Pathogenesis Of Stress Ulcers Research Articles

Application of enteral nutrition in patients with stress ulcer and nursing progress

This article reviews the pathogenesis of stress ulcer, the concept of enteral nutrition and the correlation between the two, and compares and summarizes the timing, preparation, temperature, route and mode of application of enteral nutrition in patients with stress ulcer, and summarizes the main points in nursing for enteral nutrition, in order to provide a theoretical basis for clinical medical staff to develop individualized enteral nutrition intervention programs to effectively prevent stress ulcers. Key words: Review; Enteral nutrition; Prevention; Treatment; Stress ulcer

Hemorrhagic duodenal ulcer and subsequent acute appendicitis following lobectomy for lung cancer

A 62-year-old Vietnamese male presented for an elective video-assisted thoracoscopic surgery lobectomy for treatment of a suspicious lung mass. Postoperatively, he developed a hemorrhagic duodenal ulcer requiring endoscopic hemostasis. Interestingly, he subsequently became septic secondary to perforated acute appendicitis necessitating laparoscopic appendectomy. Surgery can evoke a physiological stress response and may be a causative factor in the pathogenesis of stress ulcers in surgical patients. A recent article has found an association between the development of acute appendicitis in patients with a history of peptic ulcer disease. The pathological mechanism responsible for this association may be the result of an imbalance of the autonomic nervous system and neuromusculature spasms at the ceco-appendiceal junction.

Endothelin-1, Inducible Nitric Oxide Synthase and Macrophage Inflammatory Protein-1?? in the Pathogenesis of Stress Ulcer in Neurotraumatic Patients

To prospectively identify histologically and endoscopically the effect of omeprazole on the expression of endothelin-1 (ET-1), inducible nitric oxide synthase (iNOS) and macrophage inflammatory protein-1alpha (MIP-1alpha) in the gastric mucosa of neurosurgical patients with stress ulcer. Twenty-five patients with severe acute intracranial lesions caused by trauma were enrolled in this study. A 40 mg intravenous bolus of omeprazole (OME) was given daily for 7 days. The intragastric pH was continuously recorded for 24 hours on day 1 and 8. Endoscopic evaluation of the gastric corpus, antrum, and duodenal bulb was performed in the ICU, within 24 hours after brain injury, and at follow-up on the 7th day after admission. Paired biopsies were obtained for histologic examinations and immunohistochemical analysis was performed using a LSAB method for MIP-1alpha, ET-1, and iNOS. There were 72% and 70% of gastroduodenal mucosal lesions at the initial and follow-up endoscopies, respectively. However, the severity of mucosal lesions showed significant improvement in most patients at follow-up (p < 0.05). Mean percentages of time intragastric pH were greater than or equal to 4.0 were 20 +/- 11% and 70 +/- 17% on day 1 and 8, respectively (p < 0.05). The incidences of ET-1, iNOS and MIP-1alpha expression were not significantly different between the patients before and after OME prophylaxis. Prophylactic OME is effective in reducing the severity of stress ulcerations in severe neurotraumatic patients. High incidence of tissue ET-1 expression combined with increased activity of iNOS and MIP-1alpha may be responsible for the gastric mucosal injury. We also show that OME fails to counter the enhancement in the mucosal expression of ET-1, iNOS, and MIP-1alpha caused by severe brain damage.

Role of p38 mitogen-activated protein kinase in the pathogenesis of stress ulcer

To determine whether the activation of p38 mitogen-activated protein kinase (MAPK) is involved in the pathogenesis of stress ulcer. Model of stress ulcer was established with the treatment of rats with water-immersion restraint (WIR) stress. Ulcer index (UI) was macroscopically evaluated as a parameter of gastric mucosal lesions. Expression of phospho- and pan-p38 in gastric mucosa was detected using Western blot analysis. Tumor necrosis factor-alpha (TNF-alpha) and Interleukin 1beta (IL-1beta) gene expressions were analyzed by Northern blot analysis. As indicated in some experiments, rats were pretreated with intravenous injection of the specific p38 MAPK inhibitor CNI-1493 prior to WIR stress and then the changes of UI and TNF-alpha and IL-1beta mRNA expression were examined. The p38 MAPK was persistently activated in the gastric mucosa of rats with WIR stress, with maximal activation after 1 h of stress [(6.8 +/- 3.2) fold of baseline levels, P < 0.01]. Inhibition of p38 MAPK activation with CNI-1493 led to a marked decrease in UI in WIR stress rats. Similarly, the increased gene expression of proinflammatory cytokines TNF-alpha and IL-1beta in gastric mucosa induced by WIR stress were significantly diminished by p38 MAPK inhibition. p38 MAPK might have an important role in the pathogenesis of stress ulcer.

THE EFFECTS OF ESOMEPRAZOLE ON ALCOHOL INDUCED STRESS ULCER LESIONS IN RATS

&amp;lt;p&amp;gt;Stress ulcer presents acute lesion of gastric mucosa, which resulted from influence of different stressors: trauma,&amp;lt;br /&amp;gt;shock, burns, drugs administration, various irritants etc. Since pathogenesis of stress ulcer is not completely clarified, the&amp;lt;br /&amp;gt;most adequate therapy for the patients which suffer from it, is not defined yet. Esomeprazole is a S-isomer of omeprazole&amp;lt;br /&amp;gt;and is the first inhibitor of proton pump synthesized as an isomer. Our aim was to test effects of esomeprazole, given during&amp;lt;br /&amp;gt;pretreatment and posttreatment period, on progress of alcohol induced stress ulcer lesions. We had experiments on sexually&amp;lt;br /&amp;gt;mature Wistar rats weight 200-250 g. Alcohol stress was induced by intragastric administration of 1 mL 96% alcohol.&amp;lt;br /&amp;gt;Alcohol stress produced massive submucosal lesions in glandular part of stomach. Macroscopic lesions were verified&amp;lt;br /&amp;gt;histologicaly. Intragastric pretreatment administration of esomeprazole (20 mg/kg BW) significantly (p&amp;amp;lt;0,001) reduced gastric lesions. Intragastric post-treatment administration of esomeprazole (20 mg/kg BW) did not reduce gastric lesions. Esomeprazole (20 mg/kg BW) administrated in pretreatment period of alcohol induced stress significantly decreased dimensions of stress ulcer lesions in rats, while the same dose administrated in posttreatment period did not cause that effect.&amp;lt;/p&amp;gt;

Low seroprevalence of Helicobacter pylori infection in patients with stress ulcer bleeding--a prospective evaluation of patients on a cardiosurgical intensive care unit.

The pathogenesis of stress ulceration in seriously ill patients is uncertain and the pathogenic role of Helicobacter pylori infection is unknown. We therefore assessed the seroprevalence of patients of a cardiosurgical intensive care unit (ICU) with clinically important stress ulcer bleeding. We compared this prevalence with a control group matched for this kind of surgical intervention, missing history of peptic ulcer disease, age and gender. Prospective survey. Cardiosurgical ICU in a university teaching hospital. Two thousand five hundred seventy cardiosurgical patients with intravenous ranitidine stress ulcer prophylaxis were screened for clinically important stress ulcer bleeding. Helicobacter pylori seropositivity was measured in all patients with a clinically important bleeding and in a control group of 245 consecutive cardiosurgical patients, matched for the kind of cardiosurgical intervention, age and gender. In 56 of 2,570 (2.1%) patients signs of clinically important bleeding were seen. Endoscopical examination revealed stress ulcer bleeding in 42 cases. The incidence of stress ulcer bleeding was 1.6%. The seropositivity of the group with ulcer bleeding was 45.2 % whereas 62.4 % of the patients in the control group were Helicobacter pylori positive (p = 0.08). Our results suggest that the Helicobacter pylori infection does not play a pathogenic role in stress ulcer bleeding. Prophylactic cure of Helicobacter pylori can not be recommended in this setting.

A review of stress ulcer prophylaxis in the neurosurgical intensive care unit.

STRESS ULCERS OCCUR frequently in intensive care unit patients who have intracranial disease. After major physiological stress, endoscopic evidence of mucosal lesions of the gastrointestinal tract appears within 24 hours of injury; 17% of these erosions progress to clinically significant bleeding. Gastrointestinal hemorrhage has been associated with mortality rates of up to 50%. The pathogenesis of stress ulcers may not be completely understood, but gastric acid and pepsin appear to play significant roles. Antacids, H2 antagonists, and sucralfate are effective prophylactic agents in the medical/surgical intensive care unit. Appropriate therapy for neurosurgical patients remains unclear, however. This review summarizes the current literature regarding the pathogenesis and therapy of stress ulcers in neurosurgical patients.

Role of endothelin 1 in hemorrhagic shock-induced gastric mucosal injury in rats

Background/Aims: Gastric microcirculatory disturbances are involved in the pathogenesis of stress ulcers; however, vasomodulators regulating this process are not fully understood. This study was conducted to investigate the role of endothelin 1 (ET-1) in hemorrhagic shock-induced gastric mucosal damage in rats. Methods: ET-1 contents in plasma and gastric mucosa were measured and gastric mucosal damage was evaluated during a control period, 60 minutes of ischemia, 15 minutes of reperfusion, and 30 minutes of postreperfusion. Next, effects of BQ-123, an endothelina receptor antagonist, on the gastric mucosal damage and hemodynamics were studied. Results: Both plasma and mucosal ET-1 significantly increased after ischemia and reperfusion compared with the control values, but only mucosal ET-1 continued to increase after reperfusion, leading to the development of gastric mucosal damage. BQ-123, administered just before reperfusion, reduced mucosal damage in the postreperfusion period dose-dependently and improved mean gastric mucosal blood flow and mucosal hemoglobin oxygen saturation during the 30-minute postreperfusion period. Conclusions: These results suggest that endogenous ET-1 plays an important role in the pathogenesis of hemorrhagic shock-induced gastric mucosal damage through impairment of mucosal microcirculation. Further, endothelina antagonists may have therapeutic benefits for shock-induced gastric mucosal damage.

Role of Cytokines in the Pathogenesis of Stress Ulcer(Mechanisms of Onset in Psychosomatic diseases : Possible presence of an &quot;immune-brain-gut&quot;axis

Role of Cytokines in the Pathogenesis of Stress Ulcer(Mechanisms of Onset in Psychosomatic diseases : Possible presence of an &quot;immune-brain-gut&quot;axis

The role of the neurotransmitters acetylcholine and noradrenaline in the pathogenesis of stress ulcers

1. Adrenergic and cholinergic mechanisms seem to be involved in the pathogenesis of stress ulcers. 2. In this study, gastric ulcers were induced in rats by immobilization and cold. Prior intraperitoneal administration of both anticholinergic (atropine) as well as alpha-blocking medication (phenoxybenzamine) produced a very significant decrease in stress ulcers. 3. Additionally, using the technique of continuous intravenous perfusion in rats, acetylcholine was shown to have a gastric ulcerogenic effect, in contrast to noradrenaline. 4. It is concluded that acetylcholine is the peripheral mediator in stress ulcers, while noradrenaline intervenes at the encephalic level in stress ulcer pathogenesis.

The effect of the autonomic nervous system on cell proliferation of the gastric mucosa in stress ulcer formation

The role of the autonomic nervous system in cell proliferation of the gastric mucosa during restraint water immersion stress was investigated utilizing the spontaneously hypertensive rat (SHR) and its progenitor, the Wistar-Kyoto rat (WKY). Three hours of water-immersion restraint induced gastric lesions more frequently in WKY than in SHR, although there were few visual lesions in either strain in two hours of stress. The number of 5-bromo-2′-deoxyuridine (BrdU) positive cells in the corpus ventriculi mucosa markedly decreased in the WKY, but did not change in the SHR after two hours of water-immersion restraint stress. The acetylcholine content in the mucosa significantly decreased and the density of acetylcholinesterase (ACh-E) containing fiber of mucosa remarkably increased in only WKY after two hours stress exposure. On the other hand, there was no significant difference in either the responsiveness or the content of norepinephrine and epinephrine, which indicates sympathetic nervous function, after stress exposure in WKY and SHR. Similarly, the response of serum gastrin was not significantly different between the two strains. These results strongly suggest that the parasympathetic nerve plays an essential role in cell proliferation of the gastric mucosa in the pathogenesis of stress ulcer.

The role of thyrotropin-releasing hormone (TRH) in the pathogenesis of water-immersion stress in rats--inhibition of TRH release from the stomach by atropine, ranitidine or omeprazole.

The role of thyrotropin-releasing hormone (TRH) in the development of gastric erosions and ulcers induced by water-immersion stress was studied. Intraperitoneally administered bethanechol induced a decrease in the gastric wall immunoreactive TRH (ir-TRH) concentrations and an increase in gastric juice ir-TRH concentrations in a dose-related manner, while atropine induced an increase in gastric wall ir-TRH concentrations and a decrease in gastric juice ir-TRH concentrations under non-stress condition. Intraperitoneally administered omeprazole did not influence gastric wall ir-TRH concentrations but elevated gastric pH. Water-immersion stress induced a decrease in gastric wall ir-TRH concentrations and an increase in gastric juice ir-TRH concentrations with a decrease in gastric pH prior to ulcer formation. Pretreatment with atropine or ranitidine inhibited the development of stress ulcers, reduced changes in ir-TRH concentrations in the gastric wall and gastric juice, and induced an increase in gastric pH. Omeprazole inhibited stress ulcer formation and changes in gastric wall and gastric juice ir-TRH concentrations. These results suggest that TRH release from the stomach wall into gastric juice is of importance in the pathogenesis of stress ulcer and that its release is mediated by both muscarinergic and histaminergic (H2) systems. Furthermore, omeprazole has an inhibitory effect on TRH release under stress ulcer.

Somatostatin in the management of gastrointestinal hemorrhage: bleeding ulcers.

Stress ulcers are characterized by difficult management and poor prognosis. They currently represent a complication in the clinical course of other conditions, mainly shock states. The pathogenesis of stress ulcers is not well understood although the role of hypovolemia leading to energetic deprivation and insaturation of anaerobic cellular metabolism have been carefully studied. Somatostatin has been found to reduce the incidence of experimental stress ulcers. In the clinic, patients with duodenal ulcers were found to exhibit a low number of antral D cells and a significant decrease in tissue somatostatin. In a multicenter trial, patients with bleeding peptic or stress ulcers were treated with somatostatin or cimetidine plus pirenzepine. Results were favorable to the former substance on account of the time required to stop the hemorrhage and the demands for blood replacement. Thus, medical management of bleeding ulcers with somatostatin may represent an alternative to more radical surgical intervention.

Hemodynamics of the gastric mucosa and gastric ulceration in rats and in patients with gastric ulcer.

The microcirculation is the fundamental nutrient supply and waste removal system of all tissues. Recent improvements in spectrophotometric technique have made possible the noninvasive assessment of oxygen supply and utilization in the gastric mucosa. The authors have utilized such methods to assess gastric mucosal hemodynamics. The technique permitted further clarification of the roles of the gastric microcirculation, mucosal oxygenation, and acid secretion in the pathogenesis of stress ulcers in the stomach of rats. Furthermore, it provided important information on the function of gastric mucosal hemodynamics in the healing of gastric ulcers in man. The technique is described along with the authors' correlation studies between spectrophotometric data and other techniques for measuring gastric blood flow (hydrogen gas clearance and aminopyrine clearance methods and direct electromagnetic flowmeter techniques) and the prevention of ulcerogenesis.

Role of gastric mucosal pepsin in the pathogenesis of acute stress ulceration

AbstractMeasurements of acid and pepsin in gastric juice and the pepsin concentration in the fundic mucosa were performed in 4 patients who underwent partial gastrectomy for bleeding from acute gastric mucosal erosions (“stress ulcers”) and in 30 patients who underwent partial gastrectomy for chronic gastric or duodenal ulcers. The most striking finding was a significantly higher level of fundic mucosal pepsin in the patients with acute gastric erosions than the chronic ulcer patients. This finding was associated with a significantly lower concentration of pepsin in gastric juice, a low level of acid secretion, and the expected high plasma level of corticosteroids associated with stress. As a result, the ratio of gastric mucosal pepsin to gastric juice pepsin was significantly higher in patients with acute gastric erosions than in those with chronic ulcers. It is possible that a rapid increase in endogenous corticosteroid levels induces an increase in intracellular pepsin in the fundic mucosa, and that this sequence of events plays a role in the pathogenesis of stress ulcer.

The effects of metiamide on gastric secretion and stress ulceration in rats

The effects of metiamide, a histamine H 2 blocker, on gastric secretion and ulcer formation in stressed pylorus-occluded rats were investigated. Metiamide, like atropine, significantly reduced the volume of gastric secretion and total acid output in unrestrained pylorus-occluded rats. Both drugs produced greater decreases in the volumes of gastric secretion in stressed rats than in their corresponding unrestrained groups. Stress itself reduced both parameters. Metiamide, like atropine, significantly reduced the incidence of gastric stress ulcers. When given together these two drugs did not provide greater protection. The results obtained with metiamide indicate that histamine plays a role in basal gastric secretion and in the pathogenesis of stress ulcers. As no correlation between gastric acid secretion and ulcer formation was demonstrated in this study, it is suggested that H 2 receptors may also be involved in gastric motility. However, the possibility that metiamide could exert its ulcer-protecting effects through other mechanisms cannot yet be excluded.

Significance of gastric secretory changes in the pathogenesis of stress ulcers.

Analyses of gastric juice withdrawn 3 hours after the pylorus was ligated and of plasma corticosterone and blood glucose after animals were exposed to rotational stress revealed that gastric secretion was highest in controls, intermediate in stressed rats that developed ulcers, and lowest in stressed rats that did not develop ulcers. Neither high nor low gastric secretion correlated with stress-ulcer formation. When initial mucosal ischemia and secretory inhibition, which occurred in all stressed rats, were considered, those that developed ulcers manifested gastric hypersecretion when compared with those that did not develop ulcers. The pathogenetic significance of gastric hypersecretion in stress-ulcer formation is discussed and correlated with mucosal microvascular changes during stress. Mean plasma corticosterone was highest in stressed rats that developed ulcers, next highest in stressed rats that did not develop ulcers, and lowest in control rats. Compared with normal rats, mean blood glucose was lowest in stressed rats and highest in controls. Hypoglycemic changes were more marked in stressed rats that developed ulcers than in stressed rats that did not develop ulcers.

The role of bile in antral mucosal disruption during hemorrhagic shock.

The stress ulcers that occur in shocked dogs are averted by pyloric cross-clamping prior to shock. These experiments studied the role of bile reflux in the pathogenesis of stress ulcers in the shocked dog. Two and one-half hours of hemorrhagic shock in dogs with acute antral pouches isolated from the duodenum did not alter antral mucosal integrity as measured by gastric mucosal volume and ionic flux rates despite a fall in transgastric potential difference (PD) indicating mucosal injury (-33.5 +/- 1.7 m Volts vs -12.8 +/- 2.0, p < 0.01). Similarly 4(1/2) hours of shock did not alter mucosal integrity when the pylorus was cross-clamped during shock (PD -59.8 +/- 1.8 mV vs -42.5 +/- 7.0, p = 0.05). In contrast, 4(1/2) hours of shock in dogs in whom the pylorus was open resulted in increased hydrogen ion back diffusion (-106.3 +/- 21.5 microEq vs -300.5 +/- 63.1, p < 0.01, PD -56.8 +/- 3.6 mV vs -24.3 +/- 3.4, p < 0.01). The concentration of bile acids refluxed into the stomach during unmodified shock (8.45 +/- 3.92 mM) exceeds that necessary to disrupt the gastric mucosal barrier. These data suggest that increased hydrogen ion back diffusion initiated by refluxed bile plays an important role in the pathogenesis of gastric stress ulcers in the shocked dog.

Role of acetylcholine in the pathogenesis of stress ulcers of the gastro-intestinal tract

Role of acetylcholine in the pathogenesis of stress ulcers of the gastro-intestinal tract

Studies on the role of acid in the pathogenesis of experimental stress ulcers.

Previous studies have provided strong evidence to support the concepts that in the rat histamine is the chemical mediator of gastric acid secretion and that histamine plays an essential role in the pathogenesis of stress ulcers. The present experiments indicate that the role of histamine in the pathogenesis of stress ulcers in rats is probably mediated through stimulation of gastric acid secretion. In particular, we found a strong negative correlation between intragastric pH and the incidence of stress ulcers. Furthermore, intragastric administration of Basal-jel® (a nonabsorbable antacid) afforded significant protection against stress ulcers without preventing the sharp increase in histidine decarboxylase activity in response to stress.