Intestinal Failure

Question 1

Intestinal Failure

Answer 1

• Definition: requiring TPN for >3 months.
• 200-300 children PN dependent.
• 5 year survival: 80-95%. Reasons for death: liver disease, sepsis.

Question 2

Etiologies of SBS

Answer 2

• Atresia (30%)
• Volvulus (10%)
• Gastroschisis (17%)
• NEC (43%)

Question 3

Neuromuscular etiologies of SGS

Answer 3

• Aganglionosis
• Motility disorders
• Megacystitis-microcolon intestinal hypo peristalsis syndrome (MMIHS)

Question 4

Intestinal epithelium etiologies of SGS

Answer 4

• Congenital enteropathies: Microvillus inclusion disease, Tufting enteropathy
• Autoimmune enteropathy.

Question 5

Intestinal adaptation

Answer 5

• rapid response which continues for at least 12 months
• transient hyperacidity after resection
• villus lengthening, crypt hyperplasia, absorptive function improves.
• Diameter of small bowel increases but not length.
• Complex mechanisms: growth factors (EGF), Growth hormone, glucagon-like peptide-2 (GLP-2)

Question 6

GLP-2 in intestinal adaptation

Answer 6

• hormone secreted by intestinal L cells (present in ileum and colon).
• Release of GLP-2 stimulated by meal. causes villus and crypt hyperplasia, inhibits gastric acid secretion stimulates intestinal blood flow, improves intestinal barrier function, enhances nutrient and fluid absorption.

Question 7

Intestinal adaptation

Answer 7

• SGS malabsorption not solely due to loss of surface area or enterocyte mass. Other factors: transit time, motility disorder, SBBO.

Question 8

assessment of SGS

Answer 8

• patients with jejunocolic anastomosis: bile salt induced diarrhea and SBBO.
• patients with jejunostomy have faster transit time.
• Patients with jejunoileal anastomosis have best prognosis.

Question 9

poor prognosis

Answer 9

• less than 30cm of small bowel.
• lack of enter-colonic continuity.
• SI length is ~200cm in a little one

Question 10

How to feed

Answer 10

• breast milk: growth factors, glutamine, microbiota.
• CHO: generally avoided due to osmotic forces and bacterial overgrowth.
• Fat: combo of MCT and LCT to enhance absorption and adaptation.
• Protein: initially amino acid or hydrolyzed formula to diminish immune responses.
• Controversies: continuous vvs bolus, oral vs GT.

Question 11

Carbohydrates

Answer 11

Pros: monosaccharides enhance Na and water absorption.
Cons: avoid CHO malabsorption.
- Short chain fatty acids (SCFAs): colonic salvage of energy, direct source of nutrients for colonocytes.
-Pectin and guar gums: slows gastric emptying, enhances intestinal adaptation.
- D-lactic acidosis: bacterial fermentation.

Question 12

D lactic acidosis: patients who have large amount of colon and CHO malabsorption

Answer 12

Colonic bacteria will metabolize CHO to both L lactate and D lactate. Mammals cannot metabolize D lactate, this builds up in blood stream, presents with classic features of encephalopathy. (elevated anion gap). Tx: NPO, antibiotics. can occur repeatedly.

Question 13

Lipids

Answer 13

-Stimulates GLP2 (stimulates intestinal adaptation).
- reduces transit time.
- enhances intestinal adaptation LCT >MCT.

Question 14

SBBO

Answer 14

• SBBO causes bacterial translocation, malabsorption, bile salt deconjugation.
• Diagnosis: unreliable in intestinal failure, breath hydrogen-fasting >20ppm H2 (use glucose or lactulose).
  -therapeutic trial of antibiotics.

Question 15

TPN Complications

Answer 15

• TPN associated liver disease (definition: direct bilirubin >2mg/dl).
• catheter related thrombosis.
• catheter related sepsis
• metabolic (abnormal growth, bone disease).

Question 16

IFALD Histology

Answer 16

Nonspecific
- intracellular and canalicular cholestasis
- interlobular bile duct proliferation
- portal and lobular inflammation
- portal fibrosis > lobule > bridging > cirrhosis

Question 17

IFALD Histology slide

Answer 17

Question 18

Citrulline

Answer 18

• non-protein amino acid
• produced only by enterocytes.
• poorly represented in food (except watermelon and breast milk).
• used as a marker for intestinal mass.
• not a marker of enterocyte function.
  high sensitivity/specificity of being able to wean off TPN

Question 19

Indications for intestinal transplantation

Answer 19

• ESLD
• Loss of vascular access
• Life threatening catheter related sepsis.
• Congenital enteropathies
• Motility disorders.
• CIT <20micromole

Question 20

Intestinal transplantation

Answer 20

• Liver-SI, Multivisceral, Modified MV.
• isolated SI transplant: higher rejection rate.
• immunosuppression: monoclonal: alemtuzumab, basiliximab.
  polyclonal: anti-thymocyte globulin (ATG)

Question 21

IFALD Etiology

Answer 21

RF:
- prolonged PN, preterm, SGS, surgical procedures.
- lack of enteral intake
- intestinal anatomy
- sepsis: SBBO, CVL infections

Question 22

Intralipids

Answer 22

• Pro-inflammatory metabolites of n-6 fatty acids
• Anti-inflammatory metabolites of n-3 fatty acids.
• Phytosterols: high concentrations in soy based emulsions.

Question 23

IFALD Etiology

Answer 23

• Intestinal injury and SBBO: bacterial translocation. TLR4 dependent Kupffer cell activation by LPS
• Phytosterols: decreased BSEP expression, cholestasis
  Combo results in cholestasis, hepatocyte injury, apoptosis and inflammation.

Question 24

TPN Lipids

Answer 24

• Intralipid (soy based)
• Omegaven (fish oil)
• SMOF: 30% Soy, 30 % MCT
  25% olive oil, 15% fish oil

Question 25

Polyunsaturated Fatty Acids

Answer 25

Omega 3: alpha linolenic: EPA, DHA (good lipids, anti-inflammatory). Omega 6: alpha-linoleic: Arachidonic acid (pro inflammatory). Omega 6 alpha linoleic acid can convert to Omega 9 (oleic acid) which can convert to Mead acid - Essentially fatty acid deficiency: defined as omega 6 deficiency.

Question 26

Polyunsaturated fatty acids

Answer 26

Question 27

Essential Fatty Acid Deficiency

Answer 27

- Triene: Tetrene Ratio. -Lack of linoleic acid. Elevated mead acid compared to arachidonic acid ratio.

Question 28

IFALD Management

Answer 28

- avoid overfeeding. - use trophamine for infants. - limit Copper and Mn. - supplement with carnitine - USDA - PO abx against gut anaerobic bacteria - Push enteral feeding including oral feeding - strict catheter care/ ETOH locks. - cycling. - lipid minimization <1.0g/kg/day, vs fish oil emulsion.

Question 29

EFAD

Answer 29

- scaly rash, thrombocytopenia, FTT - linoleum acid deficiency increases production of mead acid via Omega 9 pathway. Triene: Tetraene ratio <0.05 is normal.

Question 30

CVL complications

Answer 30

-bacterial sepsis, life threatening, - fever, admission, culture, 48 hour antibiotics, antibiotic/ethanol lock for treatment.

Question 31

Micronutrient deficiencies in intestinal failure

Answer 31

- Selenium: cardiac fibrosis, hypopigmentation, muscle weakness. - Copper: neutropenia, anemia, bone abnormalities - Zinc: acrodermatitis enteropathica, FTT, diarrhea. - Iodine:

Question 32

Micronutrient Toxicities

Answer 32

- Manganese (basal ganglia deposition) - Copper: hepatotoxicity - Aluminum: bone deposition

Question 33

Micronutrients after successful intestinal rehab

Answer 33

- Fat soluble vitamins and B12 - loss of TI resulting in loss of IR/Vitamin B12 receptors and apical sodium-dependent bile salt transporter - multiple deficiencies have been reported: Vitamin D, Vitamin E, Vitamin B12, Zn, Fe.

Question 34

Vitamin E deficiency

Answer 34

Peripheral neuropathy

Question 35

Intestinal lengthening procedures

Answer 35

- Bianchi: surgery to split mesentery. - STEP: Si must be dilated: doubles intestinal length while not increasing surface area. Decreases transit time, decreases SI diameter: decreases SIBO

Question 36

Teduglutide

Answer 36

- Human GLP-2: approved for adult with SBS: rapid increase in fluid absorption. - daily Sub-q injection. Side effects: bowel obstruction, fluid overload, ? colonic polyps, increased absorption of medication.