Flashcards in Lec 12 Bronchiectasis Deck (37):
What is the definition of bronchiectasis?
permanent abnormal dilation of bronchi
What is vicious cycle hypothesis of bronchiectasis?
external insult --> causes resp tract damage --> more prone to infection --> more inflammation --> more damage etc
What are infectious causes of bronchiectasis?
other bacteria/viruses --> TB, mycobacterium
allergic bronchopulmonary aspergillosis
Who gets allergic bronchopulmonary aspergillosis?
patients with asthma or cystic fibrosis
What are some causes of recurrent airway infection?
- airway obstruction
- impaired mucous clearance
- defect in host defense
What are the 3 patterns of bronchiectasis?
- cylindrical = smooth dilation of bronchus
- varicose = focal narrowings along a dilated bronchus
- cystic = progressive dilation of bronchus which terminates in cysts or saccules
What signs of bronchiectasis?
permanently dilated airways
What causes hemoptysis in bronchiectasis?
inflammation causes increased blood supply
- bronchial arteries enlarge and increase in number; new anastamoses form between bronchial + pulm artery circulations
erosion/truama leads to rupture/hemoptysis
What do you see on physical exam with bronchiectasis?
- may have normal lugn exam or wheezing
What do you see on pulm function tests with bronchiectasis?
high RV and RV/TLC ratio
What is treatment for bronchiectasis?
- antibiotics with exacerbation
- bronchopulmonary drainage
- bronchodilators if co-existing asthma
What is epidemiology of CF?
- autosomal recessive
- mutation in gene for cystic fibrosis transmembrane conductance regulator [CFTR]
- most prevalent in pple of northern/central europe descent
What is function of CFTR?
- ion channel regulates Cl and H2O absorption/secretion
in sweat duct = Na but not fluid absorbing
in airways = fluid absorption
in pancreas/intestine = fluid secretion
What happens in lungs in CF?
- lung epithelium dried out = cilia can't move as well and stuff gets stuck
- less airway surface liquid volume
normally when high liquid volume: channels open allow Na/Cl absorption and H2O to follow in but close when low volume and net water out
in CF = can't regulate; channels always open and bring fluid in even when there is already low volume
What happens in CF in pancreas?
- CFTR is needed to secrete HCO3 and water into pancreatic ducts
in CF --> acidic secretions lead to retention of enzymes in pancreas and destruction of pancreatic tissue
What happens in CF in intestine?
intestinal epithelium can't flush secreted mucin and other macromolecules
have intestinal obstruction
What happens in CT in sweat glands?
- CFTR needed to reabsorb Cl from sweat secretions
in CF --> Cl not reabsorbed have isotonic [rather than hypotonic] sweat
What are the 6 types of CFTR mutations?
type 1 = no functional CFTR protein
type 2 = CFTR trafficking defect, never reaches surface
type 3 = defective channel regulation
type 4 = decreased channel conductance
type 5 = reduced synthesis of CFTR
type 6 = decreased CFTR stability
What is type 2 CFTR mutation?
normal transcription but abnormal folding --> have trafficking defect and CFTR never makes it to cell surface
What is type 1 CFTR mutation?
transcription abnormal = no protein produced
What is type 3 CFTR mutation?
transcription/translation normal but abnormal regulation
What is type 4 CFTR mutation?
decreased conductance of chloride in channel
What is type 5 CFTR mutation?
have some corent + some incorrect RNA due to splicing defect
so end up with reduced synthesis of CFTR
What is type 6 CFTR mutation?
have decreased CFTR membrane stability
What is major mutation causeing 70% of CF?
- 3 nt deletion
- causes protein misfolding = class II defect
What doe you always have if homozygous dF508 mutation?
always have exocrine pancreatic insufficiency
What is pulmonary pathology of CF?
- thick mucous plugs in bronchi
- early airway changes mostly in bronchioles plugged by secretions
What is pulmonary pathophysiology of CF?
- recurrent episodes of tracheobronchial infection
- leads to bronchiectasis
- get pseudomonas + MRSA colonization
- get obstructive airway disease
What are presenting features of CF?
- 10-20% develop first clinical problem in neonatal period --> usually meconium ileus = obstructed intestine
- rest have childhood presentation --> pancreatic insufficiency or recurrent bronchial infections
- occasionally diagnosed when adults
What are pulmonary complications of CF?
- allergic bronchopulmonary aspergillosis
- pulmonary HTN
- resp failure
What are non-pulmonary clinical features of F?
- nasal polyps
- chrnoic pancreatisis
- intestinal obstruction
- exocrine pancreas insuffiency [malabsorption of vit A, D, E, K]
- rectal prolapse
- infertility in males
How do you diagnose CF?
- abnormal sweat electrolytes [high Na, Cl, K]
- identify mutation in CFTR gene
What is treatment for CF?
for lungs: antibiotics, bronchopulmonary drainage, bronchodilators; give N-acetylcysteine to loosen mucus plugs
What is use of inhaled recombinant doexyribonuclease in CF?
- DNAse decreases mucus viscosity + improves clearance of secretions
What is ivacaftor?
increases time activated CFTR channels at cell surface remain open
improves respiratory symptoms in pts with G511D mutation
What is primary ciliary dyskinesia?
autosomal recessive group of structural deficits involving cilia