tissue repair Flashcards
what is the purpose of an inflammatory response
eliminate injurious agent and set in motion repair process
what are the cell types that proliferate during tissue repair
- remnants of injured tissue
- endothelial cells
- fibroblasts
labile tissues are characterized by
continuous division
stable tissues are characterized by
quiescent (in G0), only divide if necessary
permanent tissues are characterized by
they are terminally differentiated
cell proliferation in tissue repair is driven by signals from
growth factors (GFs) and within the ECM
what is the most important source of growth factors in tissue repair
macrophages
all growth factors activated signaling pathways that induce production of proteins involved in
•driving cells through cell cycle
or
•release block on cell cycle (checkpoints)
what is a scar
replacement of parenchymal cells by collagen
in angiogenesis, newly formed vessels are leaky because
•incomplete intraendothelial junctions and because VEGF increases permeability
the leakiness of newly formed vessels leads to
edema
granulation tissue is formed by
migration/proliferation of fibroblasts, deposition of loose CT, together with vessels and interspersed leukocytes
the amount of granulation tissue formed depends on
- size of tissue deficit
* intensity of inflammation
steps of connective tissue deposition (scarring)
- angiogenesis
- formation of granulation tissue
- remodeling of CT
in angiogenesis during the formation of scar, what do matrix metalloproteinases (MMPs) do
degrade ECM to permit remodeling and extension of vascular tube
what is the most important cytokine for the synthesis and deposition of connective tissue proteins
TGF-β
what does TGF-β do
•anti-inflammatory -> limit/terminate inflammatory response by inhibiting lymphocyte activation and activity of other leukocytes
what are myofibroblasts
- fibroblasts that have acquired some feature of smooth muscle
- contribute to contraction of scar over time
what do MMPs do in remodeling of CT
- degrade collagen and other ECM components
* depend on zinc (or other metal ion)
what cells produce MMPs
fibroblasts, macrophages, neutrophils, synovial cells, and some endothelial cells
how can infection influence tissue repair
prolongs inflammation and potentially increase local tissue injury
examples of nutritional deficits that might inhibit healing
vitamin c or copper deficit, which are needed for collagen synthesis
how can glucocorticoids influence tissue repair
they are anti-inflammatory, but may result in scar weakness due to inhibition of TGF-β
mechanical stress during tissue repair may result in
dehiscence
important examples of poor perfusion that could inhibit tissue repair
- atherosclerosis
- DM
- obstructed venous drainage
other factors that influence tissue repair
- foreign bodies
- diabetes (important!)
- type/extent of injury
- location
when does first intention healing/primary union occur
when injury involves only the epithelial layer
what is the primary mechanism of repair in first intention/primary union
epithelial regeneration
when cell loss is more extensive, second intention healing or secondary union occur. what does this process involve
combination of regeneration and scar formation
what are examples of extensive cell loss that would result in second intention/ secondary union
large wounds, abscess, ulcer, and ischemic necrosis
what differentiates second intention from first intention
- inflammation is more intense
- fibrin clot is larger
- more granulation tissue -> more scar tissue
- type III collagen first, then type I replaces it
- lots of wound contraction (myofibroblasts)
strength in sutured wounds
- 70% of normal skin with sutures
- when sutures removed (~1 wk) about 10% but rapidly increases over 4 wks
- ~70-80% by 3 mos, usually no substantial improvement from there
when is dehiscence of a wound most common
after abdominal surgery
when would ulceration occur in tissue repair
inadequate vascularization
what is a hypertrophic scar
raised scar from excessive collagen deposition; type I collagen dominates
what is keloid
scar grows beyond the wound; type III collagen is dominates
what is contracture
exaggeration of contraction of wound
scar formation is directly proportional to ___ and indirectly proportional to ___
amount of stromal damage; replicative ability of damage tissue
what does EGF do
epidermal growth factor
stimulates keratinocytes
what does KGF do
keratinocyte growth factor
stimulate keratinocytes
what does FGF do
fibroblast growth factor
stimulate fibroblasts AND promote angiogenesis
what does VEGF do
vascular endothelial growth factor
promote angiogenesis
what does PDGF do
platelet derived growth factor
promote granulation tissue formation (endothelium, smooth muscle, and fibroblasts)
what does TGF-α do
transforming growth factor alpha
similar to EGF- stimulate keratinocytes
what does TGF-β do
transforming growth factor beta
stimulates fibroblasts AND is anti-inflammatory (unique characteristic)
