Acute gastritis is an acute self-limiting syndrome caused by irritation of the gastric mucosa by alcohol, corrosive poisons, and the various bacterial and oral causes of food poisoning. It is characterized by anorexia, nausea and vomiting. In some patients, the same causal agents produce acute ulcers that may bleed or perforate. The role of analgesics is not clear.

Three main types of gastritis are recognized by histological examination: superficial gastritis, atrophic gastritis and gastric atrophy. Chronic gastritis is characterized by mononuclear and polymorphonuclear cell infiltration of mucosa, glandular atrophy and intestinal metaplasia. In superficial gastritis inflammation is marked and glandular atrophy is minimal, whereas in gastric atrophy inflammatory cells are few and glandular atrophy is extensive. These represent different degrees of gastritis, though not necessarily all cases that progress to atrophy must be preceded by the two lesser lesions.

With progressive degeneration of the mucosa, gastric secretion progressively fails. Hydrochloric acid secretion fails first, followed by pepsinogen secretion and finally by the secretion of intrinsic factor. As intrinsic factor secretion fails, the body becomes depleted of vitamin B₁₂ and pernicious anemia develops. Antibodies to parietal cells and intrinsic factor appear in the serum. The presence of these antibodies together with a partial response to steroids suggests that autoimmunity may play an etiologic role.

The cause of chronic gastritis is unknown, but it is probably due to a combination of genetic and acquired factors (Table 7). Among the latter may be included repeated minor trauma due to alcohol and analgesics, reflux of duodenal contents and gastric irradiation. Deficiencies of vitamin B₁₂, folic acid and iron interfere with the regenerative and functional capacity of the gastric mucosa.

Predisposition to gastric cancer is probably due to an unknown biochemical lesion within the cell that leads to secretory failure, cellular degeneration and in some cases gastric carcinoma. While most of the causes of hypochlorhydria are associated with gastritis, it remains disputed whether gastritis is necessarily associated with an increased risk of gastric cancer. Gastric cancer is 5 to 10 times as common as expected in those with chronic atrophic gastritis; the same increased incidence is also found in first-degree relatives of patients with gastric cancer and pernicious anemia.

It is uncertain whether chronic gastritis causes symptoms. Chronic gastritis can be diagnosed only by gastric biopsy of body or fundic mucosa. Marked gastric hyposecretion or anacidity is present if the lesion is diffuse.

6.2.1 COMPLETE GASTRIC ATROPHY AND PERNICIOUS ANEMIA

There are many causes of hypochlorhydria (Table 8). The ability to produce acid, pepsin and intrinsic factor is lost altogether in patients with complete gastric atrophy. However, vitamin B₁₂ deficiency - which leads to pernicious anemia or (much more rarely) to subacute combined degeneration of the spinal cord - takes several years to supervene because of the large liver stores of the vitamin. In the complete atrophy of pernicious anemia, gastric glandular and all parietal cells are lost, and the mucosa is infiltrated by large numbers of plasma cells and lymphocytes. Pentagastrin stimulation will demonstrate that the patient is achlorhydric. Studies will demonstrate antibodies to intrinsic factor and to parietal cells in serum, gastric secretions and mucosa in most patients. Though the presence of such antibodies is a useful marker, it is not diagnostic: intrinsic factor antibodies can be demonstrated occasionally (and parietal cell antibodies frequently) in patients with simple atrophic gastritis or chronic superficial gastritis without vitamin B₁₂ malabsorption.

Hydroxocobalamin has replaced cyanocobalamin for the treatment of pernicious anemia, because it is better retained in the body. A dose of 100 µg by injection every month is more than sufficient to maintain body stores after loading treatment with 200 µg on three alternate days.

6.2.2 CONGENITAL PERNICIOUS ANEMIA

Congenital pernicious anemia is a rare condition, inherited as a Mendelian recessive, and is due to an inherited inability to secrete intrinsic factor in adequate amounts. It presents as megaloblastic anemia in infancy and is associated with normal acid secretory potential. The specific failure of intrinsic factor synthesis in this condition must be distinguished from congenital ileal receptor deficiency for the vitamin B₁₂-intrinsic factor complex (the Imerslund-Graesbeck syndrome) and from vitamin B₁₂ deficiency due to gastric failure in the hypoparathyroidism-candidiasis syndrome.

The cause of pernicious anemia is unknown. The presence of autoantibodies, mucosal infiltration by plasma cells and reversibility of the gastric lesion by corticosteroids suggest an autoimmune process. There is also a small but definite genetic predisposition; like gastric cancer, the disease is slightly more common in individuals of group A than in those of the remaining ABO groups. Exogenous factors that predispose to gastric cancer also seem likely to predispose to pernicious anemia. It is unclear why most patients present with pernicious anemia while a few develop the neurological condition of subacute degeneration of the spinal cord without anemia.

In this form of gastritis, inflammatory cells, mainly polymorphonuclear, infiltrate the superficial mucosa but gastric glands are well preserved. It has been found with increased frequency in those who smoke excessively or who consume large amounts of alcohol or hot beverages. No specific symptom pattern has been correlated with it, and it does not seem necessarily to predispose to gastric atrophy. Chronic superficial gastritis is commonly found in patients with chronic gastric ulcer, but is not a universal concomitant.

With chronic atrophic gastritis, in addition to cellular infiltration, predominantly lymphocytic and plasma cell in pattern, there is a loss of gastric glands, and acid and pepsin secretory capacity is reduced in parallel. It does not cause symptoms, but in a minority of patients there is progression to the complete atrophy of pernicious anemia. Patients with atrophic gastritis probably develop eventual gastric cancer approximately as often as those with pernicious anemia.

Giant mucosal rugal hypertrophy is a histologic change occurring in association with the Zollinger-Ellison syndrome and rarely as an isolated entity. Ménétrier's disease (giant hypertrophic gastritis), a rare condition associated with mucosal hypertrophy, involves reduced acid secretion. Hypertrophic-hypersecretory gastropathy, another associated condition, involves increased acid secretion. In giant mucosal rugal hypertrophy, as a result of protein loss into the gastric lumen, the serum albumin concentration will be reduced. The condition usually occurs in males between the ages of 30 and 50, and the patient will present with pain, nausea, vomiting, weight loss, bleeding, or edema as a result of hypoalbuminemia. The condition is suspected from the presence of large rugal folds identified on upper GI series or at endoscopy. A biopsy will demonstrate hyperplasia of the parietal, chief and mucus cells. There may be cystic structures in the mucosa and submucosa as well. The condition must be distinguished from giant hypertrophic gastritis, the Zollinger-Ellison syndrome, gastric carcinoma, lymphoma and amyloidosis (Table 9).   The protein loss may be reduced with anticholinergics. If gastric hypersecretion occurs, as in the case of hypertrophic-hypersecretory gastropathy, H₂ blockers will prove useful. If pain, bleeding and protein loss persist, then a vagotomy and pyloroplasty or subtotal gastrectomy is necessary.

Chronic inflammatory changes in the gastric mucosa may occur in Crohn's disease, tuberculosis, syphilis and sarcoidosis, and granulomas may be present. These diseases are all uncommon.

The cause of eosinophilic gastritis is unknown. There is extensive infiltration of the gastric and often the small intestinal mucosa by eosinophils, in association with peripheral eosinophilia. The disease produces nonspecific dyspeptic symptoms, and antral distortion is radiographically visible. Spontaneous cure is common, but some patients require steroid therapy and in a few the disease is progressive.

The common occurrence of gastritis following gastric surgery is thought to be due to the effect of bile and alkaline duodenal secretion damaging the gastric mucosal barrier and giving rise to an inflammatory reaction. Some patients will respond to medical treatment with cholestyramine, aluminum hydroxide or sucralfate. Cholestyramine and aluminum hydroxide act by binding bile acids and pepsin, and providing a protective surface to the gastric mucosa. When the condition persists and is associated with pain or bleeding, a surgical procedure (Roux-en-Y) will be necessary.

There are two forms of gastritis that fall outside the classifications listed above. One is intestinal metaplasia, where a large number of cells with the histochemical properties of intestinal mucosal cells are found in the stomach. This is commonly associated with chronic gastritis. The second is Ménétrier's disease or giant hypertrophic gastritis, where the giant mucosal folds may be confused with neoplastic disease (Table 9); excess protein loss from the folds may cause a syndrome of protein depletion (protein-losing enteropathy). Erosive gastritis and hyperplastic atrophic gastritis are less well defined entities.