Tissue Repair Flashcards
How is tissue repair defined?
restoration of tissue architecturally and functionally
Tissue repair can occur via what two mechanisms?
regeneration of the injured tissue
replacement of lost tissue
(part of each two mechanisms play vary from tissue to tissue)
Both mechanism require:
- cell proliferation
- interaction between cells and the presence of intact or altered extracellular matrix
Compare HAV to HBV.
HAV (no chronic HepA)
- hepatic necrosis
- recover or die
- not destroying hepatocyte
HBV (chronic Hep B)
- kills hepatocyte and matrix
Describe cell proliferation.
Continuously proliferating cells can easily regenerate after injury or being used
- contains pools of stems cells close by
- immune + for CD34, CD117, Ki67
What is totipotent cell?
cell can differentiate into any cell type
Where is the first checkpoint?
G1/S - check for DNA damage
-may undergo apoptosis if defect
Where is the second checkpoint?
G2/M
What three groups are tissues of the body divided?
Continuously dividing (labile) - skin basal, GI, hair [short G0] Stable tissues - liver, kidney, lung alveoli, bond, breast, endocrine, adipose [ long G0] permanent - neurons in CNS, ganglia in PNS, cardiac, skeletal muscle [cannot divide]
Where are the three sites of stem cells in the skin?
epidermis
sebaceous gland
hair follicle bulge
Haematopoietic stem cells can differentiate into ?
RBC, WBC (lymphocyte, monocyte, eosinophil, basophil, neutrophil) , platelets
What is the actions of growth factors?
stimulate cell division and proliferation
promote cell differentiation & survival
What is EGF?
epithelial growth fact
mitogenic for skin & fibroblasts
What is TGF?
transforming growth factor
hepatocytes & epithelials
What is PDGF?
platelet derived growth factor
smooth muscle mitogens
cytokines
Cytokines can be present in which instances?
injured tissue remnant
inflammatory cells, macrophages, vascular endothelial cells
cytokines from fibroblasts
Where are cytokines stored?
extracellular matrix
- basement membrane
- interstitial matrix
What purpose does the basement membrane and interstitial matrix serve?
- sequesters water and minerals from circulation
- stores presynthesized growth factors
- give cells a scaffolding upon which to adhere and do their assigned tasks
What is the consequence if the ECM is destroyed?
can’t regenerate tissue
-scar forms instead
What does the ECM regulate?
proliferation, movement, and differentiation of the cells
What are the stages of tissue repair?
regeneration
scarring
Where does regeneration occur frequently?
labile tissues
Where does regeneration occur to a limited extent>
stable tissues
- kidney (if removed the other one undergoes hypertrophy and hyperplasia)
- liver (remove part of liver, some will grow back)
Describe the theoretical aspect of injury.
Blood clots and releases growth factors
- Inflammation
- granulation tissue
- wound contraction
At what point can regeneration not happen?
severe injury
What four components to scarring are mediated by GFs?
- new vessel formation (angiogenesis) VEGF
- fibroblast proliferation elaborating FGF, TGF
- fibroblast form an immature scar Type 1 collagen
- fibroblast remodeling with mature scar Type 4 collagen
What cells come in by 24 hours when an injury occurs?
PMNs
- endothelial cells are called upon to start proliferating
- fibroblasts emigrate-myofibroblasts appear wound contaction
With what growth factor does heeling begin with ?
PDGF
What happens by 3-5 days after an injury?
granulation (scab, eschar) tissue present
- new scaffolding upon which repair cells work
How is the scar remodeled over time?
granulation tissue changing with collagen types moving from type 1 to 4
Granulation tissue contains cross linked collagen. (T/F)
false; mainly blood vessels and fibrin
What is a trichrome stain?
stains collagen blue/green
Two types of wound healing
healing by first intention (a surgical incision)
healing by second intension (a third degree burn)
Describe scarring with 1st intention? 2nd intention?
1- small scarring
2- large scarring
How is healing by first intention accomplished?
epithelial regeneration predominates over fibrosis
- healing is faster with minimal scarring if no infection
Describe the immediate timeline of first intention.
Vasoconstriction - blood fills incision site, platelets activated
Platelets are irritated and release clotting factors.
-also release activation factors that activate edge of wound.
Describe the timeline changes one sees by 24 hours.
By 24 hours
- platelet aggregates
- release PDGF’s
- migration of cells first neutrophils then macrophages come in
- at the cut edge of lesion, stem cells are stimulated to propogate
- chemotaxasis takes place
Describe the timeline changes one sees by 3-7 days.
Macrophages come in very few PMN
Granulation tissue is formed:
- new blood vessels (VGF)
- fibroblasts (fgf) & myofibroblasts (TGF)
Collagen type 1 begins to bridge incision
very labile wound
Describe timeline changes weeks later.
Granulation tissue gone, ECM back
Collagen is remodeled type IV
epidermis full thickness, mature (w/o dermal appendage)
Fibrous union
Scars are prone to develop cancer due to lack of?
melanin
Describe healing by second intention.
wounds that have large gaps
-race between epithelial cell and fibroblasts
- fibrosis predominated over epithelial regeneration
- healing is slower with MORE inflammation
-granulation tissue formation and scarring
-more wound contraction
Ex) ischemic necrosis (infarction)
large burns and ulcers
What is gliosis?
scar in brain
How can an infarct in the brain cause epilepsy?
glial cells contract leading to epilepsy
How do skin ulcers appear?
slide, large gap between edges
surface is hyperkeratonized
At the time of suture removal the tensile strength is?
only 10% of what is was before injury
What is the wound strength of primary intention at third month?
70-80%
What are examples of wounds gone bad due to aberrant cell growth of ECM?
keloid scar
proud flesh
Why do wounds go bad?
Extrensic factors trauma acute and chronic infection diabetes steroids ischemia - lower extremity heals slower than upper personal care radiation diet
Why could tissue be so vulnerable to trauma?
blood supply is not adequate
What is a keloid scar?
hypertonic fibroblastic response
during maturation creates an overgrowth of type 1 collagen and overabundance of type IV
main proliferation below epithelium
What is proud flesh?
hypertonic granulation tissue
pyogenic granuloma
Scarring can lead to what adverse effects?
contraction –permanent dysfunction
What is cirrhosis?
fibrosis and regenerative nodules
Nephrosclerosis contains decreased what?
glomeruli
What is a tampanade?
blood escapes heart and fills pericardium
When is the heart most prone to rupture after an M.I?
1st week
What atypical collagen is laid down in scars caused by cancer?
type V
