Tissue healing and repair 08 22 14 Flashcards
regeneration
growth of cells and tissues to replace lost structures
usually what happesn to labile cells
no scar
healing with scar formation
occurs when complete restitution is not possible
usually collagen (fibrosis) gives structural support
usual response to severe/chronic damage in lung, liver, kidneys
components of tissue repair after injury
remnants of injured tissue
endothelial cells
fibroblasts
how are dead cells replaced in labile and stable tissues after injury?
stem cells undergo asymmetric replication
what growth factors induce angiogenesis in tissue repair?
vascular endothelial growth factors VEGF
fibroblast growth factors FGF
what growth factors induce production of ECM in tissue repair?
platelet-derived growth factors PDGF
transforming growth factor-beta TGF-beta
two forms of ECM
interstitial matrix
basement membrane
role of ECM
mechanical support
regulate cell proliferation (through integrins)
PROVIDES SCAFFOLD essential for healing without scar
storage of growth factors-fibroblast growth factor, hepatocyte growth factor
creates microenvironment
components of ECM
fibrous structural proteins: collagen and elastin
proteoglycans and hyaluronans-highly hydrated gels for compressibility
adhesive glycoproteins and receptors (fibronectin, laminin, adhesion molecules)
Ehlers Danlos syndrome
genetic defect in collagen synthesis or structure
Marfan syndrome
mutation affecting fibrillin-a major compoentn of microfibrils in ECM
so results in:
degeneration of aorta (aneurysm and dilatation)
dislocated lens
long legs, arms, fingers
repair by connective tissue (scar formation) occurs when?
severe or chronic tissue injury w/ destruc of stroma
injury of non-dividing cells
4 sequential steps of repair by connective tissue (scar formation)
angiognenesis
fibroblast migration and proliferation
ECM deposition (scar formation)
maturation of fibrous tissue (remodeling)
granulation tissue
specialized tissue in healing
present by 3-5 days (with new vessels, inflammatory cells, fibroblasts)
what causes vasodilatation for angiogenesis in tissue repair?
NO
vascular endothelial growth factor VEGF
where are the cells from angiogenesis for tissue repair coming from?
endothelial precursor cells (angioblasts) in bone marrow
what cellse secrete growth factors to promote fibroblast migration to site of injury and proliferation?
endothelium and inflammatory cells
what growth factors are involved in fibroblast migration and proliferation and deposition of ECM?
FGF
PDGF
TGF-beta
how does degradation of collagen and other extracellular matrix proteins occur in the remodeling of the scar?
matrix metalloproteinases (MMP) containing zinc
3 phases of cutaneous wound healing
inflammation
granulation tissue formation and re-epithelialization
wound contraction, ECM deposition and remodeling
healing by first intention steps
immediate: incisional space fills with clotted blood
within 24 hrs: neutrophils appear, begin re-epithelialization
by day 3: neutrophils replaced by macrophages, granulation tissue fills incisional space
day 5: maximal granulation tissue, collagen fibers begin to bridge incision
weeks: scar (connective tissue w/o inflam), decreased vessels
healing by secondary intention ex
large wounds (wide, not just deep)
abscesses
ulceration
healing by secondary intention definition
more intense inflam due to large firin clot and more necrotic material to be removed
larger amt of granulation tissue
WOUND CONTRACTION by myofibroblasts
substantial scar formation with THINNED EPIDERMIS
wound strength becomes 70-80% of uninjured tissue at what time post injury?
third month
what can influence tissue healing?
nutrition: vit C deficiency impairs collagen synthesis
metabolic status: diabetic pts have impaired neutrophil and macrophage fxns, impaired new vessel formation, impaired collagen syn—persisting ulcers and infec
circulatory status: poor perfusion impairs healing
hormones: steroids inhibit TGFbeta, decreases fibrosis
infection: prolongs inflam and may increase local injury
mechanical factors: increased local pres may cause closed wound to rupture
foreign bodies: prolongs inflam
keloid
raised scar due to excess collagen, is covered by epithelium
exuberant granulation
wound protrudes above surrounding skin and prevents re-epithelialization so NOT covered unlike keloid
