Acid Secretion in the Stomach
BMS2031
GASTROINTESTINAL TRACT
LECTURE 3
Acid Secretion in the Stomach Explain the control of parietal cell HCL secretion by histamine, gastrin and acetylcholine •
Gastric glands are located under gastric pits in the mucosal lining. They contain four main type of secretory cells: 1. Mucous: secretes mucous 2. Parietal (Oxyntic cells): secrete HCL and Intrinsic Factor 3. Chief: secretes pepsinogen 4. Enteroendocrine: - Enterochormaffin like (ECL) cells secretes Histamine - G- cells secrete gastrin - Both Histamine and Gastrin stimulate gastric acid secretion Activation of Pepsin from Pepsinogen: 1) Chief cells secrete pepsinogen- optimal pH =2 for activation of pepsinogen. Becomes inactivated at pH>4. 2) At the same time parietal cells secrete HCL and IF. HCL brings pH to acidic levels, allows conversion of pepsinogen to pepsin. 3) Pepsin can now breakdown proteins into peptides
•
Process of Acid secretion: o Parietal/Oxyntic cells secrete H+ into the lumen against a large H+ concentration gradient. - Parietal cells have lots of mitochondria that take 40% of the cell volume, to provide ATP for active transport of H+. Where does the H+ (and Cl-) come from? H+ ions are generated within cells (parietal). 1) Cellular metabolism occurs producing CO2 and water. In the cell CO2 + water à carbonic acid. CO2 and H2O can also diffuse from the mesenteric veins that drain the stomach. 2) Carbonic acid disassociates into carbonic ions (HCO3-) and Hydrogen ions (H+). 3) The bicarbonate ions are exchanged via an anion anti-porter for Chloride ions from the veins. Bicarbonate ions end up in the veins. 4) pH of the veins draining the stomach increases (‘Alkaline tide’) 5) Cl- ions diffuse out of the parietal cell into the lumen, H+ ions are actively pumped via an H+/K+ ATPase (proton pump) in exchange for K+ ions. This is occurring on the basal level.
BMS2031
GASTROINTESTINAL TRACT o
LECTURE 3
Receptor Mediated Acid Secretion - Parietal HCL secretion is activated by nerves and hormones when you ingest a meal. 1) The Basolateral membrane of the parietal cell is embedded with receptors (Gastrin, Histamine, Ach and Somatostatin). 2) Histamine, Gastrin and Acetylcholine stimulate gastric acid secretion above basal levels. Somatostatin (GHIH) inhibits gastric secretion (will not look at that). - Gastrin acts on G-type receptors. - Histamine acts on Histamine receptors - Acetylcholine from parasympathetic nerves innervating the parietal cells act on muscarinic receptors 3) Lead to activation of second messengers 4) Second messengers act on H+/K+ ATPase (proton pumps) which sit in vesicles in cytoplasm 5) Proton pumps inserted into luminal membrane 6) Increase in acid secretion above basal levels
Describe how gastric mucosa is protected from acidic gastric juices •
There are 3 main pathways by which the stomach protects its lining: 1. Mucosal cells tightly joined to each other by tight junctions (no leakage of gastric acid) 2. Mucous rich in bicarbonate secreted from goblet cells in mucosal lining 3. Differentiation of stem cells (every 3-5 days the lining of the stomach and digestive tract replaces itself). - The oesophagus and duodenum do not have these protective linings in place. - Body attempts to neutralise the acidic Chyme that enters the duodenum from the stomach
GASTROINTESTINAL TRACT
LECTURE 3
Acid Secretion in the Stomach Explain the control of parietal cell HCL secretion by histamine, gastrin and acetylcholine •
Gastric glands are located under gastric pits in the mucosal lining. They contain four main type of secretory cells: 1. Mucous: secretes mucous 2. Parietal (Oxyntic cells): secrete HCL and Intrinsic Factor 3. Chief: secretes pepsinogen 4. Enteroendocrine: - Enterochormaffin like (ECL) cells secretes Histamine - G- cells secrete gastrin - Both Histamine and Gastrin stimulate gastric acid secretion Activation of Pepsin from Pepsinogen: 1) Chief cells secrete pepsinogen- optimal pH =2 for activation of pepsinogen. Becomes inactivated at pH>4. 2) At the same time parietal cells secrete HCL and IF. HCL brings pH to acidic levels, allows conversion of pepsinogen to pepsin. 3) Pepsin can now breakdown proteins into peptides
•
Process of Acid secretion: o Parietal/Oxyntic cells secrete H+ into the lumen against a large H+ concentration gradient. - Parietal cells have lots of mitochondria that take 40% of the cell volume, to provide ATP for active transport of H+. Where does the H+ (and Cl-) come from? H+ ions are generated within cells (parietal). 1) Cellular metabolism occurs producing CO2 and water. In the cell CO2 + water à carbonic acid. CO2 and H2O can also diffuse from the mesenteric veins that drain the stomach. 2) Carbonic acid disassociates into carbonic ions (HCO3-) and Hydrogen ions (H+). 3) The bicarbonate ions are exchanged via an anion anti-porter for Chloride ions from the veins. Bicarbonate ions end up in the veins. 4) pH of the veins draining the stomach increases (‘Alkaline tide’) 5) Cl- ions diffuse out of the parietal cell into the lumen, H+ ions are actively pumped via an H+/K+ ATPase (proton pump) in exchange for K+ ions. This is occurring on the basal level.
BMS2031
GASTROINTESTINAL TRACT o
LECTURE 3
Receptor Mediated Acid Secretion - Parietal HCL secretion is activated by nerves and hormones when you ingest a meal. 1) The Basolateral membrane of the parietal cell is embedded with receptors (Gastrin, Histamine, Ach and Somatostatin). 2) Histamine, Gastrin and Acetylcholine stimulate gastric acid secretion above basal levels. Somatostatin (GHIH) inhibits gastric secretion (will not look at that). - Gastrin acts on G-type receptors. - Histamine acts on Histamine receptors - Acetylcholine from parasympathetic nerves innervating the parietal cells act on muscarinic receptors 3) Lead to activation of second messengers 4) Second messengers act on H+/K+ ATPase (proton pumps) which sit in vesicles in cytoplasm 5) Proton pumps inserted into luminal membrane 6) Increase in acid secretion above basal levels
Describe how gastric mucosa is protected from acidic gastric juices •
There are 3 main pathways by which the stomach protects its lining: 1. Mucosal cells tightly joined to each other by tight junctions (no leakage of gastric acid) 2. Mucous rich in bicarbonate secreted from goblet cells in mucosal lining 3. Differentiation of stem cells (every 3-5 days the lining of the stomach and digestive tract replaces itself). - The oesophagus and duodenum do not have these protective linings in place. - Body attempts to neutralise the acidic Chyme that enters the duodenum from the stomach
