Pathophysiology of Inflammation
The initial inflammation phase consists of three subphases: acute, subacute, and chronic (or proliferative). The acute phase typically lasts 1–3 days and is characterized by the five classic clinical signs: heat, redness, swelling, pain, and loss of function. The subacute phase may last from 3–4 days to ~1 mo and corresponds to a cleaning phase required before the repair phase. If the subacute phase is not resolved within ~1 mo, then inflammation is said to become chronic and can last for several months. Tissue can degenerate and, in the locomotor system, chronic inflammation may lead to tearing and rupture. Alternatively, after the subacute inflammatory phase, tissue can repair and be strengthened during the remodeling phase.
From a mechanistic point of view, the acute response to tissue injury occurs in the microcirculation at the site of injury. Initially, there is a transient constriction of arterioles; however, within several minutes, chemical mediators released at the site relax arteriolar smooth muscle, leading to vasodilation and increased capillary permeability. Protein-rich fluid then exudes from capillaries into the interstitial space. This fluid contains many of the components of plasma including albumin, fibrinogen, kinins, complement, and immunoglobulins that mediate the inflammatory response.
The subacute phase is characterized by movement of phagocytic cells to the site of injury. In response to adhesion, molecules released from activated endothelial cells, leukocytes, platelets, and erythrocytes in injured vessels become sticky and adhere to the endothelial cell surfaces. Polymorphonuclear leukocytes such as neutrophils are the first cells to infiltrate the site of injury. Basophils and eosinophils are more prevalent in allergic reactions or parasitic infections. As inflammation continues, macrophages predominate, actively removing damaged cells or tissue. If the cause of injury is eliminated, the subacute phase of inflammation may be followed by a period of tissue repair. Blood clots are removed by fibrinolysis, and damaged tissues are regenerated or replaced with fibroblasts, collagen, or endothelial cells. During the remodeling phase, the new collagen laid down during the repair phase (mainly type III) is progressively replaced by type I collagen to adapt to the original tissue. However, if inflammation becomes chronic, further tissue destruction and/or fibrosis occurs.