The airway epithelial defect in cystic fibrosis is
Correct Answer: | sodium absorption
Description: Ans. a (Sodium absorption) (Ref: Harrison's Internal medicine 16th edition, p. 1544)The 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 mEq/L) in sweat is diagnostic. Can present with contraction alkalosis and hypokalemia (ECF effects analogous to a patient taking a loop diuretic) because of ECF H20/Na+ losses and concomitant renal K+/H+ 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.
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