The role of phytosterols in the pathogenesis of liver complications of pediatric parenteral nutrition.
Clayton PT. Whitfield P. Iyer K.
Biochemistry Unit, Institute of Child Health, London, United Kingdom.
Long-term parenteral nutrition of infants who have had major gut resections is associated with a high incidence of cholestatic liver disease. Affected infants have high plasma concentrations of phytosterols--compounds that resemble cholesterol but have an alkylated side chain. The phytosterols that accumulate in patients receiving parenteral nutrition are derived from the soya oil and/or soya lecithin used to make the intravenous lipid emulsion. There is a striking association between phytosterolemia and cholestatic liver disease. This has led us to put forward the hypothesis that phytosterols can cause cholestasis in susceptible infants. Experiments using neonatal piglets indicate that phytosterols (given without any of the other components of parenteral nutrition) can indeed reduce bile flow. We suggest that increasing the content of phytosterols in cell membranes may interfere with the function of important transport proteins involved in the secretion of bile. Other factors that might contribute to cholestasis (such as inhibition of cholesterol 7 alpha-hydroxylase) are discussed.
Liver complications of pediatric parenteral nutrition--epidemiology.
Liver Unit, Birmingham Children's Hospital NHS Trust, United Kingdom.
Total parenteral nutrition (TPN)-induced liver disease develops in 40-60% of infants who require long-term TPN for intestinal failure. The clinical spectrum includes cholestasis, cholelithiasis, hepatic fibrosis with progression to biliary cirrhosis, and the development of portal hypertension and liver failure in a significant number of children who are totally parenterally fed. The pathogenesis is multifactorial and is related to prematurity, low birth weight, and duration of TPN. The degree and severity of the liver disease is related to recurrent sepsis including catheter sepsis, bacterial translocation, and cholangitis. Lack of enteral feeding leading to reduced gut hormone secretion, reduction of bile flow, and biliary stasis may be important mechanisms in the development of cholestasis, biliary sludge, and cholelithiasis. Although it is unlikely that modern TPN solutions have a major role in the etiology of TPN liver disease, manganese toxicity recently has been recognized in children with hepatic dysfunction on TPN. Although there is a definite relationship with the degree of manganese toxicity and hepatic decompensation, it is not yet clear whether this is a primary mechanism or whether the high levels are related to reduced biliary excretion of manganese. The management strategies for the prevention of TPN-induced liver disease include early enteral feeding, a multidisciplinary approach to the management of parenteral nutrition, and aseptic catheter techniques to reduce sepsis. The administration of ursodeoxycholic acid may improve bile flow and reduce gall bladder and intestinal stasis. As survival from isolated intestinal transplantation improves, this therapeutic option should be considered before TPN liver disease becomes irreversible and combined liver and small bowel transplantation is required.
Oral absorption tests: absorption site of each substrate.
Ueno T. Hamanaka Y. Oka M. Suzuki T.
Department of Surgery II, Yamaguchi University School of Medicine, Japan.
Three oral absorption tests have been used in patients with short bowel syndrome (SBS) to evaluate the absorption site of each substrate. In this study, three absorption tests were applied: the oral pancreatic function test using N-benzoyl-L-tyrosyl-p-aminobenzoic acid (NBT-PABA), the D-xylose tolerance test, and the oral fat tolerance test. Examinations were performed in eight patients with either a duodenostomy or a jejunostomy located less than 60 cm from the ligament of Treitz, and in a patient with an end ileostomy. Forty-six healthy volunteers participated as controls for the oral fat tolerance test. PABA and D-xylose concentrations were measured in urine. The serum triacylglycerol concentration was determined at 0, 1, 2, and 3 h after ingestion. All eight patients with SBS demonstrated pathologic absorption on each test. We conclude that small bowel integrity is critical for evaluation of the NBT-PABA test. We also determined that the duodenum and proximal jejunum do not play an important role in the absorption of D-xylose and triacylglycerol. We could also evaluate limitations and advantages of the other kinds of oral absorption tests and nutrients through patients with SBS.
Hepatic energy and substrate metabolism: a possible metabolic basis for early nutritional support in cirrhotic patients.
Institut fur Humanernahrung und Lebensmittelkunde, Christian-Albrechts-Universitat zu, Kiel, Germany.
In the liver, the in vivo assessment of metabolic functions is limited by methodologic problems. The present evidence suggests that the liver contributes to 20-30% of whole body energy expenditure. Hepatic fuel selection can change considerably under different circumstances. During tissue catabolism (i.e., depletion of glycogen stores, increased lipid oxidation), the "hepatic respiratory quotient (RQ)" is lower than whole body RQ, suggesting that hepatic catabolism exceeds whole body catabolism. By contrast, the hepatic RQ may exceed whole body RQ during tissue anabolism (i.e., after full repletion of hepatic glycogen stores and significant lipogenesis). In cirrhosis, both the hepatic RQ and the whole body RQ are markedly reduced. When compared with the whole body level, the cirrhosis-induced decrease in the hepatic RQ is more pronounced. Given that liver catabolism exceeds (or possibly precedes) whole body catabolism, early nutritional support is mandatory in cirrhotic patients. The assessment of hepatic, in addition to whole body, energy metabolism may provide a basis for future recommendations of more specific nutritional support in patients with liver diseases.
The 1996 Nestle International Clinical Nutrition Award for Enteral Nutrition. Enteral versus parenteral nutrition: effects on gastrointestinal function and metabolism: background.
Department of Anaesthesiology, Klinikum Grosshadern, Ludwig-Maximilians-Universitat, Munich, Germany.
Nutrition therapy for the critically ill patient is today an integral part of the treatment concept in intensive care medicine. Parenteral and enteral artificial nutrition are expensive, cost-intensive treatment procedures that are certainly not risk-free. For both ethical and economic reasons, the indications and principles of artificial nutrition must always be adapted to the latest knowledge.
Pregnant women with transient gastric obstruction managed by Naso-Jejunal nutrition.
Uchide K. Suzuki N. Oota T. Terada S. Inoue M.
Department of Obstetrics and Gynecology, School of Medicine, Kanazawa University, Ishikawa, Japan.
A pregnant woman with transient gastric obstruction was fed by enteral nutrition alone for 11 wk and 6 d. Her body mass index of 23.2 kg/m2 before pregnancy declined to 21.8 kg/m2 after delivery. Although she did not gain weight during enteral nutrition, fetal growth, estimated by ultrasonography, was normal, and she delivered a 3030-g female infant at 38 wk gestation. The blood laboratory data during pregnancy and the breast milk after pregnancy were also normal. The results suggest that factors other than maternal weight gain alone should be considered in the evaluation of nutritional status for the pregnant woman.
Appropriate nutritional support in acute and complicated Crohns disease.
Duerksen DR. Nehra V. Bistrian BR. Blackburn GL.
Department of Medicine, Beth Israel Deaconess Hospital, Boston, Massachusetts, USA.
Crohn's disease is frequently complicated by protein-calorie malnutrition. Four common clinical presentations of Crohn's disease include acute exacerbations or flares of disease, intestinal obstruction, fistulizing disease, and perianal disease. In this review, we examine the role of nutritional support in these clinical scenarios. Nutritional support is important for maintaining functional status and preventing loss of lean tissue. Determinants of lean-tissue loss include severity of underlying injury, baseline nutritional status, and duration of inadequate nutrition. One of the clinically useful measures of nutritional status is the nutritional risk index (NRI) defined on the basis of the serum albumin and weight loss. Nutritional support is important in severely malnourished patients (NRI < 83). Enteral nutrition is the route of choice, provided there are no contraindications to using the gastrointestinal tract. In acute exacerbations of Crohn's disease, enteral nutrition also has a role in the primary management of disease although it is not as effective as corticosteroids in inducing remission. The mechanisms are poorly understood and the most effective enteral formulation needs to be determined. Total parenteral nutrition is justified in severely malnourished Crohn's disease patients who are unable to tolerate enteral feeding or in whom enteral feeding is contraindicated. More clinical studies are needed on the assessment of malnutrition in Crohn's disease, the effects of nutritional management on functional status, and the timing of nutritional intervention.
Bran: may irritate irritable bowel.
Lewis MJ. Whorwell PJ.
The irritable gut is known to be hypersensitive, and it is reasonable to suspect that patients with the disorder might be hyperreactive to agents that stimulate or irritate it. This appears to be a possible explanation for the adverse effects of bran on hospital patients with this disorder, but we do not yet know how this product affects community IBS sufferers. We cannot ignore the fact that fiber and bran have major beneficial effects in other areas, not least in the reduction of colonic carcinoma. In conclusion, it is probably best to recommend that patients with IBS be left to judge for themselves whether bran helps or exacerbates their symptoms, but there is enough evidence to suggest that the current dogma of routinely treating all IBS sufferers with bran should be challenged. Proprietary sources of fiber, such as ispaghula, may be more appropriate for those IBS subjects (for example, constipated) for whom fiber supplementation is believed justified.
Glutamine-supplemented total parenteral nutrition reduces blood mononuclear cell interleukin-8 release in severe acute pancreatitis.
de Beaux AC. O'Riordain MG. Ross JA. Jodozi L. Carter DC. Fearon KC.
University Department of Surgery, Royal Infirmary, Edinburgh, United Kingdom.
Glutamine, a conditionally essential amino acid, is important for immune function. It is now being formulated for incorporation into total parenteral nutrition (TPN). The aims of this study were to examine the effect of glutamine administration on lymphocyte proliferation and proinflammatory cytokine release in patients with severe acute pancreatitis. Fourteen patients were randomized (in a double-blind fashion) to receive either conventional or isocaloric, isonitrogenous glutamine-supplemented (0.22 g glutamine x kg(-1) x d(-1) as glycyl-glutamine) TPN for 7 d. DNA synthesis (index of lymphocyte proliferation) and the 24-h release of tumor necrosis factor (TNF), interleukin (IL)-6, and IL-8 from peripheral blood mononuclear cells were measured in vitro on days 0, 4, and 7. Thirteen patients completed the study protocol (6 glutamine TPN, 7 conventional TPN). Glutamine supplementation increased median DNA synthesis by 3099 cpm over the study period against 219 cpm in the conventional group (increase not significantly different between the two groups) . Glutamine supplementation did not significantly influence TNF or IL-6 release, but, in contrast, median IL-8 release was reduced by day 7 in the glutamine group while it was increased in the conventional group (-17.7 ng/mL (median change over study period) versus +43.3 ng/mL, respectively; P=0.045). Small patient numbers and substantial interindividual variation limit the conclusions, but there is a trend for the glutamine group to have improved lymphocyte proliferation, and in the case of IL-8, reduced proinflammatory cytokine release.
Childhood Crohns disease and the efficacy of enteral diets.
Beattie RM. Bentsen BS. MacDonald TT.
Department of Paediatric Gastroenterology, Royal London School of Medicine and Dentistry, St Bartholomew's Hospital, United Kingdom.
Enteral diets, both elemental and, more recently, polymeric (whole protein), are used as primary therapy in Crohn's disease and can induce disease remission without the concomitant use of immunosuppressive drugs. Controlled trials comparing enteral nutrition with corticosteroid therapy have given mixed results but suggest, at least in children, that they are as effective as corticosteroids in inducing remission. There is no clear consensus as to which dietary therapy is best. Elemental diets do not seem to be superior to polymeric whole protein-based diets, although further work is necessary. The effect of enteral diets does not seem to be related to the site of intestinal inflammation. Enteral nutrition is particularly appropriate in children and adolescents with Crohn's disease, improving nutrition and promoting growth and pubertal development, and avoiding the systemic toxicity of corticosteroid therapy. Most centers will use it as a first line of treatment. Supplementary enteral nutrition after primary therapy and remission induction may be associated with the prolongation of remission and promotion of linear growth. Pathways by which enteral diets may affect mucosal inflammation are discussed. Enteral diets may inhibit intestinal immune responses by reducing the number of cytokine-producing cells. Enteral nutrition may also boost immunosuppressive pathways, which then endogenously suppress ongoing inflammation. Enteral diets may promote epithelial healing and reepithelialization of Crohn's ulcers and may also reduce the bacterial load in the small bowel.
Alterations in intestinal barrier function do not predispose to translocation of enteric bacteria in gastroenterologic patients.
O'Boyle CJ. MacFie J. Dave K. Sagar PS. Poon P. Mitchell CJ.
Combined Gastroenterology Unit, Scarborough Hospital, United Kingdom.
Bacterial translocation from the intestinal lumen has been demonstrated in humans. Three mechanisms have been suggested to explain the phenomenon: altered intestinal barrier function, bacterial overgrowth, and impaired host defense. The aim of this study was to determine whether changes in intestinal barrier function assessed by measurement of intestinal permeability and morphology were associated with alteration in bacterial translocation. Intestinal permeability was assessed in 43 patients by the lactulose/L-rhamnose test with a 5-h urine collection. Mucosal atrophy was assessed from the villus height-to-mucosal thickness ratio in small-bowel biopsies. Bacterial translocation was determined by microbiologic analysis of harvested mesenteric lymph nodes. No significant differences were apparent in the incidence of bacterial translocation in patients with normal permeability (5 [23%] of 22 patients translocated) compared with patients with increased permeability (4 [19%] of 21 patients translocated). Similarly, no correlation was apparent between the incidence of bacterial translocation and the index of villus atrophy. The degree of villus atrophy failed to correlate with gastrointestinal permeability. These data suggest that the incidence of bacterial translocation is not related to increased intestinal permeability or mucosal atrophy.