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Pathology of Pathology of The Stomach - 1The Stomach - 1

Dr.CSBR.Prasad, M.D.,

NORMAL ANATOMY

The normal gastric wall has the same layers as does the rest of the gut:

1. Mucosa:• Epithelium and • Lamina propria• Muscularis mucosae at the base

2. Submucosa3. Muscularis propria and 4. Subserosa

Mucosa has two compartments: 1-Superficial pit or foveolar

compartment 2-Deep glandular compartment

NORMAL CARDIAC MUCOSA (1:1)

CORPUS, FUNDIC MUCOSA (1:3)

ANTRAL (PYLORIC) MUCOSA (1:1)

GLANDULAR COMPARTMENT OF THE BODY MUCOSA

The pale cells: Parietal cells

Darker cells: Chief cells

NECK REGION OF THE ANTRAL MUCOSA

The pits are at the top and the glands at the base. In between, the tubules are lined by a mucus-containing epithelium with nuclei that are slightly larger than in either the pits or the glands. This is the neck region,

the proliferative zone for all gastric mucosae. The pale, pear-shaped cells with finely granular, gray cytoplasm at the base of the necks and glands are the gastrin-producing or G cells.

NORMAL ANATOMY• The Lamina Propria. The lamina propria is sparse throughout the normal

stomach. Most of the cells are smooth muscle, a few macrophages, and rare lymphocytes and plasma cells. Arterioles, venules, and capillaries are present at all levels. In contrast, lymphatics are present in the basal lamina propria

• The Muscularis Mucosae. The muscularis mucosae is a thin double layer of smooth muscle that defines the base of the mucosa and separates it from the submucosa.

• The Submucosa. This is a loose connective tissue layer containing blood vessels, lymphatics, nerves, and ganglion cells of the submucosal (Meissner) plexus; a few adipocytes;

• The Muscularis Propria. the stomach has three muscle layers: inner oblique, middle circular, and outer longitudinal. The nerves and ganglion cells of the myenteric (Auerbach) plexus are found between the outer two muscle layers.

• The Subserosa and Serosa. the stomach has a thin covering of subserosal collagen, the subserosa. The subserosa is covered by a single layer of flat mesothelium

ARTERIAL AND LYMPHATIC SUPPLY OF THE STOMACH

Acute Gastritis

• Transient mucosal inflammatory process• Erosion, ulceration, hemorrhages,

hematemesis, melena• Pathogenesis: Imbalance between

defensive and damaging forces

Acute Gastritis

Acute Gastric Ulceration

• Focal, acute, gastric mucosal defects• Specific names depending on location &

clinical association:– Stress ulcer (Shock, sepsis, trauma)– Curling’s ulcer (Burns)– Cushing’s ulcer (Intracranial disease)

Pathogenesis

NSAID-induced ulcers: cyclooxygenase inhibition

• synthesis of prostaglandinsRole of prostaglandins:

– Enhance bicarbonate secretion– Inhibit acid secretion– Promote mucin synthesis and – Increase vascular perfusion

Pathogenesis

Intracranial injury: • Stimulation of vagal nuclei

(Hypersecretion of gastric acid)• Systemic acidosis (lowers intracellular

pH of mucosal cells)• Splanchnic vasoconstriction (hypoxia,

reduced blood flow)

MorphologyGross:• Anywhere in the stomach • Multiple • Ulcers are round and < 1 cm in diameter• Base is frequently stained brown to black• Gastric rugal folds are normal• Margins and base of the ulcers are not indurated Microscopy:• Sharply demarcated, with essentially normal adjacent

mucosa • No scarring • Healing with complete re-epithelialization occurs after

the injurious factors are removed

Clinical Features

• S/S of underlying condition• Bleeding• Perforation • Out come depends on the underlying

precipitation condition

Chronic gastritisClinical features:• Nausea• Upper abdominal discomfort• VomitingCauses:• Helicobacter pylori – most common• Psychological stress• Caffeine, alcohol, tobacco• Autoimmune gastritis• Bile reflux• Radiation• Crohn’s• GVHD

HELICOBACTER PYLORI GASTRITIS

• H. pylori : spiral-shaped or curved bacilli • H. pylori –

– 90% chronic antral gastritis– 100% in duodenal ulcer

• Routes of infection:– Oral– Fecal-oral– Environmental spread

Pathogenesis

• Infection results in increased acid production

• Four features are linked to H. pylori virulence: – Flagella, Urease, Adhesins, Toxins

• Chronic antral H. pylori gastritis pangastritis multifocal atrophic gastritis

Morphology• The organism is concentrated within the superficial

mucus overlying epithelial cells• Frequently found in the antrum • Mucosa is erythematous • Inflammatory cells:

– Neutrophils Intraepithelial, pit abscesses – Subepithelial plasma cells

• Mucosa: – Thickened - initial stages – Atrophic - later stages

• Lymphoid aggregates, with germinal centers – May progress to Lymphoma

Intraepithelial neutrophils and subepithelial plasma cells are

characteristic of H. pylori gastritis

Helicobacter pylori gastritis: A, Spiral-shaped H. pylori are highlighted in this Warthin-Starry silver stain. Organisms are abundant within surface mucus. B, Intraepithelial and lamina propria neutrophils are prominent. C, Lymphoid aggregates with germinal centers and abundant subepithelial plasma cells within the superficial lamina propria are characteristic of H. pylori gastritis

Diagnosis

• Ab to H.pylori• Fecal bacterial detection• Urea breath test• Biopsy specimen:

– Rapid urease test– Culture– DNA detection by PCR

Urease breath test

AUTOIMMUNE GASTRITIS

• < 10% of cases of chronic gastritis • Spares the antrum• Hypergastrinemia

Autoimmune gastritis is characterized by:

• Antibodies to:– Parietal cells– Intrinsic factor

• Reduced serum pepsinogen I• Antral endocrine cell hyperplasia• Vitamin B12 deficiency• Achlorhydria

Pathogenesis• CD4+ T cells directed against parietal cell

components, including the H+,K+-ATPase, are the principal agents of injury

• Loss of parietal cells:– absence of acid production – hypergastrinemia and – hyperplasia of G cells

• Lack of intrinsic factor – Pernicious anemia

• no evidence of an autoimmune reaction to chief cells

Morphology

• Diffuse atrophy of gastric mucosa– body and fundus appears markedly thinned, and rugal

folds are lost • Infiltrated by lymphocytes, plasma cells• Inflammation extends deep into mucosa• Loss of parietal and chief cells• Intestinal metaplasia • Antral endocrine cell hyperplasia

– multicentric, low-grade carcinoid tumors

Gastric atrophy

Autoimmune gastritis:A, Low-magnification image of gastric body demonstrating deep inflammatory infiltrates, primarily

composed of lymphocytes, and glandular atrophy. B, Intestinal metaplasia, recognizable as the presence of goblet cells admixed with gastric foveolar

epithelium

Clinical Features • Slow onset • Median age at diagnosis is 60 yrs • May be associated with other autoimmune

diseases• Atrophic glossitis (beefy red tongue)• Peripheral neuropathy - paresthesias and

numbness • Spinal cord lesions: loss of vibration and position

sense • Cerebral manifestations: personality changes

and memory loss to psychosis

Clinical Features

HYPERPLASTIC HYPERPLASTIC GASTROPATHIESGASTROPATHIES

HYPERPLASTIC GASTROPATHIES

• The normal gastric folds or rugae are composed of cores of submucosa covered by mucosa

• The status of the folds depends, to a great extent, upon the degree of gastric distention

HYPERPLASTIC GASTROPATHIES• Unusually large folds, therefore, are defined as those

that persist even in the distended stomach • DEF:

– Radiographic large folds are those greater than 8 mm in width– Endoscopic large folds are greater than 1 cm in height

CLASSIFICATION OF GIANT FOLDS 1. Normal variant, including common gastritis 2. Menetrier's disease and variants 3. Zollinger-Ellison syndrome 4. Lymphocytic gastritis 5. Extensive or diffuse neoplastic infiltrates 6. Other causes

Menetrier's DiseaseThe full blown syndrome includes:• Giant folds • Gastric protein loss and

• Decreased gastric acid production Histologically:• Foveolar hyperplasia and distortion • Glandular atrophy and

• Edema but little inflammation, in the lamina propria

Menetrier's Disease

• There is no known cause • Excessive growth factors Clinical features:• Adults, mean age of 55 to 60 yrs• Epigastric pain• Peripheral edema due to hypoproteinemia

Menetrier's Disease - Morphology

• Enlarged folds in the gastric body and fundus

• Rougae have knobby, lobulated, or even cerebriform surfaces

• There is abundant mucus on the surface • Microscopy: florid pit hyperplasia

accompanied by atrophy of glands, superficial edema

Menetrier's Disease - Morphology

• The pits are unusually elongated• frequently extend from the surface to the

base of the mucosa• Occasionally, they penetrate the

muscularis mucosae – “gastritis cystica profunda”

• Replacement of the glandular compartment by the expanding pit compartment results in hypochlorhydria or achlorhydria

Tx – Resection: • The most common indication for

resection is the hypoproteinemia that leads to uncontrollable peripheral edema and even anasarca

Zollinger-Ellison SyndromeZollinger-Ellison Syndrome

Zollinger-Ellison Syndrome

Characterized by:• Intractable peptic ulcers involving

duodenum and jejunum, often multiple • Hypergastrinemia, usually from a gastrin-

producing tumor Typical features of ZE syndrome:• Hypergastrinemia • Parietal cell hyperplasia

Zollinger-Ellison Syndrome

Peptic Ulcer SyndromePeptic Ulcer Syndrome

Peptic Ulcer SyndromePeptic Ulcer Syndrome

Peptic ulcers are solitary lesion that can occur in any part of the GIT which is

exposed to acid-peptic juices

Acid peptic digestion[Acid & Pepsin are required for peptic ulceration]

Peptic UlcerPeptic Ulcer

Sites:• Duodenum• Stomach• GE junction• Gastrojejunostomy site• Jejunum in ZE-syndrome• Meckel’s diverticulum with gastric mucosa• At the “inlet patch” in esophagus


• Young adults / Middle age• Remitting & relapsing disease• H.pylori

Peptic Ulcer - Peptic Ulcer - PathogenesisPathogenesis

• Imbalance between mucosal defenses and damaging forces

• Acid and pepsin are required for peptic ulceration

• H.pylori infection

Peptic Ulcer - Peptic Ulcer - PathogenesisPathogenesis

• Increase in parietal cell mass• Increased sensitivity of parietal cells to

secretory stimuli• Increased basal acid secretory drive• Impaired inhibition of stimulatory

mechanisms eg: gastrin release

Peptic Ulcer - Peptic Ulcer - PathogenesisPathogenesis• NSAIDs• Smoking• Alcoholism• Corticosteroids• Rapid gastric emptying• Hyperparathyroidism• COPD• Cirrhosis• Psychosomatic disorder

Hypercalcemia due to any

cause stimulates

Gastrin production

Ischemia

Peptic Ulcer - Peptic Ulcer - MorphologyMorphology

• Duodenum – first part, anterior wall• Stomach – lesser curvature, junction of

corpus and antrum• 0.3cm (erosions) to 0.6cm (ulcers)• 50% measure >2cms

Peptic Ulcer - Peptic Ulcer - MorphologyMorphology

• Shape: Round to oval• Margins: Punched out • Edge: Overhanging • Floor: clean• Base: Firm• Depth may vary• Scarring -> puckering -> radiating mucosal

folds (like spokes)

Gastric ulcer:Elliptical shape

Radiating rugal folds (in spoke wheel pattern)

Clean floor

Punched out edges

Cross section of ulcer

BASE OF THE

ULCER

FLOOROF THE

ULCER

Peptic Ulcer - Peptic Ulcer - Microscopy

Four zones:1.Zone of exudation (thin layer of fibrinoid

necrosis)2.Zone of inflammatory cell infiltration3.Zone of granualtion tissue4.Zone of cicatrization - scarring

Blood vessels may show thickening of wall and thrombus in their lumina

Complications

• Bleeding• Perforation• Obstruction• Anemia

DD Benign & malignant ulcers

Feature Benign ulcer Malignant ulcer

Margins Punched out Heaped up / sloping

Floor Clean Necrotic debris

Surrounding mucosa

Spoke wheel pattern Ironed out

Malignant ulcer

Gastric carcinoma:Heaped up and sloping margins

Ironed out mucosa

Benign tumors

• Lipoma• Leiomyoma• Adenomas

Gastric Lipoma

Gastric leiomyoma – Massive upper GI bleeding

Gastric leiomyoma

E N DE N D

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