Regulation and disorders of gastric secretion Flashcards
What are the contents of gastric juice (fasting)?
→ Cations : Na+, K+, Mg2+, H+ →Anions : Cl-, HPO42+, SO42- →Pepsinogen →Lipase →Mucus →Intrinsic factor
How much does gastric juice add (volume) to intestinal contents?
→ 2.5L
What do the fundus and body secrete?
→ Mucus
→HCl
→Pepsinogen
What does the antrum secrete?
→less HCl secretion but more gastrin secretion
What kind of cells does the body have?
→ numerous epithelial cells with numerous tubular glands
What are the walls of the tubular glands lined with?
→ Parietal cells
→ HCl and intrinsic factor
What does the pylorus provide for the chyme?
→ An exit route for the chyme to pass through into the duodenum
What are the exocrine secretions of the stomach?
→mucus
→acid,
→pepsinogen
Why don’t you want histamine to be exocrine?
→ It has wide ranging effects in the body
What do ECL cells secrete?
→ Paracrine agents such as histamine
How is gastric acid made in the stomach?
→CO2 diffuses into the cell
→It forms carbonic acid via carbonic anhydrase
→Carbonic acid dissociates into bicarbonate and H+
→HCO3- is transported out and Cl- is transported in to maintain charge
→The H+ can form water and flux into the lumen
→It can be exchanged for K+ by an ATPase
→H+ and Cl- form HCl in the lumen
What is the pH of gastric juice?
→ pH 7.4 -7.7
What are the properties of mucus and what does it form?
→ thick
→ sticky
→ forms water insoluble gel on epithelial surface
What does mucus do?
→ Protects against H+
What does rennin do?
→ Curdles milk into casein clot
What does lipase break down and what are the products?
→ triglycerides
→ into fatty acids and glycerol
What happens if you don’t release lipase?
→ Steatorrhea
What is intrinsic factor for?
→ Absorption of B12
What converts pepsinogen to pepsin?
→ High acidity
What do parietal cells secrete?
→ Acid
What do non parietal cells secrete?
→ Juice similar to plasma
When does HCl secretion increase?
→ HCl secretion increases
What are the three phases of secretion?
→Cephalic phase
→Gastric phase
→Intestinal Phase
What is HCl secretion regulated by?
→neuronal pathways and duodenal hormones
What is the direct pathway?
→act on parietal cells and increase acid secretion
What is the indirect pathway?
→ Influence the secretion of gastrin and histamine increases acid secretion
What kind of a secretion is gastrin?
→ A hormonal secretion
What starts the cephalic phase?
→ Sight
→ Smell
→ taste
→ chewing
What happens during the cephalic phase?
→there is ACh release
→Increases the parasympathetic preganglionic neuron activity.
→This stimulates the enteric neurons
→ACh binds to receptors on the parietal cells and stimulates them
→Stimulates release of gastrin from G cells
→Gastrin binds to ECL cells
→ECL cells secrete histamine
→This causes secretion
What happens if there is hypersecretion of acid?
→D cells are stimulated
→secrete somatostatin which has inhibitory effects on ECL cells and parietal cells.
→Acid secretion is reduced.
What happens in the gastric phase?
→Distention of the stomach occurs
→Increased acidity
→When the food has peptides in it the food acts as a buffer
→They will stop HCL stimulating D cells
→The inhibition of acid secretion is removed
Why should people who have acid secretion problems not eat a lot of protein?
→it causes acid hypersecretion
What do proteins do to luminal acidity?
→ Proteins act as buffers in the gastric lumen so HCl secretion increases
What do neuronal inputs promote?
→ACh mediated acid secretion
→stimulation of acid called GRP (gastrin releasing peptide)
What kind of feedback do meals elicit?
→feedback inhibitory and stimulatory signals
What does the intestinal phase do?
→ Balances the secretory activity of the stomach and the digestive and absorptive capacities of the small intestine
What reflexely inhibits acid secretion?
→High acidity of duodenal contents
What does increased acidity inhibit?
→inhibits the activity of digestive enzymes, bicarbonate and bile salts
What inhibits acid secretion?
→Distension of the duodenum → hypertonic solution →amino acids → fatty acids →monosaccharides
What do enterogastrones release and what is the result of this?
→CCK →secretin →GLP-1 → GIP →these have inhibitory effects on ECL, G and Parietal cells
What does secretin release?
→ Bicarbonate
What does inhibition of acid secretion in the small intestine depend on?
→Composition of chyme
→Volume of chyme
→Distension of the duodenum
What do short and long neuronal reflexes and hormones (enterogastrones e.g CCK, secretin, GIP) inhibit ?
→Acid secretion by the parietal cells
→Gastric secretion by G cells
→This is inhibited by somatostatin (stomach, intestine, delta cells of pancreas, hypothalamus, brainstem and hippocampus)
Where do long neurones go?
→Long neurons - brain to gut
Where do short neurones go?
→Short neurons - within gut
What negatively regulates HCl secretion?
→ PGE2
How do prostaglandins work?
→ promotes bicarbonate secretion
→ mucus secretion
→ negatively regulate the hyperacidity of parietal cells.
How can acid secretion become elevated?
→ Histamine → ACh → Gastrin → Caffeine → Alcohol → NSAIDs → Nicotine → Helicobacter pylori → Zollinger-Ellison syndrome → Hyperparathyroidism (8-30%)
What are the 6 things that the concentration of HCl depends on?
→Rate of secretion →Amount of buffering provided by resting juice →Composition of ingested food →Gastric motility →Rate of gastric emptying →Amount of diffusion back into mucosa
What is HCl essential for?
→Defence
→Protein digestion : activates pepsinogen to pepsin
→Stimulates flow of bile and pancreatic juice
What does lack of HCl cause?
→Lack of HCl causes failure of protein digestion (achlorydia or hypochlorydia)
→ production of gastric acid in the stomach is absent or low
What stimulates the secretion of pepsinogen?
→Inputs to chief cells from nerve plexus
How is pepsinogen inactivated?
→Inactivated upon entry of food in the small intestine (HCO3-, peptides neutralize the H+)
How is pepsinogen activated?
→shape is altered high acidity which exposes its active site
What else do parietal cells secrete apart from acid?
→ Intrinsic factor
What is the point of pepsin secretion?
→Initiates digestion of proteins - degrades food proteins into peptides
→Pepsin is not required for food digestion
What do NSAIDs cause?
→ acidic and cause topical irritation of the gut
How do NSAIDs cause irritation?
→Impair the barrier properties of the mucosa
→Suppress gastric prostaglandin synthesis
→Decrease gastric mucosal blood flow
→Interfere with repair of superficial injury
→Inhibit platelet aggregation - takes away thromboxane A2
Why can you get bloody feces if you take NSAIDs?
→Inactivates FGF which interferes with haemostasis
What happens if there is a malformation of the GIT?
→decreased nutrient status
What are the sites affected by peptic ulcers?
→oesophagus
→ stomach
→duodenum
What is peptic ulcer caused by?
→Imbalance between protective and damaging factors of GIT
→Exposure of the tissues to the erosive effects of HCl, bile acids and pepsin
What are the symptoms of a peptic ulcer?
→Nausea →Dyspepsia →Anorexia →Vomiting blood →Black, tarry stools →Anaemia →Epigastric pain
Where are peptic ulcers common?
→Duodenal cap : first part of the duodenal cap
→Stomach - Junction of antrum and body
→Distal oesophagus - Barrett’s oesophagus
What is presence of H. Pylori a risk factor for?
→ Gastric cancer
What is the usual outcome of a peptic ulcer?
→ complete healing and replacement of tissues and some scarring
Where does chronic peptic ulcer occur?
→Occurs in upper GIT
What age group are chronic peptic ulcers common in?
→ over 50
Where does acute peptic ulcer happen?
→areas of corrosive gastritis (oesophagus, stomach, proximal duodenum)
What are the outcomes of acute peptic ulcer?
→severe bleeding
→healing without scarring
→chronic peptic ulcer
What are factors predisposing to peptic ulcers?
→Gastric and duodenal infection with H.pylori
What are factors that prevent infection of the gastric mucosa?
→Mucus production →Peristalsis and fluid movement →Seamless epithelium with tight junctions →Fast cell turnover →IgA secretion at mucosal surfaces →Peyer’s patches - protection
What are factors that prevent autodigestion of the stomach?
→Secretion of Alkaline mucus and HCO3-
→Protein content of food
→Presence of tight junctions between epithelial cells lining stomach and fibrin coat
→Replacement of damaged cells within the gastric pits
→Prostaglandins (E and I) inhibit acid secretion and enhance blood flow
What are the functions of HCl and pepsin?
→Kill aerobic microorganisms
→Decrease infection of gastric mucosa
What kind of bacterium is H. Pylori?
→ spiral shaped aerobic bacterium
How do H. Pylori get inside the stomach?
→Penetrates gastric mucosa
→Flagella enables ‘corkscrew’ motility towards gut epithelium
What does H. Pylori produce?
→Produces urease
→converts urea to ammonia which buffers gastric acid and produces CO2
What does H. Pylori insert?
→inserts pathogenicity islands and confers ulcer forming potential
What does VaCa do?
→Vacuolating toxin A (VaCA) alters the trafficking of intracellular proteins in gastric cells
How does H. Pylori break down mucus?
→Makes mucinases which breaks down mucus
What are diagnostic tests for a suspected peptic ulcer?
→Endoscopy
→Histological examination and staining of EGD biopsy
How do you test for the presence of H.Pylori?
→Stool antigen test
→Evaluate urease activity
→Urea breath test
What are complications of peptic ulcer?
→Haemorrhage (GI bleeding)
→Perforation (peritonitis) and penetration (liver and pancreas may be affected), leakage of luminal contents
→Narrowing of pyloric canal ( stricture causing acquired pyloric stenosis in stomach or oesophageal stricture)
