Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Rainer, F.
Morphologic Alterations of Small Intestinal Mucosa in Patients with Cirrhosis
[ Diplomarbeit ] Medical University of Graz; 2013. pp. 102
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Lackner Karoline
- Stauber Rudolf
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- Abstract:
- Background: Increased gastrointestinal permeability in cirrhosis is considered an important factor in the etiology of bacterial translocation & its related complications and has repeatedly been confirmed by measuring the urinary excretion of orally administered test substances. Since tight junctions represent the main barrier for macromolecules used in permeability tests, impaired function related to structural alterations is suspected to be involved in the disruption of the gut barrier. However, studies regarding the ultrastructural changes in intestinal mucosa are scarce and have given contradictory results. Methods: Twelve patients with cirrhosis at an early (n = 7) or advanced (n = 5) stage and ten healthy controls underwent distal duodenal biopsy. Alterations observed on light- and transmission-electron microscopy, with special emphasis on tight-junction ultrastructure, were correlated to intestinal permeability, assessed by the sucrose/lactulose/mannitol test. Results: Morphological abnormalities on light microscopy included a distended intercellular space (in the basal parts of enterocytes) & vacuolization of the enterocytes¿ cytoplasm at the villous tips, increased number of denuded villi, edema & fibrosis of the lamina propria and larger capillary diameters in cirrhotic patients. The lactulose/mannitol excretion ratio was increased in cirrhotics. Permeability for mannitol was only decreased in patients with advanced cirrhosis. Electron-microscopy analysis revealed preserved cell/cell-connections at the enterocytes¿ luminal borders with morphologically intact tight junctions. A slightly increased TJ-gap width was observed only in-between perishing enterocytes and in epithelial areas with distended intercellular spaces (in the basal parts of the epithelium). In contrast, density of the perijunctional actomyosin complex was increased even in areas without distended intercellular spaces or perishing cells. Furthermore, microvilli were shorter and less densely packed; distorted microvilli were only observed in perishing enterocytes. Conclusion: Among the morphological changes detected by light microscopy (distended intercellular spaces, vacuolization of the cytoplasm, denuded villi, edema & fibrosis of the lamina propria and capillary congestion), only denuded villous tips correlated with an increased lactulose/mannitol ratio. Permeability for mannitol was decreased in advanced cirrhotics, probably associated with a decreased villus/crypt ratio observed in those patients. Ultrastructural analysis revealed a widening of tight-junction gaps in epithelial areas with a distended intercellular space in the basal parts of enterocytes, but, only a tendency to correlate with the lactulose/mannitol ratio was observed. Further studies in larger cohorts are being conducted to confirm our findings and to reach statistical significance in some indicated alterations.