[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [General pathology](https://durgical.com/en/general-pathology/) › [Paediatric pathology](https://durgical.com/en/general-pathology/#a-pediatric) › Cystic fibrosis: from the CFTR channel to organ damage [General pathology](https://durgical.com/en/general-pathology/) · [Paediatric pathology](https://durgical.com/en/general-pathology/#a-pediatric) # Cystic fibrosis: from the CFTR channel to organ damage - Mechanism A faulty chloride channel leaves secretions thick; mucus plugs the bronchi, pancreatic ducts and gut, and sweat comes out very salty. Updated 2026-11-01 ## Key points - The commonest mutation is F508del: the protein misfolds and is degraded in the endoplasmic reticulum before reaching the membrane. - Airway: less chloride secretion and more sodium absorption through ENaC; the surface liquid dehydrates and mucociliary clearance fails. - Sweat gland: chloride is not reabsorbed in the duct; a raised sweat chloride confirms the diagnosis. - Infections: Staphylococcus aureus in childhood and mucoid Pseudomonas aeruginosa later; bronchiectasis and respiratory failure. - Males: congenital bilateral absence of the vas deferens and infertility; newborns: meconium ileus. ## What it is Cystic fibrosis is an autosomal recessive disease caused by mutations in the CFTR gene (chromosome 7), which encodes a cyclic AMP-regulated chloride channel in epithelia. It is the commonest lethal recessive disease in populations of European origin. The same defect has opposite effects depending on the epithelium: dehydrated secretions in the airways and pancreas, but sweat with excess salt. ## Structure - Pancreas: dilated ducts with mucus plugs and concretions, acinar atrophy and fibrosis; islets are spared at first. - Lung: bronchioles full of mucus, chronic neutrophilic inflammation, bronchiectasis and, late on, abscesses. - Newborn gut: thick meconium blocking the terminal ileum (meconium ileus). - Liver: bile plugs in the ductules that can progress to focal biliary cirrhosis. ## Step by step - A CFTR mutation reduces the amount, the opening or the delivery of the channel to the apical membrane. - In the airway less chloride leaves and more sodium and water are absorbed: mucus becomes thick and sticky. - Cilia cannot move the mucus; bacteria are trapped and chronic infection sets in. - Neutrophils release proteases and DNA that thicken the mucus and destroy the bronchial wall: bronchiectasis. - In the pancreas mucus plugs the ducts; enzymes injure the acini, leading to atrophy, fibrosis and exocrine insufficiency. - Without pancreatic enzymes there is steatorrhoea, malnutrition and deficiency of the fat-soluble vitamins (A, D, E and K). ## Clinical notes - Cystic fibrosis-related diabetes in adolescents and adults from pancreatic fibrosis. - Nasal polyps and chronic sinusitis; allergic bronchopulmonary aspergillosis. - CFTR modulators (potentiators and correctors) act on the faulty protein according to the type of mutation. ## In the lab - Newborn screening with raised immunoreactive trypsinogen in dried blood. - Sweat test by pilocarpine iontophoresis: raised chloride. - CFTR genetic testing; nasal potential difference helps in doubtful cases. - Low faecal elastase indicates exocrine pancreatic insufficiency. ## Memory aid Chloride trapped, water stuck: glue-like mucus in the tubes and too much salt on the skin. ## Test yourself Think of the answer, then tap the question to see it. ## What happens to the CFTR protein with the F508del mutation? It misfolds, is held in the endoplasmic reticulum and degraded, so it never reaches the membrane. ## Why is sweat salty when chloride secretion is missing in the airway? Because in the sweat duct CFTR serves to reabsorb chloride; if it fails, chloride and sodium stay in the sweat. ## Which cause of male infertility is linked to cystic fibrosis? Congenital bilateral absence of the vas deferens, with obstructive azoospermia. ## Which newborn screening result suggests cystic fibrosis? Raised immunoreactive trypsinogen in the dried blood sample, confirmed by a sweat test. [Add to my cards (4)](https://durgical.app/estudiar/?add=/en/general-pathology/cystic-fibrosis-from-the-cftr-channel-to-organ-damage/) ## Related - [Mendelian inheritance: autosomal dominant, recessive and X-linked](https://durgical.com/en/general-pathology/mendelian-inheritance-autosomal-dominant-recessive-and-x-linked/) - [How a single gene causes disease: enzymes, receptors and structural proteins](https://durgical.com/en/general-pathology/how-a-single-gene-causes-disease-enzymes-receptors-and-structural-proteins/) ## Related conditions - [Cystic fibrosis](https://durgical.com/en/conditions/cystic-fibrosis/) - [Bronchiectasis](https://durgical.com/en/conditions/bronchiectasis/) - [Chronic rhinosinusitis and nasal polyps](https://durgical.com/en/conditions/chronic-rhinosinusitis-and-nasal-polyps/) - [Allergic bronchopulmonary aspergillosis (ABPA)](https://durgical.com/en/conditions/allergic-bronchopulmonary-aspergillosis/) - [Chronic pancreatitis](https://durgical.com/en/conditions/chronic-pancreatitis/) - [Male infertility](https://durgical.com/en/conditions/male-infertility/) - [Cirrhosis](https://durgical.com/en/conditions/cirrhosis/) ## Elsewhere in DurgiPedia - [Airway defenses, cough and mucociliary clearance](https://durgical.com/en/physiology/airway-defenses-cough-and-mucociliary-clearance/) - [Exocrine pancreatic secretion](https://durgical.com/en/physiology/exocrine-pancreatic-secretion/) - [Patterns of malabsorption](https://durgical.com/en/physiology/patterns-of-malabsorption/) - [Membrane transport](https://durgical.com/en/biochemistry/topics/membrane-transport/) - [Protein structure and folding](https://durgical.com/en/biochemistry/topics/protein-structure-and-folding/) - [Molecular chaperones and heat shock proteins](https://durgical.com/en/biochemistry/topics/molecular-chaperones-and-heat-shock-proteins/) - [Newborn screening](https://durgical.com/en/biochemistry/topics/newborn-screening/) - [The airway: from nose to bronchioles](https://durgical.com/en/histology/the-airway-from-nose-to-bronchioles/) ## Microorganisms - [Pseudomonas aeruginosa](https://durgical.com/en/microbiology/pseudomonas-aeruginosa/) - [Staphylococcus aureus](https://durgical.com/en/microbiology/staphylococcus-aureus/) - [Burkholderia cepacia complex and Burkholderia pseudomallei](https://durgical.com/en/microbiology/burkholderia-cepacia-complex-and-burkholderia-pseudomallei/) [← All of general pathology](https://durgical.com/en/general-pathology/) Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given. Sources: [Cystic fibrosis: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/cystic-fibrosis/) (MedlinePlus, US National Library of Medicine, 2026); [What are the different ways a genetic condition can be inherited?: MedlinePlus Genetics](https://medlineplus.gov/genetics/understanding/inheritance/inheritancepatterns/) (MedlinePlus, US National Library of Medicine, 2026). ## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake Representative model, for educational purposes only. --- Source: https://durgical.com/en/general-pathology/cystic-fibrosis-from-the-cftr-channel-to-organ-damage/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/general-pathology/cystic-fibrosis-from-the-cftr-channel-to-organ-damage/