Healing process takes one of two paths, what are these paths?
Injured tissue is repaired by regeneration or scarred by fibrosis
Shortly after inflammation, a temporary scaffold is constructed and what begins?
Tissue organization
As wound healing occurs, what resolves?
Inflammation (inflammatory cells die/are cleared)
What typically occurs if regenerated tissue is less well organized?
The amount of scarring will be greater
What can determine the amount of scarring?
The type of cells in damaged tissue
What cells are short-lived and multiply constantly throughout life (GI epithelium, liver, and blood cells in the bone marrow)?
Labile cells
What cells lead to greater regeneration of injured tissues?
Labile cells
What cells can multiply when receiving external stimulus and may lead to greater fibrosis than regeneration?
Stable cells
What cells will have more fibrosis than labile cells but not as much fibrosis as permanent cells?
Stable cells
What cells cannot multiple, so damage to that tissue will only lead to fibrosis?
Permanent cells
Wound healing steps (4 stages)
-Hemostasis -Inflammation -Proliferation-Remodeling
What is involved in inflammation?
acute inflammation, edema, cell migration, removal of bacteria and dead cell debris
What is involved in proliferation?
neoangiogenesis, collagen deposition, granulation tissue formation (contracture), epithelialization, wound contraction
What is involved in remodeling?
collagen is remodeled and realigned along tension lines to increase wound strength. Cells that are no longer needed are removed by apoptosis
Hemostasis occurs at what time?
quickly, within 30 minutes to an hour after injury
When does neoangiogenesis occur?
~3 days
When does contracture occur?
~17 ish days
When does epithelialization occur?
~ 30 ish days
Clinical scenario: 4 days later what stage would that be? *** she mentioned this like 3 times to know general time Frame of stages
Neoangiogenesis stage
What is involved in hemostasis stage?
platelets and fibrinproteoglycan (scab formation)
Purpose of hemostasis
happens at time of injury and is meant to stop the bleeding
What is involved in inflammation stage?
neutrophils - main player in acute inflammation macrophages - cleaning processlymphocytescytokines and growth factors
What is the purpose of the inflammation phase?
Destroy bacteria and remove debris
Steps in proliferation phase:
-Angiogenesis (endothelial cells-forming new blood vessels and O2 supply)-Collagen deposition and granulation tissue formation (fibroblasts) -Wound contraction (myofibroblasts)-epithelialization (covering the wound)
What cells are involved in proliferation stage?
fibroblastscollagenepithelial cellsendothelial cells
What is purpose of proliferation?
To fill and cover the wound
What is involved in remodeling stage?
Collagen fibril crosslinking scar maturation
Local vasoconstriction due to local neural response and release from endothelium occurs during what stage of healing?
Hemostasis
What occurs after local vasoconstriction during the hemostasis stage of healing?
Primary hemostatic plug due to platelet adhesion, activation, degranulation, and recruitment of more platelets This is called a Primary clot
What occurs following primary hemostatic plug (primary clot) in the hemostasis phase of wound healing?
Secondary hemostasis due to activation of coagulation cascade - fibrin traps cell to form clot
What is the control mechanism that kicks in after secondary hemostasis?
Counter-regulation - to keep clot trimmed to prevent overgrowth and occlusion of the vessel This prevents the entire lumen of the vessel from being blocked by platelets
What are the main neutrophil/fibroblast chemotactic factors involved in acute inflammation?
TGF-betaplatelet factor-4PDGFFGFC3a and C5aLeukotriene B4IL-8
Proliferation phase begins with formation of granulation tissue which consists of what?
Main components are Fibroplasia - laying down of type III collagen***Neoangiogenesis - formation of new blood vessels Inflammatory cells - clean up debris Endothelial cells - repair or make new blood vessels Myofibroblasts - provide contracting forces to bring margins together Provisional extracellular matrix
What comes after formation of granulation tissue in the proliferation phase? When does this occur?
Fibroplasia Occurs 2-3 days after the wound and starts even before inflammatory phase has ended.
What is fibroplasia?
When fibroblasts divide and form granulation tissuesMakes ground substance (non collagen part) and type III collagen *** she mentioned this like 7 times
Where is type III collagen
In the wound site = scaffold for cell migration
Type III collagen is produced by
fibroblasts Proliferation phase
Collagen secretion begins
2-3 days after injury Proliferation phase
Collagen secretion peaks at
2-3 weeks after injury Proliferation phase
Collagen deposition increases what?
Wound strengthProliferation phase
Collagen deposition provides what for inflammatory, endothelial, and connective tissue cells in the proliferation phase?
Collagen provides scaffolding
At the end of the proliferation phase, the function of the fibroblast cell has been completes and fibroblasts undergo what?
Apoptosis
Apoptosis leaves the wound looking?
more collagenous, less cellular (pink -> silver look)
Angiogenesis is when blood vessels arise from
existing vessels
Vasculogenesis
When blood vessels arise from endothelial cells coming together (from nothing) Happens during fetal development
What is the formulation of new blood vessels from pre-existing vessels and production of microvascular networks with RBC perfusion?
Neoangiogensis
When does neovascularization peak?
around 5 days
New blood vessels are leaky by design which allows what?
Allows inflammatory cells and healing factors to exit bloodstream and enter tissues for healing
What forms near the end of the healing process?
Endothelial tight junctions
What is the difference between angiogenesis and vascularization?
Angiogenesis is blood vessels sprouting from pre-existing blood vessels (predominates throughout life and is involved in disease/healing) and vascularization is blood vessels arising de-novo from primitive mesenchymal cells (most common in early developmental phase)These terms are used interchangeably unwound healing, but angiogenesis is the correct term**
During epithelialization, what do epithelial cells do?
Epithelial cells migrate across granulation tissue and collagen matrix
If basement membrane is intact, epithelial cells are replaced within how many days and how?
3 days by cell division and upward migration of cells ins stratum basal
If basement membrane is disrupted, where does re-epithelialization have to come from?
From the wound margins
When does contraction of the proliferation stage start? At this time fibroblasts differentiate into what?
About one week after injury Fibroblasts differentatite into myofibroblasts
What occurs during contraction of proliferation stage?
Wound contracts to reduce size of wound (by 40-80%) around an axis of contractions
During the remodeling stage collagen production = ?
degradation
What type of collagen is degraded during the remodeling stage and what is it replaced with?
Type III is degraded and type I replaces it (stronger)
What does remodeling result in?
Wound is 50% as strong as normal tissue at 3 monthsWound is 80% as strong as normal tissue at 1 yearVessels that make scar look pink undergo apoptosis
What is the ideal scenario in healing?
Wound healing by first intention: First intention healing results when a narrow/small lesion with clean edges (such as a scalpel cut) is able to heal quickly and without much scaring, because there is smaller are to repair
Would healing by second intention results in:
Wider lesion such as ulcer or abrasion
Why is healing by second intention more difficult?
There is more "real estate" to fill in order to repair the lesion Hence, due to fibroplasia and myoepithelial actions, there is often a scar or a stricture after healing, which can impair form or function of the organ
Pathological aspects of wound repair (4)
1. Dehiscence 2. keloid3. excessive contractures4. biofilm
What is the premature opening of the wound before healing, due to poor scar formation?
Dehiscence - example of dysregulated wound healing
Risk factors for dehiscence
age, diabetes, obesity, poor nutrition, multiple trauma, trauma to wound after surgery, vitamin C (scurvy), steroids, geometry of wound
What is a benign scar/overgrowth of granulation tissue (mostly type III collagen which is replaced by type I collagen)?
Keloid
More about keloids:
- Can be itchy and painfuly- Occurs at sites of prior acne, chicken pox, piercing, surgery, etc- more common in young females- most common sites: earlobes, sternum, shoulders, upper back and places where abrasion has occurred-treat with [surgery], compression, steroids, cryotherapy, laser
How are keloids different than hypertrophic scars?
-keloids are raised, amphomorphous growths that extend beyond the original boundaries of the injury-collagen fibers in keloids are arranged randomly vs. normal scars in which the fibers are arranged parallel to skin surface-In contrast, a hypertrophic scar is a raised scar that does NOT grow beyond the boundaries of the original wound
myofibroblasts gone wild
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What is a community of micro-organisms encased in an extracellular polymeric substance (EPS), on the surface of a wound?
Biofilm
What are common bacteria in biofilm?
Staph and pseudomonas; often antimicrobial resistant. Some strains can transfer genes to each other, increasing antibiotic resistance
Neutrophils have trouble phagocytosis bacteria that are encapsulated in:
EPSThis suggests you should keep wounds clean and covered until wound healing (re-epithelialization) has occurred