Injury to cell membranes and enzymes

Excessive hydrolase activation

Exposure to various pathogenic factors, such as uncompensated acidosis, triggers the release of aggressive enzymes from lysosomes. This initiates a cascade of cell self-destruction.

A significant increase in the activity of lipases, phospholipases, and proteases plays a key role in pathogenesis. All their pools are activated: membrane-bound, free (solubilized), and lysosomal. Intensive hydrolysis of vital cellular substrates occurs:

• Phospholipids of the lipid bilayer;
• Glycoproteins;
• Cytoskeletal proteins;
• The cell's own enzymes.

The result of such enzymatic aggression is a sharp increase in plasmalemma permeability and a critical decrease in the activity of other cellular enzymes.

Detergent effect of amphiphilic compounds

Concurrently with hydrolase activation and the initiation of lipid peroxidation reactions, amphiphiles accumulate within the cell. The main accumulating compounds include free fatty acids, lipid hydroperoxides, and various glycerophospholipids (phosphatidylcholines, phosphatidylethanolamines, phosphatidylserines).

The pathogenesis of damage is based on their amphiphilicity — the unique ability to integrate and firmly anchor simultaneously in the hydrophobic and hydrophilic zones of membranes. The process unfolds in several stages:

1. Massive integration of amphiphiles into the membrane.
2. Formation of extensive lipid clusters.
3. Creation of micro-tears.
4. Complete destruction of membrane structures.

Repair failure and macromolecular conformation changes

Normally, the cell constantly repairs its structures. However, under the action of damaging factors, these processes are suppressed. Both the reparative resynthesis of altered molecules (lipid, protein, glycoprotein) and the synthesis of membrane components de novo are impaired. Insufficient repair significantly potentiates the scale of damage to the membrane apparatus.

Physicochemical shifts cause modification of the normal spatial structure of macromolecules. The tertiary and quaternary structures of proteins, lipoproteins, and glycoproteins are altered. This leads to the distortion or complete loss of their functions, including the suppression of the activity of vital biologically active substances: enzymes, hormones, and cytokines.

Osmotic overstretching and rupture

Against the background of metabolic disorders, ions and hydrophilic molecules of organic compounds—lactate, pyruvate, glucose, and albumins—accumulate excessively in the cell.

This causes a sharp increase in intracellular osmotic and oncotic pressure. Hyperhydration occurs—water rushes inward, causing the cell and its organelles to swell. The essence of this damage mechanism lies in the critical overstretching of membranes, which inevitably ends in their mechanical rupture and cell death.

Ion and fluid imbalance

Ionic imbalance occurs secondary to or simultaneously with membrane damage against the background of energy depletion. Transmembrane transport of key ions (K⁺, Na⁺, Ca²⁺, Mg²⁺, Cl⁻) is significantly disrupted. Membrane defects and impaired function of membrane ATPases lead to the following consequences:

• Dysfunction of plasmalemmal Na⁺/K⁺-ATPase causes the cell to lose K⁺ and accumulate excess Na⁺ cations in the cytosol.
• Disruption of the Na⁺/Ca²⁺ exchanger (which normally exchanges two incoming Na⁺ for one outgoing Ca²⁺) and Ca²⁺-ATPases leads to a fatal increase in intracellular Ca²⁺ concentration.
• Disruption of cation distribution inevitably entails changes in intracellular anion content (Cl⁻, OH⁻, HCO₃⁻).

The main consequences of these shifts are the development of hypo- or hyperhydration, as well as a severe disturbance of electrogenesis in excitable tissues (disrupted excitation, action potential propagation, and electromechanical coupling).

Class and exam questions

What else to study on this topic

• Mechanisms of lipid hydroperoxide accumulation and activation of lipid peroxidation reactions
• The role of intracellular calcium in irreversible organelle damage
• Impairment of electromechanical coupling and action potential during ionic imbalance
• De novo synthesis and reparative resynthesis of cell membrane components

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.