Lecture 12: Bronchiectasis

Question 1

Bronchiectasis: definition

Answer 1

Permanent, abnormal dilatation of the bronchi

Question 2

Bronchiectasis: hypothesis

Answer 2

External insult –> respiratory tract damage –> infection –> inflammation –> damage (repeat)

Question 3

What is the etiology of the initial external insult? (5)

Answer 3

Infection, aspiration, autoimmune, toxic inhalation, radiation

Question 4

Bronchiectasis: pathophysiology

Answer 4

Once airways are irreversibly dilated, defense mechanisms are disturbed (no cilia, bacterial colonization, abnormal collapsible airways)

Question 5

In bronchiectasis, small airways are often?

Answer 5

Inflamed, obstructed

Question 6

Bronchiectasis: infections causes

Answer 6

Measles/pertussis, TB, MAC, allergic bronchopulonary aspergillosis

Question 7

But recurrent infections are not common, what can cause this? (3 main causes and details)

Answer 7

Airway obstruction (tumor, foreign body, thick mucus); impaired mucous clearance (CF, primary ciliary dyskinesia); defect in host defenses (humoral/cellular immunity deficiency)

Question 8

Patterns of bronchiectasis (3)

Answer 8

Cylindrical: smooth dilation; varicose: focal narrowings along dilated bronchus, cystic: progressive dilation of bronchus which terminates in cysts or saccules

Question 9

Do you only get one bronchiectasis pattern per patient?

Answer 9

Nope–they can have all three!

Question 10

Most prominent symptom of bronchiectasis

Answer 10

Cough w/ copious sputum

Question 11

Why can a patient with bronchiectasis get hemoptysis?

Answer 11

Result of inflammation –> increased bronchial blood supply –> erosion/mechanical trauma –> hemoptysis

Question 12

Bronchiectasis: physical exam

Answer 12

May have wheezing/ronchi/crackles, clubbing

Question 13

Bronchiectasis: gas exchange

Answer 13

May be normal if disease is still localized

Question 14

Bronchiectasis: pulmonary function test

Answer 14

Normal, or obstructive ventilatory defect w/ air trapping

Question 15

Bronchiectasis: treatment (3)

Answer 15

Antibiotics, bronchopulmonary drainage, bronchodilators

Question 16

When are bronchodilators indicated?

Answer 16

W/ partially reversible co-existing airway obstruction

Question 17

Why would we want to do airway clearence techniques? What do these techniques do?

Answer 17

Because ciliary elevator isn’t working; loosen mucous via rubbing or vibration

Question 18

Why do we want to treat the hemoptysis in bronchiectasis? How do we treat?

Answer 18

It can be life-threatening via asphyxiation (block of gas exchange); electrical cauterization

Question 19

Cystic fibrosis is an _________ __________ genetic disorder

Answer 19

Autosomal recessive

Question 20

Describe CFTR

Answer 20

Epithelial Cl- channel regulatory domain

Question 21

CFTR function in different tissues

Answer 21

Sweat: salt but not volume absorbing; Airways: volume absorbing; Pancreas, intestine: volume-secreting

Question 22

In the lungs, how does cystic fibrosis affect?

Answer 22

Hyperabsorption of NaCl + water –> decreased ability for cilia to move –> decreased clearance AND bacterial adhesion

Question 23

How does CFTR gene affect Na+ channels when airway surface liquid volume is high?

Answer 23

CFTR gene keeps Na+ channel open to allow Na+ into cell –> negative EC gradient –> Cl- abosrbed; water follows

Question 24

How does CFTR gene affect Na+ channels when airway surface liquid volume is low?

Answer 24

CFTR gene closes Na+ channel –> positive EC gradient –> Cl- excreted –> water follows

Question 25

How does CFTR gene affet Na+ channels in someone w/ CF?

Answer 25

Na+ channel open always

Question 26

CFTR in pancreas. In CF?

Answer 26

CFTR needed to secrete HCO3- and water into pacreatic ducts; in CF --> viscous, acidic secretions --> retention of pancreatic enzymes --> tissue destruction

Question 27

CFTR in intestine. In CF?

Answer 27

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

Question 28

CFTR in sweat glands. in CF?

Answer 28

F

Question 29

Class II mutation. What do we need to know?

Answer 29

Transcribe, translate, but misfolded and destroyed; most common = deltaF508 missense mutation w/ aa deletion

Question 30

Various CFTR mutations mean what?

Answer 30

Different organs can be affected to different degrees

Question 31

CF: pulmonary pathology

Answer 31

Thick, uncleared mucous plugs in bronchi --> pneumonitis, frank bronchiectasis, abscess formation

Question 32

Where does CF affect the lungs the most?

Answer 32

Bronchioles (which are plugged by secretons)

Question 33

CF: pathophysiology

Answer 33

Recurrent infection and bronchiectasis --> colonization with unusual bugs (pseudomonas, staph aureus) --> obstructive airway disease

Question 34

How does CF present neonatally?

Answer 34

10-20% during neonatal period (meconium ileus = obstruction)

Question 35

What would a CF childhood presentation look like?

Answer 35

Pancreatic insufficiency, recurrent bronchial infections

Question 36

Five CF pulmonary complications

Answer 36

Pneumothorax, hemoptysis, ABPA, pulmonary hypertension, respiratory failure

Question 37

Three classes of non-pulmonary CF complications

Answer 37

1. GI: exocrine pancreatic insufficiency, obstruction, rectal prolapse; 2. Renal/endocrine: loss of salt --> hypovolemia; 3. GU: azoospermia

Question 38

Dx of CF

Answer 38

Clinical features plus abnormal sweat electrolytes, electrical potential differences, or gene

Question 39

Tx of CF

Answer 39

Diminish clinical consequences: antibiotics, bronchopulmonary drainage, bronchodilators

Question 40

How could we decrease secretion viscosity?

Answer 40

Inhale recombinant deoxyribonuclease or hypertonic saline (draws water onto airway surface)

Question 41

Newer therapies in CF are...

Answer 41

Mutation-specific

Question 42

Ivacaftor: function and the class it helps

Answer 42

Increases time activated CFTR channels at cell surface remain open (help Class III mutations)

Question 43

Lumacaftor: function and the class it helps and how it should be delivered

Answer 43

Partially corrects CFTR misfolding (helps Class II), give with Ivacaftor to help resulting Class III defect

Question 44

What is primary ciliary dyskinesia?

Answer 44

Heterogenous group of deficits involving the axoneme, spokes, or dynein arms, etc.; autosomal recessive

Question 45

Describe Kartagener's syndrome and describe why

Answer 45

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