Why Does Inflammation Become Chronic?
The transition of inflammation into a chronic form is invariably linked to the persistence of the injurious agent. This occurs due to two main groups of factors:
- Pathogen characteristics: high immunogenicity, resistance to macrophage and leukocyte hydrolases, or an excessive microbial burden that prevents resolution (e.g., parasites such as Echinococcus).
- Host defense defects: impaired macrophage production, congenital neutrophil abnormalities, inhibited chemotaxis, autoimmune reactions, or genetic predisposition.
Prolonged antigen presence and continuous tissue necrosis overload the immune system, leading to a secondary immunodeficiency: T-lymphocyte counts drop, the CD4+/CD8+ (T-helper/T-suppressor) ratio is disrupted, and neutrophil chemotaxis decreases due to the accumulation of inhibitors. Meanwhile, humoral immunity becomes hyperactive, resulting in elevated antibody production (IgG, IgA) and a significant increase in circulating immune complexes (CICs). This functional breakdown impairs phagocytosis, thereby perpetuating the infection.
Morphological Findings and Tissue Changes
The hallmark morphological feature of chronicity is the breakdown of the standard inflammatory cycle, where phases of injury (alteration) and fluid exudation continually overlap with cellular multiplication (proliferation). The focus of inflammation develops a specialized granulation tissue with the following features:
- Cellular infiltrate: predominantly lymphoplasmacytic in nature. Macrophages, active fibroblasts, and polymorphonuclear leukocytes (neutrophils) are relatively sparse.
- Vascular reactions: productive vasculitis develops. The endothelium of larger vessels proliferates, potentially leading to complete luminal occlusion (obliteration). Immune complexes and complement deposit within the vessel walls.
- Hypoxia and sclerosis: a reduced capillary network and narrowed vascular lumens decrease the partial pressure of oxygen. Hypoxia suppresses normal fibroblast function, impairing collagen synthesis (predominantly unstable type III collagen) and elastogenesis. Paradoxically, hypoxia also stimulates fibroblast proliferation, resulting in severe arterial sclerosis and organ deformation (e.g., intestinal strictures).
Main Forms of Chronic Inflammation
There are two basic forms of the pathology:
- Chronic exudative inflammation. Characterized by purulent or purulent-fibrinous exudate. A dense connective tissue capsule forms around the focus (e.g., in a chronic abscess or osteomyelitis). Fistulous tracts frequently develop, allowing pus to drain externally or into adjacent body cavities. Healing occurs with the formation of a dense scar.
- Chronic productive inflammation. Divided into several types:
- Diffuse (chronic hepatitis, idiopathic fibrosing alveolitis). Often viral in origin, leading to hepatic cirrhosis or septoalveolar sclerosis.
- Granulomatous (formation of nodular granulomas).
- Hyperplastic (characterized by inflammatory overgrowths).
- Inflammation around foreign bodies and parasites.
Granulomatous Inflammation
This is a variant of productive inflammation characterized by the formation of microscopic cellular nodules called granulomas. Their development requires a stimulus that persistently activates the mononuclear phagocyte system but resists degradation.
The morphogenesis of a granuloma includes 4 stages (the process may arrest at any point):
- Accumulation of monocytes in the injury zone.
- Maturation of monocytes into macrophages (forming a simple macrophage granuloma).
- Transformation of macrophages into epithelioid cells (epithelioid cell granuloma).
- Fusion of cells to form multinucleated giant cells (such as Langhans giant cells or foreign body giant cells; forming a giant cell granuloma).
Based on etiology, granulomas are classified as infectious (acute in typhus; chronic in tuberculosis, syphilis, leprosy), non-infectious (around dust particles in pneumoconioses), and cryptogenic (Crohn's disease, sarcoidosis, Granulomatosis with Polyangiitis).