3a. Gastric Acid Secretion CAMTASIA Flashcards
Generally, functions of the stomach?
It functions primarily as a reservoir to store large quantities of recently ingested food, thus allowing intermittent feedings, initiating the digestive process, and releasing its contents in a controlled fashion downstream to accommodate the much smaller capacity of the duodenum.
What are the 2 types of mucosa in the stomach?
Where is each located/what does each do?
- oxyntic gland mucosa: secretes acid, located in prox stomach (body, fundus).
- pyloric gland mucosa (antrum). secretes gastrin
what are the 5 layers of the stomach lining?
in what layer are all the functional secretory elements?
- mucosa (contains secretory elements)
- deep mucosa/lamina propria
- submucosa (connective tissue of collagen and elastin)
- muscularis propria
- serosa
Parietal/Oxyntic glands of the fundus: what cell types do they contain?
- surface mucus cells
- mucus neck cells
- parietal cells
- chief cells
- enterochromaffin-like cells
oxyntic glands: what do they secrete?
anatomy of the glands?
location?
- acid, intrinsic factor, most gastric enzymes
- straight, simple tubular glands
- located in fundus/body
anatomy of an oxyntic gland: what are the important areas/what cell types are located there?
each gland has 3 areas: isthmus, neck, base
Isthmus: surface mucous cells
Neck: parietal and mucous neck cells
Base: chief cells
Scattered throughout: D cells (somatostatin), enterochromaffin cells (histamine)
what is the process of creating these gastric exocrine cells? where do they start/where do they migrate?
- Start as stem cells (precursor cells above) in the midregion or neck of the gastric glands.
- Upward flow of the neck cells toward the surface is a rapid process, < 1 week, –> mucus cells
- Downward flow of neck cells into the gastric gland may require several weeks –> parietal cells and chief cells.
Motor functions of the stomach?
- reservoir for ingested food
- digestion: mixing, grinding, pepsinogen secretion (initial protein digestion)
- Empties into duodenum once particles are 50microns in size
What is the cephalic phase? what are the things that happen during this phase?
First phase of acid secretion
Cephalic = initial response to sight, smell, taste, thought of food
-Vagally mediated via direct stim of parietal cells & ECL cells; indirect stim of G cells
What is the gastric phase? what happens during this phase?
second phase of acid secretion in response to a meal
- distension
- buffering of gastric acid pH
- AA stimulation of the parietal cells and G cells
what is the intestinal phase? what happens?
third phase of acid secretion in response to a meal
- response to movement of food out of the stomach/low pH
- chyme components in duodenum w release of secretin & GIP
Cardia: begins at what location (anatomically)?
transition from what cell type to what?
what is function?
gastric pits are deep or shallow?
- begins at Z line
- transition from Squamous to Columnar (at GEJ)
- Protects surface of the stomach from corrosive gastric contents, prevents reflux
- Shallow gastric pits
Fundus/body
what is function?
gastric pits are deep or shallow?
what cell type?
- Accomodation of food
- Gastric acid secretion
- Deep gastric pits – parietal cells, chief cells, endocrine cells (ECL, D cells)
Antrum:
function?
gastric pit depth? cell types?
Mixing, grinding, sieving particles
Regulation of gastric secretory function via gastrin/somatostatin
-Gastric pits are intermediate: surface and neck mucus cells, endocrine cells (G cells, D cells)
LES and cardia: secretions?
Mucus
HCO3
Fundus and body: secretions?
H+
Intrinsic factor
mucus
HCO3
pepsinogens
lipase
antrum and pylorus: secretions?
mucus
HCO3
surface cells and neck cells: product? function?
mucus, HCO3, trefoil peptides
lubrication, protection
parietal cells: product? function?
H+, intrinsic factor
protein digestion, binding of cobalamin, protection from bacteria
chief cells: product? function?
pepsinogen, gastric lipase
Protein digestion, triglyceride digestion
endocrine cells: product? function?
gastrin (G cell), histamine (ECL cell), somatostatin (D cell)
regulation of acid secretion
what is a pareital cell? where is it located? what does it produce? what does it require?
Principle cell in oxycintic portion.
produces gastric acid
requires energy to concentrate H ions, gets it from ATP produced from mitochondria wihtin the cell
Describe the parietal cell in its resting state.
- Resting state: the cytoplasm of the parietal cells is dominated by numerous tubulovesicles.
- An intracellular canaliculus is continuous with the lumen of the oxyntic gland.
- Resting state: canaliculus is collapsed.
- Low flow of acid (note only one yellow pump on the canaliculus)
Parietal cell: what happens with stimulation?
After stimulation of acid secretion the tubulovesicles become microvilli and project into the canaliculus, which has become greatly expanded to occupy much of the cell.
Exchanges H for K and creates HCl which is released into the lumen
Carbonic anhydrase and H,K,ATPase (enzymes for the production and secretion of acid), are localized in the microvilli.
The activities of these enzymes increases dramatically during acid secretion. Acid secrtion begins within 10 minutes of administering a stimulant.
what stimulates the parietal cell?
acetylcholine (muscarinic receptor). incr cellular Ca
gastrin (CCK-B type receptor). Incr intracellular Ca
histamine (H2 receptor). most important: both efficient and a good target for meds. incr cellular cAMP and also Ca.
what are a few H2 receptor blockers?
cimetidine, ranitidine, nizatidine, famotidine (last is most potent we have)
Sites of action of some anti-acid drugs?
- Proton-pump inhibitors. inhbition of the H/K ATPase totally blocks acid secretion. ex: omeprazole
- H2 blockers
how is the parietal cell able to generate acid without becoming too alkaline?
accumulation of OH results from pumping out of H+… but bicarb is exchanged for Cl at the basolateral side of cell. (Cl goes IN to the cell, bicarb goes out)
thus the pH doesn’t change much within the cell
“alkaline tide”
what happens to the alkaline part of the alkaline tide?
architectural relationship between capillaries and the basolateral side of the mucosal cells.
The OH is picked up by the capillaires and brought to the surface cells to defend it against acid.
At low rates of secretion, what is the compositin of the gastric juice?
At high rates?
Low rates: Mostly NaCl, very low H+ and K+ (NON parietal component - basal alkaline secretion)
High rates: Mostly HCl. Low H+, Low K+ (Parietal component - result of stimulation)
Always higher than plasma for H+, Cl-, K+. Always than lower than plasma for Na+.
Always isotonic to plasma, regardless of composition!
what stimulates the secretion of mucus from the mucus neck cells?
What stimulates mucus secretion from the surface mucus cells?
Neck cells: vagal nerve stimulation and Acetylcholine.
Surface cells: physical stimulation of food.
How do mucus and bicarb protect the gastric mucosa from acidic damage?
Secreted mucus is a gel which traps the alkaline part of surface cell secretion. Present during the interdigestive phase - forms alkaline layer of lubricant.
During meal response, the mucus protects the stomach mucosa from both physical and chemical damage.
- neutralizes some acid
- prevents pepsin from contacting mucosa
- if mucus contacts acid, it precipitates it into clumps and passes it into the duodenum.
agents that disrupt the gastric mucosal barrier? (4)
- weak acids (aspirin)
- alcohol
- NSAIDs (ibuprofen)
- detergents (bile salts)
what are the 3 types of communication that mediate responses in the GI tract?
- endocrine
- neurocrine
- paracrine
describe endocrine communication in the GI tract
Endocrine: Sensory cells (in stomach) respond to mechanical or chemical stimuli by releasing transmitters (hormones) that travel by way of blood to target cells or tissues. The apical surfaces of endocrine cells have microvilli that face the intraluminal contents of the gut. These respond to a specific aspect of the intraluminal milieu such as changes in pH or osmolality or specific nutrients.
Examples of the hormones released include: cholecystokinin (CCK), gastrin, glucose insulinotropic peptide (GIP), secretin, pancreatic polypeptide (PP).
describe neurocrine communication in the gut
Neurocrine: With this mechanism the sensing and transmissions to target tissues are completely mediated by nerves and neurotransmitters.
Nerves sense stimuli such as nutrients, pH and osmolality in the luminal contents as well as the movement of the contents and the distension of the gut lumen. The message to the target tissue can be entirely within the nerves in the wall of the gut (the enteric nervous system), or it can be to the central nervous system.
In both cases, activation of nerves causes changes in the secretory or motor activity of the GI tract. These nerves are thus sometimes referred to as secretomotor neurons.
Examples of the neurotransmitters released include: acetylcholine (Ach), CCK (some mediators can act through more than one mechanism), gastrin releasing peptide (GRP), nitric oxide (NO), somatostatin, substance P, vasoactive intestinal peptide (VIP).
describe paracrine communication in the gut
Paracrine: A mechanism where the sensing cell releases a transmitter that mediates the response in neighboring cells. There are only a few paracrine responses identified in the GI tract, they help regulate gastric acid secretion.
Mediators functioning by this mechanism include: CCK, histamine, 5-hydroxytryptamine (5-HT), and somatostatin.
Hormones involved in gastric acid secretion? (4)
Gastrin
CCK
secretin
Glucose-dependent insulinotropic peptide (GIP)
paracrines involved in GA secretion?
somatostatin
histamine
neurocrines involved in GA secretion?
Ach
GRP
What phase causes the most acid secretion?
gastric (50%)
cephalic (30%)
A few things that happen during the cephalic phase?
Chemoreceptors and mechanoreceptors in the tongue, mouth and nose are stimulated.
Afferent nerve impulses are relayed through vagal nucleus to stomach –> activate enteric NS –> acid secretion.
Uses ACH!
-Directly stimulates Parietal cel, chief cell, ECL cell, G cells
Indirectly stimulates G cells via GRP (through vagal)
What does Ach do in the stomach?
- from vagus nerve, acts directly on parietal cells
- activates ECL cells to release histamine –> stimulates parietal cell
- stimulates G cell to release gastrin
what is the main mediator of gastrin release from teh G cell?
Enteric neurons stimulated during the cephalic phase by vagal stimulation GRP (gastrin-releasing peptide) which is the main mediator affecting the release of gastrin from the G cell.
Release of gastrin stimulates the ECL cell to release histamine which in turn stimulates the parietal cell through a paracrine mechanism.
Gastric phase: a few things that happen?
Food enters stomach, mixes with some acid juice and buffers the acid.
pH rises to 6 and allows release of more gastrin.
AA and protein products stimulate cells to release gastrin
Fundal distension increases parietal cell secretion via vagally-mediated reflex arc.
Gastric secretion and acidity directly after a meal?
Once stomach is empty, less gastrin is released
No longer food tehre to buffer pH so the pH lowers
Acidity stimulates D cells to release somatostatin, which inhibits G cells –> less gastrin.
Why do ulcer patients hvae relief about 2 hrs after a meal?
The food bolus buffers the acid
pH rises, gastrin is released, acid is stimulated but pH is still not very acidic
