![]() Poorly managed pulmonary manifestations are the primary cause of death in patients with CF. The result of this cascade is obstruction of the airways with the resulting failure of ventilation of the lung. Part of the inflammatory reaction includes the production of the neutrophil interleukin-8 from epithelial cells, which functions as a secretagogue, increasing mucous secretion, thereby creating a positive feedback loop of mucous secretion with persistence of inflammation, infection, and structural damage. Bronchiectasis and further thick purulent sputum production occur. As a result of obstruction, an environment optimal for bacterial growth is created within the airways. Mucus plugging in the bronchioles results in an obstructive lung disease clinical picture. Disease results as a cascade effect following infection and the subsequent inflammatory process. It is important to note that the lungs of a CF patient are normal in utero, at birth, and after birth. Lung disease occurs as a spectrum obstruction from thickened mucous secretion. Subsequently, chronic sinusitis occurs, and secondary structural damage may occur. The result of this syndrome is impaired sinus secretion clearance. These include ciliary dysfunction, increased inflammatory mediators, and increased bacterial colonization with pathogens such as Pseudomonas aeruginosa. Sinus disease occurs when secretion viscosity increases which obstruct the sinus ostia. The most commonly affected organs include the sinuses, lungs, pancreas, biliary and hepatic systems, intestines, and sweat glands. Thickened mucus secretions in nearly every organ system involved result in mucous plugging with obstruction pathologies. The increased sodium reabsorption leads to increased water resorption and manifests as thicker mucus secretions on epithelial linings and more viscous secretions from exocrine tissues. The result of all mutations is decreased secretion of chloride and consequently increased resorption of sodium into the cellular space. It includes mutations that alter the stability of mRNA and others that alter the stability of the mature CFTR protein. However, the rate of chloride ion flow and the duration of channel activation after stimulation is decreased from normal.Ĭlass 5 dysfunction is the net decreased concentration of CFTR channels in the cellular membrane as a result of rapid degradation by cellular processes. The result is a fully formed protein channel in the cellular membrane that is non-functional.Ĭlass 4 dysfunction is when the protein is produced and correctly localized to the cell surface. As a result, CFTR is unable to be moved to the correct cellular location.Ĭlass 3 dysfunction is characterized by diminished protein activity in response to intracellular signaling. This step in protein processing is essential for the proper intracellular transit of the protein. This fails to translate the genetic information into a protein product with a subsequent total absence of CFTR protein, and approximately 2% to 5% of cystic fibrosis cases result.Ĭlass 2 dysfunction results in abnormal post-translational processing of the CFTR protein. Ĭlass 1 dysfunction is the result of nonsense, frameshift, or splice-site mutation, which leads to premature termination of the mRNA sequence. The most common cause of death is end-stage lung disease. It is a chronic disease that frequently leads to chronic sinopulmonary infections and pancreatic insufficiency. Researchers now know that cystic fibrosis is an autosomal recessive disorder of exocrine gland function most commonly affecting persons of Northern European descent at a rate of 1 in 3500. Further studies led to the hypothesis that the faulty chloride channel must be situated in the apical membranes of the lung surface or glandular epithelium to explain the respiratory and systemic organ failure associated with cystic fibrosis. High levels of salt in the sweat of patients with cystic fibrosis suggested an abnormality in electrolyte transport from the sweat gland. Quinton postulated that sweat ducts in these patients were impermeable to chloride. postulated that cystic fibrosis must be caused by a genetic defect from the autosomal recessive pattern of inheritance of the disease. Until relatively modern times, cystic fibrosis was poorly understood. The curse that became folklore pronounced, “Woe to the child who tastes salty from a kiss on the brow, for he is cursed and soon will die.” Salty skin was a sign of an impending illness without cause or cure. In medieval Europe, these children were believed to be cursed by witches and doomed to die. Since ancient times, children around the world have been afflicted with cystic fibrosis that leads to shortened lifespans. ![]()
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