Gastric Secretion Flashcards
1
Q
How much fluid does the stomach/gastic system secrete each day?
A
2L fluid
2
Q
Is nutrient intake attainable if most of the stomach is removed?
A
YES (gastric bypass surgery)
3
Q
What are the five main functions of the gastric system?
A
- Highly acidic environment provides a line of defense against microorganisms
- Serves as a reservoir for large amounts of food
- Protein digestion through acid hydrolysis and pepsin cleavage
- Fragment bolus into chyme
- Empty contents into the small intestine at a controlled rate to optimize further digestion and absorption
4
Q
What are five regions of the stomach with specialized functions?
A
- LES (lower esophageal sphincter)
- Cardia
- Fundus and body/corpus
- Antrum
- Pylorus
5
Q
What is the function of the LES?
A
Prevent reflux
6
Q
What is the function of the Fundus and body/corpus?
A
Secretion, reservoir
7
Q
What is the function of the antrum?
A
Mixing, grinding
8
Q
What is the function of the pylorus?
A
Control of emptying
9
Q
Where is the oxyntic/parietal glandular mucosa most often found?
A
In the body of the stomach
10
Q
What is the function of the superficial epithelial cells?
A
Just simple, columnar cells
11
Q
What is the function of mucous neck cells?
A
Secrete mucus, bicarbonate (cell turnover every 3-5 days)
12
Q
What is the function of Parietal (oxyntic) cells?
A
Secrete HCl, intrinsic factor, gastroferrin (more stable than mucous cells)
13
Q
What is the function of Chief cells?
A
Secrete pepsinogen (more stable than mucous cells)
14
Q
How much is the cardiac area made up of gland?
A
50% gland - lots of mucous cells
15
Q
How much is the body area made up of gland?
A
70% gland - lots of parietal, chief cells
16
Q
How much is the pyloric area made up of gland?
A
40% gland - mucous cells and enteroendocrine
17
Q
What is the pathways from G cells to the secretion of acid?
A
G cells secrete gastrin (hormone) which activates parietal cells in the fundus/corpus to secrete acid.
18
Q
What is Gastrin and what does it bind?
A
- It’s a polypeptide with variable length and sequence.
- It binds CCK2 receptors.
19
Q
What two things trigger G cells (in antrum) to secrete Gastrin?
A
- Seeing food or stomach distention causes vagal stimulation causing release of Gastrin-releasing peptide (GRP).
- Aromatic amino acids in the lumen.
20
Q
What molecule activates acid secretion in parietal cells via the cAMP dependent pathway?
A
Histamine
21
Q
What molecule activates acid secretion in parietal cells via the Ca2+ dependent pathway?
A
Gastrin & ACh
22
Q
Would you expect atropine to stimulate or inhibit gastric acid secretion?
A
Inhibit. Atropine is an antagonist of muscarinic receptors (ACh), abolishing effects of parasympathetic.
23
Q
How does acetylcholine stimulate gastric acid secretion?
A
ACh is released from vagal fibers and enteric neural excitatory fibers, then it binds to muscarinic receptors on parietal cells
24
Q
What are the two ways that Gastrin promotes gastric acid secretion?
A
Gastrin is released into the blood by G cells.
- Binds to parietal cells at CCK2 receptor (Ca2+ pathway)
- Activates ECL cells (CCK2 receptor) to release histamine
25
How does histamine promote gastric acid secretion?
Histamine is released from stimulated ECL cells and it acts via the cAMP pathway to increase H+/K+ ATPase action
26
What happens to the number of H+/K+ ATPase molecules when parietal cells are stimulated?
Upon parietal cell stimulation, tubulovesicular membranes fuse with canalicular membranes increasing the density of H+, K+ ATPase molecules at the apical membrane.
27
What Ion transport is happening in parietal cells to produce acid secretion?
1. Na+, K+ ATPase in basolateral membrane and K+ flows out into the lumen
2. Protons are generated in cytosol via carbonic anhydrase II (CA II)
3. Proton pump H+, K+ ATPase pumps protons into the lumen (lots of mitochondria)
4. Bicarbonate ions are exported from the basolateral side by vesicular fusion or the chloride/bicarbonate exchanger and enters blood stream creating alkaline tide.
5. Cl- moves passively down the electrochemical gradient when the luminal Cl- channel opens and water follows.
28
What is the main inhibitor of gastrin release?
Somatostatin!
29
Where and when is somatostatin released?
Secreted from D cells in the antrum when pH is less than 3
30
What happens to gastrin and somatostatin levels when food enters the stomach?
During gastric phase, food enters, the stomach increases in pH -- and this leads to a decrease in somatostatin secretion and an increase in gastrin levels.
31
How does Somatostatin inhibit gastric acid secretion?
When pH is less than 3:
1. Inhibits G cells release of gastrin.
2. Inhibits formation of cAMP via a Gi-dependent signaling pathway in parietal cells
3. Inhibits ECL cell secretion of histamine.
32
What other molecule can also inhibit formation of cAMP in parietal cells? And cause the inhibition of gastric acid?
Prostaglandins
33
In what two ways can feedback from the duodenum inhibit gastric acid secretion?
1. Nervous reflex blocks ACh activation of parietal cells
| 2. Enterogastrones like secretin block secretion of histamine by ECL cells.
34
What are the four main phases of gastric secretion?
1. Interdigestive Phase
2. Cephalic Phase
3. Gastric Phase
4. Intestinal Phase
35
What is the Interdigestive Phase?
Low acid secretion, D cells secrete somatostatin to maintain low levels of Gastrin
36
What is the Cephalic Phase?
Dorsal vagal complex integrates input from higher centers (seeing and tasting food) to activate Vagus nerves. GRP activates gastrin release and ACh activates ECL and parietal cells
37
What is the Gastric Phase?
Distention of the stomach activates vagal afferents and the enteric nervous system. Amino acids activate gastrin secretion and food raises pH decreasing somatostatin secretion.
38
What is the Intestinal Phase?
Introduction of the gastric contents into the small intestine activates duodenal G cell secretion of gastrin. Activation of secretin and other enterogastrones and neural reflex decreases gastrin secretion.
39
What is required for B12 absorption? Where does this absorption occur?
Intrinsic Factor, Ileum
40
What is Intrinsic Factor?
A glycoprotein secreted by parietal cells that mediates uptake of B12 in ileum.
41
What do Proton-pump inhibitor drugs NOT inhibit?
Secretion of intrinsic factor.
42
What does B12 (cobalamin) deficiency result in?
Pernicious anemia and neurological deficiencies
43
What causes pernicious anemia?
Autoimmune destruction of parietal cells or intrinsic factor, bypass surgery
44
What do Chief cells look like when stained?
Dark purple/blue because they have lots of granules and are basophilic.
45
What do Chief cells secrete?
Pepsinogen
46
What is Pepsinogen?
A group of inactive proenzyme proteases.
47
What are the positive regulators of Chief Cells?
ACh, Gastrin
48
What is a negative regulator (shuts off) of Chief Cells?
Secretin
49
What activates Pepsinogen?
Acidic environment of the stomach.
50
What does Pepsinogen become in the acidic stomach?
Pepsin, a potent proteolytic enzyme
51
What is Pepsin?
An endopeptidase. It further activates pepsinogen by autolysis.
52
What do chief cells secrete beyond pepsin?
Gastric lipase which releases fatty acids
53
What does the mucous gel layer of the stomach create?
A gastric diffusion barrier
54
What do surface epithelial cells secret in response to PGE2?
Mucus and bicarbonate
55
What is the pH at cell surface? What is the pH in the lumen above the mucus?
cell surface = 7
| above mucus = 2
56
What happens to H+ and pepsin crossing the mucus barrier?
They are neutralized by bicarbonate
57
How do NSAIDs cause gastric irritation?
NSAIDs block PGE2 effects leading to reduced mucus secretion, which contributes to gastric irritation
58
What contributes to the formation of "stress ulcers" and general gastric irritation?
Catecholamines suppress mucosal bicarbonate secretion (sympathetic NS - EPI, NE)
59
What does repairing disrupted epithelium involve?
Restitution and regeneration
1. Injury
2. Detachment and cell death, exposed matrix elements
3. Expression of motogens
4. Cell migration, inhibition of cell death, trefoil factors, growth factors
5. Restored cell-matrix interaction, restored cell-cell interaction
60
What are two issues of increased acid secretion?
1. Zollinger-Ellison Syndrome (Gastrinoma)
| 2. Peptic Ulcer Disease
61
What is Zollinger-Ellison Syndrome?
- Usually caused by a gastrin-secreting tumor in the pancreas or small intestine
- Results in excess H+ secretion as well as hyperplasia and hypertrophy of parietal cells
- 95% of patients develop gastric ulcers
62
What is Peptic Ulcer Disease?
- Hyperacidity
| - Deterioration of the gastro-mucosal barrier
63
What are different contributors to Gastric and duodenal ulcers?
- Infection (Helicobacter pylori - causes inflammation of gastric mucosa (gastritis) that is often asymptomatic)
- Poor secretion of mucus, bicarbonate by the surface epithelium
- Stress (may contribute ut doesn't cause)
- Irritation by alcohol, acid, digestive enzymes, bile
64
How do you treat gastric and duodenal ulcers?
Antibiotics and proton pump inhibitors. Stop NSAIDS.
65
What are ulcer symptoms?
Increased bleeding, stomach pain
66
What organism inhibits somatostatin?
H. pylori
67
Why are gastrin levels often increased in gastric ulcers?
Since somatostatin inhibition of gastrin during the fasting state is not activated
68
What inhibits somatostatin in ulcers?
May be related to urease activity of H. pylori.
69
What can increased gastrin release in ulcers cause?
- Acid hyper secretion
- Pepsin secretion
- Hyperplasia of ECL and parietal cells
- Stomach contractions
70
What can a subset of patients get that is related to gastritis and destruction of gastric epithelial cells?
Hypochlorhydria
71
What is Hypochlorhydria or Achlorhydria?
HCl production is absent or low. [Reduced acid secretion]
72
What further contributes to ulcer formation?
Inflammatory response to H. pylori or loss of protective factors due to NSAID inhibition of PG synthesis
73
How can gastric ulcers lead to duodenal ulcers?
Infection and high acidity can spread to duodenum resulting in decreased bicarbonate and duodenal ulcers
74
What causes Achlorhydria?
- Aging, gastric resection, genetic factors, auto-immune attack of H+/K+ ATPase, taking proton pump inhibitors, infection - atrophic gastritis
- Bacterial overgrowth, diarrhea, pneumonia
- Hip fractures and iron deficient anemia-decreased Ca2+ and iron absorption
- Decrease in pepsin activation doesn't seem to cause problems (no increase in nitrogen excretion)
75
What is the function of HCL and what secretes it?
Hydrolysis; sterilization of meal, Parietal cell
76
What is the function of Intrinsic factor and what secretes it?
Vitamin B12 absorption, Parietal cell
77
What is the function of Pepsinogen and what secretes it?
Protein digestion, Chief cell
78
What is the function of mucus and bicarbonate and what secretes it?
Gastroprotection, Surface mucous cells
79
What is the function of Trefoil factors and what secretes it?
Gastroprotection, Surface mucous cells
80
What is the function of Histamine and what secretes it?
Regulation of gastric secretion, ECL cells
81
What is the function of Gastrin and what secretes it?
Regulation of gastric secretion, G cells
82
What is the function of Gastrin releasing peptide and what secretes it?
Regulation of gastric secretion, Nerves
83
What is the function of Acetylcholine (ACh) and what secretes it?
Regulation of gastric secretion, Nerves
84
What is the function of somatostatin and what secretes it?
Regulation of gastric secretion, D cells
85
What is the function of Gastroferrin and what secretes it?
Ferrous iron (Fe++) absorption, Parietal cells
86
What do Trefoil factors do?
Regenerate the epithelial layer
87
What does gastric secretion contribute to?
Digestion, host defense, absorption of nutrients
88
Generally, how does acid secretion occur?
In phases that correspond to temporal ingestion of the meal that are regulated by neurocrine, paracrine and endocrine components.
89
What are other important stomach secretions besides acid?
- Pepsinogen
- Intrinsic factor
- Mucus
- Bicarbonate
- Trefoil peptides
90
What hormones are ON during the Interdigestive Phase?
- Gastrin
- ACh
- Histamine
+ Somatostatin
91
What hormones are ON during the Cephalic Phase?
+ Gastrin (bc GRP is active)
+ ACh
+ Histamine (Gastrin activates and vagal activates)
+ Somatostatin (since pH is still the same and we are just seeing food, not altering pH with food in stomach)
92
What hormones are ON during the Gastric Phase?
++ Gastrin
++ ACh
++ Histamine
- Somatostatin
93
What hormones are ON during the Intestinal Phase?
+ Gastrin (from duodenal cell, negative feedback to the stomach)
- ACh (decreasing)
- Histamine (going down)
- first but then + as the stomach empties, Somatostatin
94
When is the stomach at very low pH?
Interdigestive phase and Cephalic phase. Somatostatin is being secreted.
