Gastrointestinal tract Physiology Dr Suaad M Ghazi MBCh

Gastrointestinal tract Physiology Dr. Suaad M. Ghazi MBCh. B, MSc, Ph. D

Objectives of lecture 3 1. Describe the mechanisms of swallowing. 2. Explain gastric anatomy and how gastric secretion and stomach motility are regulated.

Swallowing (deglutition) 1. Oral (voluntary) stage. 2. Pharyngeal (involuntary) stage. 3. Esophageal (involuntary) stage. 4. Relaxation of lower esophageal sphincter.

Food voluntarily squeezed posteriorly to oropharynx by pressure of tongue upward and backward against hard palate, soft palate and back of mouth into the pharynx. From here swallowing reflux becomes automatic.

Pharyngeal (involuntary) stage of swallowing: The bolus of food is pushed backward in the mouth stimulates swallowing receptor areas around the opening of the pharynx impulses from these pass to medulla oblongata through the sensory portions of ( 5 th and 9 th ) nerves to initiate a series of automatic pharyngeal muscular contractions by neuronal areas collectively called swallowing (or deglutition) center distributed throughout the reticular substance of the medulla and lower portion of the pons. The motor impulses from the swallowing center to the pharynx and upper esophagus that cause swallowing are transmitted by the ( 5 th , 9 th , 10 th , 12 th cranial nerves and few of the superior cervical nerves ) The swallowing center specifically inhibits the respiratory center of the medulla during swallowing, halting respiration at any point in its cycle to allow swallowing to proceed.

In order: 1. The soft palate is pulled upward closed pos. nares. 2. Approximation of the palatopharyngeal folds pulled medial ward form sagital slit. 4. Upward movement of larynx stretches opening of oesophagus. Upper 3 - 4 cm called UES (striated muscle) relaxes allowing food to move from pos. pharynx into upper oesophagus. UES between swallow tonically contracted preventing air from going into oesophagus. 3. Approximation of vocal cords and pulling the hyoid bone and larynx upward anteriorly. Swing the epiglottis backward to prevent passage of food into the trachea to keep swallowed material out of the airways. 5. Larynx is raised and UES is relaxed, superior constrictor muscle of pharynx contracts. Rapid peristalses wave downward which propels the food into oesophagus.

UES 1. Primary peristaltic wave (vagal reflexes) continuation begins in pharynx to stomach through esophagus. Reflexes transmitted through vagal afferent from eso. to medulla and back to eso. through vagal efferent fibers. 2. Secondary peristaltic wave (Enteric reflexes) initiated from distention of eso. by retained food if the primary peristaltic wave fails to move all the food that has entered eso. into the stomach.

Step 4 Relaxation sphincter of lower esophageal As the esophageal peristaltic wave passes toward the stomach, the lower esophageal sphincter relaxes. This relaxation is vagally mediated.

The lower esophageal sphincter is anatomically separate identifiable muscles. not The fundus of the stomach and lower esophageal sphincter extending about 2 -5 cm above its junction with the stomach both relax during a swallow while the bolus of food is still higher in the esophagus. This phenomenon is called receptive relaxation. Receptive relaxation is vagally mediated. Nitric oxide is the neurotransmitter thought to mediate receptive relaxation at the smooth muscle cell allowing food to pass to the stomach.

Lower Esophageal Sphincter (Gastro esophageal Sphincter) diaphragm Prevention of reflux of the gastric contents is achieved by: [1] The tonic contraction of LES. [2] Subdiaphragmatic oblique entrance of esophagus to the stomach (valve-like mechanism).

Disorders of swallowing: Esophageal reflux: Reflux of stomach acid to the esophagus causes esophageal pain (heartburn) and may lead to esophagitis. • Intragastric pressure is usually greater than atmospheric pressure. • The pressure gradient between the lumens of the stomach and esophagus would tend to facilitate the reflux of food from the stomach into the esophagus. • (LES) normally prevents this and mediates the unidirectional transfer of food. • Largest pressure gradient from stomach to esophagus would occur during inspiration. • An increase in intra-abdominal pressure will increase both intragastric pressure and the closing pressure for the LES by approximately the same amount. Therefore, the closing pressure of the LES will always exceed intragastric pressure by 30 -40 mm. Hg.

Gastroesophageal reflux initiates a cycle of increased esophageal acid exposure

The esophagitis results in chronic injury to the distal esophagus affecting the peristaltic function and causing frequent ineffective peristalsis which prolongs the acid contact secondary to reflux. The esophagitis may also cause chronic decreases in LES pressure, resulting in a damaging cycle of events that combine to perpetuate the reflux injury.

Causes that increase intraabdominal pressure : Ingestion of a very large meal. Production of intestinal gas by bacterial metabolism. Pregnancy. An abdominal mass such as a tumor. Straining (contraction of abdominal muscles) against a closed glottis. Etc. Latter maneuver increases intraabdominal pressure relative to atmospheric pressure, and just as it facilitates defecation, it will also facilitate gastro-esophageal reflux if the LES is not contracted.

Esophageal reflux may occur : [A] If the intragastric pressure rises high enough to force the lower esophageal sphincter open. [B] If the lower esophageal sphincter is unable to maintain its normal tone. [C] If the lower esophageal sphincter is forced through the diaphragm and into the thoracic cavity as in hiatus hernia. In this situation (The same may occur during pregnancy) : Intra-abdominal pressure no longer contributes to the closing pressure of the LES. Negative intrathoracic pressure would reduce the closing pressure. In either case, the low intrathoracic pressure compared to the high intra-abdominal pressure, causes LES to expand, allowing reflux to occur.

Belching (eructation): Following a heavy meal or the ingestion of large amounts of gas (e. g. , from carbonated beverages), the gas bubble that is usually in the fundus of the stomach is displaced to the cardia. When lower esophageal sphincter relaxes during the swallowing process, gas enters the esophagus and is regurgitated.

Dysphagia: Difficulty in swallowing. Persons with dysphagia usually report choking, coughing, or an abnormal sensation of food sticking in the back of the throat or upper chest when they swallow. If swallowing is painful, it is referred to as odynophagia. Dysphagia can result from altered nerve function or from disorders such as: Narrowing of the esophagus. Lesions of the central nervous system (CNS), such as a stroke, often involve the cranial nerves that control swallowing. Strictures and cancer of the esophagus and strictures resulting from scarring can reduce the size of the esophageal lumen and make swallowing difficult.

Achalasia: It is a neuromuscular disorder of the lower two-thirds of the esophagus that leads to absence of peristalsis and failure of the lower esophageal sphincter to relax. Food accumulates above this sphincter, taking hours to enter the stomach and dilating the esophagus.

Regions of the stomach lower oesophageal sphincter Pyloric sphincter Duodenum Fundus “Pacemaker zone” - peristaltic contractions Body (corpus) “acid-secreting” Antrum “muscular pump”

The stomach a. the fundus. b. the body. c. the antrum. ¨ Physiologically the fundus functions mainly as part of the body. ¨ stomach mucosa is a simple columnar epithelium composed entirely of mucous cells. ¨ They produce a cloudy, protective two-layer coat of alkaline mucus in which the surface layer consists of viscous, insoluble mucus that traps a layer of bicarbonate-rich fluid beneath it. ¨ Tubular gastric glands produce the stomach secretion called gastric juice.

The functions of the stomach 1. Storage of food ♦ Is mediated by the process of receptive relaxation of the stomach. ♦ When food enters the stomach a vago-vagal reflex greatly reduces the tone in the muscular wall of the body of the stomach. ♦ Nitric oxide is the neurotransmitter thought to mediate receptive relaxation at the smooth muscle cell. ♦ The wall can bulge progressively outward accommodating greater and greater quantities of food up to a limit of about 1 liter. ♦ Stomach accommodation depends exclusively upon an intact vago -vagal reflex. ♦ If vagal innervation is interrupted, then intra-gastric pressure increases. This is a potential cause of vomiting due to the inability of the proximal stomach smooth muscle to undergo receptive relaxation.

2. Mixing secretions of this food with gastric ♦ When the stomach is filled, weak peristaltic and segmentation (mixing) contractions move toward the antrum along the stomach wall> ♦ Propelling and mixing food with gastric juice until it forms a semifluid mixture called chyme. ♦ This is due to distension of the stomach which elicit vago-vagal reflex.

3. Emptying ♦ Slow emptying of chyme from the stomach into the small intestine at a rate suitable for proper digestion and absorption by the small intestine. ♦ The degree of constriction of the pyloric sphincter and the intensity of antral peristaltic wave (mediated by myenteric reflexes) can be varied according to signals both, from the stomach and from duodenum. ♦ The antral peristaltic waves provide a pumping action and are frequently called the pyloric pump.

The stomach is a poor absorptive area of the GIT. Because it lacks the typical villus type of absorptive membrane, and also because the junctions between the epithelial cells are tight junctions. Only a few highly lipid-soluble substances, such as alcohol and some drugs like aspirin can be absorbed in small quantities.

Regulation of gastric emptying (pyloric pump) Gastric emptying is a key control point in the GIT to ensure the orderly delivery of nutrients in a form that can be digested and to give appropriate signals of fullness (satiety). Gastroparesis (“weak stomach”) is a common complication of poorly controlled diabetes mellitus and significantly slows gastric emptying. The rate at which the stomach empties is regulated by signals both from the stomach and duodenum. Gastric emptying takes about 3 hours and very closely regulated so that nutrient absorption is maximized and H+ in the duodenum has time to be neutralized.

Gastric secretion Gastric secretions aid in the breakdown of food into small particles and continue the process of digestion which had begun by the salivary enzymes. About 2 L / day of gastric secretions are produced. The stomach mucosa contains two main types of gastric glands: [A] Gastric glands [B] Pyloric glands

THE MUCOSA OF GASTRIC GLAND BODY (oxyntic gland) ANTRUM (pyloric gland) Major cell types Functions § § surface epithelial chief (peptic or zymogen) Parietal (oxyntic) enterochromaffin-like (ECL) - mucus, HCO 3 - pepsinogen - HCl, intrinsic factor - histamine § § surface epithelial chief (zymogen) G-cells D-cells - mucus, HCO 3 - pepsinogen - gastrin - somatostatin

[A] Gastric glands Are located in the fundus and the body of the stomach. They contain these types of secretory cells: 1. Mucus secreting cells which secretes mucus. 2. Parietal (oxyntic) cells which secrete intrinsic factor and HCl. 3. Peptic (chief) cells which secrete pepsinogen, the precursor for the proteolytic enzyme pepsin. 4. Enteroendocrine cells (or enterochromaffin-like cells, ECL cell) release a variety of chemical messengers directly into the interstitial fluid of the mucosa of the stomach. Some of these are histamine, serotonin, and somatostatin.

[B] Pyloric glands Are located in the antral and pyloric regions of the stomach. They contain: G cells and some mucous cells, G cells are responsible for the release of the hormone gastrin. D cells, which release somatostatin, a hormone that inhibits the release of gastrin.

Oxyntic glands secrete: 1. mucus from mucus secreting cells 2. intrinsic factor and HCl from parietal cells 3. pepsinogen from peptic cells 4. ECL Mucus and endocrine cells throughout mucosa secrete mucus, bicarbonate, histamine and other hormones

Gastric HCl secretion HCl is secreted into the parietal cell canaliculi by the following steps: [1] CO 2 diffuses from blood to inside the parietal cells. [2] Within the parietal cells, carbonic acid is formed. The formation of H 2 CO 3 from CO 2 is catalyzed by the enzyme carbonic anhydrase. [3] HCO 3 - diffuses back into the plasma in exchange for Cl, thus providing Cl- for the initial step in the secretory process. As HCO 3 - is added to the venous blood, the p. H of the blood drained from the stomach increases (alkaline tide). The active transport process is begun by the transport of Cl- ion into the canaliculi that open to the lumen of the stomach.

[4] The H+ that is supplied by the dissociation of carbonic acid into H+ and HCO 3 - within the parietal cells is exchanged for K+ by the H+-K+ATPase pump (proton pump). [5] Chloride ions diffuse with the charged H+. [6] Water enters the canaliculi down the osmotic gradient created by the movement of HCl into the canaliculi.

Mechanism of gastric HCl secretion:

Mechanism of gastric HCl secretion: K+ H+ + HCO 3 CI-

Most of the HCl that is secreted into the stomach is neutralized and reabsorbed within the small intestine. If gastric contents are lost before they enter the small intestine as in case of vomiting, sever alkalosis may ensue. The p. H of the parietal cell secretion can be as low as 0. 8 (or almost 4 million times as great as the H+ concentration of plasma).

Parietal cells bear receptors for three potent stimulators of acid secretion, reflecting a triad of neural, paracrine and endocrine control: ¨ Acetylcholine (muscarinic type receptor) ¨ Gastrin Histamine (H 2 type receptor) A variety of substances are capable of reducing gastric acid secretion including: Prostaglandin E 2 (PGE 2), Several peptides hormones, including Secretin, Gastric inhibitory polypeptide (GIP), Glucagon and, Somatostatin.

¨ GIP (glucose-dependent insulinotropic peptide) released from duodenal and jejunal mucosa in response to the presence of chyme especially by hyperosmolarity of glucose in the duodenum and inhibits gastric gastrin release and stimulate the release of insulin from pancreas, and inhibit the GI motility and secretion of acid. ¨ The amount of insulin secreted is greater when glucose is administered orally than intravenously. ¨ It is the only GI hormone released by all three major foodstuffs (fats, proteins, and carbohydrates). ¨ PGE 2, secretin and somatostatin may be physiologic regulators. Somatostatin inhibits secretion of gastrin and histamine, and appears to have a direct inhibitory effect on the parietal cell.

The H+-K+-ATPase pump can be inhibited by the drug omeprazole. Inhibition of pump activity leads to a prolonged increase in gastric p. H and the removal of the inhibitory effect of low p. H (<3. 0) on gastrin release.

Cimetidin and ranitidine used for treatment of peptic ulcer. by two mechanisms: (1) Histamine released by ECL cells in the stomach is blocked from binding on parietal cell H 2 receptors, which stimulate acid secretion. (2) Therefore, other substances that promote acid secretion (such as gastrin and acetylcholine) have a reduced effect on parietal cells when the H 2 receptors are blocked.

Mild injury to the mucosal barrier mucus secretion and surface desquamation followed by regeneration. A more serious injury breaks mucosal barrier and exposes the mucosal surface ulcer bleeding. Breaks of mucosal barrier and exposure of the mucosal surface to damage occurs due to highly concentrated HCl, 10% ethanol, salicylic acid, or acetylsalicylic acid (aspirin). The damaged mucosa liberates histamine acid secretion and capillary permeability and vasodilatation edema. In addition, the exposure of mucosal capillaries to the digestive process bleeding.

Erosive gastritis can occur as a result of chronic use of non-steroidal anti-inflammatory drugs (NSAIDs). The mechanism by which NSAIDS cause gastritis involves the inhibition of prostaglandin synthesis in the stomach. Prostaglandins normally maintain the physicochemical barrier on the gastroduodenal mucosal surface by stimulating the secretion of mucus and bicarbonate. Loss of the protective mucus and bicarbonate barrier renders the gastric mucosa susceptible to damage by the acidic environment.

Protection of the epithelial lining of the stomach p. H 2 HCO 3 - Gastric lumen Mucus layer HCO 3 p. H 7 Mucus GI-S-19