Ghosh SK, Kahrilas PJ, Brasseur JG. Liquid in the gastroesophageal segment promotes reflux, but compliance does not: a mathematical modeling study. Am J Physiol Gastrointest Liver Physiol 295: G920 -G933, 2008. First published August 21, 2008 doi:10.1152/ajpgi.90310.2008.-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 MUCH IS UNDERSTOOD ABOUT THE biomechanics underlying gastroesophageal reflux once refluxate flow into the esophagus has occurred, such as sphincter relaxation pressures (21), transsphincteric pressure gradient (46), hiatal distension (25), and the proximal extent of reflux (11). However, the mechanical differences that distinguish normal from chronic reflux are those that manifest at the time of opening and the initiation of reflux; these are less well understood. This lack of understanding of the initiation process is primarily because the initial opening process involves a level of mechanical subtlety in the balances among multiple forces and muscle deformations that are difficult to measure accurately in vivo due to rapid changes occurring over very short times with small changes in radial distention.The opening of the gastroesophageal segment (GES) and reflux result from dynamic adjustments in the subtle force balance that are initi...