由损伤周围的同种细胞来修复Aprocessthatthenecrotic课件

Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Logo,*,Click to edit Master title style,白求恩医学院病理教研室,李 伟,Repair,of the injury,损伤的修复,2010.9.26,tissue and cellular injury,cellular injury,reversible,:,irreversible,:,Necrosis apoptosis,Adaptation,atrophy,hypertrophy,hyperplasia,metaplasia,Normal cells,irreversible,injury,reversible,injury,Adaptation,Logo,损伤,(,injury),缺损,(,defect),修复,(,repair),损伤的修复,R,epair,of the injury,Logo,修复,(repair),：损伤造成机体部分细胞和组织丧失后，机体对所形成缺损进行修补恢复的过程，,修复后可完全或部分恢复原组织的结构和功能。,Repair,is the process by which necrotic cells are replaced by viable (living) cells (regeneration) or by scar formation. The,structure and function of the tissue can be recovered by repair.,R,epair,of the injury,再生,Regeneration,纤维性修复,Repair by Scar formation,由损伤周围的,同种细胞来修复,由纤维结缔组织来修复,-,瘢痕修复,再生,Regeneration,再生,Regeneration,Logo,再生,(,Regeneration,),：由损伤周围的同种细胞来修复,A process that the necrotic,parenchymal,cells were replaced by new,parenchymal,cells of the same type,The new cells complement aging cells. Maintain the normal structure and function,The regeneration occurs after cellular and tissue defect.,R,epair,of the injury,physiologic,pathologic,Logo,Labile cells,Stable cells,Permanent cells,Cell types-Base on regenerative capacity,R,epair,of the injury,-,regeneration,Cell,cycleis defined as the period between two successive cell divisions. It is divided into 4 unequal phases.,Logo,The regenerative capacity types of cells-1,不稳定细胞,Labile cells,1,They are,continuously dividing cells.,They multiply,throughout life under normal physiologic conditions,The chances of restoration by regeneration are,excellent.,Including,: surface,epithelial cells,of epidermis,digestive, respiratory, and urinary,tracts, uterine,endometrium,haematopoietic,cells,of,bone marrow,and,cells of lymph nodes and spleen,再生,(Regeneration),R,epair,of the injury,Logo,They are,in the resting phase (G,0,),but can be stimulated to enter the cell cycle. They,retain the capacity to multiply,in response to stimuli.,Chances of,regeneration remain,Including:,parenchymal,cells of organs like,liver, pancreas,，,kidneys, adrenal and thyroid;,mesenchymal,cells like, fibroblasts and endothelium.,The regenerative capacity types of cells-2,R,epair,of the injury,稳定细胞,Stable cells (,quiescent cells),2,再生,(Regeneration),Logo,They are,non-dividing cells,which have left the cell cycle and die after injury.,Including:,neurons, skeletal muscle and cardiac muscle cells,The,peripheral nerve,has retained the capacity for,regeneration,with damage.,The regenerative capacity types of cells-3,R,epair,of the injury,永久性细胞,Permanent cells,3,再生,(Regeneration),Logo,组织的再生过程,Regenerative process of tissues,Logo,Regenerative process of tissues,The regeneration process depends on,R,epair,of the injury,1.,the regenerative ability of the cells,2.,the intact of tissues framework,Logo,Regeneration of Epithelial Tissues,It may regenerate completely if the basement,membran,is intact.,R,epair,of the injury,Original cells proliferate from the margin of injury,Migrate to cover the gap,Differentiation and maturation to reconstitute the original tissue,Covering epithelia,1,Logo,Regeneration of gastric,epithelium mucosa,in peptic ulcer,Glandular epithelial cells regeneration,mucosal surface,2,R,epair,of the injury,Logo,Partial resection-,restoration quickly and completely,Extensive necrosis with intact,stromal,network,-,restore the normal structure,Extensive necrosis accompanied by,stromal,tissues,network destroy-,hard to restore,Regeneration of Epithelial Tissues,R,epair,of the injury,Glandular epithelial cells regenerationliver,2,Logo,R,epair,of the injury,Glandular epithelial cells regenerationliver,2,Logo,Spotty necrosis-,-,The,hepatocyte,necrosis limited to scattered cells within hepatic lobules.,R,epair,of the injury,Glandular epithelial cells regenerationliver,2,Logo,Submassive,necrosis -,The,hepatocyte,necrosis,is extensive with,tissues framework destroy,R,epair,of the injury,Glandular epithelial cells regenerationliver,2,Logo,Glandular epithelial cells regenerationliver,2,R,epair,of the injury,normal,Morphology of portal cirrhosis,Logo,Regeneration of Connective tissue,Fibrocytes,(Primitive cells),Fibroblasts,Fibrocytes,Secretion of,Tropocollagen,condensation to form Collagen,fibres,Bonding and weaving,Scar tissue,R,epair,of the injury,Logo,Proliferation of Blood Vessels,-,Angiogenesis,Budding-,R,epair,of the injury,Basement membrane dissolution,Endothelial cells proliferation and migration,Vascular channels forming,Rebuilding to form arterioles, thin-walled,venules,Logo,Proliferation of Blood Vessels,-,Angiogenesis,R,epair,of the injury,Logo,Regeneration of muscular tissues,横纹肌的再生依肌膜是否存在及肌纤维是否完全断裂而有所不同,心肌再生能力极弱，破坏后一般都是瘢痕修复,平滑肌具有一定的分裂再生能力,R,epair,of the injury,Logo,正常神经纤维,神经纤维断离，远端髓鞘及轴突崩解,神经膜细胞增,生，轴突生长,神经轴突达末梢，多余部分消失,Regeneration,of nerve tissue,R,epair,of the injury,Logo,Regeneration,of nerve tissue,R,epair,of the injury,Logo,Regeneration,of nerve tissue,R,epair,of the injury,若断离的两端相隔太远，或者两端之间有瘢痕或其它组织阻隔，或者因截肢失去远端，再生轴突均不能到达远端，而与增生的结缔组织混杂在一起，卷曲成团，成为,创伤性神经瘤,，可发生顽固性疼痛。,Logo,Influential factor on cell regeneration,Cellular injury,regeneration,Cell proliferation,intra-cellular environment,extracellular environment,ECM,growth factor,Inhibin,and contact inhibition,Logo,Stem cells,Embryonic,stem,cells(ESC,),Adult stem cells,胚胎干细胞：,指起源于着床前胚胎内细胞群的,全能干细胞,，具有向三个胚层分化的能力，可以分化为成体所有类型的成熟细胞,成体干细胞：存在于胚胎、胎儿和成体,组织内的特异性干细胞，具有自我更新和一定分化潜能,干细胞：,是个体发,育过程中产生的具,有无限或较长时间,自我更新,和,多向分,化能力,的一类细胞,R,epair,of the injury,Stem cells in tissue and cellular regeneration,Logo,Self-renewal and differentiation of stem cells,R,epair,of the injury,Stem cells in tissue and cellular regeneration,横向分化,（,trans-differentiation),部分组织中的成体干细胞不仅可以向本身组织进行分化，也可以向无关组织类型的成熟细胞进行分化。,Logo,R,epair,of the injury,Stem cells in tissue and cellular regeneration,The multiple differentiation ability of,mesenchymal,stem cells (MSC),Logo,Dancing of life,Death is just a part of life, something were all destined to do.,Life was like a box of chocolates, you never know what youre,gonna,get.,Miracles happen every day.,There is one small step for a man, a giant leap for mankind.,-Forrest Gump,Logo,患者男，,37,岁，以,“,规律性上腹痛二年，加重一周,”,为主诉入院。查体：上腹部剑突下偏左有压痛。胃镜检查提示,“,胃窦部溃疡,”,。经给予甲氰咪胍等制酸剂和氢氧化铝凝胶等胃粘膜保护剂治疗，症状逐渐缓解，,6,周后复查胃镜见溃疡已愈合。,病例讨论,讨论：,在胃溃疡愈合过程中包含哪些类型的修复？,Logo,第三节 纤维性修复,Section 3,Fibrous repair,肉芽组织,（,Granulation tissue,）,瘢痕组织,（,scar,）,Logo,by removal of the inflammatory exudates,Liquefied material is removed by lymphatic,Any particulate residue is removed by macrophage,phagocytosis,.,several overlapping phases for Scar Formation,Preparation,R,epair,of the injury,The area of injury is prepared for scar formation:,Logo,Granulation tissue,肉芽组织,由新生薄壁的,毛细血管,以及增生的,纤维母细胞,构成，并伴有,炎性细胞浸润,，肉眼表现为,鲜红色颗粒状,，柔软湿润，形似鲜嫩的肉芽故而得名。,Granulation tissue,is highly,vascularized,connective tissue composed of newly formed capillaries, proliferating fibroblasts, and residual inflammatory cells,R,epair,of the injury,Logo,Gross : pink, soft, moist, and granular appearance,Granulation tissue,R,epair,of the injury,粉色,颗粒状,柔软,湿润,触之易出血,Logo,LM: fibroblasts, new capillaries, inflammatory cells,Granulation tissue,R,epair,of the injury,Logo,Granulation tissue,R,epair,of the injury,Logo,Granulation tissue,R,epair,of the injury,Logo,Granulation tissue,（,low power,）,Granulation tissue,（,high power,）,R,epair,of the injury,Logo,Granulation tissue,Granulation tissue,R,epair,of the injury,Logo,Consequences of granulation tissue,Granulation tissue,fibroblasts,New capillaries,Inflammatory cells,collagen,fibres,vascularity,diminishing,gradually,fibrocytes,Bonding and weaving,disappear,disappear,Scar tissue,water,absorption,disappear,R,epair,of the injury,Logo,Function of granulation tissue,anti-infection and protecting the surface of wound,抗感染保护创面,filling wound or tissue defect,填补创口及其它组织缺损,organization or encapsulation: granulation tissue replace necrotic tissue, blood clot, and foreign bodies,机化，包裹,R,epair,of the injury,Logo,Morphology and function of scar,R,epair,of the injury,瘢痕（,Scar),：肉芽组织经改建成熟形成的纤维结缔组织,Logo,Influence of the scar,R,epair,of the injury,Ad,vantage,：,Fill in the wound keep integrity,Strengthening the tissue,Di,sadvantage,：,scar contraction,scar adhesion,keloid,formation,organ cirrhosis,Logo,瘢痕组织,右手烫伤后瘢痕组织形成，质地较硬、缺乏弹性，因为玻璃样变，导致瘢痕收缩，使皮肤发生皱褶。,Influence of the scar,R,epair,of the injury,Logo,瘢痕组织,瘢痕收缩导致关节痉挛,Influence of the scar,R,epair,of the injury,Logo,scar of renal infarct,Morphology and function of scar,R,epair,of the injury,Logo,Influence of the scar,R,epair,of the injury,scar adhesion,organ cirrhosis,Logo,Keloid,瘢痕疙瘩,（蟹足肿）,Influence of the scar,R,epair,of the injury,Logo,The,mechanism,of granulation tissue and scar formation,Fibrosis,Tissue remodeling,Matrix Metalloproteinase (,MMPs,),Neovascularization,:,vasculogenesis,angiogenesis,Growth factors and their receptors,Extracellular matrix,The repair and regeneration of injured tissues are not only dependent on the,regenerative abilities of surviving cells, but also on many,other factors, e.g. cytokines, Growth factors, Extracellular Matrix (ECM),R,epair,of the injury,Logo,第四节 创伤愈合,Section 4,Wound healing,机体遭受外力作用，皮肤等组织出现离断或缺损后的愈合过程。,Regeneration,Repair,Logo,表皮及其它组织再生,R,epair,of the injury,Clinical Stages in,skin Wound,Healing,Hemorrhage,and acute inflammation,Contraction of the wound edges,Formation of granulation tissue,Regeneration of epidermal cells and other tissue,早期变化：出血、坏死和炎症反应，红肿，痂皮,伤口边缘收缩（,2-3,天）：肌成纤维细胞牵拉,创缘整层皮肤及皮下组织向中心移动,肉芽组织增生（第,3,天）和瘢痕形成,Logo,Clinical types of wound healing,Complete repair of the wound without a scar,Complete replacement of necrotic epithelium and connective tissue,R,epair,of the injury,Healing by first intention,一期愈合,Clean and uninfected,Surgically incised,Without much loss of cells and tissues,Edges of wound are approximated by surgical sutures,Occurs if:,Logo,一期愈合,（,Healing by first intention,）,Clinical types of wound healing,R,epair,of the injury,Logo,Clinical types of wound healing,R,epair,of the injury,Healing by,second,intention,二期愈合,Open with a large tissue defect,The wound is not approximated by surgical sutures but is left open,With infection,Occurs if:,Tissue does not have a normal structure after repair. Usually replaced by scar tissue,Logo,二期愈合（,Healing by secondary intention,）,Clinical types of wound healing,R,epair,of the injury,Logo,二期愈合与一期愈合的不同点,变性坏死严重，炎症反应明显,伤口大，收缩明显，肉芽组织多,愈合时间长，瘢痕大,Logo,病例讨论,王,，男，,12,岁，因,“,车祸左小腿疼痛活动受限,2,小时,“,入院。患者,2,小时前被车撞倒在地，当时左小腿弯曲、疼痛，不能活动。入院检查：体温,37,脉搏,100,次,/,分，血压,90/60mmHg,，左小腿肿胀，短缩，局部有压痛，可触及骨擦感，左小腿不能活动。,B,超：腹内脏器未见异常。,实验室检查：血常规、尿常规均正常,.,Logo,X,线检查：,左胫骨中下段,1/3,斜形完全性骨折，左腓骨上,1/3,骨折,Logo,临床处理：术后,X,线报告对位、对线尚可。术后一周再次复查，结果同前。一月后复查，对位、对线良好，见少量骨痂形成。牵引一月后改为石膏固定二月。术后三月复查：,骨性骨痂形成,Logo,讨论：,1.,该骨折愈合属于哪种类型的修复,?,2.,骨折愈合的基本过程如何？,3.,哪些因素可影响骨折的愈合？,Logo,Process of f,racture,r,epair,（骨折愈合）,1.,Hematoma,血肿形成,2.,Provisional Callus,纤维性骨痂,透明软骨,3.,Bony Callus,骨性骨痂,4.,Bony Remodeling,骨痂改建或再塑,肉芽组织,纤维化,骨母细胞,类骨组织,编织骨,R,epair,of the injury,Logo,HEALING OF A CLOSED FRACTURE (,Histologic,Features,Hours,After the Fracture),Features,Histology,Hemorrhage and inflammation,血肿和炎症,R,epair,of the injury,Logo,HEALING OF A CLOSED FRACTURE(,Histologic,Features,Days,After the Fracture),Organization and proliferation of,periosteal,cells,纤维性骨痂,Features,Histology,R,epair,of the injury,Logo,HEALING OF A CLOSED FRACTURE(,Histologic,Features,Weeks,After the Fracture),Formation of cartilage and immature bone,骨性骨痂,Features,Histology,R,epair,of the injury,Logo,HEALING OF A CLOSED FRACTURE(,Histologic,Features,Months,After the Fracture),Conversion to lamellar bone (remodeling),骨痂改建和重塑,Features,Histology,R,epair,of the injury,Logo,R,epair,of the injury,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,Logo,伤口类型,感染与异物,局部血液供应,伤口边缘对合,神经支配,电离辐射,R,epair,of the injury,年龄,营养,影响创伤愈合的因素,Logo,1,、,凋亡的研究进展及病理学意义,2,、干细胞在组织修复和再生医学研究中的展望,3,、血管生成的类型、过程和机制，阐述其在创伤愈合、肿瘤等病理过程中的作用和意义。,思考题,Logo,