Pediatrics Grand Rounds University of Texas Health Science Center at San Antonio

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THE WORLD OF CYSTIC

FIBROSIS GASTRO INTESTINAL AND NUTRITIONAL

CHALLENGES

Ruba Abdelhadi, MD

Lisa Matasovsky, PNP

Donna Beth Willey Courand, MD

Objectives

The CFTR gene mutation, Pathogenesis

Recent advances in diagnosis and treatment

Gastointestinal Manifestations

Nutritional Challenges and Complications

Treatment, nutritional rehabilitation, and controversies

Sixty Five Roses !

Mucoviscidosis

Transmembrane Conductance

Regulator, CFTR

Dr Dorothy Hansine

Anderson

Andersen DH. Cystic fibrosis

of the pancreas and its

relation to celiac disease: a

clinical and pathological

study. Am J Dis Child 1938;

56:344-399 Courtesy of the National Library of Medicine

picture of Dorothy Hansine Andersen

Courtesy of the Library of Congress. Rights Advisory: No information on creator or on reproduction rights found with the image, 1998.

Professor Monty Losowsky Harry Shwachman Dr Paul di Sant'Agnese Dr John Mangos

Dr Jean Feigelson Dr Charlotte Anderson Professor Mary Ellen Avery Professor Flensborg

Flume PA., O'Sullivan BP, Robinson KA, Goss CH, Mogayzel PJ Jr,

Willey-Courand DB, Bujan J, Finder J, Lester M, Quittell L,

Rosenblatt R, Vender RL, Hazle L, Sabadosa K, Marshall B. Cystic

Fibrosis Foundation, Pulmonary Therapies Committee. Cystic

fibrosis pulmonary guidelines: chronic medications for

maintenance of lung health. Amer J Respir Crit Care Med 2007;

176: 957-969

Flume PA, Robinson KA, O'Sullivan B, Finder JD, Vender RL,

Willey-Courand DB, White TB, Marshall BC. Cystic fibrosis

pulmonary guidelines: airway clearance therapies. Clinical

Practice Guidelines for Pulmonary Therapies Committee.

Respiratory Care 2009; 54:522-537

Pediatrics Grand Rounds University of Texas Health Science Center at San Antonio

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Why the lungs and pancreas?!

Nelson essentials, text book of pediatrics. Kliegman, Robert; Richard M Kliegman (2006(2006).

Nelson essentials of pediatrics. St. Louis, Mo: Elsevier Saunders. ISBN 0-8089-2325-0.

Why the lungs and pancreas?!

Respiratory tract

Sinusitis

Nasal Polyps

Pancreatic exocrine

CF related Diabetes

Gastrointestinal

Hepatobiliary

Sweat glands

Exocrine tissues

Reproductive system

Coagulation defect

CFTR Courtesy of the NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health

Pathophysiology Molecular Consequences of CFTR Mutations

Courtesy of Carol D. Guzé, Ph.D. Medical Geneticist, ABMG, - Human Genetics

Courtesy of Carol D. Guzé, Ph.D. Medical Geneticist, ABMG, - Human Genetics

Molecular Consequences of CFTR Mutations

Courtesy of Carol D. Guzé, Ph.D. Medical Geneticist, ABMG, - Human Genetics

Molecular Consequences of CFTR Mutations

Pediatrics Grand Rounds University of Texas Health Science Center at San Antonio

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Pathophysiology Molecular Consequences of CFTR Mutations

Courtesy of Carol D. Guzé, Ph.D. Medical Geneticist, ABMG, - Human Genetics

Genotypic-Phenotypic Correlation

H Witt, Kinderklinik, Charité-Campus Virchow-Klinikum, Humboldt-Universität, Augustenburger Platz 1, D-13353 Berlin,

Germany. Chronic pancreatitis and cystic fibrosis. Gut2003;52:ii31-ii41 doi:10.1136/gut.52.suppl_2.ii31

Courtesy of Louise Schnaufer, MD, Children's Hospital of Philadelphia, PA. The Radiological Society of North America

Meconium Ileus Courtesy of Eduardo Rucelli, MD, Children's Hospital of Philadelphia, PA. The Radiological Society of North America

Meconium Ileus

Immunoreactive trypsinogen

LIMITATIONS

False negative if complete pancreatic fibrosis

Meconium Ileus

Pancreatic sufficient CF

Heterozygous carriers

Degree of elevation does not correlate with severity

A Progressive Pancreatic disease

Glandular atrophy

Dystrophic calcification

Courtesy of Eduardo Rucelli, MD, Children's Hospital of Philadelphia, PA. The Radiological Society of North America

Fatty replacement

Pediatrics Grand Rounds University of Texas Health Science Center at San Antonio

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Andersen DH, Cystic fibrosis of the pancreas and its relation to celiac disease:

a clinical and pathological study. Am J Dis Child 1938; 56:344-399.

Non-CF newborn CF newborn

LIMITATIONS

Pancreatic Enzyme Replacement Therapy

Shelf Life

Storage temperature

FDA approval

Accuracy of dosage

Efficacy pH dependant

Timing with meals

Adequacy to amount of fat ingested

Porcine protein allergy

Religious beliefs

Oral ulcers – no longer a challenge

Courtesy of the Children's Hospital of Philadelphia, PA. The Radiological Society of North America

Fibrosing Colonopathy

Smyth RL, van Velzen D, Smyth AR, Lloyd DA, Heaf DP. Strictures of the ascending colon in cystic fibrosis and high strength pancreatic enzymes. Lancet 1994; 343:85-86.

Friedman JP, FitzSimmons SC. Colonic strictures in patients with cystic fibrosis: results of a survey of 114 cystic fibrosis care centers in the United States. J Pediatr Gastroenterol Nutr 1996; 22:153-156).

Smyth RL, Carty H, Heaf DP. Colonic strictures in cystic fibrosis. Arch Dis Child. 1995

August; 73(2): 184.

Fibrosing colonopathy

Hepatobiliary Abnormalities

Hepatic Steatosis

Bliary Cirrhosis

Portal Hypertension

Esophageal varices

Chronic liver disease

CBD stricture

Cholelithiasis

Courtesy of Eduardo Rucelli, MD, Children's Hospital of Philadelphia, PA

Hepatobiliary Abnormalities

Hepatic steatosis

Pediatrics Grand Rounds University of Texas Health Science Center at San Antonio

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Courtesy of Eduardo Rucelli, MD, Children's Hospital of Philadelphia, PA

Hepatobiliary Abnormalities

Biliary cirrhosis

Courtesy of Eduardo Rucelli, MD, Children's Hospital of Philadelphia, PA

Hepatobiliary Abnormalities

Biliary cirrhosis

1996 The Radiological Society of North America

- Portal Hypertension

- Esophageal varices

- Chronic liver disease

- CBD stricture

Hepatobiliary Abnormalities CF related Liver Disease

TPN related cholstasis

Line sepsis

Hapatotoxic medications

Malignancy

Risk of malignancy

Carcinomas of the digestive tract

cancers of the esophagus, stomach, small bowel, colon, liver, biliary tract,

pancreas, and rectum

Differential localization and expression of the cystic fibrosis transmembrane

regulator gene

Ancillary effects of CF

Barrett esophagus

Gallstones

Gut epithelial cell turnover

Antioxidant deficiencies

Swinson CM, Slavin G, Coles EC, Booth CC. Coeliac disease and malignancy. Lancet 1983; 1:111-115

Nutrition

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Pediatrics Grand Rounds University of Texas Health Science Center at San Antonio

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Nutrition

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Nutrition Nutrition

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Nutrition Nutrition

Nutrition

Nutrition

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Nutrition Nutrition

Nutritional Challenges

↑ caloric expenditure in CF

exacerbation

↑ metabolic rate

↑ nutritional requirements

↑ gastrointestinal losses

Chronic diarrhea in short

bowel secondary to SBS

Small bowel bacterial

overgrowth

GERD

↓ oral intake

↓ intestinal absorption in

pancreatic insufficiency

↓ / Dysmotility

DIOS

Chronic constipation

↓ Oral motor skills – mastication

Oral aversion

Distal Intestinal Obstruction Syndrome

radRounds Radiology Network, New York http://www.radrounds.com/profile/radRounds_Radiology_Network

Pediatrics Grand Rounds University of Texas Health Science Center at San Antonio

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Short Bowel Syndrome

Location

Extent

Functionality

Viscid mucus

Gastric hypersecretion

Malabsorption Small Bowel Bacterial Overgrowth

Small Bowel Bacterial Overgrowth

Structural abnormalities, SBS

Decreased gastric acidity

Reduced peristaltic activity

Mucosal damage or atrophy

Bowel mucosal integrity and mucin

Impaired immunity, Igs

Malabsorption of bile acids, fats,

carbohydrates, proteins, vitamins

Damage to the lining of the luminal

surface by bacteria

Transformation of nutrients into toxic

metabolites

DIOS

Decreased function of the enterocytes

Subsequent malabsorption

Secretory diarrhea

Deconjugation of bile acids

Steatorrhea

Carbohydrate malabsorption

CHA fermentation

Reduced pH

Osmotic diarrhea

Colonic mucosa water secretion

Small Bowel Bacterial Overgrowth

Structural abnormalities, SBS

Decreased gastric acidity

Reduced peristaltic activity

Mucosal damage or atrophy

Bowel mucosal integrity and mucin

Impaired immunity, Igs

Malabsorption of bile acids, fats,

carbohydrates, proteins, vitamins

Damage to the lining of the luminal

surface by bacteria

Transformation of nutrients into toxic

metabolites

DIOS

Decreased function of the enterocytes

Subsequent malabsorption

Secretory diarrhea

Deconjugation of bile acids

Steatorrhea

Carbohydrate malabsorption

CHA fermentation

Reduced pH

Osmotic diarrhea

Colonic mucosa water secretion

EPITHELIAL CELLS DISTENDED WITH MUCUS

Courtesy of Eduardo Rucelli, MD, Children's Hospital of Philadelphia, PA. The Radiological Society of North America

Probiotics in Small Bowel Bacterial Overgrowth

WH KU, DCY LAU, KF HUEN. Probiotics Provoked D-lactic Acidosis in Short Bowel

Syndrome: Case Report and Literature Review. HK J Paediatr (new series) 2006;11:246-254.

Pediatrics Grand Rounds University of Texas Health Science Center at San Antonio

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Probiotics in Small Bowel Bacterial Overgrowth

Minna K. Salminen,Soile Tynkkynen, Hilpi Rautelin, Maija Saxelin, Martti Vaara, Petri Ruutu, Seppo Sarna,

Ville Valtonen, and Asko Ja rvinen. Lactobacillus Bacteremia during a Rapid Increase in Probiotic Use of Lactobacillus

rhamnosus GG in Finland. • Clinical Infectious Diseases 2002; 35:1155–60

http://www.scientificamerican.com/article.cfm?id=cf-video-patients-explain-lving-cystic-fibrosis

Primum non nocere

Fibrosing Colonopathy

Proton Pump Inhibitors

Intestinal Unstirred Water Layer – NAC – PEG 3350

Hepatic Steatosis

Probiotics – Line Colonization

Survival - Quality of Life

PGD – CVS – Amniocentesis

Ethics of Termination

Ruba Abdelhadi, M.D.

Thank You!