Bronchiectasis and CF Flashcards
Bronchiectasis
Permanent, abnormal dilatation of the bronchi. Can be focal or diffuse.
How does the mucociliary system work?
Cilia beat upwards the things that are trapped in the periciliary fluid layer.
Vicious Cycle Hypothesis
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.
What does the vicious cycle cause?
Airway dilation. Irreversible dilation will disable innate defense mechanisms against infection.
What defense mechanisms against infection are disturbed in bronchiectasis?
Normal propulsive action of cilia is lost. Abnormally collapsable airways, so cough is much less effective at clearing secretions
How exactly does airway inflammation cause bronchiectasis
Inflammation causes the release of proteases, which cause bronchidilation.
Infectious causes of bronchiectasis
Measles/pertussis pneumonia.
TB, MAC
Allergic bronchopulmonary aspergillosis (happens in patients with asthma and CF)
Patterns of bronchiectasis
Cylindrical: smooth dilation of bronchus.
Cystic: progressive dilation of bronchus which terminates in cysts/saccules.
Varicose: Focal narrowings along a dilated bronchus.
Cough in bronchiectasis
Cough and copious sputum are prominent symptoms. Airway inflammation causes hypertrophy and hyperplasia of mucus secretory cells.
10-20% free of copious sputum.
Hemoptysis in Bronchiectasis
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.
Clinical features of bronchiectasis
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)
How to treat bronchiectasis
Chest PT with postural drainage. Airway oscillating devices. Mechanical vibrators. Bronchodilators. Anibiotics.
CFTR functions in…
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.
CTFR epithelium in sweat duct
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)
CFTR epithelium in airways
Volume absorbing and Cl absorbing
CTFR epithelium in pancreas/intestine
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.
Periciliary fluid layer in CF?
Hyperabsorbed so super viscous
CFTR mutations
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
DeltaF508
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.
Homozygous F deletion at 508?
Causes exocrine pancreatic insufficiency.
Pathology of CF in lungs
Thick mucous plugs. This causes trouble later – pneumonitis, bronchiectasis, abscess formation.
Pulmonary pathophysiology
Recurrent episodes of tracheobronchial inection and bronchiectasis causes eventually colonization with pseudomonas aeruginosa and staph aureus.
Presenting features of CF
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.
Do patients with CF get allergic bronchopulmonary aspergillosis?
Yes absolutely
Non-pulmonary clinical features
Chronic sinusitis. Nasal polyps. Exocrine pancreatic insufficiency. Intestinal obstruction. Biliary cirrhosis. Hypochloremic metabolic alkalosis.
What are the consequences of pancreatic imnsufficiency
Protein and fat malabsorptioon. ADEK deficiency. Beta cells spared early but function decreases w/age.
Diagnosis of CF
Abnormal sweat electrolytes. Characteristic abnormalities in nasal mucosal electrical potential. Idenification of mutations.
Treatment of CF
Diminish clinical consequences and manage complications.
What contributes significantly to increased viscosity of secretions?
DNA released from inflammatory cells. Inhaled recombinant DNAase decreases mucous viscosity and improvess clearance of secretions.
Inhaled hypertonic saline
Draws water onto airway surfaces.
Ivacaftor
used as a potentiator of CFTR in G551D mutation that causes a nonfunctional CFTR on membrane. Increases time activated CFTR stays open.
Primary ciliary Dyskinesia
Group of deficits involving the functional element of cilia. Autosomal recessive mutation
Kartagener’s syndrome
Bronchiectasis, sinusitis, and situs inversus. Primary ciliary dyskinesia
Why does kartagener’s cause situs inversus
Because normal cilia determine position of internal organs.
What type of ciliary defects cause dyskinesia
Absense of outer or inner dynein arms, lack of radial spokes, dirordered microtubule arrangements, ciliary disorientation
