Bronchiectasis and Cystic Fibrosis Flashcards
Bronchiectasis
A condition in which an area of the bronchial tubes is permanently and abnormally widened (dilated), with accompanying infection. The dilatation results from ongoing infection and inflammation.
The irreversible dilatation of airways in bronchiectasis is caused by..
inflammatory destruction of the airway walls.
Characteristics of bronchiectasis (3)
- increased diameter of the airways
- accumulation of mucus and pus
- scarring of bronchiolar wall
Why does mucus accumulate in the airways in bronchiectasis?
Because ciliated cells of the airways are destroyed by inflammation, so the mucociliary defense mechanism can no longer clear mucus from the airways.
What are the two main etiologies of bronchiectasis?
- Infection
* tuberculosis and other mycobacteria
* untreated pneumonia
* pertussis, measles
* immunodeficiency (cannot produce sufficient antibodies to prevent infection - puts you at risk of chronic or recurrent infection + inflammation)
* fungal (eg. aspergillus) - Impaired drainage
* cystic fibrosis (causes abnormal phlegm which predisposes to bacterial infections, leading to bronchiectasis)
* primary ciliary dyskinesia
* bronchial tumor (obstruction leads to mucus accumulation which eventually causes dilatation of airways)
* structural anomalies
If a patient has cystic fibrosis, but no recurrent infections, will they have bronchiectasis?
No! Bronchiectasis is caused by recurrent, chronic infection and inflammation
What are some clinical features of bronchiectasis? (symptoms)
- Cough
- Lots of sputum production (purulent, often yellow and green)
- Hemoptysis (coughing up blood)
- Localized wheezes or rhonchi, clubbing
How is bronchiectasis diagnosed? (4)
- history and physical exam
- sputum culture
- CT scan of chest
- other tests to establish the specific etiology of the bronchiectasis
How is bronchiectasis treated? (4)
- Antibiotics (directed against the infectious agent)
- Bronchopulmonary drainage (to help reduce the load of active bacteria)
- Bronchodilators (for symptom relief)
- Very rarely surgery
Cystic fibrosis is
a) autosomal recessive
b) autosomal dominant
a) autosomal recessive
*This means you need two copies of the gene to suffer from this condition.
Normally, CFTR channels secrete… into the lumen of the airways
NaCl and water
*These channels are responsible for chloride regulation
Disruption in the translocation of the CFTR channel causes…
disruption in transport of chloride to the lumen of the airways, resulting in a dehydrated, thick, sticky mucus
How does a defective CF gene cause the disease phenotype?
IMPORTANT
- Defective CF gene
- Deficient/dysfunctional CFTR protein at plasma membrane
- Decreased chloride secretion and altered ionic transport
- Increased water absorption
- Abnormal, dehydrated mucus composition
- Bronchial obstruction by abnormal, dehydrated mucus
- Accumulation of trapped mucus results in recurrent infection and inflammation of the airways
- Bronchi dilatation and bronchiectasis, leading to further mucus accumulation and airway damage
What is the diagnostic test for CF?
Testing for elevated sweat chloride levels (sweat glands have a compensatory mechanism that creates elevated chloride levels)
CFTR mutations affect…
ALL exocrine tissues
What organ systems are affected by CFTR mutations? (6) How?
IMPORTANT
Respiratory tract
Pancreas
Liver
Intestinal tract
Reproductive tract
Sweat glands
Viscous and thick secretions in all of these organ systems.
How does CF present in the respiratory tract? (5)
- Chronic bronchitis with bronchiectasis, hyperinflation and obstructive airway disease
- Persistent, productive cough and purulent sputum
- Bacterial colonization (commonly in old smokers, NOT young children)
- Pneumothorax
- Hemoptysis
Majority of CF patients also have … disease
sinus disease (i.e. sinusitis or rhinosinusitis - inflammation of the sinuses)
Who can suffer from chronic rhinosinusitis (outside of CF patients)?
CFTR mutation carriers (one copy of the mutated gene, decreases CFTR channels enough to cause rhinosinusitis)
CF affects all exocrine tissues. Name the conditions CF patients may suffer from (other than bronchiectasis in the lungs). (4)
- Pancreatic disease
- Meconium ileus
- Liver and biliary disease
- Infertility
What is the typical onset of pancreatic insufficiency?
Present from birth in most patients
What is the main mechanism of pancreatic insufficiency?
Insufficient secretion of enzymes leading to malabsorption of fat and protein
What are consequences of pancreatic insufficiency? (5)
- Steatorrhea (presence of excess fat in the stools)
- Malnutrition
- Failure to thrive
- Fat-soluble vitamins deficiency (A, E, D, K)
- CF-related diabetes
What is “meconium ileus”?
Small bowel obstruction by very thick stool in individuals with CF (newborns and children).
MI is typically seen in children and newborns. What is the equivalent in adults?
Distal ileal obstruction syndrome (DIOS)
*AKA MI equivalent
Describe liver and biliary disease in individuals suffering from CF (3)
- Focal biliary cirrhosis (areas of fibrosis within the liver, esp. bile ducts)
- Excessive loss of bile acids in the stool (i.e. production of lithogenic bile)
- Cholelithiasis (formation of gallstones in the gallbladder)
How does CF affect male and female fertility?
98% of males with CF will be infertile due to congenital bilateral absence of vas deferens
Note that this is not an issue of spermatogenesis
20% of women with CF will be infertile, due to secondary amenorrhea induced by malnutrition and abnormally tenacious cervical mucus
When and how is CF diagnosed?
Usually within the first few months of life, especially since newborn screening was introduced.
Indicative signs:
* respiratory problems
* failure to thrive
* steatorrhea
* meconium ileus
What is the gold standard for CF diagnosis?
Sweat chloride test
Chloride value of >60mEq/L indicates CF
What can lead to false positives in the sweat chloride test for CF?
- hypothyroidism
- hypoPTH
- adrenal insufficiency
- pseudohypoaldosteronism
How is CF treated? (3 main groups)
Most treatments aim to improve symptoms (antibiotics, bronchodilators, chest physiotherapy, DNAse to decrease sputum viscosity, inhaled saline)
CFTR modulators - therapy targeting specific mutations, treat the underlying cause of CF: life-changing!
Referral for organ transplant (often lungs, liver)
