Cystic Fibrosis Flashcards
What is cystic fibrosis, include:
- Inheritence pattern
- Gene mutation
- Location of gene
- Secretions
- Where in body it affects
- Autosomal recessive
- CFTR (cystic fibrosis transmembrane conductance regulator)
- Chromosome 7
- Charcterised by thick secretions
- Can lead to multisystem disease- most commonly affects respiratory system and GI tract
Explain why cystic fibrosis leads to thick mucus
- Defect in CFTR gene
- Defective CFTR protein
- CFTR codes for Cl- ion channel. In the airways, CFTR also inhibits ENaC
- Hence, in healthy individual, Cl- is transported into lumen and the movement out of Na out of lumen is reduced; the net effect of this is increased water in the lumen (and hence in secretions)
- In CF pt, Cl- transport is reduced and the ENaC are not inhibited hence Na+ moves out of lumen; the net effect of this is decreased water in the lumen
Explain why people with cystic fibrosis have salty sweat
- In sweat glands, CFTR is responsible for reabsorption of Cl- through CFTR; it also regualtes Na+ reabsorption thorugh ENaC
- CFTR mutation means less reabsorption of Na+ and Cl- hence salty sweat
Function of the CFTR is tissue specific; true or false?
True (you can see from pathophysiology behind thick secretions and salty sweat that CFTR in resp tract works differently to CFTR in sweat glands. Main idea is that it regualtes Cl- and Na+ transport)
When do symptoms of CF often start?
- Symptoms often start in early infancy
- However, in milder cases symptoms may not appear until later in childhood
- Genetic testing allows for early detection & treatment
Discuss the symptoms of cystic fibrosis include symptoms of a:
- Newborn
- Children & young adults
Newborn
- Meconium ileus
- Failure to thrive
- Rectal prolpase
- Voracious appetite (never satisfied)
Children & Young Adults
- Respiratory
- Cough
- Wheeze
- Recurrent infections
- Haemoptysis
- GI
- Steatorrhoea
- Symptoms of diabetes (thirst, polyuria, polydipsia)
- Distal intestinal obstruction syndrome
- Gallstones
- GORD
- Symptoms of liver cirrhosis
- Other
- Male infertility
- Sinusitis
- Osteoarthritis
- Nasal polyps
What is meconium ileus?
In what % of infants, with CF, does it present in?
- Meconium (baby’s first stool) is blocking the ileum because it is very thick; leads to symptoms of: vomitting, abdo distension, delay in passing meconium
- 15-20%
What % of CF patients have malabsorption?
At what age is this most evident?
- >90%
- Infancy
Discuss what you might find on clinical examination of someone with CF
- Finger clubbing
- Bilateral coarse crackles
- Evidence of pneumothorax (e.g. hyperesonant percussion, decreased breath sounds, decreased expansion etc..)
- Cyanosis
- Evidence of malnutrition
- Mass in right lower quadrant of abdomen (DIOS)
Discuss how we diagnose CF
To diagnose CF need one or more of:
- Characteristic phenotypic features of CF
- History of CF in sibling
- Positive newborn screening test
And also need one of:
- Increased NaCl concentration in sweat (positive sweat test)
- Identification of two CF mutations via genotyping
- Demonstration of abnormal nasal epitihelial ion transport (nasal potential difference)
What test is the best indicator of CF?
NaCL sweat test
Discuss what investigations you would do if you wanted to diagnose CF
- If newborn, do heel prick test (immunoreactive-trypsinogen test)
- Sweat test
- Genetic testing
What value indicates a:
- Negative sweat test
- Intermediate result
- Positive sweat test
- Negative: <30mmol/L
- Intermediate: 30-59mmol/L
- Positive: >/=60mmol/L
Explain why pancreatic insufficiency is a common symptom of CF
Explain why CF can lead to diabetes
- Thickened secretions mean that overall secretion from pancreas is reduced.
- Blocked secretions cause inflammation which leads to scarrring which leads to impaired production of insulin from pancreas
State some symptoms of pancreatic insufficiency in CF patients
- Steatorrhoea
- Abdo pain
- Excess flactulence
- Weight loss
How do you test for pancreatic insufficiency in CF patients?
How do you treat pancreatic insufficiency in CF patients?
- Test stool for faecal elastase
- Pancreatic enzyme supplements
If a pt with known CF came to seek medical help for their CF because they were experiencing a wide range of typical CF symptoms, what investigations would you do- include:
- Bedside
- Bloods
- Imaging
*For each, justify why
Bedside
- Sputum culture: check for presence of microorganisms
- Stool sample: check for faecal elastase
- BMs: check diabetes
- Spirometry: check for obstructive pattern
Bloods
- FBC: WCC
- U&Es
- LFTs: CF pts can get problems with biliary drainage but can also get fibrosis- leading to cirrhosis- of liver.
- Clotting: see above
- Vit A,D,E,K levels: obstruction of bile, decreased emulsification of fats, decreased absorption fat soluble vitamins
- CRP: check for infection/inflammation
- Aspergillus serology
Imaging
- Abdominal ultrasound: fatty liver, cirrhosis, chronic pancreatitis
- CXR: CF can cause bronchiectasis, hyperinflation
How common is liver disease in CF pts?
- ~40% have abnormalities with liver
- Only ~5-10% have symptoms/problems
CF can lead to bronchiectasis; true or false?
True; CF predisposes to recurrent respiratory infections which leads to chornic inflammation. This can cause dilation of bronchi and thickening of bronchi walls (bronchiectasis)
Compare DIOS and constipation
- DIOS= faecal obstruction confined to ileocaecum
- Constipation= faecal obstruction in whole bowel/anywhere in bowel
What are some common precipitators of DIOS in CF patients?
How would we diagnose DIOS?
- Triggers/precipitators: pancreatic insuffiency, (most often), hot weather leading to dehydration & salt deficiency (as CF pts have salty sweat)
- Diagnosis based on symptoms (palpable mass RIF, AXR may show faecal loading in ileocaecal region)
State some factors which contribute to malabsorption in CF
- Pancreatic insufficiency
- Chronic malabsorption
- Chronic sinusitis leading to impaired taste
- Fatigue & inflammatory mediated anorexia
- Chronic inflammation leading to increased energy expenditure
- Increased requirements of breathing
Discuss how we manage cystic fibrosis, think about treating:
- Respiratory problems
- Pancreatic/GI/malabsorption problems
- Psychological/emotional
Respiratory Problems
- Chest physio with postural drainage
- Mucolytics e.g.Inhaled recombinant human deoxyribonuclease 1
- Bronchodilators
- Antibiotics for acute infective exacerbations (usually give 2 antibiotics to reduce antibiotic resistancE)
- Prophylactic antibiotics (azithromycin 3x weekly proven to help)
- Inhaled antibiotics
- ICS
- Flu vaccination
- Lumacaftor-ivacaftor
- Lung transplant (in resp failure)
Pancreatic/GI/malabsorption problems
- Pancreatic enzyme replacement
- Fat soluble vitamins
- Supplements
- High calorie intake
- NG or PEG feeding
Psychological/emotional
- Support groups
- Counselling
What lifestyle advice would you give to someone with CF?
- No smoking
- Avoid other CF patiens
- Avoid people with colds/infections
- Avoid jacuzzis (spread pseudomonas)
- Clean & dry nebulisers thoroughly
- Avoid stables, compost or rotting vegetation (aspergillus risk)
- Annaul flu vaccination
- NaCl tablets in hot weather or vigorous exercise
For the drug orkambi, remind yourself:
- Two drugs it contains
- Role of each drug
- Lumacaftor: CFTR chaperone (so increases number of CFTR proteins getting to cell surface)
- Ivacaftor: CFTR potentiator which binds to channel increase probability that Cl- is open
*Shown to improve lung function & reduce pulmonary exacerbations
Remind yourself of the 6 classes of mutation found in CF
Which is class is most common?
- = no protein production
- = protein made but never gets to membrane
- = protein made and gets to membrane but doesn’t work
- = protein made and gets to membrane but only partially active
- = protein expressed at gene level but substantial reduction in synthesis or mRNA or protein or both
- = protein gets to membrane but unstable
Most common is class 4 (Phe508del)
What is the life expectancy of someone with CF
Life expectancy about 40 yrs.
Multidisciplinary team working has allowed this life expectancy to achieved
Many microrganisms can become permanently established in CF patients; state some organisms that may be found in sputum of CF pts
- Pseudomonas aeruginosa
- Burkholder cepacia
- Aspergillus
- Non-tuberculous mycobacteria
