General mechanisms of cell injury

Energy disorders and membrane alteration

Any cell injury begins with or is accompanied by disorders of its energy supply. The main problem is a decrease in the rate and efficiency of ATP resynthesis. However, energy deficiency arises not only from a shortage of molecules: simultaneously, there is a disruption in the mechanisms of ATP energy transport to organelles and a direct impairment in the utilization of ATP energy by intracellular structures.

Concurrently with energy starvation, a massive alteration of membranes and enzymes unfolds. The trigger is often the excessive generation of reactive oxygen species. This inevitably entails the intensification of free-radical reactions and the initiation of free-radical 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 embed into the lipid phase of the membranes, exerting their damaging detergent effect. Recovery becomes impossible due to the inhibition of mechanisms responsible for resynthesizing damaged membrane components and their de novo synthesis. Protein, lipoprotein, and phospholipid macromolecules 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 the imbalance of ions and water in the injured cell. Normally, the cell maintains a strict gradient, but pathology causes a shift in the ratio of individual ions in the cytosol and a gross disruption of the transmembrane ion ratio. Osmotic imbalance leads to either cellular hyperhydration (swelling) or dehydration (shrinkage). A natural consequence of ionic shifts is the impairment of electrogenesis.

Changes in the electrophysiological properties of the injured cell manifest primarily as a decrease in the amplitude of the resting potential and action potential. The cell loses its ability to generate normal electrical impulses: impaired development rates of resting and action potentials are recorded, along with a pathological change in their duration.

Genome disruptions and cell regulation failures

Profound injuries inevitably affect the information apparatus, causing disorders in the genome and gene expression mechanisms. Gene mutations form the basis of genetic failures. A characteristic pathogenetic link is the derepression of pathogenic genes (such as oncogenes) against the background of simultaneous repression of vital genes. In addition, foreign DNA (e.g., viral) may integrate into the genome. The entire protein synthesis pipeline breaks down: defects occur 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 disrupted. Inside the cytoplasm, the generation of intracellular secondary and tertiary messengers becomes impaired. All these factors combine to cause total dysregulation of metabolic processes within the cell.

Briefly: answers to topical questions

Class and exam questions

What else to study on this topic

• Mechanisms of free-radical lipid peroxidation (LPO)
• The role of secondary and tertiary messengers in metabolic regulation
• Pathogenesis of cellular hyperhydration and dehydration
• Defects in transcription, translation, and post-translational mechanisms
• Effects of oncogenes and viral DNA on the cell cycle (mitosis and meiosis)

Other topics in "Chapter 4: Cell Injury as the Basis for the Development of Various Forms of Human Pathology"

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