Ch.2 Scar formation & tissue repair Flashcards
Refers to the restoration of tissue architecture and function after an injury
Tissue Repair/healing
Type of tissure repair rxn:
issues are able to replace the damaged components and essentially return to a normal state.
Cell proliferation to survive injury and retain capacity to generate mature cell of damaged tissue.
Regeneration
Tissues like the epitheliium that are continuously dividing
Labile
injured tissues are incapable of complete restitution, or when the supporting structures of the tissue are damaged, repair occurs by the laying down of connective (fibrous) tissue
Scar formation
On what tissues is scar formation common?
- Stable tissues (not dividing) like solid organs (ex. kidneys)
- Permanent tissues (neurons, cardiac muscle)
What cells?
Labile
Cells that are **constantly being lost and must be continually replaced **by new cells that are derived from tissue stem cells and from the remaining mature tissue cells
- Hematopoetic** Stem cells **in bone marrow
- Surface epithelia cells in skin, columnar epithelia in GI tract
What tissue cells?
Cells in the G0 stage of proliferation but are capable of dividing in response to injury
parenchyma of most solid organs, such as liver, kidney, and pancreas
What cells?
consist of terminally differentiated nonproliferative cells.
Injury to these tissues is irreversible and usually results in a scar, because the cells cannot regenerate.
majority of neurons and cardiac muscle cells
undiferrentiated & can turn into any cell type
discovered in embryos as self-renewing cells that can give rise to all mature cell lineages (totipotential)
Embryonic Stem Cells
Moreparitally differentiated, no ability to revert, found in tissues, work to replace and replenish lost cells in area which they reside.
Tissue (adult) stem cells
Tissue stem cells live in specialized niches, and injury triggers signals that stimulate their ____and ____ into mature cells that repopulate the injured tissue.
Prolieferation & Differentiation
Basment membrane of tissue present after injury?
No longer present?
Present= mild injury**, regeneration possible **
Gone= severe injury, scar formation
What kind of healing?
Partial surgical resection of the liver, grows back?
Regeneration!
Residual tissue was intact
What kind of healing?
Extensive destruction of the liver with collapse of the reticulin framework, as occurs in a liver abscess,
Scar fomation
Severe damage by infection/inflamation
2 ways liver regenerates
- Proliferation of hepatocytes following partial hepatectomy.
- Liver regeneration from stem cells.
the replacement of parenchymal cells in any tissue by collagen, as in the heart after myocardial infarction
Scar
1st step in scar formation
Neutrophils & monocytes reruited to eleminate offending agents. macrophaes come in an elemintae + activate growth factors that stimulate proliferation of cells in the next stage of repair
6-48hrs
Inflammation
2nd step in scar formation
including epithelial cells, endothelial cells, and other vascular cells and fibroblasts, proliferate and migrate to close the now-clean wound
All work to form **granulation tissue **
up to 10 days
Cell proliferation
What cell type?
respond to locally produced growth factors and migrate to cover the wound.
Epithelial cell
What cell type?
roliferate to form new blood vessels, a process known as angiogenesis,
Endothelial and other vascular cells
What cell is this?
proliferate and migrate into the site of injury and **lay down collagen fibers that form the scar.
Fibroblasts
The combination of proliferating fibroblasts, ECM, and new blood vessels forms a type of tissue unique to healing wounds
Pink, soft, granular gross appearence
Granulation tissue
3-5 days of healing
3rd step in scar formation
The connective tissue that has been deposited is reorganized to produce the** stable fibrous scar**
2-3 weeks post injury
Remodeling
Healing of skin wounds, epithelial regerneration with minimal scaring
no infection, close physcially via sutures, glue, etc.
Healing by first intention (primary union)
larger wounds that heal by a combination of regeneration and scarring
tissue loss, infection.
healing by second intention (secondary union)
process by which new blood vessels form from existing vessels. First process in scar formation
Antiogenisis
improve blood flow to a heart ravaged by coronary atherosclerosis
Therapies that augment antiogenisis
New blood vessel formation
to frustrate tumor growth or block pathologic vessel growth, as in wet macular degeneration of the eye
Therapies that inhibit antiogenisis
Less blood flow
which stimulates both the migration and proliferation of endothelial cells at area of injury.
Secreted by many tumors
vascular endothelial growth factor (VEGF)
Antiogenic factor
Attract fibroblast, new vessel formationa and depositing of extracellular matrix
Fibroblast Growth Factor (FGF)
Tumors overlly secrete ____ to direct all mateiral and suppised to the tumor, body thinks this is a normal signal.
VEGF
Therapy that redcud bodys overall capactiyt to heal but also steers course away from tumor growth
Anti- VEGF medication
What do these two things result in?
- Migration of fibroblasts into the site of injury, where they proliferate
- Production and deposition of ECM proteins
Laying down of connecitve tissue
What is the first thing fibroblast produce at site of scar formation?
Type 3 Collagen
Fast acting consists of fibroblasts and an acellular component, the ECM,
what tissue is this?
consists of fibroblasts and an acellular component, the ECM, which is composed of collagen and other glycoprotein
Connective tissue
What are some 3 key functions of the ECM?
- Mechanical support
- Control of cell proliferation
- Scaffold for tissue renewal
What of the 2 forms of the ECM?
present in the spaces between cells in connective tissue, and between the epithelium and the underlying supportive vascular and smooth muscle structures in parenchymal organs
Afibrillar and nonfibrillar collagens, as well as fibronectin, elastin,
Intersitial Matrix
What of the 2 forms of the ECM?
highly organized around epithelial cells, endothelial cells, and smooth muscle cells, forming the specialized basement membrane.
Type 4 collagen + laminin
basment membrane
What component of the ECM?
major ECM component of the interstitial matrix and scar tissue.
Collagen
Fibirilla Type 1,2,3,5 scar tissue
Needed as a cofactor for synthesis of collagen
Vitamin C
What disease?
Vitamin C deficeny, results in poor healing of wound and easily bleeding
Scurvy
The action of ____ is driven by TGF-beta and Platelet Derived Growth Factor (PDGF)
Fibroblast
Promotes collagen synthesis, innhbits enzyme that break it down.
Inhibit further inflammation, missing= inflammation ensues
Transforming growth factor; TGF-Beta
secreted Platelet, T-cells, macrophages, & endothelial cells
Stimulates both fibroblas migration & collagen syntheis + smooth musle cells.
Autoimmune or fiborotic diseases have abnormalities in this factor
Platlet derived growth factor PDGF
In response to cytokines and growth factors____ enter the wound from the edges and migrate toward the center.
Fibroblast
What tissue is being observed under a microscope?
many fibroblast, new small capillary vessles, much ECM, some macrophages
Granulation Tissue
Fibroblast may differentiate into ____
contain smooth muscle actin and have increased contractile activity; they help close the wound by pulling its** margins toward the center**
Myofibroblasts
5 days after injury, once mature scar= removed via apoptosis
most important cytokine for the synthesis and deposition of connective tissue proteins. It is pr**oduced by most of the cells in granulation tissue, **including activated macrophages.
Also antiinflamatory cytokiene and develeopent of fibrosis in lungs, liver, kidneys follwoing chronic inflamation
TGF-Beta
During final remodeling process of scar formation
Type of collagen deposited shifts from type III collagen early in repair to the more resilient type ____ collagen.
Type 1
scar shrinks due to the action of what two things?
- matrix metalloproteinases (MMPs)
- Lysyl Oxidase
Zinc & copper dependent
tissues is composed of** inactive, spindle-shaped fibroblasts**, dense bundles of collagen, and other ECM components
scar or fibrosis
What does this display?
Application of ____ at the site of extraction cause stimulate the activation of fibroblast to come and start healing process
Granulation tissue formation in the oral cavity. Application collagen membranes.
Due to the contractile acitvity of _____ wound healing may result in less function because tissue is more tightly pulled together
ex. burn on palm of hand-> scar-> cant fully open hand anymore
Myofibroblasts
Cooper or zinc defficency?
Poor wound healing & maturation becuase MMPs and lysly oxidase not working.
What is this process?
- inflamation homeostasis
- clot formation
- neutrophil migration invasion
- day 3-7 macrophage replace
- angiogenisis (blood vessel formation
- Fibroblast driven by GFs
- Type 3 collagen formaton
- Myofibroblas and traction
- Day 7-weeks, type 3 replaced by type 1
- more remodeling by lysyl oxidase and MMPs to reduce size of scar.
Healing of 1st intention wound
Ulcers are an example of what?
leave significan scars
2nd intention wounds
Are scars vascular? What is the staus of their tensile strength?
No, they are avascular & acellular. Tensile strength also never goes back to normal.
What disease?
metabolic disease that compromises tissue repair and is an important systemic cause of delayed wound healing.
Diabetes
What drug?
are antiinflammatory agents that **inhibit production of TGF-β **which means no promotion of collgen depostion= prevent good wound healing
Glucocorticoids (steroids)
elderly people as a result of chronic venous hypertension, which may be caused by severe varicose veins or congestive heart failure, resulting in poor delivery of oxygen.
Venous leg ulcers
individuals with atherosclerosis of peripheral arteries, especially associated with diabetes.** Ischemia** resulting from the vascular compromise interferes with repair and may cause necrosis of the skin and underlying tissues, producing painful lesions.
Arterial Ulcers
affect the lower extremities, particularly the feet. The necrosis and failure to heal are the result of small vessel disease causing ischemia and neuropathy, as well as secondary infections. Extensive granulation tissue in underlying dermins
Diabetic Ulcers
areas of skin ulceration and necrosis of underlying tissues caused by prolonged compression of tissues against a bone, e.g.,in bedridden individuals.
Pressure Sore
contain abundant myofibroblasts and often grow rapidly but tend to then regress over several months.
4 weeks after injury, **within borders **
mostly type 3 collagen, but organized. Normally self regresses and correct
Hypertrophic scars
Rasised scar tissue that grows beyond the boundaries of the original wound and does not regres.
Excessive healing and scar formation; chaotic fibroblast and collagen (both kinds) overproduction.
Commone in ear lobe, upper back. Rare on palms soles
High reccurance if surgically removed, Cortison injections help
Keloid Scars
What cause of surgical site infection?
Staph aureus
Skin infection
What cause of surgical site infection?
streptococci
Oral cavity
What cause of surgical site infection?
Pseudomonas
Burns
What cause of surgical site infection?
Penetrating exposed wound, soil ;
tetnus
Vibrio Vulnifus is in what?
Contaminated water supply
Bacteria in blood, always travels to heart
Bacteremia
the abnormal deposition of collagen in internal organs in chronic diseases.
Fibrosis
Fibrosis is induced by what?
Cause substansial organ dysfunction & faliure.
Persistant injury!
Ex. chronic infection & immuological reactions.
