Regulation And Disorders Of Gastric Secretion Flashcards
1
Q
What are the contents of gastric juice (fasting)?
A
→ Cations : Na+, K+, Mg2+, H+ →Anions : Cl-, HPO42+, SO42- →Pepsinogen →Lipase →Mucus →Intrinsic factor
2
Q
How much does gastric juice add (volume) to intestinal contents?
A
→ 2.5L
3
Q
What do the fundus and body secrete?
A
→ Mucus
→HCl
→Pepsinogen
4
Q
What does the antrum secrete?
A
→less HCl secretion but more gastrin secretion
5
Q
What kind of cells does the body of the stomach have?
A
→ numerous epithelial cells with numerous tubular glands
6
Q
What are the walls of the tubular glands lined with?
A
→ Parietal cells
→ HCl and intrinsic factor
7
Q
What does the pylorus provide for the chyme?
A
→ An exit route for the chyme to pass through into the duodenum
8
Q
What are the exocrine secretions of the stomach?
A
→mucus
→acid,
→pepsinogen
9
Q
Why don’t you want histamine to be exocrine?
A
→ It has wide ranging effects in the body
10
Q
What do ECL cells secrete?
A
→ Paracrine agents such as histamine
11
Q
How is gastric acid made in the stomach?
A
→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- chloride shift
→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
→Accumulation of osmotically-active hydrogen ion in the cannaliculus generates outward diffusion of water - the resulting gastric juice is 155 mM HCl and 15 mM KCl with a small amount of NaCl.
12
Q
What is the pH of gastric juice?
A
→ pH 7.4 -7.7
13
Q
What are the properties of mucus and what does it form?
A
→ thick
→ sticky
→ forms water insoluble gel on epithelial surface
14
Q
What does mucus do?
A
→ Protects against H+
15
Q
What does rennin do?
A
→ Curdles milk into casein clot
→also known as chymosin
→ synthesised by chief cells
16
Q
What does lipase break down and what are the products?
A
→ triglycerides
→ into fatty acids and glycerol
17
Q
What happens if you don’t release lipase?
A
→ Steatorrhea
fatty stool
18
Q
What is intrinsic factor for?
A
→ Absorption of B12
19
Q
What converts pepsinogen to pepsin?
A
→ High acidity
20
Q
What do parietal cells secrete?
A
→ Acid
21
Q
What is the role of gastric acid?
A
→Kills bacteria; acid denaturation of digested food; creates the optimum pH for the activation of pepsinogen to pepsin for protein digestion
→Promotes the action of gastric lipase; and the secretion of pancreatic HCO3-
22
Q
What do non parietal cells secrete?
A
→ Juice similar to plasma
→resting juice = plasma; but alkaline, pH7.4; ↑HCO3-
23
Q
When does HCl secretion increase?
A
→ HCl secretion increases
24
Q
What are the three phases of secretion?
A
→Cephalic phase
→Gastric phase
→Intestinal Phase
25
What is HCl secretion regulated by?
→neuronal pathways and duodenal hormones
26
What is the direct pathway?
→act on parietal cells and increase acid secretion
27
What is the indirect pathway?
→ Influence the secretion of gastrin and histamine increases acid secretion
28
What kind of a secretion is gastrin?
→ A hormonal secretion
29
What starts the cephalic phase?
→ Sight
→ Smell
→ taste
→ chewing
30
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
ACh stimulates histamine release from ECL cells
ACh acts directly on parietal cells → HCl secretion
31
What happens if there is hypersecretion of acid?
→D cells are stimulated
→secrete somatostatin which has inhibitory effects on ECL cells and parietal cells binds to SS-R receptor on parietal
→Acid secretion is reduced.
32
What happens in the gastric phase?
→Distention of the stomach occurs
→Increased peptide concentration and 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
33
Why should people who have acid secretion problems not eat a lot of protein?
→it causes acid hypersecretion
34
What do neuronal inputs promote in gastrin release?
→ACh mediated acid secretion
| →stimulation of acid called GRP (gastrin releasing peptide)
35
What kind of feedback do meals elicit?
→feedback inhibitory and stimulatory signals
| →increase acid secretion via stimulation of gastrin secretion
36
What does the intestinal phase do?
→ Balances the secretory activity of the stomach and the digestive and absorptive capacities of the small intestine
37
What reflexely inhibits acid secretion?
→High acidity of duodenal contents
38
What does increased acidity inhibit?
→inhibits the activity of digestive enzymes, bicarbonate and bile salts
39
What inhibits acid secretion?
```
→Distension of the duodenum
→ hypertonic solution
→amino acids
→ fatty acids
→monosaccharides
```
40
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
```
41
What does secretin release?
→ Bicarbonate
| →dampens G-cells and parietal cells
42
What does inhibition of acid secretion in the small intestine depend on?
→Composition of chyme
→Volume of chyme
→Distension of the duodenum
43
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)
44
Where do long neurones go?
→Long neurons - brain to gut
45
Where do short neurones go?
→Short neurons - within gut
46
What negatively regulates HCl secretion?
→ PGE2
| →ProstaglandinE2 has a protective function.
47
How do prostaglandins work?
→ promotes bicarbonate secretion
→ mucus secretion
→ negatively regulate the hyperacidity of parietal cells.
48
How can acid secretion become elevated?
```
→ Histamine
→ ACh
→ Gastrin
→ Caffeine
→ Alcohol
→ NSAIDs
→ Nicotine
→ Helicobacter pylori
→ Zollinger-Ellison syndrome
→ Hyperparathyroidism (8-30%)
```
49
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
```
50
What is HCl essential for?
→Defence
→Protein digestion : activates pepsinogen to pepsin
→Stimulates flow of bile and pancreatic juice
51
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
52
What stimulates the secretion of pepsinogen?
→Inputs to chief cells from nerve plexus
→parallels between gastric acid secretion and pepsinogen secretion- the same factors that stimulate gastric acid stimulate pepsinogen
→Autocatalytic feedback process
53
How is pepsinogen inactivated?
→Inactivated upon entry of food in the small intestine (HCO3-, peptides neutralize the H+)
54
How is pepsinogen activated?
→shape is altered high acidity which exposes its active site
55
What else do parietal cells secrete apart from acid?
→ Intrinsic factor
56
What is the point of pepsin secretion?
→Initiates digestion of proteins - degrades food proteins into peptides
→Pepsin is not required for food digestion
57
What do NSAIDs cause?
→ acidic and cause topical irritation of the gut
58
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
59
Why can you get bloody feces if you take NSAIDs?
→Inactivates FGF which interferes with haemostasis
60
What happens if there is a malformation of the GIT?
→decreased nutrient status
61
What are the sites affected by peptic ulcers?
→oesophagus
→ stomach
→duodenum
62
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
63
What are the symptoms of a peptic ulcer?
```
→Nausea
→Dyspepsia
→Anorexia
→Vomiting blood
→Black, tarry stools
→Anaemia
→Epigastric pain
```
64
Where are peptic ulcers common?
→Duodenal cap : first part of the duodenal cap
→Stomach - Junction of antrum and body
→Distal oesophagus - Barrett’s oesophagus
→Meckel’s diverticulum – outpouching or bulge in the small intestine (congenital
→Weight loss surgery (gastroenterostomy) weight loss- direct contact with acidic chyme with the duode
65
What is presence of H. Pylori a risk factor for?
→ Gastric cancer
66
What is the usual outcome of a peptic ulcer?
→ complete healing and replacement of tissues and some scarring
67
Where does chronic peptic ulcer occur?
→Occurs in upper GIT
68
What age group are chronic peptic ulcers common in?
→ over 50
69
Where does acute peptic ulcer happen?
→areas of corrosive gastritis (oesophagus, stomach, proximal duodenum)
70
What are the outcomes of acute peptic ulcer?
→severe bleeding
→healing without scarring
→chronic peptic ulcer
71
What are factors predisposing to peptic ulcers?
→Gastric and duodenal infection with H.pylori
72
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
```
73
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
74
What are the functions of HCl and pepsin?
→Kill aerobic microorganisms
| →Decrease infection of gastric mucosa
75
What kind of bacterium is H. Pylori?
→ spiral shaped aerobic bacterium
76
How do H. Pylori get inside the stomach?
→Penetrates gastric mucosa
| →Flagella enables ‘corkscrew’ motility towards gut epithelium
77
What does H. Pylori produce?
→Produces urease
| →converts urea to ammonia which buffers gastric acid and produces CO2
78
What does H. Pylori insert?
→inserts pathogenicity islands and confers ulcer forming potential
79
What does VaCa do?
→Vacuolating toxin A (VaCA) alters the trafficking of intracellular proteins in gastric cells
80
How does H. Pylori break down mucus?
→Makes mucinases which breaks down mucus
81
What are diagnostic tests for a suspected peptic ulcer?
→Endoscopy
| →Histological examination and staining of EGD biopsy
82
How do you test for the presence of H.Pylori?
→Stool antigen test
→Evaluate urease activity
→Urea breath test
83
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)
84
What are the three ways gastrin secretion stimulated?
→Acetylcholine (ACh). This is secreted by the parasympathetic nerve fibres of both the short and long reflex pathways.
→Histamine. This is a paracrine secretion from the enteroendocrine cells in the gastric glands.
→Gastrin. This is a hormone produced by enteroendocrine G cells in the pyloric glands.
85
What are the causes of peptic ulcer?
→Hyperacidity; reflux of duodenal contents (oesophagus, stomach and duodenum)
→Presence of H. pylori is a risk factor for gastric cancer – eradication → ↓ risk
→NSAIDs; Genetic factors; Sex – being male?
86
What are the virulence factors of H.pylori?
→Motility: flagella; moves close to the epithelium (pH 7)
→Produces urease (converts urea to ammonia, which buffers gastric acid and produces CO2)
→Cytotoxin-associated antigen (CagA) – inserts pathogenicity islands and confers ulcer-forming potential
→Vacuolating toxin A (VacA) – alters the trafficking of intracellular protein in gastric cells
→Adhesins (BabA), phospholipases, porins, iron transporters, and flagellum-associated proteins
