CFTR: gene that produces an integral membrane glycoprotein that acts as a CFTR channel that transports s chloride, bicarbonate and glutathione.
Mucus: a slimy substance, typically not miscible with water, secreted by mucous membranes and glands for lubrication, protection.
What is Cystic Fibrosis?
A genetic disease resulting in abnormal secretions of the exocrine glands that influence a variety of clinical effects: chronic lung disease and pancreatic insufficiency most commonly.
What causes it?
When both parents carry one copy of the mutant gene (heterozygotes), they can pass on the recessive homozygous mutant gene
The heritable gene mutation is located on chromosome 7
Mutation of the CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) protein: when a codon (3 nucleotide bases) called delta-F508 is deleted
Deletion causes the protein coding sequence to shift up
CFTR protein misfolds and cannot bind to membrane
Due to the absence of the CFTR protein, chloride ions are not exported and they build up inside the cell
Water is attracted to the negative charge of chloride so it moves down its concentration gradient and diffuses into the cell.
The cell then becomes hyperosmotic (higher osmolality inside cell than outside) causing it to burst.
Mucus then becomes viscous due to lack of water
Guido Fanconi first recognized the disease in 1936 in his paper.
Dorothy Andersen wrote a journal based on her studies describing the clinical features and pathology of CF (1938).
What it causes:
Thickened mucus clogs ducts and airways, increases infections.
Oxygen transport decreases due to mucous blocking and collapsing airways, and due to infection causing alveoli inflammation.
Mucus clogging ducts of the pancreas or liver prevents secretion of enzymes and results in hepatic and pancreatic insufficiency.
Pancreatic Damage can cause type 1 diabetes because of reduced insulin production.
Faltering of normal growth and weight loss due to malnutrition.
Meconium ileus (distal intestinal obstruction syndrome): abnormal solid contents of the small bowel.
Male infertility: CBAVD (Congenital bilateral absence of the vas deferens): genital form of CF (when sperm cannot travel throughthe tubes in the testes-unproperly developed-to become part of semen).
Antibiotics (orally, intravenously, inhalation).
Percussive therapy (airway clearance vest).
Pancreatic enzymes (replacement therapy)
Immunosuppressive therapy (for life):