GERD

Question 1

Dfine GORD

Answer 1

• actionable GORD requires conclusive evidence of reflux-related pathology on endoscopy and/or abnormal reflux monitoring in the presence of compatible troublesome symptoms

Question 2

Describe the epidemiology of GORD

Answer 2

• 20% of western populations
• 3792 per 100000
  
  • slight female skew
• increasing prevalence in developing countries
• stable or falling prevalence in western countries

Question 3

List the four factors that contribute to pathophysiology

Answer 3

• Lower (o)esophageal sphincter – LOS/LES tone
• Anatomical disruption on LOS
• Oesophageal mucosal defences
• Motility

Question 4

Describe the sphincter

Answer 4

• 3-4 cm, tonically contracted, smooth muscle
• crural diaphragm provides an extra layer of protection
• LOS and crural diaphragm together constitute the barrier
• most of the time LOS is closed and opens in response to food in the oesophagus
• transient LOS relaxations account for 50-70% of reflux events

Question 5

Describe how TLOSR occurs and factors that decrease LOS tone

Answer 5

• where teh LOS relaxes and intragastric pressure exceeds that of LOS, allowing for reflux of gastric contents into oesophagus
• many factors decrease LOS tone
  
  • gastric distention e.g. large meal size
  • chocolate
  • caffeine
  • smoking
  • pregnancy
  • meds: nitrates, CCBs

Question 6

Describe anatomical disruptions to sphincter

Answer 6

• hiatus hernia is most common - pulls above diaphragm
• LOS is shorter and weaker due to loss of support of crural diaphragm, leading to increased TLOSR
• makes reflux more likely
• can increase severity of erosive disease due to nocturnal reflux
• volume reflux

Question 7

Describe mucosal defences

Answer 7

• pre-epithelial:
  
  • thin water layer with limited buffering capacity due to salivary bicarbonate
  • secretions from oesophageal submucosal glands
• epithelial defences
  
  • cell membranes and the intercellular junctional complex limit the rate of hydrogen ion penetration into the intracellular space or cell cytosol
  • cellular and intracellular buffers (HCO3, proteins, phos) that neutralise back-diffusing luminal acid
  • cell membrane ion transports remove acid from the cytosol when intracellular pH falls to acidic levels

Question 8

Describe how breach of mucosal defences occurs

Answer 8

• high luminal acidity, alcohol , heat causing caustic injury, smoke derived chemicals
• acid attacks and damages intracellular junctions
  
  • increased paracellular permeability ie non-erosive reflux
  • acidification of intracellular space by back diffusion of luminal acid
  • cell oedema and necrosis
  • poor epithelial repair due to reduced salivary epidermal GFs
• erosive reflux disease

Question 9

Describe the effect of altered motility

Answer 9

• reduced acid clearance by impaired oesophageal peristalsis
  
  • ineffective oesophageal motility present in about 50% of cases of acid reflux referred for manometry and pH studies - direction of causality unknown
  • swallowing of saliva which contains bicarbonate is essential to clear oesophageal acid and restoring oesophageal pH
  • primary oesophageal peristalsis is initiated by swallowing ~60/h
  • secondary peristalsis is not initiated by swallowing and can be triggered by luminal content and acid
• re-reflux can occur when refluxate is cleared but trapped in a hernia sack increases oesophageal acid exposure time

Question 10

Breakdown the symptoms

Answer 10

• oesophageal
  
  • heartburn
    
    • retrosternal burning pain, can radiate into neck, typically after meals or laying down
• regurgitation
  
  • retrograde movement of acidic gastric contents into the mouth or pharynx
• chest pain
• extraoesophageal
  
  • cough
  • asthma
  • laryngitis
  • hoarse voice
  • dental erosions
  • globus sensation - feeling of something stuck in throat around sternal notch

Question 11

What is the significance of oesophageal vs extra-oesophageal symptoms?

Answer 11

• extra- symptoms not as responsive to therapeutics
• heartburn 50-70% will experience symptom relief from PPI
• chest pain if positive pH study up to 80%
• chronic cough, asthma, hoarse voice and pH negative chest pain , less than 25% will improve, some may get worse

Question 12

Provide an overview of the diagnosis of GERD

Answer 12

• troublesome suspicious GERD symptoms
• if no alarm symptoms, empiric trial of anti-secretory therpay
• oesophageal physiologic evaluation i.e.
  
  • endoscopy (structural overview of oesophageal and stomach - see LA grades)
  • ambulatory pH monitoring
• adjunctive approach

Question 13

Describe wireless ambulatory monitoring

Answer 13

• wireless - Bravo capsule
  - attached endoscopically 3-5 cm above GOJ
  - wireless pH recording for up to 48h
  - capsule detaches spontaneously
  - attachment can cause chest pain and discomfort in some people
  - advantages: wireless, 48h
  - disadvantages: requires endoscopic insertion, possibility of chest pain post attachment, early capsule detachment, acid exposure time only (nothing else measured - look to see if pH dips below 4)

Question 14

Describe wired ambulatory monitoring

Answer 14

• wired - 24 h pH
  
  • catheter based system
  • inserted while patient is awake therefore no anaesthetic risk
  • multiple catheter options
  • impedance capacity
  • advantages: multiple catheter option (Single or dual pH sensor +/- impedance i.e. flow across oesophagus- helps to assess response to treatment, disringuish GERD from NERD), inserted in clinic setting i.e. no endoscopy, simple reinsertion if catheter dislodged, no pain
  • disadvantages: unable to pass catheter nasally e.g. due to previous ENT surgery or anatomical abnormalities, if unable to tolerate catheter insertion, attached to box for 24h -can’t have shower

Question 15

Describe the LA classificaiton

Answer 15

• A – mucosal break < 5mm ie linear erosion
  
  • B – mucosal break > 5mm
  • C – Mucosal break which extends between folds ie ulcer
  • D – Mucosal break > 75% circumference

Question 16

What do ambulatory tests lookat?

Answer 16

• acid exposure time
  
  • <4% in 24 hours is considered physiological
  • > 6 is pathological
• number of reflux events
  
  • impedance only: >80 in 24h is abnormal
  • acidic, weakly acidic, non-acidic
• symptom association

Question 17

Define SSI SI and SAP

Answer 17

SSI, SI
- SSI: the percentage of symptom- related reflux episodes
- %symptoms that occurred with associated reflux episodes
- SI: the percentage of reflux related symptom episodes
- % reflux episodes that were associated with symptoms
- >50 is considered significant

SAP
- symptom and reflux, positive and negative 2x2 table
- statistical measurement of the probability of symptoms and reflux events being related greater than chance
- >95 is statistically significant

Question 18

Describe reflux hypersensitivity and functional heartburn

Answer 18

• reflux hypersensitivity
  
  • hypersensitive to normal physiological reflux
    
    • AET <4%
    • positive symptoms index >50
    • positive SAP >95
• functional heartburn
  
  • symptoms not associated with acid reflux events
    
    • AET <4%
    • negative symptoms index <50
    • negative SAP <95

Note: people with B may or may not need further

Question 19

List anti-secretory medications

Answer 19

• H2 receptor blockers e.g. ranitidine, famotidine, nizatidine
• PPIs e.g. omeprazole, esomperazole
• P-CAB e.g. vonoprazan

Question 20

Describe the MoAs, onset and duration of aciton of anti-secretorys

Answer 20

• H2Rbs
  
  • competitive antagonists that bind to histamine receptor in parietal cell, blocking the binding of histamine
  • gastrin stimulates release of histamine from enterochromaffin-like cell sin response to food which then bind to H2 receptor on partieal cells stimulatinf acid secretion
  • onet of action 1 h
  • laasts 4-6 hours
• PPIs
  
  • irreversibly bind to and inhibit HK ATPase transporter on teh luminal membrnae of parietal cells
  • accumulate in the secretory canaliculus of the parietal cell where the active drug forms a disulphide bond with the external surface of the HK ATPase transporter
  • onset 30-60 m
  • takes 3-5 days to reach steady state
• PCAB
  
  • competitive, reversible blockade of K binding site of the HK ATPase transporter on the luminal membrane of parietal cells
  • onset of action 30m
  • lasts 21 h

Question 21

Describe what an adequate trial looks like

Answer 21

• PPI> H2RB
  
  • unless under specific circumstances e.g. younger, or younger with functional
  • vonoprazan not funded by PBS
  • recommendation: 8-12 wks of once daily standard dose
  • only advised in patients with typical reflux symptoms e.g. heartburn, regurgitation and/or chest pain
  • note: dose between PPIs means different potency

Question 22

What to do if Patient still symptomatic after trial?

Answer 22

• is the dose adequate?
• are they compliant?
  
  • 30-60m, before food, first thing in the morning
    Note: it is NOT an antiacid- won’t help to take with food, or after food, as they wont suppress post prandial acid peak
  • may provide some benefit if taken with food but if still having symptoms must optimise timing before escalating therapy

Question 23

**Timing didn’t work. What else?

Answer 23

• lifestyle and acid modification
  
  • reduce foods and drinks that trigger TLOSR
    
    • coffee, alcohol and spicy foods
  • stop smoking: cigarette smoking increases TLOSR
  • weight loss
    
    • central obesity increases intra-abdominal pressure and reduces gastric compliance
• sleep with head of bed elevated

Question 24

List some red flags

Answer 24

• dysphagia
  
  • especially progressive from solids to liquids
• weight loss
• haematemesis or melaena
• sudden change in reflux symptoms

Question 25

Describe Barrett’s

Answer 25

• the normal stratified squamous epithelium in the lower oesophagus is replaced wiht metaplastic columnar epithelium with both gastric and intestinal features
• develops as a consequence of chronic GORD
• other RFs include obesity, family Hx, smoking
• increased risk of oesophageal adenocarcinoma: <1% /y
• prevalence: 1.3-1.6/1000 endoscopies

Question 26

Describe oesophageal cancer

Answer 26

• 60% Ad, 40% SCC in Au
• SCC predominates in developing nations
• Poor prognosis, 1700/y, 23% 5ys

Question 27

When is surgery indicated, and what are some examples?

Answer 27

• especially if refractory disease
• fundoplication: stomach wrapped around lower oesophagus
• reinforces LOS
• different types: 180, 270, 360
• surgery may also be done to fix hernia