W21 - Cystic Fibrosis Flashcards
what is cystic fibrosis
a genetic autosomal recessive, systemic and multiorgan disease caused by defective ion transport
involves imbalance of fluid and electrolytes causing thick, sticky mucus and viscous secretions to accumulate in different organs
in what ethnicity is cystic fibrosis most common
caucasian
how deadly is cystic fibrosis
most lethal genetic autosomal recessive disease in the white population
What is cystic fibrosis caused by
mutation in a gene that encodes cystic fibrosis transmembrane conductance regulator
a chloride channel expressed in epithelial cells and other type of cells
what is autosomal mean
refers to any chromosomes other than the sex determining chromosomes
what does recessive mean
not expressed unless both copies are present
what does autosomal dominant mean
a gene on one of the non sex chromosomes that is always expressed, even if only one copy is present.
where is the CFTR located
apical membrane of secretory and absorptive epithelial cells of the pancreas, intestine, liver, airway, vas deferens and sweat glands + sweat glands.
What is the function of the CFTR protein
cyclic AMP dependent chloride channel, a bicarbonate channel and as a modulator of other ion channels
what does CFTR stand for
cystic fibrosis transmembrane conductance regulator
what is the CFTR
cloride channel expressed in epithelial cells that maintains
salt
fluid
pH homeostasis in various epithelial tissues
how do CFTRs form a pore
line up in parallel tail to tail forming a pore at its centre
What does NBD stand for
Nucleotide binding domain
what does RD stand for
Regulatory domain
Describe the role of NBD + RD in the channel
NBD + RD are in the cytosol and the membrane domain form the pore of the channel. RD is phosphorylated by a cAMP dep kinase, NBDs bind to and hydrolase ATP providing energy to open and close the pore.
what is the major NBD + RD function
regulating chloride conductance
What symptoms exist of pulmonary disease
copious sputum production persistent cough reduced lung function inflammation and tissue damage chronic airway infections
what is the main cause of morbidity and mortality of CF
chronic lung disease
what are 2 forms of pancreatic dysfunction
exocrine pancreatic insufficiency - impaired enzyme secretion from pancreas and malnutrition
endocrine pancreatic insufficiency - cf related diabetes mellitus
what effect does CF have on pancreatic secretions and the pancreas itself
pancreatic secretions have lower fluid volumes and increased acidity within the pancreatic lumen which leads to precipitation of the protein rich secretions which can cause plugging of small ducts and obstruction. Meaning more damage to pancreas.
what is Meconium ileus
20% of babies with CF have this, it is a condition where the content of the newborn child’s bowel (meconium) is extremely sticky and causes the bowel to be blocked at birth.
Meconium ileus is a bowel obstruction that occurs when the meconium of child intestine is even thicker and stickier than normal.
What are some gastrointestinal symptoms
thickened intestinal secretion, malabsorption, malnutrition, decreased gut motility. Salty tasting skin. Congenital absence of the vas deferens
what can result from a mutation of the CFTR
reduce transcription or translation
affect traffinking to surface
accelerate protein turnover
causes loss of protein
what are two ways in which we test for CF
blood test in new borns
sweat test in child / adult
Describe the pathophysiology of CF
CFTR gene defect
Defective ion transport
- lower chloride transport
- higher sodium absorption
- higher h20 absorption
airway surface liquid depletion
defective mucociliary clearance
mucus obstruction
infection
inflammation
At what point in the pathophysiology can we try and manage
Potentiators and correctors can be used at airway surface liquid depletion
mucoactives and physiotherapy can be used at mucus obstruction
immunomodulatory therapy, antimicrobial
what are mucoactives
increase the ability to expectorate sputum and or decrease mucus hypersecretion
What are the 4 types of mucoactives
expectorants (induce cough or increase the volume of secretions)
mucolytics (reduce the viscosity of mucus)
mucokinetic drugs (increase the mobility and transportability of mucus)
mucoregulators (control the process of hypersecretion)
what is an example of first line mucoactives
inhaled recombinant human DNase I degrades DNA
What is ivacaftor (kalydeco)
conductance regulator potentiator for CFTR channel with a G551D A “missenge” gating mutation. Ivacaftor increases the time the mutated CFTR is open, allowing chloride ions to flow through. This action partially normalises the consistency of mucous and digestive juices in cystic fibrosis.
what is lumacaftor
channel corrector
what is a channel corrector
acts as a protein folding chaperone, aiding the conformational stability of the mutated CFTR protein.
what is the purpose of chest physiotherapy
to augment clearnace of tenacious airway secretions
Help postural drainage and percussion in varied positions that help draining mucus, chest is clapped and vibrated to help dislodge mucus to large airwayts
what is postural drainage
positions to help drain mucus
