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Lec .5 GIT 24 April 2017

Dr baybeen Alselevany

Upper Gastro-Intestinal Tract (Stomach)

Stomach: Gastric Secretion
Objectives
1. Physiological anatomy
2. Blood supply
3. Innervation
4. Gastric secretion
Physiological Anatomy
The stomach is a J Shaped , pouch like organ about 20-30 cm long which hangs under the diaphragm in the upper left portion of the abdominal cavity .A pouch like organ serves to store food as well as to mix and digest it (both mechanical and chemical digestion), this process changes food into substance called chyme.The structure is made up of the same layers described previously, but muscularis has a third oblique smooth muscle layer ,which combined with presence of folds called ragae ,allow the stomach to change size and adapt its content.
Anatomically the stomach is divided into :
a. cardiac region which is a small area which separated from esophagus lower esophageal sphincter.
b. Fundic region rounded area of stomach, is temporary storage area and sometimes filled with swallowed air. This produces a gastric air bubble which be used as a landmark on an x- ray film of the abdomen.
c. Body region : is the main part of the stomach.
d. The pyloric region (antrum): lower most region of the stomach separated from duodenum by pyloric sphincter (pylorus) which prevents regurgitation of food from the intestine back into the stomach and also prevents excessive release of gastric acid into the duodenum.
Blood supply: The stomach has a very rich blood and lymphatic supply.
Gastric Innervation. Its parasympathetic nerve supply comes from vagi and sympathetic from celiac


Gastric secretion

Composition of normal gastric juice (fasting state)

Hydrochloric acid, pepsins, mucus, and intrinsic factor and hormone gastrin. .In addition to cations and ( such as Na+ ,K+ , Mg2+ , H+ ), anions ( Cl- , HCO3- , So42-,Hpo42-) and digestive enzymes (gastric lipase, lingual lipase ,.and gelatinase.
The stomach mucosa has two important types of tubular glands:
Oxyntic Glands also called gastric glands which secretes hydrochloric acid ( HCL), intrinsic factor, pepsinogen, , and mucus. These glands are located on the inside surfaces of the body and fundus of the stomach.Oxyntic (Gastric) Glands is composed of three types cells :
chief (peptic ,zymogene) cells which secrete large quantities of pepesinogen.
b. parietal ( or oxyntic cells ) which secrete HCl and intrinsic factor
c. mucous neck cells which secrete mainly mucus . Mucus is also secreted along with HCO3- by mucus cells on the surface of the epithelium between glands.
2. pyloric glands also called antrum secrete hormone gastrin. They also secrete mucus for protection of the pyloric mucosa from the stomach acid.

1. Hydrochloric Acid (HCL)

Basic mechanism of hydrochloric acid secretion
Parietal cells secrete hydrochloric acid at concentrations ranging from 150160 mmol/L in amounts of 12 L/day .The PH of this acid is 0.8 i.e. its extremely acidic.. Secretion of hydrochloric acid by the parietal cells involves special mechanisms:
carbon dioxide( CO2), either formed during metabolism in the cell or entering the cell from the blood,
CO2 is combined under the influence of carbonic anhydrase(CA)
with water to form carbonic acid (H2CO3).
carbonic acid (H2CO3) dissociates into bicarbonate (HCO3 -)and hydrogen ion (H+).
bicarbonate (HCO3 -) moves back into blood stream.
the flow HCO3 moves in exchange with chloride ion (Cl-) .Chloride ion is actively transported from the cytoplasm of the parietal cell into the gastric lumen.
Hydrogen ion (H+) is actively transported into th gastric lumen
chloride ion (Cl-) diffuse with H+ .
8.some of potassium ion (K+) are transported into parietal cell in exchange with the H+. This active exchange process is catalyzed by H- K ATPase. Water passes into the parietal cell by osmosis so there is formation of, hydrochloric acid at a concentration of about 150 to 160mEq/L .potassium chloride(KCl) ) at a concentration of 15 mEq/L.


Q: any factor inhibits the enzyme carbonic acid anhydrase (CA) or H-K ATPase will abolish the secretion of HCL from oxyntic cells. Why?
.
postprandial or enteroprandial alkaline tide) .When gastric acid secretion is elevated after a meal sufficient H+ may be secreted to raise the pH(alkaline) of the systemic blood and make urine alkaline (because large amounts of bicarbonate enters the blood ),this called postprandial or enteroprandial alkaline tide) .
Q.Explain why a slight increase in blood PH may occur following a heavy meal?
Functions of HCl: 1.kills many ingested bacteria 2.provides the necessary pH for pepsin to start protein digestion. 3. Stimulate of bile and pancreatic juice.
Stimulation of gastric acid secretion
The parietal cells, , are the only cells that secrete hydrochloric acid.
The parietal cell (oxyntic cell) membrane has separate receptors for histamine, gastrin, and acetylcholine. Acid secretion is stimulated by histamine via H2 receptors and by acetylcholine via M3 muscarinic receptors and Gastrin probably acts directly via gastrin receptors. Stimulation of these receptors( histamine, muscarinic and gastrin receptors) will activate protein kinases inside the parietal cell which is in turn increase the transport of H+ into the gastric lumen in exchange with K+ by K+ - H+ ATPase.
There is another type of cell called enterochromaffin- like cells (ECL cells), the primary function of which is to secrete histamine, which lie in the deep recesses of the oxyntic glands. ECL cells. ECL cells also contain gastrin & ACH receptors. The rate of formation and secretion of hydrochloric acid by the parietal cells is directly related to the amount of histamine secreted by the ECL cells i.e. that histamine is the most potent stimulus for HCL secretion. The ECL cells can be stimulated to secrete histamine in several different ways: (1) probably the most potent mechanism for stimulating histamine secretion is by the hormonal substance gastrin via gastrin receptors on ECL cells. (2) In addition, the ECL cells can be stimulated by acetylcholine released from stomach vagal nerve; its effects are not as pronounced as those of gastrin. Gastrin is the major regulator of the ECL cells .Gastrin and ACH are indirectly causing release histamine from parietal cells through ECL cells.

The gastrin mechanism for control of the ECL cells.

Gastrin is itself a hormone secreted by gastrin cells (G cells). When meats or other protein-containing foods reach the antral end of the stomach, some of the proteins from these foods have a special stimulatory effect on the G cells in the pyloric glands to cause release of gastrin into the digestive juices of the stomach. The vigorous mixing of the gastric juices transports the gastrin rapidly to the ECL cells in the body of the stomach, causing release of histamine directly into the deep oxyntic glands. The histamine then acts quickly to stimulate gastric hydrochloric acid secretion. Gastrin probably acts directly on parietal cells or indirectly via ECL cells. Histamine is very effective in promoting secretion of gastric acid through effective of H2- receptors.

2. Pepsinogen

Several slightly different types of pepsinogen are secreted by the peptic and mucous cells of the gastric glands and also by mucous cells of pyloric glands. Pepsin is stored and secreted as the inactive precursor
pepsinogen,. At intragastric pH lower than 5, pepsinogen is split to form the active enzyme pepsin, Pepsin functions as an active proteolytic enzyme in a highly acid medium (optimum pH 1.8 to 3.5), but above a pH of about 5 it has almost no proteolytic activity and becomes completely inactivated in a short time. Hydrochloric acid is as necessary as pepsin for protein digestion in the stomach. Acetylcholine is the strongest and most important stimulator of pepsin secretion. Pepsinogen activity can be detected in the plasma and in the urine, where it is called uropepsinogen.

3. Intrinsic factor: Intrinsic factor is secreted by the parietal cells in humans as a mucoprotein. It combines with dietary vitamin B12, forming a complex necessary for the absorption of the vitamin in the distal ileum.

4. Surface Mucous Cells The entire surface of the stomach mucosa between glands has continuous layer of a special type of mucous cells called simply surface mucous cells.They secrete large quantities of very viscid mucus: 1.that coats the stomach mucosa with a gel layer of mucus often more than 1 millimeter thick, thus providing a major shell of protection for the 2.stomach wall as well as contributing to lubrication of food transport.3. Mucus alkaline. Therefore, the normal underlying stomach wall is not directly exposed to the highly acidic, proteolytic stomach secretion. Even the slightest contact with food or any irritation of the mucosa directly stimulates the surface mucous cells to secrete additional quantities of this thick, alkaline, viscid mucus. Substances that tend to damage mucosal barriers and cause gastric irritation are: ethanol , vinegar , bile salts , aspirin , and other non steroidal anti inflammatory drugs ( NSAIDs).
5. Digestive enzymes: also gastric secretion contains digestive enzymes such as:1. a gelatinase that liquefies gelatin also found in the stomach .2. Lipases lingual lipase ,and the gastric lipase for partial digestion of fats..
Pyloric Glands
. The pyloric glands are located in the antral portion of the stomach. Pyloric glands are structurally similar to the oxynic cells but contain few peptic cells and almost no parietal cells instead contains mostly: 1.mucus neck cells which secrete a small amount of the pepsinogen and large amount of thin mucus that large amount of thin mucus a. that helps to lubricate food movement, as well as .b.to protect stomach from digestion by gastric enzymes 2. G-cell that secrete the hormones gastrin which plays an important role in the controlling gastric secretion.


Phases of Gastric Secretion
Three phases of gastric secretion are recognized:
1. Cephalic phase. 2 gastric phase. 3. Intestinal phase
1. Cephalic phase: The cephalic phase of gastric secretion occurs before food enters the stomach .It results from sight, smell, thought, or taste of food, and the greater the appetite, the more intense is the stimulation. Neurogenic signals that cause the cephalic phase of gastric secretion originate in the cerebral cortex and in the appetite centers of the amygdala and hypothalamus. They are transmitted through parasympathetic vagal nerves to the stomach enhance gastric secretion.. Loss of appetite will inhibit gastric secretion. Gastric secretion response to occurs a conditional reflex. Emotional State such as Psychic stated effects on gastric secretion that are mediated through vagi for example anger and hostility causes hypersecretion, while fear , depression and anxiety causes hyposecretion because the sympathetic division overrides parasympathetic control of digestion. This phase of secretion normally accounts for about 20 per cent of the gastric secretion associated with eating a meal. By vagal stimulation about 500ml of HCl is secret daily.

Gastric phase: begins when food enters stomach and distended the stomach. This distention actives (1) long vasovagal reflexes from the stomach to the brain and back to the stomach, (2) local enteric reflexes, and (3) the gastrin mechanism. Low acidity and caffein in stomach causes secretion of gastrin from G cells and gastrin acts to stimulate HCL and enzyme secretion. Emotional stress and high acid will inhibit gastric secretion. The gastric phase of secretion accounts for about 70 per cent of the total gastric secretion associated with eating a meal and therefore accounts for most of the total daily gastric secretion of about 1500 milliliters.), while by gastrin release about 200ml /day is released.

3. Intestinal phase: begins as food moves from stomach into the upper portion of the small intestine especially the duodenum will cause stomach to secrete a small amount of gastric juice. Fats, carbohydrates, and acid in the duodenum inhibit gastric acid and pepsin secretion via neural and hormonal mechanisms. This phase accounts for about 5% of the total secretory response to a meal. The intestinal factor that inhibits gastric secretion results from at least two influences:
1. Enterogastric inhibitory reflex: This reflex can be initiated by a.distending the small bowel, b. presence of acid in the upper intestine,
3. the presence of protein breakdown products, 4. Irritation of the mucosa. These foods in small intestine initiate enterogastic reflex which transmitted through the myenteric nervous system as well as through extrinsic sympathetic and vagus nerves, that inhibits stomach secretion.
2. Inhibitory hormones: The presence of acid, fat, protein breakdown products, hyperosmotic or hypo-osmotic fluids, or any irritating factor in the upper small intestine causes release of several intestinal inhibitory hormones such as secretin, gastric inhibitory peptide (GIP), and vasoactive intestinal polypeptide (VIP),CCK The functional purpose of inhibitory gastric secretion by intestinal factors is presumably to slow passage of chyme from the stomach when the small intestine is already filled or already overactive.













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