Cystic Fibrosis Flashcards
Inheritance of CF
Autosomal recessive
Gene prevalence of CF
1:25
Features of CF gene
Lies on chromosome 7
Cystic fibrosis transmembrane conductance regulator (CFTR)
>1800 mutations
Function of CFTR
Active transport channel for chloride
- regulates liquid volume on epithelial surface (reduced chloride efflux and increased sodium influx via ENaC)
- cilia collapse
- excessive inflammation
Presentation of CF antenatally
CVS
Echogenic bowel
Perforated meconium ileus
Presentation of CF neonatally
Picked up by screening
Meconium ileus (10%)
Gut atresia
Obstructive jaundice
Vitamin deficiencies
Presentation of CF in infants and children
Recurrent chest infections
FTT
Rectal prolapse
Pseudo-barters syndrome
Anaemia
Oedema
Hypoproteinaemia
Presentation of CF in older children and adults
Recurrent chest infections
Nasal polyps
Sinusitis
Male infertility
AP
Liver disease
Pseudobartters
Atypical mycobacteria
When is CF screened for and what is done?
Newborn blood spot day 5 (Guthrie test)
Initial screen = immune-reactive trypsinogen
If +ve = mutation analysis performed
Screen +ve referred to a sweat test
What sweat chloride level is indicative of CF?
> 60
What level of chloride sweat levels indicate CF is unlikely?
> 29 (>39 if 6 months)
What are the two cardinal features of CF?
Pancreatic insuffiency
Recurrent bronchopulmonary infection
Presentation of CF in terms of pancreatic insuffiency
Abnormal stools
- pale / orange
- very offensive
- greasy / oily
FTT
- may thrive well on breastmilk
- deficiencies of fat soluble vitamins
Treatment of pancreatic insufficiency
Enteric coated enzyme pellets
High energy diet
Fat soluble vitamins and mineral supplements
H2 antagonist or PPI
Examples of consequences of recurrent bronchopulmonary infections in CF
Pneumonitits
Bronchiectasis
Scarring
Abscess
Management of CF in early years
Pre infection
- segregation to prevent cross infection
- airway clearance and adjuncts
- mucolytics
- prophylactic Ax (against staph A)
- annual flu vaccine
Eradication of early infection (80-90%)
Common organisms causing resp problems in CF
Early years
- staph A
- H. influenzae
Later on
- pseudomonas aeurginosa
Less common organisms causing resp problems in CF
Burkholderia cepacian
Stenotrophomonas maltophilia
Alcaligenes xylosoxidans
Atypical mycobacteria e.g. M abscessus
What usually causes the chronic resp tract infections?
Pseudomonas
Staph A
Haemophilus I
Treatment of chronic resp tract infections in CF
Treat infective exacerbations
Reduce inflammation
- ibuprofen (symptomatic)
- azithromycin
- prednisolone
Suppress bacterial load
GI manifestations of CF
Dysmotility
- meconium ileus
- GORD
- distal intestinal obstruction
- constipation / rectal prolapse
Co existent disease
- crohns and coeliac
Other manifestations of CF
Meconium ileus
GORD
Distal intestinal obstruction
Constipation / rectal prolapse
Hepatopathy
Upper airway polyps and sinusitis
DM
Osteopenia
Arthropathy
Heat exhaustion
Bilateral absence of vas deferens
Vaginal candidiasis (stress incontinence)
Cornerstones of CF treatment
Proactive treatment of airway infection
Good nutrition
Active lifestyle
Airway clearance techniques
Percussion and drainage
Autogenic drainage
Active cycle of breathing
Airway clearance adjuncts
Positive expiratory pressure (PEP) mask
Cornet/flutter
High frequency chest wall oscillation
Why is sputum viscosity increased in CF?
Due to DNA released from neutrophils
Mucolytic examples
DN-ase (alfadornase)
Hypertonic saline
Types of problems in adult CF
80% recurrent pulmonary and pancreatic infections
15% recurrent pulmonary infections
5% GI problems only
DM, Liver, Osteoporosis, fertility issues
What does the CFTR abnormality lead to?
Decreased mucociliary clearance
Increased bacterial adherence
Decreased endocytosis of bacteria
Pathology of persistent resp tract infections in CF
Decreased mucociliary clearance
Increase in bacterial adherence
Decreased endocytosis of bacteria
Aggressive progressive bronchiectasis - chronic purulent sputum production
Recurrent lower resp tract infections
Progressive airflow obstruction
Resp failure
What is type I resp failure?
Decreased Pa02
What is type II resp failure?
Decreased PaO2 and increased PaCO2
Is haemoptysis common and what is it associated with?
Yes, associated with infection
Who are pneumothorax common in?
Older males
How do the patients catch pseudomonas aeruginosa?
Environment (particularly hospitals)
Other CF patients (epidemic strains, antibiotic resistance, virulent)
Treatment of pseudomonas aeruginosa in CF patients
- oral ciprofloxacin and nebulised colomycin 3 months
- If fails IV ceftazidime and nebulised colomycin
Where is bukholderia cepacia acquired from?
Environmental
Other CF patients (epidemic strains more virulent)
What bacterial infection in CF patients is a contraindication for transplantation?
Mycobacterium abscessus
Which organisms get oral antibiotics?
Staph
Haemophilus
Pneumoccocus
What organisms get IV antibiotics?
Pseudomonas
Stentrophonomas
Burkholderia
What is the drug that addresses the primary defect in CF?
Ivacaftor
Treatment of CF
Airway clearance techniques and adjuncts
Mucolytics
Early and aggressive Antibiotics
Ivacaftor
Lung transplantation
How does ivacaftor work?
CFTR potentiator, binds to CFTR, improves the transport of chloride ions
What patients can use ivacaftor and what % of patients is this?
G551D patients
5 - 10%
Features of ivacaftor
Improves lung function 10% predicted
Reduces sweat chloride
Feel much better
S/E of ivacaftor
Weight gain
What kind of lung transplant must be carried out in CF?
Double lung transplant
Indications for double lung transplant in CF
Rapidly deteriorating lung function
FEV1 < 30% predicted
Life threatening exacerbations
Estimated survival < 2 years
Survival of a lung transplant at 5 and 10 years
5 - 70 - 80%
10 - 50%
Features of pseudo barters syndrome
Metabolic alkalosis
Hypokalaemia
Hyperaldosteronism
Hyperrenism
Normal BP
Juxtaglomerular apparatus hyperplasia
