Inflammation

Acute inflammation is the initial response of body tissues to local injury. The various types of injury include those caused by blunt or penetrating trauma, infectious organisms, and irritating chemical substances. Regardless of the underlying cause, the inflammatory response consists of four overlapping events that occur sequentially (Box 1-2).

The earliest bodily response to local injury is dilation of arterioles, capillaries, and venules, leading to a dramatic increase in blood flow in and around the injury site. This hyperemia produces the heat and redness associated with inflammation. As hyperemia develops, the venules and capillaries become abnormally permeable, allowing passage of protein-rich plasma across vessel walls into the interstitium. This inflammatory exudate in the tissues results in the swelling associated with inflammation, which produces pressure on sensitive nerve endings and causes pain. The protein-rich exudate of inflammation must be differentiated from a transudate, a low-protein fluid such as that seen in the pulmonary edema that develops in congestive heart failure.

Very early in the inflammatory response, leukocytes (white blood cells, especially neutrophils and macrophages) of the circulating blood migrate to the area of injury. These white blood cells cross the capillary walls into the injured tissues, where they engulf and enzymatically digest infecting organisms and cellular debris, a process called phagocytosis.

The removal of necrotic debris and any injurious agents, such as bacteria, makes possible the repair of the injury that triggered the inflammatory response. In many tissues, such as the lung after pneumococcal pneumonia, regeneration of parenchymal cells permits reconstitution of normal anatomic structure and function. However, some tissues, such as the heart after myocardial infarction, cannot heal by regeneration. A fibrous scar replaces the area of destroyed tissue with granulation tissue. Granulation tissue refers to a combination of young developing capillaries and actively proliferating fibroblasts, which produce connective tissue fibers (collagen) that replace the dead tissue. Eventually the strong connective tissue contracts to produce a fibrous scar. In the abdomen, such fibrous adhesions can narrow loops of intestine and result in an obstruction. The accumulation of excessive amounts of collagen (more common in African Americans) may produce a protruding, tumor-like scar known as a keloid. Unfortunately, surgery to remove a keloid is usually ineffective because the subsequent incision tends to heal in the same way.

Many injuries heal by a combination of regeneration and scar tissue formation. An example is the response of the liver to repeated and persistent alcoholic injury; the result is cirrhosis, in which irregular lobules of regenerated liver cells are crisscrossed and surrounded by bands of scar tissue. Scar tissue formation consists of fibrous connective tissue, which can be divided into primary union (surgical incision) and secondary union (nonsurgical; gunshot wound).

The five clinical signs of acute inflammation are rubor (redness), calor (heat), tumor (swelling), dolor (pain), and loss of function. The localized heat and redness result from increased blood flow in the microcirculation at the site of injury. The swelling occurs because the exudate increases the amount of interstitial fluid, resulting in pressure on nerve endings and thus pain, which results in a loss of function.

Acute inflammation can also lead to systemic manifestations. Fever is especially common in inflammatory conditions associated with the spread of organisms into the bloodstream. The number of circulating white blood cells also increases (leukocytosis).

Some bacterial organisms (such as staphylococci and streptococci) produce toxins that damage the tissues and incite an inflammatory response. The presence of pyogenic bacteria leads to the production of a thick, yellow fluid called pus, which contains dead white blood cells, inflammatory exudate, and bacteria. A suppurative inflammation is one that is associated with pus formation. When a pyogenic infection occurs beneath the skin or in a solid organ, it produces an abscess, a localized, usually encapsulated, collection of pus. All pyogens, wherever they become implanted, have the ability to invade blood vessels to produce bacteremia, with the potential involvement of other organs and tissues in the body.

A granulomatous inflammation manifests as a distinct pattern seen in relatively few diseases, including tuberculosis, syphilis, and sarcoidosis. A granuloma is a localized area of chronic inflammation, often with central necrosis. It is characterized by the accumulation of macrophages, some of which fuse to form multinucleated giant cells.

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