Mechano-pathogenesis of esophageal hypertrophy and remodeling*

Esophageal hypertrophy is a chronic condition resulting from abnormal esophageal contractions during swallowing. In this study, we develop and utilize a finite growth tissue remodeling model that incorporates fiber contraction to simulate the hypertrophy of the esophagus caused by abnormal swallowing. Specifically, we investigate the differential impacts of stretch-driven and stress-driven growth mechanisms, which are respectively triggered by volume overload and pressure overload conditions. Our analysis reveals distinct growth trajectories that lead to various equilibrium states, each depicting different pathological outcomes. To validate our model, we examined the radial and circumferential components of growth, employing ultrasound clinical data from patients diagnosed with esophageal hypertrophies associated with Achalasia, Distal Esophageal Spasm (DES), and hypercontractility disorders. Clinical observations demonstrate that hypercontractility can induce a range of abnormal esophageal deformations. Extending our model, we can describe additional morphogenetic alterations in the esophagus, such as those observed in Jackhammer esophagus. This condition is characterized by hypercontractile activity leading to a winding staircase of the esophageal lumen, resembling a corkscrew.