Add Your Company Slogan 损伤的修复 白求恩医学院病理教研室 李 伟 2010.9.26
tissue and cellular injury Normal cells Adaptation irreversible injury reversible injury Adaptation hypertrophy hyperplasia atrophy metaplasia cellular injury reversible : irreversible : Necrosis apoptosis
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. 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 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): 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 physiologic The new cells complement aging cells. Maintain the normal structure and function pathologic The regeneration occurs after cellular and tissue defect.
--regeneration Cell types---base on regenerative capacity Cell cycle is defined as the period between two successive cell divisions. It is divided into 4 unequal phases. Labile cells Stable cells Permanent cells
再生 (Regeneration) The regenerative capacity types of cells-1 1 不稳定细胞 Labile cells 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
2 再生 (Regeneration) The regenerative capacity types of cells-2 稳定细胞 Stable cells (quiescent cells) 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.
再生 (Regeneration) The regenerative capacity types of cells-3 3 永久性细胞 Permanent cells 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.
组织的再生过程 Regenerative process of tissues
Regenerative process of tissues The regeneration process depends on 1. the regenerative ability of the cells 2. the intact of tissues framework
Regeneration of Epithelial Tissues 1 Covering epithelia Original cells proliferate from the margin of injury Migrate to cover the gap Differentiation and maturation to reconstitute the original tissue It may regenerate completely if the basement membran is intact.
2 Glandular epithelial cells regeneration mucosal surface Regeneration of gastric epithelium mucosa in peptic ulcer
Regeneration of Epithelial Tissues 2 Glandular epithelial cells regeneration liver 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
2 Glandular epithelial cells regeneration liver
2 Glandular epithelial cells regeneration liver Spotty necrosis--the hepatocyte necrosis limited to scattered cells within hepatic lobules.
2 Glandular epithelial cells regeneration liver Submassive necrosis --The hepatocyte necrosis is extensive with tissues framework destroy
2 Glandular epithelial cells regeneration liver normal Morphology of portal cirrhosis
Regeneration of Connective tissue Fibrocytes (Primitive cells) Fibroblasts Secretion of Tropocollagen condensation to form Collagen fibres Bonding and weaving Fibrocytes Scar tissue
Proliferation of Blood Vessels --Angiogenesis Budding-- Basement membrane dissolution Endothelial cells proliferation and migration Vascular channels forming Rebuilding to form arterioles, thin-walled venules
Proliferation of Blood Vessels--Angiogenesis
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
Regeneration of nerve tissue 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
Regeneration of nerve tissue 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
Influential factor on cell regeneration Cellular injury regeneration Cell proliferation ECM intra-cellular environment extracellular environment growth factor Inhibin and contact inhibition
Stem cells in tissue and cellular regeneration Stem cells 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 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
Stem cells in tissue and cellular regeneration Self-renewal and differentiation of stem cells 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
Stem cells in tissue and cellular regeneration The multiple differentiation ability of mesenchymal stem cells (MSC)
第三节纤维性修复 Section 3 Fibrous repair 肉芽组织 (Granulation tissue) 瘢痕组织 (scar)
several overlapping phases for Scar Formation Preparation The area of injury is prepared for scar formation: by removal of the inflammatory exudates Liquefied material is removed by lymphatic Any particulate residue is removed by macrophage phagocytosis.
Granulation tissue Granulation tissue is highly vascularized connective tissue composed of newly formed capillaries, proliferating fibroblasts, and residual inflammatory cells 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 Gross : pink, soft, moist, and granular appearance 粉色 颗粒状 柔软 湿润 触之易出血
Granulation tissue LM: fibroblasts, new capillaries, inflammatory cells
Granulation tissue
Granulation tissue
Granulation tissue(low power) Granulation tissue(high power)
Granulation tissue Granulation tissue
Consequences of granulation tissue Granulation tissue water fibroblast s New capillaries Inflammatory cells absorption disappear collagen fibres vascularity diminishing gradually fibrocyte s Bonding and weaving disappear disappear Scar tissue
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
Morphology and function of scar 瘢痕 (Scar): 肉芽组织经改建成熟形成的纤维结缔组织 scar
Influence of the scar Advantage: Fill in the wound keep integrity Strengthening the tissue scar contraction Disadvantage: scar adhesion organ cirrhosis keloid formation
Influence of the scar 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 瘢痕组织 瘢痕收缩导致关节痉挛
Morphology and function of scar scar of renal infarct
Influence of the scar organ cirrhosis scar adhesion
Influence of the scar Keloid 瘢痕疙瘩 ( 蟹足肿 )
The mechanism of granulation tissue and scar formation 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) Neovascularization: vasculogenesis angiogenesis Growth factors and their receptors Extracellular matrix Fibrosis Tissue remodeling Matrix Metalloproteinase (MMPs)
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
Clinical Stages in skin Wound Healing Hemorrhage and acute inflammation 早期变化 : 出血 坏死和炎症反应, 红肿, 痂皮 Contraction of the wound edges 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 Formation of granulation tissue 肉芽组织增生 ( 第 3 天 ) 和瘢痕形成 Regeneration of epidermal cells and other tissue 表皮及其它组织再生
Clinical types of wound healing Healing by first intention 一期愈合 Occurs if: Clean and uninfected Surgically incised Without much loss of cells and tissues Edges of wound are approximated by surgical sutures Complete repair of the wound without a scar Complete replacement of necrotic epithelium and connective tissue
Clinical types of wound healing 一期愈合 (Healing by first intention)
Clinical types of wound healing Healing by second intention 二期愈合 Occurs if: Open with a large tissue defect The wound is not approximated by surgical sutures but is left open With infection Tissue does not have a normal structure after repair. Usually replaced by scar tissue
Clinical types of wound healing 二期愈合 (Healing by secondary intention)
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
Process of fracture repair( 骨折愈合 ) 1.Hematoma 血肿形成 肉芽组织纤维化 透明软骨 2. Provisional Callus 纤维性骨痂 骨母细胞类骨组织编织骨 3. Bony Callus 骨性骨痂 4. Bony Remodeling 骨痂改建或再塑
HEALING OF A CLOSED FRACTURE (Histologic Features Hours After the Fracture) Features Histology Hemorrhage and inflammation 血肿和炎症
HEALING OF A CLOSED FRACTURE (Histologic Features Days After the Fracture) Features Histology Organization and proliferation of periosteal cells 纤维性骨痂
HEALING OF A CLOSED FRACTURE (Histologic Features Weeks After the Fracture) Features Histology Formation of cartilage and immature bone 骨性骨痂
HEALING OF A CLOSED FRACTURE (Histologic Features Months After the Fracture) Features Histology Conversion to lamellar bone (remodeling) 骨痂改建和重塑
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
影响创伤愈合的因素 伤口类型 感染与异物 局部血液供应 年龄 营养 伤口边缘对合 神经支配 电离辐射