Cystic Fibrosis - The Disease

Cystic fibrosis, or CF, is a disease which primarily effects the respiratory and digestive tracts. It is a genetically inherited disease, the flaw being the reversal of three bases on chromosome 7. Approximately 1 in 23 people in the United States are carriers of at least one mutated gene which could cause the disease, making it the most common genetic defect of its acerbity in the United States. Heterozygotes for the trait have varying degrees of affliction, depending on how many and what type of cells are defective.

CF effects epithelial-lined organs, of which the lungs are the most prone to falling prey to opportunistic diseases; infection of the lungs causes the highest mortality rate among CF patients. Impaired airway defense against infection and bacterial colonization during childhood results in progressive lung damage with bronchiectasis, leading to respiratory failure, the most common cause of premature death. Pancreatic insufficiency, hepatic cirrhosis, and diabetes mellitus are other symptoms. Thin, slippery,normal mucus aids in maintaining clean air passages in the lungs. Rapidly multiplying bacteria cause infection as they gather in the small bronchial tubes, causing respiratory problems. Other than pancreatic and other symptoms, the sweat glands are also effected, despite the fact that the condition does not cause severe problems among CF patients. In hot climates, though, large amounts of slat may be lost by a CF patient when suffering from a high fever or during long term physical activity.

There are a number of biochemical differences between normal cells and CF cells. Of these differences, a defect in epithelial chloride ion permeability has been constantly associated with the disease. The activation of chloride secretion in response to raised intracellular cyclic adenosine monophosphate (cAMP) is severely impaired. In addition, there is an increase in sodium absorption across epithelial cells in the airways, a phenomenon linked to the chloride defect. The implications of these ion transport defects lead to two repercussions. First, osmotic movement of water, linked to chloride secretion, combined with increased sodium absorption and its joint influx of water, results in dehydration of the mucosal airway surface, which, in turn, may impair mucociliary clearance of debris from the lungs. This is shown effectively in the graph below.

Second, the net balance of charge resulting from abnormal separation of the positively charged sodium ions and the negatively charged chloride ions, results in a more negative potential across the surface of CF cells, as is depicted in the following illustration of lumen cells.

Measurement of nasal potential difference establishes a useful diagnostic test for CF. Similar changes in chloride channel activity have been found in the gut and pancreatic duct epithelial cells, along with clinical abnormalities at these sites.

Symptoms of CF are often noticed at an early age. Some children experience the effects of CF in their lungs, while others may experience problems in their digestive tract. Still, a significant amount of afflicted children will experience problems with both.

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