Chronic inflammation

Why does inflammation become chronic?

The transition of inflammation into a chronic form is always associated with the persistence of the damaging agent. This occurs due to two main groups of causes:

1. Pathogen characteristics: high immunogenicity, resistance to macrophage and leukocyte enzymes (hydrolases), or too large a volume of the stimulus that prevents the process from completing (e.g., animal parasites such as Echinococcus).
2. Defects in host defense: impaired macrophage production, congenital neutrophil abnormalities, suppressed chemotaxis, autoimmune reactions, or genetic predisposition.

The prolonged presence of antigen and continuous tissue necrosis cause the immune system to become overloaded. A secondary immunodeficiency develops: T-lymphocyte levels drop, the T-helper/T-suppressor ratio is disrupted, and neutrophil chemotaxis capacity decreases due to the accumulation of inhibitors. Meanwhile, humoral immunity is hyperactive—antibody production (IgG, IgA) increases and circulating immune complexes (CICs) rise significantly. Functional breakdown occurs: immune dysfunction hinders phagocytosis, which promotes the further persistence of the infection.

Morphological picture and tissue changes

The main morphological sign of chronic progression is the disruption of cyclicity. The stages of damage (alteration) and fluid accumulation (exudation) are constantly superimposed on the cell multiplication stage (proliferation). Specific granulation tissue forms in the lesion with the following features:

• Cellular infiltrate: is predominantly of a lymphoplasmacytic nature. Macrophages, active fibroblasts, and polymorphonuclear leukocytes (neutrophils) are relatively sparse.
• Vascular reactions: productive vasculitis develops. The endothelium of large vessels proliferates to the point of complete closure (obliteration) of the lumen. Immune complexes and complement deposit in the walls.
• Hypoxia and sclerosis: due to a reduced number of capillaries and the narrowing of their lumen, the partial pressure of oxygen drops. Hypoxia suppresses the normal function of fibroblasts, disrupting the synthesis of collagen (unstable type III collagen prevails) and elastin. However, hypoxia itself stimulates fibroblasts to undergo excessive proliferation, leading to severe arterial sclerosis and organ deformation (e.g., intestinal lumen stenosis).

Main forms of chronic inflammation

Two basic forms of the pathology are distinguished:

1. Chronic exudative inflammation. Characterized by the presence of purulent or purulent-fibrinous exudate. A dense connective tissue capsule forms around the focus (e.g., in chronic abscess or osteomyelitis). Fistulas often form—channels for the outflow of pus outward or into adjacent cavities. Healing proceeds with the formation of a coarse scar.
2. Chronic productive inflammation. Divided into several types:
3. Diffuse (chronic hepatitis, idiopathic fibrosing alveolitis). Often viral in origin, leading to liver cirrhosis or septoalveolar sclerosis.
4. Granulomatous (formation of nodular granulomas).
5. Hyperplastic (with the formation of inflammatory overgrowths).
6. Inflammation around foreign bodies and animal parasites.

Granulomatous inflammation

This is a variant of productive inflammation in which cellular nodules—granulomas—are formed. Their appearance requires a stimulus that stimulates the mononuclear phagocyte system while remaining resistant to digestion.

Granuloma morphogenesis includes 4 stages (the process can stop at any of them):

1. Accumulation of monocytes in the damage zone.
2. Maturation of monocytes into macrophages (a simple macrophage granuloma forms).
3. Transformation of macrophages into epithelioid cells (epithelioid cell granuloma).
4. Fusion of cells to form multinucleated giant Langhans cells or foreign body giant cells (giant cell granuloma).

By etiology, granulomas can be infectious (acute in epidemic typhus; chronic in tuberculosis, syphilis, leprosy), non-infectious (around dust particles in pneumoconioses), and cryptogenic (Crohn's disease, sarcoidosis, Wegener's granulomatosis).

Briefly: answers to topical questions

Class and exam questions

What else to study on this topic

• Pathogenesis of connective tissue alterations (disorders of collagen formation and elastogenesis).
• Features of granulomas in epidemic typhus (the role of rickettsiae and fibrinoid necrosis).
• Specific and nonspecific granulomas: classification and differential diagnosis.
• The role of interleukin-1 (IL-1) and endothelial cells in maintaining inflammation.
• Mechanisms of secondary immunodeficiency development in prolonged inflammatory processes.

Other topics in the "Inflammation" section

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