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Flashcards in Genetics and Treatment of CF Deck (49)
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1

What is the epidemiology of cystic fibrosis?

1 in 25 people carry the gene

2

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

Moves chloride Cl- out of cell

3

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

4

What regulates CFTR, ENAC and chloride channels?

ATP

5

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

6

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

7

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

8

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

9

Why is it important to study the genetic code?

Allows you to predict mutation effects

10

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

11

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

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

12

Where are most CF patients transferred from?

Bronchiectasis clinic

13

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

14

How do CF patients get missed?

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

15

What does genetic testing for CF include?

* Detection of F508del mutation

16

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

17

What does prophylactic management of cystic fibrosis include?

* Antibiotics
* Regular Clinic Review

18

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

19

What is the effect of exocrine failure of the pancreas?

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

20

What is the treatment for exocrine failure of the pancreas?

CREON

21

Why do patients often refuse total CREON?

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

22

What are the effects of endocrine failure of the pancreas?

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

23

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

24

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

25

What is Distal Intestinal Obstruction Syndrome (DIOS)?

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

26

What is the treatment for DIOS?

* Gastrograffin
* Laxido
* Fluids

27

What are the prevention methods for DIOS?

* Laxido
* Hydration
* Keep moving (exercise encouraged)

28

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

29

What are the consequences of portal hypertension?

* Porto-systemic anastamoses
* Variceal Bleeding
* Hepatic encephalopathy

30

What procedure is used to reduce hypertension and its complications?

Transjugular intrahepatic portosystemic shunt (TIPSS)