The physiology of the healing process
The most largest organ of the body is the skin. The skin acts like a barrier between the body and environement. Composed by 3 layers (epidermis, dermis, subcutis) and associated adnexa, the skin is a complex organ with many functions and properties: thermoregulation, motion and shape, environmental protection, storage (vitamins, electrolytes, fat, etc.), immunoregulation, sensory perception, secretion, excretion, etc.
Following trauma, the skin is the first organ to undergo changes. A wound represent a disruption in the continuity on anatomical structure with deterioration of the physiological function. There are several criteria for wound classification:
– by the time that has passed since wound production: acute or chronic;
– by the thickness of the skin layer that has been injured: full-thickness or partial thickness;
– by the degree of contamination:
· clean wounds – made under aseptic conditions (surgical wounds), in which it does not penetrate into the chest cavity, gastrointestinal, genitourinary tract;
· clean contaminated wounds – in which the respiratory, gastrointestinal, or genitourinary tract is entered with minimal contamination;
· contaminated wounds – wounds with a major break in sterile technique, open traumatic wounds less than 4-6 hours old with inflammatory process without purulent discharges;
· infected wounds – traumatic wounds with purulent discharges or perforated viscera, more than 6 hours old.
After trauma, when the patient shows up in the clinic, it must be stabilized initially. If haemmorage is present, the wounds need to be bandaged with sterile gauze to stop bleeding, and emergency treatment should be initiated according to the patient’s needs. If it is not an emergency and the patient comes to the clinic with an older wound, after obtaining the complete anamnesis and examining the wound, formation of an initial plan of treatment is necessary. Thereby, depending on the type of wound, the approach differs. Four types of wound closure are described:
– primary closure, called also healing by first intention represents immediate closure of a fresh wound. This category includes recent traumatic wounds and surgical wounds.
- delayed primary closure is indicated when the injured tissue have questionable viability or infection is suspected. The closure is delayed 3-5 days in which time the wound is assessed with proper dressings. Also delay closure offers time for proper drainage and the inflammation will decrease. Approximately 5 days after wounding fibroplasia, cytokines and macrophages will protect the wound against infection and closure can be performed. This type of closure is done before granulation tissue formation.
– secondary closure is performed after granulation tissue formation. Usually 5-10 days after injury; this type of closure is indicated when necrotic tissue persists and need to be debride many times, when inflammation is prolonged or when signs of infection are still present
.- healing by second intention represents healing by granulation, contraction and re-epitelisation. This method is applicable for next types of wounds:
· moderate to large wounds in young animals that are located on trunk. Kittens and puppies have a fast rate of healing;
· wounds located in areas where the closure may create a “tourniquet effect“ (commonly on distal limbs). In this situation the circulation is compromised
;· infected wounds and those who presents questionable tissue viability;
· wounds that are closed under tension and dehiscence will occur.
How do wounds heal?
Tissue continuity is restored by the healing process. This biologic process begin immediately after injury or incision. Wound healing is a complex process that comprise three phases: inflammation and debridement, proliferation (repair), maturation and remodeling. All these three stages overlap and have a different duration.
Ø Inflammatory and debridement phase.
After wounding, to avoid exsanguination hemostasis occur. Following the breakdown of blood vessels, endotheline is produced and along with other mediators (serotonin, bradykinin, catecholamines, histamine, prostaglandins) cause contraction of muscle within the vessel walls and hemorage is stopped by vasoconstriction. After 5-10 minutes, vasodilation occur. An increased blood flow to the wound bed and extravasated fluid in the wound will be present. Subsequent vasodilation, leukocyte migration starts (neutrophils and monocytes). At this point the wound will have the classic aspect of inflammation: swelling, elevated local temperature, erythema, pain. In early inflammatory phase the neutrophils predominate and in late inflammatory phase they decrease and monocytes predominate.
The main cells: –endothelial cells: neoangiogenesis-provides oxygen and nutrients to the tissue;
–macrophages and neutrophils: debridement, phagocytosis of bacteria
and other pathogens.
- Proliferative (repair) phase. About 4-6 days later, after wound debridement, the wound enters in repair phase. This stage lasts from day 5 until day 20 but can be longer and depends on many factors: wound size, location, age, health, etc. Four stages are included in the proliferative phase: angiogenesis, fibroplasia, contraction and epitelisation. The aspect of the wound will change in this phase from red to pink and the quantity of exudate will decrease. This phase is predominated by macrophages, fibroblasts, endothelial and epithelial cells. Due to platelet-derived groth factor (PDGF) and transforming growth factor (TGF-β), fibroblasts migrate in the wound from surrounding tissue. As a response to PDGF
type III collagen is synthesized by fibroblasts. After 7-14 days, TGF-β increase synthesis of type I collagen. Collagen afford strength to connective tissue. There are more than 20 types of collagen. Type I collagen is present in unwounded dermins in 80% and type III collagen in 20%. Finally, due to TGF-β1, fibroblasts are transformed into myofibroblasts and wound contraction begin. Contraction increases with a speed of approximately 0.6 to 0.8 mm/day. As a response to epidermal growth factor (EGF) and TGF-α proliferation of epithelial cells begin. Epitelisation continue until complete epidermal thickness. The growth rate of the granulation tissue is 0.4 – 1mm/ day. The granulation tissue is very fragile in consistency and act as a barrier to infection.
- Maturation and remodeling phase. In the last phase of wound healing remodelling and strengthening of collagen take place. Care must be taken at the beginning of this phase because the scar tissue new formed is very thin and fragile and need few weeks until will gain a proper strength. Due to a changing in collagen type (only 10% of type III collagen present in the scar tissue) rigidity rise and the matrix becomes more stiff. Though, the final scar tissue will not achieve the elasticity and strength of a normal tissue. The maximum strength will be approximately 70 % – 80%. Usually this phase starts 3 weeks after wounding and continue until 1 year.
Figure 1. Illustration of approximate time of wound healing stages. Inflammatory phase last between 0-6 days,
repair phase 4-25 days and maturation and remodelling phase 21 days to months. Overlapping of healing stages is represented by the green triangles.
Figure 2. Illustration of cell distribution in the time of healing;
Conditions that delay or impede wound healing
Factors who are involved in this process are grouped into several categories:¨ Host factors: hypoproteinemia (malnutrition); age (wounds in elderly patients have a longer healing time compared to young patients); internal organ disfunctions (Cushing Syndrome- excess circulation of glucocorticoids, liver diseases – clotting factor deficiencies, diabetes mellitus, uraemia, hypothyroidism), obesity, immune disfunction, viral diseases (FeLV/FIV), cancer, coagulopathies, self trauma;¨ External factors: infection, foreign bodies (environmental – grass awns, soil; surgical metal plates, drains), radiation therapy, long surgical time and hypoperfusion;¨ Medication: chemotherapy, glucocorticoids, NSAID, anticoagulants, cytotoxic solution used for lavage; ¨ Mechanical factors: motion, tension, pressure (from bandage).
In which stage of healing we are?
In order to choose an appropriate treatment method (closure or dressing) it is necessary to recognize the phases of wound healing. Some specific aspects should be considered: macroscopic appearance (infection, contamination, blood, inflammation), time elapsed from wound appearance, amount of exudate, wound size, tissue viability, wound margins. This section will illustrate wound details in different phases of healing.
Figure 3. Ventral view of abdomen of a cat during Figure 4. Approximate 1 hour old wound located on
spay, midline approach; This is a surgical clean the left front leg, between digit IV and digit V. Small
wound. amount of unclotted blood and early inflammation
Figure 5. (a)Lateral view of digit V of left hind in a 6 years old paraplegic female dog. Healthy
granulation tissue is present 9 days post dressings treatment. Mild exudate was present following the
removal of the bandage . (b)The same pacient 18 days after wounding; a nearby photograph was made to highlight the presence of epithelisation present at the wound edge (black arrows). The white color at the
center of the wound represents the reflection of the camera light. (c) Maturation phase- complete
epithelisation present in day 44 post dressing treatment.
Figure 6. Dorsal view of the right paw of the hind limb in a cat;
The deglowing wound shows necrotic tissue, foreign materials devitalised tissue and mild exudate; High local tempreture was present on palpation. The infected wound was debride surgically, treated with dressings and later a full thickness mesh graft was applied. The cat disappeared from home for 2 weeks.
Figure 7. Left latera view of a 4 years old male Yorkshire beign bitten by a dog; Second intention healing
from the beginning until the end was chosen. Granulation tissue is in the middle followed by epithelisation
and obvious wound contraction after 4 weeks of treatment with dressings.