Lecture 12: Bronchiectasis Flashcards
Bronchiectasis: definition
Permanent, abnormal dilatation of the bronchi
Bronchiectasis: hypothesis
External insult –> respiratory tract damage –> infection –> inflammation –> damage (repeat)
What is the etiology of the initial external insult? (5)
Infection, aspiration, autoimmune, toxic inhalation, radiation
Bronchiectasis: pathophysiology
Once airways are irreversibly dilated, defense mechanisms are disturbed (no cilia, bacterial colonization, abnormal collapsible airways)
In bronchiectasis, small airways are often?
Inflamed, obstructed
Bronchiectasis: infections causes
Measles/pertussis, TB, MAC, allergic bronchopulonary aspergillosis
But recurrent infections are not common, what can cause this? (3 main causes and details)
Airway obstruction (tumor, foreign body, thick mucus); impaired mucous clearance (CF, primary ciliary dyskinesia); defect in host defenses (humoral/cellular immunity deficiency)
Patterns of bronchiectasis (3)
Cylindrical: smooth dilation; varicose: focal narrowings along dilated bronchus, cystic: progressive dilation of bronchus which terminates in cysts or saccules
Do you only get one bronchiectasis pattern per patient?
Nope–they can have all three!
Most prominent symptom of bronchiectasis
Cough w/ copious sputum
Why can a patient with bronchiectasis get hemoptysis?
Result of inflammation –> increased bronchial blood supply –> erosion/mechanical trauma –> hemoptysis
Bronchiectasis: physical exam
May have wheezing/ronchi/crackles, clubbing
Bronchiectasis: gas exchange
May be normal if disease is still localized
Bronchiectasis: pulmonary function test
Normal, or obstructive ventilatory defect w/ air trapping
Bronchiectasis: treatment (3)
Antibiotics, bronchopulmonary drainage, bronchodilators
When are bronchodilators indicated?
W/ partially reversible co-existing airway obstruction
Why would we want to do airway clearence techniques? What do these techniques do?
Because ciliary elevator isn’t working; loosen mucous via rubbing or vibration
Why do we want to treat the hemoptysis in bronchiectasis? How do we treat?
It can be life-threatening via asphyxiation (block of gas exchange); electrical cauterization
Cystic fibrosis is an _________ __________ genetic disorder
Autosomal recessive
Describe CFTR
Epithelial Cl- channel regulatory domain
CFTR function in different tissues
Sweat: salt but not volume absorbing; Airways: volume absorbing; Pancreas, intestine: volume-secreting
In the lungs, how does cystic fibrosis affect?
Hyperabsorption of NaCl + water –> decreased ability for cilia to move –> decreased clearance AND bacterial adhesion
How does CFTR gene affect Na+ channels when airway surface liquid volume is high?
CFTR gene keeps Na+ channel open to allow Na+ into cell –> negative EC gradient –> Cl- abosrbed; water follows
How does CFTR gene affect Na+ channels when airway surface liquid volume is low?
CFTR gene closes Na+ channel –> positive EC gradient –> Cl- excreted –> water follows
How does CFTR gene affet Na+ channels in someone w/ CF?
Na+ channel open always
CFTR in pancreas. In CF?
CFTR needed to secrete HCO3- and water into pacreatic ducts; in CF –> viscous, acidic secretions –> retention of pancreatic enzymes –> tissue destruction
CFTR in intestine. In CF?
CFTR needed for Cl- and water secretion; in CF –> instestinal epithelium fails to flush secreted mucins and other molecules from intestinal crypts –> dehydrated intraluminal contents
CFTR in sweat glands. in CF?
F
Class II mutation. What do we need to know?
Transcribe, translate, but misfolded and destroyed; most common = deltaF508 missense mutation w/ aa deletion
Various CFTR mutations mean what?
Different organs can be affected to different degrees
CF: pulmonary pathology
Thick, uncleared mucous plugs in bronchi –> pneumonitis, frank bronchiectasis, abscess formation
Where does CF affect the lungs the most?
Bronchioles (which are plugged by secretons)
CF: pathophysiology
Recurrent infection and bronchiectasis –> colonization with unusual bugs (pseudomonas, staph aureus) –> obstructive airway disease
How does CF present neonatally?
10-20% during neonatal period (meconium ileus = obstruction)
What would a CF childhood presentation look like?
Pancreatic insufficiency, recurrent bronchial infections
Five CF pulmonary complications
Pneumothorax, hemoptysis, ABPA, pulmonary hypertension, respiratory failure
Three classes of non-pulmonary CF complications
- GI: exocrine pancreatic insufficiency, obstruction, rectal prolapse; 2. Renal/endocrine: loss of salt –> hypovolemia; 3. GU: azoospermia
Dx of CF
Clinical features plus abnormal sweat electrolytes, electrical potential differences, or gene
Tx of CF
Diminish clinical consequences: antibiotics, bronchopulmonary drainage, bronchodilators
How could we decrease secretion viscosity?
Inhale recombinant deoxyribonuclease or hypertonic saline (draws water onto airway surface)
Newer therapies in CF are…
Mutation-specific
Ivacaftor: function and the class it helps
Increases time activated CFTR channels at cell surface remain open (help Class III mutations)
Lumacaftor: function and the class it helps and how it should be delivered
Partially corrects CFTR misfolding (helps Class II), give with Ivacaftor to help resulting Class III defect
What is primary ciliary dyskinesia?
Heterogenous group of deficits involving the axoneme, spokes, or dynein arms, etc.; autosomal recessive
Describe Kartagener’s syndrome and describe why
Characterized by bronchiectasis, sinusitis, and situs inversus; normal cilia determine position of internal organs during early embryological development –> embryos with PCD have 50% chance of developing situs inversus
