Gastric acid
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221230698
2008-06-23T16:58:43Z
Gastro-en
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/* External links */ iwiki-ru
{{unreferenced|date=April 2008}}
'''Gastric acid''' is one of the main [[secretion]]s of the [[stomach]], together with several [[enzyme]]s and [[intrinsic factor]]. Chemically it is an [[acid]] [[solution]] with a [[pH]] of 1 to 2 in the stomach [[lumen (anatomy)|lumen]], consisting mainly of [[hydrochloric acid]] (HCl), and small quantities of [[potassium chloride]] (KCl) and [[sodium chloride]] (NaCl).
== Physiology ==
[[Image:Control-of-stomach-acid-sec.png|thumb|350px|right|Diagram summarising control of stomach '''acid''' secretion, emphasising interaction between the ''body'' and ''antrum''.]]
Gastric acid is produced by [[parietal cell]]s (also called oxyntic cells) in the stomach. Its secretion is a complex and relatively energetically expensive process. Parietal cells contain an extensive secretory network (called [[Canaliculus (parietal cell)|canaliculi]]) from which the gastric acid is secreted into the lumen of the stomach. These cells are part of [[epithelium|epithelial]] [[Fundic glands|fundic gland]]s in the [[gastric mucosa]]. The [[pH]] of gastric acid is 1 to 2 in the human stomach [[lumen (anatomy)|lumen]], the acidity being maintained by the [[proton pump]] [[Hydrogen potassium ATPase|H<sup>+</sup>/K<sup>+</sup> ATPase]]. The parietal cell releases [[bicarbonate]] into the blood stream in the process, which causes the temporary rise of pH in the blood, known as [[alkaline tide]].
The resulting highly acidic environment in the stomach lumen causes [[protein]]s from food to lose their characteristic folded structure (or [[denaturation (biochemistry)|denature]]). This exposes the protein's [[peptide bond]]s.The chief cells of the stomach secrete enzymes for protein breakdown (inactive pepsinogen and renin). The gastric acid activates pepsinogen into [[pepsin]] - this [[enzyme]] then helps digestion by breaking the bonds linking [[amino acid]]s, a process known as [[proteolysis]]. In addition, many [[microorganism]]s have their growth inhibited by such an acidic environment which is helpful to prevent [[infection]].
====Secretion====
The gastric acid secretion happens in several steps. Chloride and hydrogen ions are secreted separately from the cytoplasm of parietal cells and get combined into HCl only in their canaliculi. Gastric acid is then secreted into the lumen of the oxyntic gland and gradually reaches the main stomach lumen.
The highest concentration that it reaches in the stomach is 160 mM in the canaliculi. This is about 3 million times that of [[artery|arterial]] [[blood]], but almost exactly [[isotonic]] with other bodily fluids. The lowest pH of the secreted acid is about 0.8, but the acid gets diluted in the stomach [[lumen]] to the pH between 1 and 2.
At first, negative '''chloride ions''' and sodium ions get secreted actively from the [[cytoplasm]] of the parietal cell into the lumen of the canaliculus. This creates a [[Transmembrane potential difference|negative potential]] of -40 m[[volt|V]] to -70 mV across the membrane that enables the [[diffusion]] of potassium ions and a small number of sodium ions from the cytoplasm into the [[canaliculus (parietal cell)|canaliculus]].
Another step is the production of hydrogen ions in the cytoplasm of parietal cells. The enzyme [[carbonic anhydrase]] catalyses the reaction between carbon dioxide and water, in which [[carbonic acid]] is produced. This acid immediately dissociates into hydrogen ions and hydrogen carbonate ions. The '''hydrogen ions''' leave the cell by the aid of [[Hydrogen potassium ATPase|H<sup>+</sup>/K<sup>+</sup> ATPase]] [[antiporter]].
At the same time sodium ions are actively reabsorbed. This means the largest amount of secreted K<sup>+</sup> and Na<sup>+</sup> ions return into the cytoplasm. In the canaliculus, secreted hydrogen and chloride ions combine into HCl and are then secreted into the lumen of the oxyntic gland.
There are three phases in the secretion of gastric acid:
# The cephalic phase: 30% of the total gastric acid to be produced is stimulated by anticipation of eating and the smell or taste of food.
# The gastric phase: 60% of the acid secreted is stimulated by the distention of the stomach with food. Plus, digestion produces proteins, which causes even more gastrin production.
# The intestinal phase: the remaining 10% of acid is secreted when chyme enters the small intestine, and is stimulated by small intestine distention.
===Regulation of secretion===
Gastric acid production is regulated by both the [[autonomic nervous system]] and several [[hormone]]s. The [[parasympathetic nervous system]], via the [[vagus nerve]], and the hormone [[gastrin]] stimulate the parietal cell to produce gastric acid, both directly acting on parietal cells and indirectly, through the stimulation of the secretion of the hormone [[histamine]] from [[enterochromaffine-like cell]]s (ECL). [[Vasoactive intestinal peptide]], [[cholecystokinin]], and [[secretin]] all inhibit production.
The production of gastric acid in the stomach is tightly regulated by positive regulators and [[negative feedback]] mechanisms. Four types of cells are involved in this process: parietal cells, [[G cell]]s, [[D cell (biology)|D cell]]s and enterochromaffine-like cells. Besides this, the endings of the vagus nerve (X) and the intramural nervous plexus in the digestive tract influence the secretion significantly.
Nerve endings in the stomach secrete two stimulatory [[neurotransmitter]]s: [[acetylcholine]] and [[gastrin-releasing peptide]]. Their action is both direct on parietal cells and mediated through the secretion of gastrin from G cells and histamine from enterochromaffine-like cells. Gastrin acts on parietal cells directly and indirectly too, by stimulating the release of histamine.
The release of histamine is the most important positive regulation mechanism of the secretion of gastric acid in the stomach. Its release is stimulated by gastrin and acetylcholine and inhibited by [[somatostatin]].
====Neutralization====
In the [[duodenum]], gastric acid is [[neutralisation|neutralized]] by [[sodium bicarbonate]]. This also blocks gastric enzymes that have their optima in the acid range of [[pH]]. The secretion of sodium bicarbonate from the [[pancreas]] is stimulated by [[secretin]]. This [[polypeptide]] hormone gets activated and secreted from so-called [[S cell]]s in the mucosa of the duodenum and [[jejunum]] when the pH in duodenum falls below 4.5 to 5.0. The neutralization is described by the equation:
:: HCl + NaHCO<sub>3</sub> → NaCl + H<sub>2</sub>CO<sub>3</sub>
The [[carbonic acid]] instantly dissociates into [[carbon dioxide]] and [[water (molecule)|water]], then gets eliminated through [[urine]].
====Safety mechanisms====
There are several safety mechanisms that prevent the damage of [[gastric epithelium]]. Nonetheless, when due to different reasons these fail (e.g. because of excess acid production), this can lead to [[heartburn]] or [[peptic ulcer]]s.
== Role in disease ==
In [[hypochlorhydria]] and [[achlorhydria]], there is low or no gastric acid in the stomach, potentially leading to problems as the [[disinfectant]] properties of the gastric lumen are decreased. In such conditions, there is greater risk of infections of the [[digestive tract]] (such as infection with ''[[Vibrio]]'' or ''[[Helicobacter]]'' bacteria).
In [[Zollinger-Ellison syndrome]] and [[hypercalcemia]], there are increased [[gastrin]] levels, leading to excess gastric acid production, which can cause [[gastric ulcer]]s.
In diseases featuring excess vomiting, patients develop [[chlorine|hypochloremic]] [[metabolic alkalosis]] (decreased blood acidity by [[hydrogen|H]]<sup>+</sup> and [[chlorine]] depletion).
== Pharmacology ==
The proton pump enzyme is the target of [[proton pump inhibitor]]s, used to increase gastric pH in diseases which feature excess acid. H2 antagonists indirectly decrease gastric acid production. [[Antacid]]s neutralize existing acid.
== See also ==
* [[Stomach]]
* [[Digestion]]
== External links ==
* [http://www.vivo.colostate.edu/hbooks/pathphys/digestion/stomach/parietal.html The Parietal Cell: Mechanism of Acid Secretion at vivo.colostate.edu]
* [http://www.gastroresource.com/GITextbook/en/chapter6/6-3.htm First Principles of Gastroenterology. Chapter 6. ''Salena B. J., Hunt R. H.'' The Stomach and Duodenum]
{{Gastrointestinal physiology}}
[[Category:Acids]]
[[Category:Body fluids]]
[[Category:Digestive system]]
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