Systemic consequences of ileus

Madl, Christian; Druml, Wilfred

doi:10.1016/s1521-6918(03)00022-2

Cited by 105 publications

(42 citation statements)

References 44 publications

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“…The gut has long being regarded as a ‘trigger’ or ‘promoter’ of sepsis and multiorgan failure (MOF); the important role of gut dysfunction has been illustrated in numerous studies [24-27]. Marshall aptly described the gastrointestinal tract as an ‘undrained abscess’ [28].…”

Section: Discussionmentioning

confidence: 99%

The role of intestinal mucosa injury induced by intra-abdominal hypertension in the development of abdominal compartment syndrome and multiple organ dysfunction syndrome

et al. 2013

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IntroductionAbdominal distension is common in critical illness. There is a growing recognition that intra-abdominal hypertension (IAH) may complicate nonsurgical critical illness as well as after abdominal surgery. However, the pathophysiological basis of the injury to the intestinal mucosal barrier and its influence on the onset of abdominal compartment syndrome (ACS) and multiorgan dysfunction syndrome (MODS) remain unclear. We measured intestinal microcirculatory blood flow (MBF) during periods of raised intra-abdominal pressure (IAP) and examined how this influenced intestinal permeability, systemic endotoxin release, and histopathological changes.MethodsTo test different grades of IAH to the injury of intestinal mucosa, 96 New Zealand white rabbits aged 5 to 6 months were exposed to increased IAP under nitrogen pneumoperitoneum of 15 mmHg or 25 mmHg for 2, 4 or 6 hours. MBF was measured using a laser Doppler probe placed against the jejunal mucosa through a small laparotomy. Fluorescein isothiocyanate (FITC)-conjugated dextran was administered by gavage. Intestinal injury and permeability were measured using assays for serum FITC-dextran and endotoxin, respectively, after each increase in IAP. Structural injury to the intestinal mucosa at different levels of IAH was confirmed by light and transmission electron microscopy.ResultsMBF reduced from baseline by 40% when IAP was 15 mmHg for 2 hours. This doubled to 81% when IAP was 25 mmHg for 6 hours. Each indicator of intestinal injury increased significantly, proportionately with IAP elevation and exposure time. Baseline serum FITC-dextran was 9.30 (± SD 6.00) μg/ml, rising to 46.89 (±13.43) μg/ml after 15 mmHg IAP for 4 hours (P <0.01), and 284.59 (± 45.18) μg/ml after 25 mmHg IAP for 6 hours (P <0.01). Endotoxin levels showed the same pattern. After prolonged exposure to increased IAP, microscopy showed erosion and necrosis of jejunal villi, mitochondria swelling and discontinuous intracellular tight junctions.ConclusionsIntra-abdominal hypertension can significantly reduce MBF in the intestinal mucosa, increase intestinal permeability, result in endotoxemia, and lead to irreversible damage to the mitochondria and necrosis of the gut mucosa. The dysfunction of the intestinal mucosal barrier may be one of the important initial factors responsible for the onset of ACS and MODS.

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Section: Discussionmentioning

confidence: 99%

The role of intestinal mucosa injury induced by intra-abdominal hypertension in the development of abdominal compartment syndrome and multiple organ dysfunction syndrome

et al. 2013

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“…Trauma, such as a burn, causes a disruption in normal peristalsis leading to bacterial overgrowth in the intestine and this bacterial load is even greater when alcohol ingestion precedes the injury in rats [46]. While the exact mechanism by which alcohol enhances post burn bacterial growth in the intestine remains unknown, experimental evidence points to modulation of hormonal control [54], shifts in intestinal flora population [55], and the promotion of adynamic ileus [56] as possible causes, as reviewed elsewhere [57]. Animal models report that after disruption of intestinal barrier integrity, bacteria and bacterial products such as lipopolysaccharide (LPS) translocate from the lumen of the intestine into the lymphatic [58,59] and portal [60] systems.…”

Section: Extrahepatic Mechanismsmentioning

confidence: 99%

Alcohol Modulation of the Postburn Hepatic Response

Chen

Carter

Curtis

et al. 2017

Journal of Burn Care & Research

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The widespread and rapidly increasing trend of binge drinking is accompanied by a concomitant rise in the prevalence of trauma patients under the influence of alcohol at the time of their injury. Epidemiologic evidence suggests up to half of all adult burn patients are intoxicated at the time of admission and the presence of alcohol is an independent risk factor for death in the early stages post burn. As the major site of alcohol metabolism and toxicity, the liver is a critical determinant of post burn outcome and experimental evidence implies an injury threshold exists beyond which burn-induced hepatic derangement is observed. Alcohol may lower this threshold for post burn hepatic damage through a variety of mechanisms including modulation of extrahepatic events, alteration of the gut-liver axis, and changes in signaling pathways. The direct and indirect effects of alcohol may prime the liver for the second-hit of many overlapping physiologic responses to burn injury. In an effort to gain a deeper understanding of how alcohol potentiates post burn hepatic damage, we summarize possible mechanisms by which alcohol modulates the post burn hepatic response.

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“…Inflammation (and injury) from an inflammatory bowel disease (i.e., Crohn's Disease) or bowel wall edema caused by surgical procedures can further elevate intraluminal pressures and cause abnormal motility (Granger and Barrowman, 1983). Following intestinal surgery, the bowel takes up fluid and becomes edematous, and intra-abdominal pressure can increase as high as 15–40 mm Hg above normal for several days (Williams and Simms, 1997; Madl and Druml, 2003). Furthermore, in IBD, substantial increase in colonic blood flow (i.e., 2 to 6-fold) can increase capillary pressures (Hultén et al, 1977) and also interstitial pressures.…”

Section: Introductionmentioning

confidence: 99%

Mechanosensory Signaling in Enterochromaffin Cells and 5-HT Release: Potential Implications for Gut Inflammation

et al. 2016

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Enterochromaffin (EC) cells synthesize 95% of the body 5-HT and release 5-HT in response to mechanical or chemical stimulation. EC cell 5-HT has physiological effects on gut motility, secretion and visceral sensation. Abnormal regulation of 5-HT occurs in gastrointestinal disorders and Inflammatory Bowel Diseases (IBD) where 5-HT may represent a key player in the pathogenesis of intestinal inflammation. The focus of this review is on mechanism(s) involved in EC cell “mechanosensation” and critical gaps in our knowledge for future research. Much of our knowledge and concepts are from a human BON cell model of EC, although more recent work has included other cell lines, native EC cells from mouse and human and intact mucosa. EC cells are “mechanosensors” that respond to physical forces generated during peristaltic activity by translating the mechanical stimulus (MS) into an intracellular biochemical response leading to 5-HT and ATP release. The emerging picture of mechanosensation includes Piezo 2 channels, caveolin-rich microdomains, and tight regulation of 5-HT release by purines. The “purinergic hypothesis” is that MS releases purines to act in an autocrine/paracrine manner to activate excitatory (P2Y1, P2Y4, P2Y6, and A2A/A2B) or inhibitory (P2Y12, A1, and A3) receptors to regulate 5-HT release. MS activates a P2Y1/Gαq/PLC/IP3-IP3R/SERCA Ca2+signaling pathway, an A2A/A2B–Gs/AC/cAMP-PKA signaling pathway, an ATP-gated P2X3 channel, and an inhibitory P2Y12-Gi/o/AC-cAMP pathway. In human IBD, P2X3 is down regulated and A2B is up regulated in EC cells, but the pathophysiological consequences of abnormal mechanosensory or purinergic 5-HT signaling remain unknown. EC cell mechanosensation remains poorly understood.

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Systemic consequences of ileus

Cited by 105 publications

References 44 publications

The role of intestinal mucosa injury induced by intra-abdominal hypertension in the development of abdominal compartment syndrome and multiple organ dysfunction syndrome

The role of intestinal mucosa injury induced by intra-abdominal hypertension in the development of abdominal compartment syndrome and multiple organ dysfunction syndrome

Alcohol Modulation of the Postburn Hepatic Response

Mechanosensory Signaling in Enterochromaffin Cells and 5-HT Release: Potential Implications for Gut Inflammation

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