Common Pitfalls in the Management of Patients with Micronutrient Deficiency: Keep in Mind the Stomach

Micronutrient deficiencies are relatively common, in particular iron and cobalamin deficiency, and may potentially lead to life-threatening clinical consequences when not promptly recognized and treated, especially in elderly patients. The stomach plays an important role in the homeostasis of some important hematopoietic micronutrients like iron and cobalamin, and probably in others equally important such as ascorbic acid, calcium, and magnesium. A key role is played by the corpus oxyntic mucosa composed of parietal cells whose main function is gastric acid secretion and intrinsic factor production. Gastric acid secretion is necessary for the digestion and absorption of cobalamin and the absorption of iron, calcium, and probably magnesium, and is also essential for the absorption, secretion, and activation of ascorbic acid. Several pathological conditions such as Helicobacter pylori-related gastritis, corpus atrophic gastritis, as well as antisecretory drugs, and gastric surgery may interfere with the normal functioning of gastric oxyntic mucosa and micronutrients homeostasis. Investigation of the stomach by gastroscopy plus biopsies should always be considered in the management of patients with micronutrient deficiencies. The current review focuses on the physiological and pathophysiological aspects of gastric acid secretion and the role of the stomach in iron, cobalamin, calcium, and magnesium deficiency and ascorbate homeostasis.

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Nitric oxide inhibits gastric acid secretion by increasing intraparietal cell levels of cGMP in isolated human gastric glands

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00230.2005 ◽

2005 ◽

Vol 289 (6) ◽

pp. G1061-G1066 ◽

Cited By ~ 16

Author(s):

Anna Berg ◽

Stefan Redéen ◽

Magnus Grenegård ◽

Ann-Charlott Ericson ◽

Sven Erik Sjöstrand

Keyword(s):

Nitric Oxide ◽

Gastric Mucosa ◽

Acid Secretion ◽

Gastric Acid Secretion ◽

Gastric Acid ◽

Enzymatic Digestion ◽

Human Gastric Mucosa ◽

Gastric Glands ◽

Oxyntic Mucosa ◽

No Donor

We have previously identified cells containing the enzyme nitric oxide (NO) synthase (NOS) in the human gastric mucosa. Moreover, we have demonstrated that endogenous and exogenous NO has been shown to decrease histamine-stimulated acid secretion in isolated human gastric glands. The present investigation aimed to further determine whether this action of NO was mediated by the activation of guanylyl cyclase (GC) and subsequent production of cGMP. Isolated gastric glands were obtained after enzymatic digestion of biopsies taken from the oxyntic mucosa of healthy volunteers. Acid secretion was assessed by measuring [14C]aminopyrine accumulation, and the concentration of cGMP was determined by radioimmunoassay. In addition, immunohistochemistry was used to examine the localization of cGMP in mucosal preparations after stimulation with the NO donor S-nitroso- N-acetylpenicillamine (SNAP). SNAP (0.1 mM) was shown to decrease acid secretion stimulated by histamine (50 μM); this effect was accompanied by an increase in cGMP production, which was histologically localized to parietal cells. The membrane-permeable cGMP analog dibuturyl-cGMP (db-cGMP; 0.1–1 mM) dose dependently inhibited acid secretion. Additionally, the effect of SNAP was prevented by preincubating the glands with the GC inhibitor 4 H-8-bromo-1,2,4-oxadiazolo[3,4-d]benz[b][1,4]oxazin-1-one (10 μM). We therefore suggest that NO in the human gastric mucosa is of physiological importance in regulating acid secretion. Furthermore, the results show that NO-induced inhibition of gastric acid secretion is a cGMP-dependent mechanism in the parietal cell involving the activation of GC.

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Gastrin mediates the gastric mucosal proliferative response to feeding

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1996.271.3.g470 ◽

1996 ◽

Vol 271 (3) ◽

pp. G470-G476 ◽

Cited By ~ 7

Author(s):

G. V. Ohning ◽

H. C. Wong ◽

K. C. Lloyd ◽

J. H. Walsh

Keyword(s):

Acid Secretion ◽

Gastric Acid Secretion ◽

Gastric Acid ◽

Pancreatic Secretion ◽

Proliferative Response ◽

Male Rats ◽

Oxyntic Mucosa ◽

Proliferative Zone ◽

Mucosal Proliferation

The role of endogenous gastrin in oxyntic mucosal proliferation during feeding in the rat was studied by immunoneutralization with a gastrin-specific monoclonal antibody (MAb) (CURE 051091.5). The immunochemical characteristics of this antibody were characterized by competitive radioimmunoassay, and the in vivo immunoneutralizing properties were validated by measuring effects on gastric acid and pancreatic secretion. Oxyntic mucosal proliferation in response to feeding was measured in adult male rats after a 48-h fast using bromodeoxyuridine (BrdU) immunohistochemistry. Gastrin-specific MAb inhibited gastrin-17- but not pentagastrin-stimulated gastric acid secretion and had no effect on cholecystokinin (CCK)-stimulated pancreatic secretion. In contrast, a MAb specific for the common COOH-terminal pentapeptide of gastrin and CCK inhibited gastrin-17- and pentagastrin-stimulated gastric acid secretion and CCK-stimulated pancreatic secretion. Pretreatment with gastrin-specific MAb 8 h before refeeding significantly reduced by 61% the number of BrdU-labeled cells in the oxyntic mucosal proliferative zone compared with control MAb-treated rats. These results demonstrate the importance of endogenous gastrin in the proliferative response of the oxyntic mucosa to feeding in the rat.

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Neuronal nitric oxide synthase: expression in rat parietal cells

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.2001.280.2.g308 ◽

2001 ◽

Vol 280 (2) ◽

pp. G308-G313 ◽

Cited By ~ 13

Author(s):

Shyamal Premaratne ◽

Chun Xue ◽

John M. McCarty ◽

Muhammad Zaki ◽

Robert W. McCuen ◽

...

Keyword(s):

Nitric Oxide ◽

Acid Secretion ◽

Gastric Acid Secretion ◽

Gastric Acid ◽

Intracellular Signaling ◽

Nicotinamide Adenine Dinucleotide Phosphate ◽

Parietal Cells ◽

Nadph Diaphorase ◽

Rt Pcr ◽

Oxyntic Mucosa

Nitric oxide synthases (NOS) are enzymes that catalyze the generation of nitric oxide (NO) from l-arginine and require nicotinamide adenine dinucleotide phosphate (NADPH) as a cofactor. At least three isoforms of NOS have been identified: neuronal NOS (nNOS or NOS I), inducible NOS (iNOS or NOS II), and endothelial NOS (eNOS or NOS II). Recent studies implicate NO in the regulation of gastric acid secretion. The aim of the present study was to localize the cellular distribution and characterize the isoform of NOS present in oxyntic mucosa. Oxyntic mucosal segments from rat stomach were stained by the NADPH-diaphorase reaction and with isoform-specific NOS antibodies. The expression of NOS in isolated, highly enriched (>98%) rat parietal cells was examined by immunohistochemistry, Western blot analysis, and RT-PCR. In oxyntic mucosa, histochemical staining revealed NADPH-diaphorase and nNOS immunoreactivity in cells in the midportion of the glands, which were identified as parietal cells in hematoxylin and eosin-stained step sections. In isolated parietal cells, decisive evidence for nNOS expression was obtained by specific immunohistochemistry, Western blotting, and RT-PCR. Cloning and sequence analysis of the PCR product confirmed it to be nNOS (100% identity). Expression of nNOS in parietal cells suggests that endogenous NO, acting as an intracellular signaling molecule, may participate in the regulation of gastric acid secretion.

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