Morphologic Basis for Developing Diverticular Disease, Diverticulitis, and Diverticular Bleeding

Abstract

Diverticula of the colon are pseudodiverticula defined by multiple outpouchings of the mucosal and submucosal layers penetrating through weak spots of the muscle coat along intramural blood vessels. A complete prolapse consists of a diverticular opening, a narrowed neck, and a thinned diverticular dome underneath the serosal covering. The susceptibility of diverticula to inflammation is explained by local ischemia, translocation of pathogens due to retained stool, stercoral trauma by fecaliths, and microperforations. Local inflammation may lead to phlegmonous diverticulitis, paracolic/mesocolic abscess, bowel perforation, peritonitis, fistula formation, and stenotic strictures. Diverticular bleeding is due to an asymmetric rupture of distended vasa recta at the diverticular dome and not primarily linked to inflammation. Structural and functional changes of the bowel wall in diverticular disease comprise: i) Altered amount, composition, and metabolism of connective tissue; ii) Enteric myopathy with muscular thickening, deranged architecture, and altered myofilament composition; iii) Enteric neuropathy with hypoganglionosis, neurotransmitter imbalance, deficiency of neurotrophic factors and nerve fiber remodeling; and iv) Disturbed intestinal motility both in vivo (increased intraluminal pressure, motility index, high-amplitude propagated contractions) and in vitro (altered spontaneous and pharmacologically triggered contractility). Besides established etiologic factors, recent studies suggest that novel pathophysiologic concepts should be considered in the pathogenesis of diverticular disease.

Epidemiology, Pathophysiology, and Treatment of Diverticulitis

“…[102][103][104] Alterations in collagen composition and content as well as connective tissue metabolism have been identified in colons of patients with diverticulosis. 105 Reduced numbers of ganglionic and neuronal cells, 106 as well as imbalances in neurotrophic factors and neuropeptides such as serotonin and acetyl choline, are also found in patients with diverticular disease. [107][108][109] These alternations might cause symptoms in patients with diverticulosis.…”

No neuronal loss, but alterations of the GDNF system in asymptomatic diverticulosis

“…More recently, evidence rises for an enteric neuropathy in DD, characterized by reduced nerve cells (oligo-neuronal hypoganglionosis), decreased intramuscular nerve fibers and altered neurochemical coding [ 6 – 8 ]. Since DD is associated with abnormal intestinal motility patterns [ 9 , 10 ] it is suggested that the disease could be associated with and possibly triggered by an underlying enteric neuropathy [ 11 ].…”

Impaired Expression of Neuregulin 1 and Nicotinic Acetylcholine Receptor β4 Subunit in Diverticular Disease

“…Since nAchRs are critical for gastrointestinal motility (Galligan and North, 2004) and DD is characterized by disturbed intestinal motility (Parks and Connell, 1969;Wedel et al, 2015), we investigated the mRNA expression of those nAchR subunits known to be present in the ENS: the ligand binding nAchR subunits α3, α5, α7 and the structural nAchR subunits β2, β4. While the structural nAchR subunit β4 was down-regulated both at gene and protein level in patients with DD compared to controls, the other subunits remained unaffected.…”