Definition and biological significance of inflammation
Inflammation is a standard pathological process that occurs in response to local tissue injury and is aimed at limiting, neutralizing, and removing the damaging (phlogistic) agent, as well as eliminating the consequences of injury and restoring tissue integrity.
The biological significance of inflammation lies in localizing the pathological focus: the organism deliberately sacrifices a portion of healthy tissue around the injury zone, forming a protective barrier to prevent the spread of the phlogistic agent and its metabolic products throughout the body. For example, during bacterial invasion, a demarcation wall forms, walling off microorganisms within the focus and preventing the generalization of infection and systemic intoxication.
The term originates from the Latin inflammatio and Greek phlogosis, hence the name of the damaging factor — phlogistic agent or phlogogen.
Local and systemic signs of inflammation
The classical local signs of inflammation, described since the times of Hippocrates and Celsus, are formulated as rubor, calor, tumor, dolor, functio laesa:
- Rubor — redness (a consequence of arterial hyperemia);
- Calor — local temperature increase;
- Tumor — swelling and edema due to exudation;
- Dolor — pain caused by the action of mediators and compression of receptors;
- Functio laesa — impaired function of the affected tissue or organ.
Systemic manifestations include elevated ESR, leukocytosis, fever, changes in plasma protein composition (increase in acute-phase proteins), and systemic intoxication. The development of all these symptoms is ensured by the complex interaction of inflammatory mediators, neural, and humoral regulatory influences.
Phases of inflammation
Inflammation proceeds in three phases: alteration, exudation, and proliferation. Despite being schematically represented as a sequence, these phases are triggered almost simultaneously from the moment the phlogistic agent acts and only peak at different times. Alteration increases first, joined by exudation which sustains secondary alteration, while proliferation comes to the forefront as the first two phases subside.
Alteration: primary and secondary
Alteration — tissue damage occurring under the action of a phlogistic factor during the development of inflammation.
- Primary alteration — disturbances caused by direct contact of tissue with the phlogistic agent: thermal burn, mechanical trauma, action of microbial toxins and enzymes.
- Secondary alteration — damage caused by the organism's own reaction: the action of inflammatory mediators, immune mechanisms, local acidosis due to lactic acidosis, changes in osmotic and oncotic pressure, and leukocyte enzymes.
The paradox is that secondary alteration is a defense mechanism: additional tissue destruction forms a barrier that prevents the absorption of toxins and the spread of the phlogogen.
Inflammatory mediators
Mediators are divided into two main groups:
- Plasma (humoral) mediators — constantly circulate in the blood: kinins, active components of the complement system, blood coagulation, and fibrinolysis factors.
- Cellular mediators — associated with cells. They are subdivided into those stored in granules (ready for release) and those synthesized de novo at the moment of inflammation. Sources: mast cells, endothelial cells, leukocytes, tissue macrophages, platelets, fibroblasts. These include histamine, serotonin, eicosanoids, cytokines, etc.
Mediators provide the vascular reaction, increased vascular wall permeability, leukocyte chemotaxis, and the formation of edema and pain.
Exudation and the nature of exudate
The vascular reaction in inflammation goes through the following stages: short-term spasm, arterial hyperemia (arteriolar dilation, increased blood inflow), mixed hyperemia, venous hyperemia (impaired venous outflow due to compression of veins by edematous tissue), and stasis.
Exudate — inflammatory fluid with a protein content of more than 3%, which distinguishes it from transudate (protein-poor). Exudate is formed due to increased vascular wall permeability under the action of mediators: plasma proteins, enzymes, and blood cellular elements enter the tissue.
According to the nature of the exudate, inflammation is classified as:
- serous — in aseptic damage to mucous and serous membranes;
- fibrinous — with fibrin precipitation;
- suppurative — in bacterial infection, with a large number of neutrophils;
- putrid — in anaerobic flora;
- hemorrhagic — with pronounced erythrocyte extravasation.
Proliferation and outcome of inflammation
Proliferation — the process of restoring the structure of damaged tissue, beginning as early as a few hours after injury. It includes three stages:
- Cleansing the focus of dead cells, microorganisms, and foreign elements (phagocytosis);
- Stimulation of vessel growth in the injury zone (angiogenesis) and formation of granulation tissue;
- Restoration of tissue integrity — regeneration or formation of a connective tissue scar.
Full proliferation is possible only if further damage ceases: primary and secondary alteration must end, and with them, exudation. As long as new cellular elements and mediators continue to enter the focus, alteration is sustained, and defect closure is impossible.
Key points
- Inflammation is a standard pathological process underlying the pathogenesis of many diseases.
- Local signs: rubor, calor, tumor, dolor, functio laesa.
- The three phases — alteration, exudation, proliferation — are triggered simultaneously but reach their peak at different times.
- Primary alteration is caused by the phlogistic agent, while secondary alteration is caused by the body's own mediators and immune mechanisms.
- Mediators are divided into plasma (kinins, complement, coagulation factors) and cellular (granular and synthesized de novo) mediators.
- Exudate contains more than 3% protein and differs from transudate; based on its nature, serous, fibrinous, suppurative, putrid, and hemorrhagic inflammation are distinguished.
- The vascular reaction goes through stages of arterial, mixed, and venous hyperemia up to stasis.
- Proliferation and healing are possible only after the cessation of alteration and exudation.