The Digestive System

1. The Digestive System Gastrointestinal tract Physiology Dr. Suaad M. Ghazi MBChB, MSc, PhD

2. Objectives of lecture 4 • Explain functions of gastric secretion. • Explain the Phases of gastric motility and secretion. • Explain the importance of mucus in protection of stomach.

3. The functions of HCl • It participates in the breakdown of protein. • It hinders the growth of pathogenic bacteria. • It provides an optimal pH for the activation of pepsinogen to pepsin and for the action of pepsin. (Pepsin + HCl active pepsin which is an active proteolytic enzyme in a highly acid medium).

4. Gastric mucus secretion The surface of the stomach mucosa between glands has a continuous layer of mucous cells that:  Secrete a viscid and alkaline mucus  Coats the mucosa (gastric mucosal barrier).  ˃ 1 mm thick shell of protection.  lubrication of food.  prevents digestion of the gastric wall.  reduces the absorption of most substances.

5. The components of gastric mucosal barrier enable the stomach to contain acid without injuring itself are:  The luminal membranes of the gastric mucosal cells are impermeable to H+ so that HCI cannot penetrate into the cells.  The cells are joined by tight junctions that prevent HCI from penetrating between them.  A mucus coating over the gastric mucosa serves as a physical barrier to acid penetration.  The HCO3- rich mucus also serves as a chemical barrier that neutralizes acid in the vicinity of the mucosa. Even when luminal pH is 2, the mucus pH is 7.

6. The components of gastric mucosal barrier.

7. Gastrin  Main gastrointestinal hormone, is secreted by antral G cells and has the following effects:  It stimulates the parietal cells to secret HCl.  It stimulates the chief cells to secret pepsinogen.  It stimulates the enterochromaffin-like cells (ECL cell, or enteroendorine cells) to release histamine.  It enhances muscle contractions of pyloric pump (minor effect) and has a slight constrictor effect on the gastroesophageal sphincter.  It stimulates contraction of intestinal muscle, relaxes ileocecal valve, and stimulates mass movements.

8. Gastric intrinsic factor secretion  A substance called intrinsic factor is secreted by the oxyntic cells  It is essential for absorption of vitamin B12 in the ileum.  If the acid producing cells of the stomach are destroyed as it occurs in chronic gastritis.  The person develops achlorhydria and pernicious anaemia because of failure of maturation of the RBC in the absence of vitamins B12.

9. Phases of gastric motility and secretion • The cephalic phase • The gastric phase • The intestinal phase

10. Figure 24.15a

11. Cephalic phase: • Entirely dependent on the vagal nerve. • Accounts for 30% of total volume of secretion.

12. Ghrelin •  During cephalic phase, the non-distended stomach secretes hormone Ghrelin from cells in the stomach. •  Ghrelin the "hunger hormone” is a peptide hormone produced by cells in the GIT which functions as a neuropeptide in the central nervous system. •  It acts on hypothalamic brain cells both to increase hunger, and to increase gastric acid secretion and GI motility to prepare the body for food intake. • When the stomach is empty, ghrelin is secreted. When the stomach is stretched, secretion stops. •  Ghrelin is also a stimulator of the growth hormone secretagogue receptor in the anterior pituitary, a receptor that mediates growth hormone release.

14. 2. Gastric phase: •  Account for 60% of gastric secretion. • Controlled by local, vagovagal reflexes, and by hormone gastrin. Gastric distention & ^ pH GRP

15. Gastric phase [A] The stomach excitatory signals:  Distension of the antrum by food (through myenteric reflexes)  the activity of the pyloric pump and inhibits the pyloric sphincter.  The presence of the protein (the most important determinant of acid secretion)  a reflex stimulation of G cell of mucosa to release gastrin. Consequently increase in gastric secretion and motility of pyloric pump. Therefore, carbohydrates empty fastest, followed by protein. Fats take longest to empty.  Decreasing in gastric [H+] (i.e. high pH)

16. [B] The gastric inhibitory signals: • The drop of pH (  gastric [H+]) below 2-3 is the most potent inhibitor of HCl secretion and pyloric pump activity which is mediated by: • A low pH directly inhibits G cells and gastrin secretion. Plasma gastrin levels are related inversely to acid secretory capacity because of a feedback mechanism by which antral acidification inhibits gastrin release. Thus, plasma gastrin levels are reduced in persons with duodenal ulcers. • A low pH stimulates antral D cells to release somatostatin, which inhibit secretion of parietal cells, ECL cells, and G cells  turning off the HCl-secreting cells and their most potent stimulatory pathway.

17. Gastric emptying a. The rate of gastric emptying is fastest when the stomach contents are isotonic. If hypertonic or hypotonic, gastric emptying is slowed. b.Fat inhibits gastric emptying (i.e., increases gastric emptying time) by stimulating the release of CCK. c.H+ in the duodenum inhibits gastric emptying via direct neural reflexes. H+ receptors in the duodenum relay information to the gastric smooth muscle via interneurons in the GI plexuses. d. The initial rate of the gastric emptying varies directly with the volume of the meal ingested.

18. Basal state  Phase of acid secretion occurs between meals (interdigestive phase).  Acid secretion during these times is regulated by body weight, individual, number of parietal cells, and time of day.  Acid secretion is lowest in the morning before awakening and highest at night.  The stomach secretes few milliliters of gastric juice/hr during this phase (between meals).  Entirely of non-oxyntic type.  It is composed mainly of mucus containing very little pepsin and almost no acid.  Strong emotional stimuli increase the interdigestive secretion to 50 ml or more of highly peptic and highly acidic gastric juice/hr  peptic ulcers.

19. 3. Intestinal phase: • Account for 10% of gastric secretion. • It is possibly due to hormone gastrin released from duodenum as a result of amino acid chyme.

20. Inhibition of gastric secretion X All mechanisms for the inhibition of acid secretion act to ensure effective digestion of food Intestinal signals

21. [A] The intestinal excitatory signals:  Slight stretching the wall of the upper portion of the small intestine (duodenum).  The presence of small amounts of food (especially protein digestion products).  Stimulates small amount of intestinal gastrin to be released from the duodenal mucosa.  Increase the activity of pyloric pump and gastric juice secretion.

22. [B] The intestinal inhibitory signals: 1. Nervous Feedback:  Duodenal wall distension or irritation of duodenal mucosa provokes inhibitory reflex effect from the duodenum to the stomach.  Multiple nervous reflexes are mediated through the enteric nervous system, or through long, and short nervous reflexes.  These signals depress the gastric juice secretion, decrease pyloric pump activity and increase pyloric tone.

23.  Osmolarity of the chyme: Iso-osmotic gastric contents empty faster than hyper or hypo-osmotic contents due to feedback inhibition produced by duodenal wall chemoreceptors (hyper more inhibitory than hypo).  PH of chyme: Small intestinal chyme of < 3.5-4 stimulates the duodenal wall chemoreceptos and will activate reflexes that inhibits pyloric pump.  Presence of fats and protein digestion products in the duodenum.

24. 2. Hormonal Feedback: The chyme is hypertonic, acidic, and contains high concentrations of fat, protein, and carbohydrates. • The intestinal inhibitory signals are: •  Fats entering the duodenum  stimulate inhibitory hormone CCK which inhibits the pyloric pump. •  Acidic chyme in the duodenum  stimulates inhibitory hormone secretin which inhibits the pyloric pump. • CCK and secretin hormones are collectively called enterogastrones

26. In summary In humans, gastric acid secretion by the parietal cell occurs in response to:  Excitatory neural (acetylcholine), hormonal (gastrin), and paracrine (histamine) stimuli.  Inhibitory feedback regulation of acid output also involves neural (enterogastric reflex), hormonal (enterogastrone), and paracrine (somatostatin) influences.

27.  As rapidly as these feedback signals allow chyme to enter the duodenum.  The pH of the chyme in the duodenum falls below 5.5 – 4.0, the duodenal inhibitory signals are immediately elicited  further release of acidic stomach content into the duodenum  until the duodenal chyme can be neutralized by pancreatic and other secretion.  Hypo- or hypertonic fluids will elicit the duodenal inhibitory signals to prevent too rapid flow of non-isotonic fluids into the small intestine.

28.  This feedback inhibition of the gastric glands plays an important role in protecting the stomach against excessively acid secretion, which would readily cause peptic ulceration.  The feedback mechanism is also important in maintaining optimal pH for function of the peptic enzymes in the digestive process because whenever the pH rises above 2.5 - 3.5 gastrin begins to be secreted again and more acid is secreted.

29. Peptic ulcer disease Gastric ulcer Duodenal ulcer Gastric mucosa cannot protect itself by existing level of gastric juice due to reduced defence capacity. Result of increased exposure of duodenal mucosa to gastric juice. Factors that maintaining mucosal resistance : 1. adequate blood flow to the gastric mucosa. 2. production of mucus. 3. cellular renewal. 4. chemical factors ( gastrin, PG, EGF), increase the resistance of cells to toxic conditions. ♦ Chronic use of NSAID inhibiting PG synthesis.

30. ♦ Recent studies have shown that major acquired factor responsible for both gastric and duodenal ulcers is the bacterium Helicobacter pylori. ♦ H. pylori infections are present in 95% of patients with duodenal ulcers and 100% of patients with gastric ulcers, suggesting that this is one of multiple contributing factors. ♦ H. Pylori cytotoxicity because NH4 + directly damages epithelial cells and weakens the mucosal barrier. It may also increase gastric acid production by unknown mechanism. Treatment of ulcers H2-receptor blockers or omeprazole in combination + Flagyl + Antibiotics.

31. The dumping syndrome Develop after surgery to remove all or part of stomach or after bypass stomach.  It occurs because food moves from stomach into small bowel too quickly.  Rapid emptying of the stomach can lead to low pH, elevated tonicity in the duodenum,  Incomplete digestion and absorption, particularly of fat and protein.

32.  The unabsorbed food retains osmotically water, which in conjunction with the increased rate of intestinal transport  diarrhea and steatorrhea (fat in the feces).  The by-products of the bacterial metabolism of undigested food in the terminal ileum and colon can cause intestinal cramping, gas, and bloating. Weakness, dizziness, sweating, and hypoglycemia.  Rapid entry of a hypertonic meal into the intestine promotes the movement water into the gut hypovolemia and hypotension.

33. Gastric digestion and absorption:  Carbohydrate digestion in the stomach  salivary amylase.  Protein digestion occurs in the stomach by about 10% and mediated by HCl and later by gastric pepsin.  Fat digestion is minimal in the stomach due to restriction of gastric lipase activity.  Very little absorption of nutrients takes place in the stomach (highly lipid-soluble substances e.g., the non-ionized triglycerides of acetic, propionic, and butyric acids).

34.  Aspirin at gastric pH is non-ionized and fat soluble, after absorption, it ionizes intracellularly, damaging mucosal cells and ultimately producing bleeding.  Ethanol is rapidly absorbed in proportion to its concentration.  Water moves in both directions across the mucosa. Water-soluble substances including Na+, K+, glucose, and amino acids, are very poorly absorbed.  Speed of delivery of nutrients from stomach to small intestine is as follow: CHO > protein > fat