It is generally accepted that the gastric mucosa and adjacent mucus layer
are critical in the maintenance of a pH gradient from stomach lumen to stomach
wall, protecting the mucosa from the acidic environment of the lumen and
preventing auto-digestion of the epithelial layer. No conclusive study has shown
precisely which physical, chemical, and regulatory mechanisms are responsible
for maintaining this gradient. However, experimental work and modeling efforts
have suggested that concentration dependent ion-exchange at the epithelial wall,
together with hydrogen ion/mucus network binding, may produce the enormous pH
gradients seen
in vivo
. As of yet, there has been no exhaustive
study of how sensitive these modeling results are with respect to variation in
model parameters, nor how sensitive such a regulatory mechanism may be to
variation in physical/biological parameters. In this work, we perform
sensitivity analysis (using Sobol’ Indices) on a previously reported
model of gastric pH gradient maintenance. We quantify the sensitivity of mucosal
wall pH (as a proxy for epithelial health) to variations in biologically
relevant parameters and illustrate how variations in these parameters affects
the distribution of the measured pH values. In all parameter regimes, we see
that the rate of cation/hydrogen exchange at the epithelial wall is the dominant
parameter/effect with regards to variation in mucosal pH. By careful sensitivity
analysis, we also investigate two different regimes representing high and low
hydrogen secretion with different physiological interpretations. By
complementing mechanistic modeling and biological hypotheses testing with
parametric sensitivity analysis we are able to conclude which biological
processes must be tightly regulated in order to robustly maintain the pH values
necessary for healthy function of the stomach.