CF Flashcards
What is Cystic fibrosis [2]
Inheritance
Defect in CFTR gene on chromosome 7
Inheritance: autosomal recessive
What gene loci is associated with 70% cases?
What does CFTR stand for?
Function of the CFTR gene
delta F508 on 7q
Cystic fibrosis transmembrane conductance regulator
CFTR codes for cAMP-regulated chloride channel causing increased viscosity of secretions
Function of the CFTR gene
Active transport of chloride and Na
Regular volume on epithelial surface giving cilia normal function
Abnormal viscosity interfere with clearance leading to bacteria colonisation and repeated infections
- Cilia collapse
- Excessive inflammation
Increased Na and decreased Cl inactive defences
Abnormal mucous builds up which traps bacteria
What are different classes of mutation [4]
Class 1 - no synthesis
Class 2 - no maturation
Class 3 - CFTR doesn’t work
Class 4 - decreased conductance
Get milder from class 1 to 4
What fraction of the population is carrier and affected? [2]
1 in 25 carrier
1 in 2500 affected
Pathophysiology CF
Pancrease [3]
Intestine [2]
Lungs [2]
Pancreas
- blockage of pancreatic exocrine ducts
- leading to early activation of pancreatic enzymes
- auto-destruction of exocrine pancreas
Intestine
- bulky stools and obstruction
Lungs
- Mucus retention
- Chronic infection
- Lung tissue destruction
Effects of reduced chloride out and increased Na in lead too? [2]
- Inactivates defences in airway
- CF have abnormal mucous glycoprotein which acts as binding site for bacteria
What are antenatal features? [3]
Carrier testing
Echogenic bowel
Perforated meconium ileum
What are neonatal features [4]
Meconium ileus
Intestinal atresia
Prolonged (obstructive) jaundice
Steatorrhea, FTT
What are features in children [6]
Recurrent chest infection Chronic productive cough Constipation (dysmotility) Rectal prolapse (bulky stools) Pancreatic insufficiency - DM Delayed puberty, short stature
What are common organisms in CF / chronic and their antibiotic treatments [6]
S.Aureus - flucloxacillin H. influenza - cotrimoxazole Pseudomonas: tazocin, inhaled tobramycin Mycoplasma (non-TB) - clarithromycin Burkholderia cepacia - tazocin Aspergillus -amphotericin
What are less common organisms [2]
Mycobacterium abscess
Genovar III
What are the signs of pancreatic insufficiency in CF [5]
Failure to gain weight / FTT Fat malabsorption, Vitamin deficiency Steatorrhea, Offensive stools DM Gall stones, Biliary cirrhosis
What do recurrent chest infections cause
Pneumonitis Bronchiectasis Pneumothorax Resp failure Cor pulmonale Scarring and difficult to inflate lungs / SOB Abscess Cyanosis Clubbing Coarse crackles
Clinical features more apparent in adulthood [10]
Nasal polyps, Sinusitis, Airway obstruction Clubbing in women Male infertility, female subfertility Gall stones Cirrhosis Chronic pancreatitis Pseudo-bartter Osteporosis Vasculitis
What is pseudo-bartter? [2]
- Hyperaldosterone but normal BP
- Hypokalameic
Hypochloraemic metabolic alkalosis in absence of renal pathology
How do you screen CF? [2]
- Neonatal screening as part of Guthrie tests
- High immunoreactive trypsinogen (IRT)
What is needed for diagnosis of CF [2]
Monitoring investigations [10]
- If IRT +ve then do sweat test
- Genetic testing if not definitive
CXR
HRCT
FBC, U+E, LFT
Clotting + Vit ADEK due to malabsorption
Faecal elactase = pancreatic enzyme that is raised
Sputum culture to look for bacterial colonisation
Glucose tolerance test
Spirometry = obstructive
Abdo USS (liver)
Bone scans
What is the threshold of a positive sweat test
> 60mEq/l (normal is <40)
What gives false +Ve [6]
Malnutrition Adrenal insufficeincy Glycogen storage disorder DI Hypothyroid G6PD
What gives false -ve [2]
Skin oedema due to hypoproteinaemia secondary to exocrine insufficiency
What does CXR show [4]
Scarring
Hyperinflation
Cyst
Bronchial dilation
What does CT show [3]
Dilated airway
Thickened wall
Pus
What will USS show [3]
Pancreatitis
Gall stone
Cirrhosis
