Tissue and Wound Healing

Skin

Largest organ in body

• 1.2-2.2 square meters

• 4-5 kg (9-11lbs)

Functions

• serves as 1st line of defense; waterproof barrier

• Minimizes excessive water loss

• Maintains thermoregulation

• Contains receptors for somatic sensations

• Participated in metabolism and activation of Vitamin D

2 layers

• epidermis and dermis

Epidermis

Upper layer of skin

• stratified squamous epithelial cells; keratinocytes

• Melanocytes

• dendritic (Langerhans) cells

  • weave between surrounding keratinocytes to continuously scan the skin surface for foreign invaders like bacteria and viruses.

• Tactile (Merkel) cells

  • sensory receptors for touch

Dermis

Contains

• Blood vessels

• Skin appendages

• Sensory receptors for pain, touch, temp

• Smooth and skeletal muscle cells

2 layes

• Papillary layer (superficial)

• Reticular layer (thicker and deeper)

Dermal-epidermal Junction DEJ

Barrier against passage of substances into and out of body

specialized, undulating interface that connects the outer epidermal layer of the skin to the underlying dermal layer

Framework to restore architecture of the tissue

Extracellular matrix ECM

Ground substance

Tissue growth and wound healing

Fibrous structural proteins

• collagen and elastin

complex, non-cellular 3D network of macromolecules—including proteins, glycoproteins, and polysaccharides—that surrounds, supports, and gives structure to cells and tissues in the body

Acute wound

Occurs suddenly or over brief period

Restoration of structural and functional integrity in 4-6wks

Chronic wound

occurs over long period

Does nto heal in organized and timely manner

Impairment of structural and functional integrity

Partial thickness wound

Damage extends through epidermis; dermis intact

Reepitheliailzation: epithelial cells migrate to area and replicate by mitosis

Full thickness wound

Damage extends through epidermis and dermis

Possibly extends into subcutanteous tissue, muscle, bone

Scar formation!

Primary intention (primary closure)

Wound healing

clean, opposed wound edges are brought together and closed immediately using sutures, staples, surgical glue, or adhesive strips

Surgical closure of wound

Repair

• formation of new ECM

Regeneration

• reepithealialization

Little granulation tissue

Secondary intention (secondary or spontaneous closure)

Wound healing

edges of a wound are left open and not stitched or approximated together. Instead, the wound heals gradually from the bottom and sides up

full thickness wound heals without closure attempt

large amount of granulation tissue

Longer healing time; larger scar

Tertiary intention (delayed primary closure)

Wound Healing

Combo of primary and secondary intention

wound is intentionally left open for a period of time before it is surgically closed

Contaminated wound cleaned, left open, drainage

Scarring > primary intention and < secondary intention

Hemostasis, inflammatory, proliferative, remodeling

4 phases of wound healing

1. H

   1. stops bleeding after a blood vessel is injured while keeping blood fluid in undamaged vessels

2. I

   1. ebuilding the damaged area with new tissue, blood vessels, and an extracellular matrix

3. P

   1. Rebuilding the damaged area with new tissue, blood vessels, and an extracellular matrix

4. R

   1. collagen deposited, matrix remodeling, wound contraction, vascular prunning

Cytokine

Chemical mediator

• Initiate healing process

• Produce growth factors

• Stimulate expression of growth factors

• Develop the ECM

• Coordinate intercellular communication

sbind to specific receptors on the surface of target cells—functioning like a key fitting into a lock—to instruct the cell on how to behave.

pro and anti inflammatory

Growth factors

Stimulate growth, division, differentiation of other cells

Regulate intercellular communication

proteins or polypeptides that act as signaling molecules to regulate cell growth, proliferation, differentiation, and survival

Nitric Oxide

Direct effect: bacterial killing

Indirect effect: modulate cytokine and growth factor activity

Potent vasodilator, expanding blood vessels to maximize the delivery of vital oxygen and nutrients to damaged cells.

Hemostasis

Goals

• prevent additional tissue injury

• Prepare wound for healing and regeneration

Phases

1. Platelet adhesion, platelet activation, platelet plug

2. Fibrin clot formation

• recruitment of phagocytic cells and wound debridement

prothrombin — thrombin — fibrinogen — fibrin

Inflammatory Response

Goals

• to clean the wound

• prevent additional tissue injury

• prepare wound for healing and regeneration

• Recruitment of phagocytic cells and wound debridement

Proliferative phase

____ of wound healing

Goal

• wound healing guided toward tissue repair

Steps

• Granulation tissue: foundation for collagen based matrix that replaces fibrin based provisional matrix

• Fibroblasts: produce collagen, adhesive proteins for ECM

• Myofibroblasts

• Endothelial cells: angiogenesis (neovascularization)

• Reepithealialization: regeneration of keratin

VEGF (vascular endothelial growth factors)

___ mediating angiogenesis

Remodeling Phase

____ of wound healing

• restores structural and functional integrity of skin

• Dermal matrix not regenerated; mended

Steps

• wound contraction and closure

• continuous turnover of collagen

• Decreased capillary density

• declining cellular content

• Mature scar tissue devoid of skin appendages

• Maturation of scar tissue continues for minimum of 1 yr

Stages

____ of wound healing with cellular involvement

Hypoxia

Delays or stops wound healing process, leading cause of wound infection

Inhibits fibroblast activity, collagen deposition in matrix

Infection and contamination

Badly contaminated wounds may overwhelm host defenses

Surgical wound handling

Contamination

Necrotic tissue, foreign or exogenous material, endogenous substances get into wound and cause it to get worse

non-multiplying microorganisms, foreign material, or a major break in sterile technique

Nutritional Status

Major role in wound healing

Essential macronutrients

• carbs and fats

Effect of negative nitrogen balance

• impaired immune and inflammatory responses

• Delayed wound healing; increased wound infection

• Diminished angiogenesis

Vitamin and mineral deficiencies

• associated with chronic, non-healing wounds in nutritionally debilitated people

Corticosteroids

Meds

• promote breakdown of carbs, fats, proteins

• Anti-inflammatory action impedes inflammatory phase of wound healing

• Various negative effects

Antineoplastic drugs

Med

• potent immunoscuppressants

• Impair reepithealialization, granulation tissue formation, angiogenesis

• medications used to treat malignant tumors and cancers by killing or inhibiting the growth of cancer cells

Diabetes Mellitus

Metabolic status

• insufficient insulin, insulin resistance or both

• Hyperglycemia with untreated diabetes

  • chronic macro-vascular disease

  • Atherosclerosis; tissue ischemia and hypoxia

  • Thickening of basement membranes: diabetic lesions

• With impaired perfusion

  •