Pathophysiology of CF<< Back to About CF
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Mutations in the CFTR gene can affect the quantity and/or the function of CFTR channels at the cell surface. The type of mutation has a significant impact on the extent of abnormal chloride transport and, consequently, on the patient’s symptoms.
Pulmonary disease is the most challenging aspect of managing CF and is the main cause of mortality. CFTR dysfunction is associated with a change in the composition and quantity of the airway surface liquid resulting in impaired clearance of bacteria from the airway.
Elevated sweat chloride is a hallmark symptom of CF and is used as a diagnostic marker. Abnormal CFTR inhibits the reabsorption of chloride from sweat into the cells lining the sweat duct. Retention of chloride ‘traps’ sodium ions on the skin surface leading to characteristic salty sweat.5
Although liver abnormalities are not considered a dominant manifestation in CF, 25% of sufferers of CF show signs of liver disease and about 6–8% have established cirrhosis.3 CFTR dysfunction can lead to increased viscosity of bile, obstructing hepatic ducts and causing focal biliary cirrhosis.
About 85–90% of people with CF suffer from pancreatic insufficiency, with symptoms including diarrhoea, abdominal pain, excessive bowel gas, malabsorption of nutrients and failure to thrive.1 These symptoms are caused by thickened exocrine secretions obstructing pancreatic ducts, leading to accumulation of digestive enzymes in the pancreas and auto-digestion of pancreatic tissue.2
Gastrointestinal (GI) abnormalities are frequently seen in CF and result in malabsorption of essential nutrients from the gut. Reduced chloride and water secretion into the gut can cause two predominant conditions: meconium ileus at birth and distal intestinal obstruction syndrome (DIOS) later in life.4
Virtually all men with severe CF are infertile due to a condition called congenital bilateral absence of the vas deferens (CBAVD). As the male reproductive system develops in the uterus, abnormal CFTR leads to obstruction of the vas deferens with mucus, resulting in atrophy.