Cystic fibrosis is a chronic genetic disorder caused by mutations in the CFTR gene, leading to severe respiratory and digestive issues, primarily due to thickened secretions and mucus. Common symptoms include salty skin, poor weight gain, and recurrent lung infections, with the delta F508 mutation being the most prevalent. Treatment focuses on managing symptoms and complications through antibiotics, inhaled medications, and airway clearance techniques to improve quality of life.

1. Failure to thrive: Cystic Fibrosis
By Rubab imran

2. INTRODUCTION
 Since ancient times, children around the world have been afflicted with cystic fibrosis
which leads to shortened lifespans.
 Salty skin was a sign of an impending illness without cause or cure.
 High salt levels in the sweat of patients with cystic fibrosis suggest an abnormality in
electrolyte transport from the sweat glands.
 It is a chronic disease that frequently leads to chronic Sinopulmonary infections and
pancreatic insufficiency
 The most common cause of death is end-stage lung disease

3. Definition
 Cystic fibrosis is an autosomal recessive genetic disorder with features that reflect
mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene which
encodes a protein expressed in the apical membrane of exocrine epithelial cells.

5. Epidermiology
 The most common mutation is delta F508, which is found in 70% of American white patients
with CF and two-thirds of all cases worldwide.
 The mutation is a class 2 mutation of abnormal folding of the CFTR protein, leading to
premature destruction within the Golgi apparatus.
 The delta F508 mutation commonly leads to exocrine pancreatic insufficiency and a
higher likelihood of meconium ileus.

6. Pathophysiology
 CFTR transports chloride ions across cell membranes in the lungs, liver, pancreas, digestive
tract, reproductive tract, and skin.

7. Sinus disease
 Occur when secretion viscosity increases which obstructs the sinus ostia.
 Ciliary dysfunction, increased inflammatory mediators, and increased bacterial
colonization with pathogens like Pseudomonas aeruginosa.
 Subsequently, chronic sinusitis occurs, and secondary structural damage may occur.

8. Lung disease
 A high rate of sodium absorption and low rate of chloride secretion reduces salt and water
content in mucus and depletes peri-ciliary liquid.
 The mucus adheres to the airway surface, leading to decreased mucus clearing.
 Predisposition to Staph and Pseudomonas infection.
 Bronchiectasis and further thick purulent sputum production occur.
 Poorly managed pulmonary manifestations are the primary cause of death in patients with CF.

9. Pancreatic manifestation
 Obstruction of the pancreatic ductules by thickened secretions.
 As a result, intestinal chyme is not enzymatically processed in the intestines resulting in
pathognomonic greasy stools, colicky abdominal pain, and malabsorption of nutrients
from food.
 Specifically, fat-soluble vitamins A, D, E, and K are notably deficient.

10. Cont..
 Auto-digestion of the pancreas may occur as this enzyme targets the pancreatic tissues.
 In severe, chronic cases, this can lead to endocrine pancreatic failure when the islets of
Langerhans begin to be digested by trapped pancreatic enzymes.
 The lasting impacts of this spectrum of disease mimic type-1 Diabetes Mellitus.

11. Biliary and hepatic systems
 The biliary ductules may be plugged with secretion.
 Obstructive cirrhosis and post-hepatic hyperbilirubinemia can occur.
 Gallbladder disease is more likely to occur as a spectrum of this manifestation of CF, with
up to 15% of those with cystic fibrosis having gallstones.

12. Sweat glands
 Normally sweat glands move chloride from the extracellular space into the intracellular
space. Thus, sodium and water are reabsorbed from the sweat gland tissue into the body.
 However, failure of the chloride channel to reabsorb chloride leads to a loss of sodium
onto the skin surface and a subsequent fluid loss.
 This causes the pathognomonic salty skin seen with cystic fibrosis.

13. History and Physical
 Newborns with CF may present with meconium ileus, prolonged neonatal jaundice, or
early lung infection.
 Infants and children with CF may present with failure to thrive and poor weight gain,
anemia, undescended testicles in boys, recurrent sinopulmonary infections, and a distal
intestinal obstructive syndrome with or without pancreatic insufficiency.

14. Cont.…
 Males may be infertile due to absent vas deferens.
 Females have reduced fertility due to thickened cervical mucus.

15. Investigation
 The diagnostic pathway starts with a sweat chloride test. If normal but still symptomatic, a
repeat sweat chloride test is indicated.
 If the test is abnormal, DNA testing is indicated. If one or less CFTR mutations are found,
expanded DNA analysis is indicated.
 However, the finding of 2 CF-related mutations confirms the diagnosis of cystic fibrosis.

16. Cont..
 The test for immunoreactive trypsinogen (IRT), a pancreatic enzyme, increases sensitivity
and specificity in screening newborns with meconium ileus for CF.

17. Additional Dignostic
 A chest radiography may help identify hyperinflation, bronchiectasis, and abscesses.
 Sinus radiography may demonstrate panopacification of the paranasal sinuses.
 Abdominal radiography may be helpful in neonatal who present with meconium ileus
 Bronchoalveolar lavage typically shows many neutrophils

18. Differential diagnosis
 Asthma
 Bronchiolitis
 Bronchiectasis
 Nutritional considerations in failure to thrive
 Pediatric aspergillosis
 Primary ciliary dyskinesia
 Sinusitis

19. Treatment
 Cystic fibrosis is a systemic that has broad implications for both quality and quantity of life
when poorly controlled.
 Therefore, treatment should focus on optimizing function to avoid acute illness events.
 CF guidelines recommend at least one antibiotic to cover each pathogenic bacteria
cultured from respiratory secretions and two antibiotics for P.aeruginosa infections.

20. Cont.
 Ventilation and oxygenation should be supported through the use of inhaled
bronchodilators, including albuterol and ipratropium bromide.
 Agents such as inhaled dornase Alfa or inhaled hypertonic saline are prescribed to
promote airway secretion clearance in conjunction with chest physiotherapy.
 Anti-inflammatory medicines such as glucocorticoids are also used to assist in opening
airways to relieve the obstruction.

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