Which of the following is the first step in tissue repair?

By the WoundSource Editors

The stages of wound healing proceed in an organized way and follow four processes: hemostasis, inflammation, proliferation and maturation. Although the stages of wound healing are linear, wounds can progress backward or forward depending on internal and external patient conditions. The four stages of wound healing are:

Hemostasis Phase

Hemostasis is the process of the wound being closed by clotting. Hemostasis starts when blood leaks out of the body. The first step of hemostasis is when blood vessels constrict to restrict the blood flow. Next, platelets stick together in order to seal the break in the wall of the blood vessel. Finally, coagulation occurs and reinforces the platelet plug with threads of fibrin which are like a molecular binding agent. The hemostasis stage of wound healing happens very quickly. The platelets adhere to the sub-endothelium surface within seconds of the rupture of a blood vessel's epithelial wall. After that, the first fibrin strands begin to adhere in about sixty seconds. As the fibrin mesh begins, the blood is transformed from liquid to gel through pro-coagulants and the release of prothrombin. The formation of a thrombus or clot keeps the platelets and blood cells trapped in the wound area. The thrombus is generally important in the stages of wound healing but becomes a problem if it detaches from the vessel wall and goes through the circulatory system, possibly causing a stroke, pulmonary embolism or heart attack.

Inflammatory Phase

Inflammation is the second stage of wound healing and begins right after the injury when the injured blood vessels leak transudate (made of water, salt, and protein) causing localized swelling. Inflammation both controls bleeding and prevents infection. The fluid engorgement allows healing and repair cells to move to the site of the wound. During the inflammatory phase, damaged cells, pathogens, and bacteria are removed from the wound area. These white blood cells, growth factors, nutrients and enzymes create the swelling, heat, pain and redness commonly seen during this stage of wound healing. Inflammation is a natural part of the wound healing process and only problematic if prolonged or excessive.

Proliferative Phase

The proliferative phase of wound healing is when the wound is rebuilt with new tissue made up of collagen and extracellular matrix. In the proliferative phase, the wound contracts as new tissues are built. In addition, a new network of blood vessels must be constructed so that the granulation tissue can be healthy and receive sufficient oxygen and nutrients. Myofibroblasts cause the wound to contract by gripping the wound edges and pulling them together using a mechanism similar to that of smooth muscle cells. In healthy stages of wound healing, granulation tissue is pink or red and uneven in texture. Moreover, healthy granulation tissue does not bleed easily. Dark granulation tissue can be a sign of infection, ischemia, or poor perfusion. In the final phase of the proliferative stage of wound healing, epithelial cells resurface the injury. It is important to remember that epithelialization happens faster when wounds are kept moist and hydrated. Generally, when occlusive or semiocclusive dressings are applied within 48 hours after injury, they will maintain correct tissue humidity to optimize epithelialization.

Maturation Phase

Also called the remodeling stage of wound healing, the maturation phase is when collagen is remodeled from type III to type I and the wound fully closes. The cells that had been used to repair the wound but which are no longer needed are removed by apoptosis, or programmed cell death. When collagen is laid down during the proliferative phase, it is disorganized and the wound is thick. During the maturation phase, collagen is aligned along tension lines and water is reabsorbed so the collagen fibers can lie closer together and cross-link. Cross-linking of collagen reduces scar thickness and also makes the skin area of the wound stronger. Generally, remodeling begins about 21 days after an injury and can continue for a year or more. Even with cross-linking, healed wound areas continue to be weaker than uninjured skin, generally only having 80% of the tensile strength of unwounded skin.

The stages of wound healing are a complex and fragile process. Failure to progress in the stages of wound healing can lead to chronic wounds. Factors that lead up to chronic wounds are venous disease, infection, diabetes and metabolic deficiencies of the elderly. Careful wound care can speed up the stages of wound healing by keeping wounds moist, clean and protected from reinjury and infection.

The body is a complex and remarkable machine, and the dynamic process of wound healing is a great example of how our body’s different systems, along with the proper wound care products, work together to repair and replace devitalized tissues. But how, exactly, does our body heal?

When the skin is injured, our body sets into motion an automatic series of events, often referred to as the “cascade of healing,” in order to repair the injured tissues. The cascade of healing is divided into these four overlapping phases: Hemostasis, Inflammatory, Proliferative, and Maturation.

Phase 1: Hemostasis Phase

Hemostasis, the first phase of healing, begins at the onset of injury, and the objective is to stop the bleeding. In this phase, the body activates its emergency repair system, the blood clotting system, and forms a dam to block the drainage. During this process, platelets come into contact with collagen, resulting in activation and aggregation. An enzyme called thrombin is at the center, and it initiates the formation of a fibrin mesh, which strengthens the platelet clumps into a stable clot.

Phase 2: Defensive/Inflammatory Phase

If Phase 1 is primarily about coagulation, the second phase, called the Defensive/Inflammatory Phase, focuses on destroying bacteria and removing debris—essentially preparing the wound bed for the growth of new tissue.

The 4 phases of wound healing. Healing begins with Hemostasis.

During Phase 2, a type of white blood cells called neutrophils enter the wound to destroy bacteria and remove debris. These cells often reach their peak population between 24 and 48 hours after injury, reducing greatly in number after three days. As the white blood cells leave, specialized cells called macrophages arrive to continue clearing debris. These cells also secrete growth factors and proteins that attract immune system cells to the wound to facilitate tissue repair. This phase often lasts four to six days and is often associated with edema, erythema (reddening of the skin), heat and pain.

Phase 3: Proliferative Phase

Once the wound is cleaned out, the wound enters Phase 3, the Proliferative Phase, where the focus is to fill and cover the wound.

The Proliferative phase features three distinct stages: 1) filling the wound; 2) contraction of the wound margins; and 3) covering the wound (epithelialization).

During the first stage, shiny, deep red granulation tissue fills the wound bed with connective tissue, and new blood vessels are formed. During contraction, the wound margins contract and pull toward the center of the wound. In the third stage, epithelial cells arise from the wound bed or margins and begin to migrate across the wound bed in leapfrog fashion until the wound is covered with epithelium. The Proliferative phase often lasts anywhere from four to 24 days.

Phase 4: Maturation Phase

During the Maturation phase, the new tissue slowly gains strength and flexibility. Here, collagen fibers reorganize, the tissue remodels and matures and there is an overall increase in tensile strength (though maximum strength is limited to 80% of the pre-injured strength). The Maturation phase varies greatly from wound to wound, often lasting anywhere from 21 days to two years.

The healing process is remarkable and complex, and it is also susceptible to interruption due to local and systemic factors, including moisture, infection, and maceration (local); and age, nutritional status, body type (systemic). When the right healing environment is established, the body works in wondrous ways to heal and replace devitalized tissue.

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With reporting by Chad Collins

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