lecture 3 Flashcards
how many isoforms does carbonic anhydrase have?
- 11
why is carbonic anhydrase important?
- generates bicarbonate
- allows protection of tissues
when is carbonic anhydrase III expression increased?
- in gastrooesophageal reflux disease
- increased in inflamed mucosa
- moves to cells lower in mucosa to form a barrier
what disease completely loses carbonic anhydrase III?
- LPR
where is the 20 minute acid exposure shown?
- in larynx (pH2 has greatest effect)
- has no effect on oesophagus
what happens when pig oesophagus is treated with both acid and pepsin?
- becomes damaged
- less expression at more acidic pHs
- oesophagus expression recovers if incubation at pH 7.4 (recoverable reduction)
what happens when pig larynx is treated with acid and pepsin?
- doesn’t recover
- damage with both
- decreases CA III expression permanently
what mucus is expressed in the larynx?
- MUC 4 (membrane bound mucin) - MUC5AC (gel forming surface mucin)
what mucus is expressed in LPR?
- expression of MUC 5AC is lost
what does this show MUC 5AC to have a role in?
- protection
what is OME?
- otitis media with effusion (glue ear)
what is OME thought to be due to?
- respiratory viruses
- allergy
- Eustachian tube obstruction
- bacterial infections
- dysfunctional mucocilliary clearance
what is OME actually caused because of?
- reflux of gastric juice
what were the results from the effusions tested?
- acidic protease activity found in 19/65
- 59/65 contained pepsin or pepsinogen protein
what pH does pepsin damage tissues at?
- high pHs
what was concluded from this experiment?
- 91% effusions contain pepsin/pepsinogen so source certainly gastric juice
- gastric reflux may be primary factor in OME
- reflux instigates cascade of inflammatory events
why are they called allografts?
- not perfectly matched to the patient
what lung conditions are applicable for lung transplants?
- emphysema
- idiopathic pulmonary fibrosis (destruction of lungs, fibrous tissue forming instead)
- cystic fibrosis
what is the survival rate 1 year post transplant?
- 80%
what is the mortality rate?
- 50%
- due to allograft failure
- epithelial damage and scarring occurs
how does bronchiolitis obliterates syndrome (BOS) improve years after transplant?
- with anti-reflux surgery at same time shows cured from BOS
- rest lead to deterioration of lungs
- patients with no history of reflux also have low survival rate after BOS surgery
how do you prevent reflux?
- fondoplication
what occurs in fondoplication?
- fundus of stomach wrapped around bottom of oesophagus
- strengthens cardiac sphincter
- reduces chance of reflux
- protection of lungs
what does BOS result from?
- fibrosis
- lots of inflammatory cells and collagen
- no room for air to pass through
- loses airway ability to exchange gases
- loss of FEV1 (forced expiratory volume) over time
what might cause BOS?
- measured bile acids in lung lavage samples
- high levels of bile acids in BOS
what is a lung lavage?
- put fluid (saline) into lung
- aspirated back out
- measure bile acids
what is measured in lavage fluid?
- large amounts of pepsin
- protease activity
why do some samples have no values?
- due to different patients conditions
- shows reflux is transient event (dependent on when lavage is taken)- evidence of reflux could be cleared from lungs
does it relate to evidence of inflammation?
- no
- neutrophil levels don’t directly link at same time point to pepsin
- reflux causes response to increase neutrophils (lagging)
- high neutrophils means low pepsin as reflux already occurred
what are the conclusions of this experiment?
- 75% had detectable pepsin levels
- 79% had detectable pepsin like activity
- pepsin detected in induced sputum samples
- reflux plays role in lung allograft rejection
what is the paradigm (pattern) for chronic allograft rejection?
- alloreactivity
- response to injury
- causes acute rejection, inflammation, CD4 T cell infiltrate
what is the result of this?
- chronic, cytokine driven changes
- chronic intraepithelial CD8 lymphocytosis (lots of killer T cells, inflammatory response)
- transition of epithelia to myofibrilasts
- matrix changes
- collagen scarring
what does this cause?
- allograft loss (death)
what is bronchiolitis obliterates syndrome?
- results from immunological and non immunological mechanisms
- acute rejection is linked
- pathophysiology is poorly understood
- gastro-oesophageal reflux is contributing factor
what was the aim of the pepsin as a marker of gastric aspiration study?
- to. measure pepsin as marker of gastric aspiration in lung transplant recipients with acute rejection and BOS
what subjects were included in study?
- 4 normal volunteer controls
- 17 unexplained chronic cough patients
- 36 transplant patients
