Chapter Ⅳ. Repair
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Chapter Ⅳ. Repair 修复. injured cells and tissue.  repair.   parenchyma 实质 connective tissue 间质 regeneration healing (scar, fibrosis). (Regeneration refers to the proliferation of cells and tissues to replace lost structures ).

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Chapter Ⅳ. Repair 修复

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Chapter Ⅳ. Repair


injured cells and tissue

 repair

 

parenchyma实质 connective tissue间质

regenerationhealing (scar, fibrosis)

(Regeneration refers to the proliferation of cells and tissues to replace lost structures)

Ⅰ. Control of Normal Cell Proliferation and Tissue Growth

(1). The activity of cell proliferation (增生能力)

Labile cells (continuously dividing tissues )

Surface epithelia, cells of bone marrow

hematopoietic tissues

Stem cells

Stable cells (Quiescent tissues )

Parenchyma cells of liver, kidneys, and pancreas

endothelial cells, lymphocytes, leukocytes

Permanent cells (Nondividing tissues)

Neurons, cardiac muscle, skeletal muscle







Embryonic stem cells

Stem cells


cell of skin


2012 Nobel Prize for the discovery that adult cells can be transformed back into embryo-like stem cells that may one day regrow tissue in damaged brains, hearts or other organs.

(2).The effect of Growth factors

  • EGF:mitogenicfor keratinocytes and Fb

  • PDGF:chemotacticfor PMNs, MΦ, Fb, SMC;stimulatesproduction of MMPs, Fn, HA, angiogenesis and wound contraction

  • bFGF:chemotacticfor Fb, mitogenic for Fb and keratinocytes,stimulateskeratinocyte migration, angiogenesis, matrix deposition

  • HGF: stimulatesproliferation of epithelial and endothelial cells

  • KGF: stimulateskeratinocyte migration, proliferation and differentiation

  • TGF-: chemotacticfor PMNs, MΦ, Lymphocytes, Fb, SMC;stimulatesTIMP synthesis, keratinocyte migration, angiogenesis andfibroplasia; inhibitsproduction of MMPs and keratinocyteproliferation

  • IL-1: chemotacticfor PMNs; stimulationof MMP-1 synthesis

  • TNF:activatesMΦ, regulates other cytokines

(3).Cell surface receptors and signal transduction system

General patterns of intercellular signaling

Ⅱ. Extracellular matrix, ECM


Major components of ECM:

1.fibrous structural proteins:

collagen 胶原蛋白

elastin 弹性蛋白

2.adhesive glycoproteins:

fibronectin 纤连蛋白

laminin 层连蛋白

3.proteoglycans and hyaluronan


heparan sulfate、dermatan sulfate

ECM occurs in two basic forms: interstitial matrix and basement membrane.

  • Roles of the ECM

  • Mechanical support for cell anchorage

  • Control of cell growth

  • Maintenance of cell differentiation

  • Scaffolding for tissue renewal

  • Establishment of tissue microenvironments

  • Storage and presentation of regulatory molecules

Ⅲ. Repair by Healing with connective tissue


The formation of granulation tissue is the critical stape in healing

(1).granulation tissue


Newly formed capillaries

Proliferation of Fibroblast

Inflammaroty cells

New small blood vessels


Proliferation of Fb


Inflammaroty cells

2.The process of granulation tissue formation

  • Angiogenesis

  • from pre-existing vessels

Angiogenesis from endothelial precursor cells

b) Granulation tissue formation and development

Granulation tissue Fibrous tissue Scar

c. ECM and tissue remodeling

The outcome of repair process is a balance between the synthesis and degradation of ECM

ECM degradated by

Matrix metalloproteinase (MMPs,)

①interstitial collagenase ( MMP1, MMP5)

Col and ColⅢ

②gelatinases (MMP2,MMP9)

ColⅣ and ColⅤ in BM

③stromelysin (MMP3,MMP10, MMP11)


fibronectin, Laminin, others

MMPs are inhibited by Tissue inhibitor of matrix metalloproteinase (TIMPs)



matrix metalloproteinases MMPs主要分三类:

(1)间质胶原酶如MMP-1、MMP-5,降解 Ⅰ型和Ⅲ型胶原;

(2)明胶酶,包括MMP-2、MMP-9,降解 Ⅳ型胶原和Ⅴ型胶原;



基质金属蛋白酶组织抑制因子(tissue inhibitor of matrix metalloproteinases, TIMPs)是MMPs特异性的抑制剂,


Ⅳ. wound healing



Granulation Tissue Reepithelialization




Healing by first/second intention


  • Healing processes:

  • Induction of inflammation process

  • (remove damaged and dead tissue)

  • Proliferation and migration of parenchyma

  • and connective tissue cells

  • Formation of new blood vessels and granulation

  • tissue

  • Synthesis of ECM proteins and collagen deposition

  • Tissue remodeling

  • Wound contraction

  • Acquisition of wound strength

Healing by first intention

  • Operative incision

  • Cut surface is neat and tidy

  • Less infection

  • Invaded and linked by less granulation tissue and covered by new epithelial cell

Healing by second intention

  • Large wound, abscess, ulceration

  • Infection or foreign body existing

  • More inflammation

  • Clear the wound by debridement

  • Large amounts of granulation tissue

  • Scar formation

Ⅴ. Factors that influence wound healing影响修复的因素

Systemic factors:


Metabolic sttus(代谢状况)

Circulatory sttus(循环状况)


Local factors:


Mechanical factors(机械磨擦)

Foreign bodies(异物)

Size, location and type of wound


Complications in cutaneous wound healing


Deficient scar formation瘢痕形成不足

Wound dehiscence(伤口裂开)


Excessive formation of the repair components瘢痕形成过度


aggressive fibromatoses (侵袭性纤维瘤病)

Formation of contractures挛缩

Deformities of the wound and the surrounding tissue





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