Evidence for a primary defect of pancreatic HCO3-secretion in cystic fibrosis.

Abstract

Summary function could be detected and found a wide range of pancreatic The specificity of impairment of pancreatic water and HC03secretion in cystic fibrosis (CF) and the role of this impairment in diagnosing CF were studied in 62 CF patients and 66 non-CF controls. A quantitative pancreatic stimulation test using a duodenal bromsulphthalein marker perfusion technique was performed on each subject. The hourly secretion of trypsin, HC03-, and water was measured. Over three ranges of tryptic activity (t50, 50-1000, and >I000 units per kg body weight per h, selected to represent low, intermediate, and normal acinar function respectively), mean water secretion was significantly lower in CF patients than in controls only when acinar function was low or intermediate. Mean water secretion per kg body weight per h did not vary among controls. In the CF patients, water secretion per kg body weight per h was significantly greater in those with trypsin secretion >I000 (8.28 2 3.52 ml) than in those with trypsin secretions <50 (4.22 + 5.8 ml, P < 0.02) or 50-1000 (3.07 + 2.46 ml, P < 0.001). Mean HC03- secretion in the CF patients was significantly impaired over all three ranges of tryptic activity when compared with controls. In both CF patients and controls there was a significant positive correlation between HC03- and trypsin secretion. Analysis of covariance showed that HCO3- secretion was significantly impaired in the CF patients as compared with the controls over the total range of trypsin secretion. These data demonstate that CF patients have impairment of pancreatic water secretion in association with impaired acinar function but in those with normal acinar function, water secretion appears intact. The impairment of water secretion is thus probably the result of destruction of pancreatic tissue. Pancreatic HC03secretion, however, is generally impaired in CF patients even in those with normal pancreatic enzyme and water secretion. Because impairment of HCO3- secretion appears to occur independently of the extent of pancreatic damage, it may represent a primary secretory defect which is related to the defective CF gene. Inasmuch as a few CF patients had HC03- secretory rates within the control range, the diagnosis cannot be excluded by the demonstration of HC03- values within this range. Speculation Patients with cystic fibrosis have evidence of exocrine gland dysfunction specifically in regard to electrolyte secretion. In the pancreas, impaired HC03- secretion may be the result of a primary genetic defect. Further investigation of pancreatic HC03secretion is warranted to elucidate the nature and controlling factors of secretion as they may provide evidence for the underlying abnormality in cystic fibrosis.