wound healing - kumc education/didactic... · dhaval bhavsar, wound healing (basics) skin...

Dhaval Bhavsar, Wound Healing (Basics)

Wound Healing

• Dhaval Bhavsar, MD •

Assistant Professor

Dept of Plastic, Wound and Burn Surgery

KUMC


Skin

• Largest Organ

• Provides

• When breached – infection, loss of thermal

regulation

Protection from elements, Infective organisms

Protective sensation


Normal Skin

http://www.agen.ufl.edu/~chyn/age2062/lect/lect_19/174.gif


Epidermis

http://www.ratbehavior.org/images/Epidermis.jpg


Dermis

http://neuromedia.neurobio.ucla.edu/campbell/skin/wp_images/161_dermis.gif


What is Wound

“any break in the skin or

an organ caused by

violence or surgical

incision”

http://www.udap.com/images/yellowstone


Wound Healing

• restoration of continuity after wounding

http://fulton.edzone.net/cites/winkler-science/team1/chapter%205/image11.gif


Wound Healing- 3 Classic Phases

• Inflammation • Proliferation • Remodeling

http://www.bumc.bu.edu/www/Busm/sg/Images/suturing/phase2.gif


Hemostasis

• Clot formation

• Start point of inflammation


Inflammatory phase

• Starts within 6-8 hrs

• PMN cells

• Later Monocytes (Macrophages)


Inflammation

• Reaches its height at 24-48 hrs

• Also release growth factors

• Prepares wound for proliferation


Proliferation

• Fibroplasia

• Matrix deposition

• Angiogenesis

• Re-epithelialization


Granulation tissue

http://medweb.bham.ac.uk/http/depts/path/Teaching http://www.worldwidewounds.com/2002/april/Vowden/images/WBP-Figure-5e.jpg


Fibroplasia

• Fibroblasts – activated fibrocytes

• Most important cells

• Secrete-

•Collagen

•Glycosaminoglycans

•Elastin

•Fibronectin

•Protease


Fibroplasia

• Fibroblasts increase in number as inflammatory cells decrease

• Begins 3-5 days after wounding

• Migrate and proliferate in response to fibronectin, platelet-derived growth factor (PDGF), fibroblast growth factor, transforming growth factor, and C5a


Collagen deposition

• The most important matrix component

• Deposition starts about 3rd day and

continues for 2-4 weeks depending on

wound size

• Procollagen Tropocollagen Collagen


Collagen Deposition

• Collagen deposition dependent on

• Age

• Tension

• Pressure

• Stress


Matrix

• Source- fibroblasts

• Components

GAG

Heparin Sulfate

Chondroitin Sulfate

Hyaluronic Acid

Dermatan Sulfate


Angiogenesis

• Wound healing requires rich blood supply to sustain newly formed tissue

• It is evident in erythema (redness) of the new scar

• Capillary density decreases as the need reduces and scar matures


Angiogenesis

• Macrophages release- Macrophage derived

angiogenic factor in response to low tissue

oxygen tension

• Work as chemoattractant

• Basic FGF and VEGF are also important


Angiogenesis

• Endothelial cells bud

arise from capillary

ends

• Produced in line

• Endothelial cells

coalesce and bind

fibrin

http://www.med.unibs.it/~airc/angio2.gif


Re-epithelialization

• Covers the granulation tissue with

epidermal cells and completes wound

healing

• Re-establishes the barrier


Re-epithelialization

• Actin-rich protrusions,

lamellipodia and filopodia

• Adhesions at the leading edge

• Cells move forward by

contracting the actin cytoskeleton

• Coordinated processes of

adhesion assembly, disassembly

and turnover

http://www.biochemweb.org/fenteany/research/cell_migration/


Epithelial Cell Migration

http://www.biochemweb.org/fenteany/research/cell_migration/


Wound Contraction

• Centripetal movement of wound edges

• Maximal rate of contraction - 0.75 mm/day

• Depends on the degree of tissue laxity and shape

of the wound

• Role of myofibroblast


Myofibroblast

Lab Invest 2003, 83:1689-1707

http://www.grad.ucl.ac.uk/comp/2003/research/gallery/entries/large/016.jpg


Remodeling

• Collagen remodeling – depends on balance

between new collagen formation and

collagen destruction

• Collagenase and Matrix metalloproteinase


Remodeling • Collagen becomes increasingly organized

• Fibronectin gradually disappears

• Hyaluronic acid and glycosaminoglycans are replaced by proteoglycans

• Water is resorbed

• These events allow collagen fibers to lie closer together, facilitating collagen cross-linking


Remodeling

• Begins approximately 21 days after injury

• Remodeling may continue indefinitely


Strength of Repaired Wound

• Tensile strength- load capacity per unit area

• Maximum achieved in 90 days

• Usually it is 80% of original strength

• Bursting strength- force required to break a wound

regardless of its dimension


Clinical Wound Healing

• Stages are concurrent

• Epithelial migration – 1mm/day

• Requires intervention if larger than 5 cm

http://www.anat.ucl.ac.uk/business/images/woundhealing.jpg


Burn Wound Healing

• Superficial- primary

epithelization

• Partial- From epithelial

appendages

• Deep partial- slow epithelization

from remaining epithelial

appendages

• Deep- Can not epithelize

Superficial

Partial Deep


Fetal Wound Healing

• Rapid

• Efficient

• Perfect

• Scar less


Fetal Wound Healing

• Involves mechanisms similar to cell migration and proliferation during embryonic stage of fetal life

• No inflammation

• Wound contraction takes place but no scarring


Abnormal Healing

• Hypertrophic scar

• Keloid

• Chronic non-healing wound


Hypertrophic Scar

• Imbalance in collagen

production and degradation

• Either over production OR

• Low degradation

• Red, elevated scars

http://www.51qe.cn/pic/30/12/17/42/b/01701.jpg


Hypertrophic Scar

• Usually along tension

lines

• Contracture occurs more

in areas with laxity

http://surgclerk.med.utoronto.ca/Burn/images/scar1.jpg


Keloid

• African>Asians> Caucasians

• Comparable to malignant

growth

• Extends beyond wound

margins

http://www.emedicine.com/derm/images/917dumbellear.jpg


Non healing Wound

• Wound that fails to

progress through an orderly

sequence of repair in a

timely fashion

• Arbitrary time point: 3-4

weeks

http://www.uth.tmc.edu/anes/wound/images/figure_1.jpg


Causes of Delayed Wound Healing

• Infection

• Tissue hypoxia

• Repeated trauma

• Presence of necrotic tissue or foreign body

• Systemic causes

• Diabetes

• Malnutrition- protein

• Immunodeficiency


Common Non-healing Wounds

Diabetic wound Pressure sore Venus ulcer

http://health-pictures.com/images/Decubitus.jpg http://medicine.ucsd.edu/ http://www.bu.edu/woundbiotech/bioengineered


Wound Healing & Nutrition

• Vitamin C and A

• Protein

Essential amino acids

• Micronutrients

Mg, Cu, Zn, Fe

Investigate

• Serum protein

• Hemoglobin


Tendon Repair

Gross Examination

Early phase

Intermediate phase

Late phase J Hand Surg [Am]. 2003 Sep;28(5):814-23


Nerve Repair

http://www.northland.cc.mn.us/biology/AP2Online/Fall2001/Nervous/images/neuron_regeneration.gif


Bone Repair

http://137.222.110.150/calnet/musculo/image/fracture%20repair%20scheme.jpg


THANK YOU

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