Flashcards in Cystic Fibrosis Deck (22)
CFTR present in what epithelial cells
Cystic Fibrosis Transmembrane conductance Regulator gene
ATP binding cassette transport
-protein kinase A
ATP regulated chloride channel
regulatory protein for other channels
only 5-10% activity needed for normal chloride transport
Muations are closely linked to infertility and pancreatic function but not to what?
Delta F 508
88% of all CF patients have on copy of delta 508
-3 base deletion at position 508 remove a phenylalanine
-protein does not escape ER for further processing
-dependent on ethnicity
WHat happens in class 1,2,3,4,5 mutation?
2-no maturation deltaf508
Airway surface liquid is thought to be:
ASL low volume or ASL too salty
how does this work?
abnormal submucosal gland secretion
abnormal modulation of epithelium inflammation
asl low volume-mucus stasis decreased ciliary beat-inhibited bacterial clearance
-major defect in lack of regulation of ENaC, Na is hyper-absorbed, cl follows through other pathways, water follows passively-->low volume increased mucus, delayed transport, mucus adhesion
asl too salty-salt sensitive defensins don't work
-chloride can't be reabsorbed, sodium and water reabsorption also decreased
CF lungs normal at birth
-secretions and clearance is abnormal leading to inflammation, chronic infection, obstruction, bronchiolitis and bronchiectasis
Symptoms-Chronic productive cough, dyspnea, chest tightness
-can have hemoptysis, pneumothorax as complication
What does a CF-CXR look like?
upper lobe predominant bronchiectasis
What respiratory infections are high?
Staph then pseudo
Pseudo chronic infection changes:
-loss of flagella dependent motility
What respiratory infection is associated with rapid decline?
How does CF affect the sinus?
hypertrophy/hyperplasia of secretory elements
-inflammation and edema
-transepithelial electric potential raised
How does CF affect the GI?
distal intestinal obstruction syndrome
focal biliary cirrhosis
hypoplastic GB, gallstones
How does CF affect the pancreas?
obstruction of ducts with inspissated secretions leads to dilations, destruction and fibrosis
-exocrine insufficiency/ fat malabsorption
How do they diagnose pancreatic exocrine insufficiency?
72 hour fat collection
fecal chymotrypsin or fecal elastase
vitamin ADEK levels
-dosing by fat intake, body weight or symptoms
CF related diabetes
pancreatic endocrine insufficiency
polyuria, polydipsia, weight loss, unexplained drop in lung function
How does CF affect the bones and joints
osteopenia and osteoporosis
-vit D deficiency, calc malabsorption, accelerated bone loss, hypogonadism, inactive, low bmi
How does CF affect the GU
-endocervicitis, mucus distended cervical glands
failure in transport no production
-vas deferens missing
How does CF affect the sweat glands
pronounced abnormality in Na Cl homeostasis
increased sensitivity to dehydration in hot weather
salty taste to sweat
-sweat test >60
1. airway clearance
-nebulized-tobramycin, aztreonam lysine, colistin
-iv for exacerbation
-need 3500-4500 cal/day
-better weight better outcome
7. lung transplant
refer when FEV
What is the future therapy for CF?
processing and modulation of CFTR, restoring ion transport
targeted at specific defect
potentiators-ivacaftor --class 3
-bring back lung function!