The Intestinal Mucosal Lesions in Shock

Haglund, Ulf; Abe, T.; Åhrén, C; Braide, Inger; Lundgren, Ove

doi:10.1159/000127888

Cited by 45 publications

(14 citation statements)

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“…Nevertheless, the mucosal lesions observed in the cat seem to be caused by hypoxia since they are prevented by intraluminal perfusion with oxygenated saline during the shock period but not by perfusion with nitrogenated saline (Haglund,Abe,Ahr6n,Braide,and Lundgren,to be published). The apparent paradox with hypoxic villous lesions in the face of almost unchanged villous blood flow can be explained by short-circuiting of oxygen in the intestinal countercurrent exchanger at the villous base and in the deeper layers of the mucosa (Lundgren, 1967;Ahren and Haglund, 1973;Haglund, 1973;Haglund et al, 1973). In the cat, such a 'shunting' has been demonstrated during 'resting' conditions (Kampp et al, 1967).…”

Section: Discussionmentioning

confidence: 99%

“…During hypotension plasma mean transit time in the villi is greatly reduced from about 5 s to about 25 s , and the effectiveness of the countercurrent exchanger is correspondingly increased. In this situation, the villous tip is very likely to be anoxic even in the face of unchanged blood supply (Haglund, 1973;Haglund et al, 1973). Blood flow studies on humans have revealed a close qualitative and quantitative similarity betweencatandman (Hulten et al, 1972;Hulten et al, 1976) and have also provided experimental support for the existence of an intestinal countercurrent exchanger in the human gut.…”

Section: Discussionmentioning

confidence: 99%

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Mucosal lesions in the human small intestine in shock.

Haglund¹,

Hultén²,

Åhrén³

et al. 1975

Gut

121

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SUMMARY Characteristic mucosal lesions in resected small intestinal segments from seven patients are reported. Preoperatively, four patients were in shock and general hypotension while the three remaining cases showed signs of local intestinal hypotension. The microscopic appearance of the mucosal lesions was in all patients identical with that previously observed in the feline and canine small intestine after haemorrhage or local intestinal hypotension. It is proposed that an extravascular short-circuiting of oxygen in the mucosal countercurrent exchanger and an intravascular aggregation of blood cells might produce tissue hypoxia which makes the mucosa vulnerable to enzymatic degradation.Haemorrhagic lesions in the small intestinal mucosa have regularly been reported from experimental shock studies on dogs (Wiggers, 1950;Lillehei et al., 1964;Chiu et al., 1970) and cats (Ahren and Haglund, 1973;Haglund, 1973). A characteristic feature is that these lesions appear first at the tips of the villi, and in cases where the entire villus is destroyed the deeper layers of the intestinal wall are still free from inflammatory changes (Chiu et al., 1970;Ahr6n and Haglund, 1973). Similar mucosal lesions have also been reported in patients dying in shock (see, for example, Penner and Bernheim, 1939;Marston, 1962;Bounous, 1969). Most of these studies were, however, 'based on necropsies where postmortem autolysis could not be excluded. There exist in the literature only a few exceptional cases where intestinal mucosal lesions have been reported in patients in shock based on microscopic studies of intestinal segments removed ante-mortem-for example, at operation (Carey et al., 1967;S0rensen and Vetner, 1969;Hugon and Bounous, 1971). This comparatively rare occurrence ofreports on intestinal mucosal lesions in association with clinical shock has led to the suggestion that these lesions may be a peculiarity of the dog and, therefore, it has even been proposed that only primates can be used in experimental studies of shock as it appears in clinical medicine (Brobmann et al., 1970;Swan et al., 1972).This study reports seven patients exhibiting haemorrhagic lesions in the small intestinal mucosa. The microscopic appearance is described and posReceived for publication 24 September 1975. sible pathophysiological mechanisms responsible for the development of such lesions are discussed. Methods CASE HISTORIESThis report is based on seven patients operated upon for different gastrointestinal disorders. During the preoperative period four patients exhibited obvious signs of clinical shock and, in the remaining three, the small intestine had evidently been subjected to a period of local hypotension. The detailed histories are given below.Case 1 A 52 year old man had 14 years earlier had a partial gastrectomy and a gastrojejunal anastomosis for bleeding ulcer. The patient was readmitted with clinical signs of gastric bleeding and signs of shock. Blood transfusions could not restore haemoglobin concentration above 8 g/dl and for two h...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Mucosal lesions in the human small intestine in shock.

Haglund¹,

Hultén²,

Åhrén³

et al. 1975

Gut

121

View full text Add to dashboard Cite

show abstract

“…Together these two layers provide a dynamic and regulated barrier allowing selective passage of luminal contents into the intestinal wall. Loss of the epithelial/mucus layer integrity is a common feature in gastrointestinal diseases [1], [2] and intestinal ischemia encountered in different forms of shock [3], [4], [5].…”

Section: Introductionmentioning

confidence: 99%

Breakdown of Mucin as Barrier to Digestive Enzymes in the Ischemic Rat Small Intestine

et al. 2012

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Loss of integrity of the epithelial/mucosal barrier in the small intestine has been associated with different pathologies that originate and/or develop in the gastrointestinal tract. We showed recently that mucin, the main protein in the mucus layer, is disrupted during early periods of intestinal ischemia. This event is accompanied by entry of pancreatic digestive enzymes into the intestinal wall. We hypothesize that the mucin-containing mucus layer is the main barrier preventing digestive enzymes from contacting the epithelium. Mucin breakdown may render the epithelium accessible to pancreatic enzymes, causing its disruption and increased permeability. The objective of this study was to investigate the role of mucin as a protection for epithelial integrity and function. A rat model of 30 min splanchnic arterial occlusion (SAO) was used to study the degradation of two mucin isoforms (mucin 2 and 13) and two epithelial membrane proteins (E-cadherin and toll-like receptor 4, TLR4). In addition, the role of digestive enzymes in mucin breakdown was assessed in this model by luminal inhibition with acarbose, tranexamic acid, or nafamostat mesilate. Furthermore, the protective effect of the mucin layer against trypsin-mediated disruption of the intestinal epithelium was studied in vitro. Rats after SAO showed degradation of mucin 2 and fragmentation of mucin 13, which was not prevented by protease inhibition. Mucin breakdown was accompanied by increased intestinal permeability to FITC-dextran as well as degradation of E-cadherin and TLR4. Addition of mucin to intestinal epithelial cells in vitro protected against trypsin-mediated degradation of E-cadherin and TLR4 and reduced permeability of FITC-dextran across the monolayer. These results indicate that mucin plays an important role in the preservation of the mucosal barrier and that ischemia but not digestive enzymes disturbs mucin integrity, while digestive enzymes actively mediate epithelial cell disruption.

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“…Mucin glycoprotein is the major constituent of the mucus barrier (18) whereas enterocytes with their adherens and tight junctions make up the epithelial barrier (19). During ischemia the integrity of the mucosal and epithelial barriers become compromised (20, 21); our hypothesis is that disruption of these barriers during intestinal ischemia allows pancreatic digestive enzymes to enter the intestinal wall and thereby exacerbate intestinal injury.…”

Section: Introductionmentioning

confidence: 99%

Disruption of the Mucosal Barrier During Gut Ischemia Allows Entry of Digestive Enzymes Into the Intestinal Wall

Chang

Kistler

Schmid‐Schönbein

2012

Shock

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Intestinal ischemia is associated with high morbidity and mortality but the underlying mechanisms are uncertain. We hypothesize that during ischemia the intestinal mucosal barrier becomes disrupted, allowing digestive enzymes access into the intestinal wall initiating autodigestion. We used a rat model of splanchnic ischemia by occlusion of the superior mesenteric and celiac arteries up to 30 min with and without luminal injection of tranexamic acid as a trypsin inhibitor. We determined the location and activity of digestive proteases on intestinal sections with in-situ zymography and we examined the disruption of two components of the mucosal barrier: mucin isoforms and the extra- and intracellular domains of E-cadherin with immunohistochemistry and western blot techniques. The results indicate that non-ischemic intestine has low levels of protease activity in its wall. After 15 min ischemia protease activity was visible at the tip of the villi and after 30 min enhanced activity was seen across the full thickness of the intestinal wall. This activity was accompanied by disruption of the mucin layer and loss of both intra- and extracellular domains of E-cadherin. Digestive protease inhibition in the intestinal lumen with tranexamic acid reduced morphological damage and entry of digestive enzymes into the intestinal wall. This study demonstrates that disruption of the mucosal epithelial barrier within minutes of intestinal ischemia allows entry of fully activated pancreatic digestive proteases across the intestinal barrier triggering autodigestion.

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The Intestinal Mucosal Lesions in Shock

Cited by 45 publications

References 0 publications

Mucosal lesions in the human small intestine in shock.

Mucosal lesions in the human small intestine in shock.

Breakdown of Mucin as Barrier to Digestive Enzymes in the Ischemic Rat Small Intestine

Disruption of the Mucosal Barrier During Gut Ischemia Allows Entry of Digestive Enzymes Into the Intestinal Wall

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