Gastric acid is a digestive fluid, formed in the stomach. It is composed of hydrochloric
acid as high as 0.1 M, potassium chloride and sodium chloride. The acid plays a key
role in digestion of proteins, by activating digestive enzymes, and making ingested proteins
unravel so that digestive enzymes break down the long chains of amino acids. Gastric acid
is produced by cells lining the stomach, which are coupled in feedback systems to increase
acid production when needed. Other cells in the stomach produce bicarbonate, a base, to
buffer the fluid, ensuring that it does not become too acidic. These cells also produce
mucus, which forms a viscous physical barrier to prevent gastric acid from damaging the
stomach. Cells in the beginning of the small intestine, or duodenum, further produce large
amounts of bicarbonate to completely neutralize any gastric acid that passes further down
into the digestive tract. Gastric acid is produced by parietal cells
in the stomach. Its secretion is a complex and relatively energetically expensive process.
Parietal cells contain an extensive secretory network from which the gastric acid is secreted
into the lumen of the stomach. These cells are part of epithelial fundic glands in the
gastric mucosa. The pH of gastric acid is 1.5 to 3.5 in the human stomach lumen, the
acidity being maintained by the proton pump H+/K+ ATPase. The parietal cell releases bicarbonate
into the blood stream in the process, which causes a temporary rise of pH in the blood,
known as alkaline tide. The resulting highly acidic environment in
the stomach lumen causes proteins from food to lose their characteristic folded structure.
This exposes the protein's peptide bonds. The gastric chief cells of the stomach secrete
enzymes for protein breakdown. Hydrochloric acid activates pepsinogen into the enzyme
pepsin, which then helps digestion by breaking the bonds linking amino acids, a process known
as proteolysis. In addition, many microorganisms have their growth inhibited by such an acidic
environment, which is helpful to prevent infection.
Secretion Gastric acid secretion happens in several
steps. Chloride and hydrogen ions are secreted separately from the cytoplasm of parietal
cells and mixed in the canaliculi. Gastric acid is then secreted into the lumen of the
oxyntic gland and gradually reaches the main stomach lumen. 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 negative potential of -40 mV to -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. 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
H+/K+ ATPase antiporter pumps. At the same time sodium ions are actively
reabsorbed. This means that the majority of secreted K+ and Na+ 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, 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 between 1 and 3.
There is a small continuous basal secretion of gastric acid between meals of usually less
than 10 mEq/hour. 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. It activates parietal cells
to release acid and ECL cells to release histamine. The vagus nerve also releases gastrin releasing
peptide onto G cells. Finally, it also inhibits somatostatin release from D cells.
The gastric phase: About fifty 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. Regulation of secretion
Gastric acid production is regulated by both the autonomic nervous system and several hormones.
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
cells. 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 cells, D cells and enterochromaffine-like cells. Besides this, the endings of the vagus
nerve and the intramural nervous plexus in the digestive tract influence the secretion
significantly. Nerve endings in the stomach secrete two stimulatory
neurotransmitters: 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 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 cells 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 + NaHCO3 → NaCl + H2CO3
The carbonic acid rapidly equilibrates with carbon dioxide and water 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. 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.
In Zollinger–Ellison syndrome and hypercalcemia, there are increased gastrin levels, leading
to excess gastric acid production, which can cause gastric ulcers.
In diseases featuring excess vomiting, patients develop hypochloremic metabolic alkalosis.
Pharmacology The proton pump enzyme is the target of proton
pump inhibitors, used to increase gastric pH in diseases that feature excess acid. H2
antagonists indirectly decrease gastric acid production. Antacids neutralize existing acid.
History 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 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
Stomach Digestion
Gastroesophageal reflux disease Discovery and development of proton pump inhibitors
Acidic Mouth Notes
External links The Parietal Cell: Mechanism of Acid Secretion
at vivo.colostate.edu First Principles of Gastroenterology. Chapter
6. Salena B. J., Hunt R. H. The Stomach and Duodenum
"Gastric juice" at Dorland's Medical Dictionary Physiology at MCG 6s6ch4_9