Tag-Archive for ◊ Cell biology ◊

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• Tuesday, August 03rd, 2010

Phases of healing

Early
Intermediate
Late
Terminal

Early wound healing events

Hemostasis
Platelet aggregation
Intrinsic and extrinsic coagulation cascade
Thrombin, fibrin
Vasoconstriction

Inflammation
Vasodilatation
Increase in vascular permeability
Chemotaxis
Cellular response

Intermediate wound healing events

Mesenchymal cell chemotaxis and proliferation
Angiogenesis
Epithelisation
2-4 days after injury
Mediated by cytokines

Fibroblasts- migration and proliferation
Smooth muscle

Angiogenesis- reconstruction of vasculature
Stimulate: High lactate, acidic Ph, low O2 tension
Endothelial cell migration and proliferation

Epithelisation
Partial thickness- Cells derived from wound edges and epithelial appendages.
Incisional wound: cellular migration over less then 1 mm. Wound sealed in 24-48h.

Cellular detachment
Migration
Proliferartion
differentiation

Late wound healing events

Collagen synthesis
3 helical polypeptide chains
Lysine and proline hydroxylation
Required for cross-linking

Wound contraction

Centripetal movement of the wound edges toward the center. ( 0.6-0.7 mm/day)
Begins at 4-5 days
Maximal contraction 12-15 days
Trivial component in closed incisional wounds, significant for closure of open wounds
Rate- depends on tissue
Circular wounds- slower closure but avoid stenosis

Mechanism- cell mediated processes, not requiring collagen synthesis
Myofibroblasts- fibroblasts with myofilaments in cytoplasm
Appear in wound day 3-21
Located in periphery- pull wound edges together.
Contractures- contraction across joint surface

Terminal wound healing events

Remodeling- turnover of collagen. Type 3 replaced by type 1
Day 21- net accumulation of wound collagen becomes stable
Wound bursting strength- 15% of normal.
Week 3-6- greatest rate of increase
6 weeks- 80-90% of eventual strength.
6 months maximum strength ( 90% ). Process continues for 12 months

Cytokines and growth factors

Primary mediators in wound healing.
Endo, para, auto, intracrine function
EGF
FGF
PDGF
TGF

Which of the following is primarily responsible for tensile strength in a healing wound 4 days after injury?

Collagen
Elastin
Fibrin
Fibronectin
Hyaluronic acid

Which of the following is primarily responsible for tensile strength in a healing wound 6 weeks after injury?

Myofibroblasts
Fibrin
Fibronectin
Collagen
Collagen cross linking

Infection
foreign body/ necrotic tissue, hematomas
local/ systemic factors
type of surgery

Hypoxia and smoking
O2 delivery necessary for cellular respiration and hydroxylation of proline and lysine
Smoking- vasoconstriction, atherosclerosis, carboxyhemoglobin.

Radiation
Collagen synthesized to abnormal degree- fibrosis
Fibrosis of vessels- (media)-occlusion
Thinned epidermis, pigmentation
Limited access of inflammatory cells and cytokines- impaired healing
Damage to fibrocytes and keratinocytes.

Systemic factors

Malnutrition
Limited AA supply for collagen synthesis
Consumption of proteins d/t CHD and fat deficiency.
Vit C deficiency- diminished hydroxylation of lysine and proline,
Vit D- impaired bone healing
Zinc- inhibition in cellular proliferation and defficient granulation tissur formation

Normal healing is accelerated by which of the following?
VitC
VitA
Zinc
Increased local oxygen tension
Scarlet red

Cancer
Cachexia, anorexia
Altered host metabolism.
Protein catabolism
Abnormal inflammatory cell response

Old Age

Diabetes
Impaired healing ( decreased chemotaxis and phagocyte function )
Risk of infection

Hypertrophic scars and kelloids

Excessive healing processes- increase in net collagen synthesis raised thickened scar
Keloid- Extension beyond wound margin, familial, may develop up to 1 year, rarely subside
Hypertrophic scar- Confined to wound margin, light skinned, early after injury, may subside, cause contractures
Tx- excision, steroid injection, pressure garments, radiation tx

Types of wound closure
Primary closure
Approximation of acutely disrupted tissue with sutures, staples or tape
Secondary wound closure
Open wound margins approximate by biologic contraction

If a patient requires reoperation 1 month after a midline abdominal incision which of the following promotes the most rapid gain in strength of the new incision
Separate transverse incision
Midline scar is excised with a 1 cm margin
Midline incision reopended without scar excision
Rate of strength ganed is not effected by incision technique