22nd February 2024

Pathophysiology

The genetic mutation for CFTR is located on the long arm of chromosome 7 in the region of 7q31.2.  The most common genetic abnormality is deletion of position 508 in the amino acid sequence which results in a defective CFTR protein. CFTR is a channel protein in membranes of cells which produce mucus, sweat, saliva, tears, and the digestive system. The channel is responsible for the transportation of chloride ions across cell membranes.  The mutation alters the secondary and tertiary structure of proteins, leading to a failure of the opening of chloride ion channels in response to elevated cyclic AMP in epithelial cells. This results in decreased excretion of chloride ions, increased absorption of sodium ions and subsequently increased water retention in epithelial cells. Thus, intraluminal secretions have increased viscosity and tenacity. This subsequently leads to chronic bacterial colonisation, causing more repeated episodes of infection. Each infection episode produces more inflammatory cytokines, causing organ parenchymal damage.