Cystic Fibrosis Flashcards
What systems does it affect most?
digestive, sweat glands, reproductive tract, lungs
Major cause of Morbidity and Mortality
progressive lung disease
How many genes and what chromosome
single gene, chromosome 7
What does chromosome 7 encode?
CF trans-membrane conductance regulator
(CFTR) protein
Which endocrine system does it affect?
Exocrine
Dominant or Recessive?
Autosomal recessive
CFTR protein
regulates volume and composition of exocrine secretion
How many different mutations are listed?
more than 1900
What is the most common mutation?
delta F508 (CLASS II) -- found in 70% of Caucasian CF patients
Why is it found in higher frequency in certain ethnic groups?
Founders effect
How many classes of the disease?
5
What classes cause the most severe disease?
mutations in classes I-III
Defective protein production is class…
…1
Class I Mutation
- caused by
- leads to
- Caused by nonsense, frame-shift or splice-site mutations
- Leads to premature termination of the mRNA
Founders Affect
- what pop and how frequent
- what kind of mutation
- 60% of Ashkenazi Jews
- nonsense mutation
Class II Mutation
- caused by
- leads to
- deltaF508
- prevents protein from trafficking to the correct cell location
deltaF508
class II 50% CF pts homozyg. for the deletion 90% are heterozyg.
Class III
Limited response to ATP
Class IV
rate of ion flow and duration of channel opening are reduced compared to normal function of the protein
Class V
reduced amount of the CFTR protein
can also alter stability of the mature protein
Gene Modifiers
- causes inconsistent associations between CF geno and phenotypes
- not directly related to CFTR gene but affect the clinical manifestations
Gene modifier evidence
20% pts with classic CF carry modifiers that exacerbates the pulmonary disease
Mannose-binding lectin protein
- a gene modifier
- important component of complement system
- when deficient, increases risk for infections with fevers
- risk for Burkholderia cepacia infections and early death
TGF-beta 1
- transforming growth factor-beta
- suppressor of T-cell activation
- associated with the most severe cases of CF
How long to pts survive?
Highly varriable
Chronic…
infections of the respiratory tract
Mild?
10% pts have unusually mild sx
immunoreactive trypsinogen test
- checks for immunoreactive trypsinogen chemical made by the pancreas
- when pancreas is stressed when a baby is born, more of this chemical is made
- can be high if premature or has CF
Gibson-Cooke
gauze that collects sweat in chloride sweat test
Chloride Sweat Test
value > 60 = CF
- 20% of children with middle results have DNA evidence of CF
- children with ambiguous results have (+)sweat test and some sx but not entire disease
Classic CF
diagnosed if in one or more organ systems
Non-classic
- likely in pts first diagnosed as adults
- lower frequency of delta F508 mutation
Survival rate
36.8 years
Signs and Sx
- persistant pulmonary infections
- pancreatic insufficiency
- elevated sweat chloride levels
Staph. aureus
Haemophilus
flu
pseudomonas aeruginosa
common flora found in CF cultures
burkholderia cepacia complex
- bacteria that indicates significant disease and that pt is declining
- accelerated decline in pulmonary function and shortened survival
- contraindication to transplantation
Tenacious exocrine secretions
obstruct pancreatic ducts and impair production and flow of digestive enzymes to duodenum
Pancreatic effects
loss of islet cell mass= CF-related diabetes mellitus
-30% of adults
Hepatic Effects
Multilobular cirrhosis in 4-15% of pts
Intestinal Effects
10-20% of newborns with CF have meconium ileus
Pediatric CF
- infants presenting with meconium ileus diagnosed within the first two weeks
- others diagnosed around 14.5 months
Reproductive effects
secretory obstruction of the vas deferens
-1/2 of men with bilateral absence of vas deferens have 2 CFTR mutations
DNA test
- what results should be checked?
- what how many mutations do labs test for?
intermediate sweat test results should be clarified by DNA using a CFTR multi-mutation method
- most labs in US test for 23 mutations
- California does 40
CF confirmed other ways?
- 2 CF causing mutations detected
- sweat test intermediate or positive
CRMS
CFTR-related metabolic syndrome
Nasal Potential Difference Measurements
test that shows abnormalities in epithelial chloride secretion
pseudomonas aeruginosa
CF pts are particularly susceptible to this bacterial infection and can happen as early as the first year of life
Staphylococcus
bacteria most frequently identified in CF secretions from children and infants
