Achlorhydric Patients Research Articles

Plasma secretin concentrations and gastric pH in healthy subjects and patients with digestive diseases.

Plasma secretin concentrations were determined in healthy subjects and patients with duodenal ulcer, achlorhydria, and celiac sprue. Mean fasting plasma secretin concentrations in 26 healthy subjects and 26 duodenal ulcer patients were 6.7 +/- 0.5 and 10.2 +/- 1.2 pg/ml, respectively, and were significantly different (P less than 0.02). After ingestion of a standard meat meal, pyloric pH decreased to less than 4.5 within 15 min and plasma secretin concentrations significantly increased in all 52 subjects. In 14 subjects (seven healthy subjects and seven patients with duodenal ulcer), no significant rise in plasma secretin concentration occurred when pyloric pH was maintained at greater than 5.0 by intravenous cimetidine (600 mg) and intragastric antacid. In 10 achlorhydric patients, intragastric pH remained greater than 5.0 after the meal and plasma secretin concentrations did not change. However, plasma secretin concentrations increased significantly when 0.1 N HCl was infused in the stomach (25 mEq/hr) during the postprandial period. In all eight adult patients with celiac disease (seven untreated, one partially treated), pyloric pH remained less than 4.0 after a meal. Postprandial secretin concentrations did not increase significantly in six and showed a transient rise in two. These studies show that (1) plasma secretin concentration increases significantly after meals in healthy subjects and patients with duodenal ulcer; (2) neutralization of gastric acid and the achlorhydric state show no significant postprandial rise in plasma secretin concentration; (3) achlorhydric patients do not have a defect in secretin release in response to acid; and (4) failure of postprandial rise in plasma secretin in patients with celiac disease is attributed to impaired release of secretin and in achlorhydric patients it is attributed to lack of acid secretion.

Results of corrective surgery for alkaline reflux gastritis.

Reflux alkaline gastritis and esophagitis have been incriminated as a source of symptoms in achlorhydric patients afer operation for duodenal ulcer. Documentation of such pathologic findings has increased due to widespread use of fiberoptic endoscopy. As reported in the literature, results of remedial operations have ranged from encouraging to excellent, and evaluations have been uniformly laudatory. Correlation of the extent of symptoms and of pathologic findings has been difficult, and our results have not been as good as those reported in the literature. During a six-year period, the diagnosis of bile reflux gastritis in 13 patients was based on a characteristic symptom complex, endoscopic appearance, and histopathologic confirmation. Either a Roux-en-Y gastrojejunostomy or a Tanner-Roux 19 was the corrective procedure. There was complete relief of symptoms in five patients (38%) and partial relief in four, but no apparent relief in four others. In at least three of the patients, chronic gastritis and/or esophagitis have persisted and have not improved despite biliary diversion. Tabulation of the results of 13 remedial operations for reflux alkaline gastritis disclosed that copmlete relief of symptoms was achieved in 50% of those who had the Roux-en-Y and in 20% of those who had the Tanner 19 procedure. Based on our findings, we recommend a cautious approach to the surgical management of alkaline gastritis.

Parietal cell autoantibodies and hypergastrinemia in achlorhydria and the Zollinger-Ellison syndrome

Parietal cell autoantibody (PCA), basal gastrin, and calcium-stimulated gastrin were measured in twenty patients with achlorhydria, in eight patients with the Zollinger-Ellison syndrome, and in fifty control subjects. In twelve patients with achlorhydria with a spared antrum, PCA was positive and basal gastrin was elevated. In contrast, eight achlorhydric patients with antral gastritis had negative PCA and significantly lower basal gastrin levels. Patients with the Zollinger-Ellison syndrome did not demonstrate positive PCA despite elevated levels of basal gastrin, nor was PCA present in normal controls. This study suggests that certain achlorhydric states are caused by an autoimmune response, particularly if antral function is spared.

Tetracycline absorption in elderly patients with achlorhydria.

Five elderly achlorhydric patients and five controls took 250 mg tetracycline as a capsule or as an oral solution. Venous blood samples drawn during the 12-hr period following administration and urine collected for 72 hr post-dosing were assayed fluorometrically for tetracycline. There were no differences between the two groups in either rate or extent of tetracycline absorption. The mean apparent first-order rate constant (ka) for absorption of drug from capsules was 0.58 +/- 0.17 hr-1 for patients and 0.65 +/- 0.21 hr-1 for controls. The mean extent of absorption for capsule dosage forms relative to an oral solution was 1.0 +/- 0.20 for patients and 1.0 +/- 0.24 for controls. Concurrent administration of 2 gm of sodium bicarbonate to 2 of the normal subjects resulted in no impairment of either the rate or extent of tetracycline absorption from capsules, suggesting that the effect of elevated gastric pH on tetracycline bioavailability may relate to formulation.

Morphological findings of different areas of gastric mucosa in patients with achlorhydria, extreme hypochlorhydria, normochlorhydria and their relationship to serum gastrin levels: evidence for two different types of gastritis.

The morphological changes of gastric mucosa taken from different areas has been studied in patients of approximately the same age with achlorhydria, extreme hypochlorhydria and normochlorhydria. The serum gastrin level and parietal cell antibodies were determined in the achlorhydric parietal cell antibodies were determined in the achlorhydric patients. In the latter the diffuse gastritis was localized in the corpus-fundic area, while the changes in the antral region were few and occurred mostly in the superficial zone. In normochlorhydric patients however, the diffuse gastritis was localized in the antral region, with only few changes at the corpus-fundic area. In patients with extreme hypochlorhydira either the fundic or the antral region was involved. Besides the diffuse gastritis intestinal metaplasia, pseudopyloric metaplasia, and atrophy of mucosa were also observed, although much less commonly. The increase of gastrin level could not be related to a definite morphological pattern in the gastric mucosa. It can be assumed that each of the two types of gastritis has a different natural history; the antral site of gastrititis cannot be transformed into the fundic site, nor can the fundic site be transformed into the antral site.

Antral Gastrin Cells and Serum Gastrin in Achlorhydria

Forty-five patients with achlorhydria due to severe atrophic corpus gastritis or gastric atrophy were studied by determination of serum gastrin, histological examination of multiple biopsy from the antrum, and quantitation of gastrin cells revealed by an indirect immunofluorescence technique. In a reference group of 12 persons with normal gastric secretion and without atrophic antral gastritis the mean number of gastrin cells per field of vision was 52 +/- 6.5 (S.E.M.). In a group of achlorhydric patients having normal antral mucosa (n = 24), the serum gastrin levels was 324 +/- 56 pmol/l and the number of gastrin cells was 79.6 +/- 7.5 cells/field of vision. The corresponding values for a group of achlorhydric patients with chronic superficial antral gastritis (n = 11) were 361 +/- 186 pmol/l and 88.0 +/- 14.4 cells/field of vision. In a group of achlorhydric patients with atrophic antral gastritis (n = 10) serum gastrin was 15.0 +/- 3.3 pmol/l, and the number of gastrin cells was 6.2 +/- 3.3 cells/field of vision. Compared to the subjects in the reference group, the number of gastrin cells was significantly higher in the groups of achlorhydric patients with normal or superficially inflamed antral mucosa and significantly lower in achlorhydric patients with atrophic antral gastritis. It is concluded that serum gastrin in general is a good indicator for the presence or absence of antral atrophic gastritis in achlorhydria.

Serum Gastrin and Atrophic Gastritis in Achlorhydric Patients with and without Pernicious Anemia

Forty-two patients with pernicious anemia (PA) and 35 patients with achlorhydria but without PA were investigated by means of serum gastrin determination and estimation of circulating parietal cell and thyroidal autoantibodies. In 38 of the 77 patients, gastroscopic and histopathological examinations of the antral and corpus mucosa were performed. The patient groups were similar with regard to distribution of high and normal serum gastrin levels, the frequencey of autoantibodies and antrum-sparing atrophic gastritis. In the present selection of patients, therefore, the achlorhydria group was supposed to represent a precursor state of the group with PA. A minor proportion of patients with severe atrophic gastritis of the antrum as well as of the corpus mucosa was found in the two groups.

Altered serum gastrin levels in achlorhydric states

Hypergastrinemia occurs in achlorhydric states if the antrum is not diseased, and evidence has been presented that suggests that antral gastritis diminishes gastrin levels in achlorhydric patients. There is a dramatic gastrin response to calcium challenge in patients with pernicious anemia. Only minimal response was observed in patients with atrophic gastritis. Unlike the response observed in the Zollinger-Ellison syndrome, secretin challenge suppresses gastrin in achlorhydric states. These findings add a new dimension to the utility of serum gastrin determinations.

Marginal ulcer in achlorhydric patients.

Recurrent gastrojejunal ulceration is reported in three patients with histamine-fast achlorhydria. In none of these patients was extruding suture material responsible for the ulceration. However, all three patients had a history of alcohol abuse, and one abused aspirin as well. These cases demonstrate that achlorhydria does not protect against anastomotic ulceration. It is suggested that surgical manipulation produces an increased susceptibility to mucosal damage, and that it is erroneous to consider all anastomotic ulceration as a continuation or recurrence of acid peptic disease.

Effect of Atropine on Plasma Concentration of Gastrin in Fasting Subjects

Schrumpf, E. & Myren, J. Effect of atropine on plasma concentration of gastrin in fasting subjects. Scand. J. Gastroent. 1974, 9, 123–125.The effect of atropine on the basal gastrin level, acid secretion, and gastric pH in 5 normals, and also the effect of atropine on the basal gastrin level in 8 achlorhydric patients has been determined. In the normals a considerable decrease in gastric acid output was found concomitantly with an elevation of pH of the gastric juice. There was, however, no change in the gastrin concentration, demonstrating that the decrease in gastric acid output after atropine is not due to inhibition of gastrin release. In the achlorhydric patients a significant decrease in plasma gastrin concentration was observed after atropine. suggesting a cholinergic influence on basal gastrin release in these patients.

The Effect of Secretin on Plasma Concentration of Gastrin in Fasting Patients with Carcinoma of the Stomach

Schrumpf, E. & Myren, J. The effect of secretin on plasma concentration of gastrin in fasting patients with carcinoma of the stomach. Scand. J. Gastroent. 1973, 8, 479-482.The basal gastrin level in patients with gastric carcinoma and achlorhydria has been found to be not significantly different from that in achlorhydric subjects without carcinoma. A significantly smaller decrease (p<0.05) of basal plasma level of gastrin by secretin has, however, been found in 4 achlorhydric patients with gastric carcinoma than in 6 achlorhydric patients without carcinoma of the stomach, suggesting that the gastrin-producing cells in the former patients are autonomous. In 6 patients with gastric carcinoma without achlorhydria secretin caused a significant decrease in the basal gastrin level, whereas no effect of secretin was seen on the gastrin level in 8 fasting normals. In speculating about the pathogenesis of gastric carcinoma in achlorhydria, we suggest that it may be the gastrin-producing cells which turn malignant.

The functional 'G' cell mass in atrophic gastritis.

The serum gastrin response to a standard protein meal has been determined in achlorhydric patients with atrophic gastritis and contrasted with the response in normal subjects whose gastric contents were kept continuously neutral by intragastric bicarbonate instillation. Five normal subjects showed a significant increase in serum gastrin from a mean (+/- SEM) of 17 +/- 3 pg/ml to 119 +/- 10 pg/ml but their response did not approach that of four patients with atrophic gastritis and antral sparing (605 +/- 133 pg/ml to 1418 +/- 186 pg/ml). By contrast, in four patients with antral gastritis, there was no significant change in gastrin levels (24 +/- 13 pg/ml to 55 +/- 19 pg/ml). These studies indicate that the gastrin-secreting cell mass is increased in atrophic gastritis with antral sparing and decreased in atrophic gastritis with antral involvement, as compared to the normal state. They provide further evidence for the existence in man of two distinct forms of atrophic gastritis.

Gastrointestinal Findings in Autoimmune Thyroiditis and Non-Goitrous Juvenile Hypothyroidism in Children

Gastrointestinal and immunological studies were performed on 21 patients with autoimmune thyroiditis and 10 patients with non-goitrous juvenile hypothyroidism. The patients had associated diseases as follows: atopic disease (5), agamma-A-globulinaemia (4), diabetes mellitus (4) and collagen disease (3). Achlorhydria was detected in 5 patients, one of whom had a decreased serum B12 level and an abnormal Schilling test. The gastric mucosa was found to be abnormal in 12 patients, including all 5 achlorhydric patients. Gastric atrophy and atrophic gastritis were each detected in 2 patients, and the remaining 8 patients had superficial and/or interstitial gastritis. Antibodies to gastric parietal cells were detected in 8 patients. None of the patients of this series had antibodies to intrinsic factor. The malabsorption syndrome with villous atrophy was found in 3 patients.

Quantitation of Immunoglobulins in Gastric Juice by Electroimmunodiffusion

A simple method for measurement of immunoglobulin levels in gastric juice by electroimmunodiffusion is described. This method is shown to have considerable advantages over radial immunodiffusion. It has greater sensitivity, allowing quantitative measurement of levels below 2 mg per 100 ml of immunoglobulin in gastric juice. Samples which gave unsatisfactory precipitation zones on radial diffusion consistently gave clear results by electroimmunodiffusion. In contrast to previous reports, immunoglobulin has been detected consistently in the gastric juice of acid-secreting patients, but only if adequate neutralization of acid is obtained by continuous intragastric infusion of alkali. In achlorhydric patients the immunoglobulin levels were: IgA and IgG, 10 to 200 mg per 100 ml, with most concentrations in the range of 20 to 100 mg per 100 ml; and IgM, 0 to 35 mg per 100 ml. The immunoglobulin levels in acid secretors were within these ranges.

Lipolytic Activity of Human Gastric and Duodenal Juice Against Medium and Long Chain Triglycerides

The presence of lipase in gastric aspirates containing less than 3 % contamination with duodenal reflux (as determined by tests for bile acid) was demonstrated in all samples of apparently normal gastric juice from 73 subjects when assayed with a trioctanoin substrate emulsified in sodium taurodeoxycholate and buffered at p H 6. This enzyme, in contrast to lipase(s) in duodenal aspirate, was stable at p H 2, had a lower p H optimum, was rapidly inactivated by trypsin even in the presence of bile acid, and was moderately inhibited by added fatty acid. Like duodenal lipase(s), gastric lipase had greater activity against short chain than long chain triglycerides and was more active against the fatty acids in the 1 than in the 2 position of triglyceride. It had a much smaller apparent molecular weight (40,000 to 50,000) than duodenal lipase (>500,000) by gel filtration chromatography and had only moderate esterifying properties compared with duodenal lipase(s). Synthetic triglycerides were cleaved more slowly by gastric lipase than by pancreatic lipase in pancreatic fistula juice or duodenal content. Triglycerides of human milk particles were cleaved by gastric lipase and lipases present in duodenal content, but not by pancreatic fistula juice which lacked bile acid, suggesting that milk particle triglyceride is resistant to pancreatic lipase unless bile is present. In healthy adults, the concentration of gastric lipase in gastric contents was much less than that of pancreatic lipase in duodenal contents, and gastric lipase did not contribute significantly to the lipolytic activity of duodenal content after a test meal. Gastric lipase was significantly decreased in the gastric contents of 3 achlorhydric patients. Medium chain triglyceride was not cleaved by 16 hr of incubation at p H 1.8 or 1 hr of incubation at p H 1, suggesting that acid does not occur. Gastric lipase probably contributes to digestion of milk triglyceride in infants, as well as to hydrolysis of administered medium chain triglyceride, especially in children with decreased pancreatic lipase concentrations. Its limited activity against long chain triglyceride suggests that gastric lipase has little role in normal fat digestion in adults.

Total Body Counting in the Assessment of Vitamin B12: Absorption in Patients with Pernicious Anemia, Achlorhydria Without Pernicious Anemia and in Acid Secretors

Abstract The absorption of 58Co-vitamin B12 was assessed by the method of total body counting in 25 patients with frank P.A., five with latent P.A., 47 with achlorhydria but without malabsorption of vitamin B12 and 47 acid-secreting patients. A total of 192 tests was done. With or without prior stimulation of intrinsic factor secretion by pentagastrin the upper level of absorption of vitamin B12 in patients with frank or latent P.A. was 25 per cent. Taking an equivocal result to be 21-25 per cent inclusive, the total body counting method was able to distinguish P.A. patients from those with achlorhydria without P.A. with 87 per cent accuracy and one per cent error and from non-P.A. achlorhydric patients and acid secretors combined with 91 per cent accuracy and 0.5 per cent error. Pentagastrin stimulation did not improve the separation between achlorhydric patients with and without P.A. but raised the lower limit of retention of vitamin B12 from 24 to 44 per cent in the acid secreting patients. The method of total body counting is recommended as a method of assessing vitamin B12 absorption.

Influence of achlorhydria on aspirin-induced occult gastrointestinal blood loss: studies in Addisonian pernicious anaemia.

The effect of aspirin (acetylsalicylic acid) ingestion on occult gastrointestinal blood loss has been studied in patients with treated Addisonian pernicious anaemia and proved achlorhydria and in control patients able to secrete hydrochloric acid. A highly significant increase in gastrointestinal blood loss (1.9 ml./day of treatment) occurred with aspirin ingestion in the achlorhydric patients. The control group had a significantly greater increase in blood loss (4.29 ml./day of treatment). Thus aspirin can produce occult gastrointestinal blood loss by a mechanism unrelated to hydrochloric acid. Half of the control patients had losses of similar magnitude to those in the pernicious anaemia group, and the degree of blood loss in individual control patients appeared unrelated to gastric acidity. Differences in gastric mucosal characteristics, in the rate of gastric emptying, or in systemic effects of aspirin may explain the variation between individuals in the degree of occult gastrointestinal blood loss after aspirin.

Application of whole body counting to the measurement of vitamin B12 absorption with reference to achlorhydria.

hree hundred vitamin B12 (B12) absorption tests were carried out by whole body counting: sequential scanning may detect errors due to un-absorbed and unexcreted radioactivity. There was a poor correlation between two successive absorption tests in the same patient in the fasting state. The correlation improved when B12-free meals were used, particularly in controls and achlorhydric patients without pernicious anaemia (PA). Single tests in the fasting state could not always distinguish between patients with and with-without PA. No constant relationship between intrinsic factor (IF) production following histamine or pentagastrin stimulation and B12 absorption could be found in achlorhydric patients without small intestinal disease.

Determination of vitamin B 12 absorption by a simple whole body counter.

This paper reports the results of estimating vitamin B(12) absorption by whole body counting in patients without known gastrointestinal disorder, and in patients with pernicious anaemia, idiopathic achlorhydria, achlorhydria following gastric operations, and various forms of small intestinal disease. Patients with pernicious anaemia absorbed less than 30% of the test dose; they could be distinguished from patients without gastrointestinal abnormality and from most achlorhydric patients who secreted more than 300 mg units of intrinsic factor in the post-histamine hour. Nevertheless, the wide range of normal absorption and the variable absorption from the normal gastrointestinal tract is emphasized and discussed. There is no relation between histamine-stimulated intrinsic factor production and vitamin B(12) absorption in patients with small intestinal disease.

Gastric Factors Influencing Iron Absorption in Anaemic Patients

The absorption of a tracer dose of ferric citrate given to normal human subjects together with a meal was not increased when gastric juice from an anaemic patient was given simultaneously. The increase in iron absorption which occurs in achlorhydric anaemic patients when gastric juice from another anaemic patient is given appears to be due to the acid content of the gastric juice. These findings do not support the hypothesis that there is a substance in gastric juice other than acid which influences iron absorption.