Cystic fibrosis Flashcards
What is cystic fibrosis?
Inherited genetic disorder characterised by a mutated Cystic fibrosis transmembrane conductance regulator gene (CFTR)
Cystic fibrosis is an ___________ trait
autosomal recessive
How prevalent is the mutated copy of the CFTR gene?
1 : 25
Most common in caucasian europeans
What is the prevalence of symptomatic CF?
1 : 2500
Where is the CFTR gene located?
Long arm of chromosome 7
How many phenotypic classes of cystic fibrosis are there?
Which is most common?
6
phe508del is the most common (87%)
What does the cystic fibrosis gene normally do?
Codes for an active transport channel for chloride, found in cells lining the lungs, intestines, pancreatic ducts, sweat glands, and reproductive organs
This regulates the liquid volume/consistency on epithelial surfaces
A mutated CFTR gene codes for channels that dont work properly
What effect does this have on the epithelial surfaces?
Excessive, innate inflammation with thick, sticky mucous
What are the characteristics of each class of CFTR mutations?
I - No synthesis II - Block in processing (most common) III - Block in regulation IV - Altered conductance V - Reduced synthesis
There is a 6th but fuck knows what that does
Why does a dysfunctional CFTR channel lead to chronic infection?
Increased mucous and mucostasis means microorganisms are trapped and can’t be removed using mucocilliary elevator
Excessive DNA from neutrophil apoptosis
What are the presenting features for antenatal cystic fibrosis?
Common presentations are CVS and echogenic bowel
Less commonly present with perforated meconium ileus
WHat are the presenting features of neonatal CF?
Common presentations:
- Neonatal screening
- Meconium ileus (10%) - stool stuck in bowel
Less commonly present with:
- Gut atresia
- Obstructive jaundice
- Vitamin deficiencies
What are the presenting features for CF in infants and young children?
Common:
- Recurrent chest infections
- Failure to thrive
Rare:
- Rectal collapse
- Pseudo-Bartter’s syndrome
- Anaemia, oedema, hypoproteinaemia
How might older children and adults present with CF?
Common:
- Recurrent chest infections
- Nasal polyps + sinusitis
- Infertility (males)
Rare:
- Acute pancreatitis
- Liver disease
- Pseudo-Bartter’s syndrome
- Atypical mycobacteria
Describe the process of neonatal screening for CF?
What is it’s fault?
Newborn blood spot day 5 (Guthrie test)
Positive result for CF referred for clinical assessment and sweat test (chloride levels)
CF gene mutation analysis
Both stages still miss a proportion of cases
What must the sweat test and CF gene analysis show, for an ‘inconclusive diagnosis’ of CF to be made?
Normal sweat chloride with 2 CFTR mutations (1 mutation has unclear consequences)
Intermediate sweat chloride with 0/1 CFTR mutation(s)
What is the antenatal screening process for someone with CF who is pregnant?
Pre-implantation genetic diagnosis
Chorionic villus sampling
Amniocentesis
What are the 2 cardinal features of Cystic fibrosis?
Pancreatic insufficiency
Recurrent bronchopulmonary infection
What are the signs of pancreatic insufficiency?
Steatorrhea / abnormal stools:
- Pale or orange
- Very offensive
- Greasy/oily
Failure to thrive:
- May thrive well on breast milk
- May have deficiencies of fat soluble vitamins
How is pancreatic insufficiency managed?
Enteric coated enzyme pellets
High energy diet
Fat soluble vitamin ad mineral supplementation
What are the signs/effects of recurrent bronchpulmonary infection?
Pneumonitis
Bronchiectasis
Scarring
Abscesses
Therapeutic targets for CF often target stages in the CF lung disease cycle
How is mucous obstruction and inflammation targetted?
Airway clearance physiotherapy
Dornase alfa
Hypertonic saline
How is chronic infection targetted?
Antibiotics
What antibiotic is used to target the inflammation found in CF?
Azithromycin
What pathogens are typically associated with CF?
Staph aureus and Haemophilus influenzae in early years
Pseudomonas aeruginosa later
What microorganisms are less commonly seen in CF?
Burkholderia cepacia
Stenotrophomonas maltophilia
MRSA
Atypical mycobacteria (eg M abscessus)
Lung microbiome
CF has the potential to cause problems in the GI tract and also cause Hepatopathy
What problems could it cause in the GI tract?
GI dysmotility:
- Meconium ileus
- Gastro-oesophageal reflux
- Distal intestinal obstruction
- Constipation / rectal prolapse
May also cause Crohn’s disease or coeliac disease
What proportion of CF patients suffer from hepatopathy?
5-10%
What is CFTR modulator treatment?
Basically tries to restore function of the CFTR protein or act in it’s place
What agents are used in CFTR modulator treatment?
Ivacaftor & lumicaftor
Aside from CFTR modulator treatment, what other route of therapy is being developed for CF?
Gene editing / therapy
