A Concept of Organism’s Functional Integrity and Physical Health Based on Fundamental Limitations of Cells

Abstract

Objective:
The current medical paradigm associates disorders of physical health (PH) with anatomical and functional abnormalities of organs. To diagnose functional disorders, the values of the patient’s measured life indicators should be compared with the average values of similar indicators in control populations (i.e., healthy and sick). This approach cannot recommend optimal treatment paths because the originators of slow structural and functional changes in organs are still behind diagnostic technologies. To overcome these limitations, an alternative paradigm is required.

Methods:
Systems analysis and evolutionary approach.

Results:
A new concept of integrative physiology and a new paradigm (NP) of PH’s assessment are proposed, based on an understanding of the shortcomings originating from biophysical and physiological mechanisms of cell life support. NP considers PH as an evolutionary phenomenon that appeared due to the necessity for specialized cells (SCs) to coexist in a multicellular organism (MO) that exists in an unstable environment. In MO, every SC does provide its basic functions (metabolism, cell cycle, and reactivity). The necessary substrates can be obtained from the close intercellular fluid environment (IFE) that contains metabolites of SCs. None SC consumes its metabolites (wastes), but certain metabolites, capable of stimulating or inhibiting life in other types of cells, functionally integrate them as a physiological multicellular loop (PML). Multiple PMLs provide the functional integrity of MO. However, the SC is not an ideal element to continuously play its roles in PMLs: the stimulation alters the values of SC’s cytoplasmic parameters and impairs SC’s basic functions. This creates risks of death for the impaired SCs and functional disintegration of PMLs, including organs and MO. To minimize risks, every stagnated SC, competing for common but limited substrates in IFE with other cells, must adequately increase its sucking ability. One of SCs' integral functions is to provide IFE with needed substrates. The efficiency of SCs’ coexistence critically depends on their ability to maintain an optimal-like cytoplasm. Across the sieve of evolution passed those MOs that provided an effective solution to this problem. It is shown that a group of internal organs that provide cell life enhances the intracellular mechanisms that govern cytoplasm-genes interaction to minimize the imbalance of anabolic-catabolic transformations. In every specialized organ, the elementary and dynamic functional units determining the current level of output functions are colonies of different SCs, but not SCs.

Conclusion:
Fluctuations or trends in the multidimensional parametric landscape of PH reflect the physiology or pathophysiology of SCs’ coexistence. The efficiency of coexistence is limited by mechanisms originating: i) vulnerability of cells as structural units to local instabilities; ii) interaction of genes with cytoplasmic factors and roles of internal organs in enhancing adaptive reconfiguring of each SC; iii) internal heterogeneities of common SCs in their colonies. The idea is both a novel concept that bridges mitosis, the adaptive reconfiguration of a cell, with the upper-scale physiology, and a key to approaches to personalized prevention, diagnosis, and treatment of non-trivial pathologies of PH.