Pharmacology I: Biochemical Signalling BPS2011 Notes
Gastrointestinal Tract
Function:
- Digest food and absorption of nutrients and water
Processes:
- Motility: Ingestion, mastication (chewing), deglutition (swallowing), peristalsis
(contraction and relaxation of smooth muscles), and segmentation
- Deglutition (swallowing): buccal phase (voluntary - tongue pushes bolus to
oropharynx), pharyngeal stage (involuntary - pharynx to oesophagus via
medulla oblongata), and esophageal stage (involuntary - bolus pushed by
peristalsis)
- Chyme: acidic fluid of gastric juices and digested food. Moves from stomach
to the small intestine (duodenum).
- Secretion: exocrine and endocrine
- Salivary glands: Contain acinar cells that secrete salivary amylase that turns
starch into sugars.
- Absorption: of water, ions, and small molecules
- Storage and elimination of waste
- Immune barrier to protect GIT from ingested pathogens
Stomach
- Function:
- Temporary reservoir of dietary food and liquids
- Mixing of food and water with gastric secretory products (acid and gastrin)
- Grinding food to decrease size of particulates and to enhance digestion
- Regulating exit of chyme into duodenum in response to stimuli
- Structure and components:
- Lumen: lined with mucus-producing epithelial tissues arranged to form gastric
pits
, Pharmacology I: Biochemical Signalling BPS2011 Notes
- Gastrin: Peptide hormone released from G cells in the stomach to stimulate
gastric acid (HCl) secretion to:
- Release and activate pepsin from pepsinogen in chief cells
- Trigger somatostatin release from D cells
- Breakdown proteins to aid in digestion
- Kill bacteria or foreign pathogens that are ingested or manage to
infiltrate the GIT
- Inactivate salivary amylase
- Gastric acid (HCl): is secreted from Parietal cells and functions to :
- pumps H+ into lumen of stomach via H-K-ATPase pump in exchange
K+ enters Parietal cell.
- CL- from blood capillaries travels into Parietal cells via Cl- channel to
compensate for the electrical gradient produced by H+ and HCl
secretion.
- Disease: Acid reflux and heartburn
-
- Treatment:
- ECl cells can be stimulated directly by vagal afferents. Thus, a
vagotomy is advised to prevent stimulation of ECl cells by the vagus.
- H2 blockers: Parietal cells secrete HCl in response to histamine. Thus
blocking the histamine H2 receptor will block histamine action and
thus prevent HCl secretion into the lumen of the stomach.
- Proton pump inhibitors on parietal cells: Inhibit proton movement into
lumen of the stomach
- Atropine: muscarinic receptor antagonist. Preventing binding of ACh,
therefore, preventing activation of G cells and secretion of gastrin.
- Proglumide: CCK receptor antagonist. Preventing gastrin binding to
CCKB on ECl cells, therefore preventing histamine release.
- Full signal and hormone pathway of food ingestion
- Food (stretch gut wall and activate sensory pathways) or cephalic reflexes
and enteric sensory neurons initiate gastric secretion
- Sensory pathways stimulate vagus nerve to release substances
- ACh binding to M3 receptors on parietal cells and ECL cells
, Pharmacology I: Biochemical Signalling BPS2011 Notes
- ACh activates G cells and secrete gastrin which binds to CCKB receptors.
- Gastrin indirectly stimulates ECL cells to secrete histamine which
binds to H2 receptors to release gastric acid
- Gastrin directly stimulates parietal cells to release gastric acid
- Presence of amino acids in food stimulates G cells directly too
- Acid stimulates short reflex secretion of pepsinogen from chief cells using
enteric sensory neurons
- Somatostatin release by H+ is the negative feedback signal. Somatostatin
inhibits gastric acid secretion.
- Gastric acid (HCl) release in the stomach
- ACh binds to M3 receptors on parietal cells
- Gastrin released by G cells bind to cholecystokinin (CCK) B receptors on
parietal cells and induces expression of K/H ATPase: to increase H+
secretion
- Histamine binds to H2 receptors on parietal cells and induces expression of
K/H ATPase: to increase H+ secretion
- Due to release of H+ into the stomach lumen = decrease pH = stimulates D
cells to release somatostatin to inhibit G cells from releasing gastrin
- Neurons and hormones stimulate D cells to release somatostatin which inhibit
ECL cells from releasing histamine
- Surgery
- Bariatric surgery: surgery on the stomach designed to make the stomach
smaller and to make the person feel fuller.
- Gastric sleeve surgery: surgery on the stomach, where a portion of the
stomach is removed to make the person feel fuller after eating smaller
amounts.
- Altered endocrine hormones:
- Ghrelin (hormone that stimulates appetite) drops as were remove the
part of the stomach where ghrelin is released
- Gastrin drops
- Increase in insulin, GLP, and GIP PYY
- ICC-opathy
- Gastroparesis: where the stomach can’t empty itself (delayed gastric
emptying)
- Chronic unexplained nausea and vomiting
- Fullness after a meal (postprandial fullness)
- Early satiety
- Abdominal pain and bloating
Small Intestines
- Function:
- Duodenum: Main site for enzymatic digestion of food
- Duodenum: Chyme entering triggers bile acid release
- Duodenum: Neutralising acidity of chyme
- Ileum: Absorbs vitamin B12 and bile salts
- Jejunum: Main site for absorption of nutrients
- Absorption of water and electrolytes
, Pharmacology I: Biochemical Signalling BPS2011 Notes
- Structure and components:
- Large length of small intestine aids in its functions (absorption)
- Villi: foldings of mucosa that project into lumen to increase surface area for
absorption of nutrients, water, and drugs.
- Simple columnar epithelium: absorb and secrets substances between
lumen and body
- Lacteal: drains fluid and chylomicrons from intestinal space and for fat
absorption
- Arteriole: takes nutrients to cells of villi
- Venule: drains blood and nutrients to the liver
- Microvilli: foldings of plasma membrane of villi that increase surface area for
absorption of nutrients, water, and drugs.
- Brush border enzymes: produced by intestinal epithelium and exocrine
pancreas and sticks to villi as chyme pass through. Are digestive enzymes
that help with digestion.
- Bile/bile acids: Made from cholesterol in liver and stored in gallbladder.
Released into duodenum after a fatty meal to digest fats (vitamin A, D, E, K)
- Act on GPCR TGR5 and couples to Gas to increase intracellular
cAMP.
- Bicarbonate secretion: Bicarbonate neutralises chyme that enters from acidic
stomach conditions
- Mucus: produced from intestinal goblet cells and mixed with isotonic NaCl to
protect and lubricate lumen.
- Isotonic solution of NaCl: produced from crypt cells to protect and lubricate
lumen.
- Simple columnar epithelia L-cells that stimulate insulin release to lower blood
sugar levels
- Sphincters
- Pyloric sphincter: regulates amount of chyme that enters small
intestine
- Ileocecal sphincter: Allow digested food materials to pass from the
small intestine into your large intestine.
- Proximal to distal
- Pyloric sphincter, duodenum, jejunum, ileum, ileocecal sphincter
- Secretions that breakdown food
- Fats
- Lipase (stomach and pancreas): breakdown triglycerides into fatty
acids and glycerol
- Bile (Produced in liver and stored in gallbladder): emulsify fats to
increase surface area for lipase to work on and helps absorption
across epithelial cells. Bile salts also decrease surface tension of fat
droplets.
- Proteins
- Pepsin (stomach): breakdown of proteins to amino acids
- Endopeptidases (small intestine): breakdown proteins at non-terminal
end
- Exopeptidases (small intestine): breakdown proteins at terminal end
Gastrointestinal Tract
Function:
- Digest food and absorption of nutrients and water
Processes:
- Motility: Ingestion, mastication (chewing), deglutition (swallowing), peristalsis
(contraction and relaxation of smooth muscles), and segmentation
- Deglutition (swallowing): buccal phase (voluntary - tongue pushes bolus to
oropharynx), pharyngeal stage (involuntary - pharynx to oesophagus via
medulla oblongata), and esophageal stage (involuntary - bolus pushed by
peristalsis)
- Chyme: acidic fluid of gastric juices and digested food. Moves from stomach
to the small intestine (duodenum).
- Secretion: exocrine and endocrine
- Salivary glands: Contain acinar cells that secrete salivary amylase that turns
starch into sugars.
- Absorption: of water, ions, and small molecules
- Storage and elimination of waste
- Immune barrier to protect GIT from ingested pathogens
Stomach
- Function:
- Temporary reservoir of dietary food and liquids
- Mixing of food and water with gastric secretory products (acid and gastrin)
- Grinding food to decrease size of particulates and to enhance digestion
- Regulating exit of chyme into duodenum in response to stimuli
- Structure and components:
- Lumen: lined with mucus-producing epithelial tissues arranged to form gastric
pits
, Pharmacology I: Biochemical Signalling BPS2011 Notes
- Gastrin: Peptide hormone released from G cells in the stomach to stimulate
gastric acid (HCl) secretion to:
- Release and activate pepsin from pepsinogen in chief cells
- Trigger somatostatin release from D cells
- Breakdown proteins to aid in digestion
- Kill bacteria or foreign pathogens that are ingested or manage to
infiltrate the GIT
- Inactivate salivary amylase
- Gastric acid (HCl): is secreted from Parietal cells and functions to :
- pumps H+ into lumen of stomach via H-K-ATPase pump in exchange
K+ enters Parietal cell.
- CL- from blood capillaries travels into Parietal cells via Cl- channel to
compensate for the electrical gradient produced by H+ and HCl
secretion.
- Disease: Acid reflux and heartburn
-
- Treatment:
- ECl cells can be stimulated directly by vagal afferents. Thus, a
vagotomy is advised to prevent stimulation of ECl cells by the vagus.
- H2 blockers: Parietal cells secrete HCl in response to histamine. Thus
blocking the histamine H2 receptor will block histamine action and
thus prevent HCl secretion into the lumen of the stomach.
- Proton pump inhibitors on parietal cells: Inhibit proton movement into
lumen of the stomach
- Atropine: muscarinic receptor antagonist. Preventing binding of ACh,
therefore, preventing activation of G cells and secretion of gastrin.
- Proglumide: CCK receptor antagonist. Preventing gastrin binding to
CCKB on ECl cells, therefore preventing histamine release.
- Full signal and hormone pathway of food ingestion
- Food (stretch gut wall and activate sensory pathways) or cephalic reflexes
and enteric sensory neurons initiate gastric secretion
- Sensory pathways stimulate vagus nerve to release substances
- ACh binding to M3 receptors on parietal cells and ECL cells
, Pharmacology I: Biochemical Signalling BPS2011 Notes
- ACh activates G cells and secrete gastrin which binds to CCKB receptors.
- Gastrin indirectly stimulates ECL cells to secrete histamine which
binds to H2 receptors to release gastric acid
- Gastrin directly stimulates parietal cells to release gastric acid
- Presence of amino acids in food stimulates G cells directly too
- Acid stimulates short reflex secretion of pepsinogen from chief cells using
enteric sensory neurons
- Somatostatin release by H+ is the negative feedback signal. Somatostatin
inhibits gastric acid secretion.
- Gastric acid (HCl) release in the stomach
- ACh binds to M3 receptors on parietal cells
- Gastrin released by G cells bind to cholecystokinin (CCK) B receptors on
parietal cells and induces expression of K/H ATPase: to increase H+
secretion
- Histamine binds to H2 receptors on parietal cells and induces expression of
K/H ATPase: to increase H+ secretion
- Due to release of H+ into the stomach lumen = decrease pH = stimulates D
cells to release somatostatin to inhibit G cells from releasing gastrin
- Neurons and hormones stimulate D cells to release somatostatin which inhibit
ECL cells from releasing histamine
- Surgery
- Bariatric surgery: surgery on the stomach designed to make the stomach
smaller and to make the person feel fuller.
- Gastric sleeve surgery: surgery on the stomach, where a portion of the
stomach is removed to make the person feel fuller after eating smaller
amounts.
- Altered endocrine hormones:
- Ghrelin (hormone that stimulates appetite) drops as were remove the
part of the stomach where ghrelin is released
- Gastrin drops
- Increase in insulin, GLP, and GIP PYY
- ICC-opathy
- Gastroparesis: where the stomach can’t empty itself (delayed gastric
emptying)
- Chronic unexplained nausea and vomiting
- Fullness after a meal (postprandial fullness)
- Early satiety
- Abdominal pain and bloating
Small Intestines
- Function:
- Duodenum: Main site for enzymatic digestion of food
- Duodenum: Chyme entering triggers bile acid release
- Duodenum: Neutralising acidity of chyme
- Ileum: Absorbs vitamin B12 and bile salts
- Jejunum: Main site for absorption of nutrients
- Absorption of water and electrolytes
, Pharmacology I: Biochemical Signalling BPS2011 Notes
- Structure and components:
- Large length of small intestine aids in its functions (absorption)
- Villi: foldings of mucosa that project into lumen to increase surface area for
absorption of nutrients, water, and drugs.
- Simple columnar epithelium: absorb and secrets substances between
lumen and body
- Lacteal: drains fluid and chylomicrons from intestinal space and for fat
absorption
- Arteriole: takes nutrients to cells of villi
- Venule: drains blood and nutrients to the liver
- Microvilli: foldings of plasma membrane of villi that increase surface area for
absorption of nutrients, water, and drugs.
- Brush border enzymes: produced by intestinal epithelium and exocrine
pancreas and sticks to villi as chyme pass through. Are digestive enzymes
that help with digestion.
- Bile/bile acids: Made from cholesterol in liver and stored in gallbladder.
Released into duodenum after a fatty meal to digest fats (vitamin A, D, E, K)
- Act on GPCR TGR5 and couples to Gas to increase intracellular
cAMP.
- Bicarbonate secretion: Bicarbonate neutralises chyme that enters from acidic
stomach conditions
- Mucus: produced from intestinal goblet cells and mixed with isotonic NaCl to
protect and lubricate lumen.
- Isotonic solution of NaCl: produced from crypt cells to protect and lubricate
lumen.
- Simple columnar epithelia L-cells that stimulate insulin release to lower blood
sugar levels
- Sphincters
- Pyloric sphincter: regulates amount of chyme that enters small
intestine
- Ileocecal sphincter: Allow digested food materials to pass from the
small intestine into your large intestine.
- Proximal to distal
- Pyloric sphincter, duodenum, jejunum, ileum, ileocecal sphincter
- Secretions that breakdown food
- Fats
- Lipase (stomach and pancreas): breakdown triglycerides into fatty
acids and glycerol
- Bile (Produced in liver and stored in gallbladder): emulsify fats to
increase surface area for lipase to work on and helps absorption
across epithelial cells. Bile salts also decrease surface tension of fat
droplets.
- Proteins
- Pepsin (stomach): breakdown of proteins to amino acids
- Endopeptidases (small intestine): breakdown proteins at non-terminal
end
- Exopeptidases (small intestine): breakdown proteins at terminal end
