Gastric Secretion

Question 1

Gastric mucosa regions and their secretions

Answer 1

The cardiac glandular region, located just below the
LES, contains primarily mucus secreting cells.

The remainder of the gastric mucosa can be divided into the oxyntic glandular region, which secretes acid, and the pyloric gland area which does not. Both areas secrete pepsinogen and mucus.

The pyloric gland area is the major site for the release of gastrin and somatostatin

Question 2

6 gastric secretions

Answer 2

A. H+ (from HCl) which converts pepsinogen into pepsin, kills microbes and denatures proteins

B. Pepsinogen which when converted to pepsin, partly digests protein

C. Mucus which lubricates and protects the mucosa.

D. Bicarbonate which acts to protect the mucosal surface

E. Intrinsic factor which is necessary for normal absorption of vitamin B12

F. Water which dissolves and dilutes ingested material

Question 3

Cell type - location - secretion (of gastric mucosa)

Answer 3

Mucus neck cell - primarily neck of gastric glands - Mucus

G cell - glands in pyloric antrum - Gastrin

Oxyntic (parietal) cell - glands in cardia, fundus & corpus - HCl + IF

Chief cell - glands in cardia, fundus & corpus - Pepsinogen

Surface mucous cells - entire mucosa (except cardia) - Mucus & HCO3

Question 4

PRODUCTION OF ACID BY OXYNTIC (PARIETAL) CELLS

Answer 4

ultimately dependent on the basolateral Na+/K+-ATPase (the sodium pump), the primary active transport mechanism that sets up the electrochemical gradient upon which the other processes rely.

Together, the events occurring at the apical and basolateral membranes result in net secretion of HCl and net absorption of HCO3-.

Question 5

IONIC CONCENTRATION OF GASTRIC JUICE VARIES WITH FLOW

Answer 5

With increasing rates of secretion the H+ concentration rises and the Na+ concentration falls. Always isotonic.

Question 6

SECRETION AND ACTIVATION OF PEPSINOGEN

Answer 6

The cells of the gastric pits secrete several different types of pepsinogen. Pepsinogen has no digestive activity however until it is activated by the hydrochloric acid to form pepsin.

Pepsin is most active at pH 2-3 and is inactive when the pH>5.

Question 7

SECRETION OF ACID BY OXYNTIC (PARIETAL) CELLS

Answer 7

1. Stimulation —> acetylcholine, gastrin and histamine.

Acetylcholine and gastrin both elicit acid secretion via the same intracellular pathway. Thus, because histamine acts by a different mechanism it is capable of potentiating the effects of both acetylcholine and gastrin.

2. Inhibition —> prostaglandins, secretin and somatostatin.

Question 8

Acetylcholine

Answer 8

Acetylcholine stimulates parietal cells by acting on specific cholinergic muscarinic receptors. Its effects are blocked by antagonists such as atropine that occupy this class of receptor.

Question 9

Gastrin

Answer 9

Gastrin is a hormone that is released from G-cells located in the gastric antrum and, to a lesser extent in the duodenum. It has considerable structural homology with cholecystokinin (CCK) and both can act at the same receptor subtype.

Question 10

Histamine

Answer 10

Histamine stimulates the parietal cell by acting on histamine H2 receptors. The effects of histamine are blocked by selective antagonists that act at this receptor subtype. Examples of this are cimetidine (Tagamet) and famotidine (Pepcid). Unlike acetylcholine and gastrin, there is no evidence that histamine is released physiologically in response to eating.

Question 11

Prostaglandins

Answer 11

Prostaglandins are locally released derivatives of arachidonic acid that act to decrease parietal cell acid secretion by preventing histamine-induced increases in cyclic AMP (cAMP). Since prostaglandin synthesis is inhibited by drugs such as aspirin or ibuprofen, these agents have the potential to exacerbate an existing ulcer by indirectly promoting acid release.

Question 12

Secretin

Answer 12

Secretin is a hormone released from S cells in the duodenal
mucosa in response to the presence of gastric acid in this region. Secretin opposes both the acid stimulating and the trophic effects of gastrin on the oxyntic (acid producing) mucosa of the stomach. Secretin also promotes HCO3- secretion by the pancreas which “mops up” any excess acid that leaves the stomach and enters the
duodenum.

Question 13

Somatostatin

Answer 13

Somatostatin is a paracrine agent released from D cells in the gastric mucosa that acts both to depress gastrin release from G cells and also to oppose the effects of gastrin on parietal cells. It may be released in response to the presence of large amounts of acid in the gastric lumen.

Question 14

Phases of gastric acid secretion

Answer 14

1. Cephalic
2. Gastric
3. Intestinal

Question 15

The cephalic phase

Answer 15

is mediated by the vagus nerve. Even the thought of an appetizing meal can stimulate acid secretion. This response is abolished by vagotomy.

Vagal stimulation involves two mechanisms. Vagal efferents directly stimulate parietal cells to secrete acid. This is mediated by acetylcholine and is blocked by atropine. Vagal stimulation also releases gastrin from antral G-cells.

There is good evidence that the vagal mediator for gastrin release is the peptide bombesin. Gastrin then circulates through the bloodstream back to the stomach stimulating the parietal cell. In order for gastrin to be released, the pH of the gastric contents must first be raised above 3.0. This is accomplished by the buffers present in ingested food.

Question 16

Gastric phase

Answer 16

During the gastric phase ingested food prompts the release of secretagogues which act on the parietal cells.

First, swallowed food distends the stomach and activates stretch receptors in the stomach wall causing a long (distance) neural reflex. This vago-vagal reflex is conducted by afferent fibers from the stomach to the vagal nuclei in the medulla.

The efferent vagal fibers then release acetylcholine and bombesin (gastrin releasing peptide).

Bombesin stimulates the G-cell to release gastrin and acetylcholine stimulates the parietal cell directly.

Another stretch-induced reflex is initiated via intrinsic nerves in the stomach to release acetylcholine stimulating parietal cell secretion of acid and may also promote G-cell release of gastrin.

Second, acid digestion of protein in the stomach releases peptides and amino acids both of which act directly on the G-cells of the pyloric gland mucosa to release gastrin. Gastrin circulates back to the gastric mucosa via the systemic circulation again stimulating secretion of H+ from parietal cells.

Question 17

Intestinal phase

Answer 17

During the intestinal phase acid secretion is stimulated by hormones and by absorbed amino acids. Digested proteins in the duodenum cause release of a small amount of gastrin from intestinal (duodenal) G-cells. There is also evidence that a second hormone “entero-oxyntin” is released into the blood. Both hormones circulate to parietal cells where they stimulate H+ secretion. However, these excitatory actions are overwhelmed by the inhibitory influence of the duodenum during this stage.

First, the presence of acid in the duodenum stimulates the release of secretin, a potent inhibitor of acid secretion (secretin also stimulates pancreatic HCO3- secretion).

Second, lipid (fat) in the duodenum promotes the release of several substances collectively known as “enterogastrones” which also depress release of gastric acid. Candidate substances in this class of compound include neuropeptide Y and peptide YY.

Due to the relationship of excitation versus inhibition during this time, the intestinal phase of gastric acid secretion constitutes only a small percentage of the entire secretory response to a meal.

Question 18

Phase - stimulation - % total acid (gastric phases)

Answer 18

Interdigestive - Basal - 15

Cephalic - Smell, taste & sight of food - 30

Gastric - Food in stomach - 50

Intestinal - Digestion products in the intestine - 5

Question 19

GASTRIC MUCOSAL BARRIER

Answer 19

mucus forms an unstirred layer in which convection is absent and HCO3- is trapped in this. As the HCO3- diffuses into the mucus it meets and neutralizes H+ diffusing
outwards from the lumen. Thus, the mucus layer comprises a
neutralization zone in which the concentration of H+ declines
progressively towards the mucosal surface.

Other protective mechanisms that are involved in this process include the tight connections between mucosal cells and also their rapid rate of turnover.

Prostaglandins play an important role in protecting gastroduodenal mucosa by stimulating the secretion of mucus and bicarbonate, maintaining blood flow during periods of potential injury and suppressing
acid secretion.

Question 20

GASTRIC MUCOSAL ATROPHY

Answer 20

Loss of cells that secrete acid and pepsinogen.

Accompanied by hypochlohydria or achlorhydria. This is not too serious because digestion can be adequately carried out in the small intestine. However, the loss of secretion of intrinsic factor is important because now vitamin B12 cannot be absorbed.

At the alkaline pH of the duodenum IF and B12 combine to form a complex which protects B12 during transit. When IF-B12 reaches the terminal ileum the complex dissociates and B12 is absorbed. Loss of parietal cells, as in gastritis, leads to inadequate B12 absorption and pernicious anemia over time.

Question 21

NSAIDS

Answer 21

can initiate mucosal injury topically due to their acidic properties. gastric acid and pepsin may then injure the surface epithelium.

Systemic effects of NSAIDs appear to play a predominant role through the decreased synthesis of mucosal prostaglandins. The precursor of prostaglandins, arachidonic acid, is catalyzed by the two cyclo-oxygenase isoenzymes, cyclo-oxygenase-1 and cyclo-oxygenase-2.

Question 22

ULCER FORMATION:

Answer 22

Not by stress and/or spicy foods (these aggravate, don’t cause them).

both gastric and duodenal ulcer formation are linked to the presence of the bacterium Helicobacter pylori.

It produces adhesins which bind to membrane-associated lipids and carbohydrates and help its adhesion to epithelial cells. It produces large amounts of urease enzymes which are localized inside and outside of the bacterium. Urease metabolizes urea (which is normally secreted into the stomach) to carbon dioxide and ammonia which neutralizes gastric acid.

Once H. pylori is attached, epithelial damage is thought to result from the body’s immune response to the presence of the organism resulting in the gastric mucosal barrier being broken.

Ammonia produced is toxic for the epithelial cells.

HCl and pepsin begin to erode the mucosal epithelium. The acid then stimulates the release of histamine from cells in the submucosa. The histamine causes the release of more acid and a vicious circle is set up.