Benign gastric ulceration in pernicious anemia

Summary Benign gastric ulceration occurred in a patient with pernicious anemia in association with aspirin therapy. Previous reports of benign gastric ulceration in patients with achlorhydria are reviewed, and the potential role of aspirin in the pathogenesis of benign ulceration in the absence of acid is discussed.     

Somatostatin release by human gastric mucosa. Studies in peptic ulcer disease and pernicious anemia

Somatostation has been postulated to have a paracrine modulating role in gastrin and gastric acid secretion. We applied the organ culture technique to examine somatostatin release by explants of human gastric mucosa taken from patients with active duodenal ulcer, from control subjects, and from patients with pernicious anemia. Somatostatin was found to be released at a constant rate by antral explants during 3 h of incubation. In active duodenal ulcer antral and fundic 2-h somatostatin release (18.7 +/- 2.6 pg/mg tissue (means + SE), n = 75; and 27 +/- 3 pg/mg tissue, n = 94, respectively) was significantly lower than release by control antral and fundic mucosa (83 +/- 17 pg/mg tissue, n = 39, and 72 +/- 16 pg/mg tissue, n = 42, respectively) (P less than 0.01). Somatostatin release by antral and fundic mucosa of patients with pernicious anemia was also significantly decreased (20 +/- 8 pg/mg tissue, n = 12, and 7.6 +/- 2 pg/mg tissue, n = 12, respectively) (P less than 0.05). These results imply possible impairments of the paracrine release of somatostatin in peptic ulcer disease and in pernicious anemia.     

Benign gastric ulcer in a patient with pernicious anemia.

This is the report of the presence of a benign gastric ulcer in a patient with achlorhydria and documented pernicious anemia. The pernicious anemia was established by a Histalog-fast achlorhydria, a Schilling test of 2.1% excretion of tagges vitamin B12 in a 24-hr urine, and reticulocytosis after administration of cyanocobalamine. Following Histalog (1.5 mg per kg of body weight), the gastric volume was 40 ml, there was no acid, and the pH was 8.1. The ulcer demonstrated by gastroscopy was confirmed at gastrectomy. Histological examination of the ulcer and the remainder of the stomach showed no malignancy. The principal conclusion of this paper is that the patient did not have an acid-produced ulcer, but that bile regurgitation coupled with alcohol ingestion produced the lesion. Surgical investigation of the ulcer seemed mandatory because of the known increased incidence of gastric carcinoma in patients with pernicious anemia.     

Incidence and significance of the gastric mucosal constellation in pernicious anemia

1977 cases with gastric complains but without localized findings like ulcer or cancer were investigated by gastroscopy with biopsies of corpus and antrum ventriculi. We found in 5.5% an isolated mucosal atrophy of the gastric corpus (mean age 67.2 years compared to 59.4 years in cases with normal mucosa). 0.7% showed an atrophic gastritis of the antral mucosa, 0.9% an atrophic gastritis of the body and the antrum. Most of the cases with an isolated atrophy of the gastric body gave findings of hematologic disturbances. In all cases with isolated atrophy of the gastric body, including localized findings in the stomach, we found in 10.8% neoplastic processes, in another 3.9% hyperplasiogenic polyps. It seems to us of clinical importance to evaluate the gastric histology of the antral and body mucosa routinely because of the high incidence of pernicious anemia-like gastric atrophy and its relation to gastric neoplasias.     

Erythrokinetics in pernicious anemia

Quantitative measurements of the erythropoietic activity of the marrow, ofcirculating red cell production and destruction have been made in patients withpernicious anemia in relapse and during response to vitamin B₁₂ therapy.

Total erythropoietic marrow activity as reflected by turnover of heme components proceeds at a rate of approximately 3 times normal. The delivery ofviable red cells to the circulating blood, however, does not increase above normal. This would indicate that the greater portion of marrow activity is ineffective in terms of blood production. This marrow dysfunction coupled with anincreased rate of cell destruction of approximately 3 times normal is responsiblefor the anemia. Total erythropoiesis is somewhat less, and effective erythropoiesisconsiderably less, than that which may be expected of the normal marrow underthe sustained stimulus of anemia.

The reticulocyte count is shown to be an unreliable index of blood productionin untreated pernicious anemia due to loss of reticulum from cytoplasma ofmany red cells before their delivery into circulation.

During the response to vitamin B₁₂ the ineffective erythropoiesis is convertedto effective erythropoiesis, whereas total erythropoiesis remains unchanged.The rate of blood production during recovery is 3 to 4 times normal.

Submitted on January 23, 1956 Accepted on May 3, 1956     

In vitro demonstration of delayed hypersensitivity to gastric antigens in pernicious anemia

Migration inhibition of peripheral leukocytes in the presence of various human gastric antigens was looked for in 12 patients with pernicious anemia and 8 healthy controls as an indication of the presence of abnormal delayed hypersensitivity in this disease. Gastric juice antigens caused migration inhibition in 9 of 12 patients with pernicious anemia and in 1 healthy relative of a patient with pernicious anemia at doses which did not cause migration inhibition in control subjects. Fractionation of the gastric juice showed that the antigens causing migration inhibition were in both the vitamin B₁₂ binding and the nonvitamin B₁₂ binding fractions. Where the vitamin B₁₂ binding fraction had been saturated with vitamin B₁₂, migration inhibition was still seen. There was no relation between the presence of parietal cell or intrinsic factor antibodies and migration inhibition in response to gastric juice antigens. This work confirms that abnormal delayed hypersensitivity occurs in pernicious anemia and, in addition, suggests that several antigens may be involved in these reactions.Supported in part by Training Grant T01-AM-5430, Institute of Arthritis and Metabolic Diseases, and Grant HE 09011-07, National Heart and Lung Institute, National Institutes of Health.Kai Krohn, MD, was the recipient of Public Health Service International Fellowship No. 7F05 TW 1547-01.     

Gastrin and somatostatin in plasma and gastric biopsy specimens in pernicious anemia

Five patients with megaloblastic anemia due to deficiency of vitamin B12 and achlorhydria and six normal controls participated in the study. The patients with pernicious anemia (PA) had elevated plasma gastrin levels, as expected, and lower plasma somatostatin (SST) levels than the control patients. The amount of gastrin and SST in the antral mucosa did not differ in the two groups of patients. In the fundic mucosa, the patients with PA had increased tissue concentrations of both gastrin and SST as compared with the tissue concentrations in the controls. These findings of hormone tissue concentrations were correlated to the number of argyrophilic cells. Thus, in the antral mucosa the number of argyrophilic cells did not differ in patients with PA and in the controls. In the fundic mucosa, however, the number of argyrophilic cells was significantly elevated in patients with PA as compared with the controls.     

Gastric juice in pernicious anemia

Summary The physicochemical composition of the gastric juice of 16 patients suffering from pernicious anemia was determined. The study of the relationship between chloride, sodium, and alkalinity showed that gastric juice in these patients has the same characteristics as the primary alkaline secretion of a patient with a normal stomach. The stomach of a patient with Biermer's disease, from the biologic point of view, appears to be one that has been deprived of its acid (parietal cells) and peptic (chief cells) functions and, on the other hand, has retained normal glands of alkaline secretion.The values of primary alkaline secretion determined in the study reported here seem to be more realistic than those obtained mathematically by Hollander, Gray and Butcher, in dogs, and Hunt, in humans.A better knowledge of the composition of the primary alkaline secretion makes possible—without recourse to measurement of thepH or administration of large doses of histamine, which are not always tolerated in spite of the use of antihistaminics—a simple distinction between absolute achlorhydria of cellular origin, which is characteristic of Biermer's disease, and relative or chemical achlorhydria, which disappears under the influence of certain drugs that increase the concentration of acid in the gastric juice (corticoids or larger doses of histamine). In patients having so-called achlorhydric gastric juice, the two types may be distinguished, according to Töpfer, by determination of the total alkalinity of the samples taken during intubation in stages. An alkalinity curve that does not change after injection of the usual dose of histamine dihydrochloride (0.5 mg.) indicates true achlorhydria of the Biermer type, and an alkalinity curve that reflects declining values signifies chemical achlorhydria.Cellular achlorhydrias are very rare other than in Biermer's disease; of a total of 73 patients with achlorhydrias without anemia, the authors observed 5 cases, 3 associated with cirrhosis with ascites and 2, in the course of early gastritis.