Gastric Secretion

Question 1

types of glands

Answer 1

There are two types of glands :

1. Oxyntic glands (also called as gastric glands)
2. Pyloric glands

Oxyntic glands

• secrete hydrochloric acid, pepsinogen, intrinsic factor and mucus
• located on the inside surfaces of the body and fundus of stomach, the proximal 80% of the stomach

• Secretions from the gastric (or oxyntic) glands

• mucus neck cells - secrete mainly mucus
• peptic (or chief cells) - secrete large quantities of pepsinogen
• parietal (or oxyntic cells) - hydrochloric acid and intrinsic factor
• enterochromaffin-like (ECL) cells - Histamine
• D cells containing Somatostatin

Pyloric glands

• mainly mucus for protection of the pyloric mucosa from the stomach acid.
• also secrete hormone gastrin
• pyloric glands are located in the antral portion of the stomach, the distal 20% of the stomach

• Secretions from the Pyloric glands
similar in structure but contain few peptic cells and no parietal cells
- mucus neck cells
- peptic (or chief cells) - secrete pepsinogen
- G cells - secrete hormone gastrin, which plays a key role in controlling gastrin secretion

Question 2

Composition of gastric juice

Answer 2

1) Water
2) Solutes

Solutes

a) Inorganic components
- hydrochloric acid (HCl)
- Sodium
- Potassium
- Bicarbonate

b) Organic Components
- Enzymes
• pepsin
• gastric lipase
• gelatinase
- Intrinsic factor

Question 3

Mechanism of HCl secretion

Answer 3

the parietal cell (or oxyntic cell) contains large branching intracellular canaliculi. the hydrochloric acid is formed at the villus like projections inside these canaliculi and is then conducted through the canaliculi to the secretory end of the cell

the main driving force for hcl secretion by the parietal cells is a hydrogen-potassium pump (h+-k+ adenosine triphosphatase (ATPase))

the chemical mechanism of hcl acid formation is as follows:

1) Water inside the parietal cell becomes dissociated into H+ and OH− in the cell cytoplasm. The H+ is then actively secreted into the canaliculus in exchange for K+, an active exchange process that is catalyzed by H+-
K+ ATPase.
2) Potassium ions transported into the cell by the Na+-K+ ATPase pump on the basolateral (extra-cellular) side of the membrane tend to leak into the lumen but are recycled back into the cell by the H+-K+ ATPase.

3) The basolateral Na+-K+ ATPase creates low intracellular Na+, which contributes to Na+ reabsorption from the lumen of the canaliculus. Thus, most of the K+ and Na+ in the canaliculus is reabsorbed into the cell cytoplasm, and hydrogen ions take their place in the
canaliculus.

4). The pumping of H+ out of the cell by the H+-K+ ATPase permits OH− to accumulate and form HCO3 from CO2 either formed during metabolism in the cell or entering the cell from the blood. This reaction is catalyzed by
carbonic anhydrase.

5) The HCO3
− is then transported across the basolateral membrane into the extracellular fluid in exchange for chloride ions, which enter the cell
and are secreted through chloride channels into the canaliculus, giving a strong solution of hydrochloric
acid in the canaliculus. The hydrochloric acid is then secreted outward through the open end of the canaliculus into the lumen of the gland.

6. Water passes into the canaliculus by osmosis because of extra ions secreted into the canaliculus. Thus, the final secretion from the canaliculus contains water, hydrochloric acid at a concentration of about 150 to 160 mEq/L, potassium chloride at a concentration of 15 mEq/L, and a small amount of sodium chloride.

Question 4

Regulation of HCl secretion

Answer 4

Gastric secretion occurs in 4 phases and is controlled by neural as well as hormonal mechanism.

1.CEPHALIC PHASE:-is the gastric secretion that occurs before the food enters the stomach. It is a preparatory
phase and accounts for 20% of gastric secretion.

It occurs in response to

A) Presence of Food in mouth which
stimulates tactile receptors and taste buds in mouth. Afferent impulses are carried to dorsal motor nucleus of
vagus which controls gastric secretion. This centre sends efferent impulses through the vagus to the intrinsic
plexus and gastric glands producing gastric secretion. This is an unconditioned reflex.

B) Sight Smell or Thought of food:-Here, the impulses originate from visual centre, smell centre or appetite of
hypothalamus and end on vagal centre stimulating it, which then brings about gastric secretion (appetite juice).
It is a conditioned reflex. Cephalic secretion is increased in emotions like anger and frustration hypoglycemia
and stimulation of lateral hypothalamus.

2.GASTRIC PHASE:-
Results from presence of food in stomach. It accounts for 2/3 rds of total gastric secretion. It can occur via Neural or chemical mechanism

A) Neural reflexes:-
i)Food in stomach
stimulates stretch receptors which in turn lead to Vagovagal reflex or long reflex producing gastric secretion ii)stimulation of stretch receptors also leads to activation of local Meissners
plexus which, in turn, stimulates gastric glands producing secretion (Intramural or shortreflex).

B) Hormonal Mechanism :-Operates through the hormone Gastrin It is released from G cells of pyloric glands in response to

1) distension of stomach by food which leads to a vagovagal reflex, the efferent vagal fibers terminating on G cells and release gastrin releasing peptide. Distension of stomach can also bring about gastrin release by intramural
reflexes.

2) Presence of secretagogues in stomach like alcohol, caffeine, Peptones and amino acids which directly act on G
cells. Released gastrin then enters the blood, reaches the gastric glands and stimulates them to produce gastric
secretion rich in HCL.

However excess secretion HCL is prevented by

1) inhibitory effect of acidic chyme (pH less than by 7) on gastrin
secretion.
2. Somatostatin .

In this phase, neural mechanism is week but lasts longer.

3. INTESTINAL PHASE:-Occurs due to presence to chyme in small intestine. It results from release of the hormone gastrin (enteric gastrin) from G cells in duodenum and proximal jejunum in response to distension (via intramural reflex) or presence of secretagogues, especially, amino acids. It reaches gastric glands passing through blood and stimulates them. Another hormone called enteroxyntin is also released by chyme which stimulates gastric secretion. However, chyme in the intestine also brings about release of hormones like CCK, secretion and G.I.P. which have inhibitory effect on gastric secretion and thus provide a negative feedback mechanism controlling gastric secretion.
4. INTERDIGESTIVE PHASE:-Is the gastric secretion occurring in fasting state. It is small in quantity, poor in acid and rich in mucus mediated by neural as well as hormonal mechanism.

Applied Physiology:-

1. Vagotomy helps in controlling acid secretion in peptic ulcer.
2. Excess secretion of gastrin (Gastrinoma) is associated with hyper acidity and peptic ulcer (Zollinger Ellis syndrome)

Question 5

Peptic Ulcer

Answer 5

peptic ulcer is an excoriated area of stomach or intestinal mucosa caused principally by the digestive action of gastric juice or upper small intestinal secretions.

• pathophysiology:
—basic cause of peptic ulceration
diminished effectiveness of mucosal barrier
the defense barrier of the stomach is the mucus coat on the gastric epithelium. this is called mucosal defense barrier.

1. mucus allows the ph of the epithelial cells to remain alkaline despite acidic ph of gastric content. it protects mucos epithelium from injury caused by acidic chyme
2. however when secretion of mucus is impaired, or bicarbonate production is decreased or when the mucosal coat is mechanically damaged, acid and pepsin cause ulcer formation.

such damage is usually produced by use of aspirin and nsaids that inhibit secretion of mucus and bicarbonate.
catecholamines also inhibit mucus secretion. in chronic stress, ulcer is produced (stress ulcer) by chronically Elevated level of catecholamines in the blood

—hypersecretion of acid
chronically increased secretion of acid (hyperchlorhydia) produces peptic ulcer by damaging the mucosal barrier

conditions that cause hyperchlorhydia are:
• Zollinger-Ellison Syndrome
• gastric outlet obstruction syndrome
• systemic mastocytosis (histamine Secreted from mast cells increased hcl secretion)

•specific causes of peptic ulcer
—helicobacter pylori infection
Bacterial Infection by Helicobacter pylori Breaks Down the Gastroduodenal Mucosal Barrier and Stimulates Gastric Acid Secretion.
- At least 75 percent of peptic ulcer patients have been found to have chronic infection of the terminal portions of the gastric mucosa and initial portions of the duodenal mucosa, most often caused by the bacterium Helicobacter
pylori.
- Once this infection begins, it can last a lifetime unless it is eradicated by antibacterial therapy.
- Furthermore, the bacterium is capable of penetrating the mucosal barrier both by virtue of its physical capability to burrow through the barrier and by releasing ammonium that liquefies the barrier and stimulates the secretion of hydrochloric acid. As a result, the strong
acidic digestive juices of the stomach secretions can then penetrate into the underlying epithelium and literally digest the gastrointestinal wall, thus leading to peptic ulceration.

Other Causes of Ulceration.
Other factors that predispose to ulcers include
(1) smoking, presumably because of increased nervous stimulation of the stomach secretory glands;
(2) alcohol, because it tends to break down the mucosal barrier; and
(3) aspirin and other nonsteroidal anti-inflammatory drugs that also have a strong propensity for breaking down this barrier.

Treatment of Peptic Ulcers

1. use of antibiotics along with other agents to kill infectious bacteria
2. administration of an acid suppressant drug such as ranitidine and similar newer molecules which are antihistaminic agent that blocks the stimulatory effect of histamine on gastric gland histamine2 receptors, thus reducing the gastric acid secretion by 70-80%
3. proton pump inhibitors like Omeprazole

other measures:

1. neutralizing the gastric acids by antacids
2. bismuth compounds
3. cytoprotective agents such as sucralfate, an aluminium salt of sucrose octasulfate
4. prostaglandin such as misoprostol