Cystic Fibrosis

Question 1

Inheritance pattern

Answer 1

Autosomal recessive, defect in both copies of cystic fibrosis transmembrane conductance regulator protein (CFTR)

Question 2

Role of CFTR

Answer 2

CFTR pump chloride ions across the membrane which draws water into secretions.

Question 3

Lack of CFTR causes

Answer 3

Lack of CFTR causes lesser water to be drawn into secretions causing a thick mucus instead of a normal thinner mucus. This impairs mucociliary clearance increasing risk of infection

Question 4

What can chronic bacterial infection and inflammation due to cystic fibrosis exacerbations cause

Answer 4

Bronchiectasis and eventual respiratory failure

Question 5

Consequences of CFTR gene mutation

Answer 5

Infertility in men due to absence of vas deferens, salty sweat (excess Cl- in sweat), failure to thrive, recurrent bacterial infection, pancreatic failure, liver and gallbladder disease

Question 6

Different defects in CFTR

Answer 6

Type 1 - No CFTR synthesis
Type 2 - CFTR trafficking defect
Type 3 - Dysregulation of CFTR, diminished ATP binding and hydrolysis)
Type 4 - Defective chloride conductance or channel gating
Type 5 - Reduced CFTR transcription and synthesis

Question 7

Most common mutation causing cystic fibrosis

Answer 7

DeltaF508 - Deletion of Phenylalanine in 508th amino acid

Question 8

What type of respiratory disease does CF present as

Answer 8

Obstructive

Question 9

How can CF be detected

Answer 9

Gene testing
Screen in newborns for pancreatic enzyme called immunoreactive trypsinogen (IRT) which is released in blood when pancreas is damaged by CF
Sweat glands test, if there’s high chloride in sweat

Question 10

Why high chloride in sweat in CF

Answer 10

In sweat glands, the Cl can’t be reabsorbed or come into cells, causing its buildup

Question 11

Staphyloccocus aureus colonisation antibiotics

Answer 11

Oral Flucloxacillin or Oral septrin/co-trimoxazole

Question 12

Pseudomonas colonisation in CF antibiotics

Answer 12

Oral azithromycin - Blocks protein synthesis

Question 13

Pancreatic failure in CF

Answer 13

Presents in early childhood
Exocrine failure - Sludged up ducts leading to failure of amylase and lipase enzyme leading to steatorrhea
Endocrine failure - Islets of Langerhaans are destroyed causing fatty replacement of tissue and diabetes.

Question 14

Medication for pancreatic failure in CF

Answer 14

CREON which is a mixture of lipase, amylase and protease. This helps with digestion and patient to put on weight

Question 15

Bowel problems in CF

Answer 15

Distal intestinal obstruction syndrome (DIOS) - Thick mucus blocks up the large and small intestine causing symptoms like constipation

Question 16

LIver problems in CF

Answer 16

Sludging up of intra and extra hepatic dutcts. This causes portal hypertension leading to porto-systemic anastomoses, variceal bleeding and hepatic encephalopathy

Question 17

What can be carried out in CF patients if there’s severe liver disease

Answer 17

Transjugular intrahepatic portosystemic shunt (TIPSS) which is a new connection between two blood vessels in liver

Question 18

Managing CF exacerbations

Answer 18

Antibiotics, physiotherapy to help clear chest secretions with minimal effortW, adequate hydration, increased dietary input

Question 19

How are antibiotics usually administered in CF

Answer 19

Oral or IV but always use 2 to prevent resistance

Question 20

Most common pathogens colonizing CF patients

Answer 20

Pseudomonas and Staphylococcus aureus

Question 21

What is OPAT

Answer 21

Outpatient parenteral antimicrobial therapy (OPAT) allows patients to be given intravenous antibiotics in community rather than as inpatient.

Question 22

Strategy to administer antibiotics that saves money, hospital admission and is safe

Answer 22

Outpatient parenteral antimicrobial therapy (OPAT)

Question 23

What genetic mutation is commonly found in Irish CF patients

Answer 23

Celtic gene - G551D which is a type 3 mutation. Normal CFTR produced but the channel is non-functional

Question 24

CFTR potentiator drug

Answer 24

Ivacaftor, tablet (BD), improves chloride flow through CFTR. It is used as a stand-alone medication for teh G551D mutation.

Question 25

What does Ivacaftor interact with

Answer 25

Grapefruit

Question 26

What can be used for treating F508del causing CF

Answer 26

Lumacaftor + Ivacaftor -

Lumacaftor brings more CFTR to cell membrane and Ivacaftor increases this activity

Question 27

Does Lumacaftor work on it’s own

Answer 27

No