Gastric Acid Secretion

Question 1

Components of gastric juice

Answer 1

Water
Organic compounds (intrinsic factor, pepsinogen, lipase, mucus)
Ions (Na, K, H, Cl, HCO3)

Question 2

6 types of cells you can find in the gastric mucosa

Answer 2

Superficial epithelial cells
Mucus neck cells
Stem/regenerative cells
Parietal (oxyntic) cell
Chief cell
Paracrine or endocrine cell

Question 3

Gastric glands in fundus and body:
What does
1. Parietal cell
2. Chief cell
3. Mucus neck cell
4. Paracrine cell
release?

Answer 3

1. HCl, intrinsic factor
2. Pepsinogen, lipase
3. Mucus
4. Histamine, somatostatin

Question 4

Pyloric glands in antrum
What does
1. Mucus neck cells
2. Endocrine cells
3. Paracrine cells
Release?

Answer 4

1. Mucus, bicarb
2. Gastrin
3. Somatostatin

Question 5

Intrinsic factor

Answer 5

Released from parietal cells into canaliculi

Facilitates vitamin B12 absorption in the small intestine

Question 6

Activating of the parietal cell causes…

Answer 6

Tubulovesicles (with the proton pumps and intrinsic factor) fuse with invaginated areas of the apical membrane
Leads to the formation of many microvilli
Generates canaliculi (tunnels continuous with lumen)
H/K proton pump facilitates HCl production
Bicarb is pumped into the interstitial space, enters bloodstream and buffers

Question 7

Proton pump

Answer 7

Transports H out of the cell, and K into the cell

Question 8

3 major ion transport pathways in an active parietal cell

Answer 8

1. Proton pump (H out, K in)
2. NaCl uptake drive by Na/H (basally - Na in, H out) and HCO3/Cl (HCO3 out, Cl in) - gradients driven by Na/K pump
3. K and Cl move out of the cell apically down a [ ] gradient

Question 9

4 functions of gastric acid

Answer 9

Bacteriostatic
Activates pepsinogen and lipase
Initiates protein denaturation
Facilitates absorption of iron, Ca, and vitamin B12

Question 10

Chief cells

Answer 10

Secretes pepsinogens and gastric lipases via exocytosis
Pepsinogens are inactive (zymogens), need to be activated by acid hydrolysis and autocatalysis
Gastric lipase activity is increased at low pH

Question 11

Apical mucus layer functions

Answer 11

Protects the lumenal epithelium from acid and pepsin-based hydrolysis as well as microorganisms
Barrier contains protective glycoproteins/mucins and pH neutralizing bicarb ions

Question 12

How is secreted mucus held in place?

Answer 12

By apically-targeted ‘surface active phospholipids’

Located in the lumenal membrane of mucus epithelial cells

Question 13

How is bicarb taken up into the basal surface of the mucus cells?

Answer 13

Via a Na/HCO3- co-transporter

Released into the lumen, and neutralizes acid in the mucus

Question 14

3 major secretagogues that stimulate both pepsinogen and acid production

Answer 14

Can act on chief and parietal cells
Gastrin
Histamine
Acetylcholine

Question 15

G cells

Answer 15

Secrete gastrin
Found at the base of pyloric glands
Secretory vesicles are found basally

Question 16

Gastrin

Answer 16

Polypeptide hormone released from G cells
Can act locally or travel through the blood
Binds to gastrin receptors (CCK 2/B)
Activates parietal and chief cells
Production of gastrin is stimulated by GRP from enteric neurons, and by digested protein in the gastric lumen

Question 17

Enterochromaffin-like cells

Answer 17

Found at the base of gastric glands
Produce histamine (paracrine factor)
Histamine production is stimulated by ACh from intrinsic enteric neurons, or gastrin from G-cells

Question 18

Receptors on parietal cells for

1. ACh
2. Histamine
3. Gastrin

Answer 18

1. M3 receptors
2. H2 receptors
3. CCK2/B receptors

Question 19

Cephalic stimulatory phase of acid secretion

Answer 19

Taste, smell, sight, or thought of food activates your hypothalamus
Sends signals to dorsal vagal motor nucleus
Vagus nerve travels to stomach and can act on G cells or parietal cells to increase acid secretion in prep for a meal

Question 20

Acid secretion from the stomach can be ___ or ___

Answer 20

Neuronal

Non-Neuronal

Question 21

Gastric stimulatory phase of acid secretion: neuronal

Answer 21

Hypothalamus activates dorsal vagal motor nucleus, vagus travels to stomach, activates G cells and parietal cells
Activation of stretch receptors can stimulate G cells, and can travel via the vagus to the nodose ganglion, which connects into the above path at the dorsal vagal motor nucleus

Question 22

Nodose ganglion

Answer 22

Inferior ganglion of vagus nerve

Receives visceral sensory/afferent nerves

Question 23

Gastric stimulatory phase of acid secretion: non-neuronal

Answer 23

Food enters the stomach
As its broken down you get buffering of the intragastric pH and the production of peptones and amino acids
Peptones and amino acids stimulate G cells
Food and buffering stimulate parietal cells

Question 24

Intestinal phase of acid production

Answer 24

When peptones in the chyme reach the duodenum, G cells there are stimulated to produce more gastrin that acts on the parietal and chief cells in the gastric glands
(via gastrin’s hormonal action)

Question 25

Cephalic inhibitory phase of acid secretion

Answer 25

Hypothalamic satiety and feeding nuclei are activated, activate the dorsal vagal motor nucleus Through vagus sends inhibitory signals to parietal cells

Question 26

Gastric inhibitory phase of secretion

Answer 26

Acid in the pyloric antrum stimulates somatostatin release to inhibit meal-stimulated gastrin secretion Somatostatin works in paracrine way

Question 27

Intestinal inhibitory phase of secretion

Answer 27

Chyme into the duodenum stimulates a neuronal enterogastric reflex arc through the sympathetic celiac ganglion Also stimulates the production of enterogastrones These inhibit he G cell, parietal cell, and chief cell activity, as well as smooth muscle contraction in the stomach

Question 28

Enterogastrones

Answer 28

Hormones that feedback to inhibit the G cell, parietal cell, and chief cell activity, as well as smooth muscle contraction in the stomach Include: secretin, CCK, GIP, and GLP-1

Question 29

5 functions of prostaglandins

Answer 29

Inhibit acid secretion Prevent surface epithelial cell exfoliation Increase mucosal blood flow Stimulate mucus and bicarb secretion Enhance synthesis of surface-active phospholipids *Prostaglandins are anti-secretory and protective*

Question 30

Do you want to inhibit COX1 or COX2

Answer 30

COX2! Its the pain pathway | Chronic use of COX1/2 inhibitors is problematic in the gastric mucosa

Question 31

H. pylori

Answer 31

Gram negative flagellated bacterium Produces urease (converts urea to ammonia and CO2 to protect from acid) Requires special media for growth

Question 32

H. pylori negative ulcers are usually due to...

Answer 32

NSAIDs

Question 33

6 survival factors for H. pylori

Answer 33

``` High mutation rate Motility (chemotactic - away from acid) Ability to attach to epithelial cells of the gastric mucosa (adhesions bind surface receptors on epithelial cells) Virulence factors (cagA, VacA) Urease activity Evasion of the adaptive immune response ```

Question 34

Action of H pylori's virulence factors

Answer 34

Injected into epithelial cells Cause the cells to release nutrients and urea that are used by the bacteria Also damage epithelial cells and disrupt tight junctional barrier between cells. facilitated local inflammation Inflammation results in local production of cytokines that stimulate G cells and inhibit D cells = increased acid production and further local tissue injury inflammation

Question 35

Urease

Answer 35

Converts urea into NH3 and CO2 Neutralizes acid which allows for further protection of bacteria attached to epithelial cells Facilitates further gastrin secretion

Question 36

Treatment for H pylori

Answer 36

Most often its a combined proton pump inhibitors and antibiotics