Regulatory Orientation and Electrolyte Stability: Systems Context for Bile Acid–RAAS–Chloride Interactions, V 1.3, February 2026

Version 1.3 introduces a systems orientation framework contextualizing the mechanistic continuity model established in Version 1.2, which linked bile acid receptor signaling to downstream chloride and acid–base regulation through renal nitric oxide and RAAS modulation. This update does not introduce new biological mechanisms. Instead, it provides a structural interpretation clarifying how established regulatory components function together as a continuous physiological axis connecting upstream metabolic signaling, renal execution, and downstream electrolyte outcomes. Positioning the kidney as the primary integration and execution interface highlights how renal nitric oxide production, vascular tone regulation, and renin–angiotensin signaling translate upstream receptor activity into electrolyte transport decisions. This orientation framework is interpretive and hypothesis-generating. It is intended to complement established physiology by providing a structural basis for understanding state-dependent divergence in chloride homeostasis and acid–base balance, including hyperchloremic non–anion gap metabolic acidosis phenotypes. This note is part of an ongoing mechanistic continuity series examining bile acid–RAAS–electrolyte regulatory interactions.