Green - Wound healing Flashcards
What are the phases of healing?
- Inflammatory phase
- Proliferative phase
- Maturational phase
When does the inflammatory phase occur?
Days 0-7
- Goals = stop bleeding, seal wound surface, remove necrotic tissues/FBs/bacteria
- Therefore increased vascular permeability, cytokine secretion + GF secretion, chemotaxis
- Neutrophils–>,macrophages + T cells –> IFN-y —> decrease collagen
When does the proliferative phase occur?
Day 3 to week 3
What does the proliferative phase consist of?
- Angiogenesis
- Fibroplasia: collagen synthesis “lag phase”
- Epithelization
What stimulates angiogenesis in the proliferative phase?
- FGF
- TGF-alpha
- TNF-alpha
- VEGF
What type of cells proliferate and become dominant in the proliferative phase?
Fibroblasts
What stimulates collagen synthesis in the proliferative phase?
- Ascorbic acid (Bit C)
- TGF-beta
- IGF-1
- IGF-2
O2 + Vit c = important for collagen cross-linking by hydroxylation
How does collagen and wound strength correlate throughout the proliferative phase?
Collagen rapidly increases day 5 x 3 weeks then plateaus
- First 3 weeks: correlate
- After 3 weeks: Strength increases with no increase in collagen–>reflects scar remodelling
How does epithelization occur in the proliferative phase?
- Partial thickness wounds: from remaining dermal appendages
- Full thickness wounds: migrates in from the edges at a rate of 1-2 mm/day. Rate is dependent on vascularity of underlying granulation tissue
Begins 24h post=wound, @48h enlarge, prolific, migrate contact inhibition, d/c migration hen 2 edges meet
How does collagen synthesis work?
Procollagen gene–>translation–>preprocollagen–>hydroxylation (cross linking vit C)–>glycosylation–>disulphide bonding–>pro collagen–>packaging into lysosomes–>cleavage of peptides by peptidases–>collagen monomer
What are common types of collagen?
- Type I: all connective tissue (bone) except cartilage and basement membranes
- Type II: Articular cartilage, vitreous humour, and intervertebral disks
- Type III: elastic tissues (blood vessels, uterus, skin), usually found with type I. Initial on in scars
- Type IV: basement membranes
- Type V, VI: widespread tissue distribution
- Type VII: Fibrils that anchor epidermis to dermis
- Type IX, XI: Hyaline cartilage
What are some known abnormalities of collagen?
- Osteogenesis imperfecta: deletion of 1 pro collage alpha-1 allele
- Ehlers-danlos syndrome: abnormal type III, deletion of part of type I collagen gene, abnormal copper utilization, deficiency of lysol hydroxylase
- Epidermolysis bullosa: absence of type VII that is the main component of fibrils that anchor epidermis to dermis
What are elastic fibres?
- Produced by smooth muscle cells and fibroblasts
- Composed of: amorphous elastin, microfibrils
- found in normal and hypertrophic scars
Where are elastic fibres most commonly found?
- Thoracic aorta
- Peripheral arterioles
- Skin
- Vocal cords
- Sclera
- Lungs
- Pregnant uterus
What are stimulants of elastic production?
- IGF-1
- TGF-beta
What are inhibitors of elastic production?
- Glucocorticoids
- FGF
What cofactors/coenzymes are required for hydroxylation reaction in collagen synthesis?
- Ferrous iron
- alpha-ketoglutarate
- ascorbic acid (vitamin c)
- oxygen cofactors
What are stimulants of collagen synthesis?
- Ascorbic acid
- TGF-beta
- IGF-1
- IGF-2
What are inhibitors of collagen synthesis?
- IFN-y
- Glucocorticoids
What is the best indicator of collagen breakdown?
- Hydroxyproline in urine
What are GAGS?
- Support cells
- Provide tissue turgor
- Facilitate cell-cell interaction
When does the maturational phase occur?
Week 3 to >1 year
What happens to collagen in the maturational phase?
- Collagen synthesis/degradation equilibrates: change in predominant collagen III–>I
- Cross linking of collagen occurs and random collagen fibrils are replaced with organized fibrils, therefore increased tensile wound strength
What happens to fibroblasts in the maturational phase?
- Change into myofibroblasts that contract the wound
- Can be inhibited by colchicines and corticosteroids
How does the wound strengthen during the maturational phase?
- Wound strength increases rapidly first 6 weeks
- Levels off at 70% of baseline in 6-8 weeks (why no lifting 6 weeks post-op)
Phases of healing
Phases
1) Inflammatory: 0-10 days
2) Proliferation: 4 days- 3 weeks
3) Remodeling: 3 weeks-1 year
Vascular response
1) Vasoconstriction: initial injury
2) Vasodilation: after 1 days
Cellular response
1) Neutrophils: initial-first few days
2) Macrophages: first few days- 4/5 days
3) Lymphocytes: Day 2-5/6 days
4) Fibroblasts: 4 days-1 year
Major event
1) Clot formation and hemostasis
2) Growth factor and elaboration
3) Collagen deposition
4) Collagen cross linking: remodelling phase (3 weeks-1 year)
What are the short term effects of glucocorticoids on wound healing?
- Suppress IL-2 production
- Inhibit lymphocyte activation
- Inhibit neutrophil migration to areas of inflammation
- Inhibit monocyte migration to areas of inflammation
- Inhibit histamine release and histamine-induced lysosomal degranulation by mast cells
- Inhibit B cell activation and proliferation at high doses
- Retards entry of free water into cells
- Decreases capillary permeability to water
- Weak mineralocorticoid effect
- Stimulation of angiotensin release (maintains BP)
- Inhibits PG12 (potent vasodilator)–>maintenance of BP
- Impaired collagen mRNA transcription and fibroblast activity
- Inhibit osteoclast activity
- Promotes early closure of epiphyseal plates in kids
