Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

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

Genetics and Treatment of CF Flashcards

1
Q

What is the epidemiology of cystic fibrosis?

A

1 in 25 people carry the gene

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

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

A

Moves chloride Cl- out of cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

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

A
  • Cystic fibrosis conductance regulator (CFTR) - moves Cl- out of cell
  • Epithelial sodium channel (ENAC) - flow of Na+ into cell
  • Other chloride channels
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What regulates CFTR, ENAC and chloride channels?

A

ATP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What happens if there is a failure of the CFTR?

A
  • Cannot pump chloride out of cell
  • More Na+ going in and less Cl- going out,
  • Water flows into cell
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are consequences of CFTR failure? (8)

A
  • 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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are the stages of cystic fibrosis development?

A
  • Mutation in CFTR DNA
  • Altered CFTR protein
  • Affects ion transport
  • Alters secretions
  • Blocked ducts, impaired mucosal defence
  • Infection, inflammation
  • Cystic fibrosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are kinds of CFTR defect?

A
  • 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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Why is it important to study the genetic code?

A

Allows you to predict mutation effects

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

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

A
  • F508del - most common (70%), deletion of phenylalanine

* G551D - (4-6%) substitution of glycine to asparagine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

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

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Where are most CF patients transferred from?

A

Bronchiectasis clinic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

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

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

All receive CF genetic testing

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

How do CF patients get missed?

A
  • Don’t present
  • Present out of hours
  • Present sporadically
  • Loss of continuity in care (different GPs)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What does genetic testing for CF include?

A
  • Detection of F508del mutation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What are the difficulties of CF?

A
  • 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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What does prophylactic management of cystic fibrosis include?

A
  • Antibiotics

* Regular Clinic Review

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What do antibiotics used to treat cystic fibrosis include?

A

Staph Aureus Colonised

  • Oral Fluclox
  • Oral Septrin

Pseudomonas Colonised

  • Oral Azithromycin
  • Nebulised Colomycin
  • Nebulised Tobramycin
  • Nebulised Aztreonam
  • Inhaled Tobramycin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is the effect of exocrine failure of the pancreas?

A
  • Ducts blocked with mucous
  • Failure of secretion of lipase, amylase
  • Digestive failure
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What is the treatment for exocrine failure of the pancreas?

A

CREON

21
Q

Why do patients often refuse total CREON?

A

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

22
Q

What are the effects of endocrine failure of the pancreas?

A
  • Destruction of pancreatic islet cells

* Fatty replacement of pancreatic tissue

23
Q

What is the treatment for endocrine failure of the pancreas?

A
  • Annual oral glucose tolerance test (OGTT)
  • Continuous glucose monitoring system (CGMs)
  • Usually need insulin as they have insulin production failure
24
Q

What are the effects of cystic fibrosis on the bowels?

A
  • Distal Intestinal Obstruction Syndrome (DIOS)
  • Thick mucus blocks up the large and small intestine
  • Symptoms similar to constipation
25
Q

What is Distal Intestinal Obstruction Syndrome (DIOS)?

A
  • Thick mucus blocks up the large and small intestine

* Symptoms similar to constipation

26
Q

What is the treatment for DIOS?

A
  • Gastrograffin
  • Laxido
  • Fluids
27
Q

What are the prevention methods for DIOS?

A
  • Laxido
  • Hydration
  • Keep moving (exercise encouraged)
28
Q

What are the effects of cystic fibrosis on the liver?

A
  • Sludging up of intrahepatic/extrahepatic ducts

* Portal hypertension - port-systemic anastomoses, variceal bleeding, hepatic encephalopathy

29
Q

What are the consequences of portal hypertension?

A
  • Porto-systemic anastamoses
  • Variceal Bleeding
  • Hepatic encephalopathy
30
Q

What procedure is used to reduce hypertension and its complications?

A

Transjugular intrahepatic portosystemic shunt (TIPSS)

31
Q

What is the purpose of TIPSS procedure?

A

Reduce hypertension and its complications

  • Reduces anastamoses
  • Reduction in bleeding risk
  • Can increase encephalopathy risk
32
Q

How are exacerbations of cystic fibrosis managed?

A
  • Antibiotics
  • Physiotherapy -Autogenic Drainage, ACBT (breathing techniques)
  • Adequate hydration
  • Increased dietary input
33
Q

Why are 2 antibiotics always given when treating cystic fibrosis?

A

Reduces resistance

34
Q

What are oral antibiotics to treat cystic fibrosis?

A
  • Augmentin
  • Fluclox
  • Minocycline
  • Septrin
  • Fusidin
  • Ciprofloxacin
35
Q

What are IV antibiotics to treat cystic fibrosis?

A

Pseudomonas

  • Tazocin
  • Ceftazidime
  • Tobramicin
  • Meropenem
  • Colistin

Staph Aureus

  • Flucloxacillin
  • Tigecycline

Cepacia
* Temocillin

36
Q

What is OHPAT?

A
  • Antibiotics as an in-patient for 2 weeks out of 52

* Start antibiotics as an in-patient, finish at home

37
Q

What are the advantages of OHPAT?

A
  • Well tolerated
  • Safe
  • Saves money
  • Keeps patients working
38
Q

Why are CF survival rates increasing?

A

Due to advances in treatment - treatment starting to be directed towards specific genetic mutations

39
Q

What is the G551D mutation?

A
  • The Celtic Gene - class III mutation
  • Normal CFTR
  • Delivered to epithelium normally
  • Non-functional channel
40
Q

What is used to treat a G551D mutation?

A

Ivacaftor

41
Q

What is ivacaftor?

A

CFTR potentiator - improves chloride flow through the CFTR

42
Q

Why are patients instructed not to eat grapefruit when they use Ivacaftor?

A

Doubles activity of Ivacaftor

43
Q

What percentage of patients is Ivacaftor appropriate for?

A

10%

44
Q

What are other ways to target genes other than direct effect on the protein?

A
  • Post-translational modification
  • RNA editing
  • Increased transcription
  • Gene replacement
45
Q

What is used to treat a F508del mutation?

A

Lumacaftor

46
Q

What percentage of patients is lumacaftor appropriate for?

A

70% (F508del is most common mutation)

47
Q

What is the effect of lumacaftor?

A

8.5% improvement in FEV1 at 56 days

48
Q

How does lumacaftor work?

A

Lumacaftor binds onto CFTR and changes its shape so it can pass through Golgi and embed into membrane

49
Q

Why must lumacaftor be coupled with ivacaftor?

A

The CFTR protein cannot otherwise open once embedded

Respiriatory: Airway Disease (10 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions