Overview
- Gastric secretion
- cells of gastric mucosa secrete gastric juice
- composed of hydrochloric acid (HCl), pepsinogen, intrinsic factor (IF), and mucus
- HCl and pepsinogen initiate protein digestion
- IF is required for vitamin B12 absorption in ileum
- composed of hydrochloric acid (HCl), pepsinogen, intrinsic factor (IF), and mucus
- cells of gastric mucosa secrete gastric juice
- mucus protects gastric mucosa from corrosive action of HCl and lubricates gastric contents
Gastric Glands
- Oxyntic glands
- body of stomach contains oxyntic glands
- oxyntic glands empty secretory products via ducts into lumen of stomach
- opening of ducts are called gastric pits
- oxyntic glands contain parietal cells and chief cells
- parietal cells secrete HCl and IF into oxyntic ducts
- chief cells secrete pepsinogen into oxyntic ducts
- oxyntic glands empty secretory products via ducts into lumen of stomach
- body of stomach contains oxyntic glands
- Pyloric glands
- antrum of stomach contains pyloric glands
- pyloric glands empty secretory products via ducts into lumen of stomach
- opening of ducts are called gastric pits
- pyloric glands contain G cells and mucosal neck cells
- G cells secrete gastrin into systemic circulation, not into pyloric ducts
- mucosal neck cells secrete mucus and HCO3– into pyloric ducts
- mucus forms a gel-like protective barrier between gastric mucosal cells and gastric lumen
- protects gastric mucosal cells against acid (HCl) and digestive enzymes (pepsin)
- HCO3– embeds in mucosal gel-like protective barrier
- neutralizes any HCl that may penetrate mucosal layer
- mucus forms a gel-like protective barrier between gastric mucosal cells and gastric lumen
- pyloric glands empty secretory products via ducts into lumen of stomach
- antrum of stomach contains pyloric glands
- inactivates any pepsin that may penetrate mucosal layer
Gastric Parietal Cell
- Parietal cell polarity
- apical membrane
- contains H+-K+ ATPase and Cl– channels
- basolateral membrane
- contains Na+-K+ ATPase and Cl–/HCO3– exchanger
- apical membrane
- Parietal cell secretion
- parietal cells secrete HCl and IF into oxyntic ducts that empty into lumen of stomach
- HCl acidifies gastric contents
- 1 ≤ pH ≤ 2
- low pH converts inactive pepsinogen zymogen to active pepsin enzyme
- pepsin is a protease that initiates protein digestion
- low pH converts inactive pepsinogen zymogen to active pepsin enzyme
- 1 ≤ pH ≤ 2
- Mechanism of HCl secretion
- aerobic metabolism of gastric parietal cell produces CO2
- intracellularly, CO2 combines with H2O to form H2CO3, which dissociates into H+ and HCO3–
- CO2 + H2O → H2CO3 → H+ + HCO3–
- carbonic anhydrase catalyzes hydration of CO2
- at apical membrane, H+ is secreted into lumen of stomach via H+-K+ ATPase
- H+ secretion inhibited by omeprazole, a proton pump inhibitor and an antacid
- at apical membrane, Cl– “follows” H+ and is secreted into lumen of stomach via Cl– channels
- at basolateral membrane, HCO3– is absorbed from cell into bloodstream via Cl–/HCO3–exchanger
- HCO3– moves out of cell and into bloodstream
- HCO3– is responsible for “alkaline tide” (high pH) that is observed in gastric venous blood following a meal
- eventually, HCO3– is secreted back into gastrointestinal tract in pancreatic secretions
- Cl– moves out of bloodstream and into cell
- HCO3– moves out of cell and into bloodstream
- Activation of HCl secretion
- stimuli
- smelling, tasting, and conditioned reflexes in anticipation of food
- via vagal stimulation
- direct and indirect pathways of stimulation
- via vagal stimulation
- distension of stomach
- via vagal stimulation
- direct and indirect pathways of stimulation
- via vagal stimulation
- presence of breakdown products of protein (small peptides and amino acids)
- via stimulation of gastric G cells to secrete gastrin
- phenylalanine and tryptophan are most potent stimuli for gastric secretion
- smelling, tasting, and conditioned reflexes in anticipation of food
- vagal stimulation
- direct pathway
- vagus nerve innervates gastric parietal cells
- at synapse, ACh is released and binds muscarinic M3 receptors coupled to Gq proteins
- ↑ ACh → (+) M3 receptors → (+) Gq proteins → (+) PLC → ↑ DAG and IP3
- IP3 releases Ca2+ from intracellular stores
- DAG and Ca2+ → (+) PKC → (+) H+-K+ ATPase → ↑ HCl secretion via gastric parietal cells
- indirect pathway
- vagus nerve innervates gastric G cells
- at synapse, gastrin-releasing peptide (GRP) is released
- GRP → ↑ gastrin secretion via gastric G cells
- atropine
- atropine inhibits HCl secretion via gastric parietal cells
- atropine is a cholinergic muscarinic antagonist
- atropine blocks muscarinic M3 receptors on gastric parietal cells
- blocks ACh-mediated, direct pathway of HCl secretion
- atropine does not inhibit HCl secretion via gastric parietal cells completely
- atropine does not block GRP-mediated, indirect pathway of HCl secretion
- atropine inhibits HCl secretion via gastric parietal cells
- direct pathway
- histamine
- histamine is released from enterochromaffin-like (ECL) cells in gastric mucosa
- histamine diffuses to nearby gastric parietal cells
- paracrine mechanism of delivery
- histamine binds H2 receptors coupled to Gs proteins on gastric parietal cells
- histamine → (+) H2 receptors → (+) Gs proteins → (+) adenylyl cyclase → ↑ cAMP
- ↑ cAMP → (+) PKA → (+) H+-K+ ATPase → ↑ HCl secretion via gastric parietal cells
- HCl secretion inhibited by cimetidine, a H2 receptor inhibitor and an antacid
- gastrin
- gastrin is released from G cells of antrum of stomach into systemic circulation
- gastrin is not released into pyloric ducts that empty into lumen of stomach
- gastrin is delivered back to stomach via systemic circulation
- endocrine mechanism of delivery
- gastrin stimulates HCl secretion via gastric parietal cells by 2 mechanisms
- gastrin binds CCKB receptors coupled to Gq proteins on gastric parietal cells
- gastrin → (+) CCKB receptors → (+) Gq proteins → (+) PLC → ↑ DAG and IP3
- IP3 releases Ca2+ from intracellular stores
- DAG and Ca2+ → (+) PKC → (+) H+-K+ ATPase → ↑ HCl secretion via gastric parietal cells
- gastrin binds CCKB receptors on ECL cells
- gastrin → (+) CCKB receptors → ↑ histamine secretion → ↑ HCl secretion via gastric parietal cells
- gastrin stimulates HCl secretion primarily by acting on ECL cells
- gastrin binds CCKB receptors coupled to Gq proteins on gastric parietal cells
- Zollinger-Ellison syndrome
- increased HCl secretion via gastric parietal cells caused by a gastrin-secreting tumor (gastroma)
- increased HCl (H+) secretion may cause duodenal ulcers
- increased acidification inactivates pancreatic lipase, an enzyme necessary for lipid digestion
- lipids are not adequately digested nor absorbed
- lipid excretion in feces (steatorrhea)
- increased HCl secretion via gastric parietal cells caused by a gastrin-secreting tumor (gastroma)
- gastrin is released from G cells of antrum of stomach into systemic circulation
- stimuli
- Inhibition of HCl secretion
- occurs when chyme is propelled along gastrointestinal tract from stomach to duodenum of small intestine
- HCl is no longer required to activate pepsinogen zymogen to active pepsin enzyme
- ↓ pH
- gastric contents acidify (pH lowers) when chyme is propelled along gastrointestinal tract from stomach to duodenum of small intestine
- food acts as a buffer for H+ in stomach
- food in stomach
- as gastric parietal cells secrete HCl, food buffers H+ and gastric contents acidify only slightly
- food in duodenum
- buffering capacity in stomach is reduced
- as gastric parietal cells secrete HCl, gastric contents further acidify
- pH < 1.5 initiates a negative feedback mechanism by inhibiting gastrin secretion via G cells
- gastric contents acidify (pH lowers) when chyme is propelled along gastrointestinal tract from stomach to duodenum of small intestine
- somatostatin
- somatostatin is secreted by D cells of gastric mucosa
- somatostatin binds receptors coupled to Gi proteins on gastric parietal cells
- somatostatin → (+) receptors → (+) Gi proteins → (-) adenylyl cyclase → ↓cAMP
- ↓ cAMP → (-) PKA → (-) H+-K+ ATPase → ↓ HCl secretion via gastric parietal cells
- somatostatin antagonizes stimulatory effect of histamine on HCl secretion
- prostaglandins
- prostaglandins bind receptors coupled to Gi proteins on gastric parietal cells
- prostaglandins → (+) receptors → (+) Gi proteins → (-) adenylyl cyclase → ↓cAMP
- ↓ cAMP → (-) PKA → (-) H+-K+ ATPase → ↓ HCl secretion via gastric parietal cells
- prostaglandins antagonizes stimulatory effect of histamine on HCl secretion
- prostaglandins bind receptors coupled to Gi proteins on gastric parietal cells
- occurs when chyme is propelled along gastrointestinal tract from stomach to duodenum of small intestine
- IF secretion
- IF is required for vitamin B12 absorption in ileum
- IF is only essential secretion of stomach
- IF deficiency causes pernicious anemia
Gastric Chief Cell
- Chief cell function
- chief cells secrete pepsinogen into oxyntic ducts that empty into lumen of stomach
- pepsinogen is a zymogen (inactive enzyme) that must be activated through cleavage
- increased concentration of H+ in gastric contents provides the low pH signal
- low pH converts inactive pepsinogen zymogen to active pepsin enzyme
- pepsin is a protease that initiates protein digestion
- activation of pepsinogen secretion
- stimuli
- vagal stimulation → ↑ pepsinogen secretion via chief cells
- ↑ H+ → ↑ pepsinogen secretion via chief cells
- stimuli