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Questions and Answers
CF patients face challenges with early colonization by ______ such as S. aureus and A. auruginosa, which is difficult to eradicate
pathogens
The average life expectancy of ______ has increased from 15 years to 28-31 years, but pathogen colonization remains a major factor in morbidity and mortality
CF patients
More than 1400 disease-associated mutations have been identified in ______, with 75% being Class II mutations, such as the common DF508 mutation
CFTR
______ protein consists of 2 domains of 6 transmembrane helices, 2 nucleotide binding domains (NBD), and 1 regulatory domain (R)
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Phosphorylation of the ______ is necessary but not sufficient for CFTR channel opening, and ATP hydrolysis at NBD1 opens the channel while ATP hydrolysis at NBD2 closes it
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The ______ is used to identify CF patients due to reduced salt absorption caused by mutant CFTR in sweat glands
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______ use various molecular components to regulate salt and volume absorption, including CFTR, ENaC, AQP, tight/gap junctions, ion transporters, and purinergic receptors
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______ disrupts diverse epithelial functions, including water/volume-absorbing, salt-absorbing, and water/volume-secretory processes
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______ play a crucial role in salt absorption in sweat ducts, affecting water movement and resulting in salty sweat in CF patients
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The loss of ______ in pancreas and intestine epithelia in CF patients leads to underhydrated lumenal environment, sticky mucus, and clogged ducts and villar surfaces
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Two ______, the high salt and low volume ______, have dominated thinking about the mechanisms of lung pathology in CF
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______ for CF have historically focused on palliative measures, disease-specific interventions, and long-range prospects such as gene therapy and inhalation of hypertonic saline solution
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CFTR is a regulated epithelial chloride channel and it influences the activity of other channels, especially the epithelial sodium channel (ENaC) - CF pathology is multi-systemic, affecting lungs, pancreas, intestines, male reproductive tract, and other tissues - Plasma (ECF) and ICF have similar osmolality, but different ionic composition: Na+ and Cl- are high in ECF, K+ is high in ICF - Ions move in or out of a cell based on chemical concentrat______ and on membrane potential differences
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Fixed anionic charges on large molecular weight compounds in the ICF, such as proteins and nucleic acids, generate a net negative ______ (- 55 to -75 mV) - Passive and active transport mechanisms are employed by epithelial cells in many organs to maintain osmotic balance and ion gradients - Ion gradients are especially important because cells use these to generate energy, transport other molecules, and control their extracellular environment
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In lungs and other tissues, salt can be absorbed in excess of water, resulting in decreased ionic strength in the ECF - Airway epithelial cells are covered by two distinct aqueous layers that together comprise the Airway Surface Layer (ASL): the mucus layer (ML) and the peri-cilliary layer (PCL) - In CF patients, lungs are plagued by ______, especially P.
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Carrier frequency for mutations causing CF have been estimated to be as high as 1:22-28 among caucasuian populations of northern European descent - CFTR is a regulated epithelial chloride channel and it influences the activity of other channels, especially the epithelial sodium channel (ENaC) - CF pathology is multi-systemic, affecting lungs, pancreas, intestines, male reproductive tract, and other tissues - Plasma (ECF) and ICF have similar osmolality, but different ionic composition: Na+ and Cl- are high in ECF, K+ is high in ICF - Ions move in or out of a cell based on chemical concentration gradients and on membrane potential differences
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CFTR is a large gene, making it a target for many mutations - Carrier frequency for mutations causing CF have been estimated to be as high as 1:22-28 among caucasuian populations of northern European descent - CFTR is a regulated epithelial chloride channel and it influences the activity of other channels, especially the epithelial sodium channel (ENaC)
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Passive and active transport mechanisms are employed by epithelial cells in many organs to maintain ______ and ion gradients - Ion gradients are especially important because cells use these to generate energy, transport other molecules, and control their extracellular environment - In lungs and other tissues, salt can be absorbed in excess of water, resulting in decreased ionic strength in the ECF
Signup and view all the answers
Plasma (ECF) and ______ have similar osmolality, but different ionic composition: Na+ and Cl- are high in ECF, K+ is high in ______ - Ions move in or out of a cell based on chemical concentration gradients and on membrane potential differences - Fixed anionic charges on large molecular weight compounds in the ______, such as proteins and nucleic acids, generate a net negative interior membrane potential (- 55 to -75 mV)
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CF is caused by mutations in the ______ gene
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Carrier frequency for mutations causing CF have been estimated to be as high as 1:22-28 among ______ populations of northern European descent
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CF pathology affects lungs, pancreas, intestines, male reproductive tract, and other ______
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Ions move in or out of a cell based on chemical concentration gradients and on ______ potential differences
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Fixed anionic charges on large molecular weight compounds in the ICF, such as proteins and nucleic acids, generate a net negative interior membrane ______
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Ion gradients are especially important because cells use these to generate energy, transport other molecules, and control their ______ environment
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In CF patients, lungs are plagued by persistant bacterial infections, especially ______
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Study Notes
Cystic Fibrosis and Epithelial Ion Flux
- Cystic Fibrosis (CF) patients face challenges with early colonization by pathogens such as S. aureus and A. auruginosa, which is difficult to eradicate.
- The average life expectancy of CF patients has increased from 15 years to 28-31 years, but pathogen colonization remains a major factor in morbidity and mortality.
- More than 1400 disease-associated mutations have been identified in CFTR, with 75% being Class II mutations, such as the common DF508 mutation.
- CFTR protein consists of 2 domains of 6 transmembrane helices, 2 nucleotide binding domains (NBD), and 1 regulatory domain (R).
- Phosphorylation of the R domain is necessary but not sufficient for CFTR channel opening, and ATP hydrolysis at NBD1 opens the channel while ATP hydrolysis at NBD2 closes it.
- The sweat test is used to identify CF patients due to reduced salt absorption caused by mutant CFTR in sweat glands.
- Epithelial cells use various molecular components to regulate salt and volume absorption, including CFTR, ENaC, AQP, tight/gap junctions, ion transporters, and purinergic receptors.
- CF disrupts diverse epithelial functions, including water/volume-absorbing, salt-absorbing, and water/volume-secretory processes.
- CFTR and ENaC play a crucial role in salt absorption in sweat ducts, affecting water movement and resulting in salty sweat in CF patients.
- The loss of CFTR in pancreas and intestine epithelia in CF patients leads to underhydrated lumenal environment, sticky mucus, and clogged ducts and villar surfaces.
- Two hypotheses, the high salt and low volume hypotheses, have dominated thinking about the mechanisms of lung pathology in CF.
- Treatments for CF have historically focused on palliative measures, disease-specific interventions, and long-range prospects such as gene therapy and inhalation of hypertonic saline solution.
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Description
Test your knowledge of cystic fibrosis and epithelial ion flux with this quiz. Explore key concepts such as CFTR mutations, ion transport mechanisms, pathogen colonization, and the impact of CF on epithelial functions.
