Mechano-pathogenesis of esophageal hypertrophy and atrophy

Esophageal hypertrophy and atrophy are chronic conditions associated with abnormal inner pressures during swallowing. Clinical data indicates that disease pathogenesis proceeds via remodeling of the esophageal tissue causing hypertrophy and/or atrophy and eventually leading to end-stage esophageal dilatation. However, it has remained unclear how different mechanical triggers lead to different pathways of disease progression. In this study, using a 1D anisotropic finite growth tissue remodeling model we uncover the fundamental mechanisms of esophageal wall remodeling. The model incorporates the progression of esophageal pressure during swallowing (short time scale peristalsis) on the long-time scale remodeling of the esophageal wall. We explore how different mechanical conditions lead to the emergence of different pathologies by plotting disease trajectories on a regime map (virtual disease landscape). The results reveal that while the esophageal muscle is sensitive to both radial and circumferential strains, the primary differentiator between different disease types is the circumferential stress. This work potentially provides a roadmap to investigate hypertrophies in other organ systems, for example, the mechano-pathogenesis of different types of hypertrophies of the heart.