Tissue Repair & Wound Healing-Parks Flashcards
What is hemostasis?
this is a blood volume equilibrium, you need to stop bleeding to get this
What happens w/ cell injury?
neutrophils invade & inflammation results
What are the phases of cutaneous wound healing?
- injury
- coagulation, integration of fibrin
- Early inflammation (24 hr) there are: PMN, TGFbeta, PDGF
- Late inflammation (48 hr) there are: macrophages
- Proliferation (72 hr) fibroblasts lay down collagen
- Remodeling
How do you help a diabetic ulcer heal?
it is difficult b/c people can’t feel these areas
1st thing you do tho: clear the debris, get rid of dead tissue & get down to viable tissue
You can physically do this. Macrophages also help you.
What types of things do macrophages eat? This is a part of their phagocytosis function.
dead neutrophils
debris
edema fluid
collagen
After you finish your initial healing…what are your 2 options?
Regeneration or Scarring
Aside from their phagocytosis function, what are the other functions of macrophages?
Antimicrobial Activity: via nitric acid & ROS
Chemotaxis & proliferation of keratinocytes & fibroblasts: PDGF, TGF beta, TNF, IL-1, KGF-7
Angiogenesis: VEGF, FGF-2, PDGF
Deposition & Remodeling of ECM: TGF beta, PDGF, TNF, OPN, IL-1, collagenase, MMP
Depending on where you are in the body, when you have a mild injury…what happens? What are some examples of this?
regeneration parenchymal cell death w/ an intact tissue framework superficial wounds some inflammatory process Ex: liver regeneration after donation superficial skin wounds resorption of exudate in lobar pneumonia
When you have a severe injury, what happens? What are some examples of this?
fibrosis=scarring
**like if you have parenchymal cell death & a damaged tissue framework & deep wounds
Ex: deep excisional wounds
MI
What is an example of a case where the cells were able to regenerate after an injury?
Corneal Abrasion
**small patch of corneal cells were stripped away
Green dye is used to prove that it was a corneal abrasion.
Eye patch is the treatment b/c body will heal on its own, corneal stem cells are contained in the limbus area. They migrate out & regenerate the lost patch of cells.
What are some examples of stem cells that are located in adults?
- epidermal stem cells (often located @ base of a hair follicle)
- Intestinal stem cells (located in crypts)
- Liver stem cells (oval cells–located in canals of Herring)
- Corneal stem cells (limbus)
- bone marrow
Where is the limbus located?
b/w the conjunctiva & the cornea
Where do embryonic stem cells come from?
they come from the inner cell mass of the blastocyst. These are pluripotent stem cells.
From there they become multipotent stem cells, lineage committed stem cells, & differentiated cells (could be ectoderm, mesoderm, or endoderm).
What is the body’s response in a chronic injury process, persistent tissue damage?
fibrosis, tissue scar
Ex: chronic inflammatory diseases like cirrhosis, chronic pancreatitis, pulmonary fibrosis
What’s the story of an MI & tissue healing?
coagulative necrosis occurs
cardiomyocytes can’t regenerate so they heal by scarring
scarring involves fibroblasts laying down collagen–but collagen can’t contract!!
If the infarct is too large–heart failure.
What types of cells can enter the cell cycle again & promote regeneration & healing? How do you stimulate them to do this?
quiescent stable cells & labile continuously cycling cells. These include hepatocytes, & epidermal cells.
Stimulated to reenter the cell cycle if they are kicked from Go-G1 w/ a growth factor.
What types of cells CAN’T enter the cell cycle again & promote regeneration & healing?
terminally differentiated cells. Like cardiac myocytes or neurons.
What are the sources of epidermal growth factor?
activated macrophages
salivary glands
keratinocytes
other cells
What are the functions of epidermal growth factor?
it allows keratinocytes & fibroblasts to enter mitosis
stimulates keratinocyte migration
stimulates formation of granulation tissue
Where does VEGF: vascular endothelial growth factor come from?
mesenchymal cells
What are the functions of VEGF?
stimulates proliferation of endothelial cells
increases vascular permeability
Where do fibroblast growth factors come from?
macrophages
mast cells
endothelial cells
other cell types
What are the functions of fibroblast growth factors?
allows for mitosis & chemotaxis of fibroblasts
stimulates angiogenesis
stimulates ECM protein synthesis
What is the difference b/w FGF-1 & FGF-2?
FGF-1: acidic
FGF-2: basic
Where is TGFbeta: transforming growth factor beta found?
platelets T lymphocytes macrophages endothelial cells keratinocytes smooth muscle cells fibroblasts
What are the functions of TGF beta?
allows for chemotaxis of leukocytes & fibroblasts
stimulates ECM protein synthesis
suppresses acute inflammation
If VEGF, EGF, & TGF were all acting on the same tissue…what would each’s role be?
VEGF: stimulate blood vessels
EGF: stimulate parenchymal cells
TGF: stimulate ECM
Why are scabs so important?
Scabs are fibrin clots that contain macrophages & platelets. these give out growth factors. these growth factors must be released (clot helps this) so that epithelial cells will grow again (EGF) & fibroblasts will lay down collagen for a scar (TGF beta).
What type of collagen does TGF beta prompt fibroblasts to lay down?
originally Type III, but this is later replaced by type I.
What is cross talk & how does this relate to integrins?
Cross talk: interaction b/w signals from the growth factors & signals from the ECM. Integrins relay signals from ECM. Nucleus decides what to do in terms of proliferation, remodeling & apoptosis based on the integration of these signals.
So if you have a woman w/ Type I Diabetes who is struggling to have an abdominal wound heal…what do you do? What do you want it to look like?
The wound is infected.
It must be left open.
Hydrogel or other preparations may be helpful.
What you want is angiogenesis so that you can get a healing blood supply there & make the tissue look red.
Don’t want the wounds to get wet.
Want to see granulation.
What is angiogenesis & what stimulates it?
it is the growth of new blood vessels (includes recruitment of pericytes) to an area
stimulated by VEGF
What are 3 ways to get angiogenesis?
- angiogenesis from pre-existing blood vessels (capillary sprouting)
- angiogenesis by mobilization of EPCs (endothelial progenitor/precursor cells) from bone marrow
- vessel translocation
What does granulation tissue look like?
this is what you want a wound to look like
looks edematous & vascularized (red)
has occasional inflammatory cells
**can use H2O2 to help get the wound to that red point.
What is one of the most important things you can do to help a bone heal when it breaks? What is a Colles fracture?
You need to immobilize it!
Colles fracture: fracture you get when you fall & catch yourself w/ your hand.
Describe the healing process when you break a bone.
- hematoma forms b/c blood vessels were broken.
- some spongy bone trabeculae starts to form; external & internal calluses form (filled w/ fibrous tissue & cartilage); some new blood vessels form
- Bony callus of spongy bone forms
- After bone remodeling: you have a healed fracture!
At this point, when we think ECM involvement in healing…what should we think?
FIBROBLASTS!!!
To help w/ healing how do we stimulate the fibroblasts of the ECM?
TGF or FGF
What happens with scurvy that causes wounds?
problem w/ scurvy is that you don’t have enough Vit C. hydroxylases require Vit C to function. Their fcn is cross linking collagen.
Sign of scurvy: bleeding gums
**difficult to heal wounds when you can’t cross link collagen–>this type of damage is difficult to heal. Must get Vit C!
If you had a pressure sore from a Type II Diabetes patient with neuropathy…What do you do to help it heal?
You must remove the dead tissue (debris). Then angiogenesis might be able to occur & vascularity might be able to be restored.
When the pressure sore has healed some & is granulation tissue…what will it look like?
some new blood vessels
edema in stroma
scattered inflammatory cells
When the pressure sore is in its final stage of healing & it is re-epithelializing what happens?
you see epidermis & scar tissue beneath.
it often heals from the periphery in. You also see little islands of healed tissue from basal skin stem cells growing up from the bumps of dermal papillae.
What is first & second intention healing?
first intention: this is when you suture someone’s wound to help it heal
second intention: this is when you fear infection or something & you find it appropriate to leave the wound open to heal. Note: w/ this decision there will be more scarring.
Describe some of the factors that affect wound healing.
Blood Supply Nutrition Size/Shape Wound Diabetes Infection Foreign Material Degree of Immobilization Medications
Describe how meds could play a role in wound healing in a patient who just had a mastectomy for breast cancer.
You want to put her on anti-cancer meds. You should wait a while, however, b/c they are anti-growth. It will make it difficult for her post-surgical wound to heal.
Aside from anti-cancer meds, what are other meds that are anti-wound healing?
prednisone & other steroid meds
What is a keloid?
super thick scar, hypertrophic scar that results after wound healing
thick bundles of collagen are found in it
**more common in African Americans
Describe what a serious wound infection looks like. What would a patient be at risk for?
red swollen dilated blood vessels mast cells histamine a bunch of other stuff present **if very serious, at risk for sepsis
When you have a super infected wound, how must you heal it?
via second intention, leave it open to heal
Should you use inspired oxygen to help a patient heal post-surgically?
Controversial
Downside: oxygen increases formation of ROS
**in babies we don’t b/c causes blindness
With an MI, what is the timeline for reversible injury?
0-1.5 hours
Within 4-24 hours following an MI…what do you see?
dark mottling
coagulation necrosis
edema
hemorrhage
Within 1-3 days following an MI…what do you see?
yellow-tan infarct
neutrophils are trafficked in
Within 3-7 days following an MI…what do you see?
macrophages come in & soften the area
Within 7-10 days following an MI…what do you see?
Early Granulation Tissue; at this stage very fragile tissue b/c there are no myocytes to hold everything together.
Within 10-24 days following an MI…what do you see?
Well developed granulation tissue w/ collagen deposition
After 2 months following an MI, what do you see?
dense collagenous scar
Following an MI…at the early granulation tissue stage…what problem do we have? What may result?
very fragile tissue b/c there is only edema & macrophages–>no myocytes.
It is possible to get left ventricular rupture or papillary muscle breakage. The rupture could lead to sepsis & cardiac tamponade. The heart could be unable to move b/c of the tamponade & then the patient will die via shock.
What is the significance of papillary muscles breaking? Let’s say you have an MI & during the early granulation stage when the tissue is soft the papillary muscles break…
Let’s say you break the papillary muscles connected to the mitral valve. then you experience mitral valve prolapse & the valve doesn’t work anymore. Difficult to push sufficient blood thru the heart.
Why does LV rupture lead to cardiac tamponade? What is cardiac tamponade?
LV rupture allows blood to leak out into the pericardium. It fills w/ blood & prevents the heart from pumping.
Aside from cardiac tamponade or papillary muscle breakage…what problem can you run into following an MI? How does this relate to stem cell research?
The infarct area of the heart heals which is great. But it is replaced by scar tissue. This isn’t the same as cardiac myocytes & it will not contract properly. If you can’t pump your heart well–heart failure. This is why stem cell research is so important b/c we really want to replace that tissue with cardiac myocytes instead of collagen.
What are 7 possible sources of cardiac myocytes? Which are exogenous sources & which are endogenous sources?
Endogenous Sources: Cardiomyocyte replication Cardiac stem or progenitor cells Bone marrow-derived cardiac stem or progenitor cells Epicardially derived cardiomyocytes Exogenous sources: Embryonic Stem Cells Induced Pluripotent Stem Cells Mesenchymal Progenitor Cells
What are ulcers?
chronic non-healing wounds
can result from repeated trauma or from non-healing factors
What is dehiscence?
a previously closed wound reopening.
