Reflux esophagitis is inflammation of the esophagus caused by stomach acid entering the esophagus. It is characterized by a defective lower esophageal sphincter that allows reflux. Symptoms include heartburn. Risk factors include older age and obesity. Diagnosis involves testing for acid exposure and visualization of erosions via endoscopy. Treatment focuses on lifestyle changes, antacids, H2 blockers, proton pump inhibitors, and surgery to reduce acid exposure and promote healing. Complications can include esophageal strictures, Barrett's esophagus, and esophageal cancer if left untreated.

1. REFLUX ESOPHAGITIS
Presented to: Presented by:
Dr. Mohd. Akhtar Anukrati Agnihotri

2. INTRODUCTION

3.  Reflux esophagitis is defined as inflammation of
the esophageal mucosa secondary to
gastroesophageal reflux disease (GERD), a
condition in which the stomach contents reflux
into the esophagus or beyond (oral cavity,
larynx, or the lungs), causing troublesome
symptoms and complications.
 The American College of
Gastroenterology defines GERD as “chronic
symptoms or mucosal damage incurred by the
abnormal reflux of gastric contents into the
esophagus

4.  The disease is primarily a disorder of the lower
esophageal sphincter. It can be classified based
on the presence of symptoms without erosions
on endoscopic examination (non-erosive
disease, NERD) or symptoms plus esophageal
erosions (erosive reflux disease, ERD).
 The diagnosis is usually established based on a
combination of presenting symptoms, objective
testing with endoscopy, ambulatory reflux
monitoring, and response to a proton pump
inhibitor (PPI) therapy.

6. Epidemiology
 In Western countries, the prevalence of the
disease is approximately 10% to 20%, and severe
disease is observed in 6% of the population,
 while in Asian countries, the prevalence is
approximately 5%.
 Reflux esophagitis is equally prevalent among
men and women.
 However, the predominance of esophagitis and
Barrett esophagitis in men compared to women
is 3:1 and 10:1, respectively. Some studies report
a higher frequency of reflux esophagitis in men,
whereas others report an increased frequency in
women.

7.  The incidence of reflux esophagitis is greatest at the age
of 60 to 70 years and decreases slightly thereafter.
 As observed in adults, GERD is also increasingly seen in
the pediatric population. Nelson et al. reported
incidence of GERD ranging between 12% and 50% in
children aged 0-18 years from the year 2000 to 2005.
 Approximately half of the pregnant women complain of
reflux during pregnancy: 20% to 30% in the first
trimester, 40% to 45% in the second trimester, and 60%
in the third trimester.
 Usually, these patients do not have symptoms such as
heartburn before their pregnancy.

8. Pathophysiology
 Gastroesophageal reflux is associated with defective lower
esophageal sphinchter(LES) pressure or function.
 Patients may have decreased gastroesophageal sphinchter
pressures related to:
a. Spontaneous transient LES relaxations
b. Transient increases in intra-abdominal pressure
c. An atonic LES
 The LES is a 3-4 cm tonically contracted smooth muscle segment located at
the esophagogastric junction (EGJ) and, along with the crural diaphragm
forms the physiological EGJ barrier, which prevents the retrograde
migration of acidic gastric contents into the esophagus.
 In otherwise healthy individuals, LES maintains a high-pressure zone
above intragastric pressures with transient relaxation of the LES that occurs
physiologically in response to a meal facilitating the passage of food into
the stomach.

9.  Patients with symptoms of GERD may have frequent transient LES
relaxations (TLESRs) not triggered by swallowing, resulting in exceeding
the intragastric pressure more than LES pressures permitting reflux of
gastric contents into the esophagus.
 The exact mechanism of increased transient relaxation is unknown, but
TLESRs account for 48-73% of GERD symptoms
 Problems with other normal mucosal defense mechanisms such as
abnormal esophageal anatomy, improper esophageal clearance of gastric
fluids, reduced mucosal resistance to acid, delayed or ineffective gastric
emptying and reduced salivary buffering of acid may also contribute to the
development of GERD.
 Substances that may promote esophageal damage on reflux into the
esophagus include gastric acid, pepsin, bile acids and pancreatic enzymes.

10. symptoms
 Heartburn
 Dysphagia
 Odynophagia
 Weight loss
 Anorexia
 Sore throat
 Vomiting
 Upper Gastrointestinal
bleeding (Alarm symptoms)

11. Risk factors
 Old Age
 Excessive body mass index
 Smoking
 Anxiety/ depression
 Lack of physical activity

12. Diagnosis
Diagnostic test Indication
PPI trial
Classic GERD symptoms with no
alarm symptoms.
Esophageal pH monitoring
Refractory symptoms where
GERD diagnosis is in question,
pre-operative evaluation for non-
erosive disease
Upper endoscopy
Alarm symptoms (e.g.,
dysphagia), PPI unresponsive
patients, high risk for Barrett’s
esophagus
Barium esophagram
Evaluation of dysphagia,
otherwise not recommended for
GERD evaluation
Prior to anti-reflux surgery to

13. Esophageal pH monitoring

14. Upper endoscopy

15. Barium esophagram

16. Esophageal Manometry


17. Classification of drugs used in
GERD
1.Antacids
e.g., Magnesium hydroxide, Alginic acid, calcium carbonate
2. H2 receptor antagonists
e.g., Famotidine, Ranitidine, Cimetidine, Nizatidine
3. Proton pump inhibitors
e.g., Dexlansoprazole, Esomeprazole, Pantoprazole,
rabeprazole, Tenatoprazole
4.Prokinetic Agents
e.g., Metoclopramide, Domeperidone,Tegaserod,
Mosapride

18. Therapy focused on
mucosal production
Sucralfate
(A complex of sucrose sulfate
& aluminium hydroxide)
Therapy focused on Acid
Suppression
 Histamine type-2 receptor
antagonists
 Proton pump inhibitors
 Potassium competitive acid
blocker (P-CAB)
Therapy focused on
TLESR
 GABAB receptor agonists
 mGlu R5 antagonists
Therapy focused on
gastroesophageal motility
• Mosapride & Itopride

19. Therapy focused on
visceral hypersensitivity (in
case of refractory GERD)
 Selective
norepinephrine
reuptake inhibitors
 Theophylline

20. Pharmacotherapy
 The goals of the therapy are to alleviate symptoms,
decrease the frequency of recurrent disease,
promote healing of mucosal injury, and prevent
complications.
 GERD treatment is determined by disease severity and
includes:
(a) lifestyle changes and patient-directed therapy with antacids,
nonprescription H2-receptor antagonists, and/or
nonprescription proton pump inhibitors;
(b) Pharmacologic treatment with prescription-strength acid
suppression therapy;
(c) Surgery
(d) Endoscopic therapies.

21. Mechanism of antacids
 Aluminium hydroxide- Aluminum hydroxide [Al(OH)3] dissociates
into Al3+ and OH- in the stomach.
 The freed hydroxide groups then bind to free protons, ultimately producing
water and insoluble aluminum salts, mostly Al(Cl)3, within the stomach.
The proton binding serves to increase the overall pH of the stomach, i.e.,
less acidic, reducing the symptoms of indigestion.
 The produced aluminum salt primarily gets excreted in the feces, with less
than 1% of the bioavailable aluminum absorbed within the GI tract.
 Topical aluminum hydroxide creates an acidic, hydrophilic layer over the
area of irritation; this serves as a protective barrier to prevent infection and
deter bacterial growth within the wound.

22. Mechanism of action of PPIs
 Proton pump inhibitors (PPIs) are a class of medications that cause
a profound and prolonged reduction of stomach acid
production. They do so by irreversibly inhibiting the stomach’s
H+/K+ ATPase proton pump.
 Proton pump inhibitors provide the greatest symptom relief and the
highest healing rates, especially for patients with erosive disease or
moderate-to-severe symptoms or with complications.
 This enzyme system is responsible for the final step in gastric acid
secretion, which is the exchange of potassium ions with hydrogen
ions . By blocking this exchange, PPIs reduce the amount of acid
produced by the stomach.
 PPIs are the most potent inhibitors of acid secretion available . They
have largely superseded the H2-receptor antagonists, a group of
medications with similar effects but a different mode of action, and
antacids

23. Mechanism of action of H2
receptor antagonists
 H2 receptor antagonists are a class of drugs that block
the action of histamine on parietal cells in the stomach,
thereby reducing the production of gastric acid.
 These drugs bind to the histamine H2 receptor, which is
present on the basolateral membrane of parietal cells.
 This binding inhibits the activation of adenylate cyclase,
which in turn reduces the production of cyclic AMP and
ultimately decreases acid secretion.
 The reduction in acid secretion can help alleviate
symptoms associated with gastroesophageal reflux
disease (GERD), peptic ulcers, and other acid-related
disorders.

24. Mechanism of action of Prokinetic agents
 Prokinetic agents are medications that help control acid reflux
by strengthening the lower esophageal sphincter (LES) and causing
the contents of the stomach to empty faster.
 They work by stimulating excitatory chemical messengers like
acetylcholine and suppressing inhibitory neurotransmitters like
dopamine and serotonin. This stimulates specific receptors on the
smooth muscle cells in the gastrointestinal tract, thus promoting
muscle contractions.
 The primary prokinetic mechanism is by acting as a D2 dopamine
receptor antagonist. Prokinetic agents amplify and coordinate
gastrointestinal muscular contractions, including coordination
between different segments of the gut, thereby enhancing
propulsion of intra-luminal contents.

25. Potassium competitive acid
blocker (P-CAB)
 Potassium-competitive acid blockers (P-CABs) are another class of acid
suppressants developed in the last few years and inhibit proton pumps
via a different mechanism than PPIs.
 They act by competing with binding of the potassium-binding site of
proton pump, P-CABs reversibly inhibit gastric H+/K+-ATPase and do
not require acid activation, which means that they are meal time
independent in contr
 Revaprazan (YH1885), soraprazan, and AZD0865 have been evaluated
in animal model and healthy volunteers.

26. GABAB receptor agonists
 GABA, as a major inhibitory neurotransmitter within the central nervous
system, controls TLESRS by GABAB receptors expressed in LES-
projecting neurons of the vagal nerve.
 Other than effect from central nuclei, peripheral GABAB receptors also
have inhibitory effect on gastric vagal mechanoreceptors and gastric
distention-related TLESRs.
 In patients with GERD, baclofen significantly decreases the number of
reflux events and reflux symptoms by reducing the incidence of TLESRs.
 Baclofen, usually used in the management of spasticity, is a prototypical
GABAB agonist and has effects in the control of TLESRs, initially noted in
animal and healthy human studies .
 Other agents of this class are Arbaclofen, Lesogaberan

27. mGlu R5 antagonists
 Glutamate is the primary neurotransmitter involved in signalling
from visceral and somatic primary afferents to the central nervous
system.
 Peripherally located mGluR5 receptors have been associated with
control of TLESRs, noted by animal studies initially, and mGluR5
antagonists are considered as potential therapy for patient with
GERD.
 ADX10059 is a potent selective negative allosteric modulator of the
mGluR5 and is the most extensively studied agent of mGluR5
antagonists

28. Complications
 Erosive Esophagitis (EE)
 EE is characterized by erosions or ulcers of the esophageal mucosa.
 Patients may be asymptomatic or can present with worsening symptoms of
GERD.
 The degree of esophagitis is endoscopically graded using the Los Angeles
esophagitis classification system, which employs the A, B, C, D grading
system based on variables that include length, location, and circumferential
severity of mucosal breaks in the esophagus.
 Esophageal Strictures
 Chronic acid irritation of the distal esophagus can result in scarring of distal
the esophagus leading to the formation of a peptic stricture.
 Patients can present with symptoms of esophageal dysphagia or food
impaction.
 ACG guidelines recommend esophageal dilation and continue PPI therapy
to prevent the need for repeated dilations.

29.  Barrett Esophagus
 This complication occurs as a result of chronic pathological acid exposure
to the distal esophageal mucosa.
 It leads to a histopathological change of the distal esophageal mucosa,
which is normally lined by stratified squamous epithelium to metaplastic
columnar epithelium.
 Barrett's esophagus is more commonly seen in Caucasian males above 50
years, obesity, and history of smoking and predisposes to the development
of esophageal adenocarcinoma.
 Current guidelines recommend the performance of periodic surveillance
endoscopy in patients with a diagnosis of Barrett's esophagus[41].

30. References
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In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing;
2023 Jan-. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK554462/
 Clarrett, D. M., & Hachem, C. (2018). Gastroesophageal Reflux
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 Shaik, Z.A. (2019) Gastroesophageal reflux disease (GERD), GetCured
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 Wang YK, Hsu WH, Wang SS, Lu CY, Kuo FC, Su YC, Yang SF, Chen
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