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Am J Physiol Gastrointest Liver Physiol 295: G920-G933, 2008. First published August 21, 2008; doi:10.1152/ajpgi.90310.2008
0193-1857/08 $8.00
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NEUROREGULATION AND MOTILITY

Liquid in the gastroesophageal segment promotes reflux, but compliance does not: a mathematical modeling study

Sudip K. Ghosh,1 Peter J. Kahrilas,2 and James G. Brasseur1

1Department of Mechanical Engineering, Pennsylvania State University, University Park, Pennsylvania; and 2Feinberg School of Medicine, Northwestern University, Chicago, Illinois

Submitted 28 April 2008 ; accepted in final form 18 August 2008

The mechanical force relationships that distinguish normal from chronic reflux at sphincter opening are poorly understood and difficult to measure in vivo. Our aim was to apply physics-based computer simulations to determine mechanical pathogenesis of gastroesophageal reflux. A mathematical model of the gastroesophageal segment (GES) was developed, incorporating the primary anatomical and physiomechanical elements that drive GES opening and reflux. In vivo data were used to quantify muscle stiffness, sphincter tone, and gastric pressure. The liquid lining the mucosa was modeled as an "effective liquid film" between the mucosa and a manometric catheter. Newton's second law was solved mathematically, and the space-time details of opening and reflux were predicted for systematic variations in gastric pressure increase, film thickness, muscle stiffness, and tone. "Reflux" was defined as "2 ml of refluxate entering the esophagus within 1 s." GES opening and reflux were different events. Both were sensitive to changes in gastric pressure and sphincter tone. Reflux initiation was extremely sensitive to the liquid film thickness; the protective function of the sphincter was destroyed with only 0.4 mm of liquid in the GES. Compliance had no effect on reflux initiation, but affected reflux volume. The presence of abnormal levels of liquid within the collapsed GES can greatly increase the probability for reflux, suggesting a mechanical mechanism that may differentiate normal reflux from gastroesophageal reflux disease. Compliance does not affect the probability for reflux, but affects reflux volume once it occurs. Opening without reflux suggests the existence of "gastroesophageal pooling" in the distal esophagus, with clinical implications.

gastroesophageal reflux disease; lower esophageal sphincter; compliance; stiffness


Address for reprint requests and other correspondence: J. G. Brasseur, Professor of Mechanical Engineering, Bioengineering and Mathematics, The Pennsylvania State Univ., Dept. of Mechanical Engineering, 205 Reber Bldg., University Park, PA 16802 (e-mail: brasseur{at}psu.edu)






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