Essence and Objectives of the Proliferative Stage
Every inflammatory response follows a predictable progression, and proliferation (proliferatio) represents its final, concluding stage. It is important to understand that this is an absolute, obligatory component of the inflammatory mechanism without which tissue repair is impossible.
This stage is driven by two key processes occurring directly within the inflammation focus:
- A significant increase in cell numbers. Primarily, stromal elements actively proliferate, and parenchymal cells typically become involved as well.
- Active formation of new extracellular matrix, which provides the necessary scaffold for the recovering tissue.
The ultimate goal of these cellular transformations boils down to two main tasks: the complete regeneration of altered (damaged) elements and the reliable replacement of tissue structures that were permanently destroyed during earlier stages of the pathological process.
Regulation of Cell Division
Proliferation does not happen spontaneously. Biologically active substances (BAS) play a crucial role in initiating and managing this process. Of particular importance are mitogens—specific factors that directly stimulate cell division.
Regulation is carried out by a complex network of factors affecting both stromal and parenchymal cells. They can be divided into several main groups:
| Regulator Group | Representatives and Mechanism of Action |
|---|---|
| Inflammatory mediators | Biogenic amines, kinins, and leukotrienes. They act as potent stimulators of cell division in the lesion focus. |
| Cytokines | Produced by leukocytes and platelets. Include interleukins (IL), monokines, lymphokines, and various growth factors. |
| Destruction products | Low-molecular-weight peptides (putrescine, spermidine, spermine) and nucleic acid breakdown products. Released upon tissue destruction, they signal the growth of new structures. |
| Hormones | Insulin, growth hormone (somatotropin), glucagon, thyroid hormones, and corticosteroids. |
| Other factors | Tissue enzymes (hyaluronidase, collagenase), various ions, and neurotransmitters. |
Feature of hormonal regulation: Hormones can either activate or suppress proliferation. The final effect strictly depends on their local concentration, intrinsic activity, and phenomena of synergism or antagonism. A striking example of this dualism is that mineralocorticoids actively stimulate regeneration, whereas glucocorticoids can inhibit it even at low doses.
Outcomes of Inflammation: Restitution and Substitution
The resolution of the inflammatory process and tissue repair can proceed via two different scenarios. The outcome depends directly on the initial volume of injury and the state of the organism.
- Complete regeneration (restitution). This is the optimal outcome, observed during a favorable course of inflammation. In this case, there is an exact replacement of all dead cells. Structural elements that suffered only reversible damage fully restore their integrity.
- Incomplete regeneration (substitution). This develops when there is significant, massive destruction of a tissue or organ. In this situation, the body must resort to defect replacement. Initially, granulation tissue forms at the site of destroyed elements. As it matures, it gradually condenses and transforms into a connective tissue scar.