Cystic Fibrosis

Question 1

what type of inheritance is cystic fibrosis

Answer 1

autosomal recessive

Question 2

mutation of what gene causes cystic fibrosis

Answer 2

CFTR gene (on long arm of chromosome 7)

Question 3

what mutation is most common in CF and what does it cause?

Answer 3

∆F508

results in misfolding of CTFR protein

Question 4

what role does the CFTR protein have?

Answer 4

CFTR protein is a channel protein the pumps chloride ions into various secretions
Chloride ions help draw water into secretion – thinning them out

Question 5

how does the mutation impact physiology?

Answer 5

Misfolded protein – can’t migrate from endoplasmic reticulum to the cell membrane = lack of CFTR protein on the epithelial surface – can’t pump chloride ions out, water can’t get drawn in, secretions are thick

Question 6

what is the diagnostic criteria of new-borns

Answer 6

failure to thrive, purulent sputum, meconium ileus

All of the above plus: extended period of neonatal jaundice and steatorrhea

Question 7

how does meconium ileus occur?

Answer 7

Normally, after birth, pancreatic enzymes act on the meconium, and it is passed in the stools. In CF meconium is not broken down = obstruction

Question 8

diagnostic criteria of CF in early childhood

Answer 8

same as newborn, plus pancreatic insufficiency

Bronchiectasis, Rectal prolapse, Nasal polyps, Sinusitis

Question 9

how does pancreatic insufficiency occur in CF

Answer 9

Digestive pancreatic enzymes can’t make it to small enzymes
Fat and protein aren’t absorbed
Over time poor weight gain, failure to thrive, steatorrhea
Eventually pancreas damage – the backed up digestive enzymes degrade the pancreatic duct lining cells

Question 10

what are the long term impacts of pancreatic insufficiency ?

Answer 10

acute pancreatitis
chronic pancreatitis = cysts and fibrosis
Endocrine dysfunction – insulin dependent diabetes

Question 11

what are the diagnostic features of CF in late childhood?

Answer 11

As above, chronic lung infections plus cor pulmonale, diabetes (type 2), cirrhosis, distal intestinal obstruction, pneumothorax, haemoptysis, infertility, psychological disorders, cyanosis, clubbing, osteoporosis

Question 12

what causes the lung exacerbations in CF?

Answer 12

Normally cilla clears mucous
With thick mucus – cilla becomes defective
Bacteria allowed to chronically colonise lungs
Increased bacterial load = symptoms (cough + fever) + changes on chest xray
This is an exacerbation of CF

Question 13

what bacteria are common in CF exacerbations?

Answer 13

staph aureus, h influenza early, pseudomonas aeruginosa in later life

Question 14

what are the consequences of chronic bacterial infection?

Answer 14

bronchiectasis, haemoptysis if inflammation into a blood vessel, repeated = resp failure

Question 15

what are other consequences of CF?

Answer 15

Infertility in men – lack of vas deferens
Digital clubbing
Nasal polyps
Allergic bronchopulmonary aspergillosis

Question 16

what common tests are used in the diagnosis of CF?

Answer 16

Guthrie test
Elastase in Faeces
Sweat Test

Question 17

what are other tests that can be used in CF diagnosis?

Answer 17

GGT raised
Vitamins A, D, E, K – low
CXR – hyperinflation, bronchiectasis
Abdominal US
Spirometry - Obstructive PFTs
Aspergillus skin test

Question 18

What does the Guthri Test look for?

Answer 18

Immunoreactive Trypsin (raised in CF babies)

Question 19

Elastase is

Answer 19

a pancreatic enzyme detected in faeces of CF patients

Question 20

what indicates a positive sweat test

Answer 20

o Child – >60 mmol/L chloride – is abnormal

o Adult – >90mmol/L chloride is abnormal

Question 21

what are the different parts of CF management?

Answer 21

Nutrition and healthy weight gain
Pulmonary treatment
Medications
Personalised Treatments

Question 22

what treatment options are used to manage nutrition and healthy weight gain?

Answer 22

Fat soluble vitamins
Replacement pancreatic enzymes
Extra calories – aim for normal growth and percentiles
PPIs

Question 23

What treatments options are sued for pulmonary treatment?

Answer 23

Chest physiotherapy – postural drainage 
Nebulised Saline
Prophylaxis – flucloxacillin, azithromycin 
Home oxygen and CPAP
Lung Transplant

Question 24

what medications are used in the management of CF?

Answer 24

N-acetylcysteine
DNases
Ursodeoxycholic acid

Question 25

What is the action of n-acetylcysteine?

Answer 25

cleaves disulphide bonds in mucus glycoproteins

Question 26

what is the action of DNases?

Answer 26

cuts up nucleic acid in mucus

Question 27

why are patients given ursodeoxycholic acid?

Answer 27

prevention of liver impairment

Question 28

What are the different kinds of personalised treatments and what are their actions?

Answer 28

Lumacaftor - chaperone, brings mutated CFTR to cell membrane

Ivacaftor - deisgned against G551D, improves mutated CFTR function