3a. Gastric Acid Secretion CAMTASIA

Question 1

Generally, functions of the stomach?

Answer 1

It functions primarily as a reservoir to store large quantities of recently ingested food, thus allowing intermittent feedings, initiating the digestive process, and releasing its contents in a controlled fashion downstream to accommodate the much smaller capacity of the duodenum.

Question 2

What are the 2 types of mucosa in the stomach?

Where is each located/what does each do?

Answer 2

• oxyntic gland mucosa: secretes acid, located in prox stomach (body, fundus).
• pyloric gland mucosa (antrum). secretes gastrin

Question 3

what are the 5 layers of the stomach lining?

in what layer are all the functional secretory elements?

Answer 3

• mucosa (contains secretory elements)
• deep mucosa/lamina propria
• submucosa (connective tissue of collagen and elastin)
• muscularis propria
• serosa

Question 4

Parietal/Oxyntic glands of the fundus: what cell types do they contain?

Answer 4

• surface mucus cells
• mucus neck cells
• parietal cells
• chief cells
• enterochromaffin-like cells

Question 5

oxyntic glands: what do they secrete?

anatomy of the glands?

location?

Answer 5

• acid, intrinsic factor, most gastric enzymes
• straight, simple tubular glands
• located in fundus/body

Question 6

anatomy of an oxyntic gland: what are the important areas/what cell types are located there?

Answer 6

each gland has 3 areas: isthmus, neck, base

Isthmus: surface mucous cells

Neck: parietal and mucous neck cells

Base: chief cells

Scattered throughout: D cells (somatostatin), enterochromaffin cells (histamine)

Question 7

what is the process of creating these gastric exocrine cells? where do they start/where do they migrate?

Answer 7

• Start as stem cells (precursor cells above) in the midregion or neck of the gastric glands.
• Upward flow of the neck cells toward the surface is a rapid process, < 1 week, –> mucus cells
• Downward flow of neck cells into the gastric gland may require several weeks –> parietal cells and chief cells.

Question 8

Motor functions of the stomach?

Answer 8

• reservoir for ingested food
• digestion: mixing, grinding, pepsinogen secretion (initial protein digestion)
• Empties into duodenum once particles are 50microns in size

Question 9

What is the cephalic phase? what are the things that happen during this phase?

Answer 9

First phase of acid secretion

Cephalic = initial response to sight, smell, taste, thought of food

-Vagally mediated via direct stim of parietal cells & ECL cells; indirect stim of G cells

Question 10

What is the gastric phase? what happens during this phase?

Answer 10

second phase of acid secretion in response to a meal

• distension
• buffering of gastric acid pH
• AA stimulation of the parietal cells and G cells

Question 11

what is the intestinal phase? what happens?

Answer 11

third phase of acid secretion in response to a meal

• response to movement of food out of the stomach/low pH
• chyme components in duodenum w release of secretin & GIP

Question 12

Cardia: begins at what location (anatomically)?

transition from what cell type to what?

what is function?

gastric pits are deep or shallow?

Answer 12

• begins at Z line
• transition from Squamous to Columnar (at GEJ)
• Protects surface of the stomach from corrosive gastric contents, prevents reflux
• Shallow gastric pits

Question 13

Fundus/body

what is function?

gastric pits are deep or shallow?

what cell type?

Answer 13

• Accomodation of food
• Gastric acid secretion
• Deep gastric pits – parietal cells, chief cells, endocrine cells (ECL, D cells)

Question 14

Antrum:

function?

gastric pit depth? cell types?

Answer 14

Mixing, grinding, sieving particles

Regulation of gastric secretory function via gastrin/somatostatin

-Gastric pits are intermediate: surface and neck mucus cells, endocrine cells (G cells, D cells)

Question 15

LES and cardia: secretions?

Answer 15

Mucus

HCO3

Question 16

Fundus and body: secretions?

Answer 16

H+

Intrinsic factor

mucus

HCO3

pepsinogens

lipase

Question 17

antrum and pylorus: secretions?

Answer 17

mucus

HCO3

Question 18

surface cells and neck cells: product? function?

Answer 18

mucus, HCO3, trefoil peptides

lubrication, protection

Question 19

parietal cells: product? function?

Answer 19

H+, intrinsic factor

protein digestion, binding of cobalamin, protection from bacteria

Question 20

chief cells: product? function?

Answer 20

pepsinogen, gastric lipase

Protein digestion, triglyceride digestion

Question 21

endocrine cells: product? function?

Answer 21

gastrin (G cell), histamine (ECL cell), somatostatin (D cell)

regulation of acid secretion

Question 22

what is a pareital cell? where is it located? what does it produce? what does it require?

Answer 22

Principle cell in oxycintic portion.

produces gastric acid

requires energy to concentrate H ions, gets it from ATP produced from mitochondria wihtin the cell

Question 23

Describe the parietal cell in its resting state.

Answer 23

• Resting state: the cytoplasm of the parietal cells is dominated by numerous tubulovesicles.
• An intracellular canaliculus is continuous with the lumen of the oxyntic gland.
• Resting state: canaliculus is collapsed.
• Low flow of acid (note only one yellow pump on the canaliculus)

Question 24

Parietal cell: what happens with stimulation?

Answer 24

After stimulation of acid secretion the tubulovesicles become microvilli and project into the canaliculus, which has become greatly expanded to occupy much of the cell.

Exchanges H for K and creates HCl which is released into the lumen

Carbonic anhydrase and H,K,ATPase (enzymes for the production and secretion of acid), are localized in the microvilli.

The activities of these enzymes increases dramatically during acid secretion. Acid secrtion begins within 10 minutes of administering a stimulant.

Question 25

what stimulates the parietal cell?

Answer 25

**acetylcholine (muscarinic receptor). incr cellular Ca** **gastrin (CCK-B type receptor). Incr intracellular Ca** **histamine (H2 receptor).** most important: both efficient and a good target for meds. incr cellular **cAMP and also Ca.**

Question 26

what are a few H2 receptor blockers?

Answer 26

cimetidine, ranitidine, nizatidine, famotidine (last is most potent we have)

Question 27

Sites of action of some anti-acid drugs?

Answer 27

- Proton-pump inhibitors. inhbition of the H/K ATPase totally blocks acid secretion. ex: omeprazole - H2 blockers

Question 28

how is the parietal cell able to generate acid without becoming too alkaline?

Answer 28

accumulation of OH results from pumping out of H+... but bicarb is exchanged for Cl at the basolateral side of cell. (Cl goes IN to the cell, bicarb goes out) thus the pH doesn't change much within the cell "alkaline tide"

Question 29

what happens to the alkaline part of the alkaline tide?

Answer 29

architectural relationship between capillaries and the basolateral side of the mucosal cells. The OH is picked up by the capillaires and brought to the surface cells to defend it against acid.

Question 30

At low rates of secretion, what is the compositin of the gastric juice? At high rates?

Answer 30

**Low** rates: Mostly **NaCl**, very low H+ and K+ (NON parietal component - basal alkaline secretion) **High** rates: Mostly **HCl**. Low H+, Low K+ (Parietal component - result of stimulation) Always higher than plasma for H+, Cl-, K+. Always than lower than plasma for Na+. **Always isotonic to plasma, regardless of composition!**

Question 31

what stimulates the secretion of mucus from the **mucus** **neck cells?** What stimulates mucus secretion from the **surface** mucus cells?

Answer 31

Neck cells: **vagal nerve stimulation and Acetylcholine.** Surface cells: physical stimulation of **food**.

Question 32

How do mucus and bicarb protect the gastric mucosa from acidic damage?

Answer 32

Secreted mucus is a gel which traps the alkaline part of surface cell secretion. Present during the interdigestive phase - forms alkaline layer of lubricant. During meal response, the mucus protects the stomach mucosa from both physical and chemical damage. - neutralizes some acid - prevents pepsin from contacting mucosa - if mucus contacts acid, it precipitates it into clumps and passes it into the duodenum.

Question 33

agents that disrupt the gastric mucosal barrier? (4)

Answer 33

- weak acids (aspirin) - alcohol - NSAIDs (ibuprofen) - detergents (bile salts)

Question 34

what are the 3 types of communication that mediate responses in the GI tract?

Answer 34

- endocrine - neurocrine - paracrine

Question 35

describe endocrine communication in the GI tract

Answer 35

Endocrine: Sensory cells (in stomach) respond to mechanical or chemical stimuli by releasing transmitters (hormones) that travel by way of blood to target cells or tissues. The apical surfaces of endocrine cells have microvilli that face the intraluminal contents of the gut. These respond to a specific aspect of the intraluminal milieu such as changes in pH or osmolality or specific nutrients. Examples of the hormones released include: cholecystokinin (CCK), gastrin, glucose insulinotropic peptide (GIP), secretin, pancreatic polypeptide (PP).

Question 36

describe neurocrine communication in the gut

Answer 36

Neurocrine: With this mechanism the sensing and transmissions to target tissues are completely mediated by **nerves** and **neurotransmitters**. Nerves sense stimuli such as nutrients, pH and osmolality in the luminal contents as well as the movement of the contents and the distension of the gut lumen. The message to the target tissue can be entirely within the nerves in the wall of the gut (the enteric nervous system), or it can be to the central nervous system. In both cases, activation of nerves causes changes in the secretory or motor activity of the GI tract. These nerves are thus sometimes referred to as secretomotor neurons. Examples of the neurotransmitters released include: acetylcholine (Ach), CCK (some mediators can act through more than one mechanism), gastrin releasing peptide (GRP), nitric oxide (NO), somatostatin, substance P, vasoactive intestinal peptide (VIP).

Question 37

describe paracrine communication in the gut

Answer 37

Paracrine: A mechanism where the sensing cell releases a transmitter that mediates the response in **neighboring** cells. There are only a few paracrine responses identified in the GI tract, they help regulate gastric acid secretion. Mediators functioning by this mechanism include: CCK, histamine, 5-hydroxytryptamine (5-HT), and somatostatin.

Question 38

Hormones involved in gastric acid secretion? (4)

Answer 38

Gastrin CCK secretin Glucose-dependent insulinotropic peptide (GIP)

Question 39

paracrines involved in GA secretion?

Answer 39

somatostatin histamine

Question 40

neurocrines involved in GA secretion?

Answer 40

Ach GRP

Question 41

What phase causes the most acid secretion?

Answer 41

gastric (50%) cephalic (30%)

Question 42

A few things that happen during the cephalic phase?

Answer 42

Chemoreceptors and mechanoreceptors in the tongue, mouth and nose are stimulated. Afferent nerve impulses are relayed through vagal nucleus to stomach --\> activate enteric NS --\> acid secretion. Uses ACH! -**Directly** stimulates Parietal cel, chief cell, ECL cell, G cells **Indirectly** stimulates G cells via GRP (through vagal)

Question 43

What does Ach do in the stomach?

Answer 43

- from vagus nerve, acts directly on parietal cells - activates ECL cells to release histamine --\> stimulates parietal cell - stimulates G cell to release gastrin

Question 44

what is the main mediator of gastrin release from teh G cell?

Answer 44

Enteric neurons stimulated during the **cephalic** phase by vagal stimulation **GRP (gastrin-releasing peptide) which is the main mediator affecting the release of gastrin from the G cell.** Release of gastrin stimulates the **ECL cell to release histamine** which in turn stimulates the parietal cell through a paracrine mechanism.

Question 45

Gastric phase: a few things that happen?

Answer 45

**Food** enters stomach, mixes with some acid juice and buffers the acid. **pH rises to 6** and allows release of more gastrin. **AA and protein products stimulate cells to release gastrin** Fundal **distension** increases p**arietal cell secretion via vagally-mediated reflex arc.**

Question 46

Gastric secretion and acidity directly after a meal?

Answer 46

Once stomach is empty, less gastrin is released No longer food tehre to buffer pH so the pH lowers Acidity stimulates D cells to release somatostatin, which inhibits G cells --\> less gastrin.

Question 47

Why do ulcer patients hvae relief about 2 hrs after a meal?

Answer 47

The food bolus buffers the acid pH rises, gastrin is released, acid is stimulated but pH is still not very acidic