undefined abnormalities in airway surface liquids may also contribute to the failure 
of lung defense. 
II.A.2.b. Gastrointestinal: 
The gastrointestinal effects of CF are diverse (21). In the exocrine pancreas, 
it appears that the absence of the CFTR Cl" channel in the apical membrane of 
pancreatic ductal epithelia impairs the activity of an apical membrane C 1 "-HC 03 " 
exchanger to effect net secretion of bicarbonate and Na + (by a passive process) into 
the duct. The failure to secrete Na + -HC 03 " an d water leads to retention of 
enzymes in the pancreas and ultimately destruction of virtually all pancreatic tissue. 
In CF intestinal epithelium, a lack of Cl" and water secretion impairs the ability to 
flush the secreted mucins and other macromolecules from intestinal crypts. 
Ultimately, this process can lead to obstruction of both the small and large 
intestines. In the hepatobiliary system, defective hepatic ductal salt (Cl") and water 
secretion causes retention of biliary secretions and focal biliary cirrhosis and bile 
duct proliferation in -25-30% of CF patients. The inability of the CF gall bladder 
epithelium to secrete salt and water can lead to both chronic cholecystitis and 
cholelithiasis. 
IIA.2.C. Sweat Gland: 
CF patients secrete nearly normal volumes of sweat into the sweat acinus but 
are unable to absorb NaCl from sweat as it moves through the sweat duct (2,22). 
The defect in ductal function represents the inability to absorb Cl" across the 
Cl'-impermeable CF ductal epithelia. 
II.A.3. Clinical Aspects 
Most CF patients present with signs and symptoms of the disease in 
childhood (1). Approximately 10% of patients present within the first 24 hr of life 
with gastrointestinal obstruction, termed meconium ileus. Other usual 
presentations within the first year or two of life include respiratory tract symptoms, 
most prominently persistent cough and/or recurrent pulmonary infiltrates, and 
failure to thrive. The symptoms increase with age, and major complications are 
more common in older individuals. 
IIA.3.a. Respiratory Tract: 
Upper respiratory tract disease is almost universal in CF patients. Chronic 
sinusitis is common in childhood and leads to nasal obstruction and rhinorrhea. The 
occurrence of nasal polyps approaches 15-20% and often requires surgery. 
In the lower respiratory tract, the first symptom of CF is cough. With time 
the cough becomes continuous and produces viscous, purulent, often greenish- 
colored sputum. Inevitably, periods of clinical stability are interrupted by 
"exacerbations", defined by increased cough, weight loss, increased sputum volume, 
and decrements in pulmonary function. Typically these exacerbations are treated 
with intravenous antibiotics (see below) with recovery of most lung function. Over 
the course of years, the exacerbations become more frequent and the recovery of 
lost lung function less complete, leading to respiratory failure. 
A 
Recombinant DNA Research, Volume 17 
[439] 
