A 6-year-old Caucasian boy is brought to the office by his mother due to recurrent episodes of sinusitis. He also has a chronic cough that never seems to go away. The mother says that his previous pediatrician performed a "sweat test" to help determine the cause of his frequent infections, but results were normal. DNA testing was inconclusive. Despite these results, the new physician suspects that the patient has an inherited disorder and orders nasal transepithelial potential difference measurements. In this test, an isotonic solution of sodium chloride is applied to the nasal mucosal surface, and the electrical potential overlying the mucosa is compared with that of the interstitial fluid. The results show a transepithelial potential difference that is more negative than normal. This patient's nasal mucosa is most likely to demonstrate which of the following physiologic changes?

Question

A 6-year-old Caucasian boy is brought to the office by his mother due to recurrent episodes of sinusitis.  He also has a chronic cough that never seems to go away.  The mother says that his previous pediatrician performed a "sweat test" to help determine the cause of his frequent infections, but results were normal.  DNA testing was inconclusive.  Despite these results, the new physician suspects that the patient has an inherited disorder and orders nasal transepithelial potential difference measurements.  In this test, an isotonic solution of sodium chloride is applied to the nasal mucosal surface, and the electrical potential overlying the mucosa is compared with that of the interstitial fluid.  The results show a transepithelial potential difference that is more negative than normal.  This patient's nasal mucosa is most likely to demonstrate which of the following physiologic changes?

Quizplus · Accepted Answer

11ec160b_3b35_697a_9249_eb4a4df9b8f1_MD0001_00 Chronic cough and recurrent sinusitis in a young Caucasian patient should raise suspicion for cystic fibrosis (CF). The diagnosis of CF typically is based on elevated sweat chloride concentrations, characteristic clinical findings (recurrent sinopulmonary infections, pancreatic insufficiency), and/or a positive family history. However, patients with mild mutations of the CF transmembrane conductance regulator (CFTR) gene may have normal sweat testing. In these cases, a useful diagnostic adjunct involves measuring the nasal transepithelial potential difference. In intestinal and respiratory epithelia, the CFTR channel secretes chloride ions into the lumen and also has a tonic inhibitory effect on the opening of the epithelial sodium channel (ENaC), which decreases sodium reabsorption into the cell. This high luminal salt content helps retain water in the lumen, forming well-hydrated mucus. During the nasal transepithelial potential difference test, a saline solution is applied to the nose. Because patients with CF have increased sodium absorption via the ENaC, sodium is absorbed intracellularly but chloride in the saline solution is retained in the lumen. The higher relative amounts of negatively charged chloride on the epithelial surface result in a more negative transepithelial voltage difference. CFTR channel functioning is reversed in sweat ducts compared with that in respiratory and intestinal glands. CFTR reduces the salt content of sweat by reabsorbing luminal chloride and stimulating ENaC to increase sodium absorption from the lumen into the cells. CFTR mutations therefore result in the production of sweat with high chloride and sodium content. (Choice A) CFTR mutations lower the rate of bicarbonate secretion in the pancreatic ducts, promoting mucin precipitation and the formation of intraductal concretions that cause exocrine pancreatic insufficiency. However, this effect is not related to the nasal transepithelial potential difference test. (Choice B) CFTR mutations impair the passive transport of chloride along its concentration gradient, decreasing chloride secretion by respiratory epithelial cells. (Choice C) The water content of mucus is decreased (not increased) in patients with CF, resulting in dehydrated mucus that predisposes to the formation of mucus plugs and chronic sinopulmonary infections. (Choice E) CFTR mutations do not significantly alter transmembrane potassium transport. Educational objective: In cystic fibrosis, impairment of the cystic fibrosis transmembrane conductance regulator (CFTR) protein reduces chloride secretion and increases sodium absorption by the respiratory epithelia, resulting in dehydrated mucus. When saline is applied to the nasal mucosa, the increased sodium absorption in patients with CF causes a more negative nasal transepithelial potential difference, which can be used to diagnose cystic fibrosis. __________ References: Nasal potential difference measurements to assess CFTR ion channel activity. (http://www.ncbi.nlm.nih.gov/pubmed/21594779) Cystic fibrosis. (http://www.ncbi.nlm.nih.gov/pubmed/19403164)

A 6-Year-Old Caucasian Boy Is Brought to the Office by His