Respiratory Channelopathies Flashcards
What is cystic fibrosis?
Autosomal recessive disease of the epithelial tissue that disrupts electrolyte transport
Which 6 tissues are affected by cystic fibrosis?
1) Airways
2) Liver
3) Pancreas
4) Small intestine
5) Reproductive
6) Skin
How are the airways impacted in CF?
Clogging and infection
How is the liver impacted in CF?
1) Blockage of small bile ducts - pressure build up
2) Liver function problems
How is the pancreas impacted in CF?
1) Blockage of the bile ducts:
- Prevents secretion of digestive enzymes into the small intestine from the pancreas
2) Failure of babies to thrive
How is the small intestine impacted in CF?
1) Obstructions due to thick content in 10% of newborns:
- Thick mucus
- Can’t breakdown milk
- Can’t put weight on
2) Problems with the GI tract in older people
How is the reproductive system impacted in CF?
- Absence of the vas deferens
- 95% of males INFERTILE
- Small number in women also
How is the skin impacted in CF?
Excess secretion of NaCl via sweat sweat glands
What is the condition called where the child’s intestine content is thick and sticky called?
Meconium ileus
How is CF inherited?
Why is it not always inherited in this way?
Via MENDELIAN GENETICS:
1/4 CF
1/4 normal
1/2 carriers
Not always inherited in this way because Mendelian genetics are RANDOM
Describe the protein production differences in carriers and CF patients?
Carriers - 50% of the normal protein produces
CF - 0% of the normal protein produced
Describe the structure of the CF transmembrane conductance regulator (CFTR)
- 12 transmembrane domains
- Cl- ION CHANNEL
- 2 NUCLEAR BINDING DOMAIN (NBDs)
- Regulatory domain
What are the NBDs in CFTR called
NBD1 and NBD
Does the CFTR transport Cl- in or out of the cells?
In OR out, depending on what cell the channel is found in
What do the NBD of the CFTR bind to?
What does this cause?
Bind nucleotides (such as ATP)
Regulatory mechanism - determines if the channel is open or closed
Why is the regulatory domain of CFTR important?
Site for PHOSPHORYLATION:
- When ATP –> ADP, phosphate released binds to this domain
- Important in regulating the opening/closing of the channel
What mutations cause CFTR?
>1900 mutations possible, in the: - Intracellular loops - Extracellular loops - NDB etc.
What is the most common CFTR mutation?
What % of cases this contribute to?
Delta F508 mutation in NBD1
70% of cases
Describe variable penetrance
2 individuals with the SAME mutation profile can have DIFFERENT severities due to environmental and genetic (non-coding regions) reasons
How do environmental influences impact of the phenotype of CF?
More severe disease if LESS affluent