Cystic fibrosis

HPT Group 18
Cystic fibrosis (CF)
● It’s a genetic disorder which mostly affects the lungs and organs of the digestive
system (pancreas , ).
● It’s more common in caucasians than in other races.
Definitions
● Cystic ---->fluid sacs wrapped in a membrane.
● Fibrosis ---->excess connective tissue that can replace or infiltrate normal tissues in
organs.
Causes
● CF is an autosomal recessive disorder
● It involves CFTR (cystic fibrosis transmembrane conductance regulator) gene.
● CFTR gene codes for CFTR protein.
● CF only develops when there is a mutation in CFTR gene.
● There need to be two mutated CFTR gene inherited to have CF. (one from the mother
and one from the father.)
● If both parents have one normal CFTR gene and on mutated, they are known as the
carriers and may or may not exhibit mild symptoms depending on which mutation
they have.
Comparison of normal and mutant CFTR channel

.
Mutation of CFTR channels
● CFTR protein is a channel that pumps chloride ions out of cells and into various
secretions.
● Chloride ions help to draw water into the secretions, which ends up thinning them
out.
● Most common mutation with CFTR is ΔF508 mutation on chromosome number 7.
● It means 508th amino acid out of 1480 pheylalanine is deleted and missing.
● CFTR channel with this mutation becomes misfolded and can’t migrate from
endoplasmic reticulum to cell membrane.
● I.e. there is a lack of CFTR protein at the epithelial surface, hence chloride ions can’t
be pumped out, therefore water isn’t drawn in and secretions are left overly thick.
Early childhood
● Pancreatic insufficiency is the most prominent effect of CF.
● Thick secretion jams up the pancreatic ducts, not allowing digestive enzymes to
make it to the small intestine.
● Without those enzymes, protein and fat aren’t absorbed, causing poor weight gain
and failure to thrive.
● Fat malabsorption can lead to steatorrhea(fatty stools).
● In newborns ,the first stool (Meconium) gets thick and sticky and is stuck in
intestines.
● This is called a Meconium Ileus and is surgical emergency.
(cont.)
● Eventually pancreas gets damaged, because the blocked up digestive enzymes
degrade the cells lining the pancreatic ducts.
● This causes local inflammation, which leads to acute pancreatitis and with repeated
episodes, chronic pancreatitis with the development of cysts and fibrosis giving its
name.
● Endocrine function of pancreas can also be compromised causing Insulin-dependent
diabetes.
Pancreatic duct clogged by thick mucus
Later in childhood
● Lung problem will start to crop up.
● Normally cilia lining the airway keeps the lungs clean, by moving the mucus which
catches the bacteria, dust, etc away from it towards the pharynx.
● This process is called mucociliary action.
● But with the thick mucus it makes it harder for the mucociliary action to occur.
Normal Mucociliary action in lungs
Diagnosis
● Newborn screening

__ areas where CF is common.

__detects pancreatic enzyme IRT (immunoreactive trypsinogen).

__ sweat test ---> detects high chloride ions.

Treatment
● Nutrition and healthy weight gain

__ fat soluble vitamins (.e.g. AEDK)

__ extra calories

__ replacement pancreatic enzymes

Treatment (cont.)
● Pulmonary treatment

__ chest physiotherapist

__ inhalers