticulin scaffold ),Regeneration of various tissues,3.血管(blood vessel)小血管及毛细血管 内皮出芽(sprout) -实性条索 血流冲击-形成管腔(canalization)大血管 内皮(endothelial cells )-完全再生 肌层(smooth muscles):-疤痕修复,Regeneration of various tissues,4.神经组织 (nervous tissue)(1)脑及脊髓神经细胞(nerve cell) 胶质瘢痕 (glial scar) 新知识点：可再生！,4.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长1mm/Day,创伤性神经瘤,Traumatic neuroma,三 细胞再生的分子机制,1.干细胞(stem cell)具有自我更新和分化潜能的未分化细胞自我更新(Self-renewal)分化潜能(Differentiation)不对称复制(asymmetric replication)前体细胞/特化细胞precursors/specialized cell,新概念: 再生医学,Regenerative Medicine 胚胎干细胞(Embryonic stem cells, ESC) : pluripotent cells Therapeutic cloning,成体干细胞(Adult Stem cells, ASC) :More restricted differentiation capacity Bone Marrow Haematopoietic stem cells,新概念: 再生医学,新概念: 再生医学,诱导性多能干细胞（iPSC）(induced pluripotent stem cells) :已分化成体细胞的重新编程,细胞再生与分化的分子机制,2.细胞外基质(ECM) (Extracellular Matrix) 胶原纤维,弹力纤维, 粘附蛋白,蛋白多糖,3.信号转导(Signal transduction)4.细胞因子/生长因子 (Cytokine/growth factor),Growth factors & cytokines,PDGF-platelet derived growth factorFGF-fibroblast growth factorEGF-epidermal growth factorTGF-transforming growth factorVEGF-vascular endothelial growth factorNGF- nerve growth factorHGF-hepatocyte growth factorTNF-tumor necrosis factorIL-1interleukin-1(白细胞介素-1),细胞再生与分化的分子机制,5.接触抑制(contact inhibition)6.抑素(chalone)7.基因调控(gene regulation) 原癌基因(proto-oncogene) 细胞周期基因(cell division cycle genes, CDC genes),第二节 纤维性修复 (Fibrous repair),P36,纤维性修复,瘢痕修复(Scar repair)再生能力弱或缺乏再生能力的组织(less regeneration capacity)；无原组织的结构及功能不完全修复(incomplete repair),纤维性修复特点Features of fibrous repair,肉芽组织（granulation tissue),pink, soft, wet and granular,一 肉芽组织(granulation tissue),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,柔软湿润,形似鲜嫩的肉芽Fibroblasts and new capillaries in a loose extracellular matrix.,Granulation tissue: morphology,新生毛细血管,垂直于创面Richly capillary sprouts 纤维母,肌纤维母细胞Reactive fibroblasts and myofibroblasts炎细胞:中性粒,巨噬,淋巴细胞Variable numbers of inflammatory cells,Granulation tissue: function,抗感染及保护创面 Anti-infection and protect the wound surface填补伤口及组织缺损 To make up the deficiency and repair the injured tissue机化或包裹坏死、血栓、炎症渗出物及异物 To organize blood clotting, necrotic tissues or abnormal substances 转化 疤痕组织(scar),二 瘢痕组织(scar tissue),瘢痕组织是肉芽组织逐渐成熟(纤维化)并老化（玻璃样变）的纤维结缔组织。Fibrosis/maturation and retrogradation of granulation tissuePale-gray, hard, lack of elasticity, tissue shrinkage,瘢痕组织形态(morphology),毛细血管退化消失(blood capillary)纤维母细胞/纤维细胞稀少(fibroblasts)炎细胞消失(inflammatory cells)胶原纤维大量平行交错 (collagen synthesis)间质致密玻璃样变(hyaline change),瘢痕组织的作用(function),有利(advantages) 填补创伤缺损,保持组织器官完整性 Integrity: fill the defect and repair the tissue 瘢痕中胶原纤维具有一定抗拉力,保持组织的坚固性。 Firmness: more tensile strength,Complications of Scar -Excessive scar formation,不利(disadvantages)瘢痕收缩(Scar contractures): 关节挛缩 (joint contracture),瘢痕粘连(Adhesions): 肠粘连,器官硬化(Sclerosis): 肺纤维化,Complications of Scar,肥大性瘢痕(Hypertrophic Scar):,瘢痕疙瘩（keloid)蟹足肿(cheloid),瘢痕体质(genetic predisposition)III型胶原(Deposition of Type III collagen),Complications of Scar,第三节 创 伤 愈 合(Wound healing),P40,创伤愈合(wound healing) 是指机体遭受外力作用，皮肤等组织出现离断或缺损后的愈复过程。A complex but orderly process, involving both parenchymal cells regeneration and the formation of connective tissue scar.,Whats wound healing?,一 创伤愈合的基本过程(Basic process of wound healing),1.伤口早期变化(exudate)2.伤口收缩(contraction of the wound):2-3d3.肉芽组织和瘢痕形成(granulation & mature)4.表皮等组织再生(regeneration),3d:肉芽组织5-6d:胶原纤维形成 3-4w:瘢痕完全形成,1. 一期愈合(Healing by first intention)There is a clean wound with well-apposed edges, and minimal clot formation.,二 创伤愈合的类型(Types),1一期愈合（Healing by first intention）条件: 组织缺损少,创缘整齐,对合好,无感染(regular defects, uninfected, clean, well-apposed edges)，特点: 血凝块少,炎症反应轻,表皮再生1-2d,肉芽组织3d,胶原纤维形成5-6d,完全愈合2-3w (mild inflammation reaction)结局: 线状瘢痕(linear scar),小结：Summary,2.二期愈合(Healing by second intention)Wound edges cannot be apposed, or following wound infection, or large tissue defect.More granulation 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(large irregular tissue defect/infection)特点坏死组织多,炎症反应明显(more necrosis, extensive inflammation, more granulation )伤口大,收缩明显,多量肉芽组织(contraction)愈合时间较长,形成的瘢痕较大(larger scar),小结：Summary,三 影响创伤愈合的因素 Factors affecting wound healing,1.全身因素(Systemic factors)(1)年龄(Age)(2)营养(Nutrition) 蛋白质（甲硫、胱） vitC、B、A、D, 锌(3)免疫状态(Immune status) (4)疾病(Chronic diseases)(5)药物(Corticosteroids etc),影响创伤愈合的因素(续),2.局部因素(Local factors)Type, size, and location of the woundInfectionForeign body AppositionMobilityBlood supply,Poor wound healing in a patient being treated with corticosteroids.,Key factors: 损伤的性质、程度、组织再生能力、医疗处理(清创,对合,抗感染,生长因子治疗),影响创伤愈合的因素(续),四 骨折愈合(Fracture healing),修复过程: 四个阶段(Four repair process),外伤性(Traumatic) 病理性(Pathologic),骨折,1.血肿形成期 (Hematoma formation) 1-2d Hematoma: inflammation, PDGF, IL, TGF,3d-2w纤维性暂时骨痂Soft callus: granulation tissue with osteoblasts and matrix,2. 纤维骨痂形成期(Fibrous callus formation),3. 骨性骨痂形成期(Bony callus formation),3-8w骨性骨痂(bony callus)软骨骨痂(cartilage callus)骨样组织(osteoid tissue)编织骨(woven bone)Hard callus: deposition of calcium,软骨性骨痂 (cartilage callus),Osteoblasts,骨性骨痂 (bony callus),4.骨痂改建期Bony remodelling,8w-months生物应力作用骨小梁排列及结构板层骨(lamellar bone)重塑(Remodelling): removal of excess irregular bone,骨性骨痂改建(Bony callus remodelling ),影响骨折愈合因素,骨愈合畸形及时正确复位Proper reduction 及时牢固固定Immobilization 适时功能锻炼Functional exercise,小 结(Summary),修复,再生(regeneration)纤维性修复(Fibrous repair),再生力分类,不稳定细胞(labile cells)稳定细胞(stable cells)永久性细胞(permanent cells),肉芽组织(granulation)瘢痕组织(scar tissue),新生毛细血管(capillary)纤维母细胞(fibroblast)多量炎细胞(inflammatory cells),小 结(Summary),一期 二期组织破坏 少 大 创缘 齐 不齐感染 无 有伤口对合 好 差愈合时间 一周内 长瘢痕 少 多 功能影响 很小 较大,创 伤 愈 合,骨折愈合过程,骨性肉芽,毛细血管,纤维母细胞,骨母细胞软骨母细胞,纤维性骨痂,骨性骨痂,血肿形成,骨痂改建,+钙盐,骨性骨痂 软骨性骨痂,骨样组织,编织骨,板层骨,形成性练习,granulation tissue,Keloid