1. Lecture # 13: The Digestive System 2 The Digestive System II (Chapter 25) Objectives 2- To describe how each major class of nutrient is chemically digested, and name the enzymes involved. 3- To describe how each nutrient is absorbed by the small intestine. 1- To describe the gross and microscopic anatomy of the liver and the pancreas. Anatomy of Liver and Pancreas. Chemical Digestion and Absorption.

2. Gross Anatomy of Liver Liver The liver is a reddish brown gland located immediately inferior to the diaphragm. It is the body’s largest gland weighing about 1.4 kg (3 pounds). It has a variety of functions, but only the secretion of bile contributes to digestion. Right lobe Left lobe Falciform ligament (a) Anterior view(b) Posterior view Caudate lobe Quadrate lobeRound ligament Gallbladder Inferior vena cava

4. Microscopic Anatomy of Liver Bile ductule Branch of proper hepatic artery Hepatic Triad: Central vein Blood from the intestine and stomach To the hepatic vein To the inferior vena cava Branch of hepatic portal vein Hepatic sinusoid Hepatocytes Hepatic Lobule Bile canaliculum To the right and left hepatic ducts

5. They are blood-filled channels that fill spaces between the plates of hepatocytes. Hepatic sinusoids: Hepatic sinusoids are lined by a fenestrated endothelium that separates hepatocytes from blood cells and allows plasma into the space between the hepatocytes and endothelium. Hepatocytes have brush border of microvilli that project into this space. Hepatic macrophages (Kupffer cells) are phagocytic cells in the sinusoids that remove bacteria and debris from the blood. After a meal, the hepatocytes absorb from the blood: glucose, amino acids, iron, vitamins, and other nutrients for metabolism or storage. They remove and degrades hormones, toxins, bile pigments, and drugs. They secrete into the blood: albumin, lipoproteins, clotting factors, angiotensinogen, and other products Between meals, they breaks down stored glycogen and releases glucose into the blood. Functions of the Hepatocytes:

6. Bile canaliculum Bile ductule Right hepatic ducts Left hepatic ducts Common hepatic duct Cystic duct Bile duct Pancreatic duct Accessory pancreatic duct Minor duodenal papilla Hepatopancreatic sphincter Major duodenal papilla Hepatopancreatic ampulla Pancreas Gallbladder Duodenum Jejunum It stores and concentrates bile

7. Pancreas It is a spongy retroperitoneal gland posterior to the greater curvature of the stomach. The head of the pancreas is encircled by the duodenum. Accessory pancreatic duct Head Body Tail It is both an endocrine and exocrine gland. The endocrine portion consists of the pancreatic islets that secrete insulin and glucagon. The exocrine portion is about 99% of pancreas and secretes 1200 to 1500 mL of pancreatic juice per day. Pancreatic duct

8. Endocrine pancreas (produces hormones) Exocrine pancreas (produces enzymes) Pancreatic acini They secrete large quantities of an alkaline, enzyme rich fluid. 1- Beta cells: 2- Alpha cells: 3- Delta cells: 4- F cells: Insulin Glucagon Somatostatin Pancreatic polypeptide Islets of Langerhans

9. H2OH2O 9 Enzyme H2OH2O 9 Starch (Polymer of Glucose) Glucose Aminoacids Protein (Polymer of Aminoacids) All digestion reactions consists of hydrolysis reactions: Digestion

10. Carbohydrate Digestion Starch is the most digestible carbohydrate. Cellulose and chitin are indi- gestible. Polysaccharides Monosaccharides Disaccharides

11. Starch Salivary amylase Oligosaccharides Pancreatic amylase Brush border of microvilli Amylase quickly denatured on contact with stomach acid and digested by pepsin. Dextrinase, glucoamylase, maltase, sucrase, and lactase Salivary amylase hydrolyzes starch into oligosaccharides (up to 8 glucose residues long). It works best at pH of 6.8 – 7.0 of oral cavity. 1 When reaching the small intestine, pancreatic amylase converts the remaining starch to oligosaccharides and maltose within 10 minutes. 2 Oligosaccharides and maltose contacts brush border enzymes (dextrinase, glucoamylase, maltase, sucrase, and lactase). 3 Monosaccharides are absorbed immediately. 4

12. Carbohydrate Digestion in the Small Intestine In the oral cavity, 50% of dietary starch is digested. Salivary amylase stops working in stomach at pH less than 4.5 1 When reaching the small intestine, pancreatic amylase converts starch to oligo- saccharides and maltose within 10 minutes. 2 2 Oligosaccharides and maltose contacts brush border enzymes (dextrinase, glucoamylase, maltase, sucrase, and lactase) act upon oligosaccharides, maltose, sucrose, lactose, and fructose to glucose. 3 3 4 Monosaccharides are absorbed immediately. 4

13. Protein Digestion The amino acids absorbed by the small intestine come from three sources: 3- Sloughed epithelial cells digested by enzymes 1- Dietary proteins 2- Digestive enzymes digested by each other Enzymes that digest proteins are called proteases or peptidases Peptidases are absent from the saliva. No chemical digestion of proteins occurs in the oral cavity. Pepsin ( ) hydrolyzes certain peptide bonds, breaking protein down into smaller polypeptides.

14. Small intestine Actions of pancreatic enzymes Trypsin ( ) and chymotrypsin ( ) hydrolyze other peptide bonds, breaking polypeptides down into smaller oligopeptides. Carboxypeptidase ( ) removes one amino acid at a time from the carboxyl (–COOH) end of an oligopeptide. Digestion of proteins continues in the small intestine because pepsin is inactivated when it passes into the duodenum and mixes with the alkaline pancreatic juice (pH 8). Pancreatic enzymes trypsin and chymotrypsin take over the process hydrolyzing polypeptides into even shorter oligopeptides. Pancreatic carboxypeptidase removes amino acids from –COOH end of the chain.

15. Brush border enzymes (contact digestion) also remove one aminoacid at a time. Dipeptidases split dipeptides in the middle and release two free amino acids. Aminopeptidase removes them from the –NH 2 end. Actions of brush border enzymes Carboxypeptidase removes amino acids from –COOH end of the chain. Carboxypeptidase ( ) of the brush border continues to remove amino acids from the carboxyl (–COOH) end. Aminopeptidase ( ) of the brush border removes one amino acid at a time from the amino (–NH 2 ) end. Dipeptidase ( ) splits dipeptides ( ) into separate amino acids ( ).

16. Hydrophobic quality of lipids makes their digestion and absorption more complicated that carbohydrates and proteins. Lipid Digestion and Absorption Enzymes that digest lipids (fats) are called lipases. The lingual lipase secreted by the intrinsic salivary glands of the tongue is active in mouth, but more active in stomach along with gastric lipase. 10-15% of lipids digested before reaches duodenum. Pancreatic lipase in the small intestine digest most of the fats. 1- Emulsification Components of the bile Emulsification droplets Fat globule is broken up and coated by lecithin and bile acids. 1- Emulsification2- Fat Hydrolysis3- Lipid uptake by micelles 4- Chylomicron Formation5- Chylomicron Exocytosis Lipid Digestion and Absorption

17. 2- Fat Hydrolysis Pancreatic lipase acts on triglycerides. It removes the first and third fatty acids from glycerol backbone and leaves the middle one. The product of lipase action are two free fatty acids (FFAs) and a mono-glyceride. Pancreatic lipase Emulsification droplets are acted upon by pancreatic lipase, which hydrolyzes the first and third fatty acids from triglycerides usually leaving the middle fatty acid. 3- Lipid uptake by micelles They consist of 20 to 40 bile acid molecules aggregated with their hydrophilic side groups facing outward and their hydrophobic steroid rings facing inward. Micelles are made in the liver and they are very small droplets in the bile. Micelles in the bile pass to the small intestine and pick up several types of dietary and semidigested lipids. Micelles

18. 4- Chylomicron Formation Intestinal cells absorb lipids from micelles, resynthesize triglycerides, and package triglycerides, cholesterol, and phospholipids into protein-coated chylomicrons. Lipoprotein

19. 5- Chylomicron Exocytosis Golgi complex packages chylomicrons into secretory vesicles. They are released from basal cell membrane by exocytosis and enter the lacteal (lymphatic capillary) of the villus. They enter the bloodstream when lymphatic fluid enters the subclavian vein via the thoracic duct.