Carol Rees Parrish M.S. R.D. Series Editor Short Bowel .
NUTRITION ISSUES IN GASTROENTEROLOGY, SERIES #132Carol Rees Parrish, M.S., R.D., Series EditorShort Bowel Syndrome in Adults – Part 1Physiological Alterationsand Clinical ConsequencesJohn K. DiBaiseCarol Rees ParrishShort bowel syndrome (SBS) is a malabsorptive condition resulting most commonly from extensiveintestinal resection. It is associated with significant morbidity and mortality, a reduced quality oflife and high health care costs. The management of patients with SBS is complex and requires amultidisciplinary approach including dietary, fluid and pharmacological management, co-morbiddisease management and, occasionally, surgery. An understanding of the physiological alterationsthat occur in SBS is useful to understand the treatments employed. In Part 1 of this five-partseries on SBS, we address the physiological alterations that occur, the clinical consequences ofthese changes including potential complications, and the adaptation process that the intestineundergoes in order to improve the body’s ability to digest and absorb nutrients and fluid.INTRODUCTIONShort bowel syndrome (SBS) is a disablingmalabsorptive condition associated with a highfrequency of complications and high utilization ofhealthcare resources. SBS generally does not becomeclinically apparent until about three-quarters of thesmall bowel (SB) have been removed. Because of thewide range in SB length and its capacity to compensatefor bowel resection, the definition of SBS should notJohn K. DiBaise, MD, Professor of Medicine,Division of Gastroenterology and Hepatology,Mayo Clinic, AZ Carol Rees Parrish MS, RD,Nutrition Support Specialist, University ofVirginia Health System Digestive HealthCenter of Excellence, Charlottesville, VA30be based solely on the length of remaining bowel.Experts in intestinal failure have, instead, proposeddefining SBS as a condition resulting from surgicalresection, congenital defect, or disease-associated lossof absorption, characterized by the inability to maintainprotein-energy, fluid, electrolyte, or micronutrientbalances when on a normal diet.1 Nevertheless, thepresence of 200 cm of remaining SB is often used inorder to facilitate a clinical diagnosis.Etiology and EpidemiologyIn adults, the more common causes of SBS includemultiple resections for Crohn’s disease, massiveresections due to catastrophic mesenteric vascularevents, and malignancies (Table 1).2,3 PostoperativePRACTICAL GASTROENTEROLOGY AUGUST 2014
Short Bowel Syndrome in Adults – Part 1NUTRITION ISSUES IN GASTROENTEROLOGY, SERIES #132vascular and obstructive catastrophes requiring massiveintestinal resection seem to be increasing in incidenceand in one recent series was the most common causeof SBS in adults.4 Notably, the operations leading toSBS after an open surgery appear to be different thanafter a laparoscopic approach – gastric bypass andcholecystectomy being most frequent with laparoscopyand colectomy, hysterectomy and appendectomy beingthe most common with the open approach in one series.5The major mechanisms responsible after open surgeryand laparoscopy appear to be adhesions and volvulus,respectively. While advances in the treatment ofCrohn’s disease may lead to a reduction in SBS, theseimprovements have not translated into a reduction inthe need for home parenteral nutrition (PN).6The incidence and prevalence of SBS are unknownbecause there are no reliable databases. Estimates arebased on information from home PN registries, forwhich SBS is generally the most common indication.Two recent studies limited to SBS patients reportedthe majority of patients being female and 50 yearsof age.2,3 The multifactorial etiology, uncertaintyregarding intestinal length and varying definitions ofSBS contribute to the difficulty of comparing reports.In the U.S., the annual prevalence of home PN has beenestimated at approximately 120 per million, of whomabout 25% have SBS; this amounted to about 10,000adults in 1992.7 These numbers do not reflect patientswith SBS who did not survive, were able to be weanedfrom PN during the index hospitalization, or were ableto be successfully weaned from home PN and, therefore,likely underestimate the prevalence of SBS.Relevant Anatomy and PhysiologyThree bowel anatomies may occur in SBS andare generally described in terms of location of theanastomosis after resection: Jejuno-colic Jejuno-ileocolonic End-jejunostomyThe clinical manifestations and outcome of SBSvary depending upon the remaining bowel anatomyand its residual function. Consequently, an appreciationof the bowel anatomies seen in SBS along with basicgastrointestinal physiological considerations is helpfulto better understand the prognosis and guide patientmanagement.PRACTICAL GASTROENTEROLOGY AUGUST 2014 Table 1. Causes of Short Bowel Syndrome in Adults Mesenteric ischemia Postoperative complications Crohn’s disease Trauma Neoplasms Radiation enteritisSmall BowelThe proximal 100 to 150 cm of the jejunum is theprimary site of carbohydrate, protein and water-solublevitamin absorption.8 Fat absorption may extend over alarger length of SB if more fat is ingested. In a healthyadult, about 4 L of intestinal secretions (0.5 L saliva, 2 Lgastric acid and 1.5 L pancreaticobiliary secretions) areproduced in response to the food and drink consumedeach day. Water absorption is a passive process resultingfrom the active transport of nutrients and electrolytes.Sodium transport creates an electrochemical gradientthat drives the uptake of nutrients across the intestinalepithelium. Because the junctions between jejunalepithelial cells are considerable compared to other areasof the bowel, a rapid flux of fluids and nutrients occursresulting in inefficient fluid absorption and iso-osmolarjejunal contents. Sodium absorption in the jejunumoccurs against a concentration gradient, is dependentupon water fluxes and is coupled to the absorption ofglucose.9 These factors become particularly importantin the SBS patient who only has jejunum remaining.In contrast to the jejunum, the ileum has tighterintercellular junctions resulting in less water and sodiumflux.9 In the ileum, active transport of sodium chlorideallows for significant fluid reabsorption and the abilityto concentrate its contents. The distal ileum is alsothe primary site of carrier-mediated bile salt and B12absorption. The ileum and proximal colon produceseveral hormones including glucagon-like peptides 1and 2 and peptide YY that have transit/motilitymodulating (e.g., jejunal and ileal brake phenomena)and intestinotrophic properties.10 The benefit of theileocecal valve in slowing transit and preventing reflux31
Short Bowel Syndrome in Adults – Part 1NUTRITION ISSUES IN GASTROENTEROLOGY, SERIES #132Table 2. Factors Affecting Intestinal Adaptation Hyperphagia Remaining bowel anatomyo Colon presento Ileum present Luminal factorso Whole foodso Nutrients (short chain fatty acids,glutamine)o Pancreaticobiliary secretions Hormones/Growth factorso Trophic (GH, GLP-2, IGF-1, EGF, TGF-α)o Antimotility (GLP-2, GLP-1, PYY)GH growth hormone; GLP-2 glucagon-likepeptide-2; IGF-1 insulin-like growth factor-1; TGFα transforming growth factor-α; GLP-1 glucagonlike peptide-1; PYY peptide YYof colonic contents into the SB remains controversialas the benefit may instead reflect the retention of asignificant length of terminal ileum.11ColonThe colon has the slowest transit, tightest intercellularjunctions and greatest efficiency of water and sodiumabsorption. In health, generally 1 to 1.5 L/day offluid enters the colon, where all except about 150 mLare reabsorbed. In SBS, the colon plays a vital rolein fluid and electrolyte balance given the capacity toaccommodate and absorb up to 6 L daily.12 Completeloss of the colon often leads to fluid and electrolytedisturbances. In addition to the resorptive capabilitiesof the colon, bacterial fermentation of malabsorbedcarbohydrates to short chain fatty acids (SCFA)with subsequent absorption in the colon provides anadditional 10-15% of energy needs or up to 1000 kcaldaily.13 Thus, the colon becomes an important organ forfluid and electrolyte absorption and for energy salvagein SBS.32 Stomach and PancreaticobiliaryMassive enterectomy is associated with transient gastrichypergastrinemia and hypersecretion that may last upto 12 months postoperatively.14 This may occur as aresult of the loss of inhibitory hormones producedin the proximal gut (e.g., gastric inhibitory peptideand vasoactive intestinal peptide). This increases thevolume and lowers the pH of secretions entering theproximal SB potentially aggravating fluid losses andleading to peptic complications and impairment in thefunction of digestive enzymes, further contributing tofat maldigestion. The use of antisecretory medicationsincluding proton pump inhibitors or histamine 2 receptorantagonists reduces gastric secretions, prevents pepticcomplications and may lead to improved digestionand absorption.15 Although some SBS patients withextensive proximal SB resections may lose sites ofsecretin and cholecystokinin-pancreozymin (CCKPZ) synthesis leading to diminished pancreatobiliarysecretions, the majority have extensive distal SBresections and demonstrate normal secretion of thesesubstances.16 Resection of 100 cm of terminalileum decreases the reabsorption of bile acids into theenterohepatic circulation, resulting in a reduction in thebile salt pool, eventually exceeding the ability of theliver to synthesize adequate replacement.17 This bileacid deficiency results in impaired micelle formationand fat digestion, and manifests clinically as steatorrheaand fat soluble vitamin deficiencies. In addition, theentry of caustic bile acids into the colon causes netfluid secretion into the colon and accelerated colonicmotility further increasing stool output.Intestinal AdaptationIntestinal adaptation is the process following intestinalresection whereby the remaining bowel undergoesmacroscopic and microscopic changes in responseto a variety of internal and external stimuli in orderto increase its absorptive ability (Table 2).18 Enteralnutrients are of particular importance in promotingan adaptive response, presumably by stimulatingpancreaticobiliary, gastrointestinal and gut hormonesecretions.19 Adaptation is highly variable and usuallyoccurs during the first two years following intestinalresection in adults. Both structural and functionaladaptive changes can occur depending upon the extentand site of the intestine removed and the nutrientcomponents of the diet (Table 3). The ileum is capable(continued on page 34)PRACTICAL GASTROENTEROLOGY AUGUST 2014
Short Bowel Syndrome in Adults – Part 1NUTRITION ISSUES IN GASTROENTEROLOGY, SERIES #132(continued from page 32)of both morphologic and functional adaptation. Whilethose with a jejuno-colic anastomosis demonstratefunctional SB adaptation, those with an end-jejunostomyshow little to no adaptation. The colon also appearsto undergo adaptive changes after massive intestinalresection.Determining Remaining Bowel Anatomyand its Influence on OutcomeThe large range of SB length, from about 300 to 800 cmin adults, underscores the importance of determiningthe SB length and segment/s remaining following anyresection. The length and region of the SB remainingand the presence of even a part of the colon areimportant factors affecting the outcome of the patientwith SBS. Establishing an accurate estimation of bowellength is often difficult as operative reports frequentlyrecord the amount of bowel removed rather than theamount remaining. SB length may also be estimated ona barium contrast SB series, which may also be useful todelineate other structural features such as the presenceof bowel dilatation. Recently, computed tomography(CT) enteroclysis with three-dimensional reconstructionand calculation of SB length has been shown to providesimilar information; however, this technique has notyet been adopted into clinical radiology practices.20Despite the importance of the remaining SB length indetermining the clinical outcome in SBS patients.21the ultimate determining factor of SBS severity andeventual outcome is the critical mass of functionalintestinal absorptive epithelia remaining.Because of differences in their adaptive ability,those with an ileal remnant have a better prognosis thanthose with only a jejunal remnant. In adults, terminalileal resections 60 cm generally require vitaminB12 replacement, while resections 100 cm lead todisruption in the enterohepatic circulation resulting inbile salt deficiency and fat malabsorption.22 Extensiveileal resection also results in accelerated gastrointestinaltransit due, in part, to the reduction in gut transitmodifying hormones. The presence of the colon hasbeen shown to be beneficial in SBS given its ability toabsorb water, electrolytes and fatty acids, slow intestinaltransit and stimulate intestinal adaptation. Indeed, thoseSBS patients with an end- jejunostomy are generally themost difficult to manage and are most likely to requirepermanent parenteral support.2334 Table 3. Adaptation-Related Intestinal Structuraland Functional Changes Structuralo Remnant bowel dilation andelongationo Increase in intestinal wet weight,protein and DNA contento Villus lengthening and expansionin microvillio Increase in crypt cell depth andenterocyte numbero Increases in gut muscle thickness,circumference and length Functionalo Modified brush border membraneenzyme activity, fluidity andpermeabilityo Up- or down-regulation of carriermediated transporto Slowing in the rate of transitallowing increased time forabsorption to occur ? Gut microbiota, motor activity and barrierand immune functionsComplicationsA variety of disorders may complicate the course ofthe patient with SBS. These complications may resultfrom the underlying disease, altered bowel anatomyand physiology, or treatment modalities including PNand the associated central venous catheter (Table 4).24,25Complications related to the altered bowel anatomy willbe discussed below. Fluid, electrolyte and micronutrientcomplications will be discussed in future articles inthis series.PRACTICAL GASTROENTEROLOGY AUGUST 2014
Short Bowel Syndrome in Adults – Part 1NUTRITION ISSUES IN GASTROENTEROLOGY, SERIES #132Oxalate NephropathyChronic kidney disease and calcium oxalatenephrolithiasis may complicate the course of SBS inthose with a colon segment, occasionally leading toirreversible renal failure.26 Normally, dietary oxalateis bound to intraluminal calcium and excreted in thestool. In SBS patients with fat malabsorption and acolon-in-continuity, calcium preferentially binds tounabsorbed fatty acids in the lumen leaving oxalatefree to pass into the colon to be absorbed into thebloodstream and then filtered by the kidney. Areduction in bacterial breakdown of oxalate due todecreased Oxalobacter formigenes in the colon ofSBS patients also contributes.27 Furthermore, citrateusually prevents nucleation, the first step in renal stoneformation; hypocitraturia is common in patients withmalabsorption and is thought to be due to bicarbonatewasting in the stool. In the kidney, oxalate binds tocalcium resulting in oxalate nephrolithiasis and riskof progressive obstructive nephropathy. To reduce therisk of this complication, correction of dehydration isof the utmost importance while use of calcium citratesupplementation, along with restriction of fat andoxalate-containing foods are advised. The clinical utilityof Oxalobacter formigenes supplementation to increaseoxalate destruction or cholestyramine to bind oxalateremains to be established. Urate nephrolithiasis is alsorelatively common in SBS patients with an ostomy andis related to chronic dehydration.Metabolic Bone DiseaseOsteomalacia, osteoporosis, osteopenia and secondaryhyperparathyroidism may occur in SBS patients as aconsequence of the PN, altered bowel anatomy causingmalabsorption of macro- and micronutrients (especiallyvitamin D), medication use (e.g., corticosteroid use fortreatment of an underlying disease) and other underlyingpatient factors such as gender, ethnicity, body size,and insufficient sun exposure.26 An assessment ofbone density should be undertaken in all SBS patientsand repeated every 2-3 years; annually in the patientwith osteoporosis. The identification of significantbone disease should lead to an assessment of calcium,phosphorus, magnesium, vitamin D (25-hydroxyvitamin D), and parathyroid hormone status and forthe presence of metabolic acidosis. In patients receivingPN, an assessment of the PN formula and additivesis warranted. Conventional management includesexercise, sunlight exposure, minimizing alcohol usePRACTICAL GASTROENTEROLOGY AUGUST 2014 Table 4. Short Bowel Syndrome-AssociatedComplications Central venous catheter-relatedo Infectiono Occlusiono Breakageo Central vein thrombosis Parenteral nutrition-relatedo Hepatico Biliary Bowel anatomy-relatedo Malabsorptive diarrheao Malnutritiono Fluid and electrolytedisturbanceso Micronutrient deficiencyo Essential fatty aciddeficiencyo Small bowel bacterialovergrowtho D-lactic acidosiso Oxalate nephropathyo Renal dysfunctiono Metabolic bone diseaseo Acid peptic diseaseo Anastomotic ulceration/strictureand eliminating tobacco use. Calcium, magnesium andvitamin D replacement and correction of metabolicacidosis should be implemented as needed. Giventhe very poor bioavailability of bisphosphonates,intravenous agents are preferred in SBS.28 Collaborationwith an endocrinologist is encouraged.Liver Dysfunction and CholelithiasisHepatobiliary complications including steatosis,cholestasis and cholelithiasis occur commonly in35
Short Bowel Syndrome in Adults – Part 1NUTRITION ISSUES IN GASTROENTEROLOGY, SERIES #132SBS patients and result both from contributions ofthe altered bowel anatomy and the PN required forsupport. For this reason, ‘intestinal failure-associatedliver disease’ is the preferred term to describe thesecomplications. Steatosis is more commonly seen inadults while cholestasis occurs more often in children;both can progress to end-stage liver disease. Themechanisms underlying the development of steatosisand cholestasis differ although overlap occurs.29 Theprovision of 1 g/kg/day of parenteral lipids and thepresence of chronic cholestasis have been associatedwith the development of complicated liver disease.30Particularly in those with rapid worsening of liver tests,sepsis should be considered as should medications,supplements, other toxins, lack of enteral stimulation,altered bile acid metabolism, SB bacterial overgrowth,biliary obstruction, and co-existing chronic liver diseaseincluding viral, autoimmune and metabolic disorders.The composition of the PN should also be consideredas excesses (energy content, dextrose, fat emulsion,methionine), deficiencies (choline, essential fatty acids,carnitine, taurine, glutathione) and duration of infusion(continuous versus cyclical) may contribute. The typeof lipid emulsion (e.g., soybean-based [Intralipid,Fresenius Kabi or Liposyn, Abbott Laboratories],n-3 fish oil-based [Omegaven, Fresenius Kabi],combination of soybean, medium-chain triglycerides,olive oil and fish oil [SMOF, Fresenius Kabi]) mayalso be important. In the U.S., only the soybean-basedlipid emulsion is currently available except by approvalunder a Food and Drug Administration investigationalnew drug application. Correction of an identified causeor alteration in PN or lipid composition often leads toan improvement in the liver tests. The clinical utility ofursodeoxycholic acid appears limited in this setting.29In those who continue to progress, considerationof intestinal transplantation (with or without livertransplantation) should be given.Cholelithiasis, usually cholesterol stones, occursin up to 40% of adults with SBS; the formation ofbiliary sludge is even more common.31 The predominantfactor contributing to stone development is thereduced concentration of bile acids due to t
Short Bowel Syndrome in Adults – Part 1 PRACTICAL GASTROENTEROLOGY AUGUST 2014 31 Short Bowel Syndrome in Adults – Part 1 Physiological Alterations and Clinical Consequences Small Bowel The proximal 100 to 150 cm of the jejunum is the primary site of carbohydrate, protein and water-so
Revenge of the Cyst –Part II NUTRITION ISSUES IN GASTROENTEROLOGY, SERIES #55 Joe Krenitsky, MS, RD, Nutrition Support Specialist; Diklar Makola, MD, MPH, PhD, Gastroen-terology Fellow; Carol Rees Parrish MS, RD, Nutrition Support Specialist all at Digestive Health Center of Excellence, University of Virginia Health System, Charlottesville, VA.
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WEST COAST HOTEL CO. v. PARRISH. 379 Syllabus. WEST COAST ttOTEL CO. v. PARRISH ET AL. APPEAL FROM THE SUPREME COURT OF WASHINGTON. No. 293. Argued December 16, 17, 1936.-Decided March 29, 1937. 1. Deprivatio
WEST COAST HOTEL CO. v. PARRISH. 379 Syllabus. WEST COAST ttOTEL CO. v. PARRISH ET AL. APPEAL FROM THE SUPREME COURT OF WASHINGTON. No. 293. Argued December 16, 17, 1936.-Decided March 29, 1937. 1. Deprivation of liberty to contract is forbidden by the Constitution if without due process of law; but restraint or regulation of this .
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