Energy Disorders and Membrane Alteration
Any cell injury begins with or is accompanied by energy supply disorders. The primary issue is a reduction in the rate and efficiency of ATP resynthesis. However, energy deficiency arises not only from a shortage of molecules: concurrently, disorders develop in the mechanisms transporting ATP energy to organelles, alongside a direct impairment in the utilization of ATP energy by intracellular structures.
Simultaneously with energy starvation, a massive alteration of membranes and enzymes unfolds. The trigger is often the excessive generation of reactive oxygen species. This inevitably leads to the intensification of free radical reactions and the initiation of lipid peroxidation (LPO). Within the cell, there is significant activation of hydrolases (lysosomal, membrane-bound, and free), which begin to destroy the cell's own structures. Amphiphilic compounds insert into the lipid phase of membranes, exerting their detrimental detergent effect. Recovery becomes impossible as the mechanisms for resynthesizing damaged membrane components and synthesizing them de novo are suppressed. Macromolecules of proteins, lipoproteins, and phospholipids undergo conformational disruption. Ultimately, overstretching and physical rupture of the membranes of swollen cells and their organelles occur.
Ion, Water, and Electrophysiological Imbalance
Structural destruction is closely linked to ion and water imbalance in the injured cell. Under normal conditions, the cell maintains a strict gradient, but pathology causes a shift in the ratio of individual ions in the cytosol and a gross disturbance of transmembrane ion ratios. Osmotic imbalance leads to either cellular hyperhydration (swelling) or dehydration (shrinkage). A natural consequence of ionic shifts is the disruption of electrogenesis.
Alterations in the electrophysiological properties of the injured cell manifest primarily as a decrease in the amplitude of resting and action potentials. The cell loses its ability to generate normal electrical impulses: impairments are recorded in the rate of development of resting and action potentials, as well as pathological changes in their duration.
Genomic Abnormalities and Regulatory Failures
Profound injuries inevitably affect the information machinery, causing abnormalities in the genome and gene expression mechanisms. Gene mutations form the basis of these genetic failures. A characteristic pathogenetic link is the derepression of pathogenic genes (e.g., oncogenes) against the background of concurrent repression of vital genes. Furthermore, foreign DNA (e.g., viral) may integrate into the genome. The entire protein synthesis pipeline breaks down: defects arise in transcription, processing, translation, and post-translational mechanisms. Nucleic acid replication and repair processes are disrupted, leading to impaired cell division—mitosis and meiosis.
At the final stage, the cell completely loses its connection with the organism due to regulatory failure. Receptor functions for regulatory molecules on the membrane surface are impaired. Within the cytoplasm, disorders develop in the generation of intracellular secondary and tertiary messengers. All these factors combine to cause total dysregulation of metabolic processes within the cell.