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
How often do you check for DM
Annual OGTT
How do you treat pancreatic insufficiency? [6]
- Enteric coated enzyme tablets every meal (Creon / Pabrinex)
- High energy diet, High fat
- Fat soluble vitamisn - ADEK
- H2 antagonist / PPI as increase pH and help absorption
- NG feed only if can’t maintain weight
- Insulin
Management of lung complications [7]
- Chest physio, postural drainage
- Nebulised rhdnase with saline
- Bronchodilator for obstruction
- Annual CXR
- Flu vaccine, cohorting
- Prophylactic antimicrobials
- Antibiotics for acute infection
What Ax as prophylaxis [3]
- Flucloxacillin up to 3-6yo
- Inhaled colamycin (pseudomonas)
- Oral anti-fungals
s
What do you do in advancing disease to reduce inflammation [3]
NSAID
Prednisolone
Azithromycin
Review in CF [7]
- Clinical assessment: hx, medication adherence., ex, height and weight
- SpO2 measurement
- Sputum/NPA/cough swab sample
- Spirometry
- Imaging
- Dietetic review
- Psychological review
Medication specific to homozygous for delta F508 mutation
Ivacaftor
Lumacaftor
What do you do in advance lung disease [4]
Oxygen
Diuretic if cor pulmonale
NIPPV
Transplant
Contraindications for transplant [7]
Mycoplasma abscess TB / aspergillus Other infection IVDA Peripheral vascular Malignancy in past 5 years Organ failure
Indications for transplant [5]
FEV1 <30% Hypoxia at rest Hypercapnia Life threatening exacerbation Survival <2 years
Resp complications
Obstruction = wheeze Lung parenchyma destroyed / scarring Cor pulmonale Pneumonia Bronchiectasis Lung abscess Pulmonary osteo-arthropathy Hypertrophy of bronchial artery = haemoptysis Pneumothorax Resp failure Death
How does CF lead to resp failure [3]
Obstruction leads to impairment of gas exchange
Get hypoxia and hypercapnia
Go into resp failure
What is meconium ileus
Meconium causes obstruction in GI tract
Failure to pass stool
Vomiting in 1st two days of life
Distended loops of bowel
How do you Rx
NG tube drainage
Wash out enema
Excision of gut
What can present like meconium ileus
Dehydration
What is usual cause of death
Pneumonia
Cor pulmonale
