Cystic Fibrosis Flashcards
Inheritance pattern of CF
Autosomal recessive
[if both parents are carriers, 25% of children will be genetically normal, 50% will be carriers, and 25% will have cystic fibrosis]
Cystic fibrosis is caused by an autosomal recessive defect in the _____ gene on chromosome _____ that encodes for a protein that functions as a cAMP regulated ____ channel across epithelial cells on mucosal surfaces.
CFTR; 7; chloride
Cystic fibrosis is a disease of _______ gland function that involves multiple organ systems, including the lungs, pancreas, liver, intestines, gonads, etc.
Exocrine
CF is the most common lethal hereditary disease in the white population in the US. What racial or ethnic group is associated with the highest carrier frequency?
Ashkenazi Jewish
Does CF present the same way in every patient? What are the most common clinical presentations?
No; CFTR mutations have poor penetrance
Most common clinical presentations include:
- Chronic and progressive lung disease
- Exocrine pancreatic insufficiency
CF symptoms are highly varied among individual patients, even between siblings who carry identical CFTR alleles. What is thought to be the reason for this variation?
Non-genetic factors — include environmental factors, level of care, nutritional status, and age of onset of lung infection
Modifier genes — thought to interact with CFTR mutations to influence disease severity (e.g., reduced amounts of MLB2 is associated with increased rates of CF-related bronchiectasis, in part due to earlier colonization of P.aeruginosa in the lung)
As part of the clinical presentation of cystic fibrosis, a repeating cycle of infection and neutrophilic inflammation develops. What organisms tend to colonize cystic fibrosis patients at an early age vs. later on?
During early childhood, colonization with S.aureus and H.influenzae
As patients get older, colonization with Pseudomonas aeruginosa occurs
What is often the first presenting sign of cystic fibrosis in neonates?
Meconium ileus — characterized by progressive abdominal distention, failure to pass meconium, and bilious vomiting
Describe the GI manifestation of CF that affects 90-95% of patients
Pancreatic insufficiency — pancreatic enzymes are prevented from reaching the gut
Results in fat soluble vitamin deficiency (ADEK), malabsorption of fats/proteins/carbs leading to steatorrhea, failure to thrive, flatulence, abd pain or distention, jaundice, GI bleeding, etc.
8-12% of CF pts older than 25 y/o develop ___________
Diabetes mellitus
How does CF cause liver disease?
Absence of functioning CFTR in epithelial cells lining biliary ductules leads to:
- Decreased chloride secretion
- Decrease in passive transport of water and Na, both resulting in increased viscosity of bile
- Ductules are plugged, and obstructive cirrhosis can develop
How does CF cause reduced fertility?
Most men with CF are azospermic secondary to agenesis of the vas deferens
[note that female fertility is only mildly impaired]
Common HEENT finding in cystic fibrosis patients
Nasal polyps
Main criteria for diagnosis of cystic fibrosis
A positive newborn screening test AND an elevated sweat chloride concentration on TWO or more occasions
The newborn screening test for CF is universally required in all 50 states in the US. It tests for ____________, a pancreatic protein typically elevated in infants with CF
Immunoreactive trypsinogen (IRT)
[if level is high, must repeat IRT and/or perform sweat chloride or DNA testing]
