Bronchiectasis Flashcards
what is the pathogeneic cycle of bronchiectasis?
something leads to impaired mucociliary clearance,
this leads to retained secretions
this leads to colonisation and secondary infection
this leads to inflammation
this leads to increased airway damage and destruction
where are the locations of bronchiectasis?
it is usually dependent (lower lobes)
some exceptions include:
CF, TB and ABPA - all of which affect upper lobe
what are the radiological findings of bronchiectasis?
CXR changes include:
- ring shadows (dilated airways seen end on)
- tram tracking (dilated airways in longitudinal cross section)
HRCT:
- internal airway diameters greater than the adjacent blood vessel
- lack of airway tapering
- bronchi visible within 1 cm of pleura
- bronchi adjacent to mediastinal pleura
what are the causes of bronchiectasis?
specific causes include:
- congenital - Kartagener’s, CF
- mechanic - bronchial CA
- childhood infection - measles and TB
- immune OVER activity - ABPA, IBD related (esp UC), RA
- immune UNDER activity - hypogammaglobulinaemia (IgG and IgA. There is debate about IgG subclass def)
- Aspiration - GORD, chronic EtOH
what are the genetics of CF?
it is AR
located on chromosome 7
CFTR dysfunction
what are some conditions assoc with CF?
congenital bilateral absence of the vas deferens - 70%
chronic pancreatitis - 30%
possible ABPA and asthma
what are CF clinical manifestations?
- pulmonary disease
- progressive bronchiectasis, airway colonisation, PTX
massive haemoptysis - chr panc insufficiency
- malnutrition
- persistent inflamm state
- panc insuff - distal intestinal obstruction syndrome
- thick gut lining, leads to problems - diabetes
- chronic sinus disease
- CD related biliary cirrhosis
- OP
- male infertility
- ABPA
- non-TB myco infection
how does CFTR abnormality lead to disease?
normally chloride is secreted into the mucus layer. there is already sodium in the mucus. When there is less chloride secretion, there is less tonic (and electric) drag for the sodium to stay in the mucus.
the sodium is reabsorbed by ENaC
overall this leads to a thinner, more viscous mucus layer
leads to stasis
in the pancreas, this leads to duct blockage and autolysis (from the enzymes)
obstruction also impacts vas deferens
can lead to biliary system obstruciton and cirrhosis
what are the different types of CFTR mutation?
interesting
basically there are 5 types, but the first 4 are easiest to think about because they follow the order of the production of protein
1 - mutations leading to no synthesis
2 - mutations leading to defective processing
3 - mutations leading to defective regulation
4 - mutations leading to defective conductance (after the CFTR is inserted in the membrane)
5- decreased sythn of the gene (milder version of type 1)
how do we manage acute exacerbations of CF?
two classes of AB
usually an aminoglycoside and a beta lactam
on top of this, when the patient first demonstrates colonisation, hit them with ABs. Something like nebulised colistin and oral cipro.
this all comes down to the idea that sputum sensitivity in CF, isn’t that useful. That’s because there is chronic infection, and within the biofilm there are likely to be multiple colonies with varied sensitivities
why do we use DNAse in CF patients?
white cells are pushed out in to the thick mucus layer, and die in that space. They then release a lot of DNA
this DNA is quite “sticky” (long tangled protein)
the DNAse breaks down the released WBC DNA.
are there any potential directed drugs for use in CF?
There is a drug called VX-770, which is an oral CFTR potentiator
basically it is only useful in the subgroup, where the CFTR makes it to the cell surface, but is functionally crap
this turns it on
it is really only useful in a small subgroup
commonest mutation like this is G551D
In non-CF bronchiectasis, what are the common chronic colonisers?
haemophilus ~50%
pseudo ~25%
strept, staph, moraxella
what sort of investigations would you do in an adult presenting with bronchiectasis
sputum culture, incl mycobact
RFTs
HRCT
ABPA investigations - esp if asthma (serology/skin tests)
immunoglobulins
possibly:
sweat chloride
cilial motility
what is the pathology in the most common CF mutation?
accounts for approx 70%
the delta F508 mutation is associated with defective processing of the CFTR protein. The CFTR protein actually functions normally, but the issue is getting it to cell membrane
