In cystic fibrosis, dysfunction of the exocrine glands affects multiple organ systems. The disorder is characterized by chronic airway infection leading to bronchiectasis, bronchiolectasis, exocrine pancreatic insufficiency, intestinal dysfunction, abnormal sweat gland function, and reproductive dysfunction. Cystic fibrosis is accompanied by many complications and has a median survival rate of 31 years. The disease affects males and females and is the most common fatal genetic disease in children of European ancestry. There are more than 21,000 patients with cystic fibrosis in the United States.
Inherited as an autosomal recessive trait, the responsible gene, on chromosome 7q, encodes a membrane-associated protein called the cystic fibrosis transmembrane regulator (CFTR). The exact function of CFTR remains unknown, but it appears to help regulate chloride and sodium transport across epithelial membranes.
Most cases of cystic fibrosis arise from the mutation that affects the genetic coding for a single amino acid, resulting in a protein (CFTR) that doesn't function properly. CFTR resembles other transmembrane transport proteins, but it lacks the phenylalanine in the protein produced by normal genes. This regulator interferes with chloride channels regulated by cyclic adenosine monophosphate, and with other ions, by preventing adenosine triphosphate from binding to the protein or by interfering with activation by protein kinase.
The mutation affects volume-absorbing epithelia (in the airways and intestines), salt-absorbing epithelia (in sweat ducts), and volume-secretory epithelia (in the pancreas). Lack of phenylalanine leads to dehydration, which increases the viscosity of mucous gland secretions and leads to obstruction of glandular ducts. Cystic fibrosis has a variable effect on electrolyte and water transport.
Signs and symptoms
· Thick secretions and dehydration
· Chronic airway infections
· Dyspnea and paroxysmal cough
· Failure to thrive: poor weight gain, poor growth, distended abdomen, thin extremities, and sallow skin with poor turgor
· Crackles and wheezes
· Retention of bicarbonate and water
· Obstruction of small and large intestines; biliary cirrhosis
· Fatal shock and arrhythmias
· Clotting problems, retarded bone growth, and delayed sexual development
Diagnostic test results
The Cystic Fibrosis Foundation has developed certain criteria for definitive diagnosis:
· Two sweat tests (to detect elevated sodium chloride levels) using a pilocarpine solution (a sweat inducer) and presence of an obstructive pulmonary disease, confirmed pancreatic insufficiency or failure to thrive, or a family history of cystic fibrosis.
The sweat test may be inaccurate in very young infants because they may not produce enough sweat for a valid test. The test may need to be repeated.
· Chest X-rays show an enlarged chest cavity and decreased lung markings, reflecting destruction of lung tissue.
· Stool specimen analysis indicates the absence of trypsin, suggesting pancreatic insufficiency.
These test results may support the diagnosis:
· DNA testing can locate the presence of the Delta F 508 deletion (found in about 70% of patients with cystic fibrosis, although the disease can cause more than 100 other mutations). It allows prenatal diagnosis in families with a previously affected child.
· Pulmonary function tests reveal decreased vital capacity, elevated residual volume due to air entrapments, and decreased forced expiratory volume in 1 second.
· Liver enzyme tests reveal hepatic insufficiency.
· Sputum culture reveals organisms that cystic fibrosis patients typically and chronically colonize, such as Staphylococcus and Pseudomonas.
· Serum albumin measurement helps assess nutritional status.
· Electrolyte analysis assesses hydration status.
· Diet with increased fat and sodium
· Salt supplements
· Pancreatic enzyme replacement
· Breathing exercises, chest percussion, and postural drainage
· Inhaled beta-adrenergic agonists
· Antibiotics such as azithromycin
· Sodium-channel blocker
· Uridine triphosphate
· Transplantation of heart or lungs
· Dornase alfa
· Gene therapy
· Anti-inflammatory agents such as ibuprofen
· Positive expiratory pressure devices
· Flutter valves
· High-frequency chest compression vest
SYSTEMIC CHANGES IN CYSTIC FIBROSIS