Wounds and Healing
two ways of healing?
*Primary intension:* healing of a clean wound without loss of tissue and uninfected surgical incisions approximated by sutures. *Secondary intention:* healing takes a lot longer because of large tissue losses and formation of large amounts of granulation tissue to fill the wound.
Two types of wounds?
-*Acute* Under normal physiological condition and within 30 days the epidermal barrier will be healed and functional -*Chronic*: barrier defects do not proceed through orderly and timely repair. An acute wound can become chronic.
4 phases of healing?
-coagulation and homeostasis -Inflammation -Proliferation -wound remodeling and scar tissue formation (maturation)
4- different steps of the Remodelling phase of the wound healing?
-Lasts 1-2 years or longer -Delicate balance of degradation (metalloproteinases) and synthesis of ECM -Collagen bundles increase in diameter, hyaluronic acid and fibronectin are degraded -Tensile strength of would increases progressively Collagen matrix becomes more oriented and cross-linked over time -With time: a-fibroblast and macrophage are reduced by apoptosis b-Growth of capillaries stop c-Metabolic activity at the wound stops
Where are epithelial stem cells located? 3
-St. Besale in epidermis -Hair follicle stem cells -Base of sebaceous
-Why collagen synthesis is an important component of all phases of wound healing?
Because it -Imparts integrity and strength -Creates a foundation for the intercellular matrix formation 60% type I, 40% type 3 (normal dermis=80% type 20% type 3)
Healthy granulation tissue is dependent upon what factor?
It is dependent upon the fibroblast receiving sufficient levels of oxygen and nutrients supplied by the blood vessels. Healthy granulation tissue is granular and uneven in texture; it does not bleed easily and is pink / red in color.
Uncontrolled healing or constant growth of epidermal tissue due to a genetic predisposition are symptoms of what chronic wound?
Keloid
Degradation of ECM is mediated by what?
Metalorproteinases
2- Inflammatory phase?
Two parts -*early*: -Activates complement cascade Changes in surface *selectin* on neutrophils (1) sticky and adhere to endothelial cells in venules surrounding the wound (2) roll along -*Chemokines* secreted by endothelial cells stop rolling neutrophils migrate out of venules (*diapedesis*) -*Infiltration* of neutrophils (24-36hr) into the surrounding tissue phagocytosis to prevent infections. -Once bacteria are removed neutrophils are gotten rid off by *apoptosis* and sloughing -*Late* -Macrophage appear in the wound 48-72 after wounding phagocytosis -Secrete many growth factors and other mediators that activate keratinocytes, fibroblasts and endothelial cells -72 hours after injury, lymphocytes arrive, attracted by chemoattractants (IL-1) -IL1 will be important during the remodelling stage as well.
Types of the chronic wounds that are due to poor blood flow or schemia?
Venus leg ulcer Arterial ulcer Diabetic foot ulcer Pressure sore
3-Proliferative Phase. Steps?
a-*Fibroblast Migration* -Starts on third day after injury, last for ~2 weeks -Fibroblast migration and -deposition of newly synthesized ECM -This ECM will replace the temporary network of fibrin and fibronectin -Fibroblasts change to myofibroblasts, their filipodia attach to the underlying matrix and begin the process of wound contraction (approximate wound edges) -Fibroblasts undergo apoptosis. b-*Angiogenesis* Formation of new blood vessels takes place during all phases of healing c-*Epithelizazation* -Migration of epithelial cells from the wounds edges starts hours after injury -Cells proliferate and form a basement membrane
what is a granulation tissue?
granulation tissue is comprised of collagen and extracellular matrix into which a new network of blood vessels develop.
1-coagulation and homeostasis phase steps?
it begins immediately to stop loss of blood 1-vessels constrict if they are cut transversally 2-the coagulation cascade activates 3-Platelets release growth factors and cytokines attract neutreophils firs and then later macrophages, endothelial cells adn fibroblasts 4-platles cause vasoactive amines (eg. serotonin) vasodilate causing edema.
