32) Regulation and disorders of gastric secretion Flashcards
What is the function of the Fundus?
- Allows accomodation to occur
What is the function of the body?
- Secretion of mucus, pepsinogen and HCl
- It has numerous epithelial cells which contain a number of tubular glands
- The walls of the glands are lined with parietal cells that secrete HCl and intrinsic factors
What is the function of the antrum?
- Secrets gastrin which mediates HCl secretion
What are the contents of the gastric juice?
- Cations: Na+, K+, Mg2+ and H+
- Anions: Cl-, HPO42-. SO42-
- Pepsinogen
- Lipase
- Mucus
- Intrinsic factors
(pH is around 1-3)
How is gastric acid made in the stomach?
- CO2 and H2O diffuses into the epithelial cells of the stomach where they form H2CO3 (carbonic acid) via the enzyme carbonic anhydrase
- It acid can then dissociate to form HCO3- (bicarbonate) and H+
- The bicarbonate ions are transported out of the cell into the blood via secondary active transport which (in return) brings Cl- into the cell (as a result the blood side is a bit more alkaline)
- The Cl- is released into the stomach lumen via chloride channels
- A K+/H+ ATPase pump pumps H+ into the stomach lumen and pumps K+ into the epithelial cells
- THe H+ and Cl- (in the lumen) come together to form HCl which is the gastric juice
What do ECL cells do?
- They release histamine
Why is some of the gastric juice described as resting juice?
- It is not acidic as non-parietal cells secrete HCO3- which increases the pH making it more alkaline
How does mucus affect pH?
- Mucus is alkaline and thick
- It forms a water-insoluble gel n the epithelial surface which increases HCO3- secretion and protects against H+ secretion
What is renin?
- Renin is an enzyme that is quite important in the digestion of milk at birth
- Over time renin is replaced by pepsinogen
What is lipase?
- Lipase is an enzyme that digests fats
What is the purpose of intrinsic factor?
- Absorbtion of Vitamin B12
What is the role of gastric acid?
- Kills bacteria
- Digestion/denaturation of food
- Acidic pH activates pepsinogen to pepsin for protein digestion
- Promotes action of gastric lipase and secretion of pancreatic HCO3-
What are the three phases of gastric juice secretion?
- Cephalic phase: At the start (e.g. when we smell or see food and when we are chewing)
- Gastric phase: In the stomach
- Intestinal phase: The duodenum
What regulates HCl secretion?
- Neuronal pathways and duodenum hormones
How is HCl secretion regulated?
- Direct pathways: By acting directly on parietal cells to increase acid secretion
- Indirect pathway: By influencing the secretion of gastrin and histamine which increases acid secretion
How does regulation in the cephalic phase occur?
- ACh stimulates histamine release from the ECL cells
- ACh acts directly on parietal cells to cause HCl to be released
- Gastrin stimulates histamine release from ECL cells
- Gastrin acts directly on parietal cells to promote HCl secretion
How does regulation occur at the gastric phase?
- Distension of the stomach causes neuronal reflexes to mouth a vagovagal reflex. There will be an increase in peptide concentration and also an increase in acid secretion
How does acid secretion decrease as acidity in the lumen increases?
- Gastrin interacts with ECL cells and cause them to release histamine.
- This histamine interacts with parietal cells to release HCl.
- However as more HCl is produced it promotes the somatostatin releasing cell causing them to release more somatostatin
- This somatostatin interacts with G-cells (to stop them from producing Gastrin), ECL cells (to prevent them from releasing histamine) and parietal cells (to stop them from producing further HCl)
How will meals containing proteins regulate gastric secretion?
- A meal containing proteins elicits feedback inhibitory and stimulatory signals which ultimately increases acid secretion via stimulation of gastrin secretion
How does regulation occur at the intestinal phase?
- Balances out secretory activity of stomach with absorptive capacities of the small intestines
- Increased acidity inhibits activity of digestive enzymes, bicarbonate and bile salts
- High acidity of duodenal contents inhibit acid secretion
- Distension of the duodenum, hypertonic solution, fatty acids, amino acids, monosaccharides all inhibit acid secretion
- Thus inhibition of acid secretion in the small intestine depends on composition of chyme, volume of chyme and distension of chyme
Why does stimuli in the small intestines decrease acid secretion?
- Intestinal phase stimuli causes a neural reflex that inhibit enteric neurones and so ACh is not produced and cannot work on parietal cells. Hence HCl is not secreted.
- Intestinal phase stimuli can also release CCK and secretin which have inhibitory mechanisms on G-cells, ECL cells and parietal cells and so in general HCl secretion is decreased.
What stimulates the secretion of pepsinogen?
- Inputs from nerve plexus to chief cells which secrete the pepsinogen. Vagal innervation causes pepsinogen secretion
- There are parallels between gastric acid secretion and pepsinogen secretion
- This means that stimulators and inhibitors of acid secretion during the cephalic and intestinal phase exert the same effect on pepsinogen secretion
- Secretion is activated if [H+] is too high
- It is inactivated by the entry of food into the small intestines
Why is pepsin not released in its active form by the chief cells?
- If pepsin were to be released by the chief cells it would proceed to digest the stomach
What is the function of pepsin?
- Initiates the breakdown of proteins into peptides
In protein digestion pepsin is not the only enzyme we rely on
How does prostaglandin affect the body?
- It inhibits parietal cells causing a decrease in acid secretion
- It stimulates mucus secreting cells causing more mucus to be secreted
- It causes vasodilation
What are the effects of NSAIDS on prostaglandins?
- NSAIDS inhibit prostaglandins.
- As a result acid secretion increases, vasodilation decreases and mucus production also decreases
What are the protective factors that prevent autodigestion of the stomach by HCl and pepsin?
- Mucus layer protects the gastric mucosa from low pH
- Secretion of alkaline mucus and bicarbonate (HCO3-)
- Somatostatin inhibits gastrin release and provides a negative feedback control of HCl release
- Protein buffers
- Epithelial cells can remove excess H+ via membrane transport systems and tight junctions prevent the diffusion of H+ back
- Prostaglandins inhibit acid secretion and enhance blood flow
- Blood flow removes excess acid that has diffused across the epithelial layer into the blood
- Prostaglandins maintain the mucosal integrity and repair through growth factors
- Replacement of gastric cells within gastric pits
What are the factors responsible for gastric secretions?
- Histamine, ACh, gastrin
- Food
- NSAIDS
- Zollinger-Ellison syndrome
- Hyperparathyroidism
- Stress
- Bile acids
- Genetics
- Helicoacter pylori
What are symptoms of a peptic (stomach) ulcer?
- Anaemia
- Black, tarry stool
- Nausea
- Dyspepsia (indigestion)
- Anorexia
- Vomiting (blood)
- Epigastric pain
- Chest discomfort
- Weight loss
How do NSAIDS play a role in gastric secretion disorders?
- NSAIDS are acidic that cause irritation of the gut
- They impair the barrier property of the mucosa and supress gastric prostaglandin synthesis
- This decreaes gastric mucosal blood flow and so intereferes iwth the repair of superficial injury
- It also inhibits platelet aggregation
How are ulcers formed?
- There is a breakage of the mucosal barrier as there is too much acid being secreted
- There is an imbalance between protection and damaging factors of the GI tract
- Exposure of the tissue to the erosive effects of the gastric acids and pepsin leads to ulcers
What are common areas in the alimentary tract where peptic ulcers can occur?
- Distal oesophagus
- The stomach: Junction of the antrum and body
- Duodenal cap: First part of the duodenum
- Meckel’s diverticulum: Bulge in the small intestine
- Weight loss surgery
What are acute peptic ulcers?
- Less common ulcers that develop from areas of corrosive gastritis, severe stress and shock
- Acute hypoxia of surface epithelium is also associated with acute peptic ulcers
What is H. Pylori?
- A gram negative spiral shaped aerobic bacterium
- It penetrates gastric mucosa and is able to survive harsh conditions in the stomach (i.e. pH of 1-3)
- They are highly pathogenic with many virulence factors
- It has flagella that enables it to have a “corkscrew” mechanism that provides it motility allowing it to move towards the gut epithelium
- They cause peptic ulcer in the digestive tract
What are the virulence factors of H. pylori?
- They produce urease which converts urea to ammonia which buffers gastric acid and produces CO2
- Cytotoxin-associated antigen which inserts the pathogenicity islands and confers ulcer-forming potential
- Vacuolating toxin A alters the trafficking of intracellular proteins in gastric cells
What diagnostic test can be used on someone suspected with peptic ulcer?
- Endoscopy
- Histological examination and staining of an EDG biopsy
How can we test for the presence of H. pylori?
- Stool antigen test
- Evaluate urease activity
- Urea breath test
What are the complications commonly associate with a peptic ulcer?
- Haemorrhage (GI bleeding)
- Perforation and penetration causing leakage of luminal contents
- Narrowing of pyloric canal or oesophageal stricture
