17 Wound Healing by 1st, 2nd, or 3rd Intention

Wounds

Any break in the skin is termed a wound and appropriate wound management is important in ensuring optimal healing.  Wounds can vary in size, depth, level of infection, jaggedness of edges, and extent of gap, all of which can affect the cellular and biochemical responses in tissue repair and healing.  Each one requires proper cleaning, dressing, and possibly debridement and/or suturing in order to faciliate healing.

In all cases there are four phases of wound healing:

1)  hemostasis, 2) inflammation, 3) granulation and proliferation, and 4) remodeling.

Additionally, there are 3 categories of wound healing (primary, secondary, and tertiary).

Wound Healing by Primary (1st) Intention

A wound that has resulted in minimal loss of tissue and minimal gap (e.g. an uninfected surgical incision) has been observed to heal through primary intention.  In this process, a fibrin clot is formed, neutrophils appear at the margins of the incision.  Cellular debris is phagocytosed by neutrophils and macrophages.  Angiogenesis occurs, allowing for revascularization of the site.  Granulation (highly vascular, pink, moist fragile) tissue fills in the wounded space and the ropy protein collagen is produced by fibroblasts and used to bring the two wound edges closer together as the cross-linked collagen contracts.  Many of the cells (fibroblasts, macrophages, epithelial and endothelial cells as well as platelets) in this area release growth factors to stimulate mitosis of replacement cells.  Epithelial stem cells give rise to functional daughter cells that take the place of cells that have died.  Loss of functional tissue is minimal and there is minimal scarring.

Summary of Healing Steps by 1st Intention:

1. A thin narrow wound in the skin is made (e.g. surgical incision, paper cut), and healing by 1st intention will occur if wound is clean, fresh (within 4-8hrs), free of debris, or necrosis, and the gap is minimal.
2. Closure can be stabilized and gap reduced through use of sutures, staples, or synthetic adhesive closure material (e.g. tape, glue).  This will speed healing and reduce chances of infection.
3. Within the tissue:
   1. Hemostasis phase: Cellular damage causes the release of cytokines and cellular components which attracts macrophages, neutrophils, platelets and mast cells.  Hemostasis and inflammation is stimulated.
   2. Inflammation phase:  Macrophages and neutrophils remove any pathogens and cellular debris.  Platelets create fibrin mesh.
   3. Granulation and Proliferation phase:  Activated cells (fibroblasts, macrophages, epithelial and endothelial cells) release growth factors that stimulate angiogenesis (the formation of new capillaries) and the formation granulation (pink, moist, fragile) tissue.  Epithelial and endothelial stem cells undergo mitosis creating replacement cells. Fibrobalst produce collagen which crosslinks across the wound, contracting and strengthening the zone.  This will form scar tissue (as collagen will be prevalent in area in place of some/many lost epithelial cells).
   4. Remodeling:  The scar (consisting largely of collagen) may diminish over time as it is gradually replacedy by epithelial cells.    The extent of remodelling possible will depend on the width and depth of the wound as well as underlying factors (person’s age, health, genetics etc.).

Healing by Secondary (2nd) Intention

A wound that has a large gap between tissue edges that may also be infected often heals by secondary intention.  In this case the wound is larger and/or deeper than a wound that heals by 1st intention and it is not possible to close the wound with sutures (as it would generate too much tension).  The wound edges may be jagged, and there may be external debris and infectious agents may have infiltrated throughout the wound.  As a result the wound will take longer to heal and will require more care to facilitate optimal healing.  The wound needs to be cleaned and maintained in a manner that limits exposure and growth of infectious agents.  It is likely that the amount of collagen and scar tissue that forms will be greater than in a wound healed by 1st intention.  At the tissue level, the same steps will occur in that neutrophils and macrophages will be recruited to remove debris as well as contain and eliminate any infection.  These WBCs will release pro-inflammatory cytokines and the extent of inflammation will be greater that what is observed in a wound that heals by 1st intention.  Following the steps of healing, angiogenesis will occur and granulation tissue will fill in the wound gap and any eschar or non-viable tissue will gradually be sloughed off.  At the same time, fibroblasts will produce collagen and the gap will continue to fill in with epithelial cells, fibroblasts and collagen.  In wound that heals by 2nd intention, the damaged area that is filled with scar tissue, will contain less functional cells (e.g. fewer melanocytes, fewer hair follicles, fewer sweat and sebaceous glands, fewer sensory neuron receptors) and more scar tissue than a wound that has healed by 1st intention.

Summary of Healing Steps by 2nd Intention:

1. A larger gap wound in the skin is made (that may contain debris and large jagged edges).  It is not possible to close the wound by suturing, and healing by 2nd intention will occur.  Wound should be cleaned and dressed to minimize exposure and growth of infectious agents.  Debridement at some point may be necessary.
2. Within the tissue: the same 4 steps will take place as in healing by 1st intention, but much slower and resulting in more fibrosis and scar tissue.  The 4 steps include: Hemostasis, Inflammation, Granulation and Proliferation and Remodeling

Healing by Tertiary (3rd) Intention

At times a wound that has been healing by secondary intention will be purposely interrupted in the granulation stage in order to close the wound through skin grafts or suturing or stapling.  At the point of interruption, angiogenesis and granulation may have already begun to form.  Mechanically closing the wound after an initial delay like this allows for infections to be treated and edema to clear.  In this type of proccess, debridement may also have been required prior to closing the wound mechanically.

Burn Wounds

Burns can be classified as thermal, electrical or chemical.  Just as with cuts and trauma discussed above, burns can also cause wounds to the skin.   In fact burns can additionally cause wounds within the respiratory tract due to smoke inhalation and throughout the digestive tract if chemicals are ingested.  In each of those areas, the burn can destroy or damage the surface epithelial layers and if severe, can damage underlying connective tissues and perhaps even muscle of other tissues.  The severity of the burn depends on the cause, the temperaure (if thermal), the strength (if electrical or chemical), the duration of exposure, the size of the body area exposed, and the site of damage.   Older adults, infants, and children are more at risk for deeper burns as their epithelial tissue layers (e.g. skin) are thinner.  It is also worth remembering that skin of the soles of the feet are slightly thicker that skin on the rest of the body.

When classifying burns of the skin:

Partial-Thickness 1st degree Burns:  involve part of the epidermis but not the dermis.  Inflammation is present and a burn blister may form.  Sun burns and some stove-top burns fall into this category.  It is recommended that the burn blister be left intact (not punctured), in order to reduce chances of infection and speed healing.

Partial-Thickness 2nd degree Burns:  involve the epidermis and part of the dermis.  Inflammation and blister formation will occur.  Some stove-top burns and other burns fall into this category.

Full Thickness (or 3rd degree) Burns:  involve the epidermis, the dermis, as well as the hypodermis (and perhaps even underlying tissues).  Inflammation, edema and often eschar (dead tissue) are associated with this type of wound.   The wound may be coagulated or charred and it may be necessary to relieve pressure through escharptomy

Burns that are severe can give rise to local (e.g. inflammation, pain) and systemic effects which can include:

• Dehydration: Large wounds in the skin can mean that there is signifcant loss of water through evaporation.  Often this is controlled to some degree through use of synthetic dressings or skin grafting.
• Edema:  Large wounds can mean that there is significant inflammation and associated increases in capillary permeability.  This can lead to extensive swelling and edema as well as decreased blood volume.
• Hypovolemic Shock:  Due to both dehydration and edema, burns can put a patient at risk for hypovolemic shock.  (Reminder: shock is defined as a condition in which not enough blood is pumped through the body, meaning that organs are not receiving sufficient oxygen and nutrients.  This can rapidly lead to organ failure).  The kidneys, brain and heart are especially susceptible to failure with poor blood flow.   Signs of hypovolemic shock include:  low blood pressure (hypotension), acidosis (due to hypoxia, organs perform high levels of anaerobic respiration producing lactic acid).  Not only are the brain and heart begin to fail with low blood flow (e.g. low oxygen and nutrient levels), cardiomyocytes and neurons do not function will in acidic conditions.  The failure of organs can quickly become fatal.  Hypovolemic Shock summary:  Massive inflammation → extensive vasodilation → hypotension → hypoxia → organ failure → death
• Anemia: is defined as poor oxygenation of blood and this can occur in large wounds (due to trauma or burns) as a result of blood loss.
• Respiratory problems: due to smoke inhalation which can damage bronchioles which leads to inflammation.  The ensuing swelling and  bronchoconstriction as well as the presence of inhaled ash or formation of eschar can impede air flow as well as gas exchange.
• Infection: any damaged exposed area is prone to infection.  When the damaged area is large in size or in depth, the risk of sepsis and septic shock increases.  Sepsis is defined as infection of the blood stream, which can trigger massive systemic vasodilation.  As the name suggests Septic Shock refers to the ensuing low blood pressure that occurs with massive systemic vasodilation.   As with Hypovolemic Shock, septic shock is characterized by low blood pressure (hypotension) and the inability to deliver sufficient blood flow to organs in order for their survival.  Septic shock can progress quickly to organ failure and can be fatal if not treated quickly.
• Septic Shock summary:  Infection → systemic vasodilation → hypotension → hypoxia → organ failure → death
• Hypermetabolism: Increased metabolic needs for cells occurs during healing period.  The patient must be given sufficient nutrients, water, and electrolytes.

Treatments of Severe Burns can involve:

• Cold compresses and immediate covering of clean wound to prevent infection
• Skin grafting or synthetic coverings and wound maintenance
• Antibiotics to reduce chances of infections
• Sufficient nutrients, water, and electrolytes
• Physiotherapy and stretching as soon as possible to reduce loss of range of motion associated with scarring
• Future surgeries may be necessary to release restrictive scar tissue (contractures and/or adhesions).

Factors that Affect Wound Healing:

1. Oxygenation of Tissue: Poor oxygenation of tissues lowers cellular activity and mitotic rates and delays healing
2. Age:  Older adults experience slower healing than young adults due to lower cellular activity levels.
3. Estrogen:  Older adult females tend to heal faster than older adult males
4. Infection:  The presence of an infection will delay healing
5. Foreign material:  Dirt, thorns, splinters, debris will delay healing (especially if not removed and the wound is not sufficiently cleaned)
6. Biological Stressors:  Underlying illnesses (e.g. diabetes, cancer) can delay healing
7. Obesity: May delay healing due to chronic inflammation and reduced vascularity
8. Glucocorticoid use:  Slows healing due to immunosuppressive and catabolic effects
9. NSAID and Selective COX-2 (C2s):  Can increase scarring
10. Chemotherapy:  reduces WBC proliferation and count numbers as well as cell division and angiogenesis, all of which can delay healing
11. Nutrition deficits: can reduce building blocks (proteins, carbohydrates, fats, vitamins, and elements such as zinc and magnesium) required for cellular activity and division which can delay healing
12. Alcohol: slows cellular activity which can delay healing
13. Smoking: causes vasoconstriction which can reduce oxygen and WBC delivery and delay healing

What’s the Problem with Scars?

While scars are sometimes cited as attractive or magical (e.g. the fictional character Harry Potter’s lightening bolt scar), depending on their location, extensive scarring can cause the following problems:

1. Loss of function:  For example as above in wound healing, skin will lack hair follicles, glands & sensory nerve endings.  Other tissues that are less regenerative than skin, will not be able to heal through regeneration and will exhibit far more fibrosis and loss of functional cells.  For example, heart cells, kidney cells, and neurons of the brain and spinal cord will be not be replaced by functional cells.
2. Non-elasticity of scar tissue may limit range of motion of the skin which then limits movement of underlying muscles bones and joints.  For examples large burn wounds within the face, can result in contractures that limit facial expressions and jaw movement.  Often skin grafting other techniques are used to decrease contracture formation and loss of range of motion.  At times contractures can be improved by surgery or offset by physiotherapy.
3. Adhesions or bands of scar tissue may form between internal organs, which can prevent normal movement.  For example adhesions between loops of the intestines can twist and distort tissue resulting in intestinal blockages.
4. Keloids or hypertrophic or raised scar tissue on the skin can occur when the body produces excessive collagen.  Keloid formation after wound healing is more common on the upper chest or back.  It can can cause more contracture & keloids are either regarded as disfiguring or attractive.  In some cultures, wounds are purposely created on the body to encourage keloid formation in artistic patterns.  The likelihood of keloid formation has strong genetic underpinnings, and are more likely to form on individuals with darker skin. Removal or reducation of keloids through surgery (laser, cryotherapy) and corticosteroid injection is possible.
5. Ulceration may occur if the scar impairs blood supply and causes further tissue damage.  Though more often, it is the other way around where ulcers (when healed) result in scarring.  In very rare cases scars can become cancerous ulcers and this is usually when the scar is a site of a chronic wound.