Cystic Fibrosis
In science specifically in pathology and microbiology, cystic fibrosis is a familial, autosomal recessive genetic disease of children, adolescents, and young adults in which there is abnormality of secretion by exocrine glands. Formerly, the disease had been known as pancreatic cystic fibrosis or fibrocystic pathology or disease of the pancreas because of the prominent anatomic changes in the pancreas and associated enzyme deficiencies. Later, the disease or pathology was termed mucoviscidosis, since many of the glands affected produce thick viscid mucus. It has since been observed that an abnormality of sweat such as an increase in sodium and chloride is most consistently present. The sweat test for detection of this abnormality is presently the most reliable of any general method for the diagnosis of this disorder. As yet, the genetic pathology mechanism for the disturbance in secretion by the exocrine glands in the various organs is not known. Cystic fibrosis is the most prevalent inherited pathology or disease among Caucasian children, the highest frequency being observed in persons of mid European heritage. The incidence in the United States is variously estimated as one in 1,900 to one in 3,700 live births, according to reports since 1960, and the pathology or disease is comparatively rare in blacks. Mild or incomplete forms that are difficult to recognize probably exist. Characteristic sweat electrolyte patterns as seen under the microscopes may be present in asymptomatic relatives of known patients.
The pancreas and lungs are most seriously involved and less commonly the liver and salivary glands. In the pancreas, amorphous inspissated eosinophilic material obstructs ducts, with dilation of ducts and acini. In science specifically in pathology and microbiology, there is progressive atrophy of the parenchyma and gradual replacement by fibrosis, with infiltration by some lymphocytes and other mononuclear cells. Fatty replacement of atrophic parenchyma as well as fibrosis may occur as seen through microscopy. Ultrastructural changes in the atrophic acinar cells include dilatation of ergastoplasm, decrease in zymogen granules, and spherulation of mitochondria and atrophy of microvilli as examined under the microscopes. The islets of Langerhans remain intact, although there are some reports of an increased incidence of diabetes mellitus as seen under the microscopes. The pancreas may show little gross change except to be firmer and thinner than normal as observed using the microscopes.
In about 10 percent of cases, there is meconium ileus at birth, an intestinal obstruction caused by abnormal inspissated meconium, which possibly results from deficiency of pancreatic secretion before birth. The obstruction is usually in the distal part of it small intestine, and proximally the dilated ileum is filled with a large amount of tenacious viscid meconium.
With pancreatic involvement and deficiency of the pancreatic enzymes trypsin, amylase, and lipase, food is poorly digested and absorbed. Fatty foods particularly are poorly digested, and steatorrhea is commonly present. Malnutrition, including deficiency of vitamins A, D, and K, may be a prominent feature.
Pulmonary involvement is present in almost all cases at some time during the course of the pathology or disease and is the important factor in most deaths. In a disease or pathology, the paranasal sinuses also consistently involved, and nasal polyposis is sometimes present. A respiratory infection with increased mucus production may initiate pulmonary disturbance. Inspissated abnormal bronchial secretions cause obstruction, leading to secondary infection, emphysema or atelectasis, bronchial damage, and bronchiectasis. Squamous metaplasia of bronchial linings, in which vitamin A deficiency may be a factor, complicates the problem of the removal of secretions. Mucous glands of the trachea, bronchi, and bronchioles become distended with inspissated material similar to that in pancreatic acini and ducts as observed under the microscopes. Recurrent resistant bronchopneumonia and lung abscesses are common results and often appear to be caused by Staphylococcus aureus infection as discovered through microscopy. Pulmonary hypertension and cor pulmonale develop in some patients.
The liver through microscopy may show a focal fibrosis in portal areas, with amorphous eosinophilic material plugging bile ductules. There is usually some bile duct proliferation and inflammatory reaction in the areas of fibrosis. The hepatic changes vary greatly in the severity and extensiveness of disease or pathology. A few cases may progress to widespread and severe biliary cirrhosis with portal hypertension and enlargement of the spleen.
As studied in pathology, sub maxillary glands have increased secretion and show a similar mucinous obstruction. They are consistently enlarged by the age of 6 years. On the other hand, the parotid gland produces largely a serous secretion and usually does not show obstruction of ducts as observed under the microscopes. Sweat glands show a consistent abnormality of sweat electrolytes, and sodium and chloride are increased two to four times above normal as monitored by means of microscopy. Various sweat tests such as pilocarpine iontophoresis sweat tests have been devised that are important diagnostically and as simplified screening procedures. Hand prints on filter paper or agar plates impregnated with silver chromate have been used as a simplified screening test. Abnormally high losses of sodium chloride in the sweat during hot weather may lead to massive salt depletion in these patients, which may be followed by peripheral vascular collapse, hyperpyrexia, coma, and death.
In science specifically in biology or microbiology, changes in the reproductive system have been described in the post pubertal male such as azoospermia associated with absence of vasa deferentia and small fibrotic epididymides.
By means of microscopy, of interest is the observation that the fibroblasts, obtained by culturing skin biopsies of patients with cystic fibrosis, stain metachromatically and that parents and relatives frequently show a similar change in their fibroblasts. The possibility of detecting heterozygotes for cystic fibrosis by this means has been suggested. Through microscopy, it should be noted however, that metachromasia in cultured fibroblasts has been demonstrated in other genetic disorders in which intracellular mucopolysaccharides may appear such as Hurlers syndrome, Marfans syndrome, late infantile amaurotic idiocy, certain lipid storage diseases, and other pathology. It is sometimes seen in fibroblasts of healthy individuals.
A serum factor, a protein or protein complex, as seen under the microscopes, has been identified in cystic fibrosis patients and heterozygotes, which inhibits ciliary activity in explants of rabbit tracheal epithelium and oyster gill cilia. This factor has also been identified in culture media of fibroblasts derived from cystic fibrosis patients and is produced by cells cultured from amniotic fluid of a fetus with the cystic fibrosis gene as observed in microscopy.
