Autoimmune Gastritis.

This form of gastritis accounts for less than 10% of cases of chronic gastritis. It results from the presence of autoantibodies to components of gastric gland parietal cells, including

antibodies against the acidproducing enzyme H+ ,K+ -ATPase,[27] gastrin receptor, and intrinsic factor. Gland destruction and mucosal atrophy lead to loss of acid production. In the most

severe cases, production of intrinsic factor is lost, leading to pernicious anemia. This uncommon form of gastritis is seen in association with other autoimmune disorders such as Hashimoto

thyroiditis, Addison disease, and type 1 diabetes. Patients with autoimmune gastritis have a significant risk for developing gastric carcinoma and endocrine tumors (carcinoid tumor).

Morphology.

Chronic gastritis may affect different regions of the stomach and exhibit varying degrees of mucosal damage.[19] Autoimmune gastritis is characterized by diffuse mucosal damage of the

body-fundic mucosa, with less intense to absent antral damage, probably due to the autoantibodies against parietal cells. Gastritis in the setting of environmental etiologies (including

infection by H. pylori) tends to affect antral mucosa or both antral and body-fundic mucosa (pangastritis). The mucosa is usually reddened and has a coarser texture than normal. The

inflammatory infiltrate may create a mucosa with thickened rugal folds, mimicking early infiltrative lesions. Alternatively, with long-standing atrophic disease, the mucosa may become

thinned and flattened. Irrespective of cause or location, the histologic changes are similar. An inflammatory infiltrate of lymphocytes and plasma cells is present within the lamina propria

( Fig. 17-14 ). "Active" inflammation is signified by the presence of neutrophils within the glandular and surface epithelial layer.Active inflammation may be prominent or absent.

Lymphoid aggregates, some with germinal centers, are frequently observed within the mucosa. Several additional histologic features are characteristic:

• Regenerative Change. A proliferative response to the epithelial injury is a constant feature of chronic gastritis. In the neck region of the gastric glands mitotic figures are

increased. Epithelial cells of the

surface mucosa, and to a lesser extent the glands, exhibit enlarged, hyperchromatic nuclei and a higher nuclear-cytoplasmic ratio. Mucus vacuoles are diminished or absent in the

superficial cells. When regenerative changes are severe, particularly with ongoing active inflammation, distinguishing regenerative change from dysplasia may be difficult.

• Metaplasia. The antral, body, and fundic mucosa may become partially replaced by metaplastic columnar absorptive cells and goblet cells of intestinal morphology (intestinal

metaplasia),both along the surface epithelium and in rudimentary glands. Occasionally, villus-like projections may appear. Although small intestinal features predominate, in

some instances, features of colonic epithelium may be present.

• Atrophy. Atrophic change is evident by marked loss in glandular structures. Atrophy is quite frequently associated with autoimmune gastritis and pangastritis caused by H.

pylori. Parietal cells, in particular, may be conspicuously absent in the autoimmune form. Persisting glands frequently undergo cystic dilatation. A particular feature of atrophic

gastritis of autoimmune origin or chronic gastritis treated by inhibitors of acid secretion is hyperplasia of gastrin-producing G-cells in the antral mucosa. This is attributed to the

hypochlorhydria or achlorhydria arising from severe parietal cell loss. The G-cell hyperplasia is responsible for the increased gastrinemia, which stimulates hyperplasia of

enterochromaffin-like cells in the gastric body. As will be discussed later, the ECL cell hyperplasia is the frequent background for gastric carcinoid tumor formation.

• Dysplasia. With long-standing chronic gastritis, the epithelium develops cytologic alterations, including variation in size, shape, and orientation of epithelial cells, and nuclear

enlargement and atypia. Intestinal metaplasia may precede the development of dysplasia. Dysplastic alterations may become so severe as to constitute in situ carcinoma. The

development of dysplasia is thought to be a precursor lesion of gastric cancer in atrophic forms of gastritis, particularly in association with pernicious anemia (autoimmune

gastritis) and H. pylori- associated chronic gastritis.

Figure 17-14Chronic gastritis, showing partial replacement of the gastric mucosal epithelium by intestinal metaplasia (upper left) and inflammation of the lamina propria (right)

containing lymphocytes and plasma cells.

Figure 17-15Helicobacter pylori. A Steiner silver stain demonstrates the numerous darkly stained Helicobacter organisms along the luminal surface of the gastric epithelial cells. Note

that there is no tissue invasion by bacteria.

Figure 17-16Reactive gastropathy. Gastric mucosa, showing hyperplasia of foveolar surface epithelial cells, glandular regenerative changes, and smooth muscle fibers extending into

lamina propria.

Figure 17-17Diagram of causes of, and defense mechanisms against, peptic ulceration. Diagram of the base of a nonperforated peptic ulcer, demonstrating the layers of necrosis (N),

inflammation (I), granulation tissue (G), and scar (S), moving from the luminal surface at the top to the muscle wall at the bottom.

Figure 17-18Peptic ulcer of the duodenum. Note that the ulcer is small (2 cm) with a sharply punched-out appearance. Unlike cancerous ulcers, the margins are not elevated. The ulcer

base is clean. (Courtesy of Robin Foss, University of Florida, Gainesville, FL.)

TABLE 17-3-- Complications of Peptic Ulcer Disease

Bleeding

• Occurs in 15% to 20% of patients

• Most frequent complication

• May be life-threatening

• Accounts for 25% of ulcer deaths

• May be the first indication of an ulcer

Perforation

• Occurs in about 5% of patients

• Accounts for two thirds of ulcer deaths

• Rarely, is the first indication of an ulcer

Obstruction from edema or scarring

• Occurs in about 2% of patients

• Most often due to pyloric channel ulcers

• May also occur with duodenal ulcers

• Causes incapacitating, crampy abdominal pain

• Rarely, may lead to total obstruction with intractable vomiting

tumors are designated Cushing ulcers and carry a high incidence of perforation.

The genesis of the acute mucosal defects in these varied clinical settings is poorly understood. No doubt, many factors are shared with acute gastritis, such as impaired oxygenation.

NSAID-induced ulcers are related to decreased prostaglandin production from the inhibition of cyclooxygenase. In the case of lesions associated with intracranial injury, the proposed

mechanism involves the direct stimulation of vagal nuclei by increased intracranial pressure, leading to hypersecretion of gastric acid, which is common in these patients. Systemic

acidosis, a frequent finding in these clinical settings, may contribute to mucosal injury by lowering the intracellular pH of mucosal cells. These cells are also hypoxic as a consequence of

stress-induced splanchnic vasoconstriction.

Morphology.

Acute stress ulcers are usually less than 1 cm in diameter and are circular and small. The ulcer base is frequently stained a dark brown by the acid digestion of extruded blood ( Fig. 17-19 ).

Unlike chronic peptic ulcers, acute stress ulcers are found anywhere in the stomach, the gastric rugal pattern is essentially normal and the margins and base of the ulcers are not indurated.

While they may occur singly, more often there are multiple stress ulcers throughout the stomach and duodenum. Microscopically, acute stress ulcers are abrupt lesions, with essentially

unremarkable adjacent mucosa. Depending on the duration of the ulceration, there may be a suffusion of blood into the mucosa and submucosa and some inflammatory reaction.

Conspicuously absent are scarring and thickening of blood vessels, as seen in chronic peptic ulcers. Healing with complete reepithelialization occurs after the causative factors are

removed. The time required for complete healing varies from days to several weeks.

Clinical Features.

Most critically ill patients admitted to hospital intensive care units develop histologic evidence of gastric mucosal damage. Bleeding from superficial gastric erosions or ulcers sufficient to

require transfusion develops in 1% to 4% of these patients. Although prophylactic H2 -receptor antagonists and proton pump inhibitors may blunt the impact of stress ulceration, the single

most important determinant of

Figure 17-19Multiple stress ulcers of the stomach, highlighted by dark digested blood on their surfaces.

Figure 17-20Trichobezoar, showing agglomeration of hair, food, and mucus that occurred within the gastric lumen.

Figure 17-21Hypertrophic gastropathy, showing markedly thickened gastric folds.

Figure 17-22Gastric hyperplastic polyp. Low-power microscopic view of the polyp showing hyperplastic foveolar epithelium and inflammation.

Figure 17-23Gastric adenoma. Gross photograph showing a large polyp in the stomach.

Figure 17-24Inflammatory fibroid polyp; microscopic photograph showing submucosal growth of inflamed vascularized fibromuscular tissue with prominent eosinophilic infiltrate.

TABLE 17-4-- WHO Histologic Classification of Gastric Tumors

Epithelial Tumors

Intraepithelial neoplasia: adenoma

Adenocarcinoma *

••• Papillary adenocarcinoma

••• Tubular adenocarcinoma

••• Mucinous adenocarcinoma

••• Signet-ring cell carcinoma

••• Undifferentiated carcinoma

••• Adenosquamous carcinoma

Small-cell carcinoma

Carcinoid tumor

Date: 2016-04-22; view: 740