title: A prospective observational study of the effect of critical illness on ultrastructural and microscopic morphology of duodenal mucosa.
abstract: OBJECTIVE
  Disturbed intestinal barrier function due to 'leaky' tight junctions may cause secondary sepsis via paracellular translocation across the gut wall. Our objective was to describe the effects of critical illness on duodenal morphology and ultrastructure.
  
  
  METHODS
  Prospective observational study of 12 mechanically ventilated critically ill patients in an intensive care unit and 15 control participants in an outpatient endoscopy suite.
  
  
  METHODS
  We took six endoscopic biopsy samples of the duodenum from each participant for analysis by electron and light microscopy.
  
  
  METHODS
  Our primary outcome was tight junction morphology, examined with electron microscopy. Secondary outcomes were microvillus length and density, vascular endothelium morphology and mitochondrial density and morphology, examined with electron microscopy, and morphology examined with light microscopy.
  
  
  RESULTS
  We observed no abnormalities of tight junction ultrastructure in either group. There was a tendency towards shorter microvilli in the critically ill group: mean length in critically ill patients, 1.17 µm (interquartile range [IQR], 1.05-1.60 µm) v mean length in control patients, 1.58 µm (IQR, 1.30-1.72 µm); P = 0.07. There was a tendency towards less dense microvilli in the critically ill group: mean density in critically ill patients, 7.29 microvilli/µm (IQR, 6.83-8.05 microvilli/µm) v mean density in control patients, 8.23 microvilli/µm (IQR, 7.34-9.11 microvilli/µm); P = 0.07. Vascular endothelium appeared normal in all critically ill patients and abnormal in one control participant. Abnormal mitochondrial morphology was noted in one critically ill patient and one control participant, and no differences were seen in mitochondrial density. Using light microscopy, we saw more apoptotic cells in the critically ill patients (P = 0.018), but villus height, crypt depth and lymphocyte density were normal.
  
  
  CONCLUSIONS
  We did not detect any morphological abnormalities of duodenal tight junctions in critically ill patients. Our results should be interpreted with caution because of the small sample population, but our observations challenge the concept that paracellular translocation facilitates secondary sepsis.
authors.affiliation: Discipline of Acute Care Medicine, University of Adelaide, SA, Australia.
authors.forename: Victor Y
authors.initials: VY
authors.lastname: Liew
authors.affiliation: Discipline of Acute Care Medicine, University of Adelaide, SA, Australia.
authors.forename: Marianne J
authors.initials: MJ
authors.lastname: Chapman
authors.affiliation: Centre for Research Excellence in Nutritional Physiology, University of Adelaide, Adelaide, SA, Australia.
authors.forename: Nam Q
authors.initials: NQ
authors.lastname: Nguyen
authors.affiliation: Intensive Care Unit, Royal Adelaide Hospital, Adelaide, SA, Australia.
authors.forename: Caroline E
authors.initials: CE
authors.lastname: Cousins
authors.affiliation: Discipline of Acute Care Medicine, University of Adelaide, SA, Australia.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Plummer
authors.affiliation: Discipline of Acute Care Medicine, University of Adelaide, SA, Australia.
authors.forename: Lee-Anne S
authors.initials: LA
authors.lastname: Chapple
authors.affiliation: Discipline of Acute Care Medicine, University of Adelaide, SA, Australia.
authors.forename: Yasmine Ali
authors.initials: YA
authors.lastname: Abdelhamid
authors.affiliation: Department of Anatomical Pathology, SA Pathology, Adelaide, SA, Australia.
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Manton
authors.affiliation: Department of Anatomical Pathology, SA Pathology, Adelaide, SA, Australia.
authors.forename: Adam
authors.initials: A
authors.lastname: Swalling
authors.affiliation: Department of Anatomical Pathology, SA Pathology, Adelaide, SA, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Sutton-Smith
authors.affiliation: Faculty of Health Sciences, University of Adelaide, Adelaide, SA, Australia.
authors.forename: Alastair D
authors.initials: AD
authors.lastname: Burt
authors.affiliation: Discipline of Acute Care Medicine, University of Adelaide, SA, Australia. adam.deane@adelaide.edu.
authors.forename: Adam M
authors.initials: AM
authors.lastname: Deane
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D016638:Critical Illness; D004386:Duodenum / Q000473:pathology / Q000648:ultrastructure*; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology / Q000648:ultrastructure*; D008297:Male; D008854:Microscopy, Electron; D008871:Microvilli / Q000473:pathology / Q000648:ultrastructure; D008875:Middle Aged; D011446:Prospective Studies