Flashcards in Tissue Healing and Repair Deck (18):
What are the requirements for regeneration of parenchyma?
Existing cells must be able to proliferate (in response to growth factors)
Name the three types of tissues and examples of each.
Labile: continuous renewal, hematopoietic cells in marrow, surface epithelia, mucosal epithelia
Stable: parenchyma of most solid organs, regeneration occurs but is limited; pancreas, adrenal, lung, thyroid, kidney, liver has more regenerative capabilities.
Non-dividing cells: repair by connective tissues, neurons and cardiac myofibers
What are the two types of stem cells?
Embryonic stem cells: pluripotent, able to differentiate into all tissues
Adult stem cells: lineage-specific, skin and GI epithelium
Name some of the main growth factors involved in repair.
VEGF: induces angiogenesis in injury and in tumors
FGF: induces angiogenesis; promotes migration of fibroblasts, epithelial cells, and macrophages
PDGF: induces fibroblast, smooth muscle, endothelial cell proliferation and migration; stimulates production of ECM
TGF-beta: Suppresses endothelial proliferation/migration and acute inflammation; stimulates production of ECM proteins
Name some components of the ECM.
Collagen: structural proteins providing tensile strength
Elastin: forms elastic fibers with fibrillin, allowing for recoil
Proteoglycans & hyaluronan: hydrated gels, provide compressibility
Fibronectin: interstitial ECM
Laminin: basement membrane
Adhesion molecules: CAMs
Genetic defect in collagen synthesis or structure; will have hyperextensible, fragile, easily traumatized skin, joints and ligaments will be hyper mobile, poor wound healing, rupture of internal organs
Commonly a defect in Collagen type V
Ehlers-Danlos Syndrome (EDS)
Mutation affecting fibrillin; Clinically can have degeneration of aorta (aneurysm and dilation), dislocated lens, abnormalities of aortic and mitral valves, long legs, arms, fingers, hyper-extensible joints.
What are the 4 sequential steps in repair by connective tissue?
2. Fibroblast migration and proliferation
3. Extracellular matrix deposition (scar formation)
4. Maturation of fibrous tissue (remodeling)
When is granulation tissue present?
By 3-5 days -- contains new vessels, inflammatory cells, and fibroblasts.
Which growth factors are responsible for angiogenesis?
VEGF and fibroblast growth factor (FGF)
Which growth factors are responsible for fibroblast migration and proliferation??
Which proteins degrade collagen during remodeling of the scar?
Matrix metalloproteinases (MMP) -- contain zinc
What are the three phases of skin wound healing?
2. granulation tissue formation and re-epithelialization
3. wound contraction, ECM deposition and remodeling
Describe healing by first intention.
Immediate: incisional space fills with clotted blood
Within 24 hours: neutrophils appear, begin re-epithelialization
By day 3: neutrophils replaced by macrophages, granulation tissue fills in incisional space
By day 5: maximal granulation tissue, collagen fibers begin to bridge incision
Weeks: Scar; connective tissue without inflammation, decreased vessels
Describe healing by secondary intention.
Larger wounds -- more intense inflammatory response d/t large fibrin clot and more necrotic material to be removed.
Larger amount of granulation tissue. Wound contraction by myofibroblasts. Substantial scar formation with thinned epidermis.
At the end of the first week how strong is a wound?
10% of unwounded skin
At 3rd month it plates at 70-80%
Name some factors that influence healing.
Diabetes: impaired neutrophil and macrophage function
Circulatory status: poor perfusion
Hormones: steroids inhibit TGFbeta and decrease fibrosis
Foreign bodies: prolong inflammation