Pathology of Inflammation and Tissue Response

In this stage, tissue damage and repair proceed simultaneously. Because the conflict occurs at the expense of normal tissue, the process often leads to tissue loss, fibrosis (scarring), and permanent impairment of function.

Causes of Formative Inflammation

Formative inflammation can occur following an unresolved episode of exudative inflammation (such as in bone) or can be caused directly by:

• Non-living agents: Such as dust, powders, or asbestos.
• Auto-immune processes.
• Specific microbial organisms: Such as the bacilli responsible for Tuberculosis (TB) or leprosy.

Granulomatous Lesions

A specific and highly organized type of formative inflammation is the granulomatous lesion. This is often a response to persistent infections like TB.

A granuloma is a structured mass consisting of:

• Epithelioid cells: These are transformed macrophages.
• Lymphocytes and other macrophages: Surrounding the core.
• Fibroblasts: Involved in the structural containment.
• Multi-nucleated giant cells: Formed when macrophages fuse together.

Often, the center of a granuloma becomes necrotic.

Necrosis and Tissue Response

Inflammation is frequently associated with necrosis, which is unplanned, pathological cell death. Unlike apoptosis (programmed cell death), necrosis results in a total lack of function and can trigger further inflammatory responses.

Cellular and Tissue Levels of Necrosis

At the cellular level, necrosis involves the breakdown of the nucleus and cytoplasm. The nucleus typically undergoes a three-stage dissolution:

1. Pyknosis: Condensation of the nucleus.
2. Karyorrhexis: Fragmentation of the nucleus.
3. Karyolysis: Fading and complete disappearance of the nucleus.

The appearance of necrotic tissue depends heavily on the type of tissue involved:

• Soft tissues (e.g., brain): Necrosis often results in liquefaction (colliquative necrosis).
• Solid tissues (e.g., liver, kidney): The tissue remains firm, a process known as coagulative necrosis.

The Body's Reaction to Necrotic Tissue

The immune system responds to necrosis by using neutrophils and macrophages to phagocytose and lyse the dead material, which helps speed up removal. However, this can sometimes cause further damage, such as the rupture of tissue (e.g., in the myocardium after an infarction). Depending on the tissue's regenerative capacity, the necrotic area may be replaced by fibrosis or, in highly regenerative organs like the liver, may heal without scarring.

Summary Table: Effects of Necrosis