Determining Gastric Acid Output Using a pH-sensing Capsule
Determining Gastric Acid Output Using a pH-sensing Capsule
To accurately assess GAO, both the pH and volume of secretion must be known. To assess pH, we used the SmartPill capsule (SmartPill Corporation, Buffalo, NY, USA). To quantify the volume of acid secretion in the stomach, we measured the acidification of a standard meal with a known buffering capacity—Ensure Plus (creamy milk chocolate flavour; Abbot Laboratories, Abbott Park, IL, USA). The ideal method should be able to (i) measure a wide range of secretion; (ii) have adequate mixing and sampling of gastric contents; (iii) account for residual acid in the fasting stomach; (iv) sample the stomach for sufficient time; (v) apply to diverse populations; and (vi) be reproducible. Some of these performance characteristics have already been validated (Table 1); we further confirmed and enhanced validation of these characteristics in our method as described below.
A mathematical model was constructed to determine the feasibility of measuring GAO by a meal-stimulated wireless pill method. This model helped to clarify the contribution of variables that impact the gastric acid analysis of a buffered meal. To model the buffering reaction within the stomach, we considered the reaction, B ⇄ H+ A, where B is a weak acid, H is a hydrogen ion and A is the conjugate base. We considered the stomach to be a well-mixed medium. The conjugate base (buffering agent) is added to the stomach, which increases the volume. This induces the addition of hydrogen ions through acid secretion. The entire well-mixed components within the stomach empty simultaneously. We modelled the kinetics of this reaction with the following system
where H, A and B are measured in milliequivalents (mEq) and W is water measured in millilitres; kb is the backward rate of the buffer reaction measured in min and kf is the forward rate measured in mL/mEq/min d is the emptying rate of the stomach measured in min, with d = log(2)/(emptying half-life in min); Hsec is the gastric secretion rate of acid in mEq/min; Abuf is the amount of added buffer in mEq and Wbuf is the volume of water of the added buffer in mL; g(t) is an impulse function of area one that indicates that the buffer is added as a single bolus; W0 is the baseline amount of water in the stomach measured in mL.
We assume at time zero that A and B are both zero; W = W0, and H is the initial concentration of acid multiplied by W0. Then the buffer is introduced over a brief period of time specified by g(t). We assumed that gastric acid is secreted into the stomach at a constant rate. The pH of the stomach is given by −log(H/W).
To validate this model, we performed laboratory experiments using a beaker to simulate a stomach. The beaker had a residual volume of gastric secretions, similar to that of a stomach. A stir bar simulated gastric mixing and peristaltic pumps were used to simulate fixed rates of acid secretion and gastric emptying. Ensure Plus at varying dilutions served as the meal and was rapidly poured into the beaker at time zero. The change in pH was measured over time with a Pinnacle 3-in-1 refillable pH electrode (Nova Analytics Corporation, Woburn, MA, USA) and a Corning 430 pH meter (Corning Incorporated, Corning, NY, USA).
Materials and Methods
Overview of Comprehensive Assessment
To accurately assess GAO, both the pH and volume of secretion must be known. To assess pH, we used the SmartPill capsule (SmartPill Corporation, Buffalo, NY, USA). To quantify the volume of acid secretion in the stomach, we measured the acidification of a standard meal with a known buffering capacity—Ensure Plus (creamy milk chocolate flavour; Abbot Laboratories, Abbott Park, IL, USA). The ideal method should be able to (i) measure a wide range of secretion; (ii) have adequate mixing and sampling of gastric contents; (iii) account for residual acid in the fasting stomach; (iv) sample the stomach for sufficient time; (v) apply to diverse populations; and (vi) be reproducible. Some of these performance characteristics have already been validated (Table 1); we further confirmed and enhanced validation of these characteristics in our method as described below.
Mathematical Modelling and in Vitro Study
A mathematical model was constructed to determine the feasibility of measuring GAO by a meal-stimulated wireless pill method. This model helped to clarify the contribution of variables that impact the gastric acid analysis of a buffered meal. To model the buffering reaction within the stomach, we considered the reaction, B ⇄ H+ A, where B is a weak acid, H is a hydrogen ion and A is the conjugate base. We considered the stomach to be a well-mixed medium. The conjugate base (buffering agent) is added to the stomach, which increases the volume. This induces the addition of hydrogen ions through acid secretion. The entire well-mixed components within the stomach empty simultaneously. We modelled the kinetics of this reaction with the following system
where H, A and B are measured in milliequivalents (mEq) and W is water measured in millilitres; kb is the backward rate of the buffer reaction measured in min and kf is the forward rate measured in mL/mEq/min d is the emptying rate of the stomach measured in min, with d = log(2)/(emptying half-life in min); Hsec is the gastric secretion rate of acid in mEq/min; Abuf is the amount of added buffer in mEq and Wbuf is the volume of water of the added buffer in mL; g(t) is an impulse function of area one that indicates that the buffer is added as a single bolus; W0 is the baseline amount of water in the stomach measured in mL.
We assume at time zero that A and B are both zero; W = W0, and H is the initial concentration of acid multiplied by W0. Then the buffer is introduced over a brief period of time specified by g(t). We assumed that gastric acid is secreted into the stomach at a constant rate. The pH of the stomach is given by −log(H/W).
To validate this model, we performed laboratory experiments using a beaker to simulate a stomach. The beaker had a residual volume of gastric secretions, similar to that of a stomach. A stir bar simulated gastric mixing and peristaltic pumps were used to simulate fixed rates of acid secretion and gastric emptying. Ensure Plus at varying dilutions served as the meal and was rapidly poured into the beaker at time zero. The change in pH was measured over time with a Pinnacle 3-in-1 refillable pH electrode (Nova Analytics Corporation, Woburn, MA, USA) and a Corning 430 pH meter (Corning Incorporated, Corning, NY, USA).
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