GASTROESOPHAGEAL

REFLUX DISEASE
Diana Elizabeth Cruz Galván A01641865
Alejandro Lizárraga Madrigal A01635377
Reneé Pedroza Gómez A01368829
Alondra Valenzuela Grajeda A01642100
Ximena Santillán A01562899
María Fernanda Gutiérrez Cárdenas A01641859
Ximena Cruz Tenorio A01636523
Paolo Luna Trejo A01351986
 CONTENT

01 02 03 04
Introduction Epidemiology Risk factors Etiology and
pathogenesis

05 06 07 08
Clinical features Diagnosis Treatment Complications
and BE

Clinical case
 INTRODUCTION

WHAT IS GERD?

The disease that involves the symptoms

and complications that develop when
gastric contents ascend into the
esophagus, oral cavity (including the
larynx), or lungs.

mild symptoms >=2 days a week

severe symptoms +1 day a week.

(Méndez Sánchez, 2022)

 LOWER ESOPHAGEAL
SPHINCTER (LES)

Is a 3- to 4- segment of tonically contracted smooth

muscle at the distal extreme of the tubular esophagus

Is one of the contributors to the EGC high-pressure

zone, with the crural diaphragm and the muscular
arhitecture of gastric cardia
Resting tone=10-30 mmHg
↓ posprandial state
↑ during sleep
Myogenic (intrinsic rhythm of gastrointestinal
smooth muscle contraction and relaxation) and
neurogenic tone (SNA, SNE)

(Feldman et al., 2020)

(Méndez Sánchez, 2022)
Intrinsic Component:
Clasp Fibers: maintain strong myogenic tone, innervated by
inhibitory neurons in the esophagus, utilize L-type calcium
channels.

Sling Fibers: weaker resting tone, contract vigorously to

cholinergic agonists, innervated by excitatory neurons,
responsible for maintaining angle of HIS and flap valve
function.

Extrinsic Component:
Crural Diaphragm: "External sphincter", increases pressure,
crucial during inspiration and periods of increased
intraabdominal pressure.

Phrenoesophageal Ligament: acts as a protective sleeve

over the intraabdominal esophagus, allows independent
movement

(Rosen, 2023)
 EPIDEMIOLOGY
Prevalence North America: 19.8%
Europe (15.2%)
Middle East (14.4%)
East Asia (5.2%)
Latin America (11.9–31.3%)
Mexico: 25%
(Méndez Sánchez, 2022)
Prevalence of symptoms in Mexico

regurgitation
heartburn
bitter taste in
the mouth.

Incidence?
China: 5% (reflux esophagitis), 22.5% (heartburn)
Iran: 1.77 to 2.80% (Huerta-Iga et al., 2016)
 RISK FACTORS
Obesity (Body mass index >30 kg/m2): 2.5x
Intake of fatty and non-vegetarian foods
Chocolate, mint, citrics
Weight exercise
Smoking, alcohol consumption (7 drinks/week) and caffeine
Pregnancy
Angle of His enlargement (>60º)
Iatrogenic (after gastrectomy)
Gastrointestinal malformations and tumors (gastric outlet
obstruction)
Sliding hiatal hernia
Diabetes Mellitus
Scleroderma
Zollinger Ellison syndrome
Male, caucasian, elderly

less education, NSAID use, unpurified water consumption,

gastrointestinal complaints, lower socio-economic status, antacid
consumption, acid inhibitor therapy

(Rai et al., 2021)

(Méndez Sánchez, 2022)
 ETIOLOGY AND
PATHOGENESIS

MECHANISM CAUSES

↓ LES TONE SMOKING, ALCOHOL, CAFFEINE

HIATAL HERNIA SLIDING HERNIAS

↑INTRAGASTRIC PRESSURE PREGNANCY, OBESITY, LARGE MEALS, GASTROPARESIS (DM)

↑HCL PRODUCTION NSAIDS, ALCOHOL, SMOKING, ZOLLINGER-ELLISON SYND.

(Rosen, 2023)
 TRANSIENT RELAXATIONS OF
LES vasovagal reflex
- TLESR is the spontaneous relaxation of the
. LES in the absence of swallowing Occur most frequently
postprandially during gastric
- tLESRs → crucial in GERD development distention (Fundic
- primary mechanism for reflux →
distension) air or food
→
contents triggers TLESR
Characteristics of tLESRs:
Prolonged duration (>10 seconds).
Independent of pharyngeal swallowing.
Associated with distal esophageal
longitudinal muscle contraction, causing Mechanoreceptors → activating vagal
esophageal shortening. afferent fibers projecting to the nucleus
Lack synchronized esophageal →
of the solitary tract preganglionic
peristalsis. vagal inhibitory pathway to the LES
Associated with crural diaphragm
inhibition. NO and CCK
(Méndez Sánchez, 2022)
 RELAXATION OF LES INDUCED BY
SWALLOWING
NO → main neurotransmitter
LES relaxation triggered by distention or swallowing,
mediated by postganglionic nerves.
Deglutitive LES relaxation mediated by the vagus nerve,
synapses with inhibitory neurons in the myenteric
plexus.
NO released with neural stimulation in esophagus, LES,
and stomach; NO synthase inhibitors block LES
relaxation.
VIP-containing neurons in submucosal plexus, VIP
relaxes LES via direct muscle action.
LES relaxes initially during swallow, but opens only
when bolus enters sphincter, implicating intrabolus
pressure.
EGJ opening depends on forces: intrabolus pressure
(from peristalsis) and resistance (LES tone and
mechanical properties of esophageal wall and crural
canal).
(Feldman, M., et al., 2020).
 HYPOTENSIVE SPHINCTER

Characterized by reduced basal tone.

Pressure gradient between gastric fundus and LES < 10 mmHg.

Pathology of LES hypotension unknown.

Atrophy of LES smooth muscle with fibrosis possible.
Myenteric plexus thought to be normal.

Cholinergic suppression may cause LES hypotension.

Impairment of myogenic LES tone in most cases.
LES tone may be impaired by various smooth muscle relaxing
drugs and certain hormones.
calcium channel blockers, nitrovasodilators, alpha-adrenergic
agonists
estrogens and progesterone

(Lin et al., 2019)

 HIATAL HERNIA
Hiatal hernia (HH) defined as protrusion of
stomach into thoracic cavity via esophageal
hiatus.
Compromises function of lower esophageal
sphincter (LES) and esophageal clearance.
Reduces basal pressure and shortens high-
pressure zone due to loss of intraabdominal
segment.
Eliminates LES pressure augmentation during
effort and ↑ transient LES relaxations (tLESRs)
during gastric distention.

Type I, known as sliding hiatal hernias.

Most common type, often with laxity of
phrenoesophageal ligament.
Intermittent loss of tension from diaphragmatic
crura predisposes patients to GERD

(Méndez Sánchez, 2022)

 EMPTYING OF INTRALUMINAL
CONTENTS

Clearance (or emptying) is one of the

main defense mechanisms against
reflux.
Volume clearance
Acid clearance

Clearance can be disrupted by

reduced salivation (e.g., due to
smoking) and/or decreased
peristalsis (e.g., due to inflammation).

(Méndez Sánchez, 2022)

EPITHELIAL RESISTANCE

Allows reflux episodes to occur

during the day without
manifesting symptoms.

It is composed of 3 layers:
1. Preepithelial barrier.
2. Epitelial barrier.
3. Postepitelial barrier.
GASTRIC FACTORS

They increase acid

damage to the esophagus

Pepsin injury pH dependent

 DUODENOGASTRIC REFLUX AND DELAYED
GASTRIC EMPTYING
The duodenal content can also damage the esophagus.
Duodenogastric reflux contributes to the development
of erosive esophagitis.
The diagnosis of duodenogastric reflux is defined by
measuring esophageal pH greater than 7.

Delayed gastric emptying is a risk

factor for GERD, mainly in diabetic
people with neuropathy
(gastroparesis).
 GERD AND EATING

Reflux episodes are more frequent

after eating because gastric acid is
placed above the food, forming like an
acid pocket that allows acid to enter
the esophagus.

After eating, intragastric pH rises due

to food
CLINICAL FEATURES

Heartburn Regurgitation Dysphagia

Extracardiac
Hypersalivation Globus sensation
chest pain
"Water brash"

Odynophagia Nausea

Esophageal ulcer
CLINICAL FEATURES
Extraesophageal symptoms
CLINICAL FEATURES
Aggraviating factors
Lying down shortly after meals
Fatty meals, chocolate, caffeine, alcohol, or
carbonated drinks

Red flags
Dysphagia, odynophagia
Anemia or GI bleeding
Unintentional weight loss
Vomiting
 DIAGNOSIS - APPROACH

Perform a clinical evaluation,

All patients
focusing on red flags in GERD
Rule out life-threatening differential
diagnoses of GERD and chest pain
Typical symptoms without
red flags in GERD:
Red flags Refer to gastroenterology for EGD before
initiating treatment.
in GERD:
Extraesophageal symptoms:
Rule out other diagnoses prior to
initiating treatment for GERD.

Initiate treatment for GERD; start an empiric once-

Refractory symptoms:
daily PPI trial.
Optimize PPI therapy.
If there is relief after 8 weeks of PPI: GERD is
likely; PPI can be discontinued. If symptoms are relieved: Continue
If symptoms persist on PPI or recur after PPI.
discontinuing PPI: Refer to gastroenterology for If symptoms persist: Refer to
EGD gastroenterology.
 DIAGNOSIS - EGD

Indications:

Red flags in GERD

Evaluation of GERD progression
Risk factors for Barrett esophagus
No symptomatic improvement after PPI trial /
confirmation of GERD by pH test
Red flags of dyspepsia
Characteristics:
Supportive findings: (lower third of the esophagus)
Salmon pink mucosa (suggestive of Barrett esophagus)
Proximal migration of the gastroesophageal junction (Z
line)
Erythema, edema, friability
Erosions, mucosal breaks, ulcerations

Gold standard to evaluate GERD

Allows biopsy obtention
Allows determination of dx: Barret´s esophagus or
eosinophilic esophagitis
Describes four grades of esophagitis severity (A to D), based on
the extent of esophageal lesions known as "mucosal breaks”
 Erosive esophagitis

In a px with sx suggestive of
GERD these features indicate
erosive esophagitis
 DIAGNOSIS - ESOPHAGEAL
PH MONITORING
Indications:
Supportive findings:
Gold standard
Refractory GERD symptoms despite PPI therapy Drops in esophageal pH to 4 or less that correlate with
symptoms of acid reflux and precipitating activities.
Confirmation of suspected GERD
Procedure: Types of Reflux

Measurement of esophageal pH over 24–48 hours Acidic: pH < 4

Weakly acidic: pH 4 to 7
using a telemetry capsule or a transnasal catheter Weakly alkaline: pH >7
Documentation of relevant events by the patient
Correlation between symptoms and reflux:
Symptom index → More than 50% is considered
significant.
Symptom sensitivity index → More than 5% is
considered positive.
 DIAGNOSIS - FURTHER STUDIES
Not routinely indicated --> useful if endoscopy is inconclusive.

Esophageal barium swallow

Consider if the main symptom is dysphagia or if

there is suspicion of structural abnormalities or
motility disorders.

Esophageal manometry:

Consider if achalasia or esophageal hypermotility

disorders are suspected.
 TREATMENT
01 Lifestyle changes 03 Endoscopic treatment

02 Medication 04 Surgical treatment

 LIFESTYLE CHANGES

Losing weight.
Body posture and position during sleep → sleeping over the
left side and keeping the head elevated (10-20 cm).
Stop smoking and alcohol intake.
Avoid spicy, acidic and fatty foods, peppermint, chocolate,
condiments, coffee and soda.
Avoid lying down inmediatly after a meal.
 MEDICATION
Antiacids
Neutralize gastric acid
Symptom relief

H2 receptor antagonists
Reduce acid secretion
Tolerance development

PPIs (Proton Pump Inhibitors)

Reduce acid secretion
More powerful gastric acid secretion inhibitors

Prokinetic medications
Increases the tone of the LES, improve peristalsis and
gastric emptying

GABA agonist baclofen

Inhibits transient LES relaxations
Increases LES tone
PPIS TREATMENT
ALGORITHM
 ENDOSCOPIC TREATMENT
Stretta
Uses radiofrequency energy to improve symptoms
Increases the LES tone
Decreases the transient LES relaxations

Fundoplication procedure/EsophyX procedure

Creation of a new valve mechanism at the gastroesophageal junction by wrapping and fastening a
portion of the upper stomach around the lower esophagus
Using polypropylene tape
Helps reinforce the function of the LES
 SURGICAL TREATMENT
Fundoplication
Antireflux surgery that reinforces the LES

3 different techinques
Nissen fundoplication
Dor fundoplication
Toupet fundoplication
BARRETTS METAPLASIA TREATMENT

Dysplasia Treatment

Non-dysplastic Endoscopy every 3 years

Low grade dysplasia Endoscopy every 6 months

Endoscopic or surgical treatment

Surgery
High grade dysplasia
Endoscopic resection
→
If x treatment endoscopy every 3 months
 COMPLICATIONS

The complications could be due:

1. To the local progression of

mucosal injury (esophageal)
2. To systemic effects from
worsening reflux
(extraesophageal)

(Ravindran, A., & Iyer, P. G., 2020)

 ESOPHAGEAL
COMPLICATIONS
Erosive esophagitis:
The esophageal mucosa is injured with repeated or
long-term exposure to the acidic refluxate
cytokines and inflammatory factors
Develops inflammation
Rrosive esophagitis.
Occurs in 18% to 25% of patients with GERD
symptoms -> endoscopic diagnosis,
Some of these patients may not have symptoms of
GERD -> histologic evidence of esophageal injury
a series of events that unfold from
untreated and worsening reflux.
Esophageal strictures
(stenosis)
Narrowing of the esophagus
Occur specially in older men
Key symptom is dysphagia -> limited to solids,
decreased heartburn (since stenosis helps the
anti-reflux barrier)
Good appetite and little weight loss
Lesion characterized by a smooth,
circumferential surface, with usual location in
the distal esophagus and size less than 1 cm.
(Ravindran, A., & Iyer, P. G., 2020)
(Méndez Sánchez, 2022)
 ESOPHAGEAL a series of events that unfold from
COMPLICATIONS untreated and worsening reflux.

Erosive esophagitis: Esophageal strictures

The most common complication of GERD (stenosis)
is esophagitis

(Ravindran, A., & Iyer, P. G., 2020)

 Esophageal ulcers, hemorrhage and
esophageal perforations

Not really common in patients with GERD

Associated with severe esophagitis
Clinically significant bleeding 7% and 18% of patients
with GERD and may result in the appearance of iron
deficiency anemia

(Méndez Sánchez, 2022)

 Esophageal
Barrett’s esophagus
adenocarcinoma
Intestinal metaplasia of the esophageal 85% of esophageal adenocarcinomas occur
mucosa induced by chronic reflux. in patients with BE
Columnar epithelium instead of the
normal squamous epithelium Malignant epithelial neoplasm of the
A premalignant change → esophageal esophagus with glandular or mucinous
adenocarcinoma differentiation
Diagnosis with endoscopy

(Méndez Sánchez, 2022)

 →
Intestinal metaplasia genomic instability (often TP53 inactivation) → genome doubling and
copy number alterations →malignancy

Mutations in TP53
and SMAD4 only
identified in high
grade dysplasia
and
adenocarcinoma

The histopathology of Barrett esophagus progresses from metaplasia to

dysplasia and, without treatment, can progress to adenocarcinoma. (Méndez Sánchez, 2022)
OTHER EXTRAESOPHAGEAL
COMPLICATIONS
Clinical case
Case
Case
Case
 Bibliografía
Burriel, J. I. G. (2021). Esofagitis por reflujo, eosinofílica y otras esofagitis. Pediatría Integral, 39.

Ravindran, A., & Iyer, P. G. (2020). Gastroesophageal Reflux Disease and Complications. Geriatric Gastroenterology, 1–17.
https://doi.org/10.1007/978-3-319-90761-1_42-1

Wang, R., Wang, J., & Hu, S. (2021). Study on the relationship of depression, anxiety, lifestyle and eating habits with the severity of reflux
esophagitis. BMC gastroenterology, 21(1), 1-10.

Rosen, R. D. (2023, 17 marzo). Physiology, lower esophageal sphincter. StatPearls - NCBI Bookshelf.
https://www.ncbi.nlm.nih.gov/books/NBK557452/

Feldman, M., Friedman, L. S., & Brandt, L. J. (2020). Sleisenger and Fordtran’s Gastrointestinal and Liver Disease: Pathophysiology, Diagnosis,
Management. Elsevier Health Sciences.

Méndez Sánchez, N. (2022). Gastroenterología (4.a ed.). McGraw-Hill.

Huerta-Iga, F., Bielsa-Fernández, M., Remes-Troche, J. M., Valdovinos-Díaz, M., & La Cuesta, J. T. (2016). Diagnosis and treatment of
gastroesophageal reflux disease: recommendations of the Asociación Mexicana de Gastroenterología. Revista de Gastroenterología de
México (English Edition), 81(4), 208-222. https://doi.org/10.1016/j.rgmxen.2016.09.002

Rai, S., Kulkarni, A., & Ghoshal, U. C. (2021). Prevalence and risk factors for gastroesophageal reflux disease in the Indian population: A meta-
analysis and meta-regression study. Indian Journal Of Gastroenterology, 40(2), 209-219. https://doi.org/10.1007/s12664-020-01104-0

Lin, S., Li, H., & Fang, X. (2019). Esophageal Motor Dysfunctions in Gastroesophageal Reflux Disease and Therapeutic Perspectives. Journal Of
Neurogastroenterology And Motility, 25(4), 499-507. https://doi.org/10.5056/jnm19081
THANK
YOU
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