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 repair

Chapter Ⅳ. Repair

修复

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)


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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


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Cell-cycle

细胞周期

A

Cyclins-CDKs

C、D、E

B


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Embryonic stem cells

Stem cells

Sequamous

cell of skin

Gene

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.


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(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


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(3).Cell surface receptors and signal transduction system

General patterns of intercellular signaling


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Ⅱ. Extracellular matrix, ECM

细胞外基质


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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

glycosaminoglycan:粘多糖

heparan sulfate、dermatan sulfate


Ecm occurs in two basic forms interstitial matrix and basement membrane

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


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  • 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


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Ⅲ. Repair by Healing with connective tissue

结缔组织修复

The formation of granulation tissue is the critical stape in healing

(1).granulation tissue

肉芽组织

Newly formed capillaries

Proliferation of Fibroblast

Inflammaroty cells


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New small blood vessels

(新生的小血管)

Proliferation of Fb

(成纤维细胞)

Inflammaroty cells


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2.The process of granulation tissue formation

  • Angiogenesis

  • from pre-existing vessels


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Angiogenesis from endothelial precursor cells


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b) Granulation tissue formation and development

Granulation tissue Fibrous tissue Scar


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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)

proteoglycans

fibronectin, Laminin, others

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

TIMP1, TIMP2;


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(2)基质金属蛋白酶/基质金属蛋白酶组织抑制因子

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;

(3)间质溶解素,如MMP-3、MMP-10及基质水解蛋白等,

主要作用于ECM成分的糖蛋白,如FN、LN等。

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,

主要有TIMP-1、TIMP-2、TIMP-3三类。


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Ⅳ. wound healing

创伤愈合

Inflammation

Granulation Tissue Reepithelialization

Cutaneous

Wound

Healing

Healing by first/second intention

一期愈合、二期愈合


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  • 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

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

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


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

Systemic factors:

nutrition(营养)

Metabolic sttus(代谢状况)

Circulatory sttus(循环状况)

Hormones(激素)

Local factors:

Infection(感染)

Mechanical factors(机械磨擦)

Foreign bodies(异物)

Size, location and type of wound

(大小、部位、伤口类型)


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Complications in cutaneous wound healing

(并发症):

Deficient scar formation瘢痕形成不足

Wound dehiscence(伤口裂开)

Ulceration(溃疡)

Excessive formation of the repair components瘢痕形成过度

keloid(瘢痕疙瘩)

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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keloid(瘢痕疙瘩)


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Thank you

for your attention !


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