Intestinal motility is regulated by the enteric nervous system, interstitial cells of Cajal (ICCs) and smooth muscle cells. Changes in these structures can lead to dysmotility, summarised in the term gastrointestinal neuromuscular disease (GINMD). GINMD includes a clinical heterogeneous group of primary and secondary GINMDs. The aetiology of secondary GINMDs is generally better understood than that of primary GINMDs, but histopathological features are often not systematically studied. In this thesis, the histological background of the pathophysiology of secondary motility disorders with a clear aetiology (spinal cord damage, amyloidosis and systemic sclerosis) is investigated to understand possible mechanisms of intestinal motility disorders. Chapter 2-3 describes methodological issues. We presented a straightforward semiquantitative estimation method for myenteric ICCs of the bowel, showing a good inter- and intra-observer agreement and reliability. Since this method was capable to differentiate between normal and diseased tissue, it can be used in routine diagnostics of GINMDs. Other neuromuscular structures in the bowel were semiquantitatively evaluated in this thesis, including neurons, glial cells and smooth muscle. Chapter 4 focusses on histological changes in the bowel wall in spinal cord damage. A reduction of the myenteric ICC network was shown in almost all patients, while the neuronal density was reduced in two thirds of the patients with ICC loss. Enteric glia were significantly decreased in patients with severe motility problems. Chapter 5 describes histological features of the intestinal wall in AL- and AA-amyloidosis. We found amyloid deposits in the vascular walls and in the muscularis propria, which may be the major cause of bowel dysmotility, and ICC loss. Chapter 6 focusses on histological characteristics in systemic sclerosis. Fibrosis was found in the vascular walls and in the muscularis propria. A reduction of neurons, glial cells and ICCs was shown in this patient group, but we found a large variation of characteristics between individual patients. In conclusion, the study into specific diseases has provided new insights and hypothesis within the field of GINMDs. The heterogeneity within our patient cohorts makes it difficult to derive general pathophysiological mechanisms for (primary) intestinal motility disorders.
|Qualification||Doctor of Philosophy|
|Award date||31 Oct 2019|
|Place of Publication||Enschede|
|Publication status||Published - 31 Oct 2019|
- gastrointestinal motility