Cystic Fibrosis (CF) is a genetic disorder that primarily affects the body’s exocrine glands, which produce sweat, mucus, tears, saliva, and digestive juices. These secretions are normally thin and slippery, lubricating and protecting various internal pathways. In individuals with CF, however, a genetic change causes these fluids to become abnormally thick and sticky, leading to a range of health challenges.
The Genetic Origin
Cystic Fibrosis arises from a mutation within the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. This gene provides the instructions for making the CFTR protein, which is found on the surface of cells in many organs throughout the body.
CF is inherited in an autosomal recessive pattern, meaning an individual must inherit two copies of the defective CFTR gene to develop the disease—one from each parent. If a person inherits only one copy of the mutated gene and one normal gene, they are considered a carrier. Carriers do not experience symptoms of CF because the normal gene produces enough functional CFTR protein.
When two carriers have a child, there is a 25% chance the child will inherit two copies of the defective gene and develop CF. There is also a 50% chance the child will be a carrier, like their parents, and a 25% chance the child will inherit two normal genes and neither have CF nor be a carrier. Many different mutations in the CFTR gene have been identified, with the F508del mutation being the most common.
Defective Ion Transport
The CFTR protein normally functions as a channel that transports negatively charged chloride ions across cell membranes. This movement of chloride ions regulates water flow in tissues, helping produce thin, freely flowing mucus. The CFTR protein also regulates other ion channels, such as those that transport positively charged sodium ions.
In individuals with CF, mutations in the CFTR gene lead to a faulty or absent CFTR protein. This disruption prevents the chloride channels from functioning properly, impairing the transport of chloride ions and the movement of water across cell membranes. As a result, the body’s secretions, including mucus, sweat, and digestive juices, become unusually thick and sticky.
This impaired ion transport leads to dehydration of mucus, making it stickier and harder to clear. In sweat glands, for instance, the defective CFTR prevents the reabsorption of chloride and sodium, resulting in abnormally salty sweat.
Organ System Manifestations
Lungs
The lungs are impacted by the defective CFTR protein, as the thick, sticky mucus obstructs airways. This mucus accumulation impairs the mucociliary escalator, the natural defense mechanism that clears inhaled particles and bacteria from the lungs. Without proper clearance, bacteria can colonize the airways, leading to chronic infections.
These persistent infections trigger ongoing inflammation, which causes progressive damage to the lung tissue, characterized by the widening and scarring of the airways, a condition known as bronchiectasis. Over time, this cycle of infection and inflammation can lead to severe lung damage and reduced lung function, which is a major cause of death in individuals with CF.
Pancreas
The pancreas is another organ affected by CF, with most patients experiencing pancreatic insufficiency. Thick mucus blocks the small ducts that carry digestive enzymes from the pancreas to the intestines. This blockage prevents enzymes, which are necessary for breaking down fats, proteins, and carbohydrates, from reaching the digestive system.
The enzymes then build up within the pancreas, causing inflammation, a condition known as pancreatitis. This malabsorption of nutrients leads to poor weight gain, delayed growth, and deficiencies in fat-soluble vitamins. Additionally, damage to the pancreas can impair insulin production, leading to Cystic Fibrosis-Related Diabetes (CFRD), which affects many individuals with CF.
Liver
Liver involvement in CF occurs in many patients. The thick bile, a fluid produced by the liver, can block the small bile ducts within the liver and gallbladder. This obstruction can lead to inflammation and scarring, a process known as biliary fibrosis.
In some cases, this scarring can become widespread and irreversible, leading to cirrhosis, a severe form of liver damage that impairs the liver’s ability to function properly. These complications can include jaundice, fluid accumulation in the abdomen (ascites), and high blood pressure in the portal vein (portal hypertension).
Intestines
The digestive tract is broadly affected by the thick secretions in CF. In newborns, this can manifest as meconium ileus, a complete intestinal obstruction caused by abnormally thick and sticky meconium (the first stool passed by an infant). In older children and adults, a similar condition called Distal Intestinal Obstruction Syndrome (DIOS) can occur.
DIOS involves the partial or complete blockage of the distal small intestines and/or proximal colon by thickened intestinal contents. Symptoms include abdominal pain, bloating, decreased bowel movements, and sometimes a palpable mass in the lower right abdomen. These intestinal issues are linked to reduced fluid intake and insufficient pancreatic enzyme supplements.
Sweat Glands
Individuals with CF exhibit abnormally salty sweat, a hallmark symptom used in diagnosis. This occurs because the defective CFTR protein in the sweat ducts impairs the reabsorption of chloride ions. Normally, as sweat moves through the sweat duct, chloride and sodium are reabsorbed back into the body.
In CF, the dysfunctional CFTR protein prevents this reabsorption, leading to excessive amounts of chloride and sodium remaining in the sweat. The sweat of individuals with CF contains higher sodium and chloride concentrations compared to healthy individuals.
Reproductive System
CF can impact fertility in both males and females. Most men with CF experience infertility due to congenital bilateral absence of the vas deferens. The vas deferens, the tubes that transport sperm from the testicles, are either blocked with thick mucus or are entirely absent, preventing sperm from mixing with semen. Despite this, sperm production in the testes is unaffected, and men with CF can father biological children through assisted reproductive technologies.
Women with CF have anatomically normal reproductive tracts and can conceive naturally. However, they experience reduced fertility compared to women without CF. This can be due to factors such as thicker cervical mucus, which makes it harder for sperm to reach the egg, and a higher risk of irregular or absent menstrual cycles, linked to chronic illness or low body weight.