Cystic fibrosis (CF) is a long-term, inherited genetic disorder that primarily affects the lungs and digestive system. This condition begins as a malfunction at the molecular level within individual cells, disrupting the body’s ability to maintain the proper balance of salt and water on its surfaces. Symptoms like thick, sticky mucus are a direct consequence of this cellular failure. Understanding this cellular breakdown is foundational to grasping how the condition impacts the entire body.
The CFTR Protein: The Cell’s Gatekeeper
The molecular malfunction in cystic fibrosis centers on the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein. This large protein is an ion channel, a type of gate embedded in the outer membrane of epithelial cells throughout the body. CFTR is especially prevalent on cells lining passageways in organs like the lungs, pancreas, sweat glands, and digestive tract.
The gene that provides instructions for this protein is also called CFTR and is located on chromosome 7. The protein spans the cell membrane, allowing it to control the movement of charged particles between the inside and outside of the cell. This function as a regulated gate is central to maintaining fluid balance across many organ systems.
Normal Cell Function and Ion Transport
In a healthy cell, the CFTR protein operates as a regulated conduit, primarily allowing negatively charged chloride ions to move out of the cell and onto the cell surface. This movement is typically activated when internal signals, such as a rise in cyclic AMP, prompt the channel to open. Once the chloride ions have exited, they create an electrical gradient outside the cell.
This charge imbalance naturally draws positively charged sodium ions and water to follow the chloride out of the cell via osmosis. This water movement hydrates secretions on the cell surface, such as mucus. The resulting thin, watery layer of mucus is easily swept away by cilia, effectively clearing debris and pathogens from the airways. This precise regulation of water and salt balance is necessary for the proper function of tissues that produce secretions.
How Genetic Mutations Disrupt Cell Processes
Cystic fibrosis results from inherited mutations in the CFTR gene, of which over 2,000 variations have been identified. These mutations cause a spectrum of defects in the CFTR protein, preventing it from functioning correctly as a channel. The effects are broadly categorized by how they disrupt the protein, ranging from non-production to the blockage of the channel’s opening.
The most frequent mutation, Delta F508 (or F508del), is responsible for the majority of CF cases. This specific mutation involves the deletion of a single amino acid, phenylalanine, which causes a major problem with protein folding during manufacturing. The cell’s quality control system recognizes the misfolded protein as defective and prematurely destroys it. Consequently, the CFTR protein never reaches the cell membrane where it is needed. Other mutations may allow the protein to reach the surface, but the channel remains locked shut, failing to open and allow ion transport.
Cellular Consequences and Organ Impact
When the CFTR gate fails or is missing from the cell surface, the flow of chloride ions out of the cell is severely reduced. Without these ions establishing an osmotic gradient, water is not drawn out of the cell onto the surface. This failure leads to the dehydration of the thin fluid layer that normally bathes the epithelial cells.
The immediate consequence is that the mucus covering the cells becomes abnormally thick, sticky, and viscous. This dehydrated mucus is too dense for the cilia to move effectively, leading to its accumulation and obstruction of small airways and ducts. The thick mucus creates an environment favorable for bacteria, triggering chronic infection and inflammation that progressively damages lung tissue. In the pancreas, ducts clog with thick secretions, preventing digestive enzymes from reaching the small intestine and causing malabsorption.