49-50 Gastric Flashcards
1
Q
What is the purpose of H+ secretion at the stomach?
A
Killing of microorganisms and conversion of pepsinogen → pepsin
2
Q
What is the purpose of IF secretion at the stomach?
A
Essential for absorption of vit B12 (occurs at small intestine)
3
Q
What is the purpose of mucus and HCO3- secretion at the stomach?
A
Protects gastric mucosa
4
Q
What is the purpose of water secretion at the stomach?
A
Lubricates bolus + suspension of nutrients in soln
5
Q
Which of the following are responsible for regulating motor and secretory responses of the stomach? Neural, endocrine, paracrine.
A
Neural, endocrine, paracrine
6
Q
Is neural regulation of the stomach intrinsic, extrinsic, or both?
A
Both
7
Q
Histamine is a powerful (endocrine or paracrine?) stimulator of ____ secretion.
A
paracrine
- H+
8
Q
What are the 2 major endocrine hormones of the stomach that affect secretion?
A
- Gastrin (stomach and duodenum)- stimulates gastric acid secretion.
- Somatostatin (stomach, duodenum, and pancreas) - inhibits gastric secretion.
9
Q
What is secreted from the cardia region of the stomach (+ LES)?
A
Mucus and HCO3-
10
Q
What is secreted from the fundus and body regions of the stomach?
A
Mucus, HCO3-, HCl, IF, pepsinogens, lipase
11
Q
What is secreted from the antrum and pylorus regions of the stomach?
A
Mucus and HCO3-
12
Q
What region(s) of the stomach serve(s) as a reservoir and provide a tonic force during emptying?
A
Fundus and body
13
Q
What region(s) of the stomach perform(s) the most mixing, grinding, sieving, and regulation of emptying?
A
Antrum and pylorus
14
Q
What region(s) of the stomach is/are responsible for belching, entry of food, and prevention of reflux?
A
Cardia
15
Q
Describe the regions of the stomach beginning to end.
A
Start at cardia
- Above it is fundus
- Below that is body
- Then antrum
- Then pylorus
16
Q
What type of epithelial lining does the stomach contain? What is this layer folded into?
A
- Simple columnar epithelium
- Folded into gastric pits
17
Q
Each gastric pit is the opening where _____ ______ empty.
A
gastric glands
18
Q
What happens to the muscularis mucosae layer of the mucosa during transition from esophagus to stomach?
A
Becomes less thick in stomach
19
Q
Name the 3 main parts of the mucosal invaginations in the stomach, apical to basal.
A
- Gastric pit
- Mucus neck segment
- Gastric gland
20
Q
How is stem cell renewal behavior different in the small intestine vs. the stomach?
A
- Intestines are unidirectional: sc’s at crypts’ base (paneth cells), move apically and then slough off after 3-6 days
- Stomach is bidirectional: sc’s at mucus neck segment, can move apically for rapid surface cell renewal (4-7 days til sloughing off) or basally towards slow gland cell renewal (weeks)
21
Q
What 3 regions can the stomach’s gastric mucosa be divided into based on gland structure?
A
- Cardiac glandular region (below LES)
- Oxyntic or parietal gland region (fundus)
- Pyloric gland region (antrum)
22
Q
What is primarily secreted from the cardiac glandular region?
A
Mucus and HCO3-, provides mechanical and chemical protection of gastric mucosa
23
Q
Name the 6 types of secretory cells found at the fundus of the stomach.
A
- Parietal or oxyntic cells
- Mucus neck cells
- Peptic or Chief cells
- Enterochromaffin-like cells (ELCs)
- D cells
- G cells (also found at pyloric region)
24
Q
*What do parietal/oxyntic cells release, and what do these do?
A
- HCl: kills bacteria; allows pepsinogen -> pepsin; low pH : effective pepsin action
- IF: Glycoproteins bind vit B12 so intestines can absorb it (*it’s an essential factor!)
25
What do mucus neck cells release, and what does this do?
Mucus (protection of mucosa)
26
What do peptic or chief cells release?
Pepsinogen, which is a variety of proteases (*require acidic environment for activation)
27
What do ECL cells release, and what does this do?
Histamine, *the most powerful stimulator of HCl secretion
| - Paracrine
28
What do D cells release, and what does this do?
Somatostatin: powerful inhibitor of HCl secretion
| - Endocrine
29
What do G cells release, and what does this do?
Gastrin: HCl secretagogue
| - Endocrine
30
Collectively, cells of the gastric mucosa secrete a fluid called _____________.
Gastric juice
31
In healthy humans, ___________ is the only essential component of gastric juice. (all others have redundant fcns)
IF
32
Describe the change in the resting parietal cell upon activation. (not sure how important details are)
- Resting parietal cell cytoplasm contains numerous tubules and vesicles (tubulovesicular system), their membranes contain transport proteins needed for secretion of H+ and Cl-. Intracellular secretory canaliculi are present.
- Once activated, the tubulovesicular membranes fuse with the plasma membrane of the secretory canaliculi – (increases the number of H+-K+ antiporters on the secretory canaliculi membrane) – and opens to the lumen of the gland.
33
How did the H+ of the HCl secreted from parietal cells ever get into that parietal cell?
Diffused in as CO2, then carbonic anhydrase...
34
What pumps/channels are present on the luminal side of a parietal cell?
Active H+ K+ ATPase
| Cl- passive channel
35
What pumps/channels are present on the basolateral side of a parietal cell?
NKP
Cl- HCO3- exchanger (secondary)
Also: CO2 diffuses in
36
(Not sure if important) How do increased intracellular Ca2+ and cAMP affect luminal conduction of K+ and Cl- in parietal cells?
Increase it
37
What drug inhibits the H+ K+ ATPase (found on the luminal side of parietal cells)?
What is it used to treat?
Omeprazole
| - Used to treat ulcers thru decreased H+ secretion
38
Regarding the gastric parietal cell, what is the net direction of movement of HCl and HCO3-? (lumen vs. bv)
HCl secreted to lumen, HCO3- absorbed to blood
39
Using what we just learned regarding parietal cells, explain why "alkaline tide" occurs after a meal (how does it affect gastric blood pH?)
Stimulation of parietal cell leads to HCO3- reabsorption (as Cl- enters cell), therefore high pH in gastric venous blood.
40
The surface epithelial cells of stomach secrete a watery fluid into the lumen that contains what 4 major ions?
Which of the 4 have higher concentrations than the plasma?
What is the name of the layer that this forms?
Na+, Cl-, K+, HCO3-
- K+ and HCO3-, because HCO3- is entrapped by the viscous mucus that coats the stomach lumen, forming the *gastric mucosal barrier
41
A layer of ________ protects the relatively alkaline, HCO3-rich barrier from the acidic contents of the gastric lumen.
Mucus
42
Describe the structure/texture of mucus (not exactly what it contains).
Which stomach cells secrete it?
Secretions containing mucins are viscous and sticky, collectively called mucus. 80% carb
- Secreted by mucus neck cells
43
Describe the molecular structure of mucus protein.
| What stomach enzyme can break it down via proteolysis, and why is this important?
Tetramers w/di-S center that is sensitive to proteolysis by pepsin
- *Once broken down, gel of protective mucus layer dissolves (which is why we have bicarb to neutralize the acids in that area
44
What is the STRONGEST stimulus of gastric secretion?
Parasymp stim (vagus n.)
45
Regarding parasympathetic regulation of gastric secretions, extrinsic efferent fibers terminate on intrinsic neurons that innervate what 3 cell types?
Parietal cells, ECL cells, G cells
46
What 3 mechanisms can stimulate H+ secretion by parietal cells?
Acetylcholine (neurocrine)
Histamine (paracrine)
Gastrin (endocrine)
47
What general type of receptors does ACh bind to when stimulating parietal cells, and what is the intracellular 2nd messenger?
- Binds to muscarinic (M3) receptors on the parietal cells
| - 2nd messengers: IP3/Ca++ (stimulates H+ secretion)
48
What's the name of a drug we talked about that inhibits muscarinic receptors?
Atropine
49
Recall: what types of cells release histamine?
ECL cells (have paracrine effect on parietal cells)
50
What type of receptors does histamine bind to when stimulating parietal cells, and what is the intracellular 2nd messenger?
- Binds to H2 receptors on parietal cells
| - 2nd messenger: cAMP (stimulates H+ secretion)
51
What's the name of a drug that blocks H2 receptors?
Cimetidine
52
What type of receptors does gastrin bind to when stimulating parietal cells, and what is the intracellular 2nd messenger?
- CCK-B (or CCK-2) receptors
| - 2nd messengers: IP3/Ca++
53
Define potentiation as it pertains to ACh, histamine, and gastrin's affects on parietal cell stimulation.
The rate of H+ secretion can be regulated by each of these independently as well as by interactions among the three.
- Unclear how it works
54
Will drugs like atropine and cimetidine block only their targets' stimulation of parietal cells, or all of the potentiation targets as well?
All potentiation targets, I believe
55
What percentages of HCl secretion occur during the cephalic/oral phase?
Gastric phase?
Intestinal phase?
30%
60%
10%
56
*Describe the (3) mechanisms that support HCl secretion during the oral/cephalic phase.
- Direct stimulation of parietal cells by vagus via ACh (muscarinic receptors) – neural effect.
- Indirect stimulation of the G cells by vagus via GRP (Gastrin-releasing peptide) -- gastrin-endocrine effect.
- Indirect stimulation of the ECL cells by vagus (ACh) and gastrin (CCKB receptors) to produce histamine -- paracrine effect.
57
*Describe the (5) mechanisms that support HCl secretion during the gastric phase.
(3 previous from oral phase:)
- Direct stimulation of parietal cells by vagus via ACh (muscarinic receptors) – neural effect.
- Indirect stimulation of the G cells by vagus via GRP -- gastrin-endocrine effect.
- Indirect stimulation of the ECL cells by vagus and gastrin (CCKB receptors) to produce histamine -- paracrine effect.
(+ 2 additional)
- Distension of the stomach activates vagovagal reflexes – stimulate gastrin release
- A direct effect of AAs and small peptides on G cells -- stimulate gastrin release
58
What chemicals found in beverages also stimulate HCl secretion?
Alcohol and caffeine
59
How is the (1) mechanism that supports HCl secretion during the intestinal phase mediated?
By protein digestion
60
What 2 chemicals produce feedback inhibition on gastric acid secretion by parietal cells?
How is this negative feedback loop initiated?
- Somatostatin and prostaglandins
| - Low pH chyme in antrum
61
During feedback inhibition of gastric acid secretion, how does somatostatin inhibit the direct pw?
Indirect pw?
- Direct: SS binds to receptors in parietal cells to inhibit stimulatory effect of histamine
- Indirect: SS inhibits histamine release from ECL cells and gastrin release from G cells.
62
During feedback inhibition of gastric acid secretion, how do prostaglandins cause inhibition?
Inhibit stimulatory effect of histamine
63
Why do long-term aspirin-users have gastric bleeding?
Chronic use of NSAIDs blocks negative feedback normally done by prostaglandins, causing too much HCl release.
64
Some digestion occurs in the stomach, but it's usually not vital (unless there are other, e.g. pancreatic, disorders). What digestive enzymes might you find in the stomach?
- Pepsins (20% protein digestion)
- Amylase (inactive at low pH unless substrate carb is bound)
- Lipases (10% lipid digestion)
65
Which region of the stomach has the thickest muscular wall and why?
Caudad region (mixing and propelling food)
66
Define receptive relaxation (w/r/t the stomach).
Describe how it works.
What NT is involved?
- Distension of the lower esophagus by food causes relaxation of LES + relaxation of the orad stomach.
- Vagovagal reflex: mechanoreceptors detect stomach distension and relay this to CNS via sensory neurons. CNS sends efferent information to smooth muscle of orad stomach to relax
- NT released from postganglionic peptidergic vagal fibers is VIP.
67
Describe, generally, the mixing and propulsion that occurs in the stomach when food enters.
- Caudad region- waves of strong contraction start in the mid portion of stomach and move distally, increasing in strength towards pylorus.
- They mix the gastric contents and periodically propel a portion of these in the duodenum through pylorus, followed by closure of pylorus.
68
Define retropulsion w/r/t gastric motility.
Because pyloric sphincter is often closed, much of the chyme (not emptied into duodenum) is propelled back to stomach for further mixing and break-down.
69
What types of processes (3) do vagovagal stomach reflexes help regulate?
Acid secretion, distension of gastric wall, and gastric motility
70
The rate of antral contractions is set by _________________, but the magnitude of contractions is regulated by __________________.
- a gastric pacemaker
| - parasympathetic input
71
How long does emptying into the duodenum from the stomach usually take?
How does a liquid meal (e.g. all glucose) vs. a solid meal (e.g. piece of a liver, mostly ptn) influence gastric emptying?
~ 3 hrs
| - Liquids empty rapidly, solids more slowly (must be broken down)
72
(might not be that important) Explain the different rates of gastric emptying regarding isotonic, hypotonic, and hypertonic foods.
Isotonic faster than both hyper and hypotonic.
73
Describe the general structure of the pylorus.
Consists of a two ring-like thickenings of circular smooth muscle cells.
74
*Explain the difference in gastric vs duodenal ulcers w/r/t the pylorus. (peptic ulcer disease--PUD, pertains to stomach and/or duodenum)
Which are more common?
- Gastric ulcers form because stomach is sensitive to high pH of bile that leaks back from intestines
- Duodenal ulcers form because duodenum is sensitive to low pH of gastric juice leaking into duodenum (more common than gastric because H+ rate is high)
75
What 3 major classes of regulation control the pylorus?
Neural, paracrine, endocrine
76
What 2 NTs are associated w/gastric emptying during parasymp stim?
NO and VIP (via vagus)
77
Recall: Generally, what is the cause of gastric ulcers?
What's a gram-neg bacteria that could also do this?
What are some others potential causes of gastric ulcers?
- Defects in mucosal barrier (mucosa digested)
- H. Pylori (releases cytotoxins). Surprisingly, in these pts, net H+ secretory rates are lower and thus the secretion rate of gastrin is increased (lacking the negative feedback).
- Stress, smoking, NSAIDs, alcohol
78
What is Zollinger-Ellison Syndrome (gastrinoma)?
Sx?
Tx?
Tumor (or gastrinoma) located in the pancreas, secretes high quantities of gastrin.
Effects:
- Increased H+ secretion by parietal cells
- Increased parietal cell mass
Sx: Leads to duodenal ulcers
- Sometimes fatty stool (steatorrhea) because pancreatic lipases inactivated at low pH
(there is also a lack of feedback inhibition)
Treatment includes
- Inhibitors of H+ secretion, e.g. Cimetidine, Omeprazole
- Surgical removal of tumor
