Nutrient Digestion Site of Absorption Carbohydrates Monosaccharides (glucose, galactose, fructose) Small Intestine Proteins Amino acids, dipeptides, tripeptides Lipids Fatty acids, monoglycerides, cholesterol Fat Soluble vitamins Water soluble vitamins Ileum of small Intestine

GI Hormones Hormones Site of Secretion Stimulus for Secretion Inhibitor Actions Gastrin G cells of Stomach Distention of stomach Vagus (GRP) Small peptides and amino acids H+ in the stomach Somatostatin H+ secretion and stimulate gastric mucosa growth CCK I Cells of duodenum and jejunum Fatty acids small peptides and amino acid Somatostatin pancreatic enzyme and HCO3- Secretion Growth of exocrine pancreas/gallbladder inhibits gastric emptying Secretin S –cell of duodenum H+ in duoenum Fatty acids in duodenum Somatostatin pancreatic HCO3- Secretion Billiary HCO3- Gastric H+ secretion GIP Duodenum and jejunum Fatty acids, amino acids and oral glucose Somastostatin insulin secretion Gastric H+ ecretion

Paracrines Paracrines are released from the endocrine cells in the GI mucosa and diffuse over short distances to act on the target cells located in the Gi tracts. The GI paracrines are: Paracrines Site of Secretion Inhibitor Actions Somastostatin Throughout GI tract Vagal stimulation inhibit s the release of all GI hormones Inhibits gastric H+ secretion Histamine Mast cells of the gastric mucosa Somatostatin increased gastric H+ secretion directly Also potentiate the effect of gastrin and vagal stimulation

Neurocrines Neurocrines are synthesized in neurons of the GI tract, moved by axonal transport down the axon, and release by action potentials in the nerves. The released neurocrines then diffuse across the synaptic cleft to a target cell Neurocrine Site of Secretion Actions VIP Neurone in the mucosa and smooth muscle of GI tract Relaxation of GI muscle and LES Stimulate pancreatic HCO3 secretion and Inhibit gastric H+ secretion GRP (bombesin) Vagus nerve that innervate G ccells Stimulate gastrin release from G cells Enkephalins Nerves in the mucosa and smooth muscle of the GI tract Stimulate contraction of Gi smooth muscle, particularly the lower esophageal, pyloric and ileocecal sphincters Inhibit intestinal secretion of fluid and electrolytes

a. Overview of the biliary system Physiologic Anatomy of Biliary SecretionThe hepatocytes, bile canaliculi, intrahepatic bile ducts, extrahepatic bile ducts, gall bladder and common bile ducts make up the biliary system. Bile is secreted by hepatocytes into bile canaliculi, passes through intrahepatic bile ducts to the right and left bile ducts, to the common hepatic duct, which joins the cystic duct to form the common bile duct. The CBD joins the main pancreatic duct (forming the hepatopancreatic duct) and empties into the 2nd part of the duodenum at the hepatopancreatic ampulla / sphincter (of Oddi). Bile is secreted in two stages by the liver: (1) The initial portion is secreted by the principal functional cells of the liver, the hepatocytes; this initial secretion contains large amounts of bile acids, cholesterol, and other organic constituents. It is secreted into minute bile canaliculi that originate between the hepatic cells (2) Next, the bile flows in the canaliculi toward the interlobular septa, where the canaliculi empty into terminal bile ducts and then into progressively larger ducts, finally reaching the hepatic duct and common bile duct. From these the bile either empties directly into the duodenum or is diverted for minutes up to several hours through the cystic duct into the gallbladder, second portion of liver secretion is added to the initial bile.This additional secretion is a watery solution of sodium and bicarbonate ions secreted by secretory epithelial cells that line the ductules and ducts. Figure 8-24 Secretion and enterohepatic circulation of bile salts. Light blue arrows show the path of bile flow; yellow arrows show the movement of ions and water. CCK, Cholecystokinin.

e. Enterohepatic circulation of bile salts diffuse Cholesterol 7α-hydroxylase (rate-limiting enzyme) 94% Synthesis of bile acids occurs, as needed, to replace bile acids that are excreted in the feces rather than recirculated back to the liver. The total bile acid pool returning to the liver determines the need for synthesis. If bile acids are not absorbed in the distal ileum (drugs such as cholestyramine or other “anion exchange resins” which promote bile salt excretion with feces, or ileal resection, then bile acid synthesis must occur. Bile secretion and gallbladder The hepatocytes, bile canaliculi, intrahepatic bile ducts, extrahepatic bile ducts, gall bladder and common bile ducts make up the biliary system. Bile is secreted by hepatocytes into bile canaliculi, passes through intrahepatic bile ducts to the right and left bile ducts, to the common hepatic duct, which joins the cystic duct to form the common bile duct. The CBD joins the main pancreatic duct (forming the hepatopancreatic duct) and empties into the 2nd part of the duodenum at the hepatopancreatic ampulla / sphincter (of Oddi). When chyme reaches the small intestine, CCK is released, and gall bladder smooth muscle contracts as the sphinter relaxes, ejecting gall bladder bile into the duodenum. CCK is released in response to small peptides and fatty acids in the duodenum. CCK “tells” the gallbladder that fats need to be emulsified and absorbed –in other words, bile is needed. CCK causes contraction of the gallbladder smooth muscle and relaxation of the sphincter of the hepatopancreatic ampulla (Oddi). ACh also causes contraction of the gallbladder. In the interdigestive period, the hepatopancreatic sphincter is closed and bile flows into the gall bladder, where water and electrolytes are removed (bile organic components are concentrated). The gallbladder concentrates the bile by reabsorbing Na+, Cl- and HCO3-. H2O is reabsorbed isosmotically. Bile mixes with chyme emulsifying fats and forming micelles (solubilizing fat and increasing surface area for digestion and absorption). When chyme reaches the terminal ileum, most bile acids are reabsorbed into the portal circulation and returned to the liver for resecretion into bile. The terminal ileum contains a mechanism for secondary active transport of conjugated bile acids with Na + , which recirculates bile acids to the liver. Therefore, most of the bile acids are not recirculated to the liver until they reach the terminal ileum. This ensures that bile acids will be present for maximal absorption of fats throughout the upper small intestine. Ileal resection causes steatorrhea: Bile acids lost in feces are not recirculated to the liver, and the bile acid pool becomes depleted. active transport Na+-bile salt cotransporter Figure 8-24 Secretion and enterohepatic circulation of bile salts.

Portal Circulation CCK Cholesterol 7α-hydroxylase diffuse GB Ions and water 2 + Duodenum CCK Liver + 3 Bile Bile duct Sphincter of oddi 1 Ions and water Bile salt Cholesterol Secretin Cholesterol 7α-hydroxylase (rate-limiting enzyme) diffuse 94% Bile salts 4 Portal Circulation Ileum active transport Na+-bile salt cotransporter

A Summary of Digestion of Carbohydrates, Proteins and Lipids Lingual lipase Gastric lipase colipase

A Summary of Digestion of Carbohydrates, Proteins and Lipids Site Carbohydrate Protein Nucleic Acid Fat Oral Cavity Polysaccharides Smaller polysaccharides, maltose amylase Lingual lipase Somach Proteins Small polypeptides Gastic lipase Pepsin Lumen of small Intestine Polysaccharides Maltose and other disaccharides Polypeptides Smaller polypeptides Amino acids DNA, RNA Nucleotides Fat globules Fat droplets (emulsified) Glyycerol, Fatty acids , glycerides Pancreatic amylases Tripsin, Chymotrypsin Bile salts Nucleases Lipase colipase Aminopeptidase, Carboxypeptidase Epithelium of small intestine (brush border) Monosaccharides Small peptides Dipeptidases Amino acids Nucleosides Nitrogenous bases, sugars, phosphates Nucleotidases Disaccharidases Nucleotidases Dipeptidases Aminopeptidase

Exercise: fill in the red box with appropriate enzymes.

Digestion and absorption Nutrient Digestion Site of Absorption Mechanism of Absorption Carbohydrates To Monosaccharides Small intestine Na+ dependent cotransport Facilitated diffusion (fructose) Proteins To Amino acids and peptides Small intestine Na+ dependent cotranport (amino acids) H+ dependent cotranport (di and tripeptides) Lipids To fatty acids, monoglycerides, cholesterol Small intestine Micelles form with bile salts in intestinal lumen Difussiionof fatty acids, monoglycerides, and cholesterol into cell Water soluble vitamins Small intestine Na+ dependent cotransport Vitamin B12 Ileum Intrinsic factor-Vit B12 complex Bile acids Ileum Na+ dependent cotransport Ca2+ Small Intestine Vit D dependent (Calbindin D 28K0 Fe2+ Fe3+ is reduced to Fe3+ Small Intestine Binds to apoferritin in cell Circulates in blood bound to transferrin