Classification by nature of exposure
The cause of pathology is always the impact 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 influences (injuries and compression), exposure to extremely high or low 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 the action of 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 medications when used in inappropriate 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
According to the localization of the threat source, all causes of injury are differentiated into external and internal. They are also divided according to their infectious nature into infectious (microbes, microbial endo- and exotoxins, unicellular and multicellular parasites) and non-infectious (factors of physical, chemical, or biological, but non-infectious nature).
Exogenous (external) factors penetrate from the external environment. These include mechanical injuries, electric current, temperature effects, radiation, chemical substances (acids, alkalis, ethanol, strong oxidizing agents, medications), and biological agents (viruses, bacteria, rickettsia, helminths).
Endogenous (internal) factors are formed within the organism 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 the 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.
- Influences of biological nature: aggression of cytotoxic factors of the immunosurveillance 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 influence 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 influences that trigger various forms of pathology are united by the general term mediators of injury. They act as crucial 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.
Briefly: answers to topical questions
What specific cytotoxic substances cause chemical cell injury?
Sources explicitly state that chemical factors of cell injury include cytotoxic substances and medicinal products. The specific chemical damaging agents mentioned are:
- acids and alkalis;
- heavy metal salts;
- ethanol;
- strong oxidizing agents;
- medications in inappropriate dosages.
Hepatotropic poisons and medications are separately listed for liver injury:
- ethanol;
- carbon tetrachloride;
- paracetamol;
- chloramphenicol;
- substances used for cholecystography.
Cytotoxic immunoglobulins and cytotoxic cells are classified in the sources as biological/immune factors of injury rather than chemical ones.
Which specific lysosomal enzymes are involved in endogenous autolytic cell injury?
Sources indicate hydrolases, primarily lysosomal, as well as membrane-bound and free ones, for autolytic cell injury. The following groups of enzymes are specifically named:
- lipases;
- phospholipases;
- proteases.
Their excessive activation is accompanied by intensive hydrolysis of phospholipids, glycoproteins, cytoskeleton proteins, and enzymes. The result is a sharp increase in membrane permeability and a decrease in cellular enzyme activity. Sources also indicate that upon lysosomal injury, rupture of their membranes, release of hydrolases, and cell autolysis are possible.
Which cellular organelles are the first to be damaged during hypoxic exposure?
Sources do not definitively indicate which organelles are damaged first during hypoxia. It is directly confirmed that under hypoxic injury, the following suffer:
- mitochondria: ATP synthesis decreases, swelling and destruction of cristae develop; Krebs cycle reactions, electron transfer to oxygen, and coupling of oxidation with ADP phosphorylation are disrupted;
- endoplasmic reticulum: protein and lipid synthesis is disrupted, ribosomal degranulation and vacuolization occur;
- lysosomes: membrane rupture, release of hydrolases, and cell autolysis are possible.
For hypoxic injury of cardiomyocytes, sarcolemma damage, mitochondrial destruction, and swelling of the sarcoplasmic reticulum are additionally indicated.
For quick memorization of the nature of damaging factors, use the "P-C-B" rule: Physical (injuries, temperatures, radicals), Chemical (acids, poisons, drugs), Biological (viruses, antibodies, hormones).
Class and exam questions
What is alteration?
This is a medical term denoting cell damage. During alteration, the structure, metabolism, and physicochemical properties of the cell are disrupted, leading to the loss of its normal functions.
How does direct injury differ from indirect injury?
Direct injury occurs upon direct contact of the pathogenic factor with the cell. Indirect injury is realized through a cascade of secondary reactions involving neurotransmitters, hormones, or cytokines (e.g., in shock or stress).
What are damage mediators?
These are endogenous intermediaries (e.g., inflammatory, allergy, or fever mediators) that trigger the development of a specific form of pathology in response to the initial pathogenic agent.
What else to study on this topic
- Key mechanisms of cell alteration
- The role of reactive oxygen species and lipid peroxidation
- Cytotoxic action of immunocompetent cells and antibodies
- The effect of hydrogen, potassium, and calcium ion imbalance on the cell
- Pathogenesis of indirect injury in stress and shock
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