Hypochlorhydria Abstracts 4

© 2011

Diagnosis and differential diagnosis of hypergastrinemia

            (Arnold 2007) Download

The most frequent conditions of hypergastrinemia in man are the Zollinger-Ellison syndrome with autonomous gastrin hypersecretion by the tumour cell and reactive hypergastrinemia in type A autoimmune chronic atrophic gastritis with achlorhydria causing unrestrained gastrin release from the gastrin-producing antral G-cells. Both entities differ with respect to the pH in the gastric fluid, which is < 2 in patients with Zollinger-Ellison syndrome and neutral in type A gastritis. Other conditions with moderate hypergastrinemia as treatment with proton pump inhibitors, gastric outlet obstruction, previous vagotomy, chronic renal failure or short bowel syndrome are of minor clinical importance.

Rebound acid hypersecretion after long-term inhibition of gastric acid secretion

            (Fossmark, Johnsen et al. 2005) Download

BACKGROUND: Rebound acid hypersecretion develops after the use of acid inhibitors. AIM: To estimate the duration of hypersecretion and to elucidate the role of the enterochromaffin-like (ECL) cell in rebound acid hypersecretion. METHODS: Patients waiting for anti-reflux surgery who had used a proton pump inhibitor daily > 1 year were included. All patients discontinued taking acid inhibiting drugs after the operation. Basal and pentagastrin stimulated acid output was measured at 4, 8, 16 and 26 weeks postoperatively. Oxyntic mucosal biopsies were collected before and 26 weeks after the operation for counting of histidine decarboxylase (HDC) immunoreactive cells. Serum chromogranin A (CgA) and gastrin were measured before and at 4, 8, 16 and 26 weeks after the operation. RESULTS: Pentagastrin stimulated acid secretion was higher at 4 and 8 weeks than at 26 weeks after the operation. Gastrin and CgA were significantly reduced at 4 and 8 weeks, respectively. The number of HDC immunoreactive cells was reduced by 60% at 26 weeks postoperative. DISCUSSION: Rebound acid hypersecretion lasts more than 8 weeks, but less than 26 weeks after long-term proton pump inhibition. CONCLUSION: The findings indicate that not only the parietal cell mass, but also ECL cell mass and activity are involved in the mechanism of acid hypersecretion.

Reducing Carcinogenic Acetaldehyde Exposure in the Achlorhydric Stomach With Cysteine

            (Linderborg, Marvola et al. 2010) Download

Background: Acetaldehyde, associated with alcohol consumption, has recently been classified as a group 1 carcinogen in humans. Achlorhydric atrophic gastritis is a well-known risk factor for gastric cancer. Achlorhydria leads to microbial colonization of the stomach. Several of these microbes are able to produce significant amounts of acetaldehyde by oxidation from alcohol. Acetaldehyde can be eliminated from saliva after alcohol intake and during smoking with a semi-essential amino acid, l-cysteine. The aim of this study was to determine whether cysteine can be used to bind acetaldehyde in the achlorhydric stomach after ethanol ingestion. Methods: Seven volunteers with achlorhydric atrophic gastritis were given either slow-release l-cysteine or placebo capsules in a double-blinded randomized trial. Volunteers served as their own controls. A naso-gastric tube was inserted to each volunteer. The volunteers ingested placebo or 200 mg of l-cysteine capsules, and ethanol 0.3 g/kg body weight (15 vol%) was infused intragastrically through a naso-gastric tube. Five-milliliter samples of gastric contents were aspirated at 5-minute intervals. Results: During the follow-up period, the mean acetaldehyde level of gastric juice was 2.6 times higher with placebo than with l-cysteine (13 vs. 4.7 muM, p < 0.05, n = 7). Conclusions: l-cysteine can be used to decrease acetaldehyde concentration in the achlorhydric stomach during alcohol exposure. Intervention studies with l-cysteine are needed on reducing acetaldehyde exposure in this important risk group for gastric cancer.

The art of measuring gastrin in plasma: a dwindling diagnostic discipline?

            (Rehfeld 2008) Download

The gastrointestinal hormone gastrin is measured in plasma in physiological, pathophysiological and diagnostic investigations. In the diagnosis of hypergastrinaemic diseases such as gastrinomas and gastric achlorhydria, measurement of gastrin concentrations in circulation is crucial. Gastrin circulates, however, not as a single peptide but as a mixture of peptides of different lengths and amino acid derivatizations. Moreover, in hypergastrinaemia the peptide pattern changes. Consequently, diagnostic gastrin measurements require immunoassays that recognize the pathological plasma patterns, which are characterized by a predominance of the large peptides (gastrin-34 and gastrin-71) and less, if any, of the shorter main form of gastrin in normal tissue, gastrin-17. Alternatively, and in specific cases, "processing-independent assays" (PIA) for progastrin may be considered, since hypersecreting gastrin cells also release substantial amounts of biosynthetic precursors and processing intermediates. Recently, gastrin kits that do not take the pathological plasma patterns into account have been marketed and may miss the diagnosis. Therefore, proper diagnosis of gastrinomas and other hypergastrinaemic diseases requires insight into cellular gastrin synthesis and peripheral metabolism, and also into the design of useful immunoassays. This review discusses the art of measuring gastrin in plasma with adequate diagnostic specificity.

Gastrin Treatment Stimulates beta-Cell Regeneration and Improves Glucose Tolerance in 95% Pancreatectomized Rats

            (Tellez, Joanny et al. 2011) Download

beta-Cell mass reduction is a central aspect in the development of type 1 and type 2 diabetes, and substitution or regeneration of the lost beta-cells is a potentially curative treatment of diabetes. To study the effects of gastrin on beta-cell mass in rats with 95% pancreatectomy (95%-Px), a model of pancreatic regeneration, rats underwent 95% Px or sham Px and were treated with [15 leu] gastrin-17 (Px+G and S+G) or vehicle (Px+V and S+V) for 15 d. In 95% Px rats, gastrin treatment reduced hyperglycemia (280 +/- 52 mg vs. 436 +/- 51 mg/dl, P < 0.05), and increased beta-cell mass (1.15 +/- 0.15 mg)) compared with vehicle-treated rats (0.67 +/- 0.15 mg, P < 0.05). Gastrin treatment induced beta-cell regeneration by enhancing beta-cell neogenesis (increased number of extraislet beta-cells in Px+G: 0.42 +/- 0.05 cells/mm(2) vs. Px+V: 0.27 +/- 0.07 cells/mm(2), P < 0.05, and pancreatic and duodenal homeobox 1 expression in ductal cells of Px+G: 1.21 +/- 0.38% vs. Px+V: 0.23 +/- 0.10%, P < 0.05) and replication (Px+G: 1.65 +/- 0.26% vs. S+V: 0.64 +/- 0.14%; P < 0.05). In addition, reduced beta-cell apoptosis contributed to the increased beta-cell mass in gastrin-treated rats (Px+G: 0.07 +/- 0.02%, Px+V: 0.23 +/- 0.05%; P < 0.05). Gastrin action on beta-cell regeneration and survival increased beta-cell mass and improved glucose tolerance in 95% Px rats, supporting a potential role of gastrin in the treatment of diabetes.

The Normal Range Of Gastric Acidity From Youth To Old Age

            (Vanzant, Alvarez et al. 1932) Download


Arnold, R. (2007). "Diagnosis and differential diagnosis of hypergastrinemia." Wien Klin Wochenschr 119(19-20): 564-9.

Fossmark, R., G. Johnsen, et al. (2005). "Rebound acid hypersecretion after long-term inhibition of gastric acid secretion." Aliment Pharmacol Ther 21(2): 149-54.

Friis-Hansen, L. (2006). "Achlorhydria is associated with gastric microbial overgrowth and development of cancer: lessons learned from the gastrin knockout mouse." Scand J Clin Lab Invest 66(7): 607-21.

Linderborg, K., T. Marvola, et al. (2010). "Reducing Carcinogenic Acetaldehyde Exposure in the Achlorhydric Stomach With Cysteine." Alcohol Clin Exp Res.

Rehfeld, J. F. (2008). "The art of measuring gastrin in plasma: a dwindling diagnostic discipline?" Scand J Clin Lab Invest 68(5): 353-61.

Tellez, N., G. Joanny, et al. (2011). "Gastrin Treatment Stimulates {beta}-Cell Regeneration and Improves Glucose Tolerance in 95% Pancreatectomized Rats." Endocrinology.

Vanzant, F., W. Alvarez, et al. (1932). "The Normal Range Of Gastric Acidity From Youth To Old Age." Arch Intern Med 49(3): 345-359.