Intestinal hypomotility in systemic sclerosis: a histological study into the sequence of events

Contains fulltext : 232630.pdf (Publisher’s version ) (Open Access)OBJECTIVES: The pathogenesis of intestinal involvement in systemic sclerosis (SSc) is thought to be a sequential process (vascular, neuronal, and consecutive muscular impairment), but understanding of the underlying histological changes and how they translate to symptoms, is still lacking. Therefore, we systematically investigated histological characteristics of SSc in the intestines, compared to controls. METHODS: Autopsy material from the small bowel and colon was used for histological semiquantitative evaluation of the vasculature, enteric nervous system, interstitial cells of Cajal (ICC), and muscle layers, using a combination of histochemical and immunohistochemical stainings, according to guidelines of the Gastro 2009 International Working Group. RESULTS: Vascular changes were most frequently encountered, represented by intima fibrosis in both arteries and small vessels, and represented by venous dilatation. Second, generalized fibrosis of the circular muscle layer was significantly more found in SSc patients than in controls. Third, reduction of submucosal nerve fibers and myenteric neurons was shown in the colon of four SSc patients, which may explain severe symptoms of intestinal dysmotility. The density of myenteric ICC network was decreased in the small bowel of SSc patients. CONCLUSIONS: The postulated sequential processes of intestinal involvement in SSc could not be supported by our histological evaluation. The interpatient diversity suggests that parallel processes occur, explaining the variety of histological features and clinical symptoms. Key Points • Histological analysis showed vascular changes, fibrosis in the muscularis propria, and reduction of the ENS and ICC network in the intestines of SSc patients. • Pathophysiological mechanisms leading to intestinal dysmotility in SSc may be parallel rather than sequential. • The interpatient diversity suggests parallel pathophysiological processes, explaining the variety of histological features and clinical symptoms

The enteric nervous system and the musculature of the colon are altered in patients with spina bifida and spinal cord injury

Neurogenic bowel dysfunction occurs in a large percentage of adult patients with spina bifida (SB) and spinal cord injury (SCI), significantly affecting their quality of life. Although bowel motility is autonomously regulated by the enteric nervous system (ENS), disruption of the modulation of the ENS by extrinsic innervation as present in many patients with SB and SCI might lead to motility disorders. In order to gain insight in the pathophysiology, we studied histological changes of the neuromuscular structures in the colon of SB and SCI patients. Archival colon tissue blocks from SB (n = 13) and SCI (n = 34) patients were collected nationwide in The Netherlands and compared with control samples (n = 16). Histological (semiquantitative) evaluation of the ENS, the network of interstitial cells of Cajal (ICC), and the muscularis propria was performed using hematoxylin and eosin, periodic acid Schiff, and elastic von Gieson staining, and immunohistochemistry with antibodies against HuC/D, calretinin, S100, CD117, alpha-smooth muscle actin, and desmin. Compared to controls, SB and SCI patients showed neuronal loss and decreased nerve fiber density in the myenteric plexus. Lower nerve fiber density was significantly more often found in patients with severe bowel dysfunction. Other major findings were loss of ICCs around the myenteric plexus and fibrosis in the longitudinal muscle layer. Altered histology of the ENS may explain abnormal intestinal motility in SB and SCI patients. Furthermore, loss of myenteric nerve fibers (including enteric glial cells) may play a major role in the development of severe motility complaints

Practical and reproducible estimation of myenteric interstitial cells of Cajal in the bowel for diagnostic purposes

Contains fulltext : 171221pub.pdf (publisher's version ) (Closed access)BACKGROUND: Histological assessment of the interstitial cells of Cajal (ICCs) in the bowel is important for diagnosing patients with gastrointestinal neuromuscular diseases (GINMD). Although the International Working Group on GINMD proposed reporting a decrease in ICC number of more than 50%, quantitative methods used in literature are not practical for daily routine of the pathologist. Consequently, this study presents a straightforward semiquantitative estimation method for myenteric ICCs of the bowel. METHODS: Formalin-fixed paraffin-embedded sections from small bowel (n = 87) and colon (n = 159) were collected to create two control groups and four groups composed of patients with gastrointestinal motility disorders. The control groups included material of resection and autopsy origin, respectively. Samples were stained with CD117 (c-kit) antibody to estimate the myenteric ICC network. Scores of two observers were compared to analyze inter- and intraobserver agreement and reliability. KEY RESULTS: Interobserver reliability was almost perfect for small bowel (intraclass correlation coefficient 0.847; 95% confidence interval [CI]: 0.774-0.897) and substantial for colon (0.683; 95% CI: 0.591-0.758). Almost perfect intraobserver reliability was found (intraclass correlation coefficient 0.918; 95% CI: 0.874-0.947). The small bowel showed more myenteric ICCs than the colon. Neither significant differences between colonic regions were found nor were there any differences in the orientation of the sections. CONCLUSIONS & INFERENCES: The proposed estimation method for the myenteric ICC network showed generally good agreement and reliability. As the method is semiquantitative, simple, and capable to differentiate between normal and diseased tissue, it can be used in routine diagnostics of gastrointestinal neuromuscular disorders

The autonomic nervous system

The autonomic nervous system innervates the visceral organs, the glands and the blood vessels. It regulates the internal environment, and it is largely responsible for maintaining normal bodily functions such as respiration, blood pressure and micturition. The peripheral autonomic nervous system consists of two parts, a thoracolumbar or sympathetic and a craniosacral or parasympathetic division, which usually have antagonistic effects (Sect. 12.2). The sympathetic system is organized to mobilize the body for activities, especially in stressful situations (Cannon’s fight or flight), whereas the parasympathetic system in particular stimulates the peristaltic and secretory activities of the gastrointestinal tract (also known as rest and digest response). The peripheral part of the autonomic nervous system includes neurons in the viscera and peripheral ganglia, which are innervated by the lateral horn of the spinal cord and certain brain stem nuclei. Neuronal plexuses in the gastrointestinal tract form the enteric nervous system, which is often viewed as the third component of the autonomic nervous system. Tonically active bulbar centres control vital functions such as blood pressure and respiration. The autonomic centres in the brain stem and spinal cord are reciprocally connected with the central autonomic network (Sect. 12.3), which includes the hypothalamus and several other forebrain (in particular the extended amygdala and the insula) and brain stem structures such as the periaqueductal grey and the parabrachial nucleus. This network is essential for the integration of autonomic, endocrine and somatomotor functions. The peripheral and central autonomic pathways may be affected by many diseases, which cause derangement of autonomic functions as exemplified in several Clinical Cases on disorders of the neural control of blood pressure, breathing and micturition. The English terms of the Terminologia Neuroanatomica are used throughout