Cystic Fibrosis Post 3 - How CF symptoms arise

So, as mentioned in my previous CF post, many moons ago, CF is caused by a mutation in the gene which encodes the cystic fibrosis transmembrane conductance regulator (CFTR), an ion channel which transports chloride ions across cell membranes, which helps to control the movement of water in tissues. The CFTR can also regulate the function of other channels; for example, those which transport sodium ions across the membrane. Mutations in this gene result in a non-functional CFTR protein, which results in the typical symptoms seen in CF sufferers.

The CFTR is largely found in the epithelial cells of organs such as the lungs, liver, and pancreas, as well as in skin, in the digestive tract and in the reproductive tract. When the CFTR protein is functioning normally (Figure 1a), it moves chloride ions (negatively-charged) out of epithelial cells and into the mucus lining the internal organs . This creates an electrochemical gradient across the membrane, due to accumulation of a negative charge outside the cell relative to inside. Positively-charged sodium ions move out into the mucus to balance the charge. This results in the mucus having a reduced water potential (due to the high salt concentration), which in turn results in the movement of water by osmosis into the mucus, making it more fluid, and therefore aiding its role as a lubricant.

A faulty CFTR channel (as seen in CF sufferers) prevents the movement of negatively-charged chloride ions across the membrane (Figure 1b). This means that a negative charge builds up inside the epithelial cells, and therefore sodium ions move into the cell, down the electrochemical gradient. The salt concentration in the epithelium is therefore higher than that of the mucus, and the movement of water by osmosis occurs in the opposite direction - out of the mucus and into the cell. As a result, the mucus is sticky and thick, and this can obstruct airways and glands. The thick mucus cannot be removed by the cilia (brush-like structures which line passageways, which usually 'waft' the mucus along), and so can trap bacteria, giving rise to chronic infections and inflammation. Therefore, the symptoms of CF come about due to the presence of this abnormal mucus – common problems include issues with breathing, digestion, and in some cases, fertility. In addition, due to problems with the pancreas, insulin production can become deficient, particularly in older patients, leading to diabetes mellitus. Another potential secondary symptom is bone disease (thin, brittle bones), caused by nutritional problems and the steroids taken to control lung disease.

My next CF post will look at current treatments for the disease, and the development of new strategies in tackling CF.

 EDIT: I've managed to work out how to allow comments from anyone, not just other Blogger/gmail users, so it should work now!