27- CF 1 Flashcards
What sort of defect is cf
Recessive autosomal defect in CFTR gene expressed on many organs
What are the stats in uk
10k people have it and 1 in 2500 babies
What does multisystem disease mean
Affects the lungs, liver, bones, gut, heart and pancreas / other areas due to CFTR expression
What sort of things does it cause in the lungs
Bronchitis, bronchiectasis, pneumonia and resp faulrure
What sits on top of Eli cells in normal airway
Airway surface liquid made from 2 layers and top layer is more mucusy vs ciliary layer on lower side
What does CFTR normally do affecting asl
Allows hydration through secretion of Cl and HCO drawing water out into airway for better mucus clearance
What are the 3 hallmarks of Cf
Infection,mucus and inflammation via inflam cells
Which article discusses effects of CFTR on airway surface and neutrophils
Mall 2014
Which channel does CFTR regulate so not too much na hyper absorption occurs and allows hydration
Enac
Does mucus building through dehydration always need to cause infection to cause inflammation
No. Some irritants can cause pro inflam cytokines and chemokine release without infectikn
What sorts of things can NE cause
Bronchiectasis, mucus hypersexretion, airway inflammation and cell damage
How does ne also cause more dehydration so more mucus build up
Activates the enac channel and because CFTR not functioning can’t regulate this = dehydration eg phe508 mutation
Reduced ph occurs with less HCO release. What does this impact on
Amp, lysozymes and lactoferrins action to remove pathogens
Which 3 things can help secretion clearance to manage cf
PEP (positive exp pressure) Physiotherapy
Exercise
Mucolytics / other mucoactives
How does pep physiotherapy work
Keepsairways open and better ventilation through a machine so more clearance
How would you treat the inflammation
Azithromycin or steroids
Why was cf first seen as a disease of the gut
CFTR on pancreas allows fat absorption so this dysfunction reduces fat soluble vitamin absorption eg vit a, e,d,k
What sorts of signs are fat malabsorption
Greasy stools, weight loss
What obstruction of the bowel is a sign of cf in babies or adults
Meconium ileus (in distal ileum)
In adults it’s distal bowel obstructions
Which article discusses the vitamin deficiency
Rayner 1992
What does vit k deficiency cause in cf patients
Haemorrhagic disease (important for clotting)
What does d deficiency cause
Osteomalacia, sometimes rickets and bone deformation (important for bone development)
What is E linked with to do with neurological problems
Loss of position and vibration sense in lower limbs, also muscle weakness and tremors
How does vitamin E link to inflammation in airway in cf
If present it usually blocks free radical caused inflammation eg from neutrophils
What does A deficiency cause to do with eyes
Night blindness
What is seen in the airway during vitamin a deficiency
Increased bacterial adherence to epi cells
Which article discusses meconium ileus
Sathe 2017
What does lowered ph allow to bind the mucus
Albumin and protein bound carbohydrates which cause obstruction in the terminal ileum
What % of Cf have this
20%
What CFTR class mutations is it due to
Class 1-3
Which therapy helps pancreas absorb fats helping vitamin absorption
Pert. Pancreatic enzymes replacement therapy
How are vitamins given for supplementation
Oil based
What is gastrostomy feeding
Feeding tube links to stomach for better vitamin supply
What reflux disease caused by CFTR disfunction needs treated
Gord
Why does dysbiosis of gut occur in cf
Mucus alteration and ph changes due to CFTR and inflammation due to no aea
What sorts of bacteria are reduced
Bacteroides and firmicutes
What do bacteroides help
Reduce il8 and therefore neutrophil inflammation eg b fragiliswhich binds tlr2 and causes il10 treg upreg (round 2011)
Why is diabetes associated with cf
There is destruction of islet cells in pancreas so reduced insulin
What is ABPA caused in cf
Allergic bronchopulmonary aspergillosis (allergic reaction eg with igE and eosinophils in airway to aspergillus ag)
How does cf affect reproduction
Infertility in men
What sort of things are looked for in the clinical diagnosis
Chest infection/ resp issues, malabsorption, weight loss, liver issues eg jaundice , meconium ileus
What is the newborn screening method
Heel prick to take blood sample screened for 9 diseases inc cf
What levels suggest possible cf so then genetically tested
Immunoreactive trypsinogen (irt)
What talks about Nbs more
Deboeck et al 2017
What is irt sign of
Pancreatic injury
Why is genetic tests needed even if high irt
Can be caused by perinatal stress too
Why can sometimes cf have low irt
Meconium ileus associated
What is the sweat test done on children
Measure levels of Cl release which is abnormally high in cf from sweat glands
Why does CFTR mutation cause increase na and Cl in sweat
Hypertonic sweat as CFTR usually absorbs more na and Cl in the sweat glands
Levels above whay are cf indication
60mmol/L
A few other tests are done to diagnose newborns if other ways don’t work eg sweat test. How
Bronchoscoph/Bal washing and also sputum analysis after cough swabs done
What does the issue of heterogeneity mean in Cf
Some cases missed as many signs eg abpa, asthma and bronchiectasis and pancreatitis overlooked for cf
What is done for inconclusive results ie below 60mmol/L
Put into groups of risk eg high risk would be managed more often/visit more often
What is the low risk group vs medium risk
30Cl or below levels so see them annually
Medium risk is 30-60 so see them every 6 months
