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.