Cystic Fibrosis Flashcards
Inheritance pattern
Autosomal recessive, defect in both copies of cystic fibrosis transmembrane conductance regulator protein (CFTR)
Role of CFTR
CFTR pump chloride ions across the membrane which draws water into secretions.
Lack of CFTR causes
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
What can chronic bacterial infection and inflammation due to cystic fibrosis exacerbations cause
Bronchiectasis and eventual respiratory failure
Consequences of CFTR gene mutation
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
Different defects in CFTR
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
Most common mutation causing cystic fibrosis
DeltaF508 - Deletion of Phenylalanine in 508th amino acid
What type of respiratory disease does CF present as
Obstructive
How can CF be detected
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
Why high chloride in sweat in CF
In sweat glands, the Cl can’t be reabsorbed or come into cells, causing its buildup
Staphyloccocus aureus colonisation antibiotics
Oral Flucloxacillin or Oral septrin/co-trimoxazole
Pseudomonas colonisation in CF antibiotics
Oral azithromycin - Blocks protein synthesis
Pancreatic failure in CF
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.
Medication for pancreatic failure in CF
CREON which is a mixture of lipase, amylase and protease. This helps with digestion and patient to put on weight
Bowel problems in CF
Distal intestinal obstruction syndrome (DIOS) - Thick mucus blocks up the large and small intestine causing symptoms like constipation
LIver problems in CF
Sludging up of intra and extra hepatic dutcts. This causes portal hypertension leading to porto-systemic anastomoses, variceal bleeding and hepatic encephalopathy
What can be carried out in CF patients if there’s severe liver disease
Transjugular intrahepatic portosystemic shunt (TIPSS) which is a new connection between two blood vessels in liver
Managing CF exacerbations
Antibiotics, physiotherapy to help clear chest secretions with minimal effortW, adequate hydration, increased dietary input
How are antibiotics usually administered in CF
Oral or IV but always use 2 to prevent resistance
Most common pathogens colonizing CF patients
Pseudomonas and Staphylococcus aureus
What is OPAT
Outpatient parenteral antimicrobial therapy (OPAT) allows patients to be given intravenous antibiotics in community rather than as inpatient.
Strategy to administer antibiotics that saves money, hospital admission and is safe
Outpatient parenteral antimicrobial therapy (OPAT)
What genetic mutation is commonly found in Irish CF patients
Celtic gene - G551D which is a type 3 mutation. Normal CFTR produced but the channel is non-functional
CFTR potentiator drug
Ivacaftor, tablet (BD), improves chloride flow through CFTR. It is used as a stand-alone medication for teh G551D mutation.
What does Ivacaftor interact with
Grapefruit
What can be used for treating F508del causing CF
Lumacaftor + Ivacaftor -
Lumacaftor brings more CFTR to cell membrane and Ivacaftor increases this activity
Does Lumacaftor work on it’s own
No
