B4.076 Cystic Fibrosis Flashcards
(46 cards)
what is meconium ileus
abdominal distension
failure to pass meconium (first stool after birth)
what is the CF gene?
spans 250 kilo bases on chromosome 7
encodes CFTR protein (1480 AAs)
more than 1800 CF causing mutations in CF gene have been identified
varying degrees of protein dysfunction
what is CFTR
cystic fibrosis transmembrane conductance regulator
conducts chloride and bicarbonate across the cell membrane
why do people with CF have salty sweat?
Cl cannot be transported out ductal lumen into the tissues, so more Cl binds to Na in the lumen and exits the sweat ducts
where are CFTRs found
widely throughout body in epithelial cells
what is the pathogenesis of CF
loss of CFTR function results in abnormal regulation of airway surface liquid which sets the stage for chronic infection and related inflammation
what type of disease is universal amongst CF patients?
chronic lung disease
why are mutations categorized into groups?
categories of mutations can have different effects on protein function
this can be used to provide targeted therapies
what are some examples of effects of mutations on protein function
- no functional protein made
- protein not trafficked to membrane
- defective channel regulation
- decreased channel conductance
- reduction of synthesis of CFTR
- decreased CFTR membrane stability
most common mutation
Phe508 del (86.4% of people) trafficking defect
different organ systems affected by CF
general (growth and vitamin deficiencies) nose and sinuses liver gallbladder bone intestines lungs heart spleen stomach pancreas reproductive
major lung manifestation of CF
bronchiectasis
why are many male CF patients infertile?
absence of vas deferens
80-85% of males with CF
screening algorithm for CF in newborns
immunoreactive trypsinogen/CFTR (IRT/DNA)
- look at IRT level IRT >60
-look at CFTR mutation panel
if unsure after results, check sweat chloride (>60 diagnostic)
what is immunoreactive trypsinogen (IRT)
pro enzyme for pancreatic enzyme trypsin
can accumulate in blood if not distributed appropriately due to pancreatic dysfunction
clinical symptoms consistent with CF
failure to thrive
pulmonary symptoms
meconium ileus
evidence of CFTR dysfunction
elevated IRT
sweat chloride
mutation analysis
inheritance of CF
autosomal recessive
30,000 pts in US
carrier frequency varies from 1/20 to 1/80
carrier frequency for Phe503del
1/30
most common
what is oily stool indicative of
pancreatic insufficiency
what is pancreatic insufficiency
defective CFTR function result in viscous exocrine fluids
fluid becomes inspissated in the pancreatic ducts
pancreatic duct obstruction reduced secretion o pancreatic enzymes
what is fecal elastase and what is it used for
pancreatic enzyme
will be low in pancreatic insufficiency bc not secreted correctly
used to diagnose pancreatic insufficiency
what portion of CF patients get pancreatic insufficiency
2/3
what digestion specific pancreatic enzymes are reduced in pancreatic insufficiency
amylase
lipase
phospholipases
