Gastric Secretions Flashcards
What are the different layers of the stomach (from which it is made)?
1) Outer longitudinal layer (responsible for peristalsis and stomach contraction)
2) Middle circular layer (form the pyloric sphincter and helps with mixing the food)
3) The inner oblique layer (enhances the churning and mixing of food with the gastric juices “which is unique to the stomach”)
What are the components of the gastric juice?
1) Hydrochloric acid
2) Pepsinogen
3) Intrinsic factor
4) Mucus
What is the function of hydrochloric acid?
1) Sterilization of meals
2) Hydrolysis of dietary macromolecules
3) Converts pepsinogen to pepsin
What is the function of pepsinogen?
Initiates the digestion of proteins
What is the role of the intrinsic factors?
It is required for the absorption of vitamin B12 in the ileum
What is the role of the mucus?
It protects the gastric mucosa from the corrosive actions of HCl in addition to lubricating the gastric contents
What are the motor functions of the stomach?
1) Stores large quantities of food
2) Mixing and propulsion of food
3) Slow emptying of chyme
What enables the stomach to store large quantities of food?
This is possible as stretching the stomach with food will initiate the vasovagal reflex, which will induce a reduction in the muscle wall tone (allows the stomach to expand without a significant increase in pressure)
What happens to the food in the stomach?
1) Peristaltic mixing waves are developed as the slow waves initiated by the Cajal (interstitial cells, which will initiate the basic electrical rhythm)
- During this process AP are generated along with spike potentials on top of the slow waves, these spike potentials results in a full-blown AP which is necessary for peristalsis
- Constrictor rings also forms in order to propel the food towards the antrum
2) Once the food reaches the pylorus two structures comes into play (these two structures works together to regulate the amount of chyme entering the duodenum and to aid in mixing)
- Pyloric pump (pyloric canal): which is a functional pumping mechanism that helps in regulating the flow of food into the duodenum
- Pyloric sphincter: which is a thickened muscular ring that controls the passage of chyme
What is meant by the retrograde movement/retropulsion?
In-case the food is has not been adequately mixed or semi-liquified it gets pushed back into the stomach to ensure the proper mixing with gastric juices before it passes through the pyloric sphincter
Why is the emptying of chyme from the stomach slow?
- As the small intestine is narrower and it is not designed to store food but only to absorb the nutrients, food consistency must be paste-like (as large food molecules can damage the mucosa) and the process must be controlled and slow to allow for a sufficient time to perform digestion and absorption efficiently
What are the different types of gastric mucosal cells?
1) Parietal cells
2) Chief cells
3) G-cells
4) Mucous cells
Where is the parietal cells found in the stomach?
In the body of the stomach
What does the parietal cells secrete?
1) Hydrochloric acid
2) Intrinsic factors
Where is the chief cells found?
In the body of the stomach
What does the chief cells secrete?
Pepsinogen
Where is the G-cells found in the stomach?
In the Antrum of the stomach
What does the G-cells secrete?
Gastrin
Where is the mucus cells of the stomach found?
In the Antrum of the stomach (generally through the entire stomach)
What does the mucus cells of the stomach secrete?
1) Mucus (protective, neutralizing effect on the gastric mucosa)
2) Pepsinogen
3) HCO3 (protective, neutralizing effect on the gastric mucosa)
What are the gastric mucosal cells that are found in the body of the stomach?
1) Parietal cells
2) Chief cells
What are the gastric mucosal cells that are found in the Antrum of the stomach?
1) G-cells
2) Mucus cells
3) D-cells (releases somatostatin to prevent excessive acid production)
The parietal, enterochromaffin-like and chief cells are part of which gastric gland?
Oxyntic glands
The G-cells and mucus cells are part of which gastric glands?
The antral/pyloric gland
What regulates the secretion of gastrin?
Somatostatin
Why are the G-cells found in the antrum but not in the upper part of the stomach?
To allow the gastrin regulate the acidity of the chyme
How does the oxyntic glands empty their secretory products into the stomach?
Through ducts (and their opening are called pits)
What part of the oxyntic gland secrete HCL?
The parietal cells have small spaces that are called canaliculi which will collect the HCl and get it out through the gastric pit
Where in the glands are the mucus, parietal and chief cells located?
1) Mucus cells are found in the neck of the gland
2) Parietal cells are found in the middle
3) Chief cells are found in the base of the gland, to allow for the conversion of pepsinogen as it ascends towards the HCl of the parietal gland converting it to pepsin which will aid in the digestion of protein
Which cell of the oxyntic glands is stimulated by gastrin and what does it secrete?
The enterochromaffin-like cells which secretes histamine and thus increase the production of HCl
Where does the G-cells secrete their contents into?
The circulation
What is the functions of gastrin?
1) Gastrin directly acts on the parietal cells via the bloodstream to increase HCl production
2) Gastrin stimulates the ECL cells to release histamine which enhances HCl production as a paracrine signal
3) Gastrin negatively regulates the D-cells to inhibit gastrin when the acid levels are high
What are the types of glands of the stomach?
1) Oxyntic glands
2) Pyloric glands
Where are the oxyntic glands found in the stomach?
In the body and fundus of the stomach (80% OF THE STOMACH)
Where are the pyloric glands of the stomach found?
In the antrum of the stomach
What are the cell types of the oxyntic glands?
1) Parietal cells (HCl and intrinsic factors)
2) Chief cells (pepsinogen)
3) ECL cells (histamine)
4) D-cells (somatostatin)
5) Mucus cells (mucus neck)
What are the cell types of the pyloric glands?
1) G-cells
2) Mucus neck
3) D-cells (somatostatin)
What is the function of the oxyntic cells?
1) Acid secretion for digestion and sterilization
2) Initial protein digestion
3) Hormonal and regulatory roles to modulate acid secretions
What is the function of the pyloric glands?
1) Regulation of acidic secretion via gastrin
2) Providing mucosal protection
3) Neutralization of acid near the gastric lining
4) Initiation of protein digestion
What is the key player in the secretion of HCl?
H+/K+ ATPase pump/proton pump, which are found in the canalicular membrane
Describe the process of HCl formation and secretion
The parietal cells has two membranes,
1) Canalicular membrane facing an empty space (small intracellular channel where HCl is secreted into the lumen of the stomach) and it is responsible for the production and release of HCl
- It contains the proton pump (H+/K+ ATPase), where it actively secretes hydrogen ions (H+) into the canaliculus in exchange for potassium ions (K+), using ATP as a energy source to pass the potassium against its concentration gradient and chloride ions will go into the canaliculus combining with the H+ forming the HCl which will then combine with the gastric juice
2) A basolateral membrane which faces the interstitial fluid (blood), exchanging substances between the cell and the bloodstream
- It contains two key transporters, a Na/K ATPase which pumps 3 Na+ Outside the cell and 2 K+ inside, and a Cl/HCO3 exchanger where the chloride enters the cell and travels towards the canalicular membrane exiting into the canaliculi through specific chloride channels and bicarbonate is taken outside the cell into the blood
- Finally the water follows osmosis to go into the stomach from its surrounding, adding volume to the HCl solution (which is the result of Cl and H+ combination after the removal of HCO3) this is = to Gastric Juice
What is meant by the alkaline tide?
It is the transient increase in blood alkalinity after a meal due to the release of bicarbonate via the Cl/HCO3 pump into the venous blood, during the production of HCl
What forms HCl?
Cl- + H+
What forms the Gastric Juice?
Cl- + H+ + Water + enzymes + Mucus
How is HCO3 produced?
- Carbonic anhydrase reaction
CO2 + H2O = H2CO3 (Carbonic anhydrase), which will dissociate into H+ and HCO3- (the H+ gets into the canaliculi, while the HCO3 out of the cell)
What are the Leaky K+ channels?
Found in the parietal cells and are important for maintaing potassium levels inside the parietal cells which is essential for H+/K+ ATPase proton pump
What is a conductance channel?
They are the channels that moves Cl- and K+ into the lumen of the canaliculus
What are the primary stimuli for the regulation of gastric secretions?
1) Gastrin (Released from G-cells) which is released from the G-cells and travels through the circulation influencing the activity of ECL and the parietal cells, gastrin release is negatively regulated by the release of somatostatin from the antral D-cells
2) Histamine
3) Acetylcholine
What stimulates the release of gastrin from the G-cells?
1) Proteins found in food
2) Gastrin releasing peptide from the vagus nerve
What inhibits the release of gastrin?
Somatostatin secreted by the D-cells in response to high acidity
Which neurotransmitter stimulates the parietal, chief and mucus cells?
Ach which is released by the vagus nerve
What distinguishes acetylcholine from gastrin and histamine in its effect on gastric cells?
Acetylcholine stimulates not only parietal cells but also chief cells (to release pepsinogen) and mucus cells (to secrete mucus), while gastrin and histamine exclusively stimulate parietal cells
What is the mechanism of parietal cell activation?
1) Apical surface amplification
- Increasing the density of pump, enhancing the cell’s ability to secrete acids
2) Receptor pathway
- Ach is released by the vagus nerve and binds to the M3 receptor signaled by the Ca2+ dependent pathway
- Gastrin is released by the G-cells to bind to the CCK-B receptor signaled by calcium
- Histamine is released by the ECL cells and binds to the H2 receptors via the signal of cAMP
3) Synergistic effect
4) Paracrine and Endocrine actions
What are the phases of gastric acid secretion?
1) Cephalic phase (sight, smell, taste, or thought of food stimulates acid secretion via the parasympathetic nervous system (vagus nerve))
- Via the Vagus nerve
2) Gastric phase
- Local nervous secretory reflexes
- Vagal reflexes
- Gastrin-histamine stimulation
3) Intestinal phase
- Nervous mechanism
- Hormonal mechanism
What stimulates the cephalic phase?
Sensory nerves (Sight, smell, taste, and thought), where the neurogenic signals that causes the cephalic phase gastric secretion originates in the cerebral cortex and in the appetite centers of the amygdala and hypothalamus
What is the mechanism of gastric acid secretion in the cephalic phase?
Neural stimulus (via the Vagus nerve)
What are the key-features of the cephalic phase?
It prepares the stomach for food without hormones
What stimulates the gastric phase?
Food in the stomach (distension of the stomach and proteins)
What is the mechanism of gastric acid secretion in the gastric phase?
1) Neural (Vagus reflex)
2) Hormonal (Gastrin)
What are the key features of the gastric phase?
It is dominated by gastrin, and it drives the secretion of acid
What stimulates the intestinal phase?
The chyme in the duodenum (acidity and volume)
What is the mechanism of gastric acid secretion in the intestinal phase?
1) Neural
2) Hormonal (Secretin)
What are the key features of the intestinal phase?
1) Controls the gastric activity
2) It slows emptying
Summarize the cephalic phase
- represents 30% of HCl secretion
- Sensory signal, then the vagus nerve will release neurogenic signals to the stomach (Ach) which will stimulate the parietal cells to release HCl, Chief cells to release pepsinogen and the G-cells to secrete gastrin
Which brain regions are involved in initiating the cephalic phase of gastric secretion?
1) Cerebral cortex
2) appetite center of the amygdala and hypothalamus
Summarize the gastric phase of acid secretion
- 60% of the gastric acid is produced in this phase
1) Due to the local enteric reflexes the distention of the stomach with food will stimulate the release of gastrin
2) The breakdown products of the food will also stimulate the G-cells to release gastrin
Summarize the intestinal phase
- 10% of the gastric acid is produced in this phase
- It inhibits the secretion of gastrin via intestinal factors to slow the passage of chyme
- Reverse enterogastric reflex, which is mediated by the myenteric nervous system & ANS, which can be initiated by (distension, acidity, protein breakdown or even the irritation of the mucosa of the small bowel)
- Irritation of the mucosa inhibits stomach secretions by release of several hormones like secretin, gastric inhibitory peptide, vasoactive intestinal polypeptide, and somatostatin
What are the hormones produced by the duodenal mucosa that regulates the intestinal phase?
1) Secretin: Inhibits gastric acid secretion and motility
2) Cholecystokinin (CCK): Slows gastric emptying, stimulated by fats
3) Gastric Inhibitory Peptide (GIP): Reduces gastric secretion.
4) Vasoactive Intestinal Peptide (VIP): Decreases gastric secretion
5) Somatostatin: Inhibits both gastric acid secretion and gastrin release.
- FYI: Secretin, GIP, VIP, and somatostatin-> inhibits gastric secretion and motility, while CCK->slows gastric emptying by targeting the pyloric pump and sphincter
How is pepsinogen secreted?
- Secreted by the chief and mucus cells
- Pepsinogen is a active proteolytic enzyme in a highly acidic medium (it is inactivated above the pH of 5), the acid in the stomach combines with pepsinogen to form pepsin
What stimulates the release of pepsinogen?
Acetylcholine from the vagus nerve and the enteric nervous plexus
How is the gastric emptying regulated?
Promoted by the intense peristaltic contractions in the antrum and opposed by the resistance at the pylorus, gastric emptying is controlled by two factors
What are the factors that controls the gastric emptying?
1) Gastric factors
2) Duodenal factors
What are the gastric factors that controls the gastric emptying?
- Stimulated by the increased volume of food (stretching the stomach wall), the pyloric pump is stimulated and the pyloric sphincter is inhibited (via the local myenteric reflexes), in addition to the secretion of gastrin by the G-cells of the antral mucosa which will enhance the pyloric pump activity and motility
- This will all promote the gastric emptying
What are the duodenal factors that control the gastric emptying?
1) The distention of the duodenum
2) Presence of fat digestion products
3) Acidity of the chyme (The acidity of the chyme will increase the release of secretin, which will contract the pyloric sphincter decreasing the rate of gastric emptying)
4) Hyperosmotic chyme (slows the rate of gastric emptying)
- These will all inhibit the gastric emptying
What is the mechanism of inhibiting the gastric emptying by the duodenal factors?
1) Enterogastric reflexes (Neural inhibition of the pyloric pump and increased pyloric sphincter tone)
2) Hormonal regulation (1) CCK will inhibit the motility and tightens the sphincter “stimulated by fat”, secretin will decrease the motility and tighten the sphincter “stimulated by the acidity”, GIP will slow the motlity and secretion “stimulated by fats and carbohydrates”)
Which hormone is released in response to fats in the duodenum and slows gastric emptying?
CCK
What is the role of gastrin in gastric emptying?
stimulating the pyloric pump + relaxing the pyloric sphincter= increases the motility of the stomach ->promoting the emptying
How does the duodenum regulate gastric emptying in response to acidic chyme?
Acidic chyme stimulates the release of secretin = decreases gastric motility & increases the pyloric sphincter tone = slow gastric emptying
Describe the gastric mucosa
- It is lined with highly resistant mucus cells with tight junctions in between the epithelial cells
1) Pre-epithelial
- Surface mucus secretions
- Bicarbonate secretions (neutralizes the acid near the stomach lining)
2) Epithelial
- Epithelial cells with tight junctions to prevent the backflow of HCl and the enzymes
- Regenerative capacity
- Prostaglandins
3) Subepithelial
- Mucosal blood flow (rich vascular network)
- Leukocytes
What are the substances that can damage a normal mucosal barrier?
1) Gastric acidity (H+)
2) Peptic enzymes (pepsin)
What factors can impair the 3-layer defensive forces of the mucosal barrier?
1) Ischemia
2) Shock
3) Delayed gastric emptying
4) Host factors
What are the factors that can directly damage the mucosa?
1) H.Pylori infection
2) NSAID
3) Cigarette smoking
4) Alcohol
5) Hyperacidity
What is peptic ulcer?
It is when the protective mechanisms of the gastric or duodenal mucosa are disrupted by acid and pepsin
- So either decrease in mucosal defense or hypersecretion of the acid
What are the causes of peptic ulcer?
1) Diminished effectiveness of the mucosal barrier:
- Use of aspirin or NSAID
- Increased catecholamines (like in stress)
2) Hypersecretion of the acid:
- Chronic anxiety
- Zollinger Ellison syndrome (“gastrin” secreting tumor in the pancreas)
- Systemic mastocystosis
What are other causes of peptic ulcer?
1) Irritation
2) Poor blood supply
3) Poor secretion of mucus
4) Infection (like with H.pylori, which colonizes the gastric mucus often in the antrum, attaching to the gastric epithelial cells and releasing cytotoxins (like cagA toxin), breaking down the mucous barrier, in addition H.pylori will inhibit somatostatin secretion from the D-cells leading to the increased secretion of HCl
5) Smoking (reduces the mucosal blood flow, inhibits the mucosal prostaglandin production, accelerates gastric emptying, and it also inhibits pancreatic bicarbonate secretion = “insufficient neutralization of acidic chyme =mucosal irritation and damage”)
What are the different treatments of peptic ulcers?
1) H2 “histamine” receptor antagonist (cimitidine), which will lower the stomach acidity and thus promotes the healing of peptic ulcers
2) PPI (proton pump inhibitor (omeprazole), it inhibits the H+/K+ ATPase which is stronger and lasts more compared to the H2 receptor antagonist
3) Antibiotics for H.pylori
4) Stoppage of NSAID use
What stimulates the gastric secretion in the cephalic phase?
- Chewing, swallowing, taste, smell of food
- These will all result in the excitement of the enteric secretomotor neurons to the parietal, G-cells and the ECL cells via the Vagus nerve
What stimulates the gastric secretion in the gastric phase?
1) Gastric distention
- Local and vagovagal reflexes stimulate parietal cells and release of histamine and gastrin
2) The peptides and amino acids in the lumen
- Release gastrin from G cells in stomach
What stimulates the gastric secretion in the intestinal phase?
1) Protein digestion products in the duodenum
- Release of gastrin from G cells in intestine and enetrooxyntin
2) Distension of the duodenum
- Enteric and vagovagal reflexes to ECL, G and parietal cells
3) Peptides and amino acids in the blood
- Release of gastrin from G cells in stomach
What inhibits the gastric secretion in the cephalic and gastric phases?
1) Vasovagal and enteric neural impulses
- Release of gastrin promotes release of somatostatin from the D cells
2) Low pH in the lumen
- Inhibition of parietal and G cells
What inhibits the gastric secretion in the intestinal phase?
1) Low pH in the duodenum
- Vagovagal and enteric reflexes that inhibit HCl secretion
2) Digestion products of fat and proteins
- Secretin, CCK and GIP inhibit parietal cells
3) Hypertonicity in the duodenum
- Unidentified enterogastrone inhibits HCl secretion
