GERD

GERD

Gastroesophageal Reflux Disease

By

Ahmed Abudeif Abd ElaalResident in tropical medicine & gastroenterology department

2009

Definitions:

Gastroesophageal Reflux (GER): Escape of gastric contents into the esophagus. This process may or may not produce symptoms.

Reflux esophagitis: Esophageal inflammation caused by the refluxed material.

Gastroesophageal Reflux Disease (GERD): Any symptomatic condition or anatomic alteration caused by the reflux of noxious material from the stomach into the esophagus.

Pathogenesis of GERD

Pathogenesis of GERD:

A)Antireflux mechanisms.

B) Gastric Factors.

C) Esophageal Clearance Mechanisms.

D) Esophageal Epithelial Resistance.

A) Antireflux Mechanisms:

Normally, there is a positive pressure gradient between the abdomen and the thorax that tends to promote the reflux of material from the stomach into the esophagus. In the absence of effective antireflux mechanisms this pressure differential would result in continuous gastroesophageal reflux.

1) Lower Esophageal Sphincter (LES)

It is a 1-3.5 cm segment of specialized circular muscle in the wall of distal esophagus.

It maintains a resting pressure of 10-45 mmHg higher than that of the stomach.

Types of LES dysfunction:

1) Intrinsic weakness of the LES muscle:

The resting pressure in the LES remains at or near 0.

Responsible for > 25% of reflux episodes in patients with severe GERD.

2) Inadequate LES response to increased abdominal pressure.

3) Transient LES relaxation (TLESR):

Normally, the LES relaxes for 3-10 seconds to allow the swallowed bolus to enter the stomach.

TLESR is not preceded by swallowing & lasts for up to 45 seconds.

It is responsible for 70% of reflux episodes in patients with severe GERD.

Incompetent LES

2) Crural Diaphragm

When the crural diaphragm contract e.g. inspiration the crurae come together & pinch the distal esophagus.

3) Anatomic Features:

a) The oblique angle of insertion of the esophagus into the stomach (angle of His).

b) The circular muscle fibers of the fundus encircle the lower end of the esophagus.

c) The presence of an intraabdominal segment of the esophagus.

d) The mucosal rosette of the upper end of the stomach forming a plug to the lower end of the esophagus.

B) Gastric Factors:

1) Irritant potency of the refluxed material

Esophageal injury occurs when the refluxed material is caustic to the esophageal mucosa.

Caustic agents that can be found in the stomach include acid, pepsin, bile & pancreatic enzymes.

2) Delayed gastric emptying

It causes gastric distention that can stimulate gastric acid secretion & trigger TLESR.

Causes:

1- Pyloric channel or duodenal ulcers.

2- Mechanical obstruction e.g. by tumour.

3- Neuromuscular abnormalities e.g. DM, collagen diseases, hypothyroidism, …

C) Esophageal Clearance Mechanisms:

The esophagus is cleared of acid by 4 mechanisms:

1)Gravity.

2) Peristalsis.

3) Salivation.

4) Intrinsic esophageal bicarbonate production.

Impaired esophageal clearance can occur in:

Sleep: due to

1) Elimination of the effect of gravity.

2) Salivation & swallowing cease during sleep “no peristalsis due to absent swallowing”.

Scleroderma: due to impaired peristalsis.

Cigarette smoking: due to decreased salivation.

Hiatus hernia.

D) Esophageal Epithelial Resistance:

a) Pre-epithelial defenses:

1) Mucous layer:

Acts as a lubricant & a protective barrier against noxious &irritant luminal contents.

2) Unstirred water layer:

Lies under the mucous layer & its rich in bicarbonate.

It provides a protective alkaline microenvironment.

b) Post-epithelial defenses.

Diagnosis of GERD

A) Clinical Presentation

1) Heartburn (Pyrosis):

Substernal burning sensation radiating to the chest sometimes to the throat or the back.

The pain is usually relieved by ingestion of antacids. within 5 minutes

The pain is aggravated by

- Ingestion of foods that decrease the LES pressure as chocolate, onions, peppermint, coffee, tea & foods that have a high content of fat & sugar.

- Ingestion of foods that irritate the esophageal mucosa directly as spicy foods, citrus products and tomato products.

- Practices that increase the intraabdominal pressure e.g. bend over, lift a heavy object, strain to defecate or run.

2) Regurgitation:

Reflux of sour or bitter material into the mouth usually at night, when lying down or bending over.

It suggests severe reflux.

3) Dysphagia:

Difficulty in swallowing.

Usually indicates narrowing or stricture of the esophagus.

It may occur due to inflammation & oedema.

4) Odynophagia:

Pain on swallowing.

It suggests the presence of esophageal ulceration.

5) Water brash:

Filling of the mouth suddenly with saliva.

Its due to reflex salivary secretion stimulated by acid in the esophagus.

6) Chest pain:

Resembles anginal pain.

This pain may result from:

• Acid induced irritation of the nerve endings.

• GER-induced esophageal spasm.

• GER-induced angina pectoris.

7) Haemorrhage

8) Pulmonary symptoms:

e.g. chronic cough, hoarseness of voice, wheezing, haemoptysis, asthma & recurrent aspiration pneumonia.

The above manifestations may be due to aspiration or vagus mediated neural reflexes.

9) Nighttime GER may cause:

Sleep apnoea.

Poor sleep.

Insomnia.

Daytime sleepiness.

B) Diagnostic tests:

Indications:

1) Patients with atypical signs or symptoms.

2) Patients with typical signs & symptoms that don’t respond well to acid suppression.

1) Endoscopic examination:

EGD identifies the presence and severity of esophagitis and the possible presence of Barrett’s esophagus

More sensitive than radiology for diagnosis of esophagitis & biopsy can be taken from any abnormal areas.

Endoscopic evidence of esophagitis is present in 50-70% of patients with typical history of GERD so a normal EGD (NERD) doesn’t exclude GERD.

GradGradee

DescriptionDescription

AAOne or more mucosal breaks no longer than 5 mm, none of which extends between the tops of the mucosal folds.

BBOne or more mucosal breaks more than 5 mm long, none

of which extends between the tops of two mucosal folds.

CCMucosal breaks that extend between the tops of two or more mucosal folds, but which involve less than 75% of the esophageal circumference.

DDMucosal breaks which involve at least 75% of the esophageal circumference.

The Los Angeles Classification System for the The Los Angeles Classification System for the endoscopic assessment of grade of esophagitisendoscopic assessment of grade of esophagitis

The Los Angeles Classification System for the The Los Angeles Classification System for the endoscopic assessment of grade of esophagitisendoscopic assessment of grade of esophagitis

GRADE A: One or more mucosal breaks

no longer than 5 mm, non of which extends between the tops of the mucosal folds

The Los Angeles Classification System for the The Los Angeles Classification System for the endoscopic assessment of grade of esophagitisendoscopic assessment of grade of esophagitis

GRADE B:GRADE B:

One or more mucosal One or more mucosal breaks more than 5 breaks more than 5 mm long, none of mm long, none of which extends between which extends between the tops of two mucosal the tops of two mucosal foldsfolds

The Los Angeles Classification System for the The Los Angeles Classification System for the endoscopic assessment of grade of esophagitisendoscopic assessment of grade of esophagitis

GRADE C:GRADE C:

Mucosal breaks that extend Mucosal breaks that extend between the tops of two or between the tops of two or more mucosal folds, but more mucosal folds, but which involve less than 75% which involve less than 75% of the oesophageal of the oesophageal circumferencecircumference

The Los Angeles Classification System for the The Los Angeles Classification System for the endoscopic assessment of grade of esophagitisendoscopic assessment of grade of esophagitis

GRADE D:GRADE D:

Mucosal breaks which Mucosal breaks which involve at least 75% of involve at least 75% of the oesophageal the oesophageal circumferencecircumference

The Los Angeles Classification System for the The Los Angeles Classification System for the endoscopic assessment of grade of esophagitisendoscopic assessment of grade of esophagitis

Savary-Miller Classification of esophagitis

Grade I: Single or multiple erosions are found on a single fold; erosions may be erythematous or exudative.

Savary-Miller Classification of esophagitis

Grade II: Multiple erosions affect multiple folds.

Savary-Miller Classification of esophagitis

Grade III: Multiple circumferential erosions.

Savary-Miller Classification of esophagitis

Grade IV: Ulcer, stricture, and esophageal shortening.

Savary-Miller Classification of esophagitis

Grade V: Barrett’s epithelium.

2) Barium swallow:

Can reveal:

a)Signs of esophagitis including:

1- Thickening of the esophageal folds.

2- Erosions.

3- Ulcerations.

4- Strictures.

b) GER of barium.

Disadvantages:

1) Less sensitive than endoscopy for demonstrating esophagitis.

2) Biopsy specimens can't be taken.

3) Ambulatory monitoring of esophageal pH:

Its used to document the pattern, frequency & duration of acid reflux & to seek correlation between reflux episodes & symptoms.

Normally, esophageal pH remains below 4 for less than 4.5% of the 24-hour monitoring period.

Acid reflux episode: a drop in esophageal pH below 4 & the total Reflux episodes exceed 5% of the total monitoring time.

4) Acid perfusion (Bernstein) test:

It has been used to support acid reflux as the cause of symptoms.

The esophagus is perfused with 0.1 N HCl. Reproduction of chest pain with acid perfusion implicates GERD as a cause of chest pain.

5) Histology:

Histological changes of esophagitis:

1) Lengthening of the papillae so that they occupy more than 2/3 of the thickness of the squamous mucosa.

2) Hyperplasia of cells in the basal zone so that it occupies more than 15% of the mucosal thickness.

3) Infiltration of the epithelium with eosinophils & PMNLs.

Treatment of GERD

A)Medical Treatment:

a) Lifestyle Modifications.

b) Pharmacologic Therapy:

1) H2 blockers

2) Proton Pump Inhibitors.

3) Antacids.

4) Prokinetic Drugs.

5) Sucralfate.

B) Antireflux Surgery.

C) Endoscopic Antireflux Procedures.

A)Medical Treatment:

a) Lifestyle Modifications:

1) Elevation of the head of the bed by 4-6 inch blocks or 6 inch foam-rubber wedge in place of or under the pillow.

2) Weight loss for obese patients.

- Obesity increase the intraabdominal pressure.

3) Avoid:

a) Smoking

- It decrease LES pressure & salivation.

b) Alcohol

- It decrease LES pressure.

c) Fatty meal, chocolate, onion, tea, coffee & carminatives.

- They decrease LES pressure & delay gastric emptying.

d) Spicy foods, citrus & tomato products.

- They cause direct irritation of the esophageal mucosa.

e) Drugs that decrease LES pressure & delay gastric emptying as Ca++ channel blockers, nitrates, drugs that have anticholinergic effects “e.g. phenothiazines, TCA”, theophylline preparations, progesterone & benzodiazepines.

4) Encourage small frequent meals, the evening meal should be light & easy to digest.

5) No eating 3 hours prior to sleep.

- Bed time snacks stimulate gastric acid secretion & trigger TLESR.

b) Pharmacologic Therapy:

1) H2 Blockers:

These drugs block the effect of histamine on H2 receptors which is present normally in gastric mucosa, vascular smooth muscle & the heart.

They reduce the basal, food stimulated & nocturnal secretion of gastric HCl.

Usually effective in controlling symptoms of mild to moderate GER & heal esophagitis (grade I,II) within 12 weeks in about ½ to 2/3 of patients.

DrugIndicationDoseDuration

Cimetidine- Erosive esophagitis diagnosed by endoscopy.

- 800 mg BDS or 400 mg QDS

- 12 w

Famotidine- Short term ttt of symptoms.

- Esophagitis due to GERD including erosive or ulcerative disease diagnosed by endoscopy

- 20 mg BDS

- 20-40 mg BDS

-6 w

- 12 w

Nizatidine- Esophagitis due to GERD. including erosive or ulcerative disease & associated heartburn.

- 150 mg BDS- 12 w

Ranitidine- Treatment of symptoms.

- Esophagitis due to GERD including erosive or ulcerative disease diagnosed by endoscopy

-150 mg BDS

- 150 mg QDS

No limit specified

2) Proton Pump Inhibitors (PPIs):

These drugs inhibit parietal cell proton pump (H+ K+ - ATPase).

Proton pump is responsible for extrusion of H+ into the gastric lumen in exchange of K+ which is the final step in gastric acid production.

PPIs are effective in control of symptoms & signs of GERD, heal erosive esophagitis & diminish formation of esophageal strictures.

PPIs improves dysphagia & decrease the need for esophageal dilatation in patients who have esophageal strictures.

PPIs are effective if taken 15-30 minutes before breakfast or dinner.

Drugs of this group include:

- Omeprazole 20 mg - 40 mg.

- Lansoprazole 15 mg – 30 mg.

- Rapeprazole 20 mg.

- Pantoprazole 20 mg – 40 mg.

- Esomeprazole 20 mg – 40 mg.

- Omeprazole NaHCO3 20 mg – 40 mg.

Side effects of PPIs:

- Headache, nausea & vomiting.

- Diarrhoea & Clostridium difficile colitis.

- Theoretically, they may cause gastric bacterial overgrowth, vitamin B12 & iron malabsorption & gastric cancer. However, there is no clinical support.

- Hypocalcaemia (give Ca++ supplements as Ca++ citrate).

3) Antacids:

Antacids may be aluminum, magnesium, or calcium based

Antacids neutralize the acid in the stomach so that there is no acid to reflux.

Antacids emptied from the empty stomach quickly so they should be given an hour after meal to prolong their duration of action.

Effective in controlling mild symptoms of GERD.

4) Prokinetic Drugs:

These agents act by:

a) Increasing LES pressure.

b) Enhancing gastric & esophageal emptying.

Examples:

1) Metoclopramide HCl.

2) Domperidone.

3) Mosapride citrate.

1) Metoclopramide HCl:

- Dopamine antagonist, centrally acting antiemetic.

- Its effective in treatment of mild disease.

- It crosses BBB so, it has many central side effects.

Side effects:

Agitation, restlessness, somnolence, anxiety, insomnia, extrapyramidal manifestations & galactorrhoea.

2) Domperidone:

- Dopamine antagonist & produce effects similar to metoclopramide.

- Unlike metoclopramide it doesn’t cross BBB so there is no central side effects.

3) Mosapride citrate:

- 5-HT4 receptor agonist & partial 5-HT3 antagonist.

- Unlike cisapride it doesn’t block K+ channels so no cardiac toxicity will occur, also doesn’t block D2 receptors, so there is no extrapyramidal manifestations.

5) Sucralfate:

- An aluminum sucrose polysulfate.

- Effective in treatment of mild reflux esophagitis.

- It is efficacy is comparable to that of H2 blockers.

B) Antireflux Surgery:

There are a number of different antireflux operations (e.g. Nissen, Belesy, Toupet fundoplication).

The most popular is Nissen fundoplication (open or laparoscopic).

Nissen fundoplication

Principle of antireflux surgery:

The surgeon

1) Creates an intraabdominal segment of esophagus.

2) Reduces the hiatal hernia.

3) Approximates the diaphragmatic crurae.

4) Wraps a portion of gastric fundus around the distal esophagus.

- There is relief of symptoms & signs in > 85% of patients.

- Antireflux surgery was associated with a significant decrease in long term survival so it should be restricted to:

1) Patients who no longer need to take antisecretory medications.

2) The procedure will prevent esophageal cancer

C) Endoscopic Antireflux Procedures:

The Bard endoscopic suturing system:

This system uses an endoscopic sewing machine device to plicate the esophagogastric junction from the mucosal side.

The Stretta system:

The Stretta system delivers radiofrequency energy that creates thermal lesions in the LES muscle.

Injection of collagen circumferentially at the LES.

Complications of GERD

1) Esophageal Stricture:

Peptic strictures form when reflux induced ulceration stimulates fibrous tissue production & collagen deposition in the esophagus.

Up to 11% of patients with GERD seem to develop strictures.

Factors predisposing to stricture formation:

- Prolonged GER.

- Reflux while supine.

- Nasogastric intubation.

- Duodenal ulcer disease.

- Gastric hypersecretory states.

- Postgastrectomy states.

- Scleroderma.

- Treated achalasia.

Site of esophageal stricture:

- Usually in the distal 1/3 of the esophagus.

- In some cases of Barrett’s esophagus the stricture is located in the middle or less commonly in the proximal 1/3 of the esophagus.

Clinical Picture:

- Esophageal stricture produce no symptoms until the esophageal intraluminal diameter < 12 mm.

- Typically there is a slowly progressive dysphagia initially for solids & later on for liquids.

- Profound weight loss is uncommon.

Investigations:

a)Barium Swallow:

- Peptic strictures have a smooth tapered appearance.

- More sensitive than endoscopy for demonstrating subtle esophageal narrowing.

b) Endoscopy:

- Endoscopic examination with biopsy & brush cytology of the esophagus is necessary to exclude cancer.

Treatment:

- Intensive medical treatment with PPIs both improves dysphagia & decreases the need for esophageal dilatation.

- Progressive dilatation with:

• Mercury filled rubber bougies.

• Savary-Gillard dilators.

• Balloons that can be inflated within the stricture.

- Surgical treatment, usually combined with an antireflux operation.

- Resection with esophageal reconstruction using a segment of bowel in cases of intractable stricture.

B) Barrett’s Esophagus:

- A condition in which a metaplastic columnar epithelium replaces squamous epithelium in the distal esophagus.

- Barrett’s esophagus is a strong risk factor for adenocarcinoma of the esophagus & gastroesophageal junction.

- It is usually discovered in middle aged & older adults. However its found in children as young as 5 years.

- Barrett’s esophagus predominates in white males. Its uncommon in blacks & asians.

Histology:

Any of 3 types of columnar epithelia can be found in Barrett’s esophagus.

1) Gastric fundic type epithelium.

2) Junctional type epithelium.

3) Specialized intestinal metaplasia “Specialized columnar epithelium”.

- Dysplasia & carcinoma are associated with intestinal metaplasia.

Diagnosis

Clinical Picture:

- The Barrett’s epithelium causes no symptoms.

- Most patients have symptoms of GERD, the GERD associated with Barrett’s esophagus often is severe & associated with esophageal ulceration, stricture & haemorrhage. However, many patients have no symptoms of GERD.

- Cancer risk is about 0.5% annually.

Endoscopy:

- Columnar epithelium can be recognized by it’s characteristic red colour & velvet like texture that contrast sharply with the pale glossy appearance of the adjacent squamous epithelium.

- According to the length of the lining columnar epithelium Barrett’s esophagus can be classified into:

- Short segment Barrett’s esophagus: intestinal metaplasia lines < 3 cm of the distal esophagus.

- Long segment Barrett’s esophagus: intestinal metaplasia lines > 3 cm of the distal esophagus.

- Long segment Barrett’s esophagus is associated with high risk for developing adenocarcinoma.

Management

• Patients with Barrett’s esophagus should undergo surveillance endoscopy & biopsy at an interval determined by the presence & grade of dysplasia:

• For patients with no dysplasia, surveillance endoscopy is recommended at an interval of every 2-3 years.

• For patients with low grade dysplasia, surveillance endoscopy every 6 months for the 1st year is recommended, followed by yearly endoscopy if the dysplasia hasn’t progressed in severity.

• For patients with high grade dysplasia 2 options are available:

1) Intensive endoscopic surveillance until intramucosal cancer is detected.

2) Esophageal resection.

- GERD should be treated aggressively prior to surveillance endoscopy to minimize confusion caused by inflammation in the interpretation of biopsy specimens.

Refractory GERD

Refractory GERD: patients who continue to have symptoms of gastroesophageal reflux despite standard treatment with proton pump inhibitors (PPIs).

Patients who experience refractory GERD usually fall into one of two groups:

- Those who need more aggressive treatment

- Those who have other causes of their reflux symptoms

1) Inadequate response to PPIs

Factors contributing to inadequate PPI response:

1) Nocturnal Acid Breakthrough (NAB)

2) Reduced bioavailability

3) Effect of food and dosing interval

4) Differences in metabolism

5) Gastric acid hypersecretion

6) Helicobacter pylori status

7) Drug resistance, slow healing

Nocturnal Acid Breakthrough (NAB)

Nocturnal acid exposure while on PPI.

Responsible for majority of patients with refractory GERD.

May be reduced by H2 blockers and by increasing PPI dose.

Sometimes difficult to eliminate.

Reduced Bioavailability

Bioavailability of PPI influenced by environmental and manufacturing conditions.

For most patients, difference in bioavailability are not clinically significant.

Effect of food and dosing interval

Administration 15-30 min prior to meals improve gastric acid suppression.

PPI usually given once daily and sometimes twice daily improve gastric acid suppression.

Differences in metabolism

PPI metabolized through the CYP 2C.

CYP 2C absent:

- 3% of Caucasian patients.

- In more than 10% in Asians.

Gastric acid hypersecretion

Patients with BAO > 10mEq/h may predisposed to refractory GERD.

Helicobacter pylori status

Role not established in refractory patients.

Helicobacter pylori infection may protect the esophagus from GERD & its complications perhaps by decreasing gastric acidity.

No evidence that eradication exacerbates GERD.

Drug Resistance

Resistance is a rare condition caused by mutations of the proton pump.

Patients can be treated by H2 blockers.

2) Other causes of reflux symptoms

Other Causes Of Reflux Symptoms:

1) Other pathological situations.

2) Esophageal hypersensitivity.

3) Non acid reflux.

Other Pathological Situation

1) IBS and dyspepsia with overlap syndrome.

2) Atypical GERD (cough, asthma, NCCP).

3) Achalasia.

4) Cancer or stricture.

5) Caustic and Infectious esophagitis.

6) NSAID (more susceptibility to acid related E disease).

Esophageal Hypersensitivity

There is hypersensitivity to physiologic acid reflux (visceral hyperalgesia).

Patients have heartburn but without endoscopic or pH evidence of GERD.

Treatment:

Acid suppressive therapy and low dose antidepressants

Non Acid Reflux

Mixed acid and bile refluxate (more aggressive than acid alone).

Duodenogastroesophageal reflux (DGER): in patients with gastric surgery.

Treatment of Refractory GERD

Medical treatment

-Give PPI twice daily.

-PPI dose before dinner may reduce NAB.

-PPI 15-30 min before meals.

- Stepwise increase dose of PPI to achieve adequate acid suppression (an increase in dose of Omeprazole to 80 mg/ day→ significant decrease in acid secretion (Vs 20 mg bid) (pH <4: 33% Vs 74%).

- Addition of a nighttime dose H2 blockers to control NAB.

- H2 blockers not as effective as PPI for maintenance therapy.

- Switching to another PPI for patients refractory to one PPI ( rare mutations in the PP induce resistance).

- Effectiveness of adding prokinetic drug not established.

- Add Baclofen (GABA-B agonist ):

• Effective to treat GERD with chronic cough.

• Inhibits TLESR.

• With Esomeprazole both decrease total acid and non acid reflux.

Endoscopic treatment

Surgical treatment