regeneration in tissue repair Flashcards
regeneration in tissue repair occurs in tissues comprised of?
labile (epitheium) and stable cells (parenchymal organs)
-CT framework must be intact
scar formation is the replacement of ____ cells with?
replace parenchymal cells with CT
8 severe or persistent tissue injury with damage to both parenchymal cells and stromal framework
scar formation steps
1) angiogenesis
2) migration and proliferation of fibroblasts
3) deposition of CT
4) maturation and reorganization of fibrous tissue
**accumulation of CT matrix= scarring (dense fibrosis)
scar formation repairs begin when? granulation begins?
repair begins within 24 horus
*granulation tissue within 3-5 days
angiogenesis
CRITICAL for healing! MUST HAVE!
- development of collateral circulation at sites of ischemia
- tumor growth
Healing by first intention (primary union)
most ideal situation
- *clean, uninfected surgical incision
- epithelial regeneration predominates over fibrosis
1) 24 hours: PMN migration toward clot - –increase mitotic activity of basal cells
2) 24-48 hours: migration and proliferation of epithelial cells, deposition of BM components
3) PMNs replaced by macrophages, granulation tissue, collagen at margin of incision, ep proliferation
4) day 5: granulation tissue fill incision, collagen more abundant, normal ep thickness
5) second week: continued collagen accumulation
6) 1st month: scar comprises CT surfaced by ep, destruction of dermal appendage - TENSILE STRENGTH increases
Healing by second intention (secondary union)
- more extensive tissue loss and inflammation
- more granulation= more scarring
- LARGER defect > necrotic debris > exudate fibrin > inflammation
what are factors that influence repair?
1) infection
- - most common cause of delayed wound healing
2) nutrition
3) glucocorticoids
4) mechanical factors
5) poor perfusion
- -NEED oxygen
6) foreign bodies in area
7) fibrosis associated with chronic inflammation disease
8) cirrhosis, pulmonary fibrosis, rheumatoid arthritis
9) persistent fibrogenesis +/- collagen degradation
keloids
exuberant collagen, more of an issue in asian/africans
list growth factos in cell regeneration and fibrosis
- epidermal growth factor (EGF)
- platelet-derived growth factor (PDGF)
- fibroblast growth factor (FGF)
- transforming growth factor beta (TGF-beta)
- vascular endothelial growth factor (VEGF)
- cytokines IL-1 and TNF
epidermal growth factor (EGF)
mitogenic factor for epithelial cells and fibroblasts
platelet-derived growth factor (PDGF)
important in activating endothelial and smooth muscle cells to produce new vessels
-induction of fibroblast, smooth muscle cell, and monocyte migration and proliferation
fibroblast growth factor (FGF)
stimulate new vessel formation
-recruits macrophages and fibroblasts to site of injury, angiogenesis
transforming growth factor beta (TGF-beta)
principally responsible for the fibrosis that accompanies chronic inflammatory states
- low conc. (indirectly mitogenic), contributes to fibrosis
- high conc. (inhibits growth) blocks expression of PDGF receptors
vascular endothelial growth factor (VEGF)
promotes angiogenesis, especially in neoplasms
-tumor angiogenesis and healing wounds
cytokines IL-1 and TNF
stimulates fibroblasts
-IL-1 and TNF stimulate fibroblasts, collagen production
two processes that are involved in tissue repair
1) regeneration of injured tissue by the SAME type
2) replacement by CT (fibrosis)–> scar
of cells in a tissue = rate at which
cells enter and exit the population
- entry depends on proliferation rate
- exit depends on cell death or differenciation
what is the most important regulatory control of growth in cell cycle?
the induction of of resting cells (G0) from outside the cycle
what is the cell cycle
1) G1 - presynthetic growth
2) S - DNA synthesis
3) G2 - premitotic growth
4) M - mitosis
5) G0 - quiescent cells
labile cells
- continuously dividing and dying
- regenerate from stem cells
- stem cell division = one daughter cell retains capacity to divide, the other differentiate
stable cells
- quiescent or low level replicative cells
- parenchyma of most colid glandular organs
- can be called upon to enter cell cycle
- *parenchyma of most colid organs (kidney, liver, pancreas)
permaent cells
- terminally differentiated and non-proliferative postnatally
- neurons, cardiac muscle, skeletal muscle
- injury = sacr formation
- *skeleta/cardiac muscle (limited regenerative capacity)
stem cells
- replenish cells of continuously dividing tissues
- embryonic stem cells are pluripotent
- regenerative medicine
properties of stem cells
1) self renewal capacity
2) asymmetric replication
1) autocrine signaling
2) paracrine
3) synaptic
4) endocrine
1) SELF
- -soluble mediators act on cell that secrets it
2) NEIGHBOR
- -mediators affect cells in immediate vicinity
3) NERVE SYNAPSE
- -activated neural tissue secretes transmitters at a synapse onto target
4) hormones released into bloodstream act on DISTANT cells
relationship between singnaling molecules conc and affinity
indirect
*low conc = high affinity and specific for target cell receptor binding
cell surface vs intracellular receptors
intracellular receptors= associated with DNA, receptor ligand enters cell, Vit D.steroid.thyroid/hormones
cell surface= bind to ligend, cascade of intraecellular events, increase intracellular C++, cyclic AMP, activation of repression, PROTEIN
describe growth factors
- pleiotropic
- stimulate protooncogenes
- expansion of cell populations
extracellular matrix
dynamic, constantly changing, support for soft tissues
interstitial matrix
present between cells in CT
- 3D amoirphous gel
- synthesized by mesenchymal cells
- fibrillar and nonfibrillar collagens
basement membrane
- highly organized
- beneath epithelium, synthesized by epithelium and mesenchymal cells
- type 4 collagen, adhesive proteoglycans
