Modeling, mechanics and physiology of the esophagus and lower sphincter

by Ghosh, Sudip Kumar.

The process of deglutition includes a series of coordinated neuro-muscular interactions that produce bolus transport and mixing along the human gastrointestinal tract. In this thesis, we use a combination of mathematical modeling and physiological data analysis to study the mechanics and macrophysiology underlying antegrade and retrograde bolus transport through the esophagus and the esophago-gastric segment (EGS). Specifically, we analyze normal and abnormal antegrade transport (a) through the esophageal body, (b) across the EGS associated with swallowing, and (c) EGS opening and retrograde flow of gastric fluid associated with gastro-esophageal reflux. The manometrically measured pressure wave, which is associated with peristaltic muscle contraction in the esophagus, consistently displays a trough called the transition zone (TZ) in the neighborhood of the aortic arch. A previous computer model study suggested that the TZ is associated with distinct upper and lower contraction waves that must be coordinated spatially and temporally for successful bolus transport. Through a study of concurrent high resolution manometry and fluoroscopy, we demonstrate that the existence of two distinct contraction waves above and below the esophageal TZ, with a well-defined jump between them, comprises normal neuromuscular physiology. The space-time structure of pressure surrounding the jump shows that the TZ is a region of segmental contraction. In a patient group with higher bolus retention (2.18 ml vs. 0.20 ml), the separation between the two contraction waves was nearly twice as large as iii normal controls (6.00 cm vs. 3.32 cm), with significantly weaker muscle squeeze pressure in the TZ. We conclude that pathological bolus retention in the aortic arch region of the esophagus is related to an adverse modulation of the neurophysiology that controls the coordination between upper and lower esophageal contraction waves, resulting in inefficient bolus transport. Next, we studied the mechanics of esophageal emptying from a " distal bolus cavity " across the hiatal canal of the EGS to the stomach in normal subjects, and its modulation after fundoplication. Temporal changes in geometry of the distal bolus cavity and hiatal canal and cavity driving pressure were quantified. These data were combined with mathematical models of esophageal emptying and muscle tension driving transhiatal flow. All esophageal emptying events post fundoplication were incomplete (51% retention). Whereas there was no significant difference in the period of emptying between controls and patients, average emptying rates were 40% lower in the post-fundoplication group. The mathematical model predicted three distinct phases during esophageal emptying. A rapid increase in muscle tone and driving pressure forced normal hiatal opening. In the post-fundoplication group, a severe impairment of cavity muscle tone resulted in causing deficient hiatal opening and flow and consistent bolus retention. In the final phase of our study, we developed a solid-fluid interaction model of gastro-esophageal reflux in which a model of esophageal tension is combined with a lubrication-theory-based fluid flow model to study the mechano-physiology of EGS opening and reflux. The external sphincter tone associated with the crural diaphragm is modeled as external pressure. Passive elastic tension associated with both internal and external muscle components are modeled through stress-strain constitutive relationships. iv Viscoelasticity is added through an ad-hoc damping term. We find that gastric pressure plays a crucial role in the initiation of opening of a relaxed EGS, and that both stiffness of the EGS and gastric pressure are important determinants of the degree of opening. We demarcate the reflux/no-reflux barrier associated with a weakened EGS and conclude that reduced stiffness of the EGS is a potentially important aspect of reflux disease. Model results predict that the probability of reflux is much higher when the basal lumen radius is only 1 mm > normal, suggesting that abnormally high resting luminal distension leads to more frequent reflux, and may underlie much gastroesophageal reflux disease, especially with hiatal hernia. v