L17 - Cystic Fibrosis Flashcards
Genetics: CF is….
Autosomal Recessive
CF arises from…
- Mutation affecting gene in long arm of chromosome 7.
- Gene coding for chloride channel
- known as cystic fibrosis transmembrane conductance regulator. CFTR
Genetic defect of the CFTR gene will cause?
- Increase in Na+ and Cl- content in sweat.
- Increased resorption of Na+ and water from respiratory epithelium.
How may CF lead to bronchectasis?
- Dehydration of airway epithelium is thought to predispose
- to chronic bacterial infection
- and ciliary dysfunction.
Describe how a CFTR channel works?
- Chloride channel on apical membrane
- controlled by cAMP
- indirectly controlled by B adrenoreceptor stimulation
- Mutation in CFTR leads to absent or defective function Cl- channel
- leads to reduced chloride secretion
- excessive sodium resorption
- dehydration of airway lining
Neonatal screening for CF involves?
- Immunoreactive trypsin
- Genetic testing of newborn blood sample
Children with CF will have their lungs commonly infected with…
Staph. aureus
Adults with CF will commonly have their lungs infected with…
P. Aeruginosa
Gram negative bacilli
Stenotrophomonas
Why are most men with CF infertile?
- Failure of development of vas deferens.
- Seminal vesicular dysfunction
- means that ejaculates are low in volume.
State some respiratory complications of CF
- Progressive airway obstruction
- infective exacerbation of bronchiectasis
- respiratory failure
- spontaneous pneumothorax
- haemopytsis
- lobar collapse due to secretions
- pulmonary hypertension
- nasal polyps
GI complications associated with CF
- Malabsorption
- Steatorrhoea
- Distal intestinal obstruction syndrome
Hepatic complications associated with CF
- Biliary cirrhosis
- progressive destruction of bile ducts of liver - Portal hypertension
- increases BP within portal venous system - Varices
- enlarged veins - Splenomegaly
- enlarged spleen
5.Gallstones
Other complications associated with CF
- Diabetes! –> 25% patients with CF often require insulin therapy.
- Delayed puberty
- Male infertility
- Osteoporosis
- Arthropathy –> inflammation of joints
- Cutaneous vasculitis –> vasculitis affecting vessels in skin and subcutaneous tissue but not internal organs.
Treatment / management of CF
- Daily chest physiotherapy - for patients producing sputum.
- Staph aureus infection managed: oral antibiotics
- Psuedomonas infection: IV treatment
- Patients with coexistent asthma: inhaled bronchodilators and glucocorticoids
Many patients with CF will eventually be colonised by antibiotic resistant bacteria.
How might malabsorption due to CF be treated?
- Due to exocrine pancreatic failure.
- Treated with oral pancreatic enzyme
- vitamin supplements.
Describe role of CFTR potentiators and give an example
Small molecules to correct function of particular CFTR channel.
e.g. Ivacaftor
State common upper respiratory infections ?
- Coryza (Common cold)
- Acute pharyngitis
- Acute tracheobronchitis
Coryza (Common cold) most likely due to what type of organism?
Due to Rhinovirus infection
What causes whooping cough?
Bordetta Pertussis
- highly contagious
Symptoms of Rhinosinusitis?
Combination of :
- nasal congestion
- blockage
- discharge.
Bronchiectasis
Abnormal dilation of bronchi
Chronic inflammation
Infection in airway
Describe briefly the pathophysiology behind bronchiectasis?
- Destruction of smooth muscle and elastic tissue
- by chronic necrotizing infection
- leading to permanent dilation of bronchi and broncioles.
Congenital causes of bronchiectasis
- CF
- Ciliary dysfunction syndrome
- Primary ciliary dyskinesia (immotile cilia syndrome)
- Kartagener’s syndrome (sinusitis and transposition of viscera) - Primary hypogammaglobulinaemia
How may bronchiectasis be acquired in children?
- Severe infection in infancy : whooping cough, measles
- Primary TB
- inhaled foreign body
Acquired bronchiectasis in adults
- Suppurative (production of pus) pneumonia
- pulmonary TB
- allergic bronchopulmonary aspergillosis.
- bronchial tumor
Allergic bronchopulmonary aspergillosis
- Allergic
- hypersensitive reaction
- to fungus Aspergillus fumigatus.
Localised bronchiectasis due to?
- Due to accumulation of pus
- beyond an obstructing bronchial lesion
- such as hilar lymph nodes, bronchial tumour or inhaled foreign body.
Symptoms of bronchiectasis
- Cough, sputum, pleuritic pain.
- Haemoptysis
- streaks of blood
- massive will require bronchial artery embolisation - Halitosis
- bad breath
What might be a physical sign of bronchiectatic airways with secretions blocking proximal bronchi?
Diminished breathing sounds
What might we hear if large amounts of sputum were in bronchiectatic space?
Numerous coarse crackles may be heard over affected area.
Describe investigations which may be done for a patient with suspected bronchiectasis?
CT
- Sensitive, shows thickened dilated airways
X-ray
- usually not apparent, but in advanced diseases thickened airway, cystic bronchiectatic spaces, pneumonia consolidation collapse may be seen.
How might we test patient with suspected ciliary dysfunction syndrome?
Measure time taken for saccharin pellet in anterior chamber of nose to reach pharynx, patient will be able to taste it.
Should be about 20mins.
If greatly prolonged indicated patient with ciliary dysfunction.
State how physiotherapy might be used for management of bronchiectasis?
- Daily, assists in drainage of bronchial secretions.
- Prevents recurrent episodes of bronchopulmonary infection.
- Deep breathing followed by forced expiratory manoeuvres.
State how antibiotic therapy might be used to manage bronchiectasis?
Psuedomonas secondary infection.
- Oral ciprofloxain
- IV anto-psuedomonal B-lactams
Describe primary ciliary dyskinesia?
- Ciliary dysfunction
- due to defect in ciliary motor protein mutations : dynein.
- Contributes to retention of secretion and recurrent infection that in turn leads to bronchiectasis.
- Autosomal recessive
Kartagener’s syndrome involves
- Situs Inversus
- major visceral organs are reversed. - Chronic sinusitis
- inflammation nose sinuses - Bronchiectasis
CFTR function is activated by…
What else will then activate chloride secretion
cAMP.
Prostaglandin E2, serotonin, heat stable enterotoxin E-coli, cholera
Describe key areas CFTR proteins are found?
- Airway
- sweat duct
- pancreatic duct
- biliary tree
- vas deferen’s epithelia.
State common mutation of CFTR protein
DF508
D-delta
Composition of airway surface liquid
- Thin periciliary layer
2. Thicker innermost mucus layer
Potential therapies for CF
- Combined therapy for class 2 mutations
- lumacaftor and ivacaftor (orkambi) - Premature truncation codon therapy.
- Gene replacement therapy.
