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4 Stages of Healing

How Do Wounds Heal?

Research work on acute wounds in an animal model shows that wounds heal in four phases. It is believed that chronic wounds must also go through the same basic phases. Some authors combine the first two phases.

The phases of wound healing are:

  • Hemostasis
  • Inflammation
  • Proliferation or Granulation
  • Remodeling or Maturation

Once the source of damage to a house has been removed and before work can start, utility workers must come in and cap damaged gas or water lines. So too in wound healing damaged blood vessels must be sealed. In wound healing the platelet is the cell which acts as the utility worker sealing off the damaged blood vessels. The blood vessels themselves constrict in response to injury but this spasm ultimately relaxes. The platelets secrete vasoconstrictive substances to aid in this process but their prime role is to form a stable clot sealing the damaged vessel. Under the influence of ADP (adenosine diphosphate) leaking from damaged tissues the platelets aggregate and adhere to the exposed collagen. They also secrete factors which interact with and stimulate the intrinsic clotting cascade through the production of thrombin, which in turn initiates the formation of fibrin from fibrinogen. The fibrin mesh strengthens the platelet aggregate into a stable hemostatic plug. Finally platelets also secrete cytokines such as platelet-derived growth factor (PDGF), which is recognized as one of the first factors secreted in initiating subsequent steps. Hemostasis occurs within minutes of the initial injury unless there are underlying clotting disorders.

Inflammation Phase:
Clinically inflammation, the second stage of wound healing presents as erythema, swelling and warmth often associated with pain, the classic “rubor et tumor cum calore et dolore”. This stage usually lasts up to 4 days post injury. In the wound healing analogy the first job to be done once the utilities are capped is to clean up the debris. This is a job for non-skilled laborers. These non-skilled laborers in a wound are the neutrophils or PMN’s (polymorphonucleocytes). The inflammatory response causes the blood vessels to become leaky releasing plasma and PMN’s into the surrounding tissue. The neutrophils phagocytize debris and microorganisms and provide the first line of defense against infection. They are aided by local mast cells. As fibrin is broken down as part of this clean-up the degradation products attract the next cell involved. The task of rebuilding a house is complex and requires someone to direct this activity or a contractor. The cell which acts as “contractor” in wound healing is the macrophage. Macrophages are able to phagocytize bacteria and provide a second line of defense. They also secrete a variety of chemotactic and growth factors such as fibroblast growth factor (FGF), epidermal growth factor (EGF), transforming growth factor beta (TGF-__ and interleukin-1 (IL-1) which appears to direct the next stage.

Proliferative Phase ( Proliferation, Granulation and Contraction):
The granulation stage starts approximately four days after wounding and usually lasts until day 21 in acute wounds depending on the size of the wound. It is characterized clinically by the presence of pebbled red tissue in the wound base and involves replacement of dermal tissues and sometimes subdermal tissues in deeper wounds as well as contraction of the wound. In the wound healing analogy once the site has been cleared of debris, under the direction of the contractor, the framers move in to build the framework of the new house. Sub-contractors can now install new plumbing and wiring on the framework and siders and roofers can finish the exterior of the house. The “framer” cells are the fibroblasts which secrete the collagen framework on which further dermal regeneration occurs. Specialized fibroblasts are responsible for wound contraction. The “plumber” cells are the pericytes which regenerate the outer layers of capillaries and the endothelial cells which produce the lining. This process is called angiogenesis. The “roofer” and “sider” cells are the keratinocytes which are responsible for epithelialization. In the final stage of epithelializtion, contracture occurs as the keratinocytes differentiate to form the protective outer layer or stratum corneum.

Remodeling or Maturation Phase:
Once the basic structure of the house is completed interior finishing may begin. So too in wound repair the healing process involves remodeling the dermal tissues to produce greater tensile strength. The principle cell involved in this process is the fibroblast. Remodeling can take up to 2 years after wounding and explains why apparently healed wounds can break down so dramatically and quickly if attention is not paid to the initial causative factors.