gastrins and Anemia

Gastric exocrine secretion, both acid and non-acid, is required for micronutrients absorption, such as iron, calcium and vitamin B12, drugs absorption, protein digestion. Clinical presentation of a gastric secretion impairment might be then characterized by the presence of both gastrointestinal and non-gastrointestinal specific symptoms (i.e. anemia) or to a non-response to therapies. The main factor that impairs gastric exocrine secretion homeostasis is mucosal chronic inflammation that principally occurs after colonization by Helicobacter pylori (Hp). The extent and distribution of gastritis ultimately determine the clinical outcome linked to differences in gastric acid secretion status, the involvement of gastric body leading to a decrease in gastric exocrine secretion with possible progression to mucosal atrophy towards cancer. A correct clinical strategy in the management of Hp infected patients should be then to early identify body involvement, a diagnosis generally missed in that body biopsies are not routinely performed. The use of gastric serological markers, gastrin and pepsinogens, are helpful in suspecting the presence of mucosal atrophy but their diagnostic accuracy for non-atrophic chronic gastritis topography is not adequate despite a good specificity due to the low sensitivity, of all the available biomarkers. Gastric serology associated to anemia/iron-deficiency screening might nevertheless been helpful in the framing of patients that undergo endoscopy in order to highlight the need of extensive mucosal biopsies sampling.

Topics: Absorption; Anemia; Biomarkers; Biopsy; Gastric Acid; Gastrins; Gastritis; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Intrinsic Factor; Micronutrients; Models, Biological; Parietal Cells, Gastric; Pepsinogens; Secretory Rate; Stomach

Topics: Anemia; Anti-Bacterial Agents; Anti-Ulcer Agents; Comorbidity; Disease Susceptibility; Drug Therapy, Combination; Duodenal Diseases; Duodenal Ulcer; Enzyme Inhibitors; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Kidney Failure, Chronic; Malabsorption Syndromes; Prevalence; Proton Pump Inhibitors; Renal Dialysis; Stomach Diseases; Stomach Ulcer; Urea

Topics: Acetazolamide; Anemia; Body Weight; Drug Synergism; Female; Gastric Juice; Gastrins; Histamine; Humans; Insulin; Male; Parathyroid Hormone; Sex Factors; Stimulation, Chemical; Thyroxine

By whole exome sequencing, we recently identified a missense mutation (p.R703C) in the human ATP4a gene, which encodes the proton pump responsible for gastric acidification. This mutation causes an aggressive familial type I gastric neuroendocrine tumor in homozygous individuals. Affected individuals show an early onset of the disease, characterized by gastric hypoacidity, hypergastrinemia, iron-deficiency anemia, gastric intestinal metaplasia and, in one case, an associated gastric adenocarcinoma. Total gastrectomy was performed as the definitive treatment in all affected individuals. We now describe the generation and characterization of a knockin mouse model for the ATP4a(R703C) mutation to better understand the tumorigenesis process. Homozygous mice recapitulated most of the phenotypical alterations that were observed in human individuals, strongly suggesting that this mutation is the primary alteration responsible for disease development. Homozygous mice developed premalignant condition with severe hyperplasia, dysplasia and glandular metaplasia in the stomach. Interestingly, gastric acidification in homozygous mice, induced by treatment with 3% HCl acid in the drinking water, prevented (if treated from birth) or partially reverted (if treated during adulthood) the development of glandular metaplasia and dysplasia in the stomach and partially rescued the abnormal biochemical parameters. We therefore suggest that, in this model, achlorhydria contributes to tumorigenesis to a greater extent than hypergastrinemia. Furthermore, our mouse model represents a unique and novel tool for studying the pathologies associated with disturbances in gastric acid secretion.

Topics: Anemia; Animals; Disease Models, Animal; Gastric Acid; Gastrins; Gene Knock-In Techniques; H(+)-K(+)-Exchanging ATPase; Homozygote; Humans; Hydrochloric Acid; Hyperplasia; Mice, Inbred C57BL; Mice, Mutant Strains; Mutation; Neuroendocrine Tumors; Phenotype; Stomach; Stomach Neoplasms

A 60-year-old patient developed signs and symptoms of glucagonoma syndrome (dermatitis, weight loss, anemia and hypoaminoacidemia). However, diabetes mellitus was absent. Glucagonoma was suspected because of markedly elevated plasma glucagon levels and the tumor was subsequently removed by surgery. Acidethanol extraction of the tumor and immunohistochemistry provided evidence of the presence of all four islet hormones, particularly that of glucagon and pancreatic polypeptide and to a lesser extent of somatostatin and insulin. Immunohistochemistry of the tumor (but not plasma) also showed the presence of alpha-HCG. Plasma glucagon immunoreactivity consisted to a large extent (approx. 90%) of a high molecular form of glucagon, probably proglucagon. In spite of the presence of alpha-HCG - which is assumed to be a marker of malignancy - the patient has been free of recurrence for the 2 1/2 years since surgery. The increasing number of cases reported during the past few years demonstrates that the syndrome is more common than previously suspected. Glucagon secretion and its typical clinical picture may be a valuable marker of a multihormonal pancreatic tumor. In a case of suspected glucagonoma, diagnosis can be established simply by obtaining a plasma glucagon level measurement.

Topics: Adenoma, Islet Cell; Anemia; Body Weight; Dermatitis; Gastrins; Glucagon; Glucagonoma; Humans; Insulin; Insulin Secretion; Male; Middle Aged; Pancreatic Neoplasms; Pancreatic Polypeptide; Secretin; Syndrome

Many alterations in metabolic and endocrine function occur in end-stage renal disease. Glucose intolerance is almost always present with uremia; it improves shortly after institution of regular hemodialysis. Hyperlipidemia (type IV) is prevalent, and atherosclerotic cardiovascular disease causes death in about 50% of patients receiving long-term hemodialysis. Although plasma levels of growth hormone usually are elevated, children with chronic renal failure show growth retardation. The occurrence of thyroid disorders is difficult to determine, since many clinical features of uremia are similar to those of hyperthyroidism and hypothyroidism. The incidence of duodenal ulcer is high, possibly due to high gastrin levels. Sex hormone disturbances are common. Anemia is a constant feature of chronic renal failure; patients usually tolerate it well.

Topics: Anemia; Blood Glucose; Gastrins; Gonadal Steroid Hormones; Growth Hormone; Humans; Hyperlipidemias; Insulin; Kidney Failure, Chronic; Renal Dialysis; Thyroid Diseases; Triglycerides; Uremia

One hundred and twelve consecutive patients selected for surgical treatment for duodenal ulcer disease were treated by a graded gastrectomy according to the Moynihan modification of the Billroth II partial gastrectomy. A large partial gastrectomy (R) (2/3-3/4 gastrectomy) was done in patients who after maximal stimulation with histamine showed a high acid output (MAO greater than 30 mEa/hr), and a small resection (r) (1/3-1/2 gastrectomy) in low secretors (MAO less than 30 mEq/hr). The material was prospectively controlled by admission to hospital at 3 months, 1 year and 5 years postoperatively. The preoperative values of MAO found in R and r were 42.8 and 21.5 mEq/hr (p less than 0.001), respectively. The postoperative MAO values at the 3-month control were 4.5 and 3.0 mEq/hr by R and r, respectively, which shows that the grading of resection had been successful. Atrophic gastritis increased in frequency from 4% at the time of operation to 72% at the 1-year control...

Topics: Adolescent; Adult; Aged; Anemia; Biopsy; Body Weight; Celiac Disease; Child; Duodenal Ulcer; Female; Folic Acid Deficiency; Follow-Up Studies; Gastrectomy; Gastric Juice; Gastric Mucosa; Gastrins; Histamine; Humans; Male; Middle Aged; Norway; Postgastrectomy Syndromes; Prospective Studies; Recurrence; Work Capacity Evaluation

Topics: Adult; Anemia; Fasting; Female; Gastrins; Humans; Immune Sera; Iodine Isotopes; Liver Cirrhosis; Male; Middle Aged; Radioimmunoassay

Topics: Anemia; Anemia, Pernicious; Duodenal Ulcer; Gastric Acidity Determination; Gastric Juice; Gastrins; Histamine; Humans; Injections; Injections, Subcutaneous; Male; Pharmacology; Physiology