Model Of Wound Healing Flashcards
Acute wound
Wound that heals in timely fashion
Chronic wound
Wound that have failed to proceed through an orderly and timely process to produce an anatomical and function integrity
- Medicare says presence longer than 30 days
Healing rate affected by…
Depth, location, cause of wound, patient age, physical condition
Acute inflammatory phase
Innate immunity lasting 24-48 hours
Subacute inflammatory phase
Involves both innate and acquired immunization lasting from 2-10 days
Proliferation phase
Lasting 2-20 days
Remodeling phase
Lasting from 9-up to 2 years
Inflammatory phase (acute and subacute) involves
- Vascular response to injury
- Cellular response to injury
- Chemical mediators of inflammation (histamine, leukotrienes, prostaglandins, bradykinin)
Vasoconstriction during inflammatory phase of wound healing
- Curtail blood flow via platelets
- Reduce oxygen delivery to wound -> producing hypoxia signaling to control wound healing via recruiting endothelial cells and facilitates angiogenesis in repair phase
- Wound space becomes hyperlactic & acidotic
Too much O2 during this phase impedes healing
Local hypoxia causes shift to…
Anaerobic glycolysis -> increase in lactate production -> activating angiogenesis and collagen synthesis
Platelets role in vasoconstriction
- First to arrive at injury site (activate, adhere, aggregate)
- Release serotonin -> vasoconstrictor
- Release PDGF (platelet derived growth factor) which is chemotaxic for neutrophils & macrophages
- Platelet derived fibrinogen converted to fibrin
- Seals injured area -> delays bacterial invasion
Vasodilation during inflammatory phase of wound healing
- Follows brief arteriolar vasoconstriction (once wound is closed from platelets)
- Histamine, prostaglandins, and leukotrienes released secondary to damaged tissue and mast cell degranulation
- Opens micro vascular beds -> increased heat, redness, cellular mediators & increased intravascular pressure
Cellular response during inflammatory phase of wound healing
- Polymorphonuclear leukocytes released from blood
- Neutrophils, eosinophils, basophils, mast cells
Neutrophil cellular response to inflammatory phase
- Proliferate in hypoxic acidotic environment
- Most phagocytic of granulocytes
- Produce superoxide to fight bacteria
- Secrete proteases and collagenases to hydrolysis necrotic tissue
- Wound pours forth pus (accumulation of dead cells that have phagocytized debris in wound)
- Short lifespan
Eosinophil cellular response to inflammatory phase
Modulate allergic inflammatory response, kill parasites
Basophil cellular response during inflammatory phase
Release histamine and heparin
Mast cell cellular respond during inflammatory phase
- Chemotactic factor (histamine) for leukocytes and macrophages
- Release histamine
- Release heparin -> stimulates migration of endothelial cells (for transition into proliferative phase) also accelerates activity of leukocyte phagocytosis
Macrophage cellular response during inflammatory phase
- Most important regulatory cell type
- Differentiate from monocytes when they leave the bloodstream
- Large phagocytotic cells that can ingest large microorganisms & debris
- Excrete ascorbic acid, hydrogen peroxide -> more recruitment (prolonging inflammatory phase)
- Tolerate severe hypoxia and acidotic environment
- Attracts fibroblasts, endothelial cells and vascular smooth muscle cells
- Essential for transition between inflammatory and repair phase
- Transcend all phases of wound healing (continue)
Leukocytes emigration sequence
- Margination & rolling (Sialyl-Lewis body & L-selectin)
- Adhesion (E-selectin)
- Transmigration (diapedesis - squeezing through cell membrane)
- Chemotaxis and activation
Lymphocyte cellular response to inflammatory phase
- Occurs slowly
- B & T lymphocytes
- Helper B cells
- Suppressor B cells
- Part of acquired immune response
- Complement system
Rubor
Indicative of increased blood flow
- Cardinal sign of inflammation, considered normal
Tumor
Fluid accumulation (plasma protein and blood cells)
- Cardinal sign of inflammation, considered normal
Calor
Increased blood flow to superficial tissues, histamine release
- Cardinal sign of inflammation, considered normal
Dolor
Pain, chemical mediators, nerve compression
- Cardinal sign of inflammation, questionably normal
Functio laesa
Start to loss of function
- Cardinal sign of inflammation, not normal
Proliferative phase sequence
- Re-enforcement of injured tissue (fibroplasia)
- Blood supply (neovascularization)
- Permeability barrier (re-epithelialization)
How do you know you’re in the proliferative phase?
- Presence of fibroplasia - yellow slough (considered okay early)
- Presence of pink granulation dots - indicative of neovascularization
- Contraction - wound edges pulled together
- Endothelial cells - white/pink crushed glass appearance
Fibroplasia during proliferative phase
- Most important cells in production of dermal matrix is the fibroblast - stimulated by low O2
- Extracellular matrix: collagen, fibronectin, laminin (for structural and metabolic support), hyaluronic acid (for fibroblast proliferation)
- Cross-linkage welding together of the collagen matrix producing durability & tensile strength -> better the organization cross-linkage better the tensile strength of the scar
Cross-linkage is…
Vitamin C dependent ie. Scurvy
Myofibroblasts
- Contain actin & myosin
- Differentiate from fibroblasts
- Contract & extend
- Draw edges of wound together
- Influence rate & amount of wound contraction
Neovascularization during proliferative phase
- Angiogenesis from pre-existing vessels sending out capillary-like sprouts
- Endothelial cells response to angiogenesis growth factor secretions of macrophages & hypoxic environment
- Development of new blood vessels gives bright red appearance (granulation tissue)
- Pink, soft granular appearance underneath wound (fibroblasts and angiogenic tissues in ECM)
- Provides matrix upon which epithelial cell migration occurs
Re-epithelialization during proliferative phase
- Keratinocytes respond to epidermal defect by migrating from wound edges
- Superficial wounds heal by this
- Epithelial islands - epithelial cells line skin appendages (hair follicles, sweat glands)
- Epithelial cells migrate towards center of wounds, best in moist environment
- Contact inhibition stops migration
- Migration is O2 dependent (want high levels)
New skin is initially … strength of original
15%
Remodeling phase of wound healing
- Fibroblasts disappear
- Collagenase increases; enzyme responsible for regulation of fibroplasia (balance between synthesis & lysis of collagen)
- As wound mature collagen lysis increases
Note: too much O2 causes hyper granulation (synthesis is O2 dependent, lysis is not)
Hypertrophic scar
- Remodeling error
- Red, raised off surface, rigid
Keloid formation
- Remodeling error
- Genetic inhibition of lysis, unbalance synthesis and lysis of collagen
- Appears larger than original region of injury
Causes of chronic inflammation
- Wound sealed by necrotic tissue
- Presence of pathogens (critical contamination)
- Foreign material that cannot be phagocytized
- Inefficient cellular activity
- Misused of cytotoxic agents
- Frequent irritation
- Repeated trauma
- Granuloma (fibroblasts produce large amount of collagen to surround foreign material)
Wound closure methods
- Superficial wound healing
- Primary intention
- Delayed primary intention
- Secondary intention
Superficial wound healing
Just repairing epidermis
Primary intention
- Direct side to side closure
- Flap
- Graft
Direct side to side closure
Primary intention wound closure method
- Suture or stapled
Flap
Primary intention wound closure method
- Adjacent tissue is moved into the wound defect (flap maintains own blood supply provided by pedicle)
Graft
Primary intention wound closure method
- Skin taken from distant location
Delayed primary intention wound closure
Would occur if infection present following primary intention wound & opens back up
Secondary intention wound healing
Damage to epidermis and dermis, how we heal wounds (physical therapy)
- Used for chronic wounds
