cystic fibrosis

Pathol.

a hereditary chronic disease of the exocrine glands, characterized by the production of viscid mucus that obstructs the pancreatic ducts and bronchi, leading to infection and fibrosis.

[1950-55]

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▪ pathology

also called  mucoviscidosis , formerly  cystic fibrosis of the pancreas 

      an inherited metabolic disorder, the chief symptom of which is the production of a thick, sticky mucus that clogs the respiratory (respiratory disease) tract and the gastrointestinal tract (alimentary canal).

      Cystic fibrosis is an inherited disorder mainly affecting people of European ancestry. It is estimated to occur in 1 per 2,000 live births in these populations and is particularly concentrated in people of northwestern European descent. It is much less common among people of African ancestry (about 1 per 17,000 live births) and is very rare in people of Asian ancestry. The disorder was long known to be recessive—i.e., only persons inheriting a defective gene from both parents will manifest the disease. The disease has no manifestations in heterozygotes—i.e., those individuals who have one normal copy and one defective copy of the particular gene involved. When both parents are heterozygous, however, they may expect that, on the basis of chance, one out of four of their offspring will have the disease. In 1989 the defective gene responsible for cystic fibrosis was isolated. The gene, called cystic fibrosis transmembrane conductance regulator, or CFTR, lies in the middle of chromosome 7 and encodes a protein of the same name, designated CFTR. The discovery of mutations associated with cystic fibrosis has led to the development of screening tests to identify adult carriers (heterozygotes), who may pass a mutation on to their offspring, as well as to identify newborns who may be at risk for the disorder.

      Cystic fibrosis affects the functioning of the body's exocrine glands—e.g., the mucus-secreting and sweat glands—in the respiratory and digestive systems. Within the cells of the lungs and gut, the CFTR protein transports chloride across cell membranes and regulates other channels. These functions are critical for maintaining and adjusting the fluidity of mucous secretions. Most cases of cystic fibrosis are caused by a mutation that corresponds to the production of a CFTR protein that lacks the amino acid phenylalanine. As a result, chloride and sodium ions accumulate within cells, thereby drawing fluid into the cells and causing dehydration of the mucus that normally coats these surfaces. The thick, sticky mucus accumulates in the lungs, plugging the bronchi and making breathing difficult. This results in chronic respiratory infections, often with Staphylococcus aureus or Pseudomonas aeruginosa. Chronic cough, recurrent pneumonia, and the progressive loss of lung function are the major manifestations of lung disease, which is the most common cause of death of persons with cystic fibrosis.

      In the digestive system, the abnormally thick mucous secretions interfere with the passage of digestive enzymes and thus block the body's absorption of essential nutrients. The resulting maldigestion and malabsorption of food can cause affected individuals to become malnourished despite an adequate diet. Bulky, greasy, foul-smelling stools are often the first signs of cystic fibrosis. About 10 percent of infants with cystic fibrosis have intestinal obstruction at birth due to very thick secretions.

      Cystic fibrosis causes the sweat glands to produce sweat that has an abnormally high salt content. The high salt content in perspiration is the basis for the “sweat test,” which is the definitive diagnostic test for the presence of cystic fibrosis.

      The treatment of cystic fibrosis includes the intake of pancreatic enzyme supplements and a diet high in calories, protein, and fat. Vigorous physical therapy on a daily basis is used to loosen and drain the mucous secretions that accumulate in the lungs. Antibiotics are regularly ingested in order to fight the accompanying lung infections; the enzyme deoxyribonuclease also is administered to clear mucus and reduce infection. Cystic fibrosis was not recognized as a separate disease until 1938 and was then classified as a childhood disease because mortality among afflicted infants and children was high; by the mid-1980s, however, more than half of all victims of cystic fibrosis survived into adulthood owing to the aggressive therapeutic measures described above. Adult males who have cystic fibrosis usually are sterile.

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