• Increased transport of fluids and proteins, called transcytosis, through the endothelial cell. This process, documentedinexperimentalmodels, mayinvolve intracellular channels that open in response to certain factors, such as vascular endothelial growth factor (VEGF), that promote vascular leakage. Its contribution to the vascular permeability seen in acute inflammation in humans is unclear.
Although these mechanisms of increased vascular permeability are described separately, all probably contribute in varying degrees in responses to most stimuli. For example, at different stages of a thermal burn, leakage results from endothelial retraction caused by inflammatory mediators and direct and leukocyte-dependent endothelial injury.
Responses of Lymphatic Vessels and Lymph Nodes
In addition to blood vessels, lymphatic vessels also participate in acute inflammation. The system of lymphatics and lymph nodes filters and polices the extravascular fluids. Lymphatics drain the small amount of extravascular fluid that seeps out of capillaries under normal circumstances. In inflammation, lymph flow is increased to help drain edema fluid that accumulates because of increased vascular permeability. In addition to fluid, leukocytes and cell debris, as well as microbes, may find their way into lymph. Lymphatic vessels, like blood vessels, proliferate during inflammatory reactions to handle the increased load. The lymphatics may become secondarily inflamed (lymphangitis), as may the draining lymph nodes (lymphadenitis). Inflamed lymph nodes are often enlarged because of increased cellularity. This constellation of pathologic changes is termed reactive, or inflammatory, lymphadenitis (Chapter 12). For clinicians the presence of red streaks near a skin wound is a telltale sign of an infection in the wound. This streaking follows the course of the lymphatic channels and indicates the presence of lymphangitis; it may be accompanied by painful enlargement of the draining lymph nodes, indicating lymphadenitis.
Leukocyte Recruitment to Sites of Inflammation
Leukocytes that are recruited to sites of inflammation perform the key function of eliminating the offending
Vasodilation is induced by inflammatory mediators such as histamine (described later), and is the cause of erythema and stasis of blood flow.
Increased vascular permeability is induced by histamine, kinins, and other mediators that produce gaps between endothelial cells, by direct or leukocyte-induced endothelial injury, and by increased passage of fluids through the endothelium.
Increased vascular permeability allows plasma proteins and leukocytes, the mediators of host defense, to enter sites of infection or tissue damage. Fluid leak from blood vessels (exudation) results in edema.
Lymphatic vessels and lymph nodes also are involved in inflammation, and often show redness and swelling.
agents. The most important leukocytes in typical inflammatory reactions are the ones capable of phagocytosis, namely, neutrophils and macrophages. Neutrophils are produced in the bone marrow and rapidly recruited to sites of inflammation. Macrophages are slower responders. The principal functions of these cell types differ in subtle but important ways—neutrophils use cytoskeletal rearrangements and enzyme assembly to mount rapid, transient responses, whereas macrophages, being long-lived, make slower but more prolonged responses that often rely on new gene transcription (