Buffl

Pathophysiology

FC
von Felix C.

Describe the pathophysiology.

  • General considerations

    • The CFTR gene encodes the CFTR protein, which is an important component of the ATP-gated chloride channel in cell membranes.

    • Mutated CFTR genemisfolded protein → retention for degradation of the defective protein in the rough endoplasmic reticulum (rER) → absence of ATP-gated chloride channel on the cell surface of epithelial cells throughout the body (e.g., intestinal and respiratory epithelia, sweat glands, exocrine pancreas, exocrine glands of reproductive organs) [6][7]

  • In sweat glands

    • The chloride channel is responsible for transporting Cl- from the lumen into the cell (reabsorption).

    • Defective ATP-gated chloride channel → inability to reabsorb Cl- from the lumen of the sweat glands → reduced reabsorption of Na+ and H2O → excessive loss of salt and elevated levels of NaCl in sweat

  • In all other exocrine glands (e.g., in the GI tract or lungs)

    • The chloride channel is responsible for transporting Cl- from the cell into the lumen (secretion).

    • Defective ATP-gated chloride channel → inability to transport intracellular Cl- across the cell membrane → reduced secretion of Cl- and H2O → accumulation of intracellular Cl- → ↑ Na+ reabsorption (via ENaC) → ↑ H2O reabsorption → formation of hyperviscous mucus → accumulation of secretions and blockage of small passages of affected organs → chronic inflammation and remodeling → organ damage (see “Clinical features” below)

    • ↑ Na+ reabsorption → transepithelial potential difference between interstitial fluid and the epithelial surface increases (i.e., negative charge increases; e.g., from normal -13 mv to abnormal -25 mv)


Author

Felix C.

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