This paper presents a systems-level formulation of Directional Pressure Failure (DPF), a physiological state in which fluid distribution, pressure gradients, and regulatory signaling become misaligned, resulting in continued system activity without completion of fluid redistribution or metabolic and acid–base resolution. Physiological regulation depends on alignment between physical conditions and the signals used to interpret them. On Earth, gravity organizes fluid distribution and pressure gradients, allowing baroreflex, hormonal, and renal systems to coordinate responses that converge toward equilibrium. In microgravity, the absence of gravitational direction alters fluid distribution and gradient structure. Pressure sensing mechanisms remain intact, but operate under changed physical conditions, producing responses that are internally consistent yet insufficient to fully resolve cardiovascular and fluid transitions. A parallel pattern is observed in hyperchloremic states associated with non–anion gap metabolic acidosis, where electrolyte and acid–base changes reflect regulatory output rather than restoration of equilibrium. In these cases, renal and hormonal systems execute signals appropriately, but those signals are mismatched to physiological conditions, resulting in persistent imbalance despite preserved organ function. This work integrates these observations into a unified framework in which regulatory control persists but is mismatched to the environment, resulting in incomplete physiological resolution. A mechanistic layer is introduced linking fluid distribution, compartmental hydration, electrolyte shifts (chloride and bicarbonate), and regulatory signaling (including RAAS and vasopressin), demonstrating how self-consistent but unresolved system states can emerge across both environmental and clinical contexts. This paper complements prior work describing the expression of DPF across microgravity and clinical states by developing the underlying systems model of alignment, signaling, and resolution.
Beth Ann Martell (Mon,) studied this question.