Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Case Conference • 51 year old woman with longstanding stricturing crohn’s disease(small bowel) on chronic steroids, short gut syndrome from multiple prior ileal resections presents to clinic. Pt is on chronic tpn and has been on TPN(non-compliant) for years. She has 6-8 loose watery bowel movements a day and that is non bloody. She does still do some po intake. She has been losing weight and now weighs 98 pounds. • • • • • Surg: 6 ileal resections, nephrectomy, appendectomy, hysterectomy. Pmh: kidney stones, crohns dz, multiple line infections, narcotic dependency Home TPN since 2007 Social: +tobacco Meds: prednisone 10, ms contin, TPN, lexapro, B12, • • Vitals: weight 93 pounds Exam: cachectic, +surgical scars, PICC line, • Labs: Ca 7.6, • Hg 9, MCV: 78, plt: 552, – Had blood transfusion in September of 2 units – Prior Hg 6.8 and mcv of 68 • albumin 3 • Pt cannot afford octreotide • She has tried lomotil and immodium Short Bowel Syndrome • Short bowel syndrome is a malabsorptive state that may follow massive resection of the small intestine. • Significant amount of malabsorption of both micro and macronutrients • Most common cause of intestinal failure • Usually from Crohn’s dz, malignancy, radiation, or vascular event (mesenteric arterial embolism, venous thrombosis, etc) • Functional SBS can occur in cases of severe malabsorption where small bowel length intact (refractory sprue, chronic intestinal pseudoobstruction,) Short Bowel Syndrome • • • Patients can be divided into 2 groups Intact colon and Non-intact colon Colon can become an important digestive organ----absorbs sodium, water, and energy from short chain fatty acids Incidence SBS • Incidence is 2 per million. • This is largest group of patients that require home TPN – 35% of home TPN patients SBS---Anatomy Lesson • Infants—normal length of intestine is 250cm at term. – <75cm at risk for SBS • Adults---small intestine is about 480 cm – Less than 180cm of bowel REMAINING are at risk for SBS – This is an approximation • Several Factors contribute to determining intestinal function – – – – – – Site of intestinal resection Length and Health of Remaining Bowel Presence of absence of ICV Whether the colon is present Gradual process of intestinal adaptation after surgical resection Intestinal motility Intestinal Adaptation • Symptoms associated with bowel resection are highly dependent upon the physiology of the remaining small bowel, because each segment has unique characteristics for absorption, and ability to adapt after intestinal resection. • Intestinal adaptation---refers to changes that occur after intestinal resection that tend to increase absorptive surface and capacity – Lengthening of the intestinal villi, small bowel dilation – Most intestinal adaptation occurs in the ileum – Ileum can pick up many functions of jejunum – Jejunum cannot adapt to pick up b12 and bile salts • Length of remaining bowel necessary to prevent dependence on TPN is 100cm in absence of functioning colon or 60cm in presence of completely functioning colon – Degree of adaptation and TPN dependence is highly individualized Implications of the Site of Intestinal Resection----Jejunum • • • Jejunal resection – Jejunum has long villi, large absorptive surface, highly concentrated digestive enzymes, and many transport carrier proteins – Jejunum is absorptive site for most nutrients and water soluble vitamins. Modest adaptive changes to intestinal resection – Many changes are functional(changes in transport and enzyme activity) – Not much change in absorptive area Water soluble vitamins, iron, and phosphorous predominantly absorbed in Prox Small intestine. (Most pts with sbs have intact duodenum and prox jejunum) Implications of the Site of Intestinal Resection---- Ileum • • • • • Vitamin b12 absorption---occurs in ileum in presence of intrinsic factor Resection of TI can lead to b12 def B12 malabsorption tends to occur if more than 60cm of ileum is resected Resection of Ileum can lead to disruption of Enterohepatic Circulation Can also lead to excessive absorption of oxalate, leading to kidney stone formation Disruption of Enterohepatic Circulation • Bile Salt Diarrhea----In general, when less than 100cm of TI resected, the reduction of bile salt absorption is modest and the liver can compensate by increasing the synthesis and secretion of conjugated bile salts. Fat malabsorption is modest. Malabsorbed bile salts and their metabolites stimulate colonic secretion of electrolytes and water with resultant diarrhea – Rx: Cholestyramine • Fatty Acid Diarrhea---When >100cm of TI removed, active absorptive surface for bile salts is absent resulting in a massive loss of bile salts into the colon. This loss exceeds capacity of the liver to compensate. This results in a diminished bile salt pool, resulting in a low postprandial intraluminal bile salt concentration and steatorrhea. This leads to malabsorbed fatty acids which lead to diarrhea. Can be severe and lead to malnutrition. – Rx: low fat diet. – Can be made worse with cholestyramine • In addition, cholestyramine binds to many medications, including warfarin, antibiotics, beta-blockers, diuretics, oral hypoglycemia agents, and others. Implications of the Site of Intestinal Resection---- Ileum • Ileal Brake—Unabsorbed lipids reaching the ileum cause delay in gastric emptying (the “ileal brake”), which is beneficial because it facilitates absorption of nutrients within the small intestine. Ileal resection may be associated with the loss of this compensatory mechanism, which exacerbates diarrhea observed in SBS • Fluid absorption---ileum normally re-absorbs large portion of fluid secreted by jejunum during digestive process. IF substantial portion of ileum resected, fluid and electrolyte loss will occur. • Intestinal adaptation—ileum has a greater capacity for intestinal adaptation as compared to jejunum** Loss of ICV • • ICV is important barrier to reflux of colonic material from the colon into the small intestine. It also helps regulate the passage of fluid and nutrients from the ileum into the colon Loss of ICV is generally considered an important negative predictor of ability to wean a patient from parenteral nutrition* – Reduction of small intestine transit time, which impairs nutrient absorption – Promotion of small bowel bacterial overgrowth, which may further exacerbate malabsorption of vitamin b12, fats, and further exacerbate diarrhea. Loss of Colon • • • • Colon has important role in absorption of water, electrolytes and short chain fatty acids Loss of colon in combination with extensive small bowel resection is poorly tolerated and is likely to lead to dehydration and electrolyte depletion. Thus, patients with retained colon more likely to tolerate small intestinal resection. Can undergo some adaptation Ileal Adaptation • • Ileum has shorter villi and reduced surface area compared to jejunum. However, it is capable of undergoing marked adaptation after small bowel resection Significant growth in villus surface area, as well as increases in intestinal length, diameter, and function – Leads to increased nutrient uptake Adaptation----Nutrient effects • • • Best established stimulant of intestinal adaptation is presence of nutrients in the intestinal lumen; as a result, enteral feeding is a cornerstone of management of patients with SBS – Will not occur with just TPN Adaptation enhanced when primary anastamosis(rather than ostomy) Intestinal adaptation can take up to 1-2 years to occur Gut Hormones • Gastrin, CCK, secretin, are produced by endocrine cells in prox GI tract. – Usually intact in SBS • Glucagon like peptide 1 and 2 and peptide YY are produced in ileum and prox colon. – In SBS, deficiency of these hormones can result in rapid gastric emptying and shortened intestinal transit time and hypergastrinemia. Gut Hormones • Glucagon like peptide 2---growth factor that can enhance adaptation in remaining intestine. – Induces villus hyperplasia of the ileum and jejunum within four days of administration to mice – Now approved in humans • Gastrin elevation present in pts with SBS –can lead to ulcer disease or esophagitis -recommend h2 blocker or ppi Microbiome • • • Bacterial population is altered in SBS There is Reduced bacterial diversity and lactobacillus is over-represented In pts with residual colon, colonic bacteria participate in metabolism and recovery of malabsorbed nutrients and improve overall absorption – Over representation of lactobacillus probably enhances absorption of sugars in the colon • Facultative anaerable capable of fermenting carbohydrates Chronic Complications • TPN associated----liver and biliary disease, Line infection • Malabsorptive nutritional abnormalities—metabolic bone dz, vitamin deficiencies • small bowel bacterial overgrowth – induced arthritis and colitis • D-lactic acidosis • Enteric Hyperoxaluria—leading to renal stones Liver Disease • • • Liver Disease associated with TPN can be a significant problem Steatosis, Steatohepatitis, cholestasis Can lead to cirrhosis and portal htn • Cholestatic liver disease more common in pts with SBS than many other patients on TPN Severity of liver Disease related in part to • – – – – – • • Recurrent sepsis Bacterial translocation Small bowel overgrowth Cholangitis Lack of enteral feeding also may contribute by leading to reduced gut hormone secretion, reduced bile flow, and biliary stasis Chronic cholestasis observed after 6 months in 65% of patients Complicated liver dz (HE, portal htn) developed in 42% of pts after 17 months of tpn Prevention of Liver Disease • • • No specific therapy available Try to limit less than 1g/kg/day of lipids per day Ursodeoxycholic acid---can be used and has little side effects • Gallstones---high rate of gallstone formation in those on TPN – Interruption of enterohepatic circulation – Some experts recommend cholecystectomy in patients dependent on TPN Bacterial overgrowth • • • • • • • Increased numbers of species of bacteria in small intestine Normal Colon controlled by gastric acid, pancreatic enzyme activity, enterocyte turnover, normal peristaltic activity and the ICV – Compromise of this can lead to susceptibility of bacterial overgrowth Generally, bacteria can worsen the malabsorption associated with the short bowel syndrome. Bacterial deconjugation of bile acids diminishes intestinal absorption of fatty acids – Can also lead to inflammatory reaction which can damage intestinal lining and absorptive surface causing protein loss and malabsorption – Weight loss, increase in caloric requirement Enteritis can resemble crohns disease and can even lead to arthritis Dx: usually made by breath test Rx: reduce carbohydrate load and give antibiotics • Gastric Hypersecretion – Parietal cell hyperplasia and Hypergastrinemia – Likely secondary to loss of negative feedback from inhibitors produced in resected intestine Nutrient abnormalities Calcium oxalate stones • Oxalate found in food usually precipitates as Calcium oxalate in intestinal lumen and is lost in stool. • In SBS, unabsorbed fatty acids compete with oxalate for luminal calcium. • More oxalate is absorbed in colon and is excreted in kidneys. • Leads to increased kidney stones • Calcium citrate po D-Lactic Acidosis • • • D-Lactic Acidosis This is a complication of SBS in patients with intact colon. Deliver of unabsorbed carbohydrate to the colon can lead to the production and subsequent absorption of D-lactate by gram positive anaerobes – Bifidobacterium, Lactobacillus, Eubacterium • Normally L-Lactate is produced. • Usually asymptomatic, but carbohydrate loading can produce severe metabolic acidosis and – Neurologic symptoms consisting of confusion, cerebellar ataxia, and slurred speech Treatment of D-lactic acidosis consists of acute NA bicarb and oral antibx to decrease number of D-lactate producing bacteria Low carbohydrate diet • • Summary • • • • • Chronic complications of short bowel syndrome associated with TPN Nutritional abnormities, small bowel bacterial overgrowth(and sbo induced colitis and arthritis), D-lactic acidosis, and catheter related sepsis Pts with long term TPN at risk for liver dz and cholelithiasis Diagnosis of sbo made by breath testing – Recommend dietary interventions and antibiotics – Dietary intervention involves low carbohydrate diet to reduce substrate available for bacterial metabolism Nutrient deficiencies are common once patients weaned from TPN – Recommend vitamin and mineral levels at time of discontinuation, then every 3 months for the first year, and then as needed based on the requirements for supplementation – Annual DEXA Management of SBS in Adults---Early Management • • • • • Early Management---During Early period after intestinal resection, goals are the administration of parenteral nutrition and prevention of fluid and electrolyte abnormalities. Monitor glucose frequently and insulin may need to be added to solution Large volume gastric or proximal small bowel fluid losses are relatively common in early phase Fluid protocols with na, kcl, and mg H2 blocker or ppi to suppress gastric acid hyper-secretion, may improve nutrient absorption Management of SBS in Adults---Early Management • • • Early management mostly involves replacement of fluid and electrolytes. Enteral feeding should begin once the patient stabilizes Slow introduction of enteral feeding is indicated once the patient stabilizes. We suggest continuous enteral feeding or small frequent feedings Complications should be anticipated and addressed based upon the remaining intestinal segments Enteral Feeding • 1. Composition • 2. Frequency of Feeding • 3. Tapering of parenteral nutrition Enteral feeding • • • • • Composition—many enteral formulations high in carbohydrate content. This can be a disadvantage in short bowel syndrome because carbohydrates cause a much higher osmotic load in the small intestine than fats or proteins------can lead to malabsorbed carbohydrate Protein diets containing higher fats and are better tolerated Fiber supplementation can be helpful by enhancing adaptation – May also decrease watery nature of stool by absorbing water Oxalate restriction is important in those with an intact colon and fat malabsorption to avoid stone formation Oral electrolyte solutions may be useful adjuncts especially in those with feeding tube and high output fluid losses. Enteral Feeding • Frequency of feeding—continuous enteral feeding initially advantageous. – Permits constant saturation of transport proteins taking full advantage of absorptive surface area – Facilitates intestinal adaptation Tapering TPN • Tapering Parenteral Nutrition---enteral feedings should be advanced slowly and parenteral calories decreased slowly to maintain nutrition, fluid losses, and to ensure gut adaptation – Eg: initiate enteral feedings by providing approximately 5% of the patients total daily caloric intake. Advance every 3-7 days as tolerated – Can measure success of enteral feeding by measurement of enteral fluid losses, which reflect degree of carbohydrate malabsorption. Can be measured by Testing the stool or ostomy fluid glucose. Though often unnecessary as fluid losses almost always indicated significant carbohydrate malabsorption. Tapering TPN • • Risk of nutrient deficiency is greatest during and after the transition to enteral feeding, since the degree of intestinal adaptation and the absorption of nutrients are unpredictable. Selenium, calcium, magnesium, zinc, and fat soluble vitamins K, A, D, E should be measured frequently Getting patient ready for home TPN • • • • Home environment should be clean—do not use kitchen or bathroom for tpn Have a dedicated refrigerator Support groups for Home TPN TPN should be ideally compressed into night time infusion over 10 hours Pharmacologic Therapy • • Pharmacologic Therapy Octreotide reduces fluid losses – Can predispose to gallstones and can interfere with adaptation • Loperamide---can decrease stool output and can be helpful in pts without small bowel bacterial overgrowth • Glucagon Like peptide 2---enteroendocrine peptide released in response of luminal nutrients, initiates and maintains small bowel adaptive responses to resection and improves nutrient absorption Teduglutide(Gattex)---safe and well tolerated GLP-2 analogue can reduce the volume and number of days of parenteral support required by patients with short bowel syndrome with intestinal failure. • – Side effect was increased risk of adenomas in bile duct, small, and large intestines – Colonoscopy suggested within first 6 months of staring Gattex and then, in absence of polyp, at least every 5 years. Surgical Options • Patients who develop significant persistent, recalcitrant or recurrent complications while on TPN have indication for surgery Surgical Steps Intestinal Transplantation • Pts with SBS who develop life threatening complications related to TPN – – • • Life threatening line infections, Loss of central venous access When have portal htn and cirrhosis, can get combined liver and small bowel transplant 1 year survival in adults aged 18-34 is 89% Our patient • • • IF patient cannot afford octreotide, She will try Gattex if we can get this approved She had a colonoscopy which was normal in preparation for Gattex. • • • QUESTION #1: A 45 yo male with Crohn’s disease of the ileum undergoes her third small bowel resection. Previously, she had 2 ileal resections for an ileal stricture and then recurrent disease. It is estimated that 150 cm of ileum has been resected. After the third resection and resumption of a normal diet, she develops severe diarrhea. The diarrhea has persisted for weeks. Stool studies for enteric pathogens are negative. CT enterography does not reveal any evidence of Crohn’s disease. CBC, LFT’s and renal profiles are normal. A fecal Sudan stain is positive. Colonoscopy and EGD are normal. Which of the following is the most appropriate treatment. A. Cholestyramine B. Ursodeoxycholicacid(urosodiol) C. Low fat diet D. Immodium • 40 year old male undergoes a jejunal resection of 75 cm due to small bowel obstruction. His post-op recovery is uneventful. His appetie has returned to normal and he is eating his usual normal diet. Which of the following is true? • • • • A) he will likely have chronic large volume diarrhea B) he will malabsorb fat C) he may have no malabsorptive sequelae D) he will develop folate deficiency Arginine and Citrulline • • • • Arginine and citrulline may reduce intestinal permeability May enhance intestinal adaptation when added to TPN In children with sbs, low levels of citrulline correlate with cather related bloodstream infections Citrulline level can also help predict if will have permanent vs transient intestinal failure Microbiome • • • Another cause of diarrhea in SBS is the osmotic load generated by malabsorbed carbohydrates, particularly in patients who lack a colon The use of continuous or small bowel bolus feedings reduces the osmotic load Diets high in fat may reduce osmotic load and may help stimulate gut adaptation.