The gastric mucus is a complex gel-like layer of various proteins and solutes coating the epithelial surface of the stomach. This layer is widely recognized to serve a protective function, shielding the epithelium and the rest of the gastric mucosa from the extremely low pH and digestive enzymes present in the stomach lumen. Often described as a “diffusion barrier” the mucus layer is thought to hinder the transport of diffusive species from the lumen to the stomach wall. However, there is still a lack of consensus on the mechanism by which the mucus layer hinders lumen-to-wall transport while allowing acid and enzymes secreted from the mucosa unimpeded transport to the lumen. Using a physical model of electro-diffusion within a multi-component fluid, we test one hypothesis from the physiology literature and show that physiological relevant pH gradients can be maintained in steady state. We then leverage the model in conjunction with Sobol Indices and other techniques from Sensitivity Analysis (SA) to explore what regulatory mechanisms are necessary to segregate an acidic stomach lumen from a pH neutral stomach wall robustly, in the face of dynamic/random parameter perturbations. Finally, we discuss the mathematical and numerical challenges inherent in large-scale simulation of electro-diffusive processes in biology, and propose some possible avenues forward.