Cystic Fibrosis in Children and Adults Flashcards
What type of genetic disease is CF?
Autosomal recessive
What is the difference between recessive and dominant diseases. Which is homozygous and which is heterozygous?
recessive means you need 2 faulty alleles, one functioning allele is enough to maintain normal functioning, however, if 2 mutant alleles are present (homozygous state), there are no healthy alleles so disease is present.
Whereas when it is dominant, the faulty allele overides the funtioning allele and causes disease with just one faulty set of genes. This means that genetic disorders can occur in heterozygous state.
Is CF the most common autosomal recessive disease? What proportion of people are carriers?? Most common mutation? What causes death?
Yes
1 in 25 are carriers in the UK
Most common mutation is deltaF508
Most common cause of death is respiratory failure
What are the chances of being affected/carier/unaffected if m+d both arecarrier?
- 25 completely unaffected and inherit 2 healthy genes
- 5 carriers - 1 healthy and 1 mutated
- 25 affected with condition
What happens to the transmembrane conductance regulator protein (CFTR) in CF and what are the effects of it? Which chromosome codes the CFTR protein?
The transmembrane conductance regulator protein (CFTR) is either blocked/partially blocked, basically doesn’t allow CL- ions through.
This means in sweat glands (for example) both Cl- and Na+ are completely sweated out of the body (Na+ has opposite charge and is pair of Cl-).
In the lungs it traps the Cl- within the cell, Na+ and H20 follow into cell. Causing the mucus to become extremely sticky as it is dehydrated and missing/has a reduced airway suface liquid layer. This can lead to shearing and impaired bacterial killing via neutrophils.
The protein is coded for on chromosome 7
How many mutation classes are there? Which classes cause severe disease/mild disesae? Which is most common disease type?
more than 2500 mutation classes.
Types 1-3 are completely dysfunctional and so cause severe disease
Types 4-6 have some function and so cause mild disease.
Most common is Delta F508 which is Type 2. Type 2 account for 75% all CF cases.
When is antenatal testing done and what tests are done?
With baby in womb following identified parent/sibling with CF.
Tests include:
Pre-implantation genetic diagnosis
Chorionic villous sampling
Amniocentesis (Amniotic fluid)
What is the Guthrie test?
A simple heel prick blood test for CF done on day 5 after birth.
What is a sweat test and when is it done?
Done after a positive Guthrie test and on day 5,
Measures concentration of chloride in sweat. Less reliable in infants under 6 months and in adults.
Nb a faecal elastase can also be done to measure gut absorption.
Sweat chloide levels for diagnosis
Over 60 mm/L is abnormal - high chance of CF
30-59 = inconclusive
30 and below probably not CF.
Usually repeated to confirm
What is SPID?
screen positive inconclusive diagnosis - chloride and genetic analysis don’t match, grey area.
(Normal sweat chloride with 2 CFTR mutations
Intermediate sweat chloride with 1 (or no) CFTR mutations)
Is CF a multisystem disease?
yes
2 common presentation of CF?
pancreatic insufficiency and lungs (infection and bronchiectasis)
What does the pancreas do ususally? How can this be affected in CF and which enzymes are affected?
Release enzymes to break down food.
Most people with CF do not make pancreatic enzymes. The pancreatic duct cells also secrete bicarbonate into the intestine to neutralize stomach acid via the CFTR channel. The inability to neutralize stomach acid contributes to malabsorption in many cf patients.
Enzymes are trypsin and colistin
What is the effect of the lack of enzymes (trypsin and colistin) in CF?
Malabsorption
Abnormal stools - pale, offensive, float
Failure to thrive
Which classes are insufficient pancreatic? What % function do you need, so why may CF patients be asymyptomatic?
1-3 produce no pancreatic enzymes, types 4-6 produce some, which is enough to hit the 5% needed to function, so they may be pancreatically asymptomatic.
What is the second common presentation of CF throughout life? What can underlying causes be be caused by?
Recurrent bronchoplumonary infection. pneumonia Bronchiectasis Scarring Abscesses
What are “tram lines” and what are they most likely to be a result of?
They’re fat tram lines on a CT of a patients lung, caused by bronchiectasis (widening of the bronchioles), caused by recurrent infections and scarring in CF.
What is the airway surface layer?
The layer of watery substance that sits on top of the cilia in the respiratory tract and helps keep everything flowing (up the way)
Why does pulmonary infection occur? (what does the CFTR abnormality cause?
Abnormal electrolyte transport across cell membrane
Dehydration of airway surface layer (water later which allows mucous to slide easily up airway to be coughed up)
decreased mucociliary clearance
Mucous sticks to mucosal surface and causes shearing and inflammation
decreased access to bacteria
decreased bacteria killing
How does bronchiectasis occur?
you get reduced mucociliary clearance, increased bacterial adherence to the mucosa and reduced killing of bacteria. As a result, you get bacterial colonization within the mucus that causes inflammation, mucus plugging, Airway ulceration and airway damage, and ultimately bronchiectasis.
how much sputum can a CF patient cough up in a day?
Several cups a day!!
Survival related to what
Lung function (FEV1)
What would you see on a ct with cf?
Tram lines, signet rings (big brinchiOle O with vessel next to it), mucous plugging and potentially some consolidation (infection)
