Editing Parietal cell

{{Short description|Epithelial cell in the stomach}}
{{More citations needed|date=March 2009}}
{{Infobox cell
| Name        = Parietal cell
| Latin       = exocrinocytus parietalis
| Image       = File:Parietal cell.png
| Caption     = A parietal cell.
| Image2      = Control-of-stomach-acid-sec.png
| Caption2    = Control of stomach acid
| Precursor   =
| System      =
| Location = [[Stomach]]
| Function = [[Gastric acid]], [[intrinsic factor]] secretion
}}
'''Parietal cells''' (also known as '''oxyntic cells''') are [[epithelium|epithelial cells]] in the [[stomach]] that secrete [[hydrochloric acid]] (HCl) and [[intrinsic factor]].  These [[Cell (biology)|cells]] are located in the [[gastric glands]] found in the [[gastric mucosa|lining]] of the [[Stomach#Sections|fundus]] and [[Stomach#Sections|body]] regions of the stomach.<ref name=BMJ2014>{{cite journal|last1=Hunt|first1=A|last2=Harrington|first2=D|last3=Robinson|first3=S|title=Vitamin B12 deficiency.|journal=BMJ|date=4 June 2014|volume=349|pages=g5226|pmid=25189324|doi=10.1136/bmj.g5226|s2cid=28782021|url=http://frankhollis.com/temp/BMJ%20B12%20deficiency%20review.pdf|url-status=dead|archive-url=https://web.archive.org/web/20170312074341/http://frankhollis.com/temp/BMJ%20B12%20deficiency%20review.pdf|archive-date=12 March 2017|access-date=9 May 2018}}{{free access}}</ref> They contain an extensive secretory network of [[#Canaliculus|canaliculi]] from which the HCl is secreted by [[active transport]] into the stomach. The enzyme [[hydrogen potassium ATPase]] (H<sup>+</sup>/K<sup>+</sup> ATPase) is unique to the parietal cells and transports the H<sup>+</sup> against a [[concentration]] gradient of about 3 million to 1,{{Citation needed|date=October 2019}} which is the steepest{{Citation needed|date=October 2019}}<!-- Need a specific reference for this exact claim: i.e. the claim that it's the steepest of ALL ion gradients in the human body --> ion gradient formed in the human body.  Parietal cells are primarily [[#Regulation|regulated]] via [[histamine]], [[acetylcholine]] and [[gastrin]] signalling from both central and local modulators.

==Structure==
===Canaliculus===
A '''canaliculus''' is an adaptation found on gastric parietal cells.  It is a deep infolding, or little channel, which serves to increase the surface area, e.g. for secretion.  The parietal cell membrane is dynamic; the numbers of canaliculi rise and fall according to secretory need.  This is accomplished by the fusion of canalicular precursors, or '''tubulovesicles''', with the membrane to increase surface area, and the reciprocal endocytosis of the canaliculi (reforming the tubulovesicles) to decrease it.<ref name="Sahoo">{{cite journal |last1=Sahoo |first1=N |last2=Gu |first2=M |last3=Zhang |first3=X |title=Gastric Acid Secretion from Parietal Cells Is Mediated by a Ca(2+) Efflux Channel in the Tubulovesicle. |journal=Developmental Cell |date=8 May 2017 |volume=41 |issue=3 |pages=262–273.e6 |doi=10.1016/j.devcel.2017.04.003 |pmid=28486130|pmc=5497767 }}</ref>

==Function==
===Hydrochloric acid secretion===
Hydrochloric acid is formed in the following manner:
* Hydrogen ions are formed from the dissociation of carbonic acid. Water is a very minor source of hydrogen ions in comparison to carbonic acid. Carbonic acid is formed from [[carbon dioxide]] and water by [[carbonic anhydrase]].
* The bicarbonate ion (HCO<sub>3</sub><sup>−</sup>) is exchanged for a chloride ion (Cl<sup>−</sup>) on the basal side of the cell and the bicarbonate diffuses into the venous blood, leading to an [[alkaline tide]] phenomenon.
* [[Potassium]] (K<sup>+</sup>) and chloride (Cl<sup>−</sup>) ions diffuse into the [[Parietal cell#Canaliculus|canaliculi]].
* Hydrogen ions are pumped out of the cell into the canaliculi in exchange for potassium ions, via the [[hydrogen potassium ATPase|H<sup>+</sup>/K<sup>+</sup>-ATPase]]. These pumps are increased in number on luminal side by fusion of tubulovesicles during activation of parietal cells and removed during deactivation. This pump maintains a million-fold difference in proton concentration.<ref>{{cite journal |last1=Abe |first1=Kazuhiro |last2=Irie |first2=Katsumasa |last3=Nakanishi |first3=Hanayo |last4=Suzuki |first4=Hiroshi |last5=Fujiyoshi |first5=Yoshinori |title=Crystal structures of the gastric proton pump |journal=Nature |date=April 2018 |volume=556 |issue=7700 |pages=214–218 |doi=10.1038/s41586-018-0003-8}}</ref> ATP is provided by the numerous mitochondria.

[[File:Parietal cells.jpg|thumb|Human parietal cells (pink staining) – stomach.]]
As a result of the cellular export of hydrogen ions, the gastric lumen is maintained as a highly acidic environment. The acidity aids in digestion of food by promoting the unfolding (or [[Denaturation (biochemistry)|denaturing]]) of ingested [[protein]]s.  As proteins unfold, the [[peptide bonds]] linking component [[amino acids]] are exposed.  Gastric HCl simultaneously cleaves [[pepsinogen]], a [[zymogen]], into active [[pepsin]], an endopeptidase that advances the digestive process by breaking the now-exposed peptide bonds, a process known as [[proteolysis]].

===Regulation===

Parietal cells [[secretion|secrete]] acid in response to three types of [[stimulus (physiology)|stimuli]]:<ref>{{cite book|last=Boulpaep|first=Walter|title=Medical Physiology|year=2009|publisher=Saunders|location=Philadelphia|isbn=978-1-4160-3115-4|pages=898–899}}</ref>
* [[Histamine]], stimulating [[Histamine H2 receptor|H<sub>2</sub> histamine receptors]] (most significant contribution).
* [[Acetylcholine]] (ACh), from [[parasympathetic]] activity via the [[vagus nerve]] and enteric nervous system, stimulating [[Muscarinic acetylcholine receptor M3|M<sub>3</sub> receptors]].<ref name="M3 receptor">{{cite web|title=Gastric acid secretion - Homo sapiens|url=http://www.genome.jp/dbget-bin/show_pathway?hsa04971+1131|publisher=KEGG|access-date=June 1, 2011}}</ref>
* [[Gastrin]], stimulating [[Cholecystokinin B receptor|CCK2 receptors]] (least significant contribution, but also causes histamine secretion by local [[Enterochromaffin-like cell|ECL cells]]).
Activation of histamine through H<sub>2</sub> receptor causes increases in the intracellular [[Cyclic adenosine monophosphate|cAMP]] level, while ACh through M<sub>3</sub> receptor and gastrin through CCK2 receptor increases intracellular calcium level. These receptors are present on basolateral side of membrane.

Increased cAMP level results in increased protein kinase A. Protein kinase A phosphorylates proteins involved in the transport of [[Hydrogen potassium ATPase|H<sup>+</sup>/K<sup>+</sup>-ATPase]] from the cytoplasm to the [[cell membrane]].  This causes resorption of K<sup>+</sup> ions and secretion of H<sup>+</sup> ions. The [[pH]] of the secreted fluid can fall by 0.8.

Gastrin primarily induces acid-secretion indirectly, increasing histamine synthesis in [[Enterochromaffin-like cell|ECL cells]], which in turn signal parietal cells via histamine release and H<sub>2</sub> stimulation.<ref>Waldum, Helge L., Kleveland, Per M., et al. (2009)'Interactions between gastric acid secretagogues and the localization of the gastrin receptor', Scandinavian Journal of Gastroenterology, 44:4,390—393.</ref> Gastrin itself has no effect on the maximum histamine-stimulated gastric acid secretion.<ref>Kleveland PM, Waldum HL, Larsson M. Gastric acid secretion in the totally isolated, vascularly perfused rat stomach. A selective muscarinic-1 agent does, whereas gastrin does not, augment maximal histamine-stimulated acid secretion. Scandinavian Journal of Gastroenterology, 1987;22:705–713.</ref>

The effect of histamine, acetylcholine and gastrin is synergistic, that is, effect of two simultaneously is more than additive of effect of the two individually. It helps in non-linear increase of secretion with stimuli physiologically.<ref>{{Cite book|title = Ganong's Review of Medical Physiology 24th edition|publisher = Lange}}</ref>

===Intrinsic factor secretion===
Parietal cells also produce a [[glycoprotein]] known as [[intrinsic factor]]. Intrinsic factor is required for the absorption of [[Vitamin B12|vitamin B{{sub|12}}]] in the diet.  A long-term [[Vitamin B12 deficiency|deficiency in vitamin B<sub>12</sub>]] can lead to [[megaloblastic anemia]], characterized by large fragile [[red blood cells]]. [[Pernicious anaemia]] results from autoimmune destruction of gastric parietal cells, precluding the synthesis of intrinsic factor and, by extension, absorption of vitamin B<sub>12</sub>. Pernicious anemia also leads to megaloblastic anemia. [[Atrophic gastritis]], particularly in the elderly, will cause an inability to absorb B<sub>12</sub> and can lead to deficiencies such as decreased DNA synthesis and [[nucleotide]] metabolism in the bone marrow.

==Clinical significance==
[[File:GASTRIC PARIETAL CELL ANTIBODIES.jpg|thumb|[[Immunofluorescence]] staining pattern of gastric parietal antibodies on a stomach section]]
[[File:Histopathology of fundic gland polyp, high magnification, annotated.jpg|thumb|Parietal cells are part of [[fundic gland polyp]]s (here shown in high magnification).<ref name=PathologyOutlines-fundic-gland>{{cite web|url=https://www.pathologyoutlines.com/topic/stomachfundicgland.html|title=Stomach Polyps - Fundic gland polyp|website=PathologyOutlines|author=Naziheh Assarzadegan, M.D., Raul S. Gonzalez, M.D.}} Topic Completed: 1 November 2017. Minor changes: 11 December 2019</ref>]]
* ''[[Peptic ulcer]]s'' can result from over-acidity in the stomach. Antacids can be used to enhance the natural tolerance of the gastric lining. [[Antimuscarinic]] drugs such as [[pirenzepine]] or H<sub>2</sub> [[antihistamine]]s can reduce acid secretion. [[Proton pump inhibitor]]s are more potent at reducing gastric acid production since that is the final common pathway of all stimulation of acid production.
* In ''[[pernicious anemia]]'', [[autoantibody|autoantibodies]] directed against parietal cells or intrinsic factor cause a reduction in vitamin B<sub>12</sub> absorption. It can be treated with injections of replacement vitamin B<sub>12</sub> ([[methylcobalamin]], [[hydroxocobalamin]] or [[cyanocobalamin]]).
* ''[[Achlorhydria]]'' is another [[autoimmune]] disease of the parietal cells. The damaged parietal cells are unable to produce the required amount of gastric acid. This leads to an increase in gastric pH, impaired digestion of food and increased risk of [[gastroenteritis]].

== See also ==
* [[Gastric chief cell]]
* [[Digestion]]
* [[Gastroesophageal reflux disease]]
* [[Discovery and Development of Proton Pump Inhibitors]]
* [[List of human cell types derived from the germ layers]]

== References ==
{{Reflist}}

==External links==
* [http://www.anatomyatlases.org/MicroscopicAnatomy/Section01/Plate0105.shtml Illustration of Chief cells and Parietal cells at anatomyatlases.org]
* [http://www.vivo.colostate.edu/hbooks/pathphys/digestion/stomach/parietal.html The Parietal Cell: Mechanism of Acid Secretion at vivo.colostate.edu]
* {{BUHistology|11303loa}} - Digestive System: Alimentary Canal: fundic stomach, gastric glands, lumen"
* {{cite book| title= Essentials of Human Physiology| first= Thomas M. |last= Nosek| chapter=Section 6/6ch4/s6ch4_8 |chapter-url=http://humanphysiology.tuars.com/program/section6/6ch4/s6ch4_8.htm |archive-url=https://web.archive.org/web/20160324124828/http://humanphysiology.tuars.com/program/section6/6ch4/s6ch4_8.htm|archive-date=2016-03-24}}
* {{cite book| title= Essentials of Human Physiology| first= Thomas M. |last= Nosek| chapter=Section 6/6ch4/s6ch4_14 |chapter-url=http://humanphysiology.tuars.com/program/section6/6ch4/s6ch4_14.htm |archive-url=https://web.archive.org/web/20160324124828/http://humanphysiology.tuars.com/program/section6/6ch4/s6ch4_14.htm|archive-date=2016-03-24}}
* [http://www.antibodypatterns.com/gpc.php Parietal cell antibody]
* [http://www.ii.bham.ac.uk/clinicalimmunology/CISimagelibrary/GPC.htm Antibody to GPC]

{{Gastrointestinal physiology}}
{{Authority control}}

[[Category:Epithelial cells]]
[[Category:Animal cells]]
[[Category:Human cells]]
[[Category:Acid secreting cells]]
[[Category:Stomach]]