Tissue repair Flashcards
Cells and tissue regeneration
•Regeneration of injured cells and tissues involves cell proliferation, which is driven by ________ and is dependent on the integrity of the extracellular matrix.
Control of cell proliferation:
What is the role of vascular endothelial cells?
growth factors
Proliferative capacities of tissues:
What are the thre groups?
Most mature tissues contain variable proportions of the three cells types with the exception of what tissues?
•Intrinsic proliferative capacity influences ability to repair
Three groups
- Labile (continuously dividing) tissues (stem cells in epidermis)
- Stable tissues (fibroblasts)
- Permanent tissues (cannot replicate; for example- cardiac and striated muscle).
** With exception of permanent tissues, most mature tissues contain variable proportions of three cell types (i.e. continuously dividing cells, quiescent cells, and cells that have lost replicative ability)
Labile cells
What are some examples?
Stable tissues
What are some examples?
Permanent tissues
What type of repair dominates here?
Stem cells
What two properties characterize stem cells?
What are the two types of stem cells?
In which type can result in all three germ layers?
Which one is important in tissue homeostasis?
Self-renewal and assymetric replication
1.Embryonic stem cells - most undifferentiated, present in inner cell mass of blastocyst can form all three germ cell layers: ectoderm, endoderm, mesoderm
2.Adult stem cells – aka tissue stem cells, less undifferentiated than ES cells and found among differentiated cells within an organ or tissue. More limited self-renewal capacity, and more restricted lineage potential. Important in tissue homeostasis
Growth factors
what cells produce growth factors?
Growth factors
Role of extracellular matrix in tissue repair:
What is the ECM?
what does it regulate?
Serves as a reservoir for what?
What is the function of the fibrous structural proteins in ECM?
What is the function of water-hydrated gels (proteoglycans and hyaluronan in ECM?
ECM definition:
–Complex of several proteins that assembles into a network that surrounds cells and constitutes a significant proportion of any tissue
–Regulates proliferation, movement and differentiation of cells
–Provides substrate for cell adhesion and migration
–Serves as reservoir for growth factors.
•Components
1.Fibrous structural proteins (collagens, elastins)
•Tensile strength and recoil
2.Water-hydrated gels (proteoglycans and hyaluronan)
•Resilience and lubrication
3.Adhesive glycoproteins
•Connect the matrix elements to one another and to cells
What are the two basic forms of extracellular matrix?
Interstitial matrix is synthesized by?
What are some of the major components of the interstitial matrix?
Who synthesizes the basement membrane?
What type of collagen is a major component of the basement membrane?
•Two basic forms
1.Interstitial matrix
- Present in spaces between cells in connective tissue
- Synthesized by mesenchymal cells
- Major components: Fibrillar and non-fibrillar collagens, fibronectin, elastin, proteoglycans, hyaluronate
2.Basement membrane
- Beneath epithelial, endothelial and smooth muscle cells
- Synthesized by overlying epithelium and underlying mesenchyme
- Major components: Amorphous non-fibrillar *type IV collagen and *laminin
What is the main function of the extracellular matrix?
In terms of tissue regeneration, if the ECM is damaged, what happen?
•Main functions
–Mechanical support
–Control of cell proliferation
–Scaffolding for tissue renewal
–Establishment of tissue microenvironments
**An intact ECM is required for tissue regeneration, and if the ECM is damaged, repair can be accomplished only by scar formation
Vitamin C deficiency
What can be seen in patients with vitamin C deficiency?
–Impaired collagen synthesis and compromised tensile strength, as cross linking of fibrillar collagens = dependent of vitamin C
–Skeletal deformities, easy bleeding (weak vascular wall Basement Membrane) including perifollicular hemorrhage, ecchymoses, poor wound healing
Clinical correlates:
____________
–>Genetic disorder involving collagen synthesis genes
–>Skin hyperextensibility, joint hypermobility, tissue fragility
________2__________
–Inherited connective tissue disorder (“brittle bone disease”) affecting type I collagen synthesis
–Multiple fractures, osteoporosis
_______3_______
–Mutations in FBN1 gene encoding fibrillin, required for structural integrity of CT and regulation of TGF-beta signaling
–Tall stature, long fingers, mitral valve prolapse, aortic aneurysm, aortic dissection
1- Ehlers-Danlos Syndrome
2- Osteogenesis imperfecta
Marfan syndrome
Regeneration in tissue repair
For labile tissues to proliferate, what needs to be intact?
Stable tissues have limited capability to regenerate, with the exception of the _________.
Labile tissues
–Injured cells rapidly replaced by proliferation of residual cells and differentiation of tissue stem cells (provided underlying basement membrane is intact).
Stable tissues
–Regeneration can occur, but (with exception of liver) usually more limited process
Liver regeneration
The liver can regenerate even if ______ is lost due to numeros causes.
- Liver unique in robust regenerative capacity
- As much as 40-60% of liver can be removed in living-donor transplantation
- Liver also can also regenerate after other insults (hepatitis, etc.) if enough of tissue framework intact
Scar formation
What are the steps in scar formation?
- Angiogenesis (formation of new blood vessels)
- Migration and proliferation of fibroblasts and deposition of connective tissue (granulation tissue).
- Maturation and reorganization of the fibrous tissue to produce stable scar.
Describe the angiogenesis process?
Angiogenesis: Process of new blood vessel development from existing vessels.
Steps:
1) Vasodilation in response to nitric oxide and increased permeability induced by VEGF
2) Separation of pericytes from abluminal surface and breakdown of basement membrane to allow formation of vessel sprout.
3) Migration of endothelial cells toward the areas of tissue injury
4) Proliferation of endothelial cells just behind leading front of migrating cells
5) Remodeling into capillary tubes
6) Recruitment of periendothelial cells (pericytes, smooth muscle cells) to form mature vessel.
7) Suppression of endothelial proliferation and migration and deposition of basement membrane
Factors that could influence tissue repair at a SYSTEMIC level:
What diseases can delay tissue repair?
Glucocorticoids can inhibit what?
Factors that could influence tissue repair? LOCAL
Pathologic aspects of repair:
Which type regreses?
Which type does NOT regresses?
Healing of skin wounds:
Wound contraction in secondary intention is due to?
•Healing by first intention
–Epithelial regeneration is the principal mechanism of repair
•Healing by second intention
–More complex repair involving combination of regeneration and scarring.
Differences between them: t
- Larger clot or scab rich in fibrin and fibronectin
- More intense inflammation to remove greater volume of necrotic debris, exudate and fibrin
- More granulation tissue to fill the gaps and provide framework for regrowth of tissue epithelium à greater mass of scar tissue
- Wound contraction (attributed to myofibroblasts)
Wounds strenght
- Sutured wounds have ~70% strength of normal skin
- Sutural removal ~10%
- Three months and beyond 70-80%
