Chapter 2.5 Wound Healing Flashcards
At what point in inflammation is healing initiated?
healing is initiated when inflammation begins
combination of regeneration and repair (replace tissue with a scar; collagen and fibrosis)
What is regeneration?
replacement of damaged tissue with native tissue
- dependent on regenerative capacity of tissue
- 3 types of tissues based on regenerative capacity
What are some examples of labile tissues?
has SC constantly regenerating the tissue
(bowel, skin, RBC, WBC, platelets)
- small and large bowel (stem cells in mucosal crypts) …can regenerate after infection in GI tract or diarrhea
- skin (stem cells in basal layer) superficial layer of epithelium knocked out, SC/basal cells can regenerate that tissue constantly
- bone marrow (hematopoietic stem cells)
Where are the stem cells in the labile tissues?
- small and large bowel (stem cells in mucosal crypts)
- skin (stem cells in basal layer…innermost layer of epi? dermis)
- bone marrow (hematopoietic stem cells)
What is the marker of hematopoietic stem cells?
CD34
bone marrow stem cells are CD34+
What is stem cell of alveoli of lung?
Type II pneumocytes
Describe stable tissues.
Give two classic examples and provide a clinical example for each.
quiescent, but can reenter cell cycle
regeneration of liver by compensatory hyperplasia after partial resection
(each hepatocyte in liver can come out of quiesence and reenter cell cycle and divide and allow for regeneration of the liver)
proximal renal tubule of kidney (when patients undergo ATN=acute tubular necrosis, they get destruction of PT cells… can regenerate but takes time, so may have to place patient with ATN on dialysis to support them until kidney regenerates PT)
What are the permanent tissues in the body?
lack significant regenerative potential
myocardium
skeletal muscle
neurons
(don’t have much SC capability so when damaged can’t regenerate)
If permanent tissues are damaged, how do they heal?
with repair
repair replaced damaged tissue with fibrous scar
occurs when regenerative stem cells are lost or when tissue lacks regenerative capacity
(permanent tissues are myocardium, skeletal muscle, neurons)
What is the end result of MI?
always a fibrous scar bc the heart does not have the ability to regenerate tissue
If you get a deep cut why does a scar sometimes form instead of regenerative repair?
if basal cells are removed, get scar instead of replacement with skin
repair replaces damaged tissue with fibrous scar when tissue lacks regenerative capacity
What is the initial phase of repair?
granulation tissue
What three things does the initial phase of repair, granulation tissue, consist of?
fibroblasts (deposit type III collagen)
capillaries (provide nutrients)
myofibroblasts (contract wound)
What is the difference between a granuloma and granulation tissue?
Describe the mechanism by which each is formed.
granuloma is a subtype of chronic inflammation: hallmark is epitheliod histiocyte, granuloma formed by IL-12 from macrophage converting CD4 T cell converting it to Th1 helper cell which secretes IFN gamma that gives macrophage an epitheliod appearance)
granulation tissue is the inital phase of repair when forming a scar (consists of fibroblasts, capillaries, and myofibroblasts)
Eventually granulation tissue produces a scar. What distinguishes a scar from granulation tissue?
How does granulation tissue become a scar?
type III collagen is replaced with type I collagen (provides stability in final scar)
(type III prod. by fibroblasts)
collagenase removes type III collagen and requires ZINC as a cofactor.
Describe the key features of the four types of collagen and where each is predominantly seen.
Type I collagen (seen in bone…bONE, tendons, skin, and most organs) key feature is its strong tensile strength, provides support
Type II collagen (seen in cartilage, carTWOlage)
Type III collagen (classic for its pliability, see it in blood vessels which need to stretch, in granulation tissue (needs to stretch to form scar), see in embryonic tissue/uterus bc baby growing and needs to stretch, keloids)
Type IV collagen (predominantly seen in basement membrane)
What cofactor is requires in the reaction to convert granulation tissue to a scar?
zinc is the cofactor required
collagenase removes type III collagen
What is the mechanism of regeneration and repair?
mediated by paracrine signaling via growth factors (factors secreted by macrophages will bind receptors and these interactions result in regeneration and repair)
interaction of factors with receptors results in gene expression and cellular growth
Describe the following growth factors:
TGF alpha
TGF beta
TGF-alpha = epithelial and fibroblast growth factor
TGF-beta = important fibroblast growth factor; stimulates ECM synthesis, inhibits inflammation,
Describe the following growth factor:
PDGF
platelet derived growth factor (platelets help seal blood vessel that has been damaged… if platelets activated they releaes PDGF which helps endothelium and smooth muscle regrow, and fibroblasts come in)
endothelium, smooth muscle, fibroblast growth factor, stimulates ECM protein synthesis
Describe the following growth factor:
FGF
fibroblast growth factor
angiogenesis; skeletal development
ECM protein synthesis
Describe the following growth factor:
VEGF
vascular endothelial growth factor
angiogenesis
Cutaneous healing occurs via primary or secondary intention. Distinguish between the two.
primary - wouund edges brought together; minimal scar formation (big cut, suture two edges together…)
secondary - edges are not approximated/stitched together, granulation tissue fills in the defect
get BIG scar, granulation tissue will cause contraction of that wound
Patient has large wound that has healed by secondary intention. Six weeks later the wound has reduced significantly in size. What mechanism?
myofibroblasts
(granulation tissue has three properties; capillaries, fibroblasts that lay down type IIl collagen, myofibroblasts (have contractile function)
…can contract wound and make it smaller
