Fig. 7.5 Mild to moderate changes of CF in the pancreas. The ducts are dilated and plugged with eosinophilic mucin, and the parenchymal glands are atrophic and replaced by fibrous tissue.
Fig. 7.6 Lungsofapatientwhodiedofcysticfibrosis.Extensivemucousplugginganddilationofthetracheobronchialtreeareapparent.Thepulmonaryparenchymaisconsolidatedbyacombinationofbothsecretionsandpneumonia;thegreenishdiscolorationistheproductofPseudomonas infections.(Courtesy of Dr. Eduardo Yunis: Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania.) bronchiectasis.Developmentoflungabscessesiscommon.Staphylococcus aureus, Haemophilus influenzae, andPseudomonas aeruginosa arethethreemostcommonorganismsresponsibleforlunginfections.Evenmoresinisteristheincreasingfrequencyofinfectionwithanotherpseudomonad,Burkholderia cepacia.Thisopportunisticbacteriumisparticularlyhardy,andinfectionwiththisorganismhasbeenassociatedwithfulminantillness(“cepaciasyndrome”).Theliver involvement followsthesamebasicpattern.Bilecanaliculiarepluggedbymucinousmaterial,accompaniedbyductularproliferationandportalinflammation.Hepaticsteatosis (“fattyliver”)isacommonfindinginliverbiopsies.Withtime,cirrhosisdevelops,resultingindiffusehepaticnodularity.Suchseverehepaticinvolvementisencounteredinlessthan10%ofpatients.Azoospermia andinfertility arefoundin95%oftheaffectedmaleswhosurvivetoadulthood;bilateral absence of the vas deferens isafrequentfindinginthesepatients.Insomemales,thismaybetheonlyfeaturesuggestinganunderlyingCFTRmutation.
In few childhood diseases are clinical manifestations as protean as those of CF (
Fig. 7.4 ). Approximately 5% to 10% of the cases come to clinical attention at birth or soon after because of an attack of meconium ileus. Exocrine pancreatic insufficiency occurs in a majority (85% to 90%) of patients and is associated with “severe” CFTR mutations on both alleles (e.g., ΔF508/ΔF508). By contrast, 10% to 15% of patients, who have one “severe” and one “mild” CFTR mutation, or two “mild” CFTR mutations, retain sufficient pancreatic exocrine function that enzyme supplementation is not required—the pancreas-sufficient phenotype. Pancreatic insufficiency is associated with malabsorption of protein and fat and increased fecal loss. Manifestations of malabsorption (e.g., large, foul-smelling stools; abdominal distention; poor weight gain) appear during the first year of life. The faulty fat absorption may induce deficiency states of the fat-soluble vitamins, resulting in manifestations of avitaminosis A, D, or K. Hypoproteinemia may be severe enough to cause generalized edema. Persistent diarrhea may result in rectal prolapse in as many as 10% of children with CF. The pancreas-sufficient phenotype usually is not associated with other gastrointestinal complications, and in general, these patients demonstrate excellent growth and development. In contrast to exocrine insufficiency, endocrine insufficiency (i.e., diabetes) is uncommon in CF and occurs late in the course of the disease especially with improved survival of patients with CF.