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HIGH-YIELD FACTS

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

  • Most patients with CF have the classic triad of manifestations: chronic pulmonary disease, malabsorption due to pancreatic insufficiency, and elevated concentrations of sweat chloride and sodium.

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

  • In a patient known to have CF, the most common reason for presenting to the emergency department (ED) is for a pulmonary exacerbation.

  • Gastrointestinal (GI) complications include malabsorption, obstruction, and hematemesis.

  • In this era of universal newborn screening, it is rare for a patient to present with undiagnosed CF.

ETIOLOGY

Cystic fibrosis (CF) is caused by mutations in the gene that encodes the cystic fibrosis transmembrane conductance regulator (CFTR) protein.1–4 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.3,4 CFTR also plays a role in bicarbonate transport from the cell into the lumen. CFTR is involved in regulating sodium channels for airway epithelial cells, helping to limit sodium and water reabsorption from the lumen to the cells. In sweat gland ductal cells, CFTR is responsible for transport of chloride into the cell, leading to increased salt in sweat when CFTR is defective. These mechanisms help explain the clinical manifestations of the disease.

GENETICS

The CFTR gene is located on the long arm of chromosome 7. The most common mutation that causes CF is F508 deletion. There are more than 1500 less-common mutations grouped into six classes.1,5,6

PATHOPHYSIOLOGY

The sinuses, lungs, pancreas, liver, biliary tract, gastrointestinal tract, and reproductive system express the CFTR gene and are affected by its mutation.2–4 However, the relationship between genotype and clinical manifestations is not always consistent. 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.4 Mucus and exocrine secretions are more viscid, and they are difficult to clear, causing airway and ductal obstruction.3,7 In the airways, these mucus and possibly other abnormalities predispose to chronic inflammation as well as chronic infection with a characteristic group of bacterial organisms including Pseudomonas aeruginosa, Aspergillus, and Staphylococcus aureus.2,4 This predisposition to specific infections has yet to be fully elucidated. Various hypotheses have been proposed (Table 39-1).3,4

TABLE 39-1Factors Hypothesized to Predispose to Airway Infection with Characteristic Organisms in CF Patients

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