Harrison - Cystic Fibrosis Flashcards
Percentage of patients >18?
> 46%.
Percentage of patients over 30?
16.4%.
Median survival in CF?
> 37.4
What is the general picture of CF?
- Chronic bacterial infection of the airways that leads to bronchiectasis and bronchiolectasis.
- Exocrine pancreatic insufficiency.
- Intestinal dysfunction.
- Abnormal sweat gland function.
- Urogenital dysfunction.
The mutations in the CFTR gene fall into how many categories?
5.
Severe CFTR mutations?
Class I, II, III –> Pancreatic insufficiency + high sweat NaCl values.
Mild CFTR mutations?
Class IV and V –> pancreatic insufficiency and intermediate/normal sweat NaCl values.
Prevalence of CF?
Variable - 1/3.000 in Caucasian of Europe and North America. 1/90.000 in Asian population of Hawaii.
What is the MC mutation in CF?
Class II –> 3bp deletion that results in an absence of phenylalanine at amino acid position 508 (ΔF508).
Class I mutations involve?
Defective protein synthesis of CFTR.
Class II mutations involve?
Defective processing of CFTR.
Class III mutations involve?
Defective regulation
Class IV mutations involve?
Defective conduction.
Class V mutations involve?
Reduced functioning CFTR.
Epithelial dysfunction in CF?
Diverse and organ specific.
- Some are volume absorbing - airways and distal epithelia.
- Some are salt- but not volume absorbing - sweat duct.
- Some are volume secretory - proximal intestine and pancreas.
Epithelial dysfunction in CF - What is the unifying concept?
All affected tissues express abnormal ion transport function.
Diagnostic biophysical hallmark of CF airway epithelia?
The raised transepithelial electric potential difference (PD) - reflects both the rate of active ion transport and epithelial resistance to ion flow.
Central hypothesis of CF airways pathophysiology?
Faulty regulation of Na absorption and inability to secrete Cl via CFTR reduce the volume of liquid on airway surfaces i.e. They are “dehydrated”.
The infection that characterizes CF airways involves?
The MUCUS layer rather than epithelial or airway wall invasion.
O2 tension in CF mucus?
Is very LOW - Adaptations to hypoxemia are important determinants of the physiology of bacteria in the CF lung.
Both mucus stasis and mucus HYPOXEMIA contribute to?
- The propensity for Pseudomonas to grow in biofilm colonies within CF airway mucus.
- The presence of strict anaerobes in CF lungs.
Percentage of patients with hepatobiliary problems (focal biliary cirrhosis, bile-duct proliferation)?
25-30%.
CF and gallstones?
Inability of the CF gallbladder epithelium to secrete salt and water can lead to both chronic cholecystitis and cholelithiasis.
How is the sweat gland dysfunction measured in CF?
By measuring Cl concentrations in sweat collected after iontophoresis of cholinergic agonists.
What percentage of CF patients presents within the first 24h?
Approx. 20% –> GI obstruction, termed meconium ileus.
CF - Respiratory clinical features?
- Almost universal.
- Chronic sinusitis in childhood - High incidence of nasal polyps (25%).
- First symptom of lower respiratory tract is cough - productive with greenish color.
- Asymptomatic periods with periods of pulmonary exacerbations, often triggered by viral infections –> Eventually, respiratory failure.
CF - Characteristic sputum microbiology:
- H.influenza.
- S.aureus.
- P.aeruginosa - often multi-resistant.
- Burkholderia cepacia.
- Other gram(-) rods –> Alcaligenes xylosoxidans, B.gladioli, and occasionally Proteus, E.coli, Klebsiella.
- Up to 50% –> A.fumigatus - Up to 10% exhibit ABPA.
- M.tuberculosis is RARE.
First lung-function abnormalities in CF children?
Incr. RV/TLC –> Suggest that SMALL-airways disease is the first functional lung abnormality in CF.
What happens to lung function as CF progresses?
BOTH reversible and irreversible changes in FVC and FEV1 develop.
REVERSIBLE component –> Reflects the accumulation of intraluminal secretions and/or airway reactivity, which occurs in 40-60% of patients with CF.
IRREVERSIBLE component –> Reflects chronic destruction of the airway wall and bronchiolitis.
CXR findings in CF - Early?
Hyperinflation –> reflecting small airway obstruction.
CXR in CF - Late?
Signs of luminal mucus impaction, bronchial cuffing, and finally bronchiectasis, eg ring shadows are noted.
Where do we find the earliest findings in CF?
The right upper lobe displays the earliest and most severe changes - For reasons that remain speculative.
Respiratory complications of CF?
- Pneumothorax in >10% of patients.
- Production of small amounts of blood –> Advanced disease.
- Life-threatening massive hemoptysis.
- Clubbing.
- LATE EVENTS –> Respiratory failure, cor pulmonale.
Distal intestinal obstruction syndrome (DIOS) in CF?
In children and young adults –> RLQ pain, loss of appetite, occasionally emesis, often a palpable mass –> Confused with appendicitis.
Percentage of CF patients with exocrine pancreas insufficiency?
> 90%.
Diabetes in CF?
LATE - Inflammation-induced insulin resistance + dysfunction of beta cells –> Hyperglycemia that requires insulin –> IN >29% of patients >35.
CF - Genitourinary system?
- Late onset of puberty is common in BOTH males and females with CF.
- > 95% of male patients with CF are azoospermic - obliteration of the vas deferens due to defective liquid secretion.
- Some 20% of CF women are infertile due to effects of chronic LUNG disease on the menstrual cycle and thick, tenacious cervical mucus that blocks sperm migration.
Most CF pregnancies produce?
Viable infants, and CF women breast-feed infants normally.
Diagnosis of CF?
Rests on the combination of clinical criteria and abnormal CFTR function as documented by sweat tests, nasal PD measurements, and CFTR mutation analysis.
Cl sweat concentration for CF diagnosis?
Varies with age - Typically >70mEq/L.
Percentage of CF patients with the clinical syndrome of CF and normal sweat Cl values?
1-2%.
Major objectives of CF therapy?
To promote clearance of secretions and control infection in the lung, provide adequate nutrition, and prevent intestinal obstruction.
More than 95% of CF patients die of complications from?
Lung infection.
The time-honored techniques for clearing pulmonary secretions are?
- Exercise.
- Flutter valves.
- Chest percussion.
Role of inhaled hypertonic saline 7% in CF treatment?
Efficient in restoring mucus clearance and pulmonary function in short term studies and in reducing acute exacerbations in a long-term (1-yr) study –> It is becoming standard of care.
Why the antibiotic doses in CF are higher?
Because of increased total-body clearance and volume of distribution of antibiotics in CF patients.
Antibiotics for CF?
- EARLY –> May eradicate Pseudomonas for extended periods.
- LATE –> Suppression is the goal.
A. Azithromycin 250mg/d or 500mg 3x/wk is often used chronically
B. Inhaled aminoglycosides (Tobramycin 300mg bid).
Role of INHALED beta-agonists and ORAL steroids in CF?
INHALED beta-agonists –> useful to control airways constriction - NO long term benefit.
ORAL steroids –> Reduce inflammation - Limited by side effects/ May be useful for treating ABPA.
NSAIDS in CF?
A subset of adolescents with CF may benefit from long-term, HIGH-dose ibuprofen.
Atelectasis in CF?
Requires treatment with inhaled hypertonic saline, chest physio, and antibiotics.
Massive hemoptysis in CF?
Bronchial artery embolization.
Most ominous complications of CF?
- Respiratory failure.
2. Cor pulmonale.
Most effective conventional therapy for respiratory failure and cor pulmonale in CF patients?
- Vigorous medical management of the lung disease.
- O2 supplementation.
- -> Ultimately, TRANSPLANTATION is the only solution.
2-yr survival for lung transplantation?
Exceeds 60%, and transplant-patient deaths result principally from obliterative bronchiolitis.
Pancreatic insufficiency treatment in CF?
> 90% of patients.
Capsules 4.000-20.000 units of lipase.
Typically no more than 2.500/kg per meal, to avoid fibrosing colonopathy!
Percentage of CF patients with cholestatic liver disease?
In about 8% of CF patients - Treatment with ursodeoxycholic acid.
Percentage of CF patients with end-stage liver disease?
5% and is treated with transplantation.
CF have an increase risk for?
- Osteoarthropathy.
- Renal stones.
- Osteoporosis.
PARTICULARLY FOLLOWING TRANSPLANT.
CF patients that are diagnosed as adults?
5%
