Classification by Nature of Impact
The cause of pathology is always the effect of pathogenic factors on the cell as a whole or on its individual components. By their nature, these factors are divided into three major groups:
- Physical factors. These include various mechanical effects (trauma and compression), extreme temperatures (hyperthermia, hypothermia), electric current, and various types of radiation (electromagnetic waves, ionizing radiation). At the microlevel, physical causes also include changes in intracellular osmotic pressure and an excess of free radicals.
- Chemical factors. Cells can be destroyed by organic and inorganic acids, alkalis, heavy metal salts, ethanol, and strong oxidizing agents. Specific cytotoxic substances play an important role in chemical injury, as do conventional drugs when used in inadequate dosages.
- Biological factors. These encompass microorganisms (viruses, bacteria, fungi, rickettsia) and multicellular parasites (helminths). In addition, injury can be caused by the body's own resources: cytotoxic immunoglobulins (antibodies), cytotoxic immunocompetent cells, as well as a pronounced deficiency or excess of biologically active substances—hormones, enzymes, and cytokines.
Exogenous and Endogenous Causes
Depending on the localization of the threat source, all causes of injury are differentiated into external and internal. They are also divided by their infectious nature into infectious (microbes, microbial endo- and exotoxins, single-celled and multicellular parasites) and non-infectious (factors of physical, chemical, or biological, but non-infectious nature).
Exogenous (external) factors penetrate from the environment. These include mechanical trauma, electric current, temperature effects, radiation, chemical substances (acids, alkalis, ethanol, strong oxidizing agents, medications), and biological agents (viruses, bacteria, rickettsia, helminths).
Endogenous (internal) factors originate within the body itself. These include:
- Agents of physical nature: an excess of reactive oxygen species and/or oxidized lipids in the intracellular or extracellular environment, as well as significant fluctuations in the osmotic pressure of interstitial fluid.
- Chemical compounds: ion imbalance (excess or deficiency of $H^+$, $K^+$, $Ca^{2+}$, and others), changes in oxygen and carbon dioxide levels, accumulation of metabolites, organic and inorganic peroxide compounds.
- Biological impacts: aggression by cytotoxic factors of the immune surveillance system, deficiency or excess of kinins, hormones, and enzymes. Agents released from already injured or dead cells (e.g., proteins, lysosomal enzymes, metabolites) pose a particular danger.
Mechanisms of Action and Mediators of Injury
According to the mechanism of effect on cellular structures, the impact can be direct and/or indirect.
- Direct action on the cell is observed upon direct contact of an exogenous or endogenous, infectious or non-infectious factor with the cell.
- Indirect action is realized through the formation of a chain of secondary, often multi-step, pathogenic reactions. In this case, the cell is injured as a result of altered neural or endocrine influences upon it. Mediators in such reactions include neurotransmitters, hormones, cytokines, and other active substances. A similar mechanism is typical for conditions such as stress, shock, and various allergic reactions.
Many of the listed factors or impacts that trigger various forms of pathology are united by the general term mediators of injury. They act as critical intermediaries between the initial pathogenic agent and the development of a specific disease. Depending on the developing process, inflammatory mediators, allergy mediators, carcinogenesis mediators, fever mediators, and hypoxia mediators are distinguished.