Download intestinal adaptation

Case Conference
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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.
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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,
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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
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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
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Infants—normal length of intestine is 250cm at term.
– <75cm at risk for SBS
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Adults---small intestine is about 480 cm
– Less than 180cm of bowel REMAINING are at risk for SBS
– This is an approximation
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Several Factors contribute to determining intestinal function
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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
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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.
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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
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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
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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
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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
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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
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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
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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
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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.
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Intestinal adaptation—ileum has a greater capacity for intestinal adaptation as
compared to jejunum**
Loss of ICV
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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
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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
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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
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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
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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
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Gastrin elevation present in pts with SBS –can lead to ulcer disease or esophagitis
-recommend h2 blocker or ppi
Microbiome
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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
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Liver Disease associated with TPN can be a significant problem
Steatosis, Steatohepatitis, cholestasis
Can lead to cirrhosis and portal htn
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Cholestatic liver disease more common in pts with SBS than many other patients on
TPN
Severity of liver Disease related in part to
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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
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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
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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
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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
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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
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Bifidobacterium, Lactobacillus, Eubacterium
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Normally L-Lactate is produced.
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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
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Summary
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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
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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
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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
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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
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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
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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
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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
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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
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Pharmacologic Therapy
Octreotide reduces fluid losses
– Can predispose to gallstones and can interfere with adaptation
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Loperamide---can decrease stool output and can be helpful in pts without small
bowel bacterial overgrowth
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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.
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– 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
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Pts with SBS who develop life threatening complications related to TPN
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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
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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.
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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
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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?
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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
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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
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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.