Cystic Fibrosis Flashcards Preview

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Flashcards in Cystic Fibrosis Deck (26):
1

Mutation of what gene causes cystic fibrosis?

cystic fibrosis transmembrane regulator (CFTR)

2

What is the inheritance pattern of cystic fibrosis?

autosomal recessive

3

structure and function of the CFTR protein

structure:

  • resides in plasma membrane
  • protein has 3 components

function:

  • chloride channel
  • HCO3 channel
  • negatively regulates Epithelial Sodium Channel
  • positively regulates alternative chloride channel

4

Class 1 CFTR mutation

premature stop codons

very little normal protein is made

5

Class 2 CFTR mutation

abnormal maturation

mutations in which mRNA is transcribed, protein is made, but folding is abnormal, degraded intracellularly

6

Class 3 CFTR mutation

defective activation

7

Class 4 CFTR mutation

decreased conductance

8

Class 5 CFTR mutation

decreased abundance

splice mutants, noncoding regions of the gene, diminished normal RNA transcript produced

9

clinical manifestations of CF

chronic sino-pulmonary infections

  • bronchiectasis and chronis sinusitis/nasal polyposis

GI/nutritional abnormalities

  • pancreatic exocrine/endocrine insufficiency
  • liver cirrhosis
  • small and large bowel obstructions, constipation

male infertility

10

 methods of diagnosing CF

sweat testing (pilocarpine iontophoresis)

nasal potential difference

genotyping

11

How does a CF sweat gland differ from a normal one?

lack of chloride absorption due to mutant CFTR creates hypertonic sweat

12

How does nasal potentials differ in CF patients?

lower baseline resting potential

isuprel in the presence of amiloride gives a polarization response in normal and almost no response in CF patients

13

Class 6 CFTR mutation

 turnover more rapid in the membrane

14

What is the most common CFTR mutation?

Delta F508

15

characteristics of bronchiectasis

effect of CFTR mutations in the mucosa of upper airways

obliteration of the airways as inflammatory cells and bacteria fill the lumen

severe obstruction and end stage emphysema

leads to respiratory failure and death in 85%-90% of affected individuals

16

features of a CF CT

signet ring sign

dilated distal bronchi

dilated bronchi in relation to adjoining vessel

17

signet ring signs

an indication in a CT where the airways are bigger than the adjoining pulmonary arteries

18

Describe the viscious cycle of infection in CF lungs.

begins with airway infection and impaired secretions impairs the immunity

out of proportion immune response

infections can last for decades and mutate frequently

biofilms form and make them very hard to treat

19

most common bacteria in airway infections

Staphylococcus aureus and Pseudomonas aeruginosa

20

How does CF affect the upper ariways?

Abnormal CFTR function, hyperabsorption of sodium and water across the cell

CF has a much thinner layer of mucous later - relative dessication of the mucous layer

Compression of the cilia, preventing them from working in a normal fashion

buildup of mucous and foreign debris

21

What are some predictive factors for outcomes in CF patients?

FEV1 and frequency of severe exacerbations of bronchiectasis

polymorphisms in transforming growth factor-beta 1

female gender

low socioeconomic status

22

CF treatment

mucolytics - DNAase (pulmozyme), hypertonic saline, mannitol (osmotic agent that introduces water secretions int he airway)

bronchodilators - beta2-agonists

anti-inflammatory agents - corticosteroids and ibuprofen

antibiotics

CPT and postural drainage

flutter

HFCWO - high frequency chest wall oscillatory device

exercise

23

CF nutritional supplements

pancreatic enzymes

vitamins

supplements

nocturnal feeds - G-tube and nasogastric tubes

24

gentamicin treatment

ongoing study that this drug may allow reading through a premature stop codon

modest success in clinical trials

25

VX-770 or Ivacaftor

augments chloride channel function for mutant and wild-type CFTR that sits in the plasma membrane

very effective for the G551D (class 3) mutation

26

F508del mutation

mutations that causes the CFTR protein to be trapped in the ER and then degraded in the cell