Mapping Hyperchloremia's Paradoxes Across RAAS, HPA, and Mitochondria, Lantern of Sulfur, Concept A, v12.1, March 2026

This preprint presents a systems-based reinterpretation of persistent hyperchloremia, reframing it not as a primary renal or acid–base disorder, but as a system-level signal of upstream regulatory misalignment. While elevated chloride is typically viewed in isolation, this work shows that it frequently appears alongside non–anion gap metabolic acidosis (NAGMA), fluid instability, and hormonal dysregulation in the absence of intrinsic kidney dysfunction. This creates a clinical paradox: laboratory values indicate disturbance, yet conventional mechanisms fail to fully explain the pattern. Using a translational framework developed through longitudinal observation and systems mapping, this paper links hyperchloremia to coordinated disruptions across hydration state, bile flow, neuroendocrine signaling (HPA axis), RAAS interpretation, and mitochondrial function. In this model, chloride reflects the conditions under which renal electrolyte handling occurs, rather than acting as a primary driver of pathology. The Lantern of Sulfur framework is introduced as a diagnostic and interpretive tool that translates fragmented clinical signals into a coherent regulatory architecture. By shifting focus from isolated pathways to system organization, the model offers a new way to interpret hypertension without volume overload, unexplained NAGMA, RAAS instability, and metabolic dysfunction. This work is presented as a hypothesis-generating framework intended for clinical observation, testing, and cross-disciplinary collaboration. This paper is part of the Lantern of Sulfur (LoS) Version 12 series, which unifies prior work into a single translational systems model.