Pathophysiology of cystic fibrosis with emphasis on salivary gland involvement

Cystic fibrosis (CF) is a fatal autosomal recessive disorder which affects all exocrine glands, or perhaps all epithelial surfaces. The three organs most consistently affected are the eccrine sweat gland, which produces excessively salty sweat; the lung, in which chronic obstructive pulmonary disease invariably develops and is usually the cause of mortality; and the pancreas, which fails to produce adequate bicarbonate ion and water in nearly all patients, and produces inadequate digestive enzymes in most, giving rise to pancreatic insufficiency. However, the liver, reproductive tracts, intestine, sinuses, and salivary glands are also regularly affected. In the sweat gland and in the airways, passive chloride permeability is reduced, accounting for the salty sweat and probably contributing to the dehydrated mucus in the airways. In organs apart from the sweat gland, a common feature of the disease is the plugging of glandular acini and ductules by precipitated secretions. Salivary glands have been extensively studied in CF because of both the accessibility of the glands and their products, and the mix of mucous and serous components in the salivary glands. However, there is no unanimity in the results from parotid and submandibular glands. In the labial (mucous) glands, the sodium content of secreted product and in the secretory granules is markedly elevated, and histologically the acini are plugged with eosinophilic material. Functional studies of CF salivary glands have also yielded inconsistent data. Cultured cell systems combined with molecular biologic approaches offer promise in tracing the fundamental CF defect in salivary and other epithelial systems.