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Lec.2
Pediatrics
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Cystic fibrosis
Etiology and epidemiology
Cystic fibrosis (CF) is an autosomal recessive disorder that is the most
common life limiting genetic disease in whites. In the united states, the
incidence of CF is approximately1 in 3200 whites, 1 in 15000 African
American, and 1 in 31000 persons of Asian heritage. The gene for CF,
located on the long arm of chromosome 7, encodes for a polypeptide,
the cystic fibrosis transmembrane regulator (CFTR), a chloride channel
located on the apical surface of epithelial cells.
CFTR is important for the proper movement of salt and water across cell
membranes and maintaining the appropriate composition of various
secretions. Especially in the airways, liver, and pancreas. The most
common mutation is a deletion of three base pairs resulting in the
absence of phenylalanine at 508 position. More than 1500 mutations of
CFTR gene have been identified.
The secretory and absorptive characteristics of epithelial cells are
affected by abnormal CFTR, resulting in the clinical manifestations of CF.
The altered chloride ion conductance in the sweat gland results in
excessively high sweat sodium and chloride levels. The defect in CFTR
may also reduce the function of airway defenses and promote bacterial
adhesion to the airway epithelium. This all leads to chronic airway
infections and eventually to bronchial damage (bronchiectasis).
Clinical manifestations
CF is a chronic progressive disease that can present with protein and fat
malabsorption( failure to thrive, hypoalbuminemia, steatorrhea), liver
disease ( cholestatic jaundice), chronic respiratory infection. The most
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common bacterial infection are staphylococcus aureus and
pseudomonas aeruginosa.
Chronic brochial infection results in persistent or recurrent cough that is
often productive of sputum. Chronic airway infections lead to airway
obstruction and bronchiectasis ,eventually to pulmonary insufficiency
and premature deaths. The median age of survival is currently in mid
30s. Digital clubbing is common in patient with CF . chronic sinusitis and
nasal polyposis are common.
Allergic bronchopulmonary aspergillosis is a hypersensitivity reaction to
aspergillus in CF airways
Ninety percent of patients with CF are born with exocrine pancreatic
insufficiency.this leads to malabsorption of proteins, sugars and fat. Fat
malabsorption manifests clinically as steatorrhea, deficiencies of fat
soluble vitamins (A,D,E and K), and failure to thrive.
Ten percent of patients with CF are born with intestinal obstruction
caused by inspissated meconium(meconium ileus). In older patients
intestinal obstruction may results from thick inspissated mucus in the
intestinal lumen ( distal intestinal obstruction syndrome). In adolescent
or adults a progressive pancreatic damage can lead insulin deficiency.
The failure of the sweat ducts to conserve sodium and chloride may lead
to hyponatremia and hypochloremic metabolic alkalosis. Inspissation of
mucus in the reproductive tract leads to reproductive dysfunction in
both males and females.
CF should be in the differential diagnosis of children with respiratory or
gastrointestinal symptoms, especially if there is digital clubbing. Any
child with nasal polyps, especially those younger than 12 years should be
evaluated for CF.
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Diagnostic studies
The following criteria should met to establish diagnosis of CF:
1.two elevated sweat chloride tests (positive the value is >60mEq/L,
borderline if 40to 60mEq/L, a negative if <40 mEq/L, with adequate
sweat collection)
2.two mutations known to cause CF identified by DNA analysis or
3.a characteristic abnormality in ion transport across nasal epithelium
(nasal potential difference testing).
Identification of carriers and prenatal diagnosis of children with
mutation is offered at most medical centers.
Complications of cystic fibrosis
Respiratory complication
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Bronchiectasis, bronchitis, pneumonia
Atelectasis,hemoptysis, pneumothorax, nasal polyp, sinusitis, cor
epulmonale, respiratory failure.
GIT complications
Meconium ileus
Meconium plug syndrome
Volvulus
Distal intestinal obstruction syndrome
Rectal prolapse
Intussupception
Fibrosing colonopathy
Appendicitis , pancreatitis
Hepatic cirrhosis
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Growth failure
Diabetes
*Other complications
Infertility
Delyed puberty
Electrolytes disturbance(hyponatremia, hypokalemia,
hypochloremia,metabolic alkalosis)
Treatment
The treatment of CF is multifactorial, but primarily directed toward the
GIT and pulmonary complications.
Chest physiotherapy help remove mucus from the airways, antibiotic
therapy is important in controlling infections( oral, aerosolized and IV).
Exocrine pancreatic insufficiency is treated with enteric coated
pancreatic enzyme capsules and the patients should follow high calorie
diets.
Lipase dose exceeding 2500 U/Kg/meal are contraindicated because
they have been associated with fibrosing colonopathy. Fat soluble
vitamins are recommended.
Newborns with meconium ileus may require surgical intervention, but
some can be managed with contrast( gastrografin) enemas.