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Path - Healing + Repair (i) (polypeptide GFS (pleiotropic effects (prolif,…
Path - Healing + Repair (i)
healing
replacement of destroyed/lost tissue by viable tissue
factors affecting the healing process
ability to remove causative agent + inflammatory debris
degree of architectural + ECM damage
ability of cell to prolif
labile
continuously dividing
derived from stem cells
e.g. epidermis, mucosal/GIT epithelium
heals by regeneration if stroma intact (if not then fibrosis)
stable
low levels of rep
but can be stimulated to divide
e.g. hepatocytes. renal tubular epithelium, pancreatic acini
heals by regeneration of stroma + regenerative stem cells intact
permanent
no division
no regeneration
replaced by connective tissue
e.g. neurons, cardiac myocytes, skeletal muscle
local
vasc supply (site)
presence of infection/foreign material
excess movement (can disrupt granulation tissue)
poor approximation
size
type of injury
systemic
age (young people have better vasc supply)
malignancy
chemo / radio tx
hormones (steroids impair healing)
metabolic status
DM: poor vasc supply, impaired neutrophil function, increased infection risk due to hyperglycaemia
nutritional status
protein
vit c (collagen)
copper (collagen cross-linking)
zinc (collagen conversion)
tissue response to injury
acute inflamm, followed by...
resolution
no tissue destruction, can return to pre-injury state (e.g. mild burn)
regeneration
replacement of lost tissue by tissue of same type
though cell division
supporting framework must be intact
= stroma
structural + connective role
= ECM (incl interstitium + basement membrane), mesenchymal cells, vessels
ECM regulates growth, motility, differentiation, consists of...
fibrous structural proteins (collagen + elastin)
adhesive glycoproteins
proteoglycans (filler substance between cells)
return to pre-injury state
controlled by stimulatory/inhibitory factors + cell-ECM interactions
repair by fibrosis
replacement of lost tissue by fibrous scar
occurs when...
both parenchymal + stromal cells are destroyed
permanent cells die
organisation of inflamm
production of granulation tissue (fibroblasts + myofibroblasts + capill buds for angiogenesis)
emigration + prolif of fibroblasts
deposition of ECM (type 3 collagen)
remodelled by collagenase + zinc to type 1 collagen
polypeptide GFS
most important cell growth mediators
in serum/produced locally
control gene expression + cell prolif (signal transduction via tyrosine kinase phosphorylation)
pleiotropic effects
prolif
migration
differentiation
tissue remodelling
EGF, PDGF, VEGF, F(fibroblast)GF, T(transforming)GF beta
interactions
cell-cell
via GFs, CKs, growth inhibitors
cell-matrix
via integrins
cells surface attachment Rs
transduce signals from ECM to cells