Cystic Fibrosis (+ABPA) Flashcards
Describe the molecular basis of cystic fibrosis
- CFTR transports Cl- and bicarbonate (+ regulates ENAC)
- Cl- is transported out of cells into airways + H2O follows
- critical role in the hydration of mucous in the airway tract
- defective CFTR function leads to reduced airway surface hydration > thick sticky mucous + impaired mucociliary clearance
What is cystic fibrosis?
- Autosomoal recessive disorder | chromosome 7
- Mutation in the cystic fibrosis transmembrane conductance regulator
What is the inheritance pattern in cystic fibrosis?
Autosomal recessive
How common is cystic fibrosis?
1 in 2,500 babies
What is the most common mutation in cystic fibrosis?
Phe508del CFTR protein
What does a mutation in the Phe508del CFTR protein cause?
- defective intracellular processing + trafficking
- decreased stability > reduces quantity of CFTR protein at apical surface of epithelial cells
- exhibits defective channel gating
How do you diagnose cystic fibrosis?
- One or more of the characteristic phenotypic features
- or history of CF in sibling
- or positive newborn screening test result
AND
- increased sweat chloride conc. sweat test
- or identification of 2 CF mutations by extended genotyping
- or demonstration of abnormal nasal epithelial ion transport
What investigations are used for diagnosis of cystic fibrosis?
New born heel prick test
Sweat test
Outline the sweat test used to diagnose cystic fibrosis
- pilocarpine is applied to patch of skin
- electrodes placed either side of patch
- small current passed between
- causes skin to sweat
- sweat absorbed with gauze or filter paper
- sent to lab for chloride conc testing
- >60mmol/L is diagnostic
Classic clinical presentations of cystic fibrosis
Meconium ileus
Intestinal malabsoption + pancreatic insufficiency
Recurrent chest infections
Newborn screening
What is meconium ileus?
Newborn baby’s first poo (meconium) is stuck due to sticky secretions in the bowel
Signs and symptoms of cystic fibrosis
- chronic productive cough
- recurrent chest infections
- steatorrhoea
- abdominal pain + bloating + distention
- ‘skin tastes salty’
- poor weight + height gain
- nasal polyps
- finger clubbing
- crackles + wheezes on auscultation
Complications of cystic fibrosis
- bronchiectasis
- recurrent chest infections
- pneumothorax
- cardiac failure
- chronic liver disease
- oesophagitis
- distal intestinal obstruction syndrome
- low BMI
- male infertility
- gallstones
- pancreatic insufficiency
- osteoporosis
- arthritis
- cystic fibrosis related diabetes
What factors contribute to the impaired nutritional status in cystic fibrosis?
- pancreatic insufficiency
- chronic malabsorption
- chronic inflammation > increased energy expenditure
- increased energy requirements for breathing
Lung complications of cystic fibrosis
Bronchiectasis
Pneumothorax
Haemoptysis
Respiratory failure
Recurrent chest infections
Liver complications of cystic fibrosis
Chronic liver disease
Portal hypertension
What lifestyle advice is given to a patient with cystic fibrosis?
- no smoking
- avoid friends with colds/infections
- avoid jacuzzis
- clean + dry nebulisers thoroughly
- avoid stables, compost or rotting vegetation - risk of aspergillus fumigatus inhalation
- flu vaccine
- pneumococcal vaccine
- sodium chloride tablets in hot weather or after vigorous exercise
Clinical management of cystic fibrosis
- holistic care
- up to date flu + pneumococcal vaccines
- chest physio + infection management to maintain lung health
- optimal nutritional state - BMI, vitamins etc.
- fat soluble vitamin replacement A,D,E,K
- pancreatic enzyme replacement therapy if pancreatic insufficient
- long term antibiotics
- novel CFTR modulators/potentiators e.g. Kaftrio
What is the only cure for cystic fibrosis?
Lung transplant
Why should you advise a patient with cystic fibrosis to avoid jacuzzis?
Avoid risk of pseudomonas aeruginosa infection
Why are patient with cystic fibrosis at higher risk of becoming underweight?
Due to malabsoprtion from GI tract: increased mucous prevents digestive enxyme from working > harder for patients to get correct nutrients
Why should you advise patient with cystic fibrosis to avoid farms + compost?
Reduce risk of aspergillus fumigatus inhalation
What is allergic bronchopulmonary aspergillosis?
- Condition characterised by exaggerated response of immune system to Aspergillus fumigatus exposure
- Repeated damage from the immunological reactions > bronchiectasis
Who is allergic bronchopulmonary aspergillosis more common in?
Asthma
Bronchiectasis
Cystic fibrosis
Diagnosis of allergic bronchopulmonary aspergillosis
Made by a combination of:
- symptoms e.g. dry cough + wheeze
- positive blood tests: raised aspergillus IgE levels + high total IgE
Blood results of allergic bronchopulmonary aspergillosis
Raised aspergillus IgE
High total IgE
High eosinophil level
Treatment of allergic bronchopulmonary aspergillosis
Oral corticosteroids + antifungals
