The human rectum: innervation in health and impact of surgery on function

Abstract

Much current understanding of the function and (neuro)physiology of the human colon and rectum is based on studies of small animals, with a relative paucity of literature using human tissue. Furthermore, the impact of surgery on hindgut function, most commonly encountered through anterior resection of the rectum, remains inconsistently described. This thesis looks to better understand and characterise hindgut afferent and intrinsic innervation using human tissue, and to clinically and physiologically assess bowel dysfunction following anterior resection. In Part I, ‘ex vivo’ studies of the intrinsic and extrinsic innervation of the colon and rectum were performed to determine whether differences exist that might explain the rectum’s unique ability to provide sophisticated sensory information to the brain in its function in the storage and elimination of faeces. Electrophysiological studies were successful in recording extracellular nerve activity in hindgut afferents and demonstrated that rectal tissue was more mechano- and chemo-sensitive than colonic tissue. Wholemount immunostains of human hindgut myenteric plexuses were prepared, and this allowed the quantitative assessment and neurochemical profiling of myenteric ganglia. Despite differences in their extrinsic afferent innervation, there was no regional variation in intrinsic innervation between colon and rectum. In Part II, clinical assessment of bowel function following anterior resection confirmed that objective symptoms of bowel dysfunction are ubiquitous following surgery. Phenotypes of ‘anterior resection syndrome’ (ARS) were identifiable based on types of symptoms reported. Data from control groups, both in the community and those following surgery on other abdomino-pelvic organs (right hemicolectomy and cystectomy), confirmed that the symptom constellation comprising ‘ARS’ is unique to patients following anterior resection. There is marked clinical heterogeneity in patients following anterior resection. Future studies are required to establish a pathophysiological taxonomy for patients with ‘ARS’ now that symptom phenotypes have been identified. Whether identification of these subgroups influences outcomes of treatments for post-operative bowel dysfunction remains to be determined.