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.
