Pathophysiology of Cystic Fibrosis

Cystic fibrosis is an autosomal recessive disorder in which mutation occurs on the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The gene encodes a protein, CFTR that regulates multiple ion channels, the chloride channel – CFTR, sodium channel – EnaC etc. that involve in mucus secretion and other cellular processes.

Dehydration of mucus layer in cystic fibrosis
In epithelial cells, epithelial sodium channel (ENaC) is normally inhibited by CFTR. However in cystic fibrosis, ENaC activity is markedly increased while chloride secretion into the lumen is reduced. This leads to an increased reabsorption of sodium into the cells. The ion changes increase passive water reabsorption. Thus in cystic fibrosis, the mucus layer coating respiratory and intestinal epithelial cells becomes dehydrated, thick and sticky. In the lungs, the dehydration leads to defective action and the accumulation of hyperconcentrated secretions. This may obstruct the air passages and predispose to recurrent pulmonary infections.

CFTR in transport of bicarbonate ions
In pancreas, a mutated CFTR can have completely or partially preserved chloride transport, but markedly abnormal bicarbonate transport. The absence of bicarbonate ions decreases luminal pH, which leads to a variety of adverse effects.

Increased salt content in sweat
The function of CFTR in the sweat gland ducts is to reabsorb luminal chloride ions and ENaC to reabsorb sodium. Thus, in the sweat ducts, mutated CFTR gene results in a decreased reabsorption of sodium chloride.