Cystic Fibrosis

Cystic Fibrosis is a topic covered in the Washington Manual of Medical Therapeutics.

To view the entire topic, please or .

The Washington Manual is an award-winning, complete mobile solution for nurses and students. Look up information on diseases, tests, and procedures; then consult the database with 5,000+ drugs or refer to 65,000+ dictionary terms. Explore these free sample topics:

-- The first section of this topic is shown below --

General Principles

Definition

CF is an autosomal recessive disorder caused by mutations of the CF transmembrane conductance regulator gene (CFTR), which results in multisystem exocrine organ dysfunction.

Epidemiology

  • In the US, >30,000 people are affected by CF, and about 1000 new cases are diagnosed every year.1,2
  • CF is the most common life-shortening genetic disease in Caucasians; however, the diagnosis should be considered in patients of diverse ethnic backgrounds as well.
  • The prognosis of CF has continuously improved, and today >50% of patients with CF in the US are aged ≥18 years.

Etiology

  • CF is caused by mutations in the CFTR gene, a cyclic adenosine monophosphate–regulated chloride channel, which normally maintains hydration of exocrine organ secretions.
  • Abnormal CFTR function causes decreased chloride secretion and increased sodium absorption on the surface of epithelial cells, which can result in thickened secretions in the airways, sinuses, pancreatic ducts, biliary tree, intestines, and reproductive tract.
  • CFTR mutations are categorized into five classes: (1) defective synthesis, (2) defective processing and maturation, (3) defective regulation, (4) defective conductance, and (5) reduced function/synthesis.
  • The most common mutation is F508del, a class II mutation resulting from the deletion of DNA coding for phenylalanine (F) amino acid at position 508. The majority of the resultant misfolded protein is destroyed intracellularly and does not reach the cell surface. More than 85% of patients in the US with CF have at least one copy of this mutation.2
  • To date, >2000 other potentially causative mutations in the CFTR gene have been identified.2

Pathophysiology

  • The primary pulmonary manifestations of CF are related to the malfunction of chloride transport across the airway epithelium, resulting in diminished airway surface liquid and impaired mucociliary clearance.
  • Poor mucociliary clearance, infection, inflammation, and chronic airway obstruction often result in bronchiectasis, chronic infection, respiratory failure, and premature death.
  • Similarly, thickened secretions in the pancreatic and biliary ducts lead to maldigestion, malabsorption, and, occasionally, liver disease and diabetes.3

-- To view the remaining sections of this topic, please or --

General Principles

Definition

CF is an autosomal recessive disorder caused by mutations of the CF transmembrane conductance regulator gene (CFTR), which results in multisystem exocrine organ dysfunction.

Epidemiology

  • In the US, >30,000 people are affected by CF, and about 1000 new cases are diagnosed every year.1,2
  • CF is the most common life-shortening genetic disease in Caucasians; however, the diagnosis should be considered in patients of diverse ethnic backgrounds as well.
  • The prognosis of CF has continuously improved, and today >50% of patients with CF in the US are aged ≥18 years.

Etiology

  • CF is caused by mutations in the CFTR gene, a cyclic adenosine monophosphate–regulated chloride channel, which normally maintains hydration of exocrine organ secretions.
  • Abnormal CFTR function causes decreased chloride secretion and increased sodium absorption on the surface of epithelial cells, which can result in thickened secretions in the airways, sinuses, pancreatic ducts, biliary tree, intestines, and reproductive tract.
  • CFTR mutations are categorized into five classes: (1) defective synthesis, (2) defective processing and maturation, (3) defective regulation, (4) defective conductance, and (5) reduced function/synthesis.
  • The most common mutation is F508del, a class II mutation resulting from the deletion of DNA coding for phenylalanine (F) amino acid at position 508. The majority of the resultant misfolded protein is destroyed intracellularly and does not reach the cell surface. More than 85% of patients in the US with CF have at least one copy of this mutation.2
  • To date, >2000 other potentially causative mutations in the CFTR gene have been identified.2

Pathophysiology

  • The primary pulmonary manifestations of CF are related to the malfunction of chloride transport across the airway epithelium, resulting in diminished airway surface liquid and impaired mucociliary clearance.
  • Poor mucociliary clearance, infection, inflammation, and chronic airway obstruction often result in bronchiectasis, chronic infection, respiratory failure, and premature death.
  • Similarly, thickened secretions in the pancreatic and biliary ducts lead to maldigestion, malabsorption, and, occasionally, liver disease and diabetes.3

There's more to see -- the rest of this topic is available only to subscribers.