Plasma citrulline concentration: a reliable marker of small bowel absorptive capacity independent of intestinal inflammation

OBJECTIVES: Postabsorptive plasma citrulline concentration has been proposed as a reliable marker of small bowel absorptive capacity in short bowel patients. The aim of this study was to address the potentially confounding impact of intestinal inflammation. METHODS: Fifty-five patients were selected according to diagnosis, small bowel length, and degree of bowel inflammation. (a) Crohn's disease (CD) with massive small bowel resection leaving 220) (N = 7), (d) CD without resection or active inflammation (normal CRP and CDAI <150) (N = 9), (e) mesenteric infarction (MI) with resection leaving 相似文献   

The contaminated small bowel syndrome.

Contamination of the small bowel with an abnormal microflora causes a variety of disturbances of intraluminal digestion and of mucosal function resulting in malabsorption of fat, protein, carbohydrate, electrolytes and vitamin B12. Indirect clinical tests for the presence of small bowel bacterial overgrowth must be supported by careful roentgenologic examination of the small intestine and intestinal aspiration studies to establish a firm pretreatment diagnosis. However, the reversal of absorptive defects by antibacterial therapy is valuable confirmatory evidence.     

Functional tests in small bowel diseases (author's transl)

D-xylose-, Schilling-test, and fecal fat analysis are still the most important functional tests in small bowel diseases despite rapid progress in enterology. The segmental intestinal perfusion technique can be considered to be the most appropriate method at the moment to measure absorptive or secretory capacity of defined gut segments. Under well-defined conditions the tissue accumulation technique with fresh small bowel biopsy specimens may offer valuable results on absorptive capacity of the gut tissue in specialized laboratories.     

Short bowel syndrome

Short bowel syndrome is an uncommon disease that results from extensive intestinal resection. Short bowel patients develop severe malabsorption of macronutrients, micronutrients, electrolytes and water, and pose difficult management problems. This report describes a typical patient with the short bowel syndrome and how each component of the malabsorption syndrome is managed to maintain nutritional, electrolyte, and water balance. In practice, some short bowel patients become dependent on parenteral nutrition for life, while others become independent with time due to intestinal adaptation and can be managed on oral intake and supplementations. Short bowel patients are at risk of developing gallstones, oxalate kidney stones and, rarely, d-lactic acidosis, and the pathophysiology of these disease processes is outlined. A minority of short bowel patients may ultimately require intestinal transplantation due to irreversible complications, and the current status of this intervention is reviewed. Finally, growth factors that stimulate intestinal growth and, thus, enhance absorptive capacity, are currently being identified and may eventually be introduced in the treatment of these patients.     

Glucagon-like Peptide-2 Induces a Specific Pattern of Adaptation in Remnant Jejunum

Glucagon-like peptide-2 (GLP-2) is an enteroendocrine hormone which is uniquely trophic for the intestine; a physiological role in regulating nutrient absorptive capacity is becoming apparent. GLP-2, independent of enteral feeding, stimulates a classical pattern of intestinal adaptation in terminal ileum following resection. Herein we investigate the effects of GLP-2 on the jejunal remant using a rat model of short bowel syndrome (SBS). Juvenile 250- to 275-g SD rats underwent 80% distal small bowel resection, leaving 20 cm of proximal jejunum and venous catheterization. Animals were maintained with total parenteral nutrition (TPN) or TPN+10 μg/kg/hr GLP-2 (n=8 per group). After 7 days, intestinal permeability was assessed by urinary recovery of gavaged carbohydrate probes. Animals were euthanized, and the intestines taken for analysis of morphology, crypt cell proliferation, apoptosis, and expression of SGLT-1 and GLUT-5 transport proteins. GLP-2 treatment reduced intestinal permeability and increased in vivo glucose absorption, small intestinal weight, surface area, villus height, crypt depth, and microvillus height. Intestinal mucosal DNA and protein content per unit length of the small bowel were increased (P < 0.05 for all comparisons). However, in contrast to previous studies examining GLP-2’s effects on remnant ileum, the jejunal crypt apoptotic index was increased in GLP-2-treated animals, with no increase in SGLT-1 or GLUT 5 expression. These results show that exogenous GLP-2 treatment of animals with jejunal remnant reduces intestinal permeability, increases glucose absorption, and stimulates morphological features of intestinal adaptation including increased micovillus height and surface area. However, the pattern of changes seen is different from that in remnant ileum. This suggests that GLP-2’s effects are specific to different regions of the bowel. Nonetheless, remnant jejunum is responsive to GLP-2 in the absence of enteral nutrition. Further studies are warranted to establish the mechanisms of action and therapeutic potential of GLP-2 in modulating nutrient absorptive capacity.     

Management of the short bowel syndrome after extensive small bowel resection

Short bowel syndrome (SBS) is a global malabsorption syndrome that results from extensive intestinal resections. It used to be a typical complication of repetitive bowel resections in patients with Crohn's disease. However, due to improved medical and surgical therapies for these patients it currently occurs more frequently as a consequence of vascular disorders in adults (intestinal infarction) and congenital aberrations in children, respectively. Adequate therapy depends on the degree of (small) bowel losses and on resulting functional disturbances. Moreover, it must be adjusted to the postoperative adaptation process, which consists of three phases: The immediate acute phase lasts less than 4 weeks and serves to stabilise the patient. The subsequent year should be used to induce maximal adaptation by gradually increasing nutrient exposure. When maximal stimulation of nutrient absorption has been achieved, permanent maintenance nutrition treatment should be defined individually, dependent on extent and quality of nutritive deficits. In patients with Crohn's disease, optimal treatment of the underlying disease is of pivotal importance in order to avoid a further reduction of absorptive capacity or other complications. Current investigations aim at improving the adaptation process by administration of specific diets and growth hormones. With these, it appears possible to treat even some patients with very short bowel, i.e. less than 50 cm of small intestine left, with oral nutrition, only. Still, a considerable proportion of patients will need long-term parenteral nutrition. If young patients experience intolerable complications of parenteral nutrition, intestinal transplantation may be considered as a high risk therapy of last choice.     

Diagnosing small bowel malabsorption: a review

Malabsorption encompasses dysfunctions occurring during the digestion and absorption of nutrients. A small proportion of patients presents with chronic diarrhoea. A clinical history supportive of malabsorption may guide investigations toward either the small bowel or pancreas. Serological testing for coeliac disease will determine most cases without invasive investigations. In the clinical context of persisting weight loss and malnutrition, small bowel enteropathy may be investigated with small intestinal biopsies. Small bowel absorptive capacity and permeability might be measured by oral sugar-mix ingestion. Further, approaches to the investigation of malabsorption might also involve the detection in faeces of a substance that has not been absorbed. A variation of the latter is the use of breath testing which relies on the breakdown of the malabsorbed test substance by colonic flora. Measurement of protein absorption is difficult and unreliable; it is, therefore, rarely advocated in clinical settings. No single biological marker confirming a diagnosis of small bowel malabsorption or small bowel integrity is presently available in clinical practice. Plasma citrulline concentration, an amino acid not incorporated into endogenous or exogenous proteins, has been extensively used in research studies and supportive results are establishing its concentration as a reliable quantitative biomarker of enterocyte absorptive capacity.     

Longitudinal mechanical tension induces growth in the small bowel of juvenile rats

INTRODUCTION: The aim of our study was to apply longitudinal force to the small bowel to increase the length of intestine in juvenile rats. METHODS: Fifty juvenile rats had double barrelled, blind loop ostomies created using an isolated segment of bowel. Our intestinal lengthening device was inserted into one of the loops and the second loop served as a control. Once the device was deployed, the experimental, control, and in situ segments of bowel were evaluated for length, weight, histology, and disaccharidase enzyme activity. RESULTS: Mechanical tension increased intestinal length by 149%. The lengthened bowel also exhibited a greater total weight (218%), greater mucosal weight (122%), and increased protein mass (164%) compared with the control limb of bowel. Histologically, there was a markedly increased thickness of the muscularis propria in the lengthened bowel (200% increase compared with the control limb). Functionally, we found increased total disaccharidase activity in the lengthened bowel (between 47% and 350%, depending on the particular enzyme tested; p<0.01). CONCLUSION: Mechanical tension induces intestinal growth by increasing length, weight of the bowel and mucosa, and protein mass. Histological changes, such as increases in Paneth cells, suggest that increased proliferation and reorganisation of the mucosa and muscularis propria are a response to mechanical tension. Functionally, increased intestinal length corresponds with increased disaccharidase activity, thus implying potential increased absorptive capacity of the lengthened bowel.     

Chronic intestinal pseudo-obstruction in patients with extensive bowel resection for Crohn's disease

We report three cases of severe chronic intestinal pseudo-obstruction after extensive bowel resection for Crohn's disease. The patients retained less than or equal to 150 cm jejunum in continuity with the left half of the colon and had no evidence of inflammatory activity in the remaining bowel. Total parenteral nutrition was required, since even very small meals caused abdominal distention, pain, and vomiting. Two patients had a sigmoidostomy constructed, which alleviated the symptoms and enabled a normal oral intake, but only temporarily in one of the patients. Even with a sigmoidostomy the patients needed supplementary parenteral nutrition because of severe malabsorption with high stomal output.     

Advances in the management of short bowel syndrome

Short bowel syndrome (SBS) is the predominant cause of intestinal failure and is thus associated with a high degree of morbidity and mortality. One of the reasons this occurs is the dramatic reduction in nutrient absorptive capacity. Of the many causes of SBS, the most common cause is extensive surgical resection. The impressive ability of the bowel to adapt functionally and morphologically is critical for decreasing morbidity and mortality in these patients. The degree of adaptation is vital in decreasing the dependence on parenteral nutrition (PN) and for improving patient quality of life and long-term outcome. Provision of appropriate and sufficient nutritional and fluid support is essential for the management of these patients. The primary goal is to prevent or eliminate the need for PN. Recent developments have promoted a greater understanding of the process of intestinal adaptation. Various intestinal trophic factors have been recognized. These efforts have led to the early development of hormonal therapy to stimulate intestinal adaptation and enhance intestinal absorption. Intestinal transplantation remains an option for those who have developed life-threatening complications from PN and cannot be managed using more conservative techniques.     

Effect of total colectomy and mucosal proctectomy on intestinal absorptive capacity in dogs

Changes in intestinal absorptive capacity for water and electrolytes were investigated in dogs after total colectomy and mucosal proctectomy reconstructed with interposing jejunum into the anorectal area. Rate of abosorption of water and sodium from the ileum increased significantly at 29 weeks postoperatively. The absorption of water, sodium, and chloride in the jejunum was significantly higher than in the neorectum. The net secretion rate of potassium increased significantly in the ileum and neorectum. The authors suggest that intestinal adaptation achieved after proctocolectomy is enhanced in the jejunum and ileum rather than in the neorectum.     

Thermal imaging in the detection of bowel ischemia

PURPOSE: The aim of this study was to introduce thermal imaging in the intraoperative detection of bowel ischemia by comparing thermal imaging with conventional techniques in detecting acutely ischemic bowel, using histologic evidence for intestinal necrosis as the standard. METHODS: A prospective study was performed using a porcine model. Laparotomy was performed on four pigs under general anesthesia. A 25-cm segment of mid jejunum was tagged with proximal and distal sutures, and its mesentery was ligated and divided. Thermal imaging, visual inspection, Doppler ultrasound, and fluorescence with Wood's lamp after fluorescein were used to estimate the extent of bowel ischemia five minutes after ligation of the mesentery. Measurements were taken in reference to both the proximal and distal tags to obtain two data points per animal for each method. After two hours of warm ischemia, the jejunum was harvested and sectioned longitudinally. Comparisons were made between the estimated region of necrosis for each method and microscopic evidence of necrosis. RESULTS: Visual inspection was the only method unable to detect a difference between vascularized and devascularized bowel for each of the eight data points. Fluorescein dye missed 3 cm of ischemic bowel. Doppler ultrasound and thermal imaging were 100 percent sensitive for necrotic bowel, with thermal imaging overestimating necrosis to a greater extent than Doppler ultrasound. The positive predictive value of fluorescein dye, Doppler ultrasound, and thermal imaging for determining nonviable bowel was 91.8, 80.8, and 69.5 percent, respectively. CONCLUSIONS: Thermal imaging has the potential to be a useful adjunct in the intraoperative determination of bowel ischemia. Further studies are indicated to study this technique.     

Morphological and functional changes in the gut after massive small bowel resection and colon interposition in rhesus monkeys

An experimental model of massive small bowel resection and colonic autograft in an antiperistaltic fashion in between the remnants of jejunum and ileum was developed in Rhesus monkeys. The gross morphological changes showed significant (p less than 0.001) lengthening and dilatation of the remnant jejunum, ileum and the colonic graft. Hypertrophy and hyperplasia of the mucosal and muscular layers of all the 3 segments was revealed by morphometric studies and the estimation of the nucleic acid content of the mucosa. All the 3 segments of the bowel showed a significant increase (p less than 0.001) in the uptake of D-glucose, L-alanine and L-phenylalanine when compared to the control animals. These changes were more pronounced in the animals kept for longer duration. Phlorizin was found to be inhibitory for the uptake of D-glucose in the grafted colon, suggesting the induction of an active nonelectrolyte transport process in the autografted colon. The present study suggests that the colonic loop adapts itself to the functions of the small bowel along with the compensatory adaptation of the remnant jejunum and the ileum for the loss of absorptive surface secondary to massive small bowel resection .     

Short bowel syndrome

Opinion statement Treatment of short bowel syndrome (SBS) is often a difficult endeavor due to the high variability among patients with SBS in regard to remaining anatomical structure and functional capacity. Research efforts to substantiate the use of existing therapies in the treatment of SBS are ongoing, with newer developments yet to be fully explored. Current therapy for SBS begins with the implementation of a modified diet based on the presence or absence of the colon. Patients with difficulty ingesting enough nutrients and fluids for weight maintenance and fluid balance may benefit from nocturnal enteral nutrition and hydration. Those with inadequate absorptive capacity despite maximization of oral and enteral intake will need parenteral nutrition (PN) or hydration. Medications, including antisecretory agents, antidiarrheals, pancreatic enzymes, bile acid sequestrants, and antibiotics, often are useful in abating symptoms commonly associated with SBS. Growth factors, including recombinant human growth hormone and glucagon-like peptide 2, may be trialed to stimulate intestinal adaptation and enhance absorption in PN-dependent SBS patients. The gradual refinement of surgical procedures for SBS, including small bowel transplantation, has led to improved outcomes, and early referral of SBS patients to centers of excellence will optimize care.     

Small bowel volvulus among adults

BACKGROUND: To elucidate clinical experience associated with rare cases of small bowel volvulus among adults, we conducted a retrospective study. METHODS: From January 1993 to March 2003 inclusively, we reviewed the presentation and management of 19 patients featuring small bowel volvulus. All study-included patients underwent surgical treatment to confirm their diagnosis. We also analyzed their signs, symptoms, radiological examination details, clinical course and surgical results. RESULTS: The mean age of the study-included 19 patients (13 males, six females) was 61.3 years (range = 16-83 years). All patients suffering from small bowel volvulus were categorized as displaying either primary (no obvious predisposing factors) or secondary volvulus (specific predisposing anatomical abnormalities present). Among them, nine patients were categorized as having primary volvulus, and the remaining 10 were patients with secondary volvulus; this comprised one pregnancy, two malignant stromal tumors of the jejunum, six jejunal diverticula, and one adhesion band. Nine examples of volvulus occurred in the jejunum, four in the ileum, and six in both jejunum and ileum. There were five examples of a counter clockwise rotation of small bowel volvulus. Two patients exhibited bowel wall gangrene, both of whom died subsequent to surgery. The overall mortality rate was 11%. CONCLUSIONS: Although small bowel volvulus is rarely seen among adults, when a patient presents with intestinal obstruction, the possibility of small bowel volvulus must be considered. Early surgical intervention should be undertaken in order to prevent vascular compromise.     

Gene expression in the adapting small bowel after massive small bowel resection

Background Intestinal adaptation occurs in the residual bowel following the loss or resection of a proportion of the small bowel. The purpose of the adaptive response is to return absorptive and digestive properties to near normal levels. This study employed a rat model of massive small bowel resection (MSBR) to study the adaptive response in the residual terminal ileum and the jejunum. The time points were chosen to reflect changes in gene expression early on in the response, because these are the genes that alter to initiate and maximize the response observed during adaptation. Methods Sprague Dawley rats underwent an 80% resection. Differential display polymerase chain reaction (DD-PCR) analysis was performed on mRNA extracted from the remnant ileum and jejunum 0, 1, 2, 4, and 7 days post-MSBR. Results DD-PCR identified 11 genes that were possibly regulated following MSBR. Genes confirmed to be regulated were 16S ribosomal RNA, lymphocyte antigen 6 (LY6)-like molecule, Krüppel-like factor-3 (KLF-3), G-protein-binding protein (CRFG), system A transporter 2 (SAT2), and an intestine-specific gene (similar to mKIAA0493). Conclusions DD-PCR analysis showed regulation of a number of genes not previously known to be involved in adaptation after MSBR or previously characterized in the intestine. These genes may be important in bringing about the complement of changes seen during the adaptive response.     

Intestinal motility in patients with small bowel diverticulosis

It has been demonstrated that motility disorders may be responsible for esophageal and colon diverticulosis. Recently anatomic alterations of both small bowel muscular layers and myenteric plexus have been described in patients with small bowel diverticulosis. Such pathological features could be responsible for motility disorders and small bowel diverticulosis formation. The aim of this work was to study the small bowel motility in patients with small bowel diverticulosis. Ten patients (mean age: 69.2 +/- 6 years mean +/- SEM) with more than 3 diverticula in the jejunum or the ileum (excepting duodenal diverticulum) were studied. After an overnight fast, a 4 lumen probe (side holes 10 cm apart) was used to record duodeno-jejunal motility for 4 hours. Esophageal manometry was also performed in 8 patients. The mean number of phase 3 of the migrating motor complex (mean +/- SEM) during 4 hours was significantly lower in patients with small bowel diverticulosis (0.15 +/- 0.05/hours; mean +/- SEM) than in 10 normal volunteers (0.52 +/- 0.07/hours; mean +/- SEM) (P less than 0.01); 5 patients had zero phase 3 during the 4 hours of recording; one patient displayed intestinal hypomotility associated with aberrant phase 3 like activity; 4 patients showed simultaneous minute-rhythm during more than 80 percent of the phase 2 of the migrating motor complex. Esophageal manometry was also disturbed in 6 patients (low amplitude contractions less than 30 cm H2O in the distal esophagus). Bacterial overgrowth was investigated in 8 patients by means of a glucose breath-test and was found in 6 cases. In conclusion, duodeno jejunal motility is altered in patients with small bowel diverticulosis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ion transport in the experimental short bowel syndrome of the rat.

The adaptational changes of epithelial ion transport in the short bowel syndrome were studied. Ileal remnants of rats were investigated 8 weeks after 70% proximal small intestinal resection. Pure epithelial resistance measured by impedance analysis decreased from 27 +/- 1 to 21 +/- 1 omega.cm2, and polyethylene glycol 4000 fluxes increased from 2.5 +/- 0.3 to 3.6 +/- 0.3 nmol.h-1.cm-2, indicating increased permeability of the short bowel. Unidirectional flux measurements in control ileum showed absorptive net fluxes of Na+ and Cl- that were assigned to electroneutral NaCl absorption and a short-circuit current that was accounted for by the residual flux (HCO3- secretion). Neither NaCl absorption nor HCO3- secretion were altered in the short bowel. Also, electrogenic Cl- secretion, defined after maximal stimulation by theophylline and prostaglandin E1 was not changed in the short bowel. In contrast, electrogenic Na+/glucose cotransport increased in Vmax from 2.0 +/- 0.3 in controls to 5.0 +/- 1.0 mumol.h-1.cm-2 in the short bowel. Tight junction structure was studied by freeze-fracture electron microscopy. The number of horizontal strands was unchanged, whereas tight junction depth was slightly increased in the short bowel. Microvillus area of short bowels was increased by 20% in villus regions. Under the light microscope, villus height was increased by 30%. In conclusion, the short bowel mucosa undergoes adaptive responses to reduced overall absorptive area by increasing glucose-dependent electrogenic Na+ absorption to 250%, which is partly caused by increased villus and microvillus surface area. Electrogenic Cl- and HCO3- secretion and electroneutral NaCl absorption remained unchanged. The decreased epithelial resistance is caused by mucosal surface amplification.     

Effect of enteric pacing on intestinal motility and hormone secretion in dogs with short bowel.

The present study was designed to examine the role of electrode position during retrograde pacing in dogs with short bowel syndrome and unsevered intact duodenum. In nine beagle dogs a subtotal resection of the small bowel and jejunoileostomy was performed. In five of these dogs, an isolated blind loop (jejunum) with preserved mesenteric connections was left in situ as an additional place for a stimulation electrode. Small intestinal motility and plasma levels of insulin, glucagon, gastrin, somatostatin, and glucose were examined during pacing of the residual jejunum or the isolated loop, respectively, compared with control experiments in the same dogs without pacing. During pacing of the loop a significant (P less than 0.05-0.01) decrease in the postprandial small intestinal motility index was observed combined with a significant (P less than 0.05) increase in plasma insulin levels, whereas the postprandial increase in glucagon, somatostatin, gastrin, and glucose levels was not different from that in controls. In contrast, pacing of the jejunum increased postprandial small intestinal motility index (less than or equal to 68%), whereas the levels of the four hormones and plasma glucose were not different from those in controls. The data suggest that in dogs with intact duodenum, pacing on an excluded loop is required to obtain the desired effect of reduced intestinal motility and improved anabolic pancreatic hormone secretion.     

Sandostatin impairs postresection intestinal adaptation in a rat model of short bowel syndrome

Because of its antisecretory properties, sandostatin has been advocated for the treatment of patients with short bowel syndrome (SBS). This study was conducted to determine the effect of sandostatin on structural intestinal adaptation, cell proliferation and apoptosis in a rat model of SBS. Sprague-Dawley rats were divided into three experimental groups: Sham rats underwent bowel transection, SBS rats underwent 75% small bowel resection, and SBS-sandostatin rats underwent bowel resection and were treated with sandostatin (SBS-SND). Parameters of intestinal adaptation, enterocyte proliferation, and enterocyte apoptosis were determined on day 14 following operation. We have demonstrated that SBS-SND animals demonstrated lower (vs SBS rats) duodenal and jejunal bowel weights, jejunal and ileal mucosal weight, jejunal and ileal mucosal DNA and protein, jejunal and ileal villus height, cell proliferation index in the ileum, and enterocyte apoptosis in jejunum and ileum. We conclude that in a rat model of SBS sandostatin decreases cell proliferation and inhibits structural intestinal adaptation.