Bronchiectasis and CF

Question 1

Bronchiectasis

Answer 1

Permanent, abnormal dilatation of the bronchi. Can be focal or diffuse.

Question 2

How does the mucociliary system work?

Answer 2

Cilia beat upwards the things that are trapped in the periciliary fluid layer.

Question 3

Vicious Cycle Hypothesis

Answer 3

External insult causes respiratory tract damage. This causes respiratory infection, which causes bronchial inflammation. Bronchial inflammation will cause respiratory tract damage and the cycle will repeat.

Question 4

What does the vicious cycle cause?

Answer 4

Airway dilation. Irreversible dilation will disable innate defense mechanisms against infection.

Question 5

What defense mechanisms against infection are disturbed in bronchiectasis?

Answer 5

Normal propulsive action of cilia is lost. Abnormally collapsable airways, so cough is much less effective at clearing secretions

Question 6

How exactly does airway inflammation cause bronchiectasis

Answer 6

Inflammation causes the release of proteases, which cause bronchidilation.

Question 7

Infectious causes of bronchiectasis

Answer 7

Measles/pertussis pneumonia.

TB, MAC

Allergic bronchopulmonary aspergillosis (happens in patients with asthma and CF)

Question 8

Patterns of bronchiectasis

Answer 8

Cylindrical: smooth dilation of bronchus.

Cystic: progressive dilation of bronchus which terminates in cysts/saccules.

Varicose: Focal narrowings along a dilated bronchus.

Question 9

Cough in bronchiectasis

Answer 9

Cough and copious sputum are prominent symptoms. Airway inflammation causes hypertrophy and hyperplasia of mucus secretory cells.

10-20% free of copious sputum.

Question 10

Hemoptysis in Bronchiectasis

Answer 10

Due to inflammatory changes in the bronchial wall, blood supply is increased. Arteries enlarge and increase in number, new anastamoses form between bronchial and pulmonary artery circulations. Erosion or trauma is often responsible for hemoptysis.

Question 11

Clinical features of bronchiectasis

Answer 11

Lung auscultation can be normal, or may reveal wheezing, rhonchi, or crackles.

Clubbing.

Gas exchange can be normal, but those with more severe disease may develop hypoxemia and hypercapnia.

PFTs reveal obstructive lung defect (low FEV1/FVC) , and air trapping (RVincreased RV/TLC increased)

Question 12

How to treat bronchiectasis

Answer 12

Chest PT with postural drainage. Airway oscillating devices. Mechanical vibrators. Bronchodilators. Anibiotics.

Question 13

CFTR functions in…

Answer 13

Epithelial ion channel that is imporatn i nthe regulation of cl and water absorption and secretion. Serves as a chloride channel, modulates the activity of other plasma membrane channels and perhaps regulates exocytotic and endocytotic events.

Question 14

CTFR epithelium in sweat duct

Answer 14

Salt, but not volume absorbing. CFTR is needed to resorb cl from sweat secretions, but in CF, the duct lumen cannot absorb Cl which leads to salty sweat (hypotonic)

Question 15

CFTR epithelium in airways

Answer 15

Volume absorbing and Cl absorbing

Question 16

CTFR epithelium in pancreas/intestine

Answer 16

Volume and salt secreting. In CF the secretions are viscous and acidic, and lead to the retention of enzymes in the pancreas and destruction of virtually all pancreatic tissue. In intestines, CF causes failure to flush secreted mucins and other macromolecules from intestinal crypts, leading to dehydrated intraluminal contents and intestinal obstruction.

Question 17

Periciliary fluid layer in CF?

Answer 17

Hyperabsorbed so super viscous

Question 18

CFTR mutations

Answer 18

I: Translation problem, no functional CFTR protein
II: Full length CFTR RNA but misfolded
III: Defective channel regulation
IV: Defective CFTR channel
V: Reduced synthesis of CFTR
VI: Decreased membrane stability of CFTR

Question 19

DeltaF508

Answer 19

Responsible for 70% of cases. Gives a Class II mutation that causes a misfolded protein and trafficking defect (retention in the ER). Phenylalanine is missing at 508.

Question 20

Homozygous F deletion at 508?

Answer 20

Causes exocrine pancreatic insufficiency.

Question 21

Pathology of CF in lungs

Answer 21

Thick mucous plugs. This causes trouble later – pneumonitis, bronchiectasis, abscess formation.

Question 22

Pulmonary pathophysiology

Answer 22

Recurrent episodes of tracheobronchial inection and bronchiectasis causes eventually colonization with pseudomonas aeruginosa and staph aureus.

Question 23

Presenting features of CF

Answer 23

10-20 develop first clinical problem in neonatal period. Meconium ileus (intestinal obstruction with thick meconium). Remander have childhood reprentation with pancreatic insufficiency. Occasionally diagnosed when adults.

Question 24

Do patients with CF get allergic bronchopulmonary aspergillosis?

Answer 24

Yes absolutely

Question 25

Non-pulmonary clinical features

Answer 25

Chronic sinusitis. Nasal polyps. Exocrine pancreatic insufficiency. Intestinal obstruction. Biliary cirrhosis. Hypochloremic metabolic alkalosis.

Question 26

What are the consequences of pancreatic imnsufficiency

Answer 26

Protein and fat malabsorptioon. ADEK deficiency. Beta cells spared early but function decreases w/age.

Question 27

Diagnosis of CF

Answer 27

Abnormal sweat electrolytes. Characteristic abnormalities in nasal mucosal electrical potential. Idenification of mutations.

Question 28

Treatment of CF

Answer 28

Diminish clinical consequences and manage complications.

Question 29

What contributes significantly to increased viscosity of secretions?

Answer 29

DNA released from inflammatory cells. Inhaled recombinant DNAase decreases mucous viscosity and improvess clearance of secretions.

Question 30

Inhaled hypertonic saline

Answer 30

Draws water onto airway surfaces.

Question 31

Ivacaftor

Answer 31

used as a potentiator of CFTR in G551D mutation that causes a nonfunctional CFTR on membrane. Increases time activated CFTR stays open.

Question 32

Primary ciliary Dyskinesia

Answer 32

Group of deficits involving the functional element of cilia. Autosomal recessive mutation

Question 33

Kartagener’s syndrome

Answer 33

Bronchiectasis, sinusitis, and situs inversus. Primary ciliary dyskinesia

Question 34

Why does kartagener’s cause situs inversus

Answer 34

Because normal cilia determine position of internal organs.

Question 35

What type of ciliary defects cause dyskinesia

Answer 35

Absense of outer or inner dynein arms, lack of radial spokes, dirordered microtubule arrangements, ciliary disorientation