A five-domain functional framework for integrative physiology: a coherent and operational approach to whole-body function

Because the body is commonly described in a six-layered structural hierarchy starting from molecules and cells to tissues, organs, organ systems, and finally to the whole organism, bodily functions (physiological and pathophysiological) are often approached in the same layered way. This is familiar and convenient, but it has clear limitations. Many important functions, such as homeostasis, thermoregulation, stress responses, and so on, emerge from coordinated causal processes that span multiple levels. They cannot be understood by assigning them to a single anatomical layer, yet integrative physiology still lacks a functional framework that is both conceptually coherent and practically useful for representing such multi-level interactions. This article introduces a 5-domain functional framework, developed through logical analysis of how intracellular fluid compartment(s) (ICF or ICFs) operate collectively within the shared extracellular fluid compartment (ECF). From this enveloping ECF–ICF relationship, five relational functional domains emerge. This perspective organizes bodily processes according to their operational logic rather than their anatomical position, allowing multi-level coordination to be visualized in a unified and flexible way. This framework and logic further lead to the development of a second functional platform that can organize bodily functions described by quantitative/mathematical relationships (e.g., oxygen-hemoglobin dissociation curve, Nernst equation, Michaelis-Menten equation, etc.). The platform is named Blueprint for Quantitative Functional Organization (BQFO). When mathematical expressions of function are placed into the BQFO, they form a systematically organized hierarchy rather than remaining scattered across topics. Together, the 5-domain functional framework and the BQFO provide not only practical tools for integrating complex functions but also a more realistic epistemology and methodology for understanding how bodily functions operate. These developments potentially establish new principles and offer new tools for integrative physiology and interdisciplinary teaching and research.