The Digestive System

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

2. Objectives of lecture 6 1. Explain the role of the bile secretion in digestion and absorption of fat and its regulation in small intestine. 2. Explain the regulatory hormones in the GIT.

3. Bile secretion  Bile is a yellow-green, alkaline solution.  Bile is required for the digestion and absorption of fats and for the excretion cholesterol, bilirubin, and some drugs.  Bile is formed by liver epithelium (hepatocytes) and by epithelial cells lining the bile ducts (ductal cells).  Between 250 - 1200 ml of bile is formed daily which is normally stored in 30 - 60 ml volume of gallbladder.

4.  5-18 fold concentrated by continual absorption of water, sodium, chloride, and most other small electrolytes through the mucosa of gallbladder by an active transport of sodium through the gallbladder epithelium.  The bile electrolyte concentrations are similar to those of plasma except more HCO3- and less Cl- (pH 7.5-9.0).

5. Bile composition • Bile salts (11%). • Bile pigments (1%). • Lipids (cholesterol 0.5%, lecithin 3%). • Water and electrolytes (84%).

6. (1) The bile salts  0.2 – 0.4 g/day.  The precursor of bile salts is cholesterol which is converted by liver to cholic acid or chenodeoxycholic acid.  These acids combined with amino acid glycine and taurine glyco- and tauro- conjugated bile acids  sodium and potassium salts in the alkaline hepatic bile.

7.  Bile salts have the propensity to form micelles. Which are small spherical globules composed of 20 - 40 molecules of bile salt.  Each bile salt molecule is composed of a sterol nucleus which is highly fat soluble and a polar group that is highly water soluble.  The polar groups is project outward to cover the surface of micelle, they are electrically charged  allow the entire micelle globule to become dissolved in the water of the digestive fluids.

8. Bile salt & the formation of micelle

9. Bile salts have two important actions: • Break the fat globules into minute sizes • Bile salts have a detergent action (or emulsification action) on the fat particles in the food which decreases the surface tension of the particles and allows the agitation in the intestinal truct to break the fat globules into minute sizes. Arrangement of micelles over the surface of lipid droplet.

10. Making lipid droplets highly water soluble •  Bile salts help in the absorption of lipids and other fat-soluble substances by forming minute complexes with micelles  become highly water soluble. •  The lipids are ferried to the mucosa  absorbed. •  Without bile salts, up to 40% of the lipids are lost into the stool the fat-soluble vitamins A, D, K, and E are not absorbed.

11.  Approximately 94% of the bile salts are reabsorbed by an active transport process (Na-bile salt cotransport) through the intestinal mucosa in the distal ileum.  Bile salts enter the portal blood and pass to the liver  reabsorbed almost totally on the first passage through the venous sinusoids into the hepatic cells and then resecreted into the bile.  The small quantities of bile salts lost into the feces are replaced by new amounts formed by the liver cells.

12.  The recirculation of the bile salts is called the enterohepatic circulation. Removal of the terminal ileum can lead to diarrhea and steathorrea.  Bile salts are necessary for adequate digestion and absorption of fat.

13.  In the absence of the terminal ileum increase in the amounts of bile acids and fatty acids delivered to the colon.  Fats and bile salts in the colon increase the water content of the feces by promoting the influx (secretion) of water into the lumen of the colon.

15. (2) The bile pigments  Mainly bilirubin and biliverdin which are responsible for the golden yellow color of bile and they are formed as a major end product ofHb degradation.  Bilirubin is fat soluble (highly soluble in all cell membranes) and very toxic.  Its excretion in the bile is one of the very important functions of the liver.

16.  The bilirubin released into the plasma is immediately combined very strongly with the plasma albumin and is transported in this combination throughout the blood and interstitial fluids.  This type of bilirubin is called “unconjugated bilirubin” or “indirect bilirubin”.

17.  Unconjugated bilirubin is fat soluble (insoluble in water) and cannot be excreted by the kidneys.  It can enter the brain or the subcutaneous adipose tissues, In premature infant, lack of subcutaneous fat exposes them to greater danger of unconjugated bilirubin entering the nervous system where it deposited in the basal ganglia kernicterus.

18.  Hyperbilirubinaemia will only develop when the serum albumin is unable to bind further unconjugated bilirubin.  Within hours, the unconjugated bilirubin is absorbed through the hepatic cell membrane  released from the plasma albumin  combined with one of two proteins (called Y and Z proteins) inside the hepatic cells that trap the bilirubin inside the cells.

19.  Conjugated bilirubin is water-soluble and so readily excreted in the urine or bile.  it is not soluble in fat, it is not toxic to the nervous system.  A small portion of the conjugated bilirubin formed by the hepatic cells returns to the plasma.  This causes a small portion of the bilirubin in the extracelluler fluids always to be of the conjugated type.

20.  By bacterial action in the intestine, about 1/2 bilirubin is converted urobilinogen (the brown color of stool).  Some of it is reabsorbed through the intestinal mucosa into the blood.  Most of this is re-excreted by the liver back into the gut (enterohepatic circulation).  About 5% is excreted by the kidneys into the urine.  In the urine, the urobilinogen oxidized to urobilin.  In the faces, it  oxidized to stercobilin.

21. Jaundice A yellowish tint to the body tissues, yellowness of the skin, mucous membrane and the deep tissues. This is due to a large quantities of bilirubin in the extracellular fluids (conjugated or unconjugated).

22. It may result from: • Excess production of bilirubin caused by excessive RBC destruction as in haemolytic anaemia. • Inability of hepatocytes to conjugate the plasma free bilirubin as in parenchymal liver diseases. • Obstruction of the bile ducts or liver cells preventing the secretion of conjugated bilirubin.

23. (3) Cholesterol, phospholipids (primarily lecithin), and fatty acids.  Cholesterol is almost insoluble in water.  The bile salts and lecithin in bile combine physically with cholesterol to form ultramicroscopic micelles that are soluble in water.

24. Regulation of gallbladder emptying • [1] the fat and also partially digested protein in the food entering the small intestine cause the release of the hormone CCK from the mucosa of the upper region of small intestine which in turn is absorbed into the blood and on passing to the gallbladder, causes contraction of the gallbladder muscle. • CCK is the major stimulus for gallbladder contraction and sphincter of Oddi relaxation. • [2]Vagal stimulation associated with the cephalic phase of gastric secretion or via a vagovagal reflex during the gastric phase of digestion, causing contraction of the gallbladder. .

25. Secretion of Bile

27. Control of biliary secretion from the liver cells [1] The availability of bile salts: The greater the quantity of bile salts in the enterohepatic circulation, the greater the rate of bile secretion. [2] Secretin also increases bile secretion  secretion of a bicarbonate rich watery solution by the epithelial cells of the liver ductules and ducts. This bicarbonate + bicarbonate from the pancreas  neutralizing the acid from the stomach.

28. Secretin Bile Water, Bicarbonate & Electrolytes

30.  Bile salts are required for proper digestion and absorption of fats.  Ileal resection or small intestinal diseases leads to a decreased bile acid pool and malabsorption of fat and fat-soluble vitamins  steatorrhoea and nutrition deficiency.

31. An increase in fecal losses of bile salts results in watery diarrhea, since bile salts inhibit water and Na+ absorption in the colon. Bile, and not the gallbladder, is essential to digestion. After removal of the gallbladder, bile empties slowly but continuously into the intestine, allowing digestion of fats sufficient to maintain good health and nutrition. Only high-fat meals need to be avoided.

32. Gallstones Cholesterol, secreted by the liver, may precipitate in the gallbladder to produce gallstones.  Excess cholesterol in the bile due to a high-cholesterol diet  gallstones.  A gallstone passes out of the gallbladder and enters the cystic duct, blocking the release of bile  must be removed surgically.  If the gallstone moves far enough down the duct, it can also block the pancreatic duct, resulting in pancreatitis.

33. Regulatory hormones in the GIT

35. Gastrin: It is released from G cells of the antral mucosa. The functions of gastrin are: 1. ↑ Gastric H+ secretion, 2. Stimulates growth of gastric mucosa. 3. Increases antral muscle mobility and promotes stomach contractions. 4. Strengthens antral contractions against the pylorus, and relaxes the pyloric sphincter, which increases the rate of gastric emptying. 5. Plays a role in the relaxation of the ileocecal valve. 6. Induces pancreatic secretions and gallbladder emptying. 7. May impact lower esophageal sphincter (LES) tone, causing it to contract. 8. Gastrin contributes to the gastrocolic reflex.

36. Gastrin release is stimulated by: A. The antral distension. B. The presence of protein digesting products in the antrum (the most potent are phenylalanine and tryptophan), coffee, and alcohol. C. Vagal stimulation via GRP (bombesin). Gastrin release is inhibited by: A. High H+ concentration in the stomach (pH < 3). B. Somatostatin.

37. CCK: It is released from I cells of the mucosa of duodenum and jejunum. The functions of gastrin are: 1. Stimulates contraction of gallbladder and relaxation of sphincter of Oddi. 2. ↑ Pancreatic enzyme and HCO3– secretion. 3. ↑ Growth of exocrine pancreas/gallbladder. 4. Inhibits gastric emptying 5. It stimulates gallbladder contraction, and intestinal motility, while inhibits gastric emptying.

38. CCK release is stimulated by: A. The presence of fat digesting products in the small intestine (triglycerides do not stimulate the release of CCK because they cannot cross intestinal cell membranes). B. The presence of protein digesting products in the small intestine.

39. Secretin: It is released from S cells of the mucosa of the duodenum and jejunum. 1. Inhibits gastric emptying. 2. ↑ Pancreatic HCO3–, secretion, 3. ↑ Biliary HCO3– secretion, 4. ↓ Gastric H+ secretion Its release is stimulated by the H+ in the lumen of the duodenum. Motilin: It stimulates migrating motor complex.

40. Glucagon-Like Peptide I: (the incretins)  enhance the secretion of insulin. L-cells found in the lining of the small intestine are the major source. Food is the main stimulus of glucagon-like peptide 1 release, with increased hormone levels detectable after 10 minutes of starting to eat and remaining raised in the blood circulation for several hours after that. The hormone somatostatin holds back the production of glucagon-like peptide 1. 1. Glucagon-like peptide 1 increases the feeling of fullness during and between meals by acting on appetite centers in the brain and by slowing the emptying of the stomach. 2. It slows gastric emptying. 3. Enhances the secretion of insulin

41. Glucose-dependent insulinotropic peptide (GIP) also called Gastric inhibitory polypeptide (GIP):  It is released from duodenum and jejunum.  The stimulus for secretion is the fatty acids and amino acids and the presence of oral glucose load.  Oral glucose is more effective than intravenous glucose in causing insulin release.  GIP is the only GI hormone that is released in response to the three main food groups (fat, protein, and carbohydrate). 1. ↑ Insulin secretion 2. ↓ Gastric H+ secretion 3. Inhibits the gastric and GI motility causing

42. Somatostatin: is secreted by cells throughout the GI tract in response to H+ in the lumen. Its secretion is inhibited by vagal stimulation. 1. Inhibits the release of all GI hormones. 2. Inhibits gastric H+ secretion. Histamine: is secreted by mast cells of the gastric mucosa. It increases gastric H+ secretion directly and by potentiating the effects of gastrin and vagal stimulation.

43. Neurocrines: Are synthesized in neurons of the GI tract, moved by axonal transport down the axon, and released by action potentials in the nerves. Neurocrines then diffuse across the synaptic cleft to a target cell. A. Vasoactive intestinal peptide (VIP): contains 28 amino acids and is homologous to secretin. It is released from neurons in the mucosa and smooth muscle of the GI tract. 1. Produces relaxation of GI smooth muscle, including the lower esophageal sphincter. 2. Stimulates pancreatic HCO3– secretion and inhibits gastric H+ secretion. In these actions, it resembles secretin.

44. B. GRP (bombesin): is released from vagus nerves that innervate the G cells. It stimulates gastrin release from G cells. C. Enkephalins (met-enkephalin and leu-enkephalin) are secreted from nerves in the mucosa and smooth muscle of the GI tract. 1. Stimulate contraction of GI smooth muscle, particularly the lower esophageal, pyloric, and ileocecal sphincters. 2. Inhibit intestinal secretion of fluid and electrolytes. This action forms the basis for the usefulness of opiates in the treatment of diarrhea.