New Insights into the Pathogenesis of Cystic Fibrosis

Abstract

Cystic fibrosis (CF) is the most frequent inheritable disease with a lethal course during childhood. The characteristic high viscosity of the mucoid secretion products in the lungs, pancreas, and gut cause plugging and secondary damage of these organs. In the past 20 years effective treatment of intestinal obstruction in the neonatal period and the infections of the lungs has improved the prognosis significantly. Many patients will reach adulthood in the near future. In the past 10 years new insights into the cause of the disease changed diagnostic procedures and, it is to be hoped, soon also treatment. The first development was the estimation of brush-border enzymes in amniotic fluid. With this method prenatal diagnosis is possible in the 17th—18th week of pregnancy. The recent discovery of the gene on chromosome 7 and its structure is the most important breakthrough. At the same time the process of CI transport across the mucosal membrane of many types of epithelium was subject to investigation by several laboratories. We have studied the transport of ions in the small and large intestines of CF patients. The effect of all three types of intracellular signal transfer is abnormal, although the second messengers themselves (cAMP, cGMP, and Ca∼^f) are present. Evidence is found for K⁺ instead of Cr secretion after addition of secretagogues.

Key Words:

• Chloride transport
• cystic fibrosis
• heterozygotes
• intestine
• short-circuit current