Principles of cell defense against injury

Natural Mechanisms of Adaptation to Injury

Cells regularly encounter resource shortages or pathogen exposure. The organism responds with multilevel reactions:

• In hypoxia (reduced energy supply), transport systems are stimulated at the systemic level: blood circulation and respiration are activated. At the cellular level, compensation occurs through enhanced tissue respiration and glycolysis.
• In hypoglycemia, a humoral response is triggered. The production of hormones that raise plasma glucose and its tissue transport increases sharply: glucagon, adrenaline, glucocorticoids, and growth hormone (somatotropin). Simultaneously, the sensitivity of cellular receptors to these substances increases.
• In ischemia (reduced local blood supply), adaptation aims to increase blood flow via collateral (bypass) vessels. The cells themselves in the ischemic zone reduce their functional intensity to minimize the demand for oxygen and substrates.

Three Basic Principles of Cellular Protection

Medical interventions are divided into three main groups according to their focus:

1. Etiotropic principle. Directed strictly at the cause of the injury. The task is to eliminate, stop, or reduce the intensity and duration of the pathogenic factor, as well as to remove conditions contributing to its manifestation.
2. Sanogenetic principle. Focuses on activating the body's own defense forces (sanogenesis). This involves stimulating mechanisms of compensation, protection, repair, and cell adaptation to altered conditions.
3. Pathogenetic principle. Its goal is to break the links in the mechanism of disease development.

Main targets of pathogenetic intervention:

• Correction of energy supply.
• Protection of membranes and enzymes.
• Normalization of transmembrane transport and intracellular ion distribution.
• Control of cell volume.
• Protection of the genetic apparatus and correction of regulatory influences.

Correction of Energy Supply During Alteration

Since energy deficit inevitably leads to injury, therapy must restore the balance between resource delivery and consumption.

Increasing ATP delivery and synthesis:

• To ensure the transport of oxygen and substrates, $O_2$ inhalation and a glucose-insulin-potassium (polarizing) mixture are used.
• To facilitate transmembrane transport into mitochondria, hyaluronidase (improves permeability) and carnitine (fatty acid carrier) are used.
• To directly stimulate glycolysis and tissue respiration, antihypoxants are prescribed.

Decreasing energy consumption: Cells are placed in conditions of "functional unloading." To reduce the level of function, sympathoadrenal system blockers, calcium antagonists, phosphodiesterase and protein kinase inhibitors are used. Hypothermia is also effective, globally reducing the metabolic demands of tissues.

Protection of membranes and enzyme systems

Destruction of cell membranes is a critical stage of the pathological process. The protection strategy is implemented along three vectors:

1. Combating free radical reactions. To reduce the formation of toxic lipid peroxidation (LPO) products, the coupling of oxidation and phosphorylation is enhanced (antihypoxants, carotenes). Free radicals are neutralized by antioxidants (tocopherols, superoxide dismutase), while already formed peroxides are destroyed by enzymes (catalase, glutathione peroxidase).
2. Blockade of hydrolases. To reduce the degree of membrane alteration, calcium antagonists (preventing calcium activation of enzymes), as well as phospholipase and protease inhibitors, are used.
3. Stabilization of lysosomal membranes. It is critical to prevent the release of excess hydrolases from lysosomes into the cytoplasm, as this causes autolysis (self-digestion) of the cell. For this purpose, membrane-stabilizing drugs are used: glucocorticoids and non-steroidal anti-inflammatory drugs (NSAIDs).

Prevention and Resistance Training

Preventive measures aim to prevent injury to still healthy (intact) cells. An excellent non-pharmacological method is dosed conditioning of the body: hypoxia according to a special schedule, physical exercise, and cooling.

The result of such training is cross-resistance. The organism increases its resistance not only to the training factor but also to completely different agents: significant ischemia, infections, and ionizing radiation.

The pathophysiological basis of this phenomenon lies in increasing the capacity of regulatory systems, improving energy supply, activating DNA repair, accelerating protein synthesis, and forming new subcellular structures.

Class and exam questions

What else to study on this topic

• Mechanisms of lipid peroxidation (LPO) and the functioning of the antioxidant system.
• The role of calcium ions in the activation of cellular hydrolases during alteration.
• Pathophysiology of ischemic injury and mechanisms of collateral opening.
• Transmembrane ion transport and cell volume control mechanisms.
• Humoral regulation in hypoglycemia: synergism of counter-regulatory hormones.

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

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.