Mod 8 Cystic Fibrosis Flashcards
Cystic fibrosis [CF] is a life-limiting autosomal recessive genetic disorder;
- caused by mutations in which pair of genes?
Autosomal recessive gene disorder that has mutations are located on Chromosome 7
Cystic fibrosis [CF] is responsible for production of which protein?
Cystic fibrosis transmembrane regulator [CFTR]
Why is Cystic fibrosis transmembrane regulator a problem?
prevents/regulates chloride and bicarbonate cross-membrane transport. leading to:
- abnormal electrolyte and water movement in and out of epithelial cells
- problems w/water movement
Indicators of cystic fibrosis in infants
Development of meconium ileus; something about delay bowel movemnts?
- big meconium that can’t pass through-
- low birth weight; inability to absorb nutrients.
True or False:
- males are infertile while females aren’t
True, males lack the vas deferens
insert slide 8
why is Cystic fibrosis only a 25% chance of being passed on by parents?
It is a recessive gene; offspring will either be carries or will require both parents will need to have a copy
- 25% chance of no disease (or having it)
- 50% of being a carrier
Describe the pathophysiology of Cystic fibrosis [CF] that causes problems
Airway surface liquid dehydration due to uncontrolled activity of epithelia sodium channels
Morbidity and mortality of CF pts is due to what?
Chronic airway infection, leading to irreversible end stage resp. failure.
Cystic fibrosis [CF] will be encountered by which routes?
Referral from paediatric clinics and new diagnosis in adult life
slide 11
CFTR malfunction results in what alterations in the lungs?
Build up of thick mucous in airways leading to resp. insufficiency.
In Cystic fibrosis [CF] what a causes bacterial colonization of the resp. tract?
A combo of decreased mucociliary clearance and an altered ion transport.
- dehydration limits mucus covering cilia, and hence fluid movement
Cystic fibrosis [CF] common bacteria? slide 12
Pseudomonas aeruginosa
Impaired mucociliary clearance leads to small bronchi and broncioles becoming
partially or fully obstructed
Partial obstruction in bronchi lead to
overdistenion of alveoli
complete obstruction in bronchi leads to
atelectasis and bronchiectasis
Heterogeneity of lung function of Cystic fibrosis [CF] presents what symptoms in advance stages?
slide 13 + slide 14?
what other systems are affected by Cystic fibrosis [CF]?
- recall, CF is a systemic condition
GI tract (malabsorption)
- fat solvable vitamin deficiency (a,d,e,k(
Recurrent pancreatic
Gerd
Increased risk of Chrons disease
Constipation
What are common clinical scenarios in late Cystic fibrosis [CF]? (5)
- Recurrent chest infections
- widespread bronchiectasis
- poorly controlled asthma
- Nasal polyps, severe chronic rhinosinutis
- electrolyte distrubances
For pathway and responses for management; refer to charts one slide 16-18 for early -> advanced stages
Diagnosis of Cystic Fibrosis [CF] is based on what clinical findings?
Sweat chloride test = gold standard
- both clinical and functional criteria must be met to diagnose CF
Clinical indicators of Cystic Fibrosis [CF] in the pulmonary system?
- wheezing
- chronic cough
- sputum collection
- freq. resp. infections
- nasal polyps
- abnormal CxR [obst/restrictive proccess]
- parainsuitis
-digital clubbing
Clinical indicators of Cystic Fibrosis [CF] in the GI system?
slide 21
Sweat chloride test interpretation in infants 6 months or younger
- ≤29 mmol/L: Normal (CF very unlikely)
- 30-59mmol/L: Intermediate (Possible CF)
- ≥60 mmol/L: Abnormal (Diagnosis of CF
Sweat chloride test interpretation in infants older than 6 months and adults
- ≤39 mmol/L: Normal (CF very unlikely)
- 40-59mmol/L: Intermediate (Possible CF)
- ≥60 mmol/L: Abnormal (Diagnosis of CF)
What is a Nasal potential difference?
- hint it’s a diagnostic tool
edit
Impairment of sodium and chloride across the epithelial cells lining the airways of CF pts measurement
As sodium moves across the epithelial cell membrane; they generate electrical potential diff.
- the energy required to move an electrical charge from 1 point to another.
- measuring the difference is the nasal potential difference
How do you interpret the Nasal potential difference?
An increased in nasal potential difference [more negative] strongly suggests CF
Add slide 24 - 26
If both parents test positive for CF, what are the chances their children will have CF?
1 in 4 chance
Testing CF in newborn babies involves pricking the heel of babies, what is screened from their blood work?
Immuonoreactive trypsinogen (IRT)
What is the following CxR?
Cystic fibrosis
What can you expect to see on a CxR for cystic fibrosis?
**- Pulmonary Hyperinflation/expansion
- large main pulmonary artery segments **
From google:
- peribronchial thickening and dilatation,
- peribronchial cuffing
- mucoid impaction
- cystic radiolucencies,
- increase in interstitial marking, and scattered nodular densities
Is cystic fibrosis obstructive or restrictive?
Obstructive
What gene is altered in CF
Chromosome 7
- autosomal recessive disorder (2 r alleles)
- Most common mutation is DeltaF508
What happens to Fluid transport in CF?
The transport channels are stop working properly and creates a massive secretion production
First indications of CF
Myconium ileus
Failure to thrive
Foul smelling stools
GI issues
90% noticed within first 2 wks of birth
Common bacteria that can build up because of CF?
- Pseudomonas aeruginosa
- Hemophilus influenza
- Staphylococcus auerus
What happens in airways because of CF?
- what happens to unchecked/treated CF?
** - Impaired mucociliary clearance leads to: increased mucous production (thick!!!!)**
- small bronchi and bronchioles become partially/fully obstructed.
- Check-valve phenomenon
Can lead to atelectasis and bronchiectasis with complete obstructions
What happens in airways because of CF?
- what happens to unchecked/treated CF?
** - Impaired mucociliary clearance leads to: increased mucous production (thick!!!!)**
- small bronchi and bronchioles become partially/fully obstructed.
- Check-valve phenomenon
Can lead to atelectasis and bronchiectasis with complete obstructions
What happens in airways because of CF?
- what happens to unchecked/treated CF?
** - Impaired mucociliary clearance leads to: increased mucous production (thick!!!!)**
- small bronchi and bronchioles become partially/fully obstructed.
- Check-valve phenomenon
Can lead to atelectasis and bronchiectasis with complete obstructions
CF causes impaired mucociliary clearance leads to: increased mucous production; what can happen if secretions aren’t cleared?
- small bronchi and bronchioles become partially/fully obstructed.
- Can lead to atelectasis and bronchiectasis with complete obstructions
What are other body symptoms of CF?
- Think systemically and not specific to airways
- malabsorbition
- GERD
- increased risk of Chrons disease
- Constipation
GOLD standard diagnosis of CF
Sweat chloride test
GOLD standard diagnosis of CF
Sweat chloride test
Infant sweat chloride for possible CF
- Think numerical range
30-59mmol/L
Infant sweat chloride for confirmed CF
> 60mmol/L
Adult sweat chlorde for possible CF
40-59mmol/L
adult sweat chloride for diagnosis of CF
same as infant, >60mmol/L
adult sweat chloride for diagnosis of CF
same as infant, >60mmol/L
Early management of CF
** - Mucous clearance (CPT, mucolytics)**
- Prevent infection (vaccinations)
- Symptomatic relief ( SABA as needed)
- Eradication of infection (high dose antibiotics
Intermediate management of CF
- Suppression of bacterial load (inhaled antibiotics)
- Exacerbations (oral or IV antibiotics)
- Reduce inflammation ( long term azithromycon)
- Prevent reoccurance (OCS)
- rhDNase (mucolytic- pulomaze)
Advanced management of CF
- Halt hemoptysis (tranexamic acid)
- Pneumothorax ( tube drainage or pleurodesis if recurrent)
- End-stage respiratory failure- reduce airway inflammation ( LTOT, optimize tx, referral for lung transplant)
Advanced management of CF
- Halt hemoptysis (tranexamic acid)
- Pneumothorax ( tube drainage or pleurodesis if recurrent)
- End-stage respiratory failure- reduce airway inflammation ( LTOT, optimize tx, referral for lung transplant)
Nasal potential difference?
- What does a negative potential difference mean?
A measurement of the voltage across the nasal epithelial cell determined by using a high impedance voltmeter between two electrodes.
- More negative potential difference confirms CF
Nasal potential difference?
- What does a negative potential difference mean?
A measurement of the voltage across the nasal epithelial cell determined by using a high impedance voltmeter between two electrodes.
- More negative potential difference confirms CF
Why is Tobramycin relevant for CF?
- hint its a antibiotic
Inhaled antibiotic
used in treatment if Pseudomonas aeruginosa for CF
CxRs for CF typically have what traits?
hyperinflation of lungs
large main pulmonary artery segments
Immunoreactive protein testing is usually peformed for CF:
- When is it done?
- Are high or low values normal?
- usually done a few days after birth.
2.high number is normal for CF patients
Clinical indicators/ symptoms of CF
Wheezing
Chronic cough
Sputum production
Frequent respiratory infections
Abnormal CXR
Nasal polyps
GI: Failure to thrive, GI issues, unable to tolerate milk…etc
What is Pleurodeisis?
A procedure where the lungs are forced against the thoracic cavity.
Purpose
- pushes out any air/fluid out of the pleura
Recurrent pneumothoraces and pleural effusions are typical problems associated with Cystic Fibrosis. What treatment can be considered with these recurrent issues?
Pleurodesis
True or False:
Inhaled antiobiotics, such as tobramycin, are used to treat and prevent the recurrance of fungal infections in patients with Cystic Fibrosis
False; Tobramycin is a antibiotic, not fungal.
What purpose is Pulmozyme, an rhDNase, used in the treatment of Cystic Fibrosis?
To assist in bronchopulmonary hygiene
(helps clear mucous secretions)
