Lecture 4 Flashcards
how do you measure tissue damage?
can measure a fluorescent assay for DNA, look at DNA release
at what pH is there more DNA release?
pH2 and there is even more DNA release with pepsin + pH2
what are the 5 tissues in the larynx?
supra glottic, posterior commissure, ventricle, vocal fold and sub glottic
what tissue type is the sub glottic?
columnar epithelium
what tissue type is supra glottic?
squamous epithelium
what is the tissue type in the vocal chords?
there is a mixture of types
what is the highest level of pepsin in gastric juice?
1mg/ml
what tissue in the larynx is the most damaged by pepsin?
sub glottis
what tissue in the larynx is the least damaged by pepsin?
the posterior commissure
what in the stomach gives you pH gradient across the mucus layer?
a bicarbonate secretion with the mucus layer
what tissue type is the oesophagus?
squamous epithelium
how does the oesophagus protect itself from gastric juice If it doesn’t contain a mucus layer?
it sheds dead cells
what organ is more sensitive the oesophagus or the larynx?
the larynx, as the oesophagus is more protected
what symptoms can you get from LPR?
hoarseness and globus pharyngeanus, chronic cough
what is LPR?
larynx-pharyngeal reflux
what is globus pharyngeus?
a lump in your throat which is related to reflux
why isn’t heart burn common in LPR?
because generally stays in the oesophagus, heart burn doesn’t happen in the larynx
how many isoforms are there of carbonic anhydrase?
11
what does carbonic anhydrase do?
it generates bicarbonate, to protect the tissue from acid reflux - bicarbonate neutralises it
what type of carbonic anhydrase is increased in GORD?
carbonic anhydrase 3
what does carbonic anhydrase do when its expression is increased?
moves the expression away from the surface of the cells down into the mucosa to form a barrier
what can be seen in LPR patients regarding carbonic anhydrase 3?
there is none - it is completely lost
in different pHs in in the oesophagus is the expression of carbonic anhydrase 3 affected by acid exposure?
No, in the oesophagus acid does not affect the expression of carbonic anhydrase at any pH
does acid exposure affect the larynx at different pHs?
yes, there is high expression of carbonic anhydrase at ph7.4, then a reduction at ph4, and an even bigger reduction at pH2
can the tissue recover in the larynx from pH2 with acid exposure?
yes if you incubate the tissue at pH7.4 for 4 hours
what happens to the expression of carbonic anhydrase when acid and pepsin exposure occurs in the oesophagus?
at ph4 there is a reduction and an even bigger Reduction at ph2
can the oesophagus recover after its been exposed to acid and pepsin?
yes if it is incubated for 4 hours at a pH of 7.4
what happens to the expression of carbonic anhydrase when acid and pepsin exposure occurs in the larynx?
there is little or no expression of carbonic anhydrase at pH4 and Ph2
is the larynx able to recover after exposure of acid and pepsin?
no, it becomes irreversible
what is the normal expression of mucus in the larynx?
MUC4 and MUC5AC
what is MUC4?
it is a membrane bound mucin
what is MUC5AC?
it is a gel forming surface mucin
what happens to MUC5AC in LPR?
the expression of MUC5AC is lost - the surface mucus has a role in protection and now it is gone
what is the treatment for OME (glue ear)?
Pierce the eardrum and suck out the mucus effusion and fit the grommet which helps the pressure
what is the hearing loss for people that have glue ear?
20 decibel loss
what can pepsin damage?
can damage tissues at high pH
what can be associated with supra-oesophageal disease?
pepsin can be found which means reflux has happened
what are lung transplants called?
allografts
what are allografts?
they are not perfectly matched
what are isografts?
they are a perfect match
what happens if after 5 years of a lung transplant there is epithelial damage or scarring?
could be linked to gastroesophageal reflux
what happens as a result from fibrosis in lung transplant rejection?
FEV1 is lost over time, no air can go through and lungs lose the ability for gas exchange =
what syndrome can result from fibrosis?
Bronchiolitis obliterates syndrome (BOS)
what happens if you develop BOS early in time after a transplant?
higher bile acids
what happens to bile acids during liver failure?
bile acids increase
what is a test that measures bile acids in liver failure?
colorimetric test
what does it mean if you have acid in the lungs?
must have come from a double reflux event, acid would have come from the duodenum in the stomach and up into the oesophagus and then aspirated into the lungs
what event is reflux?
it is a transient event
what could reflux play a role in?
lung allograft rejection
describe the paradigm for chronic allograft rejection?
alloreactivity and response to injury (acute rejection), then get a cytokine response (killer T lymphocytes) with a transition of the epithelia to myofibroblasts, matrix changes and collagen scarring which leads to an allograft loss and death
what must of happened if you are developing BOS?
must have had an acute rejection event
what do clinicians provide to patients that develop BOS?
steroids to dampen down the inflammatory response
