A 21st-century update of Claude Bernard's Theory about the Constancy of the Internal Environment.

The discovery of the functioning of intra- and extracellular ion compartments and cell membranes' operation opened the possibility of extending Claude Bernard's theory to intracellular ions. In contrast, by underestimating the role of ions, many misconceptions have prevailed. The author points out that maintaining the constancy of carbon dioxide is especially important. CO2 is one of the most decisive signalling molecules, a mediator connecting the body and the soul. It interacts with intracellular pH, Ca2+, H2PO4- and HPO42- ions, but the intracellular ion pattern, as a whole, also has a primary signalling function. Chronic stress changes the intracellular ion patterns, increasing or decreasing the pCO2 level, an increase in the HCO3-/Cl- ratio leads to Metabolic Syndrome. The HCO3-/Cl- ratio decrease due to chronic hypocapnia results in hyperarousal mental disorders, which seem reversible for decades. The organism starts to get exhausted around 50, and it is not excluded that respiratory alkalosis could turn into metabolic acidosis, making the kidneys reactor organs. (The hypothesis still needs to be verified.) The background of stress-caused age-related diseases is the threat of intracellular acidosis and the organism's fighting against it. With chronic hypo- vs hypercapnia, the humoral counter-regulation cannot fulfil its function and can result in (e.g.) salt-sensitive vs salt-resistant hypertension, respectively. Preserving the original ion pattern is essential but impossible without euventilation. We could control ventilation and stress by administering H2PO4- and HPO42- ion salts. The life span correlates with the Body Cell Mass (BCM); we should preserve it as long as possible. (Neuropsychopharmacol Hung 2024; 26(4): 227-242)