Chapter 38: Cystic Fibrosis

High-Yield Facts

• Cystic fibrosis (CF) is the most common, life-limiting, autosomal recessive disease among Caucasians in the United States.

• It occurs in approximately 1 in 3500 White births and is being diagnosed increasingly in non-Caucasians as well.¹ (Fig. 38-1)

• Most patients with CF have the classic triad of manifestations:

  • Chronic pulmonary disease

  • Malabsorption due to pancreatic insufficiency

  • Elevated concentrations of sweat sodium and chloride.²

• There is considerable individual variation in the clinical manifestations, severity, and course of the disease.

Etiology/Pathophysiology

Cystic fibrosis (CF) is caused by mutations in the gene that encodes the cystic fibrosis transmembrane conductance regulator (CFTR) protein.^1,3–5 This protein, which is located in the epithelial cell membrane, functions normally as a cAMP-activated chloride channel, transporting chloride (and passively water) out of the cell into the adjacent lumen.^1,4,5 CFTR also plays a role in bicarbonate transport from the cell into the lumen.^1,4,5 CFTR is involved in regulating sodium channels for airway epithelial cells, helping to limit sodium (and water) reabsorption from the lumen to the cells.^1,4,5 In sweat gland ductal cells, CFTR transports chloride in the opposite direction, that is, from the lumen into the cell.¹ These mechanisms help explain the clinical manifestations of the disease.

The CFTR gene is located on the long arm of chromosome 7. The most common mutation that causes CF (F508del)—and more than 1500 less-common mutations—has been identified.^1,4 Five classes of mutations have been identified.⁶ Organs that express the CFTR gene (particularly the sinuses, lungs, pancreas, liver, gastrointestinal [GI] tract, and reproductive system) are the ones affected by the mutations.⁴ The relationship between genotype and clinical manifestations is not always straightforward, however.^1,4

The most important pathophysiologic consequence of these CFTR “defects” is diminished water in mucus and most exocrine secretions (along with associated electrolyte and other abnormalities).^1,2,4 Mucus and exocrine secretions are more viscid, and they are difficult to clear, causing airway and ductal obstruction.^1–4,7 In the airways, these mucus (and possibly other) abnormalities predispose to chronic infection with a characteristic group of bacterial organisms and inflammation.^1–5,7 Exactly why this predisposition to specific infections occurs has yet to be fully elucidated. Various hypotheses have been proposed which are discussed in some detail in the references^1–5 (Table 38-1).