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Gastric acid or stomach acid is the
acid An acid is a molecule or ion capable of either donating a proton (i.e. Hydron, hydrogen cation, H+), known as a Brønsted–Lowry acid–base theory, Brønsted–Lowry acid, or forming a covalent bond with an electron pair, known as a Lewis ...
ic component –
hydrochloric acid Hydrochloric acid, also known as muriatic acid or spirits of salt, is an aqueous solution of hydrogen chloride (HCl). It is a colorless solution with a distinctive pungency, pungent smell. It is classified as a acid strength, strong acid. It is ...
– of gastric juice, produced by parietal cells in the gastric glands of the stomach lining. In humans, the pH is between one and three, much lower than most other animals, but is very similar to that of
carrion Carrion (), also known as a carcass, is the decaying flesh of dead animals. Overview Carrion is an important food source for large carnivores and omnivores in most ecosystems. Examples of carrion-eaters (or scavengers) include crows, vultures ...
-eating
carnivore A carnivore , or meat-eater (Latin, ''caro'', genitive ''carnis'', meaning meat or "flesh" and ''vorare'' meaning "to devour"), is an animal or plant Plants are the eukaryotes that form the Kingdom (biology), kingdom Plantae; they ar ...
s that need protection from ingesting
pathogen In biology, a pathogen (, "suffering", "passion" and , "producer of"), in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a Germ theory of d ...
s. With this higher acidity, gastric acid plays a key protective role against pathogens. It is also key in the
digestion Digestion is the breakdown of large insoluble food compounds into small water-soluble components so that they can be absorbed into the blood plasma. In certain organisms, these smaller substances are absorbed through the small intestine into th ...
of
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
s by activating digestive enzymes, which together break down the long chains of amino acids. Gastric acid is regulated in feedback systems to increase production when needed, such as after a meal. Other cells in the
stomach The stomach is a muscular, hollow organ in the upper gastrointestinal tract of Human, humans and many other animals, including several invertebrates. The Ancient Greek name for the stomach is ''gaster'' which is used as ''gastric'' in medical t ...
produce
bicarbonate In inorganic chemistry, bicarbonate (IUPAC-recommended nomenclature: hydrogencarbonate) is an intermediate form in the deprotonation of carbonic acid. It is a polyatomic anion with the chemical formula . Bicarbonate serves a crucial bioche ...
, a base, to buffer the fluid, ensuring a regulated pH. These cells also produce
mucus Mucus (, ) is a slippery aqueous secretion produced by, and covering, mucous membranes. It is typically produced from cells found in mucous glands, although it may also originate from mixed glands, which contain both Serous fluid, serous and muc ...
– a viscous barrier to prevent gastric acid from damaging the stomach. The
pancreas The pancreas (plural pancreases, or pancreata) is an Organ (anatomy), organ of the Digestion, digestive system and endocrine system of vertebrates. In humans, it is located in the abdominal cavity, abdomen behind the stomach and functions as a ...
further produces large amounts of bicarbonate, secreting this through the pancreatic duct to the
duodenum The duodenum is the first section of the small intestine in most vertebrates, including mammals, reptiles, and birds. In mammals, it may be the principal site for iron absorption. The duodenum precedes the jejunum and ileum and is the shortest p ...
to neutralize gastric acid passing into the
digestive tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the Digestion, digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascula ...
. The secretion is a complex and relatively energetically expensive process. Parietal cells contain an extensive secretory network (called canaliculi) from which the hydrochloric acid is secreted into the lumen of the stomach. The pH level is maintained by the proton pump H+/K+ ATPase. The parietal cell releases
bicarbonate In inorganic chemistry, bicarbonate (IUPAC-recommended nomenclature: hydrogencarbonate) is an intermediate form in the deprotonation of carbonic acid. It is a polyatomic anion with the chemical formula . Bicarbonate serves a crucial bioche ...
into the bloodstream in the process, which causes a temporary rise of pH in the blood, known as an alkaline tide. The gastric juice also contains digestive enzymes produced by other cells in the gastric glands – gastric chief cells. Gastric chief cells secrete an inactivated pepsinogen. Once in the stomach lumen gastric acid activates the proenzyme to
pepsin Pepsin is an endopeptidase that breaks down proteins into smaller peptides and amino acids. It is one of the main digestive enzymes in the digestive systems of humans and many other animals, where it helps digest the proteins in food. Pe ...
.


Secretion

A typical adult human stomach will secrete about 1.5 liters of gastric juice daily. Gastric juice is the combination of gastric gland secretions including the main component of
hydrochloric acid Hydrochloric acid, also known as muriatic acid or spirits of salt, is an aqueous solution of hydrogen chloride (HCl). It is a colorless solution with a distinctive pungency, pungent smell. It is classified as a acid strength, strong acid. It is ...
(gastric acid), gastric lipase and pepsinogen. Once in the stomach pepsinogen is changed by gastric acid to the digestive enzyme
pepsin Pepsin is an endopeptidase that breaks down proteins into smaller peptides and amino acids. It is one of the main digestive enzymes in the digestive systems of humans and many other animals, where it helps digest the proteins in food. Pe ...
adding this enzyme to the gastric juice. In humans, the pH of gastric acid is between one and three, much lower than most other animals, but is very similar to that of
carrion Carrion (), also known as a carcass, is the decaying flesh of dead animals. Overview Carrion is an important food source for large carnivores and omnivores in most ecosystems. Examples of carrion-eaters (or scavengers) include crows, vultures ...
eating
carnivore A carnivore , or meat-eater (Latin, ''caro'', genitive ''carnis'', meaning meat or "flesh" and ''vorare'' meaning "to devour"), is an animal or plant Plants are the eukaryotes that form the Kingdom (biology), kingdom Plantae; they ar ...
s, needing extra protection from ingesting
pathogen In biology, a pathogen (, "suffering", "passion" and , "producer of"), in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a Germ theory of d ...
s. Gastric acid secretion is produced in several steps. Chloride and hydrogen ions are secreted separately from the cytoplasm of parietal cells and mixed in the canaliculi. This creates a negative potential of between −40and−70 mV across the parietal cell membrane that causes potassium ions and a small number of sodium ions to diffuse from the cytoplasm into the parietal cell canaliculi. Gastric acid is then secreted along with other gland secretions into the gastric pit for release into the stomach lumen. The enzyme carbonic anhydrase catalyses the reaction between carbon dioxide and water to form
carbonic acid Carbonic acid is a chemical compound with the chemical formula . The molecule rapidly converts to water and carbon dioxide in the presence of water. However, in the absence of water, it is quite stable at room temperature. The interconversion ...
. This acid immediately dissociates into hydrogen and bicarbonate ions. The hydrogen ions leave the cell through H+/K+ ATPase
antiporter An antiporter (also called exchanger or counter-transporter) is an integral membrane protein that uses secondary active transport to move two or more molecules in opposite directions across a phospholipid membrane. It is a type of cotransporte ...
pumps. At the same time, sodium ions are actively reabsorbed . 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 mM in the canaliculi. This is about 3 million times that of arterial
blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood is com ...
, but almost exactly isotonic with other bodily fluids. The lowest pH of the secreted acid is 0.8, 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 10mEq/hour.Page 192 in: There are three phases in the secretion of gastric acid which increase the secretion rate in order to digest a meal: # 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 (Cranial Nerve X). It activates parietal cells to release acid and ECL cells to release
histamine Histamine is an organic nitrogenous compound involved in local immune responses communication, as well as regulating physiological functions in the gut and acting as a neurotransmitter for the brain, spinal cord, and uterus. Discovered in 19 ...
. The vagus nerve (CN X) also releases gastrin releasing peptide onto G cells. Finally, it also inhibits
somatostatin Somatostatin, also known as growth hormone-inhibiting hormone (GHIH) or by #Nomenclature, several other names, is a peptide hormone that regulates the endocrine system and affects neurotransmission and cell proliferation via interaction with G ...
release from D cells.Lecture, "Function of the Stomach and Small Intestine" Deakin University School of Medicine. October 15, 2012 # 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 Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the Proteinogenic amino acid, 22 α-amino acids incorporated into p ...
present in the food. # The intestinal phase: The remaining 10% of acid is secreted when
chyme Chyme or chymus (; ) is the semi-fluid mass of partly digested food that is expelled by the stomach, through the pyloric valve, into the duodenum (the beginning of the small intestine). Chyme results from the mechanical and chemical breakdown ...
enters the small intestine, and is stimulated by small intestine distension and by
amino acids Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the Proteinogenic amino acid, 22 α-amino acids incorporated into p ...
. The duodenal cells release entero-oxyntin which acts on parietal cells without affecting gastrin.


Regulation of secretion

Gastric acid production is regulated by both the
autonomic nervous system The autonomic nervous system (ANS), sometimes called the visceral nervous system and formerly the vegetative nervous system, is a division of the nervous system that operates viscera, internal organs, smooth muscle and glands. The autonomic nervo ...
and several
hormone A hormone (from the Ancient Greek, Greek participle , "setting in motion") is a class of cell signaling, signaling molecules in multicellular organisms that are sent to distant organs or tissues by complex biological processes to regulate physio ...
s. The
parasympathetic nervous system The parasympathetic nervous system (PSNS) is one of the three divisions of the autonomic nervous system, the others being the sympathetic nervous system and the enteric nervous system. The autonomic nervous system is responsible for regulat ...
, via the
vagus nerve The vagus nerve, also known as the tenth cranial nerve (CN X), plays a crucial role in the autonomic nervous system, which is responsible for regulating involuntary functions within the human body. This nerve carries both sensory and motor fibe ...
, and the hormone
gastrin Gastrin is a peptide hormone that stimulates secretion of gastric acid (HCl) by the parietal cells of the stomach and aids in gastric motility. It is released by G cells in the pyloric antrum of the stomach, duodenum, and the pancreas. ...
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 Histamine is an organic nitrogenous compound involved in local immune responses communication, as well as regulating physiological functions in the gut and acting as a neurotransmitter for the brain, spinal cord, and uterus. Discovered in 19 ...
from enterochromaffin-like cells (ECLs). 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 Negative feedback (or balancing feedback) occurs when some function (Mathematics), function of the output of a system, process, or mechanism is feedback, fed back in a manner that tends to reduce the fluctuations in the output, whether caused ...
mechanisms. Four types of cells are involved in this process: parietal cells, G cells, D cells and enterochromaffin-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 A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a Chemical synapse, synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell. Neurotra ...
s:
acetylcholine Acetylcholine (ACh) is an organic compound that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Par ...
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 enterochromaffin-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 Somatostatin, also known as growth hormone-inhibiting hormone (GHIH) or by #Nomenclature, several other names, is a peptide hormone that regulates the endocrine system and affects neurotransmission and cell proliferation via interaction with G ...
.


Neutralization

In the
duodenum The duodenum is the first section of the small intestine in most vertebrates, including mammals, reptiles, and birds. In mammals, it may be the principal site for iron absorption. The duodenum precedes the jejunum and ileum and is the shortest p ...
, gastric acid is neutralized by
bicarbonate In inorganic chemistry, bicarbonate (IUPAC-recommended nomenclature: hydrogencarbonate) is an intermediate form in the deprotonation of carbonic acid. It is a polyatomic anion with the chemical formula . Bicarbonate serves a crucial bioche ...
. This also blocks gastric enzymes that function optimally in the acid range of pH. The secretion of bicarbonate from the
pancreas The pancreas (plural pancreases, or pancreata) is an Organ (anatomy), organ of the Digestion, digestive system and endocrine system of vertebrates. In humans, it is located in the abdominal cavity, abdomen behind the stomach and functions as a ...
is stimulated by secretin. This
polypeptide Peptides are short chains of amino acids linked by peptide bonds. A polypeptide is a longer, continuous, unbranched peptide chain. Polypeptides that have a molecular mass of 10,000 Da or more are called proteins. Chains of fewer than twenty ...
hormone gets activated and secreted from so-called S cells in the mucosa of the duodenum and
jejunum The jejunum is the second part of the small intestine in humans and most higher vertebrates, including mammals, reptiles, and birds. Its lining is specialized for the absorption by enterocytes of small nutrient molecules which have been pr ...
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 Carbonic acid is a chemical compound with the chemical formula . The molecule rapidly converts to water and carbon dioxide in the presence of water. However, in the absence of water, it is quite stable at room temperature. The interconversion ...
rapidly equilibrates with
carbon dioxide Carbon dioxide is a chemical compound with the chemical formula . It is made up of molecules that each have one carbon atom covalent bond, covalently double bonded to two oxygen atoms. It is found in a gas state at room temperature and at norma ...
and
water Water is an inorganic compound with the chemical formula . It is a transparent, tasteless, odorless, and Color of water, nearly colorless chemical substance. It is the main constituent of Earth's hydrosphere and the fluids of all known liv ...
through catalysis by carbonic anhydrase enzymes bound to the gut epithelial lining, 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.


Clinical significance

Gastroesophageal reflux disease (GERD) is a common disorder that occurs when stomach acid repeatedly flows back into the
esophagus The esophagus (American English), oesophagus (British English), or œsophagus (Œ, archaic spelling) (American and British English spelling differences#ae and oe, see spelling difference) all ; : ((o)e)(œ)sophagi or ((o)e)(œ)sophaguses), c ...
, this backwash of acid (reflux) also known as
heartburn Heartburn is a burning sensation felt behind the breastbone. It is a symptom that is commonly linked to acid reflux and is often triggered by food, particularly fatty, sugary, spicy, chocolate, citrus, onion-based and tomato-based products. Ly ...
can irritate the lining of the esophagus. Most people are able to manage the discomfort of GERD with lifestyle changes and medications, notably proton pump inhibitors, and H2 blockers. Antacids may also be used to neutralise gastric acid. Sometimes, surgery may be needed to ease symptoms. Chronic inflammation of the gastric mucosa can lead to atrophic gastritis resulting in a decreased secretion of gastric acid, and consequent digestive problems. In hypochlorhydria and
achlorhydria Achlorhydria and hypochlorhydria are states where the production of hydrochloric acid in gastric secretions of the stomach is absent or low, respectively. Achlorhydria is commonly a complication of some other disease, such as chronic '' Helicobac ...
, gastric acid is either low or absent, respectively. This can potentially lead to less protection against ingested pathogens such as '' Vibrio'' or '' Helicobacter''
bacteria Bacteria (; : bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of Prokaryote, prokaryotic microorganisms. Typically a few micr ...
. In Zollinger–Ellison syndrome
gastrin Gastrin is a peptide hormone that stimulates secretion of gastric acid (HCl) by the parietal cells of the stomach and aids in gastric motility. It is released by G cells in the pyloric antrum of the stomach, duodenum, and the pancreas. ...
levels are increased, leading to excess gastric acid production, which can cause gastric ulcers. Hypercalcemia also increases gastrin and gastric acid and can cause ulcers. In diseases featuring excess vomiting, hypochloremic metabolic alkalosis (decreased blood acidity by H+ and
chlorine Chlorine is a chemical element; it has Symbol (chemistry), symbol Cl and atomic number 17. The second-lightest of the halogens, it appears between fluorine and bromine in the periodic table and its properties are mostly intermediate between ...
depletion) may develop.


History

The role of gastric acid in
digestion Digestion is the breakdown of large insoluble food compounds into small water-soluble components so that they can be absorbed into the blood plasma. In certain organisms, these smaller substances are absorbed through the small intestine into th ...
was established in the 1820s and 1830s by William Beaumont on Alexis St. Martin, who, as a result of an accident, had a
fistula In anatomy, a fistula (: fistulas or fistulae ; from Latin ''fistula'', "tube, pipe") is an abnormal connection (i.e. tube) joining two hollow spaces (technically, two epithelialized surfaces), such as blood vessels, intestines, or other h ...
(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.


See also

*
Discovery and development of proton pump inhibitors Proton pump inhibitors (PPIs) block the gastric hydrogen potassium ATPase (H+/K+ ATPase) and inhibit gastric acid secretion. These drugs have emerged as the treatment of choice for acid-related diseases, including gastroesophageal reflux disease (G ...


References


External links


The Parietal Cell: Mechanism of Acid Secretion; Colorado State University
{{DEFAULTSORT:Gastric Acid Acids Body fluids
Acid An acid is a molecule or ion capable of either donating a proton (i.e. Hydron, hydrogen cation, H+), known as a Brønsted–Lowry acid–base theory, Brønsted–Lowry acid, or forming a covalent bond with an electron pair, known as a Lewis ...