General changes in the focus of inflammation
The transition of the inflammatory reaction into its final phase is accompanied by a noticeable decrease in the acuteness of local processes. Vascular blood filling (hyperemia) decreases, exudation intensity drops, and the active emigration of formed blood elements, primarily neutrophils, ceases. At the cellular level, metabolism is rearranged: catabolic reactions are replaced by the predominance of anabolic processes.
The main task of this stage is to clear the damaged area of bacterial agents and necrotic debris. To achieve this, monocytes, histiocytes, and macrophages dramatically increase the synthesis of intracellular enzymes (lysosomal hydrolases). Polymorphonuclear leukocytes, having completed their digestive function, undergo mass apoptosis.
In aseptic inflammation, where only altered autologous antigens are present, leukocytes leave the focus after 18–24 hours. Only after their departure is the space filled by macrophages, which allows the latter to avoid destructive lysis by neutrophil hydrolases.
Formation of an inflammatory infiltrate
Gradually, the cellular landscape changes: dead neutrophils are replaced by mononuclear cells and cells responsible for repair. A new inflammatory infiltrate is formed.
It includes:
- Hematogenous macrophages and monocytes.
- Cells of the immune system (T- and B-lymphocytes, plasma cells).
- Platelets.
- Fibroblasts.
Infiltrate cells act as regulators of healing. They release interleukins (IL), which trigger the proliferation of fibroblasts. Together with the endothelium, neoangiogenesis—the formation of new blood vessels—is activated. Synthesized inflammatory mediators and growth factors stimulate DNA synthesis, initiating regeneration or fibrosis processes.
Feature: if immunoglobulins (Ig) accumulate in the cell cytoplasm, intercellular space, or vascular walls, this can lead to the formation of granulomas.
Regulation of proliferation
Cell multiplication has a complex control mechanism. At the same time, local processes in the focus serve as a signal to activate systemic mechanisms, transforming local changes into a reaction of the entire organism.
Proliferation activators:
- Anti-inflammatory mediators: glucocorticoids, antioxidants, and hydrolase inhibitors.
- Growth factors: fibroblast, epidermal, nerve, as well as insulin-like growth factor.
- Cytokines: IL-1 and IL-2–7.
Proliferation inhibitors:
- Tumor necrosis factor (TNF).
- Chalones.
Humoral and hormonal regulation play a huge role. Somatotropin, thyroxine, and hormones exert a direct stimulating effect. Furthermore, regeneration processes are significantly enhanced under the influence of endogenous opiates.
Healing dynamics and outcomes
As cells of the inflammatory infiltrate break down, fibroblasts—originating from local cambial elements—become dominant. Active fibrogenesis begins: cells synthesize RNA, DNA, and the ground substance, gradually turning into fibrocytes.
The damage zone is filled with granulation tissue. As described by M.N. Nikiforov (1895), it possesses high resorptive capacity and builds a reliable barrier against pathogens.
The process ends with the maturation of granulations and the formation of mature connective tissue. Two outcome variants are possible:
- Substitution (incomplete regeneration). Most characteristic of inflammation. Granulation tissue matures into a connective tissue scar, the mass of which depends on the depth of the injury.
- Restitution (complete regeneration). Restoration of the original tissue, including all its specific structures and features.
Briefly: answers to topical questions
From which precursor cells do fibroblasts form in the focus of inflammation?
Fibroblasts in the focus of inflammation are formed from local cambial elements. They begin to dominate the damage zone during the stage of healing dynamics and granulation tissue formation, following the destruction of inflammatory infiltrate cells. Subsequently, during fibrogenesis, active synthesis of DNA, RNS (RNA), and ground substance takes place, leading to the final transformation of fibroblasts into mature fibrocytes.
What functions does granulation tissue perform in the focus of inflammation?
Granulation tissue fills the entire damage zone, possesses high resorptive capacity, and serves as a barrier against pathogens.
What morphological layers are distinguished in maturing granulation tissue?
Two main morphological layers are distinguished in the structure of granulation tissue.
- Superficial layer — covered with purulent-necrotic masses (products of leukocyte degeneration and necrosis of superficial granulations); neutrophils and macrophages predominate in its cellular composition.
- Deep layers — characterized by the predominance of fibroblasts; histiocytes and mast cells are also found here.
Between vertically oriented vessels lies the ground substance, represented by a network of fibrils.
In what cases do granulomas form during inflammation?
Granulomas during inflammation form as a result of local tissue infiltration, as well as the accumulation of immunoglobulins in the cell cytoplasm, intercellular space, or vascular walls.
The following cases of granuloma formation are distinguished:
- Specific infections — in tuberculosis, syphilis, leprosy, and scleroma.
- Nonspecific infections — in echinococcosis, alveolar echinococcosis, brucellosis, fungal infections, and rickettsiosis.
- Non-infectious and systemic pathologies — around foreign bodies, in sarcoidosis, primary biliary cholangitis, and lesions of allergic and drug-induced genesis.
Inflammation outcomes are easy to remember by their first letters: Restitution — Real tissue (complete restoration). Substitution — Scar tissue (scar formation).
Class and exam questions
What happens to neutrophils during the proliferation stage?
After performing their main function—digesting pathogens and necrotic debris—polymorphonuclear leukocytes die, yielding to macrophages and reparative cells.
What are the characteristic features of macrophages in chronic granulomatous inflammation?
In this type of inflammation, the antigenic structure of the pathogen is already known to the body. Macrophages often exhibit incomplete phagocytosis, and immune system stimulation leads to an increase in their number to wall off the focus.
How is granulation tissue formed?
Local cambial elements give rise to fibroblasts. They actively synthesize DNA, RNA, and ground substance (fibrogenesis), gradually transforming into fibrocytes and forming granulations that fill the damage zone.
What else to study on this topic
- Mechanisms of neoangiogenesis in inflammation and the role of endothelium
- The role of interleukins and growth factors in fibroblast activation
- Pathogenesis of granuloma formation and the role of immunoglobulins
- Differences in cellular reactions during aseptic and infectious inflammation
- The effect of endogenous opiates and hormones on the rate of tissue regeneration
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