Lecture 4

Question 1

how do you measure tissue damage?

Answer 1

can measure a fluorescent assay for DNA, look at DNA release

Question 2

at what pH is there more DNA release?

Answer 2

pH2 and there is even more DNA release with pepsin + pH2

Question 3

what are the 5 tissues in the larynx?

Answer 3

supra glottic, posterior commissure, ventricle, vocal fold and sub glottic

Question 4

what tissue type is the sub glottic?

Answer 4

columnar epithelium

Question 5

what tissue type is supra glottic?

Answer 5

squamous epithelium

Question 6

what is the tissue type in the vocal chords?

Answer 6

there is a mixture of types

Question 7

what is the highest level of pepsin in gastric juice?

Answer 7

1mg/ml

Question 8

what tissue in the larynx is the most damaged by pepsin?

Answer 8

sub glottis

Question 9

what tissue in the larynx is the least damaged by pepsin?

Answer 9

the posterior commissure

Question 10

what in the stomach gives you pH gradient across the mucus layer?

Answer 10

a bicarbonate secretion with the mucus layer

Question 11

what tissue type is the oesophagus?

Answer 11

squamous epithelium

Question 12

how does the oesophagus protect itself from gastric juice If it doesn’t contain a mucus layer?

Answer 12

it sheds dead cells

Question 13

what organ is more sensitive the oesophagus or the larynx?

Answer 13

the larynx, as the oesophagus is more protected

Question 14

what symptoms can you get from LPR?

Answer 14

hoarseness and globus pharyngeanus, chronic cough

Question 15

what is LPR?

Answer 15

larynx-pharyngeal reflux

Question 16

what is globus pharyngeus?

Answer 16

a lump in your throat which is related to reflux

Question 17

why isn’t heart burn common in LPR?

Answer 17

because generally stays in the oesophagus, heart burn doesn’t happen in the larynx

Question 18

how many isoforms are there of carbonic anhydrase?

Answer 18

11

Question 19

what does carbonic anhydrase do?

Answer 19

it generates bicarbonate, to protect the tissue from acid reflux - bicarbonate neutralises it

Question 20

what type of carbonic anhydrase is increased in GORD?

Answer 20

carbonic anhydrase 3

Question 21

what does carbonic anhydrase do when its expression is increased?

Answer 21

moves the expression away from the surface of the cells down into the mucosa to form a barrier

Question 22

what can be seen in LPR patients regarding carbonic anhydrase 3?

Answer 22

there is none - it is completely lost

Question 23

in different pHs in in the oesophagus is the expression of carbonic anhydrase 3 affected by acid exposure?

Answer 23

No, in the oesophagus acid does not affect the expression of carbonic anhydrase at any pH

Question 24

does acid exposure affect the larynx at different pHs?

Answer 24

yes, there is high expression of carbonic anhydrase at ph7.4, then a reduction at ph4, and an even bigger reduction at pH2

Question 25

can the tissue recover in the larynx from pH2 with acid exposure?

Answer 25

yes if you incubate the tissue at pH7.4 for 4 hours

Question 26

what happens to the expression of carbonic anhydrase when acid and pepsin exposure occurs in the oesophagus?

Answer 26

at ph4 there is a reduction and an even bigger Reduction at ph2

Question 27

can the oesophagus recover after its been exposed to acid and pepsin?

Answer 27

yes if it is incubated for 4 hours at a pH of 7.4

Question 28

what happens to the expression of carbonic anhydrase when acid and pepsin exposure occurs in the larynx?

Answer 28

there is little or no expression of carbonic anhydrase at pH4 and Ph2

Question 29

is the larynx able to recover after exposure of acid and pepsin?

Answer 29

no, it becomes irreversible

Question 30

what is the normal expression of mucus in the larynx?

Answer 30

MUC4 and MUC5AC

Question 31

what is MUC4?

Answer 31

it is a membrane bound mucin

Question 32

what is MUC5AC?

Answer 32

it is a gel forming surface mucin

Question 33

what happens to MUC5AC in LPR?

Answer 33

the expression of MUC5AC is lost - the surface mucus has a role in protection and now it is gone

Question 34

what is the treatment for OME (glue ear)?

Answer 34

Pierce the eardrum and suck out the mucus effusion and fit the grommet which helps the pressure

Question 35

what is the hearing loss for people that have glue ear?

Answer 35

20 decibel loss

Question 36

what can pepsin damage?

Answer 36

can damage tissues at high pH

Question 37

what can be associated with supra-oesophageal disease?

Answer 37

pepsin can be found which means reflux has happened

Question 38

what are lung transplants called?

Answer 38

allografts

Question 39

what are allografts?

Answer 39

they are not perfectly matched

Question 40

what are isografts?

Answer 40

they are a perfect match

Question 41

what happens if after 5 years of a lung transplant there is epithelial damage or scarring?

Answer 41

could be linked to gastroesophageal reflux

Question 42

what happens as a result from fibrosis in lung transplant rejection?

Answer 42

FEV1 is lost over time, no air can go through and lungs lose the ability for gas exchange =

Question 43

what syndrome can result from fibrosis?

Answer 43

Bronchiolitis obliterates syndrome (BOS)

Question 44

what happens if you develop BOS early in time after a transplant?

Answer 44

higher bile acids

Question 45

what happens to bile acids during liver failure?

Answer 45

bile acids increase

Question 46

what is a test that measures bile acids in liver failure?

Answer 46

colorimetric test

Question 47

what does it mean if you have acid in the lungs?

Answer 47

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

Question 48

what event is reflux?

Answer 48

it is a transient event

Question 49

what could reflux play a role in?

Answer 49

lung allograft rejection

Question 50

describe the paradigm for chronic allograft rejection?

Answer 50

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

Question 51

what must of happened if you are developing BOS?

Answer 51

must have had an acute rejection event

Question 52

what do clinicians provide to patients that develop BOS?

Answer 52

steroids to dampen down the inflammatory response