Wound Healing

Learning Outcomes

  • Explain the process of wound healing

Inflammation is the standard, initial response of the body to injury. Whether biological, chemical, physical, or radiation burns, all injuries lead to the same sequence of physiological events. Inflammation limits the extent of injury, partially or fully eliminates the cause of injury, and initiates repair and regeneration of damaged tissue. Necrosis, or accidental cell death, causes inflammation. Apoptosis is programmed cell death, a normal step-by-step process that destroys cells no longer needed by the body. By mechanisms still under investigation, apoptosis does not initiate the inflammatory response. Acute inflammation resolves over time by the healing of tissue. If inflammation persists, it becomes chronic and leads to diseased conditions. Arthritis and tuberculosis are examples of chronic inflammation. The suffix –itis denotes inflammation of a specific organ or type, for example, peritonitis is the inflammation of the peritoneum, and meningitis refers to the inflammation of the meninges, the tough membranes that surround the central nervous system

The four cardinal signs of inflammation—redness, swelling, pain, and local heat—were first recorded in antiquity. Cornelius Celsus is credited with documenting these signs during the days of the Roman Empire, as early as the first century AD. A fifth sign, loss of function, may also accompany inflammation.

Upon tissue injury, damaged cells release inflammatory chemical signals that evoke local vasodilation, the widening of the blood vessels. Increased blood flow results in apparent redness and heat. In response to injury, mast cells present in tissue degranulate, releasing the potent vasodilator histamine. Increased blood flow and inflammatory mediators recruit white blood cells to the site of inflammation. The endothelium lining the local blood vessel becomes “leaky” under the influence of histamine and other inflammatory mediators allowing neutrophils, macrophages, and fluid to move from the blood into the interstitial tissue spaces. The excess liquid in tissue causes swelling, more properly called edema. The swollen tissues squeezing pain receptors cause the sensation of pain. Prostaglandins released from injured cells also activate pain neurons. Non-steroidal anti-inflammatory drugs (NSAIDs) reduce pain because they inhibit the synthesis of prostaglandins. High levels of NSAIDs reduce inflammation. Antihistamines decrease allergies by blocking histamine receptors and as a result the histamine response.

After containment of an injury, the tissue repair phase starts with removal of toxins and waste products. Clotting (coagulation) reduces blood loss from damaged blood vessels and forms a network of fibrin proteins that trap blood cells and bind the edges of the wound together. A scab forms when the clot dries, reducing the risk of infection. Sometimes a mixture of dead leukocytes and fluid called pus accumulates in the wound. As healing progresses, fibroblasts from the surrounding connective tissues replace the collagen and extracellular material lost by the injury. Angiogenesis, the growth of new blood vessels, results in vascularization of the new tissue known as granulation tissue. The clot retracts pulling the edges of the wound together, and it slowly dissolves as the tissue is repaired. When a large amount of granulation tissue forms and capillaries disappear, a pale scar is often visible in the healed area. A primary union describes the healing of a wound where the edges are close together. When there is a gaping wound, it takes longer to refill the area with cells and collagen. The process called secondary union occurs as the edges of the wound are pulled together by what is called wound contraction. When a wound is more than one quarter of an inch deep, sutures (stitches) are recommended to promote a primary union and avoid the formation of a disfiguring scar. Regeneration is the addition of new cells of the same type as the ones that were injured (Figure 1).

This diagram shows the wound healing process in three steps. Each step shows a cross section of wounded skin. The wound extends through the upper layer of skin, labeled the epidermis, about halfway through the dermis, the lower deeper layer of skin. At the base of the cross section, an artery runs horizontally through fatty tissue below the dermis. Several small capillaries branch from the artery and travel into the upper regions of the dermis. In the first step of healing, inflammatory chemicals, symbolized with green dots, are released from the injury site. The chemicals travel through the dermis and enter the horizontal artery. Clotting proteins and plasma proteins also initiate clotting within the wound, forming a scab, which is clearly visible in the second step as a black and brown mass covering the upper regions of the wound. Below the scab, epithelial cells in the epidermis multiply and begin to fill in the wound. In the dermis, three fibrocytes are binding the wound area with white tissue. This tissue is granulation tissue. Laying down granulation tissue restores the vascular supply, as indicated by capillaries growing around the wounded area. In the third step, the scab is gone and the epidermis has grown in and contracted to seal the upper portion of the wound. In the deeper regions, the wound is now completely filled with granulation tissue with is now considered scar tissue.

Figure 1. During wound repair, collagen fibers are laid down randomly by fibroblasts that move into repair the area.

Inflammation is the classic response of the body to injury and follows a common sequence of events. The area is red, feels warm to the touch, swells, and is painful. Injured cells, mast cells, and resident macrophages release chemical signals that cause vasodilation and fluid leakage in the surrounding tissue. The repair phase includes blood clotting, followed by regeneration of tissue as fibroblasts deposit collagen. Some tissues regenerate more readily than others. Epithelial and connective tissues replace damaged or dead cells from a supply of adult stem cells. Muscle and nervous tissues undergo either slow regeneration or do not repair at all.

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