Inflammation and Healing

• Inflammation is the body’s protective response to injury or infection. It involves the activation of vascular, cellular, and chemical mediators that aim to eliminate the causative agent, limit the tissue damage, and initiate the healing process. 

• Inflammation can be acute or chronic, depending on the duration and nature of the stimulus. Some examples of inflammation are:

• Acute inflammation: a rapid and short-lived response to a mild or transient injury or infection. It is characterized by the cardinal signs of inflammation: redness (rubor), heat (calor), swelling (tumor), pain (dolor), and loss of function (functio laesa). It involves three main stages: vascular changes, cellular changes, and chemical changes.

  • Vascular changes: include vasodilation (increased blood flow) and increased vascular permeability (leakage of fluid and proteins) that result in local hyperemia (increased blood volume) and edema (accumulation of fluid).

  • Cellular changes: include the migration of white blood cells (WBCs) from the blood vessels to the site of injury or infection through a process called chemotaxis. The main WBCs involved in acute inflammation are neutrophils, which phagocytose (ingest) and destroy the causative agent and release enzymes that digest the necrotic tissue.

  • Chemical changes: include the release of various inflammatory mediators that amplify and regulate the inflammatory response. The main mediators involved in acute inflammation are histamine, serotonin, prostaglandins, leukotrienes, cytokines, complement, and clotting factors.

• Chronic inflammation: a prolonged and persistent response to a severe or recurrent injury or infection. It is characterized by the presence of lymphocytes, macrophages, plasma cells, fibroblasts, and granulomas (nodules of chronic inflammatory cells). It involves four main features: tissue destruction, fibrosis (scar formation), angiogenesis (new blood vessel formation), and impaired healing.

 



The outcome of healing depends on several factors, such as the type, extent, and location of tissue injury; the presence of infection or foreign bodies; the nutritional and immunological status of the individual; and the quality and timing of medical intervention. Some possible outcomes are:

Resolution: is the complete restoration of normal tissue structure and function after an injury that involves minimal tissue damage and no complications. For example: healing of a superficial cut or a mild sunburn.

Primary intention: is the healing of a clean surgical incision or a small wound that involves minimal tissue loss and no complications. It is characterized by a thin scar that is barely visible. For example: healing of an appendectomy or a sutured laceration.

Secondary intention: is the healing of a large wound that involves significant tissue loss or complications, such as infection, necrosis, or foreign bodies. It is characterized by a wide scar that may impair function or appearance. For example: healing of a pressure ulcer or a burn wound.

Tertiary intention: is the delayed closure of a wound that was initially left open to allow for drainage, debridement, or infection control. It is characterized by a deep scar that may require grafting or reconstruction. For example: healing of an abdominal wound after peritonitis or a gunshot wound.

Inflammation: is the same as described above, but in the context of repair, it also prepares the wound for healing by removing debris, bacteria, and necrotic tissue.

Proliferation: is the phase of repair that involves the formation of granulation tissue, which is a highly vascularized and cellular tissue that fills the wound defect. It also involves the re-epithelialization of the wound surface by the migration and proliferation of epithelial cells from the wound edges or hair follicles.

Remodeling: is the phase of repair that involves the maturation and reorganization of collagen fibers and other extracellular matrix components to form a scar that strengthens the wound. It also involves the contraction of the wound by the action of myofibroblasts, which are specialized fibroblasts that have contractile properties.

The process of repair involves four main phases: hemostasis, inflammation, proliferation, and remodeling.

Hemostasis: is the cessation of bleeding from injured blood vessels. It involves the formation of a platelett plug and a fibrin clot that seal the wound and prevent further blood loss.

Healing is the process of restoring the normal structure and function of injured or infected tissues. It involves two main mechanisms: regeneration and repair. Regeneration is the replacement of damaged cells with identical cells that restore the original tissue structure and function. Repair is the replacement of damaged cells with connective tissue that forms a scar that restores some but not all tissue structure and function. Some examples of healing are:

Regeneration: occurs in tissues that have a high capacity for cell division, such as epithelial tissues, bone marrow, liver, and lymphoid organs. It depends on the presence of stem cells that can differentiate into various cell types.

Repair: occurs in tissues that have a low capacity for cell division, such as cardiac muscle, skeletal muscle, nervous tissue, and cartilage. It depends on the presence of fibroblasts that synthesize collagen and other extracellular matrix components.