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