Changes in Colonic Structure and Mucosal Inflammation

Diverticula are sac-like protrusions of the mucosal and submucosal layers through weak colonic wall areas (“locus minoris resistentiae”). These areas mainly include the points where intramural blood vessels, the perforating arteries (“vasa recta”), are brought into the mucosa to distribute blood by punching through the circular muscular layer. So defined, the existence of diverticula is a congenital or an acquired anomaly whose etiology has just begun to be understood but, because of its multifactorial condition, still has some unclear points. The study of changes in the structure of the colon and inflammation of the mucosa is the starting point for understanding the sequence of events that leads to the formation of diverticula and, consequently, to the setting of proper treatment of the pathology. In Western industrialized countries, the site most affected by diverticular disease is the left colon, but, in the Asian population, right-sided diverticulosis is more common. The incidence reported is in 17.5% of the general population, and it represents up to 42% of all endoscopic diagnosis, increasing steadily with age, reaching around 30% at 65 years, 50% in those over 75 years, and 71% in those aged =80 years [1]. No difference has been found in the sex distribution of diverticulosis [2]. Left-sided diverticulosis almost invariably involves the sigmoid colon and may extend proximally, but the involvement of the ascending colon and cecum occurs in fewer than 10% of cases. The extraperitoneal rectum is not affected [3]. Left-sided diverticulosis is also known as pulsion diverticulosis. The demographic profile of the typical patient with diverticulosis perfectly matches the natural history of diverticular disease. According to Laplace’s law in organs with a distensible wall, it is commonly believed that high colonic pressure will develop tension in response to the elongation, thus leading to the development of diverticula at the weakest point of the colonic tissue. However, there is no validated theory to support these claims; even severe mechanical stress is a significant factor driving tissue remodeling [4, 5]. Patel et al. developed an experimental model on swine’s descending colon based on simultaneous inflation and extension tests evaluating the result obtained using the Finite Element (FE) software. This approach simulates a physical phenomenon occurring during diverticula formations and reports the results with a computational model using a numerical mathematical technique to prove that the mechanical stress could be critical in diverticulum genesis and in the increase of the diverticulum’s volume [6]. The model was designed keeping in mind the typical anisotropic nature of the colonic tissue, which in turn depends on its microscopic characteristics. Thus, the model has shown that the highest stress values are concentrated around the luminal side of the pouch’s neck. The increase in stress increases with increasing pressure until it reaches two to three times the maximum values observed in a normal colon. A significant elevation of stress could occur in a colon with diverticulosis than in a normal colon, which implicates elevated stresses in this condition that are responsible for diverticular wall remodeling. In this manner, computational structural mechanics can investigate potential changes in stress distribution that could be introduced in the colonic tissue due to the presence of a pouch-like structure. More interesting, the analysis shows a correlation between stress elevation and size of the pouch. It is known that pouch size increases over time in diverticulosis and that mechanical stress is a significant factor driving biological tissue remodeling. These two elements would explain the overall pouch size increase in response to elevated stress values around the pouch, leading to a vicious cycle where the pouch size is further increased. The distance from the center of the pouch (zone of influence) increases with pressure, reaching a plateau value after a specific pressure elevation that correlates with the area of the pouch neck, suggesting that the size of the pouch neck is more important than the surface area of the pouch itself in pouches under high stress and with a greater zone of influence. Besides, a significant luminal pressure drop would be necessary to restore stress to an average level, explaining the low effectiveness of a high-fiber diet as a stand-alone treatment solution once pouches are developed. A diverticulum is expected to be more compliant than a normal tissue constituted by only the mucosal and submucosal layers. The mucosa has been reported to be extremely expansible, and the submucosa could withstand deformations four to five times greater than the muscular layer [7]. Notably, even if the colon is a collapsible tube with curves, the stress values would undoubtedly change, but the high-stress value observed at the neck of the pouch with a relative increase in pressure and pouch size will not change. Luminal pressure (pressure on the inner wall of the tissue with an external force equal to zero) values above 1.5 kPa lead to permanent tissue damage. The computational simulations pushing this value to visualize the evolution of stress values and luminal pressure might explain the variation in diverticular shape and volume. Moreover, it might also try to explain tissue remodeling until a complication appears.