IIA.2. Organ-specific pathophysiology 
IIA.2.a. Lung: 
The diagnostic biophysical hallmark of CF is the raised transepithelial 
electric potential difference (PD) detected in airway epithelia (15). The 
transepithelial PD reflects components of both the rate of active ion transport and 
the resistance to ion flow of the superficial epithelium. CF airway epithelia exhibit 
both raised transport rates (Na + ) and decreased ion permeability (CF) (16,17) 
(Figure 1). The Cl" transport defect appears to be the result of abnormal regulation 
of Cl" transport (17,18). CF epithelia do not respond to (3-agonists or agonists that 
activate protein kinase C with Cl" secretion as normal airway epithelia do (19,20). 
This failure to regulate cellular Cl" transport is a direct consequence of mutations in 
the CFTR protein (shown by "cap" on Cl" CFTR in Figure 1). 
NORMAL CYSTIC FIBROSIS 
AIRWAY LUMEN AIRWAY LUMEN 
Figure 1. Epithelial ion transport by normal and CF airway epithelia. 
Raised Na + absorption is a feature of CF airway epithelia. Na + transport 
abnormalities in CF are not a widespread feature of the CF epithelial phenotype 
and appear confined to volume absorbing epithelia. The mechanisms for Na^" 
hyperabsorption reflect in part an increase in apical cell membrane Na + channel 
activity. It is not yet known how the abnormal CF gene product, CFTR, produces 
the Na + transport defect. 
The central hypothesis of CF airways pathophysiology has been that the 
abnormal Na + and Cl" transport rates produce secretions that are dehydrated and 
poorly cleared. The unique predisposition of CF airways to chronic infection by 
Staphylococcus aureus and Pseudomonas aeruginosa raises the issue that other as yet 
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Recombinant DNA Research, Volume 17 
