60 - Gastric Secretions

Question 1

Cells located in the cardia of the stomach

Answer 1

Cardia has NO PARIETAL CELLS – reason for this is because the cardia is located just below the esophagus. Having acid producing cells right outside of the esophagus makes damage more likely due to acid reflux.

Question 2

Cells located in the body of the stomach

Answer 2

Stomach body has parietal, chief, neck and Enterochromaffin-like cells

These are located within the gastric pits.

Question 3

Secretions of parietal cells

Answer 3

Parietal cells secrete HCl (protein digestion, sterilization, and nutrient absorption) as well as intrinsic factor (B12 absorption – complexing occurs mainly in duodenum)

Question 4

Secretions of chief cells

Answer 4

Chief cells produce pepsinogen (protein digestion once converted).

Question 5

Secretions of neck cells

Answer 5

• Pepsinogen

- Also produce mucous and bicarb - a balance between aggressive factors and protective factors

Question 6

Secretions of enterochromaffin-like cells

Answer 6

ECL cells produce histamine – stimulates HCl secretion

Question 7

Cells located in the antrum of the stomach

Answer 7

Antrum has chief cells, G cells and D cells

Question 8

Secretions of G cells

Answer 8

G cells produce gastrin (promote HCl secretion)

Question 9

Secretions of D cells

Answer 9

D cells produce somatostatin (remember delta cells of the pancreas? Function is to suppress HCl secretion

Question 10

Are G and D cells found exclusively in the antrum of the stomach?

Answer 10

No - C and D cells are found elsewhere as well but in the highest concentration in the antrum

Question 11

What lines the entire stomach?

Answer 11

The entire stomach is lined by superficial epithelial cells, which secrete mucous and bicarb (function in gastroprotection from acid)

Question 12

Gastric glands produce ___ L of fluid per day

Answer 12

2 L

Question 13

What two ions are secreted from gastric glands?

Answer 13

Na+ rich secretions (non-parietal cells)
H+ rich secretions (parietal cells)

Also note that as secretory rate increases, H+ concentration does as well

Question 14

Which two ways is the secretion of acid by the stomach regulated?

Answer 14

Directly and indirectly

Question 15

What three pathways contribute to this regulation?

Answer 15

Neuronal
Paracrine
Endocrine

Question 16

What does the neuronal pathway use to regulate acid secretion?

Answer 16

ACh

Promotes HCl secretion

Question 17

What does the paracrine pathway use to regulate acid secretion?

Answer 17

Histamine

Promotes HCl secretion

Question 18

What does the endocrine pathway use to regulate acid secretion?

Answer 18

Gastrin

Promotes HCl secretion

Question 19

How does gastrin function both directly ad indirectly to stimulate HCl secretion?

Answer 19

Directly
- Gastrin is secreted into the blood by the endocrine G cells of the stomach and can directly stimulate the parietal cells to increase H+/K+ ATPase pump activity (this is a H+ pump that transports H+ ions into the stomach)

Indirectly
- After gastrin is secreted into the blood it can also act indirectly by inducing the release of histamine from ECL cells

Question 20

How does acetylcholine function both directly and indirectly to stimulate HCl secretion?

Answer 20

Directly
- Stimulation of the parietal cell

Indirectly
- Stimulation of ECL cells resulting in the release of histamine (same as gastrin indirect)

Question 21

How does histamine function directly to stimulate HCl secretion?

Answer 21

Directly
- Histamine is released from ECL cells onto neighboring parietal cells in order to stimulate the H+/K+ ATPase pump to increase the amount of H+ being secreted into stomach lumen

Question 22

How does the paracrine release of prostaglandins (PGE2) regulate the HCl secretion in the stomach?

Answer 22

Prostaglandins (PGE2) decrease or negatively regulate the H+/K+ ATPase pump on the apical surface of parietal cells, which decreases the amount of HCl secreted into the stomach and decreases the acidity of the stomach

Question 23

How does the release of somatostatin into the blood regulate the HCl secretion in the stomach?

Answer 23

The release of somatostatin into the blood by gastric D cells decreases acid secretion by inhibiting the release of gastrin from G cells, inhibiting the release of histamine from ECL cells and inhibiting H+/K+ ATPase activity

Overall, the acidity of the stomach will decrease

Question 24

Refresher: neuronal, paracrine, endocrine

Answer 24

Neuronal
- Hormones from the nervous system (released from axons for signalling)

Paracrine
- Paracrine signaling is a form of cell-cell communication in which a cell produces a signal to induce changes in nearby cells, altering the behavior or differentiation of those cells

Endocrine
- Secrete hormones from endocrine organs via ducts into the circulation to carry a signal to a distant location

Question 25

What are the five functions of gastric acid (HCl)?

Answer 25

1 - Protein digestion (conversion of pepsinogen to pepsin) 2 - Provide a sterile environement 3 - Prevent bacterial and fungal growth 4 - Facilitate absorption 5 - Promote bile and pancreatic enzyme flow

Question 26

How is pepsinogen converted into the active protease pepsin in the lumen of the stomach?

Answer 26

Pepsinogen is a zymogen, meaning it’s converted into its active form by HCl Pepsinogen can also be auto-activated by other pepsin molecules This process functions optimally at pH 1.8-3.5 and is inhibited beyond pH of 3.5

Question 27

How is the pH restriction a protective measure?

Answer 27

The pH difference serves a protective role by preventing not only damage from the acid but also prevents the protease from cleaving proteins expressed on the surface of duodenal mucosa

Question 28

What two secretions in the stomach breakdown proteins?

Answer 28

- HCl and Gastrin - HCl by pepsinogen -> pepsin -> protein breakdown - Gastrin directly

Question 29

What is the site of intrinsic factor secretion?

Answer 29

Parietal cells secrete intrinsic factor

Question 30

What is the function of intrinsic factor?

Answer 30

Intrinsic factor - Forms a complex with vitamin B12 which has been released from food being broken down in stomach - Complexing occurs in the duodenum - IF-B12 is absorbed in the ileum

Question 31

Damage to parietal cells will result in...

Answer 31

What is important is that intrinsic factor is coming from the parietal cells, so if you have damage to parietal cells, you will not only have decrease in acid secretion, but also a decreased absorption of vitamin B12 due to the lack of intrinsic factor being released

Question 32

What are the components of mucous?

Answer 32

- Mucin - Phospholipids - Electrolytes - Water All of these are protective factors

Question 33

What else is secreted and has a protective function?

Answer 33

Bicarb

Question 34

Describe the multiple levels of protection

Answer 34

- Mucous acts as a physical barrier - Mucous has a high viscosity, allowing for slow diffusion - Chief and parietal cell membranes are highly resistant - High pH of bicarb inactivates pepsin and acts as a bufffer

Question 35

What is the overall result of these protective measures?

Answer 35

Physical barrier, in addition to high pH and buffering capacity prevents easy access of pepsin to underlying epithelium – even if they get there, they’re close to the point of irreversible inhibition (pH 7.2)

Question 36

What are the two key stimuli for mucous secretion by epithelial and neck cells of the stomach?

Answer 36

Neurocrine regulation - ACh Paracrine regulation - prostaglandin

Question 37

What do prostaglandins do?

Answer 37

- Promote mucous and bicarb secretion - Suppress HCl - Increase gastric blood flow

Question 38

How to NSAIDS work?

Answer 38

NSAIDS inhibit cyclooxygenase, which is a rate-limiting enzyme in the production of prostaglandins. This means that use of NSAIDS can inhibit mucous and bicarb secretion, increase HCl secretion, and reduce gastric blood flow --> increase the chances of damage to the stomach

Question 39

What are the four phases of gastric acid secretion?

Answer 39

1 - Interdigestive phase 2 - Cephalic phase 3 - Gastric phase 4 - Intestinal phase

Question 40

Interdigestive phase

Answer 40

lowest in early morning rises throughout the day. pH varies from 3-7 depending on parietal cell number, body weight and presence of food in the stomach (this is why eating breakfast is important).

Question 41

Cephalic phase

Answer 41

Accounts for 30% of acid secreted – activated by stimuli like sight or smell or food – trigger vagal response --> acid secretion.

Question 42

Gastric phase

Answer 42

Similar to cephalic – vagal stimulation mediates secretion but stimulus is from stomach distention. Protein products in the stomach increase acid secretion – inhibited by D cells (most secretion – 50-60% during this phase)

Question 43

Intestinal phase

Answer 43

10% of acid secretion – mediated by presence of peptides in the duodenum. These induce release of gastrin to increase activity of parietal cells – may be also regulated by amino acids absorbed in the duodenum (p5 handout). Remember – the majority of your gross protein digestion occurs in the stomach, if some inappropriately digested product comes out into the duodenum, it will send out the signal to slow things down and get a more thorough digestion to occur.

Question 44

Describe the role of secretin in the stomach and its target cells

Answer 44

Secretin - Secretin is produced in the S cells of the duodenum, which are located in the crypts of Lieberkühn - Secretin also helps regulate the pH of the duodenum by inhibiting the secretion of gastric acid from the parietal cells of the stomach - Also regulates pH by stimulating the production of bicarbonate from the centroacinar cells and intercalated ducts of the pancreas

Question 45

Pathophysiology of gastritis

Answer 45

- Gastritis is characterized by inflammation of the gastric mucosa caused by damage to the protective mucosal barrier - The inflammation does not necessarily cause a break in the mucosal lining but the inflammation has the potential to result in ulcer formation

Question 46

Pathophysiology of H. pylori infection

Answer 46

- Helicobacter pylori are spiral shaped bacteria that colonize the luminal surface of the gastric epithelium and can cause inflammation and ulceration of the stomach - 70% to 90% of patients with gastric or duodenal ulcers are positive for H. pylori - The bacterium is a causative agent of ulcer formation, but its precise role in initiating ulcer formation is unclear at this time - In addition to playing a role in ulcer formation, H. pylori infections have been linked to gastric lymphomas and adenocarcinomas. - Transmission of H. pylori is generally through the fecal-oral route by ingestion of waste tainted food or water - H. pylori can also be transmitted from person to person by passing bacteria from the stomach to the mouth by reflux or belching.

Question 47

Pathophysiology of peptic ulcers

Answer 47

- Impaired regulation of gastric acidity or the loss of mucosal protection, for example by excessive secretion of gastrin or impaired secretion of mucus, can lead to a break down in the epithelial lining or mucosal layer of the gastrointestinal tract (ulcer) - There are multiple types of ulcers (see handout if necessary)

Question 48

Pathophysiology of Zollinger-Ellison syndrome

Answer 48

- One or more tumors form in your pancreas or the upper part of your small intestine (duodenum) - These tumors, called gastrinomas, secrete large amounts of the hormone gastrin, which causes your stomach to produce too much acid - The excess acid, in turn, leads to peptic ulcers