DurgicalDurgical
EN
Open the app

General pathology · Paediatric pathology

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

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

  1. A CFTR mutation reduces the amount, the opening or the delivery of the channel to the apical membrane.
  2. In the airway less chloride leaves and more sodium and water are absorbed: mucus becomes thick and sticky.
  3. Cilia cannot move the mucus; bacteria are trapped and chronic infection sets in.
  4. Neutrophils release proteases and DNA that thicken the mucus and destroy the bronchial wall: bronchiectasis.
  5. In the pancreas mucus plugs the ducts; enzymes injure the acini, leading to atrophy, fibrosis and exocrine insufficiency.
  6. 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.

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)

Elsewhere in DurgiPedia

Microorganisms

← All of 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 (MedlinePlus, US National Library of Medicine, 2026); What are the different ways a genetic condition can be inherited?: MedlinePlus Genetics (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.