Cystic fibrosis
Cystic fibrosis: Excerpt from Handbook of Diseases
Sometimes called mucoviscidosis, cystic fibrosis is a generalized dysfunction of the exocrine glands that affects multiple organ systems. Transmitted as an autosomal recessive trait, it’s the most common fatal genetic disease of white children.
Cystic fibrosis is a chronic disease; however, recent improvements in treatments have increased the average life expectancy from age 16 to age 28 and older.
Incidence of cystic fibrosis is highest (1 in 3,000 live births) in Whites of northern European ancestry and lowest in Blacks (1 in 17,000 live births), Native Americans, and people of Asian ancestry. The disease occurs equally in both sexes.
Causes
Cystic fibrosis is an autosomal recessive disease resulting from mutations in a gene located on chromosome 7. The gene responsible for cystic fibrosis encodes a protein that involves chloride transport across epithelial membranes. The most common mutation in the cystic fibrosis gene involves a deletion resulting in absence of phenylalanine at the cystic fibrosis transmembrane regulator. There have been more than 800 mutations identified to date.
The immediate causes of symptoms are increased viscosity of bronchial, pancreatic, and other mucous gland secretions and consequent obstruction of glandular ducts. Cystic fibrosis accounts for almost all cases of pancreatic enzyme deficiency in children.
Signs and symptoms
The clinical effects of cystic fibrosis may become apparent soon after birth or may take years to develop. They include major aberrations in sweat gland, respiratory, and GI functions.
Sweat gland dysfunction
In cystic fibrosis, sweat gland dysfunction is the most consistent abnormality. Increased concentrations of sodium and chloride in the sweat lead to hyponatremia and hypochloremia and can eventually induce fatal shock and arrhythmias, especially in hot weather.
Respiratory symptoms
Such symptoms reflect obstructive changes in the lungs: wheezy respirations; a dry, nonproductive, paroxysmal cough; dyspnea; and tachypnea. These changes stem from thick, tenacious secretions in the bronchioles and alveoli and eventually lead to severe atelectasis and emphysema.
Children with cystic fibrosis display a barrel chest, cyanosis, and clubbing of the fingers and toes. They suffer recurring bronchitis and pneumonia and associated nasal polyps and sinusitis. Death typically results from pneumonia, emphysema, or atelectasis.
GI symptoms
The GI effects of cystic fibrosis occur mainly in the intestines, pancreas, and liver. One early symptom is meconium ileus; the newborn with cystic fibrosis doesn’t excrete meconium, a dark green mucilaginous material found in the intestine at birth. He develops symptoms of intestinal obstruction, such as abdominal distention, vomiting, constipation, dehydration, and electrolyte imbalance.
Eventually, obstruction of the pancreatic ducts and resulting deficiency of trypsin, amylase, and lipase prevent the conversion and absorption of fat and protein in the intestinal tract. The undigested food is then excreted in frequent, bulky, foul-smelling, and pale stool with a high fat content.
This malabsorption induces poor weight gain, poor growth, ravenous appetite, distended abdomen, thin extremities, and sallow skin with poor turgor. The inability to absorb fats produces deficiency of fat-soluble vitamins (A, D, E, and K), leading to clotting problems, retarded bone growth, and delayed sexual development. Males have been found to have congenital bilateral absence of the vas deferens, causing sterility; females may experience secondary amenorrhea but can reproduce.
A common complication in infants and children is rectal prolapse. This stems from malnutrition and wasting of perirectal supporting tissues.
In the pancreas, fibrotic tissue, multiple cysts, thick mucus and, eventually, fat replace the acini (small saclike swellings normally found in this gland). This results in signs of pancreatic insufficiency: insufficient insulin production, abnormal glucose tolerance, and glycosuria.
About 15% of patients are pancreatic sufficient, having adequate pancreatic exocrine function for normal digestion. These patients have a better prognosis.
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.
Diagnosis
The Cystic Fibrosis Foundation sets the following standards for a definitive diagnosis:
❑ Two sweat tests using a pilocarpine solution (a sweat inducer) are clearly positive; the patient also has either an obstructive pulmonary disease, confirmed pancreatic insufficiency or failure to thrive, or a family history of cystic fibrosis.
Clinical tip Due to the large number of cystic fibrosis mutations, DNA analysis isn’t used for primary diagnosis.
❑ Chest X-rays indicate early signs of obstructive lung disease.
❑ Stool specimen analysis indicates the absence of trypsin, suggesting pancreatic insufficiency.
The following test results may support the diagnosis:
❑ Deoxyribonucleic acid testing can now locate the presence of the Delta F 508 deletion (found in about 70% of cystic fibrosis patients, although the disease is caused by more than 800 different mutations). This test can also be used for carrier detection and a prenatal diagnosis in families with a previously affected child.
❑ Pulmonary function tests reveal decreased vital capacity, elevated residual volume from air entrapments, and decreased forced expiratory volume in 1 second. This test is used if pulmonary exacerbation already exists.
❑ Liver enzyme test may reveal hepatic insufficiency.
❑ Sputum culture reveals organisms that cystic fibrosis patients typically and chronically colonize, such as Staphylococcus and Pseudomonas.
❑ Serum albumin levels help assess nutritional status.
❑ Electrolyte analysis assesses dehydration and glucose levels.
Treatment
The aim of treatment is to help the child lead as normal a life as possible. Specific treatment depends on the organ systems involved.
❑ To combat sweat electrolyte losses, treatment includes generous salting of foods and, during hot weather, administration of sodium supplements.
❑ To offset pancreatic enzyme deficiencies, treatment includes oral pancreatic enzymes with meals and snacks. The child’s diet should be low in fat but high in protein and calories, and it should include supplements of water-miscible, fat-soluble vitamins (A, D, E, and K).
❑ Management of pulmonary dysfunction includes chest physiotherapy, postural drainage, and breathing exercises several times daily to aid removal of secretions from the lungs; a flutter valve may be used in some cases. Antihistamines are contraindicated; they have a drying effect on mucous membranes, making expectoration of mucus difficult or impossible.
Aerosol therapy includes intermittent nebulizer treatments before postural drainage to loosen secretions. Dornase alfa, a genetically engineered pulmonary enzyme given by aerosol nebulizer, helps thin airway mucus, improving lung function and reducing the risk of pulmonary infection.
A patient with pulmonary infection will need mucopurulent secretions loosened and removed, using an intermittent nebulizer and postural drainage to relieve obstruction. Use of a mist tent is controversial because mist particles may become trapped in the esophagus and stomach and never even reach the lungs. Broad-spectrum antimicrobials help combat infection. Oxygen therapy is used as needed.
Recently, some patients have undergone lung transplantation to reduce the effects of the disease. Also, clinical trials of aerosol gene therapy show promise in reducing pulmonary symptoms.
Special considerations
❑ Suggest the use of air conditioners and humidifiers to help decrease vulnerability to respiratory tract infections. Emphasize keeping these units clean to prevent accumulation of organisms that increase the risk of infection.
❑ Throughout this illness, teach the patient and his family about the disease and its treatment.
❑ Provide emotional support, and refer the patient and his family for genetic counseling and to the Cystic Fibrosis Foundation.
Clinical tip Recent research indicates that the genetic defect responsible for cystic fibrosis has also been identified in individuals experiencing some forms of unexplained pancreatitis. These individuals should be offered DNA testing.
Book Source Details
- Book Title: Handbook of Diseases
- Author(s): Springhouse
- Year of Publication: 2003
- Copyright Details: Handbook of Diseases, Copyright © 2003 Lippincott Williams & Wilkins.
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Copyright notice for book excerpts: Copyright © 2008 Lippincott Williams & Wilkins. All rights reserved.
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More About This Book:
Title: Handbook of Diseases
Authors: Springhouse
Publisher: Lippincott Williams & Wilkins
Copyright: 2003
ISBN: 1-58255-266-5
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