A New Physiological Framework: The Human Interstitial System as the Body's Relational Matrix

The classical organ-based model of human physiology provides an essential but incomplete framework for understanding whole-body integration. While the nervous and endocrine systems are acknowledged master regulators, they operate upon a continuous physical substrate whose system-level function has been largely overlooked. For centuries, anatomists, physiologists, and clinicians have documented the interstitial spaces—the fluid-filled, matrix-supported regions between cells—as passive conduits and structural supports. Here, we synthesize this vast body of knowledge to propose the Human Interstitial System (HIS). We define the HIS as a fundamental physiological system, characterized by its body-wide continuity and its primary role as a relational matrix that physically and functionally interconnects all discrete anatomical units. We posit that the dynamic architecture of the HIS governs the flow of information, nutrients, and mechanical forces, thereby influencing systemic state emergence. The framework is articulated through four core functions—mediation, filtration, integration, and emergence—and a testable biophysical model based on confined hydrodynamics and wave interference. We propose three decisive, falsifiable experiments to challenge the core tenets of this theory. Establishing the HIS provides a novel paradigm for understanding physiological integration, with profound implications for redefining diseases like fibrosis and developing novel therapeutic strategies.