Tissue repair Flashcards
What does it mean to repair a tissue?
Both restoration of tissue architecture and function after an injury
Complete recovery rarely achieved
What are the two mechanisms of tissue repair?
Regeneration of injured tissue
Replacement of lost tissue
Which mechanism of tissue repair require cell proliferation of intact or altered cellular matrix?
Both
Stem cells produce a baseline cell population which do ____ or ____.
Proliferate, die via apoptosis
What are the types of continuously dividing (labile) cells?
Skin basal, hematopoietic, hair follicles and GI cells
What does the G0 phase look like for the continuously dividing cells?
Short
What are the stable cells and what does it mean to be stable?
Liver, kidney, lung alveoli, bone, breast, endocrine, adipose, vessels
Only need to proliferate when necessary
What does the G0 phase look like for stable cells?
Long
What are the permanent tissues and what does that mean?
Neurons in CNS, ganglia in PNS, cardiac, skeletal muscle
Cannot divide functionally
What are some characteristics of continuously generating cells?
Can easily regenerate after injury with a infinite life span
Dependent on age and health
Contains pools of stem cells
Immune positive for CD34, CD117, Ki67
What are the three locations for skin stem cells?
Epidermis, sebaceous gland, hair follicle bulge
What are the actions of growth factor?
Stimulate cell division and proliferation
Promote cell differentiation and survival
What some examples of growth factors?
Epithelial growth factor (skin, fibroblasts)
Transforming growth factor (hepatocytes, epithelials)
Platelet derived growth factor (s muscle, cytokines)
Erythropoietin
Granulocyte growth factor
What does each growth factor have on its target cell?
A specific receptor
When cells are injured and proliferate what is released?
Cytokines
Where do the cell injury responsive cytokines come from?
Damaged tissue, inflammatory cells, macrophages and vascular endothelial cells and fibroblasts
What are the two forms of the extracellular matrix?
Interstital matrix and basement membrane
What does the extracellular matrix do?
Sequesters water and mineral from circulation
Stores presynthesized growth factors
Gives cells a scaffolding upon which to adhere and do their assigned tasks
What does the ECM regulate overall?
Proliferation, movement, and differentiation of cells living in or on it
If the ECM is completely destroyed what happens?
It cannot regenerate and a scar forms
When does regeneration occur in labile tissues?
All the time, can make as much as needed
When does regeneration occur in stable tissue?
A limited extent, only some can come back or compensate for lost tissue
Only occurs if the residual tissue is healthy and intact
When does regeneration occur in permanent tissue?
Pretty much never and will always form scar tissue
What are the steps to injury healing?
- Cut
- Inflammation
- Blood clotting
- Granulation tissue - scab,eschar
- Wound contraction
- Wound recovery
- Scar tissue
If an injury is too severe…
regeneration can’t happen
What are the four components used in regeneration mediated by growth factor?
New vessel formation VEGF
Fibroblast proliferation FGF, TGF
Fibroblast synthesis of immature scar - type 3 collagen
Fibroblast remodeling with mature scar - type 1 collagen
What is an eschar?
A scab
Granulation tissue does not contain….
Cross linked collagen
What are the three examples of wound healing?
First intention - sew shut
Second intention - leave open
Third degree burn
What does it mean when a wound is healed by first intention?
Occurs in small wounds that close easily
Suturing or butterfly tape possible to use
Epithelial regeneration predominates over fibrosis
Healing is fast, minimal scarring
well vascularized, no dead tissue
What is the time line to see changes for first intention healing?
Immediately
By 24 hours
By 3-7 days
Weeks later
During the phase of immediate healing for first intention, what is seen?
Vasoconstriction - platelet activation Vasodilation - fills with blood Blood clots release of mediators - PDGF Fibrinogen in blood converted to Fibrin by platelets Temporary scaffold
What happens in 24 hours in first intention wound healing?
Platelets aggregate Release PDGF's and firm clot formation Migration of cells first of neutrophils and then macrophages In Cut edges, stem cells wake up Chemotaxasis
By 3-7 days what has happened in first intention wound healing?
More macrophages with few PMN Granulation tissue formed - new blood vessels, fibroblasts (acted on by TGF) & myofibroblasts Collagen type 1 begins to bridge ECM starts to be made Newly made epithelium thickens
What happens after a few weeks in first intention wound healing?
Granulation tissue gone; ECM back
Collagen type IV
Epidermis full thickness
Little scar forms
What happens in healing by second intention?
Large wound gap occurs and fibrosis predominates over epithelial regeneration
Healing is slower, more inflammation, granulation of tissue formations and scaring (less wound contraction)
Why can good wounds (that could heal well) go bad?
Trauma, acute or chronic infection, diabetes, steroids, ischemia, radiation
What is a keloid scar?
Hypertrophic fibroblast response (more collagen)
too much type 1 leads to too much type 4 collagen
What is a proud flesh scar?
Hypertrophic granulation tissue (more vessels present)
also called Pyogenic granuloma
When is a scar good and when is it bad?
Good - forms well and is resilient
Bad - permanent contraction dysfunction
How does HBV lead to scarring but HAV not?
HBV injures the matrix as well which leads to scarring
HAV only damages the cells
what can store cytokines?
extracellular matrix
what does basement membrane consist of?
Type IV collagen
Laminin
Proteoglycan
what does interstitial matrix consist of?
fibrillar collagens
Elastin
Proteoglycan
Hyaluronan
what mediates the process of Scarring?
Growth factors
- New vessel formation (angiogenesis) by VEGF
- Fibroblast proliferation elaborating FGF, TGF
- Fibroblast synthesis of immature scar - Type 1 collagen
- Fibroblast remodeling with mature scar - Type 4 collagen
After a cut, a clot forms and within seconds
heeling begins with PDGF
Fibrinogen is converted to Fibrin for
temporary scaffolding for WBCs
By 24 hrs after an injury,
PMNs, platelets, Macs take over
Endothelial cells begin to proliferate
Fibroblasts emigrate - become myofibroblasts and wound contraction begins
By 3-5 days after an injury,
granulation tissue is present
-scab, eschar
New firm scaffolding is present that repair cells can work
Weeks after an injury
there is dense fibrosis - scar
scar remodeled in months from pink to white then wrinkled
Granulation tissue has
no crosslinked collagen
mainly blood vessels and fibirin
no PMNs
Examples of some injuries that heal by second intention?
Ischemic necrosis - infarction
large burns
Ulcers
Ulcer caused by
some ischemia and pressure
cirrhosis is
fibrosis and regenerative nodules
Trichrome
stains collagen blue
Proper Repair occurs
with architecture and function
what collagen change is seen in breast cancer?
Collagen type 5 is seen
Nephrosclerossi
scarring of glomeruli from hypertension induced damage
contraction of scars in the brain leads to
seizures
Lung infarctions are
hemorrhagic
