Cystic Fibrosis
A chronic, progressive, inherited disease, cystic fibrosis affects the exocrine (mucus secreting) glands. The disease is transmitted as an autosomal recessive trait and is the most common fatal genetic disease of white children. When both parents are carriers of the recessive gene, they have a 25% chance of transmitting the disease with each pregnancy.
Cystic fibrosis increases the viscosity of bronchial, pancreatic, and other mucus gland secretions, obstructing glandular ducts. The accumulation of thick, tenacious secretions in the bronchioles and alveoli causes respiratory changes, eventually leading to severe atelectasis and emphysema. Cor pulmonale occurs in advanced cases.
The disease also causes characteristic GI effects in the intestines, pancreas, and liver. Obstruction of the pancreatic ducts results in a deficiency of trypsin, amylase, and lipase, which prevents the conversion and absorption of fat and protein in the intestinal tract. This interferes with the digestion of food and the absorption of fat-soluble vitamins (A, D, E, and K). In the pancreas, fibrotic tissue, multiple cysts, thick mucus, and fat replace the acini (small, saclike swellings normally found in this gland), producing signs of pancreatic insufficiency (insufficient insulin production, abnormal glucose tolerance, and glycosuria).
The incidence of cystic fibrosis is highest in people of northern European ancestry. The disease is less common in Blacks, Native Americans, and Asians. It occurs with equal frequency in both sexes.
Cystic fibrosis is incurable. But as medical research seeks to find better treatment, life expectancy has greatly increased. Previously, patients with cystic fibrosis died by age 16; today, they live to age 28 or older.
Causes
Cystic fibrosis is inherited as an autosomal recessive trait. The responsible gene is on chromosome 7. Researchers have found that most cases of cystic fibrosis arise from a mutation in this gene that causes it to encode a single amino acid, resulting in an abnormal protein that adversely affects membrane transport.
The defective protein resembles other transmembrane transport proteins. However, it lacks a phenylalanine that appears in proteins produced by normal genes. Researchers speculate that this abnormal protein may interfere with chloride transport by preventing adenosine triphosphate from binding to the protein or by interfering with activation by protein kinases. This leads to dehydration and mucosal thickening in the respiratory and intestinal tracts and may explain the characteristic elevated sweat chloride levels that occur in cystic fibrosis.
However, this abnormal protein is only the major defect in the cystic fibrosis gene. Other gene mutations remain to be found.
Complications
Cystic fibrosis can cause bronchiectasis, pneumonia, atelectasis, hemoptysis, dehydration, distal intestinal obstructive syndrome, malnutrition, gastroesophageal reflux, nasal polyps, rectal prolapse, and cor pulmonale. Other inevitable complications include hepatic disease, diabetes, pneumothorax, arthritis, pancreatitis, and cholecystitis.
A deficiency of fat-soluble vitamins can lead to clotting problems, retarded bone growth, and delayed sexual development. Male patients may experience azoospermia; female patients may experience secondary amenorrhea.
Hypochloremia and hyponatremia from increased sodium and chloride concentrations in sweat can induce cardiac arrhythmias and potentially fatal shock, especially in hot weather, when sweating is profuse.
Biliary obstruction and fibrosis may prolong neonatal jaundice. In some patients, cirrhosis and portal hypertension may lead to esophageal varices, episodes of hematemesis and, occasionally, hepatomegaly.
Assessment
A neonate with cystic fibrosis shows meconium ileus—failure to excrete meconium, the dark green mucilaginous material found in the intestine at birth. Your assessment of such an infant may reveal signs of intestinal obstruction, such as abdominal distention, vomiting, constipation, and dehydration.
Sweat gland dysfunction ranks as the most consistent abnormality. Other signs, which may be apparent soon after birth or years later, include aberrations in sweat gland and GI functions. The patient may also complain of frequent upper respiratory tract infections, dyspnea, paroxysmal cough, frequent bouts of pneumonia, and other types of severe respiratory dysfunction.
Pediatric pointerA young child typically has a history of poor weight gain and poor growth, despite a healthy appetite. The parents may describe the child’s stools as frequent, bulky, foul-smelling, and pale.
Inspection of the child may reveal a barrel chest, cyanosis, and clubbing of the fingers and toes. He may cough up tenacious, yellow-green sputum. Palpation may show a distended abdomen. On auscultation, you may hear wheezy respirations and crackles.
Diagnostic tests
A pilocarpine iontophoresis sweat test confirms cystic fibrosis. Separate tests on 2 consecutive days are required for diagnosis. The sweat test shows elevated electrolyte (sodium and chloride) concentrations in a patient with pulmonary disease or pancreatic insufficiency. The sweat test requires stimulation of sweat glands, collection of specimens, and laboratory analysis. It may show that the volume of sweat is normal but that it has an increased weight because of concentrated chloride and sodium. (Sweat normally has a sodium concentration of less than 40 mEq/L; in cystic fibrosis, this rises to more than 60 mEq/L.)
The sodium and chloride concentrations of sweat normally rise with age, but any value greater than 50 mEq/L, even in adults, strongly suggests cystic fibrosis and calls for repeated testing.
Deoxyribonucleic acid (DNA) testing can locate the presence of the Delta 508 deletion and help to confirm the diagnosis. Most cystic fibrosis patients have this deletion, although the disease can also cause more than 100 other mutations. In some families, DNA analysis may allow prenatal diagnosing, which can identify about 70% of white carriers.
