Gastritis and Esophagitis

Objectives:

1. Identify the risk factors for gastritis
2. Distinguish between acute and chronic gastritis
3. Compare and contrast the characteristics of autoimmune gastritis and H. pylori driven gastritis
4. Describe the different causes of oesophagitis
5. Understand the link between GERD and Barrett’s Oesophagus

Fundus/Body

surface mucous cells and deep glands with:

• Parietal cells: Hydrochloric acid, Intrinsic Factor
• Chief cells: Pepsinogen (-> Pepsin)
• Endocrine cells: Histamine, Somatostatin

Antrum

surface mucous cells and mucous glands

• Mucous-producing cells
• Endocrine cells (G cells): Gastrin

Microscopic

• Gland pits lined by Columnar mucous cells (protective)
• Deep parietal cells
• Antral mucosa has many neat circular rings of gland “tubes”

Gastritis

“Inflammation/Irritation/Swelling of the stomach”

• May damage stomach tissue

Acute Gastritis	Chronic Gastritis
short term inflammation neutrophilic infiltrate (quick response)	Long standing inflammation mononuclear cell infiltrate especially lymphocyte and macrophages

Causes:

1. Infection with H.pylori
2. Autoimmune gastritis

(rarer): Radiation, Chronic Bile reflux, Mechanical injury,

Systemic disease (Crohn’s disease, amyloidosis-protein build-up,graft-vs-host-disease)

Acute Gastritis

Scenario: Depletion in mucosal protection sys. Acid/enzyme injury to mucosal “Erosive” & “Non-erosive” Inflammation, mucosal congestion, oedema, erosion, ulceration of the gastric mucosal Increased blood supply to area (inflammation) Erosion can lead to Gastric Haemorrhage

Risk Factors/ Causes Drugs (NSAIDs) Alcohol (acute excess) Bile (reflux) Infections (Bacterial, viral or fungal) Heavy smoking Chemotherapy (radiation) Acute ill patients/ ICU trauma, sepsis, shock extensive burns (Curling’s ulcer) Neurological disease (Cushing’s ulcer) Risk factor: Cocaine

Complications

• Bleeding (haemorrhage of blood vessels)
• Perforation (into peritoneum)
• Ulcers

Non-erosive Acute Gastritis

Bacterial: H.pylori

• Infection usually acquired during childhood
• Prevalence depends on age, socioeconomic class, and country of origin
• Typically starts as an acute gastritis in the antrum
• Generally asymptomatic but as spreads can lead to chronic gastritis

Treatment

1. Discontinue use of chemicals causing problem (i.e. NSAIDs / Alcohol)
2. Antacids (to counter acidic nature – stop ulceration)
3. Proton pump inhibitors (stop production of HCl)
4. Histamine (H-2) blockers (stop production of HCl)

Chronic Gastritis

• Type I: Autoimmune gastritis (approx. 10%)
• Type II: Helicobacter gastritis (approx. 90%)
• (Type III: Chemical gastropathy NSAIDs) – rare
  • Symptoms are less severe than acute gastritis but more persistent.

Type I: Autoimmune Gastritis

Progressive immune destruction of mucosal:

1. Chronic superficial gastritis
2. Chronic atrophic (wasting of wall) gastritis
3. Gastric atrophy
4. Pernicious anaemia

• Circulating auto-antibodies (anti-GPC, intrinsic factor, proton pump)
  • Associated with other auto-immune diseases
• Inflammation and atrophy involving fundus/corpus
  • Typically spares the antrum
• Low secretion of acid +/- enzymes
  • Compensatory high serum gastrin levels
• Secretion of intrinsic factor decreased
• Associated with low serum B12/ megaloblastic anaemia & pernicious anemia

Type II: Helicobacter Pylori Gastritis
(non autoimmune in origin)

• Acid secretion often increased (however gastrin levels are generally normal)
• Distribution: Antral-predominant (lower: collection of the bacteria)
  • Can progress to multifocal atrophy (wasting)

Helicobacter Pylori

• spiral shape, flagella facilitate its passage through the mucus layer
• H. pylori then attaches to gastric epithelial cells by means of specific receptor-mediated adhesion

Epidemiology

• 90% of patients with duodenal ulcer
• 70% with gastritis/gastric ulcer (80-90% if not taking NSAIDs)

Treatment effect

(antibiotics)

• H. pylori clearance leads to ulcer healing
• High recurrence after ulcer healing without bacterial clearance

Diagnosis of H.Pylori infection

1. Blood test: Antibodies to H. pylori in blood
2. Breath test: 13C urea blood test
3. Stool test: test for foreign antigens associated with H.pylori
4. Endoscopy exam: Biopsy analysed for H. pylori infection

Type III: NSAIDs related
Inhibition of prostaglandin production

• Prostaglandins, especially those of the E class, protect against acute mucosal injury due to NSAIDs and other injurious substances by several mechanisms, including the stimulation of mucus and bicarbonate secretion, and maintenance of mucosal blood flow

Risk Factors (for NSAIDs Gastritis)

Prior history of an adverse GI event (ulcer, hemorrhage) increases risk 4-5 fold Age >60: increases risk 5-6 fold High (more than twice normal) dosage of a NSAID: increases risk 10-fold Concurrent use of glucocorticoids increases risk 4-5 fold Concurrent use of anticoagulants increases risk 10-15 fold

Patients with a history of uncomplicated or complicated peptic ulcers should be tested for H. pylori prior to beginning a NSAID or low dose aspirin.

• If present, H. pylori should be treated with appropriate therapy, even if it is believed that the prior ulcer was due to NSAIDs

Oesophagus

Muscular tube – function to move food bolus down

Layers:

• Mucosa:
  • Stratified Squamous epithelium (protection against friction)
  • Mucous secretion: moist lubricant
• Submucosa: Glands for mucous
• Muscle: Food movement
• Outer layer: peritoneum

Oesophagitis

“inflammation/Irritation/Swelling of the oesophagus”

• May damage tissue of the oesophagus

Clinical Presentation

High degree of specificity	Requires Differential Diagnosis
Dysphagia (difficulty swallowing) Heartburn Odynophagia (painful swallowing)	Chest pain Functional dyspepsia Pericarditis

Dysphagia

• Can be caused by :
  • Peptic Stricture (narrowing lumen due to inflammation of lining) / Adenocarcinoma (blockage) / Oesophagitis

Heartburn (acid “burning” of lining)

• Episodic substernal pain – worse after meals and on reclining and relieved, at least temporarily, by antacids
  • Relief by antacids is NB as links pain with acidity
• Often a burning discomfort, commonly radiates toward the mouth
  • Heartburn is frequently accompanied by complaints of a bitter taste in the mouth (regurgitation) or a welling up in the mouth of a salty tasting (salivary derived) fluid

• Substernal pain relieved by antacids recurs at east once per week over an extended period – diagnosis of gastroesophageal reflux disease (GERD).

Odynophagia

(Painful swallowing)

• Implies an acute and severe form of esophagitis, typically with mucosal ulceration.
• Odynophagiasis experienced substernally as an aching or stabbing pain that is aggravated by the act of swallowing, even swallowing saliva.

• Common in oesophagitis caused by infection, pills, and radiation but rare in oesophagitis caused by reflux (does not usually cause ulceration)

 

Investigative Procedures – Oesophagitis: Upper Endoscopy

For most upper gastrointestinal lesions

• Sensitivity (about 90%)
• Specificity (nearly 100%)
• Direct visualization
  • more accurate and sensitive evaluation of mucosal lesions
• Biopsy specimens from superficial lesions
• Perform therapeutic interventions (resection?)

Types of Oesophagitis

1. Lacerations
2. Chemical Oesophagitis
3. Infectious Oesophagitis
4. Eosinophilic Oesophagitis (Autoimmune)
5. Reflux Oesophagitis
6. Barrett Oesophagus

Lacerations (Mallory Weiss Tears)
Longitudinal tears near the gastroesophageal junction: Mucosal defect of varying range (usually involves mucosa and/or submucosa) Cause: Associated with alcoholic binges Most likely due to trauma in conjunction with failure of gastroesophageal muscular relaxation (tense)	Therapy: Usually supportive is sufficient. Complications: Mild/Moderate hemorrhage, rarely rupture (Boerhaave Syndrome)

Chemical Oesophagitis
Cause: alcohol, corrosive acids or alkalis, heavy smoking, hot fluids Children ingest Household Chemicals Pill induced oesophagitis	Kissing ulcers (opposite each other) Bleeding can occur

Infectious Oesophagitis
(Most commonly seen in immunocompromised patients) Candida (yeast) Herpes Simplex Virus (HSV) CMV

Eosinophilic (autoimmune) Oesophagitis

Uncommon, immunologically mediated entity (food allergy). Body over-responds to an allergen Common triggers: milk, soy, eggs, wheat, tree nuts. Acid reflux is not a prominent cause, with proton pump inhibitors rarely providing relief Can manifest as chest pain or heartburn, but solid food dysphagia and food impaction are characteristic. Can manifest as feeding intolerance or GERD like symptoms in children.

Histologically characterised by large numbers of intraepithelial eosinophils

Reflux Oesophagitis (GERD)
Condition in which the stomach contents (food or liquid) leak backwards from the stomach into the oesophagus. When the sphincter of muscle fibres called the lower oesophageal sphincter, or LES, doesn’t close well, food, liquid, and stomach acid can leak back into the oesophagus.	Reflux (acidic chyme) Irritates the oesophagus, causing heartburn and other symptoms (Also known as Peptic esophagitis)   Epidemiology ~ 44% of the adult population have heartburn at least once a month ~ 14% of adults have symptoms weekly ~ 7% have symptoms daily
Risk Factors Hiatal hernia Pregnancy Scleroderma (autoimmune disease of connective tissue) Obesity Cigarettes Alcohol Certain medicines: Anticholinergics, Beta blockers, Bronchodilators, Dopamine, Sedatives/anxiety meds, tricyclic antidepressants	Causes: Abnormal lower esophageal sphincter Functional (frequent transient LES relaxation) Mechanical (hypotensive LES) (Decreasing pressure of LES) Foods (eg, coffee, alcohol), Medications (eg, calcium channel blockers), Location : hiatal hernia (upper part of stomach squeezes up through diaph.) (Increased abdominal pressure) Obesity Pregnancy Increased gastric volume

Because the primary barrier to gastroesophageal reflux is the lower esophageal sphincter (LES)

• LES normally works in conjunction with the diaphragm
  • Weakness in diaphragm → lower pressure of LES
• If barrier disrupted, acid goes from stomach to esophagus

Diagnosis

Upper endoscopy – erosions, ulcers, stricturesor Barrett’s oesophagus

Esophageal biopsy – basal cell hyperplasia, oedema or inflammatory findings

 

Esophageal pH monitoring: the “gold standard” for identifying acid reflux, is performed by fixing a small pH probe in the oesophagus, 5 cm above the LES, and recording all episodes in which esophageal pH drops to less than 4 over a 24- to 48-hour period

GERD diagnosis

preferred method for establishing GERD as the cause of symptoms (e.g., chest pain, wheezing) is an empirical trial of acid suppression with a PPI (e.g.omeprazole, 20 mg twice daily),

• which normalizes esophageal acidity in approximately 95% of subjects
• Symptoms improve with PPI (evaluative condition)

GERD Complications

1. Erosive oesophagitis
   1. Responsible for 40-60% of GERD symptoms
   2. Severity of symptoms often fail to match severity of erosive esophagitis

1. Esophageal stricture (narrowing of lumen due to scarring of epithelium)
   1. Result of healing of erosive oesophagitis
   2. May need dilation

1. Barrett’s Esophagus
   1. Intestinal metaplasia of the esophagus
   2. Associated with the development of
   3. Adenocarcinoma

(difference between GERD and Barrett’s is that GERD is a range of effects due to reflux whilst Barrett’s is the change in the cells type – abnormal growth – genetic instability → cancer prone)

Barrett’s Esophagus

Acid damages lining of esophagus and causes chronic oesophagitis

• Damaged area heals in a metaplastic process and abnormal columnar cells replace squamous cells
• This specialized intestinal metaplasia can progress to dysplasia (permanent change) and adenocarcinoma

(The risk of cancer in Barrett’s esophagus is estimated to be 40 to 100 times)

Endoscopic surveillance is recommended for all patients with Barrett’s esophagus. Endoscopy is performed every 2 years, and biopsies are taken from the area of abnormal mucosa.

• If the biopsies reveal low-grade dysplasia, then the frequency of endoscopies is increased.
• If high-grade dysplastic changes are seen and confirmed by a second pathologist, then the risk of subsequent adenocarcinoma is greater than 25%, and surgical resection should be considered.

Treatment of GERD

The goals of treatment are to relieve symptoms and prevent relapse and complications.

• All patients should be advised about lifestyle modifications that help reduce symptoms and prevent relapse. (food/medication)

• Antacids or antacid-alginate combinations are recommended for safe, prompt, inexpensive relief of heartburn.

Lifestyle modifications	Medication
Elevate the head of the bed 6 inches Stop smoking Stop excessive alcohol consumption Reduce dietary fat Reduce meal size Avoid bedtime snacks Lose weight (if overweight) Avoid: chocolate, carminatives (spearmint, peppermint), coffee (caffeinated and decaffeinated),tea, cola beverages, tomato juice, citrus fruit juices	Antacids H2 Blockers – Examples of histamine antagonists available Cimetidine (Geramet and Tagamet), Famotidine (Pepcid), Ranitidine (Zantac, Pylorid and Gertac). PPI Tx options – Esomeprazole (Nexium), Omeprazole (Losec), Pantoprazole (Protium)