GRANULOMATOUS INFLAMMATION

(Tuberculosis vs. Sarcoidosis)

Objectives: To define: 1) the hallmarks of cells and events of granulomatous inflammation; 2) the mechanisms of foreign body and immunologic granulomas; 3) compare and contrast the features and mechanisms of granolomatous inflammation seen in tuberculosis vs. sarcoidosis; and 4) the outcomes of granulomatous inflammation.

SUMMARY

When acute inflammatory processes are unable to resolve the trauma this often leads to a sustained or continuing inflammatory reaction known as chronic inflammation. Generally, chronic inflammation can be histologically divided into two broad categories: diffuse chronic inflammation and granulomatous inflammation. Both of forms of chronic inflammation are histologically characterized by the appearance of infiltration of mononuclear cells including macrophages, lymphocytes and plasma cells. Additionally, chronic inflammation is often associated with the proliferation of fibroblasts as well as increased present of connective tissue or fibrosis. In a diffuse chronic inflammation, the distribution of mononuclear cells is generally even throughout the involved tissue. In contrast, granulomatous inflammation is characterized by a distinct pattern of small granular appearing accumulation of epitheloid macrophages ringed by lymphocytes, known as granulomas. A second key histologic feature of these granulomas is the presence of Langhans or giant cells. These giant cells represent the coalescence or fusion of multiple macrophages, and are characterized by being multinucleated. The etiologic agents responsible for chronic inflammation may range from infectious agents to indigestible particles, as well as a role for immunologic factors which are involved in cell-mediated immunity. Regardless of the underlying agent or cause of chronic inflammation, often tissue destruction is a major feature of chronic inflammation. This tissue destruction may take the form of total loss of tissue architecture and function as occurs in cavitation in the lungs of tuberculosis patients.

In summary, inflammation represents a complex group of vascular and cellular events which are generally under the control of a variety of chemical signals known as inflammatory mediators. These mediators control the movement of fluid and cells into tissue, as well as the activation of these leukocytes in the tissue. If the insighting agent is removed by acute inflammation, the formation of granulation tissue and healing proceeds. Alternatively, if acute inflammation does not resolve the trauma, it often leads to chronic inflammation and the ultimate destruction of the tissue. Thus, inflammation remains at two-edge swords that can both protect and destroy with equal swiftness and effectiveness.

LECTURE OUTLINE

I. Purpose, Definition and Causes

II. Hallmarks of Chronic Inflammation

A. Time

B. Cells (mononuclear)

III. Cells

A. Macrophage

B. Lymphocytes

C. Epitheliod cells

D. Giant cells

IV. Granulomas

A. Foreign body

B. Immunologic

VI. Foreign Body Reactions

A. Features and mechanisms

VII. Immunologic Reaction

A. Features and mechanisms

VIII. Definition of Granulomatous Inflammation

IX. Tuberculosis

A. Etiology: mycobacteria

B. Pathology

C. Pathogenesis

1. Virulence of organism

2. Immune status

3. Tissue destruction

D. Primary Tuberculosis

E. Secondary or disseminated tuberculosis

F. Outcome

X. Sarcoidosis

A. Etiology: unknown

B. Pathology

C. Pathogenesis

1. Role of microorganisms

2. Role of immune system

D. Outcome

Required Reading: Pathological Basis of Disease, Robbins et al., pp. 324-327 and 712-714.

Study Questions:

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