Control of Gastric secretions

Dr Raghuveer Choudhary Associate Professor Dept. of Physiology

Gastric secretion
Gastric juice
- hydrochloric acid - conversion of pepsinogen to pepsine - bacteriostatic effect - pepsin - protein digestion - replaceable by pancreatic enzymes - mucus - protective coating, lubricant - part of gastric mucosal barrier

- intrinsic factor - binds B12 vitamin, absorption in the ileum - the only indispensable substance in gastric juice

Gastric juice & its secretion * Nature, Compositions & functions pH 0.9~1.5, colorless, 1.5~2.5 L/day Hydrochloric acid (HCl) Secreted by parietal cells Basic secretion: 0~5 mmol/h Max secretion: 20~25 mmol/h Mechanism of HCl secretion

Functions of HCl:

Turn pepsinogen into pepsin & provide a

medium of low pH favoring pepsin action;

Kill many swallowed virulent organisms;

Promote the secretion of pacreas & bile; Promote the absorption of calcium & ferrus Pepsinogen Secreted by chief cells & activate by HCl

Function: digest proteins into proteoses, peptones,

polypeptides, with little free amino acids

Parietal cell - secreting

Tubulovesicles fuse with canaliculus, increased surface area and numbers of H+K+ATP ase increases acid secretion into lumen of gut.

H+
Acid secretion is against a 3 million fold concentration gradient H+ inside = 4x 10-8M H+ outside = 0.1 M NEEDS ENERGY

MECHANISM OF GASTRIC ACID SECRETION

The oxyntic cells produce and secrete acid,described as follows

H+ is produced through the action of carbonic anhydrase, which produces carbonic acid from CO2 and H2O. The H+/ K+-ATPase is used to pump H+ from the cytoplasm into the stomach lumen in exchange for K+. K+ used in this exchange process is available from food or saliva, but it is also secreted via a luminal membrane K+ channel.

Cl must be secreted to yield HCl. Cl uptake into oxyntic cells from the extracellular fluid occurs via the Cl/HCO3exchange at the basolateral cell membrane. HCO3 exits the cell in such a large quantity that the gastric venous blood becomes alkaline; this is known as the postprandial alkaline tide.

Cl is secreted into the lumen via a Cl channel in the luminal membrane, which results in the generation of a large lumennegative transepithelial potential difference across the stomach mucosa. H+ is transported against a large electrochemical gradient, which is reduced by a lumen-negative voltage.

Regulation of Gastric Function

Gastric secretion and motility is divided into three stages: 1) Cephalic 2) Gastric 3) Intestinal phases

1) The Cephalic Phase

The cephalic phase is stimulated by the sight, smell, taste, or mere thought of food.

2) The Gastric Phase

- is stimulated by food in the stomach - accounts for two-thirds of gastric secretion.

3) The Intestinal Phase After entering small intestines, chyme inhibit gastric secretion and mobility via:

a) b)

the enterogastric reflex. local hormones Secretin Cholecystokinin gastric inhibitory peptide

Cephalic Phase
1. The taste or smell of food, tactile
sensations of food in the mouth, or even thoughts of food stimulate the medulla oblongata (green arrow). Taste or smell of food Tactile sensation in mouth

2. Parasympathetic action potentials

are carried by the vagus nerves to the stomach (pink arrow).
Medulla oblongata

3. Preganglionic parasympathetic
vagus nerve fibers stimulate postganglionic neurons in the enteric plexus of the stomach.

1 5
Vagus nerves Secretions stimulated

4. Postganglionic neurons stimulate

secretion by parietal and chief cells and stimulate gastrin secretion by endocrine cells.

3
Gastrin

4
Circulation

5. Gastrin is carried through the

circulation back to the stomach (purple arrow), where it stimulates secretion by parietal and chief cells. Stomach

Cephalic Phase Taste or smell of food Tactile sensation in mouth

Medulla oblongata

The taste or smell of food, tactile sensations of food in the mouth, or even thoughts of food stimulate the medulla oblongata (green arrow).

Cephalic Phase

Vagus nerves

Parasympathetic action potentials are carried by the vagus nerves to the stomach (pink arrow).

Cephalic Phase

Vagus nerves

Preganglionic parasympathetic vagus nerve fibers stimulate postganglionic neurons in the enteric plexus of the stomach.

Cephalic Phase

Gastrin Stomach Postganglionic neurons stimulate secretion by parietal and chief cells and stimulate gastrin secretion by endocrine cells.

Cephalic Phase

Secretions stimulated Gastrin Circulation

Gastrin is carried through the circulation back to the stomach (purple arrow), where it stimulates secretion by parietal and chief cells.

Stimulation of acid secretion cephalic phase

blocked by vagotomy sham feeding hypoglycemia

role of GRP (bombesin)

Medulla oblongata

Vagus nerves

Gastric Phase
1. Distention of the stomach activates a
parasympathetic reflex. Action potentials are carried by the vagus nerves to the medulla oblongata (green arrow).

Secretions stimulated

Distention

2. The medulla oblongata stimulates stomach

secretions (pink arrow).

3. Distention of the stomach also activates

local reflexes that increase stomach secretions (purple arrow). Stomach

Local reflexes stimulated by stomach distention

Gastric Phase

Medulla oblongata

Vagus nerves

Distention Local reflexes stimulated by stomach distention

Stomach

Distention of the stomach activates a parasympathetic reflex. Action potentials are carried by the vagus nerves to the medulla oblongata (green arrow).

Gastric Phase

Vagus nerves

Secretions stimulated
Decreased gastric secretions

Stomach

The medulla oblongata stimulates stomach secretions (pink arrow).

Gastric Phase

Distention Local reflexes stimulated by stomach distention

Stomach

Distention of the stomach also activates local reflexes that increase stomach secretions (purple arrow).

Gastric phase
60 % of acid response distension peptides

calcium alcohol caffeine

Experiment of Sham feeding by Pavlov

Intestinal Phase
1. Chyme in the duodenum with
a pH less than 2 or containing fat digestion products (lipids) inhibits gastric secretions by three mechanisms. Medulla oblongata Vagus nerves

2. Sensory vagal action potentials

to the medulla oblongata (green arrow) inhibit motor action potentials from the medulla oblongata (pink arrow). Vagus nerves

Decreased gastric secretions

2 1
pH<2 or lipids

Local reflexes

3. Local reflexes inhibit gastric

secretion (orange arrows).

4. Secretin, gastric inhibitory

polypeptide, and cholecystokinin produced by the duodenum (brown arrows) inhibit gastric secretions in the stomach.

Secretin, gastric inhibitory peptide, cholecystokinin

4
Circulation

Intestinal Phase

pH<2 or lipids

Chyme in the duodenum with a pH less than 2 or containing fat digestion products (lipids) inhibits gastric secretions by three mechanisms.

Intestinal Phase Mechanism One Vagus nerves

Medulla oblongata Vagus nerves pH<2 or lipids

Decreased gastric secretions

Sensory vagal action potentials to the medulla oblongata (green arrow) inhibit motor action potentials from the medulla oblongata (pink arrow).

Intestinal Phase Mechanism Two

Decreased gastric secretions Local reflexes

pH<2 or lipids

Local reflexes inhibit gastric secretion (orange arrows).

Intestinal Phase Mechanism Three

Decreased gastric secretions pH<2 or lipids Circulation Secretin, gastric inhibitory peptide, cholecystokinin

Secretin, gastric inhibitory polypeptide, and cholecystokinin produced by the duodenum (brown arrows) inhibit gastric secretions in the stomach.

Stimulation of gastric acid secretion

Regulation of gastrin release

Acetylcholine

Gastrin Cell Somatostatin Cell