1. Stage of Initial Structural Hyperfunction
This phase reflects the very beginning of the pathological process. Researchers often refer to it as the "emergency stage", because in experiments, damage occurs acutely, although clinically the process may develop gradually.
Pathogenesis of the emergency stage:
- The load on structures performing the specific function of the organ increases.
- Work requires a sharp increase in metabolism and energy consumption.
- Mitochondria present in the cell begin to work to the limit of their capacity.
- Hyperfunction leads to accelerated destruction of the internal mitochondrial structures — destruction of cristae.
- An acute energy deficit arises because damaged mitochondria cannot produce the required volume of ATP.
This energy starvation serves as the main signal for triggering compensation—it stimulates the intensification of biosynthetic processes to create new intracellular structures.
2. Stage of Relatively Stable Compensation
At this stage, the organ adapts to the increased load through structural remodeling. Morphologically, this is manifested by hyperplasia of intracellular structures (an increase in the number of organelles, primarily mitochondria), as well as hypertrophy and hyperplasia of the cells themselves.
Due to the increase in the number of mitochondria, the energy deficit decreases sharply. However, during a chronic course of the disease, a hidden threat forms. All generated energy is divided into two streams:
- Ensuring organ function (absolute priority).
- Resynthesis of structures that are destroyed during intensive work.
Since function reigns supreme, the lion's share of energy goes toward it. Energy begins to fall short for the full restoration of organelles. A vicious cycle is formed: due to a lack of resynthesis, fewer cristae are formed $\rightarrow$ the load falls on the remaining structures $\rightarrow$ they work even more intensively $\rightarrow$ they break down faster $\rightarrow$ the energy deficit increases again.
3. Stage of Energy Depletion (Decompensation)
The finale of the compensatory process, in which the breakdown of intracellular structures progressively prevails over their resynthesis. The organ can no longer cope with the load.
Key tissue changes:
- Disappearance of cell heterogeneity. Normally, cells work in turns, but upon exhaustion, the organ has to engage the potential of absolutely all cells simultaneously.
- Loss of regenerative capacity. To recover, a cell needs to put function "on pause," which is impossible under conditions of continuous overload.
- Tissue hypoxia. It paradoxically increases even with a normal supply of oxygen to the blood. The reason is the physical absence of fully functional mitochondria capable of utilizing this oxygen.
Increasing acidosis leads to labilization of lysosomal membranes. Lysosomal hydrolases enter the cytoplasm, triggering autolysis (self-digestion) of structures. Energy production drops to a critical minimum, and the specific function of the organ fades.
Role of Intermitochondrial Contacts
Under conditions of energy deficit, mitochondria try to survive through cooperation. They unite into clusters, forming intermitochondrial contacts (IMC).
This allows for the synchronization of organelle function: the activity of proton ATP synthase increases within the clusters, sharply boosting energy production. However, this mechanism has a limit. If the number of mitochondria or their cristae falls below a certain threshold level due to exhaustion, cluster formation becomes impossible. A rapid breakdown of compensation occurs.