Gastric acid is a digestive fluid, formed in the stomach. It has a pH of 1.5 to 3.5 and is composed of hydrochloric acid (HCl) (around 0.5%, or 5000 parts per million), and large quantities of potassium chloride (KCl) and sodium chloride (NaCl). The acid plays a key role in digestion of proteins, by activating digestive enzymes, and making ingested proteins unravel so that digestive enzymes can break down the long chains of amino acids.
Gastric acid is produced by cells lining the stomach, which are coupled to 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.
The presence of gastric acid in the stomach and its function in digestion was first characterized by U.S. Army surgeon William Beaumont around 1830. Beaumont was able to study the stomach action of fur trapper Alexis St. Martin due to the latter's gastric fistula.
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Contents
- 1 Physiology
- 1.1 Secretion
- 1.2 Regulation of secretion
- 1.3 Neutralization
- 2 Role in disease
- 3 Pharmacology
- 4 History
- 5 See also
- 6 Notes
- 7 External links
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Physiology
Diagram summarising control of stomach
acid secretion, emphasising interaction between the
body and
antrum.
Gastric acid is produced by parietal cells (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 canaliculi) 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 1.35 to 3.5 [1] 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 (or denature). This exposes the protein's peptide bonds. The chief cells of the stomach secrete enzymes for protein breakdown (inactive pepsinogen and rennin). HCl 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,[2] but the acid is diluted in the stomach lumen to a pH between 1 and 3.
There are three phases in the secretion of gastric acid:
- 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.
- The gastric phase: Sixty percent 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.
There is also a small continuous basal secretion of gastric acid between meals of usually less than 10 mEq/hour.[3]
Regulation of secretion
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 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 (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 cells, D cells and enterochromaffine-like cells. Besides 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 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[4], 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 ulcers.
In diseases featuring excess vomiting, patients develop hypochloremic metabolic alkalosis (decreased blood acidity by H+ and chlorine depletion).
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
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This section requires expansion. (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.[5]
See also
- Stomach
- Digestion
- Gastroesophageal reflux disease
- Discovery and development of proton pump inhibitors
Notes
- ^ Marieb EN, Hoehn K (2010). Human anatomy & physiology. San Francisco: Benjamin Cummings. ISBN 0-8053-9591-1.
- ^ Guyton, Arthur C.; John E. Hall (2006). Textbook of Medical Physiology (11 ed.). Philadelphia: Elsevier Saunders. p. 797. ISBN 0-7216-0240-1.
- ^ Page 192 in: Elizabeth D Agabegi; Agabegi, Steven S. (2008). Step-Up to Medicine (Step-Up Series). Hagerstwon, MD: Lippincott Williams & Wilkins. ISBN 0-7817-7153-6.
- ^ http://www.ncbi.nlm.nih.gov/pubmed/2506730
- ^ Harré, R. (1981). Great Scientific Experiments. Phaidon (Oxford). pp. 39 – 47. ISBN 0-7148-2096-2.
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 6/6ch4/s6ch4_9
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Digestive system, physiology: gastrointestinal physiology
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| GI tract |
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Upper GI
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Exocrine
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Chief cells (Pepsinogen) · Parietal cells (Gastric acid, Intrinsic factor) · Goblet cells (Mucus)
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Processes
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Swallowing · Vomiting
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Fluids
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Saliva · Gastric juice
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Lower GI
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Enteric nervous system
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Meissner's plexus · Auerbach's plexus
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Endocrine/paracrine
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G cells (gastrin) · D cells (somatostatin) · ECL cells (Histamine)
enterogastrone: I cells (CCK) · K cells (GIP) · S cells (secretin)
Enteroendocrine cells · Enterochromaffin cell · APUD cell
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Fluids
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Intestinal juice
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Processes
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Segmentation contractions · Migrating motor complex · Borborygmus · Defecation
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Either/both
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Processes
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Peristalsis (Interstitial cell of Cajal · Basal electrical rhythm) · Gastrocolic reflex · Digestion
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| Accessory |
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Fluids
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Bile · Pancreatic juice
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Processes
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Enterohepatic circulation
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| Abdominopelvic |
Peritoneal fluid
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anat(t, g, p)/phys/devp/enzy
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noco/cong/tumr, sysi/epon
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proc, drug(A2A/2B/3/4/5/6/7/14/16), blte
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1. 電解質：Na+,Cl-,K+,H+
特に、Cl-,H+の濃度が高い
2 .有機物：ペプシノゲンI、ペプシノゲンII、粘液、内因子
1. 蛋白分解(変性)作用、
2. ペプシンの至適pH (pH1.5-2.0)までpHを低下させる
3. ペプシノゲンをペプシンに変換する。
→ペプシンは不活性型(ペプシノゲン)で分泌され、塩酸と触れて初めて発生を持つ
4. 細菌発育阻害
1. 頭相
全食事中の約1／2分泌
味覚、嗅覚(無条件性)
聴覚、視覚(条件性)
2. 胃相
全食事中の約1／2分泌
2-1) 食物流入→頭相による胃液の中和(pH↑)→G細胞のガストリン分泌抑制が解除される
2-2) 食物流入→胃体部・胃幽門洞拡張→胃壁伸展受容器→(迷走神経-迷走神経反射 or 局所反射)
→ACh→壁細胞が塩酸を分泌、G細胞がガストリンを分泌、主細胞がペプシノーゲンを分泌
2-3) 胃液→pH↓→粘膜受容器→局所反射→主細胞がペプシノーゲンを分泌
2-4) 食物中のペプチド、アミノ酸→G細胞がガストリンを分泌
3. 腸相
少量
糜粥→十二指腸粘膜からガストリンとセクレチン分泌の分泌→セクレチンにより主細胞からペプシノゲン分泌、HCO3-に富む膵液分泌
1. 壁細胞による塩酸の分泌
塩酸分泌↑
細胞内における二次メッセンジャー(Ca2+、cAMP)の濃度上昇が引き金となり、Cl-チャネル活性化、H+-K+-ATPase活性化、K+チャネル活性化が起こる。
アセチルコリン→M3ムスカリン受容体→[Ca2+]↑
ヒスタミン→H2受容体→[cAMP]↑
ガストリン→ガストリン受容体→[Ca2+]↑
塩酸分泌↓
セクレチン，GIP→壁細胞の塩酸産生が抑制される。
2. 主細胞によるペプシノーゲンの分泌
迷走神経→ACh→主細胞がペプシノーゲンを分泌
pH↓→局所反射→主細胞がペプシノーゲンを分泌
胃粘膜防壁 Gastric mucosal barrier
1. 粘液分泌
2. 粘膜上皮細胞の増殖・分化
細胞新生が早く、3日で新しい粘膜に置換
