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Flashcards in Bronchiectasis Deck (15):
1

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

2

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

3

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:
1. internal airway diameters greater than the adjacent blood vessel
2. lack of airway tapering
3. bronchi visible within 1 cm of pleura
4. bronchi adjacent to mediastinal pleura

4

what are the causes of bronchiectasis?

specific causes include:

1. congenital - Kartagener's, CF
2. mechanic - bronchial CA
3. childhood infection - measles and TB
4. immune OVER activity - ABPA, IBD related (esp UC), RA
5. immune UNDER activity - hypogammaglobulinaemia (IgG and IgA. There is debate about IgG subclass def)
6. Aspiration - GORD, chronic EtOH

5

what are the genetics of CF?

it is AR
located on chromosome 7

CFTR dysfunction

6

what are some conditions assoc with CF?

congenital bilateral absence of the vas deferens - 70%

chronic pancreatitis - 30%

possible ABPA and asthma

7

what are CF clinical manifestations?

1. pulmonary disease
- progressive bronchiectasis, airway colonisation, PTX
massive haemoptysis

2. chr panc insufficiency

3. malnutrition
- persistent inflamm state
- panc insuff

4. distal intestinal obstruction syndrome
- thick gut lining, leads to problems

5. diabetes

6. chronic sinus disease

7. CD related biliary cirrhosis

8. OP

9. male infertility

10. ABPA

11. non-TB myco infection

8

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

9

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)

10

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

11

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.

12

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

13

In non-CF bronchiectasis, what are the common chronic colonisers?

haemophilus ~50%

pseudo ~25%

strept, staph, moraxella

14

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

15

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