CHRONIC INFLAMMATION

CHRONIC INFLAMMATION

Objectives: To define: 1) the causes of chronic inflammation, and 2) the forms of chronic inflammation, and 3) the hallmark cells and events of chronic inflammation.

SUMMARY

Chronic inflammation is usually a result of the inability of acute inflammation to resolve tissue trauma, particularly trauma induced by bacteria, parasites or foreign bodies (e.g. silica, asbestos, oil, etc.). Histologically, chronic inflammation is characterized by a predominance of mononuclear leukocytes (macrophages and lymphocytes), as well as the presence of a unique connective tissue referred to as granulation tissue. The presence of mononuclear leukocytes, such as macrophages and lymphocytes, in chronic inflammation generally is a result of the inability of the polymorphonuclear leukocyte of acute inflammation to resolve the trauma. The nature of the trauma often dictates whether the predominant mononuclear cell is macrophage (foreign body) versus lymphocyte (immunologic based) chronic inflammation. The control of chronic inflammation is multifaceted, major contribution to chronic inflammation are wide-ranging chemical signals that are released from necrotic tissue. These include factors from tissue cells, leukocytes, connective tissue, complement, as well as tissue mass cells and platelets. For example, the recruitment of specific mononuclear leukocyte is generally believed to be under the control of the chemical signals known chemotactic factors which are released from the injured tissue. The granulation tissue, which appears as a consequence of chronic inflammation, differs from traditional connective tissue in that it has a high density of cells (fibroblasts, macrophages, and other assorted inflammatory cells), new blood vessels (neovascularization), and scant collagen fibers. This granulation tissue ultimately lays the foundation for the formation of fibrosis within the injured tissue. This fibrosis is a consequence of new collagen synthesis by fibroblasts. If granulation tissue forms between two opposing serosal surfaces, it is referred to as an adhesion. Adhesions, like inflammation, represent two-edged swords. For example, in the case of the abdomen, adhesions which can wall off inflamed appendix, preventing peritonitis can be of particular importance. Alternatively, the adhesions which can occur and obstruct bowel function can have extremely detrimental consequences, even life-threatening consequences. Broadly speaking, chronic inflammation can be histologically seen in the form of either diffuse (non-focal form of inflammation), or as granulomatous inflammation. Granulomatous inflammation is characterized by focal collections of mononuclear leukocytes (macrophages and/or lymphocytes). These collections or islands of mononuclear leukocytes are generally the result of either an indigestible foreign particle (e.g. silica, bacteria, oil, etc.) or the consequence of immunological disease (sarcoidosis). The underlying mechanisms and mediators of granulomatous disease are discussed in detail in a later lecture.

In summary, chronic inflammation is the result of the body's inability to eliminate the tissue trauma utilizing acute inflammation (particularly the PMN). This chronic inflammation driven by chemical signals released from injured and necrotic tissue ultimately results in tissue fibrosis via granulation tissue. Although acute inflammation is explosive and can be life threatening in a short period of time, the extended and invasive nature of chronic inflammation makes chronic inflammation in its many forms and causes, the major form of chronic disease and tissue destruction in the world. Thus, understanding the underlying mechanism mediators will ultimately lead to a better approach to therapeutic management of this important disease process.

CHRONIC INFLAMMATION OUTLINE

I. Cause

A. Bacterial

B. Parasite

C. Indigestible Foreign Bodies

II. Histology

A. Mononuclear Leukocytes (Macrophages and Lymphocytes)

B. Diffuse vs. Granulomatous

C. Granulation Tissue

III. Forms of Chronic Inflammation

A. Abscess