Intestinal Failure and Short Gut Syndrome Flashcards
Intestinal Failure Definition
Requiring TPN for >3 months.
Prevalence 1:1 million.
Causes of death: liver disease and sepsis
Etiologies of SBS total.
- Atresia: 30%
- Volvulus: 10%
- Gastroschisis 17%
- NEC 43%
Neuromuscular disorders:
- Aganglionosis
- Motility Disorders
- Megacystis-microcolon intestinal hypoperistalsis syndrome (MMIHS)
Intestinal epithelium:
- Congenital enteropathies: Microvillus inclusion disease; Tufting enteropathy.
- Autoimmune enteropathy
Neuromuscular disorders causing SBS:
- Aganglionosis
- Motility Disorders
- Megacystis-microcolon intestinal hypoperistalsis syndrome (MMIHS)
Intestinal epithelium disorders causing SBS:
- Congenital enteropathies: Microvillus inclusion disease; Tufting enteropathy.
- Autoimmune enteropathy
Intestinal adaptation: SBS
- Rapid response: continues for at least 12 months.
- Transient hyperacidity
- Increase absorption by expansion of mucosal surface area
- Villus lengthening, crypt hyperplasia, absorptive function improves
- Diameter of SB increases but not length.
- Complex mechanisms: growth factors (EGF), Growth hormone. Glucagon-like peptide -2 (GLP-2)
GLP-2 in intestinal adaptation
- Hormone secreted by intestinal L cells: ileum and colon.
- Release of GLP-2 stimulated by meal:
- causes villus and crypt hyperplasia,
- inhibits gastric acid secretion, intestinal motility
- stimulates intestinal blood flow, improves intestinal barrier function
- enhances nutrient and fluid absorption
Assesment of patient with SBS:
Bowel anatomy:
- Jejunocolic anastomosis problematic with bile salt induced diarrhea and SBBO.
- Jejunostomy: fast transit time.
- Jejunoileal anastomosis with intact ICV and colon: best prognosis.
Poor prognosis signs:
<30cm of small bowel.
- Lack of entero-colonic continuity
- 40% of kids with <40cm SI and no ICV with TPN dependent at 8 years of age.
Enteral Nutrition with SGS
- Breast milk: growth factors, glutamine, microbiota.
- CHO: generally avoided due to osmotic forces and bacterial overgrwoth.
- Fat: combination of MCT and LCT to enhance absorption and adaptation.
- Protein: initially amino acids or hydrolyzed recommended to diminish immune responses.
Carbohydrates
Pros: monosaccharides enhance Na and water absorption.
Cons: avoid CHO malabsorption.
SCFA: colonic salvage of energy, direct source of nutrients for colonocytes.
Pectin and guar gums: slow gastric emptying, enhances intestinal adaptation.
D-lactic acidosis: bacterial fermentation. presentation: encephalopathic, elevated anion gap. Treatment: NPO, antibiotics.
Lipids
- Stimulates GLP-2, stimulates intestinal adaptation
- reduces transit time
- enhances intestinal adaptation: LCT>MCT
SBBO
- Bacterial translocation, malabsorption, bile salt deconjugation.
- Diagnosis: unreliable in intestinal failure. Direct culture of intestinal contents: not reproducible. Breath hydrogen fasting >20 ppm H2. Glucose or lactulose. Therapeutic trial.
TPN Complications
- IFALD: Direct bili >/= 2mg/dl
- Catheter related thrombosis/sepsis
- Metabolic: abnormal growth, bone diesease
IFALD Histo
- Intracellular and canalicular cholestasis
- interlobular bile duct proliferation
- Portal and lobular inflammation
- Portal fibrosis > Lobule > Bridging > Cirrhosis
Citrulline
-Produced only by enterocytes
-Nonprotein amino acid, circulated in the blood. Is a bypass in arginine metabolism.
Can be a marker for intestinal mass (prognostically helpful). Not a marker of enterocyte function.
Intestinal transplantation indications
- ESLD
- Loss of vascular access
- Life threatening catheter related sepsis
- Congenital enteropathies
- Motility disorders
- Citrulline <20 microM
Versions of Intestinal Transplant
- Liver and SI
- Isolated SI has a higher rejection rate.
- Multivisceral: pancreas, gallbladder, liver, SB
- Modified Multivisceral. Liver is spared (used in motility disorders).
Immunosuppression:
- Monoclonal -alemtuzumab, basiliximab
- Polyclonal-anti-thymocyte globulin
Graft survival: 70% at 1 year, 50% at 5 years, 41% at 10 years.
New strateies
- minimize IFALD: allow intestinal adaptation
- new surgical techniques
- limit catheter related complications: ETOH locks, antibiotic locks.
- enhance intestinal adaptation
- effectively treat SBBO
IFALD Risk Facotrs
- Pre-term
- SGS
- Surgical Procedures
- Lack of enteral intake
- Intestinal anatomy
- Sepsis: SBBO, CVL infections
IFALD and lipids
- Pro-inflammatory metabolites of omega-6 fatty acids
- Anti-inflammatory metabolites of omega-3 fatty acids
- Phytosterols: high concentrations in soy based emulsions.
IFALD Etiology
- Intestinal injury and SBBO: Bacterial translocation, then TLR4 dependent Kupffer cell activation via LPS
- Phytosterols: decreased BSEP expression, cholestasis.
Combination results in cholestasis, hepatocyte injury, apoptosis and inflammation.
Lipid options
Plant: soy based emulsions (intralipid)
Omegaven: fish oil
Mixture: SMOF: 30% soy, 30% MCT, 25% olive oil, 15% fish oil.
Polyunsaturated Fatty Acids
Omega 3: Linolenic. EPA and DHA Anti-inflammatory
Omega 6: Linoleic. Arachidonic Acid. Pro-inflammatory. (essential fatty acid deficiency).
Omega 9: Oleic. Mead Acid
Essential Fatty Acid Deficiency
- Lack of Omega-6 Linoleic acid. When this occurs, Omega-9 produces more Mead acid, this is the basis of the triene-tetrene ratio.
EFA Metabolism
IFALD Management
- Avoid overfeeding
- Limit Cu and Mn
- Supplement with Carnitine
- Ursodiol
- PO antibiotics against gut anaerobic bacteria
- Lipid minimization <1.0g/kg/day vs fish oil emulsion
- Cycling
- Strict catheter care/ETOH locks
- Push enteral feedings
Essentially Fatty Acid Deficiency
- Sxs: Scaly rash, Thrombocytopenia, FTT
- Linoleic acid deficiency increases production of Mead Acid via Omega 9 pathway.
- Triene: Tetraene ratio <0.05 is normal.
Micronutrient Deficiencies in IF
- Selenium Deficiency: cardiac fibrosis, hypopigmentation, muscle weakness.
- Copper Deficiency: Neutropenia, anemia, bone abnormalities.
- Zinc Deficiency: Acrodermatitis enteropathica, FTT, diarrhea
- Iodine
Selenium Deficiency
- Selenium Deficiency: cardiac fibrosis, hypopigmentation, muscle weakness.
Copper Deficiency
- Copper Deficiency: Neutropenia, anemia, bone abnormalities.
Zinc Deficiency
- Zinc Deficiency: Acrodermatitis enteropathica, FTT, diarrhea
Micronutrient Toxicities
- Manganese: basal ganglia deposition
- Copper-hepatotoxicity
- Aluminum: bone deposition.
Micronutrients after successful intestinal rehab
- Fat soluble vitamins and B12 in patients who have lose their ileum.
Vitamin E deficiency
Peripheral neuropathy
Intestinal Lengthening Procedures
STEP: SI dilated, doubles intestinal length while not increasing surface area. Decreases transit time and decreases SI diameter, decreasing SBBO.
Teduglutide
Human GLP-2 short half life: 7 minutes
SIngle amino acid substitution for GLP-2
- Daily sub-q injection.
Rapid increase in fluid absorption
Side effects: bowel obstruction, fluid overload, increased absorption of medication, ?colonic polyps?
Bad prognostic feature:
Gastroschisis: injured by amniotic fluid and ischemia.
