Cystic Fibrosis Flashcards
What is pilocarpine iontophoresis?
the sweat test for CF
CF is autosomal recessive. Do individuals who are heterozygous have any risk of symptoms?
Yes! over the past 15 years it was been observed that persons who carry one copy or a mutant CF gene are at increased risk for pancreatitis. CFTR mutations have also been associated with increased risk for liver cirrhosis, male infertility, bronchiectasis and chronic sinusitis.
What effect does the CFTR channel have on bicarbonate?
it regulates bicarbonate uptake in the pancreas and airways, affecting the pH and is associated with the etiology of lung disease
What effect does the CFTR channel have on epithelial sodium channels? (ENaC)
negative regulation
in disease, that means that sodium is not as well regulated, in addition to chloride
What is the most common type of CFTR mutation leading to disease?
Group II F508del
a missense mutation leading to misfolding and protease degradation of the channel
also associated with Group IV mutations that affect plasma membrane stability and are rescued by therapeutic correctors?
How many CFTR mutation groups are there?
6 -
1 = no functional production due to a stop mutation
3 through 6 are missense mutations that affect folding, regulation, function, numbers, and turnover respectively
What is the mutation associated with the most severe forms of CFTR?
group 1 stop codon mutations that prevent any functional CFTR production
What is the inciting event in CF lung disease?
infection
What makes up the vicious cycle of CFTR lung disease?
Infection leading to tissue damage leading to inflammation leading to altered airway secretion leading back to infection
What are the signs of tissue damage that emerge with CF lung disease within months?
bronchiectasis (signet ring sign)
chronic sinusitis
nasal polyposis
areas from cystic areas and fibrosis in the lungs
What pathological change in the lungs causes respiratory failure and death in 85% to 90% of affected CF individuals?
bronchiectasis
How is pseudomonas auruginosa infection different in CF patients compared to acute infections in the general population?
Patients with CF have PA infection that can last for decades and mutates frequently in their CF patient host which leads to multiple phenotypic differences compared to PA in the environment or in acute PA infections. One such difference is the presence of a mucoid phenotype and its development in CF portends a poorer long-term prognosis. In addition PA will also grow in small mushroom shaped communities termed biofilms. Biofilms serve to protect PA from antibiotics and inflammatory cells.
What GI problems do approximately 90% of CF patients have?
Approximately 90% of affected patients have pancreatic exocrine insufficiency and malabsorption due to pancreatic obstruction and fibrosis.
What GI problems tend to occur in untreated or undertreated CF patients?
Malnutrition and deficiencies of fat-soluble vitamins occur in untreated or undertreated subjects.
How does abnormal viscous secretions and dysmotility in the GI tract lead to problems in CF patients?
Abnormally viscous secretions and dysmotility in the intestinal tract leads to constipation and a variety of intestinal obstruction syndromes, including meconium ileus in newborns and distal intestinal obstruction syndrome (DIOS) in others.
What are two signs of liver involvement in young or infant CF patients?
Liver involvement includes obstructive jaundice in infants and cirrhosis in children and young adults.
What risk do pancreatic sufficient CF patients have?
pancreatitis, leading to pancreatic insufficiency over time
What percentage of new CF diagnosis are made during the first year of life?
66% - still room for adult screening!!
What is the first step in screening for CF?
Immunoreactive trypsin
If you get a positive IRT, what is the next step in screening for CF?
repeat IRT or genotyping
If a patient has a positive genotype or continually elevated IRTs, what is the next step in CF screening?
Sweat testing
What is the cutoff for sweat testing that makes CF likely or intermediately likely?
30 to 59 mmol is intermediate
60 mmol is likely
What percentage of CF males are infertile? why?
Obliteration of the vas deferens in males leads to infertility in 98% of CF men.
How is fertility affected in CF women?
Females have increased viscosity of cervical and vaginal mucus and an increased frequency of anovulatory menstrual cycles which contribute to diminished fertility; Nevertheless CF women can become pregnant and carry successfully to term.
During exposure to high environmental temperatures, what are CF patients at risk for
increased Na+ and Cl- loss lead to metabolic alkalosis and dehydration, particularly during exposure to high environmental temperatures
What is a rare complication of CF due to vitamin A deficiency?
xerophthalmia and night blindness
What are 2 blood related complications of CF?
anemia due to nutritional depletion (Iron deficiency) or hemolysis (vitamin E deficiency or antibiotic mediated, immune mediated-rare);
bruising/ bleeding due to deficiency of vitamin K-dependent clotting factors or liver disease
What is a heart related complication of CF?
cor pulmonale leading to CHF
What neural Vitamin E deficiency complication is associated with CF? Vitamin A
peripheral neuropathy due to vitamin E deficiency; pseudotumor cerebri due to vitamin A deficiency (rare).
What percentage of CF patients develop cystic fibrosis related diabetes mellitus?
30% due to pancreatic fibrosis
What is a complication of chronic infection treatment among CF patients?
nephrotoxicity due to frequent aminoglycosides and vancomycin
auditory and vestibular toxicity due to aminoglycosides
What 4 things are predicted by the degree of CFTR function?
degree of pancreatic insufficiency, lung disease, sweat chloride dysregulation, and age of presentation
What complicates the effect of genotype on lung phenotype in CF?
environment - it is responsible for more of the lung severity, which is a problem because lung function is the main predictor of mortality and morbidity in CF
What are two important risk factors for earlier mortality in CF?
female gender and low SES
What is a test for CF that is not clinically used but frequent in research?
nasal potential difference
nasal catheter looks at response to Na inhibition followed by Chloride inhibition
Why are there now more adults living with CF than childreN?
improved treatment and nutrition support at earlier ages
We are much better at preventing decompensation than we are at treating decompensation once it begins
What kind of mutations are associated with improved survival in Cf?
those that allow for pancreatic sufficiency
How is pancreatic insufficiency detected?
low fecal elastase levels
What are three types of gene therapies being trialed or that have been approved recently for CF?
- read through drugs of aminoglycoside analogs
- Ivacaftor channel augmentors for class III mutations
- F508del chaperones/correctors
