Josie Grace Causing Castillo, MD

Gastritis and Gastropathy of Childhood

FIG. 1. Anatomic regions of the stomach. Reprinted with permission from Rudolph AM, Hoffman JIE, Rudolph CD, eds.Rudolph's Pediatrics. 20th ed. 1996, Appleton & Lange, Stanford, CT.

Copyright 2010 Journal of Pediatric Gastroenterology and Nutrition. Published by Lippincott Williams & Wilkins.

Anatomic / Gland area

Cardiac

Cell type
Mucous cells Endocrine cells

Secretory products
Mucus, pepsinogen

Fundus

Parietal cells Chief Enterochromaffin cells (ECL) G cells

G cells D cells ECL cells

Hydrochloric acid Pepsinogen Histamine, serotonin Gastrin

Gastrin Somatostatin Histamine, serotonin

Antral / pyloric

 Pathogenesis is multifactorial

Final common pathway

Action of acid and pepsin-laden contents of the stomach

on the gastric and duodenal mucosa and the inability of the mucosal defense systems to allay those effects

 Gastritis
Microscopic evidence of inflammation affecting the

gastric mucosa
Peptic ulcers
Deep mucosal lesions that disrupt the muscularis

mucosa coat of the gastric or duodenal wall

Peptic erosions
Superficial mucosal lesions that do not penetrate the

muscularis mucosa

 Primary or unexplained gastritis Caused by gastric infection with Helicobacter pylori (86%) with chronic & relapsing course Secondary gastritis or ulceration Gastric or duodenal in location Occur in association with severe stress (e.g. systemic illness, burns, head injuries), ingestion of drugs (NSAIDs, alcohol, aspirin) Crohns dse, eosinophilic gastritis Life threatening in acute phase but after healing, recovery is complete

 H. pylori is acquired in childhood, before 5 y/o

In absence of treatment, infection is lifelong

Major risk factor Poor socioeconomic conditions Unsanitary conditions Prevalence: 80% in children <10 y/o Prevalence of infection increases with age

 Transmission Fecal-oral, oral-oral, gastric-oral Human stomach only known reservoir Waterborne transmission (?) Mechanisms of disease H. pylori synthesize products that directly or indirectly damage the gastric mucosa Cause persistent inflammatory response Alter the regulation of acid secretion

 Bacterial virulence factors Motility

Presence of flagella allows movt through gastric mucus

Adherence of organism to gastric mucosa alone

Specific adhesion-receptor interaction (?)

Enzyme (urease) & toxin (VacA) production

Urease protects the organism against gastric acid Ammonia generated by urease is toxic to all mammalian cells

& thus may damage the gastric epithelium

 Host inflammatory response Stimulate interleukin-8 production which recruits & activates neutrophils & leukocytes Severity of mucosal injury is directly correlated with extent of neutrophil infiltration Gastric acid secretion Acute infection is associated with transient hypochlorhydia lasting for several months Acute hypochlorhydia facilitate transmission of infection H. pylori gastritis cause an increase in gastrin release due to depletion of somatostatin-producing D-cell density

 Symptoms Gastritis
No evidence that H. pylori gastritis in the absence of duodenal

ulcer dse cause symptoms in children

Duodenal ulcer disease
Associated with chronic & recurrent symptoms Episodic epigastric pain frequently associated with vomiting &

nocturnal awakening acute episode of hematemesis may indicate primary or secondary ulceration 80% will have symptoms that persist into adulthood

 Diagnosis
Upper GI endoscopy Gold standard for diagnosis of gastritis & PUD Endoscopic appearance of stomach correlates poorly with the presence or absence of gastritis Histologic evidence of mucosal inflammation is essential to establish a diagnosis of gastritis Biopsies of antrum & corpus, duodenum should be obtained Nodularity of antral mucosa is associated with H. pylori gastritis in children

Gastritis and Gastropathy of Childhood

FIG. 3 (A) Endoscopic view of the proximal corpus to show the striking, large, "juicy" nodules typical of chronic varioliform gastritis. Typically, these are present in the corpus and fundus and not in the antrum. (B) Chronic varioliform gastritis. The specimen is of the gastric body, which is mildly edematous and inflamed with a mixture of leukocytes, plasma cells, and eosinophils. Note in the superficial subepithelial zone, there is a layer of collagen deposition (arrows) indicative of collagenous gastritis. This is not a constant finding in chronic varioliform gastritis. Hematoxylin and eosin; magnification, 100.

Copyright 2010 Journal of Pediatric Gastroenterology and Nutrition. Published by Lippincott Williams & Wilkins.

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 Histology Warthin-Starry silver stain Giemsa stain or Cresyl violet stain Culture Routine culture is difficult due to its fastidious requirements Inoculate minced biopsy specimens in blood agar plates under microaerophilic conditions at 37C Visible colonies require 5 7 days of culture Organism is identified if (+) urease, catalase, oxidase & (-) for hippurate hydrolysis, nitrate reduction

 Urease test
Rapid test to identify H. pylori in antral mucosa
A specimen is placed on urea medium; hydrolysis of urea

leads to a color change of the medium from tan to pink Color change occurs in 30 mins 24 hrs depending on the # of bacteria present

 Urea breath test (UBT) Safe & non-invasive method 100% sensitive, 92% specific Isotopic urea is ingested by the patient; if H. pylori is present in the stomach, breakdown of the labeled urea by H. pylori urease results in the production of labeled CO2 which is measured in expired air Following treatment, UBT is 100% sensitive & specific in assessing H. pylori status Should not be carried out for at least 1 month after the completion of treatment

 Serology Infection provokes a specific serum IgG response Antibody response takes up to 60 days to develop Mean antibody levels in young children are significantly lower than in older children & adults Maximum antibody titers seen at 7 y/o Commercially available serologic tests do not have sensitivity & specificity to diagnose H. pylori in children < 12 y/o Stool antigen enzyme immunoassay (HpSA) Detect H. pylori antigen in feces 94% sensitive, 92% specific for the diagnosis of infection and in following treatment

 Treatment No evidence demonstrating a link between H. pylori gastritis & abdominal pain except in children in whom ulcers are present If infection is incidentally diagnosed, it should be treated Treatment regimens are given for 1 week Eradication rates: <90% PPI: inhibit gastric acid secretion, promoting increased effectiveness of acid-sensitive antibiotics like clarithromycin

1st line option

1

Medications
Amoxicillin Clarithromycin PPI (Omeprazole) Amoxicillin Metronidazole PPI Clarithromycin Metronidazole PPI

Dosage
50mkday BID x 14 days 15mkday BID x 14 days 1mkday BID x 1 month 50mkday BID x 14 days 20mkday BID x 14 days 1mkday BID x 1 month 15mkday BID x 14 days 20mkday BID x 14 days 1mkday BID x 1 month

 Treatment failure
Poor patient compliance
Inadequate drug delivery Antimicrobial resistance

 Stress gastritis or acute erosive gastritis

Occurs within 24 H of onset of a critical illness in which physiologic

stress is present sepsis, burns, severe head injury, multiple trauma, coagulopathy, respiratory failure 75% are asymptomatic 25% of children in PICU with macroscopic evidence of GI bleeding Presenting feature: hematemesis or melena; NO abdominal pain Pathogenesis:

Local mucosal ischemia w/ impaired blood flow cause stress erosions Increased acid & pepsin secretion Decreased gastric somatostatin levels Decreased mucus production

 Drugs & Toxins Corticosteroids

Inhibitory effect on local production of PG & gastric mucus

NSAIDs Damage the gastric mucosa directly through irritant effects Inhibit PG synthesis, adversely affecting the function of normal host mucosal defenses
Causing focal loss of surface mucus layer, inhibiting mucosal HCO3 secretion, decreasing mucosal blood flow

Alcohol Induce gastric erosions & hemorrhage

 Clinical features
Abdominal pain & upper GI blood loss
Massive hemorrhage or intestinal perforation Site & mealtime relationships of abdominal pain are

often not present Associated with high mortality

 Diagnosis Role of upper GI endoscopy is controversial Presumptive Dx can be made without direct visualization of the bleeding lesion Endoscopy is useful if the diagnosis is in doubt or if therapeutic endoscopy is considered High risk of perforation Stress gastritis multiple areas of florid inflammation with or without hemorrhage

 Treatment Stress gastritis / ulcer

H2-receptor antagonists (ranitidine/cimetidine) Mucosal protectant (sucralfate)

Drug-induced gastritis H2RAs PPIs