Intrinsic Factor Secretion Research Articles

Gastric secretion of acid and intrinsic factor during histamine infusion in 14 cases of duodenal ulcer.

The secretion of hydrochloric acid and of intrinsic factor was studied in 14 subjects with chronic duodenal ulcer before and during six 15 minutes periods of intravenous histamine infusion. The amount of infused histamine was increased with every 15 minutes period. The volume of gastric juice increased successively during the first four periods and was maximal and equal in the last three periods of increasing histamine stimulation. The secretion of hydrochloric acid increased steadily during the increasing rate of histamine infusion, reaching a maximal and equal output in the last two periods. The concentration of intrinsic factor, however, was maximal in the first period and decreased steadily in the following periods of histamine stimulation. The output of intrinsic factor was maximal during the first three periods and decreased during the following periods in spite of increasing rate of histamine infusion. Since the volume of gastric juice was maximal and equal during the last three periods the fall in intrinsic factor concentration was more marked than the decrease in its output. The concentration of intrinsic factor in the last period was lower than basally. These results indicate that histamine causes a ‘wash‐out’ of stored intrinsic factor. The output of intrinsic factor was, however, still significantly higher than basally even 75–90 minutes after the histamine infusion had started. This could be due to a late ‘wash‐out’ mechanism or to a stimulation of intrinsic factor production and secretion.

Effect of 1-hyoscyamine on gastric secretion of acid and intrinsic factor in man.

Effect of 1-hyoscyamine on gastric secretion of acid and intrinsic factor in man.

Childhood Pernicious Anemia

Summary The secretion of acid, pepsin, and intrinsic factor was studied in 9 children having true juvenile pernicious anemia (JPA), 6 children having Imerslund's syndrome (IS) and 3 children having pernicious anemia associated with gastric atrophy (PA). Biopsies of gastric mucosa were studied using the techniques of light and electron microscopy. Instrinsic factor secretion was low in JPA and PA patients, but normal to moderately reduced in IS patients. By our own examinations, acid secretion was normal during periods of adequate vitamin B 12 therapy both in JPA and IS patients. By history, during periods of vitamin B 12 deficiency in these same patients, histamine fast achlorhydria (not augmented) was frequent. Gastric biopsies appeared normal both in JPA and IS patients, but revealed gastric atrophy in all 3 patients having achlorhydria despite their adequate vitamin B 12 replacement. No fine structural abnormalities were detected with the electron microscope. The therapeutic status correlated poorly with the histological data. Duodenojejunal biopsies appeared normal although vitamin B 12 malabsorption had been demonstrated in IS. These data offer no certain explanation of the pathogenesis of gastric atrophy in pernicious anemia of adults.

Intrinsic Factor Secretion in Response to Continuous Histamine Infusion

Summary The mode of intrinsic factor secretion following continuous intravenous infusion of 40 μg per kilogram per hour of histamine was studied in 12 subjects. Intrinsic factor was demonstrated to be secreted in two phases, an immediate relatively high secretion followed after 1 hour by a low rate constant secretion which was significantly higher than the basal rate of secretion. It is suggested that the first hour secretion may represent a washout of preformed intrinsic factor and the second hour the rate of formation of intrinsic factor. The intrinsic factor secretion following serial increases of the dose of infused histamine was studied in 5 subjects, and on each occasion a "maximal" level of secretion in the first hour was demonstrated when 40 μg per kilogram per hour were infused. A close correlation was also demonstrated between the first and second hour secretion. In 24 subjects, a close correlation has been demonstrated between the intrinsic factor secretion during the first hour and the peak acid secretion during the second hour. The relevance of these findings to the site of intrinsic factor secretion is discussed. Intrinsic factor secretion following subcutaneous and intravenous infusion of 40 μg of histamine per kilogram has been compared in 5 subjects. Subcutaneous injection was shown to produce a mean of 75% of the secretion obtained following intravenous infusion.

Quantitative Determination of Gastric Intrinsic Factor after Large Histamine Doses in Healthy Persons

Rødbro, P. & Christiansen, P. M. Quantitative Determination of Gastric Intrinsic Factor after Large Histamine Doses in Healthy Persons. Scand. J. din. Lab. Invest. 19, 186-189, 1967. In 30 healthy persons the average secretion of gastric intrinsic factor after augmented histamine stimulation was 15400±6650 ng vitamin B12 units/hour.A modification of the protein-coated charcoal assay for intrinsic factor-using a variable ratio between amounts of gastric juice and vitamin B12-is described in detail.

Intrinsic factor and gastric juice secretion induced by pentagastrin.

Intrinsic factor and gastric juice secretion induced by pentagastrin.

Tubeless gastric analysis as a tool to measure gastric secretory activity.

SummaryThis report discusses the tubeless techniques available to evaluate the capability of the gastric mucosa to secrete acid, pepsinogens, and intrinsic factor. The presence of gastric acid can be determined by proper application of the azure A ion‐exchange resin technique. Pepsinogen and intrinsic factor activity may be inferred from measurement of the urinary pepsinogens and the absorption of an oral dose of radioactive vitamin B12 with or without added intrinsic factor, respectively. A normal serum vitamin B12 level may be present in a patient with a recent failure of intrinsic factor secretion: however, a decreased level is suggestive of the absence of intrinsic factor in individuals who have no evidence for malabsorption. The value of the rapid charcoal method developed in Herbert's laboratory for measuring serum vitamin B12 is discussed.The results of the tubeless tests have clinical significance in the diagnosis of gastritis and vitamin B12 deficiency, in the management of a patient with a gastric ulcer niche, and in suggesting further studies for early detection of gastric malignancy.

Quantitative Estimation of Parietal Cell Secretory Function in Man.

With measurement of volume, acid, and intrinsic factor after maximal histamine stimulation the gastric secretory patterns in healthy persons and patients with duodenal ulcer, atrophic gastritis, and pernicious anaemia are described. In duodenal ulcer patients a higher than normal secretion of acid and intrinsic factor was found, but the secretory patterns in duodenal ulcer patients and healthy persons were identical, the essential difference being a higher secretory volume in duodenal ulcer patients corresponding to a greater but normally functioning parietal cell mass. In atrophic gastritis the gastric secretion of acid and intrinsic factor was decreased compared to that of healthy persons. The acid secretion was more reduced than the secretion of intrinsic factor, and the findings may indicate a dissociation between these parietal cell secretory components in hyposecretory states. In patients with pernicious anaemia an abolished parietal cell function was found.

Gastric intrinsic factor secretion after partial gastrectomy

Gastric intrinsic factor secretion after partial gastrectomy

Diagnostic significance of antibody to intrinsic factor.

A circulating substance present in patients with pernicious anaemia and inhibiting the action of intrinsic factor was first demonstrated independently by Schwartz (1958) and Taylor (1959). Subsequent work has confirmed that this substance has the characteristics of an antibody (Abels et al., 1963a ; Ardeman and Chanarin, 1963). Its action is thought to be specifically directed against human intrinsic factor (Ramsay and Herbert, 1965), and it is thus an autoantibody, though cross-reactions with hog intrinsic factor do occur with certain techniques (Schwartz, 1958 ; Taylor and Morton, 1959 ; Lowenstein et al., 1961 ; Gullberg and Kistner, 1963). Using a charcoal absorption technique, Ardeman and Chanarin (1963) detected antibody to intrinsic factor in 57% of patients with pernicious anaemia. Other methods, such as starch-gel electro phoresis (Jeffries et al., 1962), dialysis (Abels et al., 1963b ; Ramsey and Herbert 1965), and tests in vivo (Schwartz, 1958 ; Taylor, 1959), yield a lower proportion of positive results. Antibody to intrinsic factor has not been found in healthy control subjects (Ardeman and Chanarin, 1963 ; te Velde et al., 1964 ; Ramsey and Herbert, 1965). However, apart from its well-documented association with pernicious anaemia of the adult type, the antibody has also been found in those cases of juvenile pernicious anaemia in which histamine-fast achlorhydria and atrophie changes in the gastric mucosa are encountered (Herbert et al., 1964 ; Mclntyre et al., 1965). The antibody has not been demonstrated in those patients with juvenile pernicious anaemia who have a selective lack of intrinsic factor secretion and in whom the secretion of acid and the histology of the stomach are both normal (Mclntyre et al., 1965). The presence of antibody to intrinsic factor in 6 to 7% of patients with Graves's disease (Doniach and Roitt, 1964) emphasizes the close relationship between thyroid disease and pernicious anaemia.

Family Study in Addisonian Pernicious Anemiax

AbstractAddisonian pernicious anemia was present in 6 of 9 siblings (Generation II). All 9 siblings had evidence of gastric pathology as judged by the presence of antibodies against parietal cells, abnormalities in the gastric biopsy, and diminution of secretion of acid and intrinsic factor.Parietal cell antibodies were present in 10 of 17 offspring of these 9 siblings who were available for study. Gastric biopsy in the older members of this generation (III) showed atrophic gastritis; some of the younger members showed superficial gastritis.Loss of intrinsic factor was always accompanied by loss of gastric secreting cells and there was no evidence that decline of intrinsic factor secretion occurred independently of hydrochloric acid.

Intrinsic factor secretion in gastric atrophy.

EDITORIALSYNOPSISTheappearanceofthegastric biopsy histologically hasbeencorrelated with assayoftheintrinsic factor andacid content ofthegastric juice, andalso withvitamin B12absorption studies. Theloss ofintrinsic factor parallels theloss ofgastric secretory cells. Theassayofintrinsic factor proved a better indexofsecretory capacity ofthemucosa thaneither acidproduction or vitamin B12absorption. Theloss ofsecreting cells fromthegastric mucosa results inthedecline ofacidproduction andinsome cases inloss ofintrinsic factor ofsufficient degree toimpair vitamin B12absorption (Siurala, Eramaa, andNyberg, 1960; Glass, Speer, Nieburgs, Ishimori, Jones, Baker, Schwartz, andSmith, 1960; Whiteside, Mollin, Coghill, Williams, andAnderson, 1964). However, since normalvitamin B12absorption requires onlyabout1to2% ofthedaily intrinsic factor output(Ardeman andChanarin, 1965a), impaired absorption ofvitamin B12represents almost complete loss ofintrinsic factor secretion. Reduced secretion ofintrinsic factor withnormal vitamin B12 absorption hasbeenreported inpatients withgastric atrophy (Ardeman andChanarin, 1963; Irvine, 1965). Thepurpose ofthis paperistodescribe the

INTRINSIC-FACTOR SECRETION IN STOMACH DISEASES

INTRINSIC-FACTOR SECRETION IN STOMACH DISEASES

The Pharmacology of Intrinsic Factor Secretion in Man

Summary An in vitro technique based on the interaction between intrinsic factor and intrinsic factor antibody, was used to measure gastric intrinsic factor secretion following histamine, betazole hydrochloride, and methacholine stimulation in man. The secretion of intrinsic factor was augmented by each of these gastric secretory stimuli. The maximal secretion of intrinsic factor was observed during the first 15 min of stimulation and preceded the maximal secretion of acid and water.

Recovery of Gastric Mucosal Structure and Function in Pernicious Anemia During Prednisolone Therapy

Summary A patient with pernicious anemia was treated with prednisolone, 20 mg daily, for 4 months. During this therapy, there was a return of acid and intrinsic factor secretion, normal vitamin B 12 absorption, and a regeneration of gastric mucosal glands containing abundant chief and parietal cells. Although there was a decrease in the titer of intrinsic factor antibody in the patient's serum, there was no change in the titer of parietal cell antibodies. This steroid effect is consistent with the hypothesis that gastric mucosal atrophy in pernicious anemia is due to autoimmune destruction of the gastric glands, and that prolonged suppression of these immunologic processes may lead to mucosal regeneration with acid and intrinsic factor secretion.

STUDIES ON SECRETION OF GASTRIC INTRINSIC FACTOR IN MAN.

STUDIES ON SECRETION OF GASTRIC INTRINSIC FACTOR IN MAN.

Relationships between vitamin B6 and B12.

RELATIONSHIPS between vitamin B6 and B12 were demonstrated first of all by Hsu and Chow1, who have shown a partial impairment in the absorption of vitamin B12 of adult rats deficient in pyridoxine. This fact might be caused, at least in part, by a decrease in the secretion of gastric juice and intrinsic factor, as Yeh et al.2 had directed to our notice in B6 deficiency.

The differential diagnosis of megaloblastic anaemia.

SUMMARYIn a series of 179 adult patients with megaloblastic anæmia there were 95 cases of pernicious anæmia and 38 cases of nutritional megaloblastic anæmia. These two conditions were difficult to distinguish clinically in many instances, especially if the patient was elderly and did not have an obviously faulty diet. The estimation of serum vitamin B12 concentration and radioactive vitamin B12 absorption tests were valuable in differential diagnosis ; but there was some overlap in results in the two groups, and these tests need interpretation in the light of other clinical and laboratory findings.Fourteen patients suffered from post‐gastrectomy megaloblastic anæmia. In five, the mechanism appeared to be lack of intrinsic factor secretion, in five, nutritional deficiency of folic acid, and in four, intestinal malabsorption.

Megaloblastic and transitional megaloblastic anaemia following partial gastrectomy. Study of 27 cases.

SUMMARYStudies of nine patients with megaloblastic anæmia and 18 patients with transitional megaloblastic erythropoiesis following partial gastrectomy are reported.The 27 patients had had either gastric ulcer or duodenal ulcer and had been operated on by the Pólya or Billroth I technique. Free acid had been present in the gastric secretion before surgery in those patients on whom the test had been performed, and the histological picture of the stomach removed at operation had not resembled the gastric atrophy of Addisonian pernicious anæmia. A long latent period (average 10 years) elapsed between gastric surgery and the diagnosis of anæmia. Atrophic glossitis was detected in seven patients, and subacute combined degeneration of the spinal cord was present in two patients. Loss of weight, weakness, anorexia, fullness after eating, the “dumping” syndrome, bilious vomiting and diarrhœa were frequent symptoms after operation.The majority of the patients were shown to have subnormal levels of vitamin B12 in the serum, reduced levels of iron in the serum, impaired absorption of labelled vitamin B12 which was corrected by intrinsic factor, steatorrhœa, achlorhydria, reduced uropepsinogen excretion, atrophic gastritis and jejunitis. Considered as a group, patients with megaloblastic anæmia had lower serum levels of vitamin B12, greater degrees of anæmia and less severe iron deficiency than patients with transitional megaloblastic erythropoiesis.It is considered that the present study provides evidence that megaloblastic anæmia is not a chance association with gastrectomy, and that the relationship is causal. Megaloblastic anæmia and transitional megaloblastic erythropoiesis after partial gastrectomy are usually due to a deficiency of vitamin B12. Resection of part of the stomach which secretes intrinsic factor, together with progressive atrophy of the remaining stomach, leads to the reduced secretion of gastric intrinsic factor and so to defective absorption of vitamin B12 contained in food. Clinical vitamin B12 deficiency develops many years later.

STUDIES ON THE ABSORPTION OF VITAMIN B12

In order to investigate the secretion of intrinsic factor in patients with gastric diseases, intestinal absorption of Co60-B12 was studied by means of Schilling's urinary excretion test. Additional study was made as well on the relation between intrinsic factor secretion and the findings of the gastric mucosa as observed by gastrocamera.1. Intrinsic factor secretion was well preserved in all the patients with gastric cancer, polyp, ulcer and gastritis, with only one exceptional case of cancer. Thus it was suggested that these gastric diseases did not necessarily involve the intrinsic factor secretion.2. The exception was a case of cancer of the cardia. A slight decrease of intrinsic factor secretion was noted in this case. But the decreased output of intrinsic factor may have resulted from the tissue destruction of the cardia due to cancer. The possible spread of the cancer over other part of the stomach may account for the decrease as well.3. For detecting the atrophic changes of the gastric mucosa, gastrocamera was employed in this study. But because of its inability to differentiate gastric atrophy of pernicious anemia from the similar findings of other gastric diseases, the interpretation of whether intrinsic factor secretion is preserved or not was sometimes confused. That is, in all the patients with various gastric diseases, in whom gastric atrophic changes were observed, urinary excretions were within the normal range, while three pernicious anemia patients could not excrete normal amounts of radioactivity in the urine unless hog intrinsic factor was added.4. Some comments were made on the significance of the diagnosis of gastric atrophy as made by gastrocamera technique.5. Additional discussions were made on the relation between gastric atrophy and pernicious anemia or gastric cancer. However, further studies are needed for the clarification of the problem.