Examine individual changes

'{{More citations needed|date=March 2022}}{{Short description|Digestive fluid formed in the stomach}} [[File:Determinants of Gastric Acid Secretion.svg|alt=Determinants of Gastric Acid Secretion|thumb|Determinants of gastric acid secretion]] '''Gastric acid''', '''gastric juice''', or '''stomach acid''' is a digestive fluid formed within the [[gastric mucosa|stomach lining]]. With a [[pH]] between 1.5 and 3, gastric [[acid]] plays a key role in digestion of [[protein]]s by activating [[digestive enzyme]]s, which together break down the [[Amino acid#General structure|long chains of amino acids]] of proteins. Gastric acid is regulated in feedback systems to increase production when needed, such as after a meal. Other cells in the [[stomach]] produce [[bicarbonate]], a base, to [[Buffering agent|buffer]] the fluid, ensuring a regulated pH. These cells also produce [[mucus]] – a [[viscosity|viscous]] barrier to prevent gastric acid from damaging the stomach. The [[pancreas]] further produces large amounts of bicarbonate and secretes bicarbonate through the [[pancreatic duct]] to the [[duodenum]] to neutralize gastric acid passing into the [[Gastrointestinal tract|digestive tract]]. The primary active component of gastric acid is [[hydrochloric acid]] (HCl), which is produced by [[parietal cells]] in the [[gastric glands]] in the stomach. The secretion is a complex and relatively energetically expensive process. Parietal cells contain an extensive secretory network (called [[Canaliculus (parietal cell)|canaliculi]]) from which the "hydrochloric acid" is secreted into the [[Lumen (anatomy)|lumen]] of the stomach. The pH of gastric acid is 1.5 to 3.5 in the human stomach lumen, a level maintained by the [[proton pump]] [[hydrogen potassium ATPase|H⁺/K⁺ ATPase]].<ref>{{cite book | vauthors = Marieb EN, Hoehn K |title=Human Anatomy and Physiology |edition=11th |publisher=Pearson Education |year=2018 |pages=1264 |url=https://books.google.com/books?id=6MrdswEACAAJ |isbn=978-0-13-458099-9}}</ref> The parietal cell releases [[bicarbonate]] into the bloodstream in the process, which causes a temporary rise of pH in the blood, known as an [[alkaline tide]]. The highly acidic environment in the stomach lumen degrades [[protein]]s (e.g., food). [[Peptide bond]]s, which comprise proteins, are labilized. The [[gastric chief cell]]s of the stomach secrete [[enzyme]]s for protein breakdown (inactive [[pepsinogen]], and in infancy [[rennin]]). The low pH activates pepsinogen into the enzyme [[pepsin]], which then aids digestion by breaking the amino acid bonds, a process called [[proteolysis]]. In addition, many [[microorganism]]s are inhibited or destroyed in an acidic environment, preventing [[infection]] or sickness. ==Secretion== A typical adult human stomach will secrete about 1.5 liters of gastric acid daily.<ref name="eb">{{cite book | url=https://www.britannica.com/science/human-digestive-system/Gastric-secretion | title=Human digestive system: gastric secretion | publisher=Encyclopædia Britannica Inc. | vauthors = Dworken HJ | year=2016}}</ref> Gastric acid secretion is produced in several steps. Chloride and hydrogen [[ion]]s are secreted separately from the cytoplasm of parietal cells and mixed in the canaliculi. Gastric acid is then secreted into the lumen of the [[gastric gland]] and gradually reaches the main stomach lumen.<ref name=eb/> The exact manner in which the secreted acid reaches the stomach lumen is controversial, as acid must first cross the relatively pH-neutral gastric mucus layer. Chloride and sodium ions are secreted actively from the [[cytoplasm]] of the parietal cell into the lumen of the canaliculus. This creates a [[Transmembrane potential difference|negative potential]] of between −40{{nbsp}}and{{nbsp}}−70{{nbsp}}[[millivolt|mV]] across the parietal cell membrane that causes potassium ions and a small number of sodium ions to [[diffusion|diffuse]] from the cytoplasm into the parietal cell canaliculi. The enzyme [[carbonic anhydrase]] catalyses the reaction between carbon dioxide and water to form [[carbonic acid]]. This acid immediately dissociates into hydrogen and bicarbonate ions. The hydrogen ions leave the cell through [[Hydrogen potassium ATPase|H⁺/K⁺ ATPase]] [[antiporter]] pumps. At the same time, sodium ions are actively reabsorbed{{Citation needed|reason=I can not find a single reference to sodium reabsorption in any literature|date=June 2023}} . This means that the majority of secreted K⁺ (potassium) and Na⁺ (sodium) ions return to the cytoplasm. In the canaliculus, secreted hydrogen and chloride ions mix and are secreted into the lumen of the [[oxyntic gland]]. The highest concentration that gastric acid reaches in the stomach is 160{{nbsp}}[[millimolar|mM]] in the canaliculi. This is about 3 million times that of [[artery|arterial]] [[blood]], but almost exactly [[Isotonicity|isotonic]] with other bodily fluids. The lowest pH of the secreted acid is 0.8,<ref>{{Cite book| edition = 11| publisher = Elsevier Saunders| isbn = 0-7216-0240-1| page = 797| vauthors = Guyton AC, Hall JE | title = Textbook of Medical Physiology| location = Philadelphia| year = 2006}}</ref> but the acid is diluted in the stomach lumen to a pH of between 1 and 3. There is a small continuous basal secretion of gastric acid between meals of usually less than 10{{nbsp}}mEq/hour.<ref name=agabegi2nd192>Page 192 in: {{cite book | vauthors = Agabegi ED, Agabegi SS |title=Step-Up to Medicine (Step-Up Series) |publisher=Lippincott Williams & Wilkins |location=Hagerstwon, MD |year=2008 |isbn=978-0-7817-7153-5 |url-access=registration |url=https://archive.org/details/stepuptomedicine0000agab }}</ref> There are three phases in the secretion of gastric acid which increase the secretion rate in order to digest a meal:<ref name=eb/> # The [[cephalic phase]]: Thirty percent of the total gastric acid secretions to be produced is stimulated by anticipation of eating and the smell or taste of food. This signalling occurs from higher centres in the brain through the [[Vagus Nerve|vagus nerve (Cranial Nerve X)]]. It activates [[parietal cells]] to release acid and [[ECL cells]] to release [[histamine]]. The vagus nerve (CN X) also releases [[Gastrin Releasing Peptide|gastrin releasing peptide]] onto [[G cells]]. Finally, it also inhibits [[somatostatin]] release from [[D cells]].<ref name="ReferenceA">Lecture, "Function of the Stomach and Small Intestine" [[Deakin University School of Medicine]]. October 15, 2012</ref> # The [[gastric phase]]: About sixty percent of the total acid for a meal is secreted in this phase. Acid secretion is stimulated by distension of the stomach and by [[amino acids]] present in the food. # The [[intestinal phase]]: The remaining 10% of acid is secreted when [[chyme]] enters the small intestine, and is stimulated by small intestine distension and by [[amino acids]]. The duodenal cells release [[entero-oxyntin]] which acts on parietal cells without affecting gastrin.<ref name="ReferenceA"/> ==Regulation of secretion== {{See also|Regulation of gastric function}} [[Image:Determinants of Gastric Acid Secretion.svg|thumb|Diagram depicting the major determinants of gastric acid secretion, with inclusion of drug targets for peptic ulcer disease (PUD) and gastroesophageal reflux disease (GERD).]] 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. Beside this, the endings of the vagus nerve (CN 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]]<ref>{{Cite web|title=acetylcholine {{!}} Definition, Function, & Facts {{!}} Britannica|url=https://www.britannica.com/science/acetylcholine|access-date=2021-12-13|website=www.britannica.com|language=en}}</ref> 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]].<ref>{{Cite web|title=Somatostatin|url=https://www.hormone.org/your-health-and-hormones/glands-and-hormones-a-to-z/hormones/somatostatin|access-date=2021-12-13|website=www.hormone.org}}</ref> ==Neutralization== In the [[duodenum]], gastric acid is [[Neutralization (chemistry)|neutralized]] by [[sodium bicarbonate|bicarbonate]]. This also blocks gastric enzymes that have their optima in the acid range of [[pH]]. The secretion of 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 the duodenum falls below 4.5 to 5.0. The neutralization is described by the equation: :HCl + NaHCO₃ → NaCl + H₂CO₃ The [[carbonic acid]] rapidly equilibrates with [[carbon dioxide]] and [[water (molecule)|water]] through catalysis by carbonic anhydrase enzymes bound to the gut epithelial lining,<ref>{{cite journal | vauthors = Lönnerholm G, Knutson L, Wistrand PJ, Flemström G | title = Carbonic anhydrase in the normal rat stomach and duodenum and after treatment with omeprazole and ranitidine | journal = Acta Physiologica Scandinavica | volume = 136 | issue = 2 | pages = 253–262 | date = June 1989 | pmid = 2506730 | doi = 10.1111/j.1748-1716.1989.tb08659.x }}</ref> leading to a net release of carbon dioxide gas within the lumen associated with neutralisation. In the absorptive upper intestine, such as the duodenum, both the dissolved carbon dioxide and carbonic acid will tend to equilibrate with the blood, leading to most of the gas produced on neutralisation being exhaled through the lungs. == 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]]⁺ and [[chlorine]] depletion). [[Gastroesophageal reflux disease]] occurs when stomach acid repeatedly flows back into the [[Esophagus]], this backwash (acid reflux) can irritate the lining of the esophagus. Many people experience acid reflux from time to time. However, when acid reflux happens repeatedly over time, it can cause <abbr>GERD</abbr>. Most people are able to manage the discomfort of <abbr>GERD</abbr> with lifestyle changes and medications. While it is uncommon, some may need surgery to ease symptoms.<ref>{{Cite web |title=Gastroesophageal reflux disease (GERD) - Symptoms and causes |url=https://www.mayoclinic.org/diseases-conditions/gerd/symptoms-causes/syc-20361940 |access-date=2023-09-10 |website=Mayo Clinic |language=en}}</ref> == Pharmacology == The proton pump enzyme is the target of [[proton pump inhibitor]]s, used to increase gastric pH (and hence decrease stomach acidity) in diseases that feature excess acid. [[H2 antagonist|H₂ antagonists]] indirectly decrease gastric acid production. [[Antacid]]s neutralize existing acid. == Comparison between humans and other animals == The pH of gastric acid in humans is 1.5-2.0. This is a much lower pH level than that of most animals and very close to [[scavenger]]s, which eat [[carrion]].<ref name=":0">{{cite journal | vauthors = Beasley DE, Koltz AM, Lambert JE, Fierer N, Dunn RR | title = The Evolution of Stomach Acidity and Its Relevance to the Human Microbiome | journal = PLOS ONE | volume = 10 | issue = 7 | pages = e0134116 | date = 2015-07-29 | pmid = 26222383 | pmc = 4519257 | doi = 10.1371/journal.pone.0134116 | bibcode = 2015PLoSO..1034116B | doi-access = free }}</ref> This suggests that carrion feeding could have been more important in [[human evolution]] than previously thought.<ref name=":0" /> == History == {{Expand section|date=November 2010}} The role of gastric acid in [[digestion]] was established in the 1820s and 1830s by [[William Beaumont]] on [[Alexis St. Martin]], who, as a result of an accident, had a [[fistula]] (hole) in his stomach, which allowed Beaumont to observe the process of digestion and to extract gastric acid, verifying that acid played a crucial role in digestion.<ref>{{cite book | vauthors = Harré R | title = Great Scientific Experiments | publisher = Phaidon (Oxford) | year = 1981 | pages = [https://archive.org/details/greatscientifice00romh/page/39 39–47] | isbn = 0-7148-2096-2 | author-link = Rom Harré | url-access = registration | url = https://archive.org/details/greatscientifice00romh/page/39 }}</ref> == See also == * [[Stomach]] * [[Digestion]] * [[Discovery and development of proton pump inhibitors]] * [[Heartburn]] == References == {{Reflist|30em}} == External links == {{Commons category|Gastric acid}} * [http://www.vivo.colostate.edu/hbooks/pathphys/digestion/stomach/parietal.html The Parietal Cell: Mechanism of Acid Secretion; Colorado State University] {{Gastrointestinal physiology}} {{Authority control}} {{DEFAULTSORT:Gastric Acid}} [[Category:Acids]] [[Category:Body fluids]] [[Category:Stomach|Acid]]'