Cystic fibrosis Flashcards
Describe the genetics of cystic fibrosis
-autosomal recessive disorder in caucasions
-Delta F508 most common mutation(deletion) = block in processing CTFR protein
-if both parents are carriers:
1 in 4 chance child will be affected
2 in 4 chance carrier
1 in 4 chance unaffected
What is cystic fibrosis?
- genetic disorder that affects lungs and other organs (pancreas, liver, kidneys, intestine)
- difficulty breathing and coughing up mucous due to chest infection
- pulmonary disease main cause of death
Describe the mechanism of cystic fibrosis
- mutation in transmembrane conductance regulator protein( CTFR) coded on chromosone 7
- results in reduced chloride secretion from epithelium+ reduced Na absorption from lumen
- As a result to abnormal CL-/Na+ , leads to:
- reduced aiway surface liquid ( dehydrates mucous layer)
- thick sticky mucous
- shearing
- impaired bacterial killing via neutrophils
Diagnosis of CF - Antenatal screening(before birth)
- pre implantation genetic diagnosis
- chronionic villous sampliing ( removal + testing of sample of cells in placenta)
- amniocentesis( amniotic fluid removed from uterus for testing/treatment. Contains fetal cells + proteins
Diagnosis of CF - neonatal( premature )
- Newborn bloodspot day 5 ( guthrie test)
- screen positive - referred for clinical assestment + sweat test
Diagnosis of CF - postnatal (after birth)
- sweat testing ( measures conc of chloride excreted in sweat ( high in CF)
- High Na+(>60mmol/L) and chloride
- Mutation analysis
Systems CF can affect
see slide 14
Cardinal features of CF throughout life
1.
Pancreatic insufficiency:
-abnormal stools: pale/prange, difficult to flush, poly/greasy
-Failure to thrive; trhive well on breast milk, deficiencies of fat soluble vitamins
-diabetes
- Recurrent bronchopulmonary infection; pneumonia, bronchiectasis, scarring, abscesses
Importance of record, growth charts etc
Effect of CF on pancreas
6 classes of CF disease
Class 1-3 are pancreatic insufficient
Class 4-6 have some pancreatic function (more commn)
5% of CTFR function to have sufficent pancreatic function + be asymptomatic
Why does pulmonary infection occur?
- CFTR abnormality:
- decreased mucocillary clearance
- increased bacterial adherence
- decreased endocytosis of bacteria
Patients get repeated RI due to viscous circle of events
see slide 21
Investigation of CF
CXR
- signs of chronic infection; exagerrated bronchial markings
- signs of bronchiectasis ( dilated bronchioles with thickened walls [tramlines] )
CT scan
- bronchiecstasis (tramlines)
- signet rings ( round dilated airway + smaller adjecent BV)
- mucous plugging ( airways to stiff to clear secretions>infection)
- consolidation (infection)
Spirometry
- obstructive as disease progresses: ( FEV1 < 80%, FEV1:FVC < 70%)
- restrictive/obstructive patter (mucous = obstructive, damage to lung = restrictive)
Finger clubbing ( as a result of low O2 in blood, and sign of lung disease. Linked with inflammatory bowel disease, CVD, LD and aids)
Treatment of pancreatic insufficiency in CF
- enteric coated enzyme pellets(thins mucous)
- high energy diet(no low fat)
- fat soluble vitamin + mineral supplements (breaks down mucous)
Treatment of Mucous obstruction inflammation in CF
-Airway clearance via physiotherapy, mucolytics(less thick and sticky and easier to cough up), bronchodilators
Treatment of chronic infection in CF
-Antibiotics ( oral/IV/nebuliser)
Treatment in increased inflammation in CF
-Azithromycin ( low dose, antibiotic + antiinflammatory properties to reduce number of infective exacerbations of CF)
Treatment in fibrosis/scarring/bronchiectasis in CF
-supportive treatment + management of symptoms
Otherr diseases CF is linked with
Diabetes;
-T2 DM(insufficient insulin/receptor doesnt work
Osteoporosis;
-CF failure to reach peak bone mass in childhood, adolescence + accelerated bone loss in adulthood. -Increased risk of fractures. BMD falls in first few wks after lung transplant but escalates thereafter
Pneumothorax
Haemoptysis:
-CF BV more leaky so this occurs. Bronchial arteris can leak
Microbiology in CF: Young + Adults
Young:
- Staph.areus
- Haemophillus influenzae
Adults:
- pseudenomas aeruginosa( colonisation increases with age, low life expectance + rapid decline lung function)
- burkholderia cepacia
- myobacerium abscessus
- stenotrophomonas
ABSOLUTE Contraindications to transplant
- Other organ failure
- malignancy within 5 years
- significant PVD
- drug, nicotine, alcohol dependency
- active systemic infection
- microbiological issues(M.absesscus)
Relative contraindictions to lung transplant
- other organ dysfunction
- non compliance
- steroids > 20mg daily
- osteoporosis
- low/high BMI
- surgical risks ( previous thoracic surgery)
Other things to consider to improve Qol
- O2 + NIV
- exercise
- advanced care planning
- DNAR
