Genetics and Treatment of CF Flashcards Preview

Respiriatory: Airway Disease > Genetics and Treatment of CF > Flashcards

Flashcards in Genetics and Treatment of CF Deck (49)
Loading flashcards...

What is the epidemiology of cystic fibrosis?

1 in 25 people carry the gene


What is the purpose of the cystic fibrosis transmembrane conductance regulator?

Moves chloride Cl- out of cell


What are the components that work in association with the cystic fibrosis conductance regulator?

* Cystic fibrosis conductance regulator (CFTR) - moves Cl- out of cell
* Epithelial sodium channel (ENAC) - flow of Na+ into cell
* Other chloride channels


What regulates CFTR, ENAC and chloride channels?



What happens if there is a failure of the CFTR?

* Cannot pump chloride out of cell
* More Na+ going in and less Cl- going out,
* Water flows into cell


What are consequences of CFTR failure? (8)

* Salty Sweat
* Intestinal Blockage
* Fibrotic Pancreas
* Failure to Thrive
* Recurrent bacterial lung Infections
* Congenital Bilateral absence of Vas Deferens
* Filled Sinuses
* Gallbladder and Liver disease


What are the stages of cystic fibrosis development?

* Mutation in CFTR DNA
* Altered CFTR protein
* Affects ion transport
* Alters secretions
* Blocked ducts, impaired mucosal defence
* Infection, inflammation
* Cystic fibrosis


What are kinds of CFTR defect?

* Class I - no CFTR synthesis, death
* Class II - CFTR trafficking defect, CFTR protein made but missense mutation so protein cannot pass through Golgi into membrane
* Class III - Deregulation of CFTR (diminished ATP binding and hydrolysis), CFTR embeds in membrane but channel cannot open so chloride cannot pass through it
* Class IV - defective chloride conductance/channel gating - channel does not open to the correct stimuli
* Class V - reduced CFTR transcription and synthesis, CFTR is correct shape etc but just not enough of it


Why is it important to study the genetic code?

Allows you to predict mutation effects


What are the 2 main mutations that affect the CFTR gene?

* F508del - most common (70%), deletion of phenylalanine
* G551D - (4-6%) substitution of glycine to asparagine


In recessive diseases, will the same mutation affect both genes?

No, you can have different mutations in each copy of the gene


Where are most CF patients transferred from?

Bronchiectasis clinic


In what circumstances would a patient in bronchiectasis clinic undergo CF genetic testing?

* Bronchiectasis under 40
* Upper lobe bronchiectasis
* Colonisation with Staph
* Infertility
* Low weight

All receive CF genetic testing


How do CF patients get missed?

* Don’t present
* Present out of hours
* Present sporadically
* Loss of continuity in care (different GPs)


What does genetic testing for CF include?

* Detection of F508del mutation


What are the difficulties of CF?

* Massive treatment burden
* Much treatment is ‘preventative’ (do not feel better after taking it, just prevent symptoms from worsening)
* Complications can be rapid in onset


What does prophylactic management of cystic fibrosis include?

* Antibiotics
* Regular Clinic Review


What do antibiotics used to treat cystic fibrosis include?

Staph Aureus Colonised
* Oral Fluclox
* Oral Septrin

Pseudomonas Colonised
* Oral Azithromycin
* Nebulised Colomycin
* Nebulised Tobramycin
* Nebulised Aztreonam
* Inhaled Tobramycin


What is the effect of exocrine failure of the pancreas?

* Ducts blocked with mucous
* Failure of secretion of lipase, amylase
* Digestive failure


What is the treatment for exocrine failure of the pancreas?



Why do patients often refuse total CREON?

Without it they can’t absorb energy – purposely don’t take it to lose weight


What are the effects of endocrine failure of the pancreas?

* Destruction of pancreatic islet cells
* Fatty replacement of pancreatic tissue


What is the treatment for endocrine failure of the pancreas?

* Annual oral glucose tolerance test (OGTT)
* Continuous glucose monitoring system (CGMs)
* Usually need insulin as they have insulin production failure


What are the effects of cystic fibrosis on the bowels?

* Distal Intestinal Obstruction Syndrome (DIOS)
* Thick mucus blocks up the large and small intestine
* Symptoms similar to constipation


What is Distal Intestinal Obstruction Syndrome (DIOS)?

* Thick mucus blocks up the large and small intestine
* Symptoms similar to constipation


What is the treatment for DIOS?

* Gastrograffin
* Laxido
* Fluids


What are the prevention methods for DIOS?

* Laxido
* Hydration
* Keep moving (exercise encouraged)


What are the effects of cystic fibrosis on the liver?

* Sludging up of intrahepatic/extrahepatic ducts
* Portal hypertension - port-systemic anastomoses, variceal bleeding, hepatic encephalopathy


What are the consequences of portal hypertension?

* Porto-systemic anastamoses
* Variceal Bleeding
* Hepatic encephalopathy


What procedure is used to reduce hypertension and its complications?

Transjugular intrahepatic portosystemic shunt (TIPSS)