<prompt> The airway epithelial defect in cystic fibrosis issodium absorptionsodium absorptionchloride secretionNone of the above  <response>: Ans. a Sodium absorption Ref: Harrisons Internal medicine 16th edition, p. 1544The normal basal pattern for ion transport is absorption of Na from the lumen via an amiloride-sensitive Na channel. This process is accelerated in CF, The capacity to initiate cyclic AMP mediated Cl secretion is diminished in CF airway epithelia due to absence dysfunction of the CFTR Cl channel. The accelerated Na absorption in CF reflects the absence of CFTR inhibitory effects on Na channels.CYSTIC FIBROSIS: Pathophysiology The diagnostic biophysical hallmark of CF airway epithelia is the raised transepithelial electric potential difference PD. The transepithelial PD reflects both the rate of active ion transport and epithelial resistance to ion flow. CF airway epithelia exhibit abnormalities in both active Na absorption and active CT secretion. An important observation is that there is also a molecularly distinct Ca2-activated CT channel CaCC expressed in the apical membrane. This channel can substitute for CFTR with regard to CT secretion and may be a potential therapeutic target. The central hypothesis of CF airways pathophysiology is that the faulty regulation of Na absorption and inability to secrete CT via CFTR reduce the volume of liquid on airway surfaces, i.e., they are dehydrated.Cystic fibrosis: SummaryGENETICSAutosomal recessive; defect in CFTR gene on chromosome 7; commonly a deletion of Phe508. Most common lethal genetic disease in Caucasian population.CFTR encodes an ATP-gated CI- channel that secretes CI- in lungs and GI tract, and reabsorbs CI- in sweat glands.PaTHOPHYSIOIOGYMutations--misfolded protein-protein retained in RER and not transported to cell membrane, causing CI- and H20 secretion; T intracellular CI- results in compensatory Na reabsorption via epithelial Na channels - H2O reabsorption- abnormally thick mucus secreted into lungs and GI tract, Na reabsorption also causes more negative transepithelial potential difference. DIaGNOSIS Cl- concentration 60 mEqL in sweat is diagnostic. Can present with contraction alkalosis and hypokalemia ECF effects analogous to a patient taking a loop diuretic because of ECF H20Na losses and concomitant renal KH wasting.COMPIICaTIONSRecurrent pulmonary infections e.g., Pseudomonas, chronic bronchitis and bronchiectasis - reticulonodular pattern on CXR, pancreatic insufficiency, malabsorption and steatorrhea, nasal polyps, and meconium ileus in newborns. Infertility in males absence of vas deferens, absent sperm. Fat-soluble vitamin deficiencies A, D, E, K.TREaTMENTN-acetylcysteine to loosen mucus plugs cleaves disulfide bonds within mucus glycoproteins, dornase alfa DNAse to clear leukocytic debris. 