Rao 2 - Gastric Secretions Flashcards
What are the 5 major secretory products of the stomach?
• What are there functions?
1. Hydrogen Ion
• Activates Conversion of Pepsinogen to Pepsin
• Kills Bacteria
• Digests Protein
-
Pepsinogens
• Pepsin digests protein by cleaving interior peptide bonds (Endopeptidase) -
Mucus
• Lubricates Food
• Protects Lining of the Stomach -
Intrinsic Factor
• Necessary for absorption of B12 -
Water
• Dissolves and Dilutes undigested material
What cells secrete intrinsic Factor?
Parietal Cells
Where is the Oxyntic gland mucosa located and what does it secrete?
Located in the Fundus and the Body and secretes HCL
Where is the pyloric mucosa located?
• what does it secrete?
Pyloric mucosa is found in the antrum and releases Gastrin (from G cells)
What cells are found in the Oxyntic Region of the Stomach (body and fundus)?
• Where within the gastric glands are the STEM cells located?
• What is the relationship of these cells relative to each other in the gland?
Cells: Parietal, Chief (peptic), Neck mucous cells, Stem cells, Enterochromaffin-like cells
Stem cells - are in the Neck of the Gastric gland
Stem cells that migrate upward will differentiate into mucous cells and cells that migrate downward will be Chief Cells (deepest in pit), ECL cells, or Parietal cells
How many Stem cells are there per gastric gland?
What are the primary products of the following cells:
• Mucous
• Parietal Cells
• ECL cells
• Chief cells
Mucus Cell => HCO3- secretion
Parietal Cell => Acid and Intrinsic Factor Secretion
ECL Cell => Paracrine release of Histamine (basal granules?)
Chief Cells => Release of Pepsinogen (APICAL granules)
What key features would you expect to see in a peptic cell?
- Well developed ER for synthesis of Pepsinogen
- Zymogen Granules filled with Pepsinogen
What key features would you expect to see in an endocrine cell in the stomach?
Granules at the Base of the cell
Apical Microvilli that can sense stimuli
What happens to the Tubulovesicles (TV) and Intracellular Canaliculus (IC) When a parietal cell is stimulated?
• what do the TV and ICs consist of?
Tubulovesicles:
• Has Carbonic Andydrase and H+, K+ ATPase (or proton pump) needed for H+ secretion
Intracellular Canaliculus:
• Infolding to which TVs fuse so that their enzymes are expressed on the cell surface
In an activated Parietal cell the TVs fuse with the IC so that it increases in size and has more proteins expressed so that more acid can be secreted
What happens to an intracellular canaliculis when the stimulus is removed from a parietal cell?
It returns to its NL configuration and TVs are reformed
What Enzyme located at the apical portion of the Parietal Cell is responsible for pumping protons into the lumen of the stomach?
• what drug inhibits this pump?
• what drug might you expect to inhibit this pump that does not?
• Why are drugs that inhibit this pump so effective?
H/K ATPase
Inhibited by PPIs (omeprazole) - these are effective because this is the ONLY hydrogen pump in the stomach so if you block it, you block >99% of proton secretion.
H/K ATPase is 60% homologous to Na/K ATPase, but is not affected by ouabain
What is the role of carbonic anhydrase in parietal cells?
• where is it located?
• how does this explain why vomitting leads to metabolic alkalosis?
- Carbonic anhydrase (CA) is located in the cytoplasm works by taking CO2 and H2O to make H+ and HCO3- that can then be pumped out of the cell with the H/K ATPase and Cl/HCO3- exchanger respectively
- In extreme vomiting you lose lots of acid so CA will be pulling CO2 and H2O out of the blood to make more H+, however for every H+ it puts into the lumen, it will put one HCO3- into the blood, this leads to metabolic acidosis
How does the Cell Prevent the K+ gradient from building up so high with the K/H exchanger that ATP cleavage will no longer be sufficient to pump protons?
A potassium channel on both the apical and basal side cycles K+ back into the cell after the K/H ATPase and Na/K ATPase pump it out
How does chloride get to the stomach lumen to combine with H+ and make HCl in the stomach?
Enters on the basolateral side via the HCO3/Cl exchanger and diffuses through the cytoplasm to the apical side of the cell and exits via a Chloride Channel
Other than to form HCl, why is chloride secretion so important in the stomach?
• how back diffusion of Cl- down its gradient prevented?
Cl- is important for maintaining a Negative Lumen potential in the stomach so that H+ is drawn out of the parietal cell
The mucosal barrier prevents Cl- from diffusing back down its graient from the apical side
What are some commonly used substances that break down the mucosal barrier in the stomach and allow for diffusion of Cl- back down its gradient?
Ethanol and Asprin
Note: Typically there is no change in the Potential Difference over time but Asprin and Ethanol Break down the mucous barrier that allows for the creation a potential difference by chloride
Why do people become hypokalemic with vommiting?
• Increased Acid production that occurs during vomitting leads to more cellular INFLUX of K+, but this influx is only allowed because of EFFLUX through the K+ channels that allow for K+ cycling. All K+ used by the K/H ATPase therefore comes from the blood via the Na/K ATPase on the basolateral side of the cell.
• K+ will be drawn out of the cell with each vomitting episode and “new” K+ will be put in stomach lumen from the blood
How does the electrolyte composition of the gastric mucosa change at low and high flow (secretory) rates?
_Low Flow (secretory) Rate:_ • **NaCl** is the predominant secretion - NON-parietal cell secretions
_High Flow (secretory) Rate:_ • **HCl** is the predominant secretion - PARIETAL CELL secretions
***Potassium levels stay pretty constant
What is the two component change is gastric juice composition?
Says that non-oxyntic secretion is produced continually at low rates and is overwhemed when secretion is stimulated from the parietal cells
Through what pathway does histamine work to increase acid secretion in the stomach?
Gs cAMP pathway
How does Ach increase gastric acid secretion?
Directly through M3 agonism => Gq (IP3/Ca) pathway activation
Indirectly through ECF cell activation triggering histamine release
How does Gastrin increase Acid production by the stomach?
• what triggers the release of gastrin itself?
Gastrin increases stomach acid directly through Gastrin-CCK2 agonism and through ECF cell activation so that it produces histamine
Gastrin release is triggered by Protein, Gastric Distention, and Vagal n. stimulation
Why would atropine not be that effective at decreasing gastric acid secretion?
It only blocks Ach so gastrin and histamine can still act on parietal cells
**Additionally GRP release from the vagus can still occur
Why might somone be more likely to experience heartburn in the around 10 in the evening as opposed to early in the morning?
• what factors mediate this effect?
Gastric acid secretion is diurnal in that it increases to 10-15% maximal stimulation INDEPENDENT OF GASTRIN at around 10 in the evening
What mediators are responsible for the Cephalic phase of gastric acid secretion?
• is this a vasovagal response?
Yes, this is a vasovagal response, chemo and mechano receptors detect the presence of food and relay and efferent message that causes release of:
• Ach
• GRP
***THINK ABOUT A VAGOTOMY or ATROPINE, this would DESTROY the CEPHALIC phase****
Compare the release of Gastrin when eating Steak vs. Rice.
Gastrin is released in response to PROTEINs (distention, and vagal stimulation), NOT Carbs
What is the PREDOMINANT REFLEX that controls acid secretion in the stomach?
Pyloro-pyloric reflex that occurs with distention of the stomach where short and long intramural cholinergic reflexes happen
What factors inhibit gastrin release?
Negative Feedback at Gastric pH below 3 by H+ stimulating D-cells to secrete somatostatin (inhibits G cells, ECL cells, and parietal cells)
Summary of Mechanisms Stimulating Gastrin Secretion
What is the major regulation method of gastrin release in the Oxyntic Gland area and Antrum of the stomach?
• Stimulus
• Mediation
• Inhibits Gastrin Release?
• Directly Inhibits Acid Secretion?
What is the major regulation method of gastrin release in the duodenum ONLY?
• Stimulus
• Mediation
• Inhibits Gastrin Release?
• Directly Inhibits Acid Secretion?
What is the major regulation method of gastrin release in the Duodenum and Jejunum?
• Stimulus
• Mediation
• Inhibits Gastrin Release?
• Directly Inhibits Acid Secretion?
Response to a meal
Pepsin
• What are the stimuli for release?
• what is the most potent stimulus for release?
• During what phases of stomach secretion is pepsin secreted?
1. Ach mediates secretion in the Cephalic and Gastric Phases = #1 most potent
2. Acid mediates release in a few ways:
• Stimulates LOCAL cholingergic reflex to stimulated Cheif (peptic) Cells
• Stimulates SECRETIN release from S cells of the duodenum that stimulates Chief (peptic) Cells
- Gastrin weakly stimulates pepsinogen release
What is required for pepsinogen to get activated?
Acid Cleavage
What is the predominant Defect leading to the formation of a gastric ulcer?
What are the causes of a duodenal ulcer?
