wound healing Flashcards
What are the 5 wound healing models?
- Superficial wound healing: only affects epidermis
- Primary intention-surgical;
- Delayed primary intention-surgical;
- Partial-thickness wound healing: epidermis destroyed, wound into dermis
- Full-thickness wound healing
What do Rete Pegs do?
Prevent shearing of dermis
The Simplified phases of healing
- inflammatory: platlets, fibrin, neutrophils, macrophages, mast cells
- Proliferative: fibroblasts, myofibroblasts, endothelial cells, keratinocytes
- Remodeling: collagen
What are platlets, neutrophils, & monocytes
- Platlets: small fragments in blood involved in homeostasis
- Neutrophils: phagocytic, clean up debris/bacteria
- Monocytes: WBC in response to inflammation will differentiate into macrophage
What are Endothelial cells, fibroblasts, myofibroblasts?
- EC: form endothelium, lining of blood vessels
- Fibro: produce protein fibers (collagen) and ECM
- Myofib: cell differentiated from fibroblast, contains actin/myosin system.
What are keratinocytes, mast cells?
- Ker: main cell in epidermis
- Mast cells- specialized secretory cell that helps promote fibroblast proliferation
What are Cytokines?
- Signaling molecules (peptides, proteins; essential for cell communication
- Play role during inflammation: attract immune cells for defense
Growth Factors?
- Proteins that are able to effect cell reproduction, movement, and function
- Can act on distant cells (endocrine stimulation), adjacent cells (paracrine stim), or on themselves (autocrine)
- Released in response to homeostatic control signals
What are Chemokines?
- Regulate trafficking of leukocyte population during normal health/development
- Direct activation of neutrophils, lymphocytes, macrophages, during inflammation.
What are MMP’s?
- Matrix metalloproteinases
- Family of 20 proteolytic enzymes; critical in achieving tissue degradation
- Require Ca ions for structural conformation; Zinic to function
What are TIMPS?
- Tissue inhibitors of metalloproteinase
- Synthesized by same cells that produce MMPs
What are some initial characteristics of the inflammatory phase?
- Begins at time of injury; lasts 3-7 days
- Clotting takes place hemostasis; factors released to rid debris, bacteria, damaged tissue
- Redness, warmth, pain, edema, dec ROM
What are the first initial steps in the inflammatory phase?
- Clotting & vasoconstriction to reduce BF
- Break down pre-existing tissue scaffolding; clean up debris
- Epidermal barrier disrupted; platelets are activated by collagen exposed by the injury (trigger vasoconstriction)
What is Hemostasis?
- Clot is formed made of cytokines, GF’s, fibrin, fibronectin, thrombosponinds (clotting cascade)
- Serves as scaffolding for migration of leukocytes, keratinocytes, fibroblasts, and endothelial cells (foundation for collagen deposition)
- Reservoir of GF’s
What do platelets secrete during the inflammatory phase?
- Multiple cytokines and GF’s: EGF, PDGF, TGF-B, IL-1
- Attract neutrophils to wound
- Monocyotes are transformed into macrophages
Describe wound space hypoxia during inflammatory phase?
- Vasoconstriction= dec O2; hypoxia controls wound healing
- Neutrophils, macrophages; stimulates endothelial cells- angiogenesis
- Shift to anaerobic glycolysis= inc lactate; wound becomes hyperlactic
The role of Neutophils during inflammatory phase
-Cleanse the wound; there w/in 24 hours; like hypoxic environment; part of pus
The role of Macrophage during inflammatory phase?
- Initiate angiogenesis & granulation tissue formation during proliferation
- Phagocytosis of debris (excrete lactic acid)
- Secrete collagenases- help break down damaged collagen that is there, being to lay new collagen
- Produce NO, secrete GF’s
Mast Cells during inflammatory phase
- Promote fibroblast proliferation- TNF-a
- Release histamines (vascular dilation-edema), produce heparin, accelerate activity of neutophils
Nitric Oxide?
-Vasodilatation; role in angiogenesis, most abundant during first 10-14 days
Complement system?
- Noncellular group of substances that are responsible for acute inflammation
- Facilitate bacterial destruction; antibodies IgG & IgM activate it
Temperature during inflammatory phase
- Vasodilatation of surrounding tissue- perfusion aids in moving cells to the injury (inc temp)
- Injured nerve endings cause hyperemia (inc temp)
- Inc cell metabolism (inc temp)
- If no dec in temp by 4th day possible infection
Current of injury
-Cells posses currents of ion movement; current flowing b/t normal and injured tissue is stimulus for repair process
What are the initial characteristics of proliferative phase?
- Begins around 3rd-5th day, can last up to 21 days
- Angiogenesis, granulation tissue formation, collagen deposition, epithelialization, wound contraction
- Fill in tissue defect with shiny new tissue
- Restore integrity of skin (collagen syn (fibroplasias), angiogenesis, contraction
- Macrophages releases GF/cytokines- attract fibroblasts to wound (produce collage/elastin (foundation of connective tissue
- Act as scaffolding that will support blood vessel growth by endothelial
Describe elastin/collagen
- Elastin: form network of fibers that stretch/recoil; gives ECM elasticity
- Collagen: predominate fiber; resists stretching forces
- Ground substance- fills space b/t cells/fibers, high water content, GAGS/proteoglycans/glycoproteins
Examples of collagen in Proliferative phase?
- Type 1- dermis, bone, tendon, fascia, disk
- Type 2- hyaline & elastic cartilage
- Type 3- smooth muscle, arteries, lung, uterus, kidney
Angiogenesis during Proliferative phase
- Restores vascular integrity; macrophages induce this by releasing TNF-a, VEGF
- New capillary buds arise from intact blood vessels- supply O2/nutrients; capillary loops have appearance of granulation tissue, are fragile
- Endothelial cells proliferate and grow into wound space
Contraction during Proliferative phase
-Myofibroblasts connect the wound margin to pull epidermal layer inward; closes wound
-Re-epithelialization during Proliferative phase
- Re-establishment of intact epidermis over newly formed tissue
- Keratinocytes near basal lamina migrate across the granulation tissue
- Epithelial migration from intact hair follicles and sebaceous glands
Remodeling phase
- Occurs 6 mongths-3 years post injury
- Collagen becomes parallel & creates stronger bonds, most endothelial cells, macrophages, myofibroblasts undergo apoptosis
Collagen during remodeling phase?
- Type 3 was laid down during proliferative
- Type 3 is lysed and replaced with type 1 (stronger)
- Collagen lysis: collagenase produced during inflammatory/proliferative phases cleave topocollagen molecules aiding in resorption
Stress on remodeling?
- Stress affects shape, strength, pliability
- Collagen, elastin, and ground substance are affected by the direction and magnitude of mechanical stress applied to scar (Wolfe’s Law)
- Laid in response to lines of stress
- Tension causes inc in collagen fibers
- Stress will increase population of connective tissue cells to remodel the tissue, too much stress can pull scar apart
Scar formation during remodeling phase
- Vascularity/ cellularity diminish; becomes less red and flattens out
- Ratio of collagen breakdown to production determines type of scar
- —>Break down > production= flat pliable scar
- —–>Breakdown < production= hypertrophic scar (red, elevated, itchy, confined to original area of injury (pictures in slides)
Keloid scar
-Type of hypertrophic scar, extends outside the area of injury, tumor like appearance
Scar- Remodeling phase
- Essential & hindrance; begins highly vascular and becomes aceullar/avascular
- Changes to collagen- basket weave= small parallel bundles
- Intact skin: collagen (basket weave), elastin fibers, Ground substance
- Scar tissue- Collagen (bundles), Ground Substance
- Mature scar 80% of strength- rete pegs lost with scar
- Heals centipedially
Chronic Wound- Factors that affect wound healing
- Wound that deviates from the expected sequence of repair (time, appearance, response to tx)
- Inflammatory phase: stimulus for repair; inside-out; inadequate perfusion (vascular insufficiency)
- Proliferative phase: diminished keratinocyte migration lack of moisture, large surface area, rolled edges, thickened edges, hypergranulation tissue
- Proliferative phase: repeated trauma/infection, long term hypoxia (dec fibroblast production, negative effect on collagen production
- Remodeling phase: imbalance b/t collagen synthesis. Over production (hypertrophic) or underproduction (wound breakdown)
Intrinsic factors that affect wound healing
-Related to medical status of patient: Age, chronic disease, perfusion, immunosuppressant, neuropathy
-Extrinsic factors that affect wound healing
-Those that come from environment that affect body: medications (anticoagulants, immunosuppressant’s), nutrition (protein intake), irradiation, chemotherapy, psychological, wound bioburden & infection
Iatrogenic Factors
- Related to way wound is managed
- Local ischemia (pressure from bony prominence, compression)
- Inappropriate wound care; trauma, time to heal
Transforming Growth Factor β
- TGF-β1: platlets –> chemotatic for fibroblasts
- TGF-β2 : fibroblasts–> promote ECM formation
- TGF-β3: Machrophages–> inc collagen/TIMP syn, dec MMP syn. Reduce scarring ( Dec collagen/fibronectin
-Platelet-Derived GF
- PDGF-AA, PDGF-BB: platlets –> activates immune cells and fibroblasts
- VEGF: macrophages (promote ECM formation), Keratincocytes (inc collagen/TIMP syn), fibroblasts (dec MMP syn, inc angiogenesis)
Fibroblast GF
- Acidic FGF, basic FGF: macrophages (inc angiogensis)
- KGF: endothelial cells ( inc keratinocyte proliferation/migration) & fibroblasts (inc ECM deposition)
Insulin-Like GF
- IGF-I, IGF-II: liver –> inc keratinocyte/fibroblast proliferation
- Insulin: skeletal mm (inc angiogenesis), fibroblasts (inc collagen syn), macrophages (inc ECM formation), neutrophils (inc cell metabolism)
Epidermal GF
-EGF, HB-EGF, TGF-α: keratinocytes –>inc Keratinocyte proliferation and migration
Connective Tissue Growth Factor
-CTGF: fibroblasts (inc collagen syn), endothelial cells (mediates action of TGF-βs on collagen syn)
Table in Wound healing lecture
slide 32
