Gastrointestinal Physiology PDF

Gastrointestinal Physiology 1 Human digestive system 2 3 A. Structure of the gastrointestinal (GI) tract 1. Epithelial cells are specialized in different parts of the GI tract for secretion or absorption. 2. Muscularis mucosa Contractio...

Gastrointestinal Physiology 1 Human digestive system 2 3 A. Structure of the gastrointestinal (GI) tract 1. Epithelial cells are specialized in different parts of the GI tract for secretion or absorption. 2. Muscularis mucosa Contraction causes a change in the surface area for secretion or absorption. 3. Circular muscle Contraction causes a decrease in diameter of the lumen of the GI tract. 4. Longitudinal muscle Contraction causes shortening of a segment of the GI tract. 5. Submucosal plexus (Meissner’s plexus) and myenteric plexus comprise the enteric nervous system of the GI tract. integrate and coordinate the motility, secretory, and endocrine functions of the GI tract. 4 B. Innervation of the GI tract The autonomic nervous system (ANS) of the GI tract comprises both extrinsic and intrinsic nervous systems. 1. Extrinsic innervation (parasympathetic and sympathetic nervous systems) Efferent fibers carry information from the brain stem and spinal cord to the GI tract. Afferent fibers carry sensory information from chemoreceptors and mechanoreceptors in the GI tract to the brain stem and spinal cord. a. Parasympathetic nervous system is usually excitatory on the functions of the GI tract. is carried via the vagus and pelvic nerves. Preganglionic parasympathetic fibers synapse in the myenteric and submucosal plexuses. Cell bodies in the ganglia of the plexuses then send information to the smooth muscle, secretory cells, and endocrine cells of the GI tract. 5 Innervation of the GI tract….(Cont’d) b. Sympathetic nervous system is usually inhibitory on the functions of the GI tract. Fibers originate in the spinal cord between T-8 and L-2. Postganglionic sympathetic adrenergic fibers synapse in the myenteric and submucosal plexuses. Direct postganglionic adrenergic innervation of blood vessels and some smooth muscle cells also occurs. Cell bodies in the ganglia of the plexuses then send information to the smooth muscle, secretory cells, and endocrine cells of the GI tract. 6 2. Intrinsic innervation (enteric nervous system) coordinates and relays information from the parasympathetic and sympathetic nervous systems to the GI tract. uses local reflexes to relay information within the GI tract. controls most functions of the GI tract, especially motility and secretion, even in the absence of extrinsic innervation. a. Myenteric plexus (Auerbach’s plexus) primarily controls the motility of the GI smooth muscle. b. Submucosal plexus (Meissner’s plexus) primarily controls secretion and blood flow. receives sensory information from chemoreceptors and mechanoreceptors in the GI tract. 7 ory Substances In The Gastrointestinal Tract….(Cont’d) Four substances meet the requirements to be considered “official” GI hormones; others are considered “candidate” hormones. The four official GI hormones are  gastrin, cholecystokinin (CCK), secretin, and glucose-dependent insulinotropic peptide (GIP). 1. GASTRIN a. Actions of gastrin (1) Increases H+ secretion by the gastric parietal cells. 8 ory Substances In The Gastrointestinal Tract….(Cont’d) b. Stimuli for secretion of gastrin Gastrin is secreted from the G cells of the gastric antrum in response to a meal. Gastrin is secreted in response to the following: (1) Small peptides and amino acids in the lumen of the stomach (2) Distention of the stomach (3) Vagal stimulation, mediated by gastrin-releasing peptide (GRP) Atropine does not block vagally mediated gastrin secretion because the mediator of the vagal effect is GRP, not acetylcholine (ACh). c. Inhibition of gastrin secretion H+ in the lumen of the stomach inhibits gastrin release. This negative feedback control ensures that gastrin secretion is inhibited if the stomach contents are sufficiently acidified. 9 ory Substances In The Gastrointestinal Tract….(Cont’d) 2. CHOLECYSTOKININ (CCK) a. Actions of CCK (1) Stimulates contraction of the gallbladder and simultaneously causes relaxation of the sphincter of Oddi for secretion of bile. (2) Stimulates pancreatic enzyme secretion. (3) Potentiates secretin-induced stimulation of pancreatic HCO3– secretion. (4) Stimulates growth of the exocrine pancreas. (5) Inhibits gastric emptying. Thus, meals containing fat stimulate the secretion of CCK, which slows gastric emptying to allow more time for intestinal digestion and absorption. b. Stimuli for the release of CCK CCK is released from the I cells of the duodenal and jejunal mucosa by: (1) Small peptides and amino acids (2) Fatty acids and monoglycerides Triglycerides do not stimulate the release of CCK because they cannot cross intestinal cell membranes. 10 ory Substances In The Gastrointestinal Tract….(Cont’d) 3. SECRETIN a. Actions of secretin are coordinated to reduce the amount of H+ in the lumen of the small intestine. (1) Stimulates pancreatic HCO3– secretion and increases growth of the exocrine pancreas. Pancreatic HCO3– neutralizes H+ in the intestinal lumen. (2) Stimulates HCO3– and H2O secretion by the liver, and increases bile production. (3) Inhibits H+ secretion by gastric parietal cells. b. Stimuli for the release of secretin Secretin is released by the S cells of the duodenum in response to: (1) H+ in the lumen of the duodenum. (2) Fatty acids in the lumen of the duodenum. 11 ory Substances In The Gastrointestinal Tract….(Cont’d) 4. GLUCOSE-DEPENDENT INSULINOTROPIC PEPTIDE (GIP). a. Actions of GIP (1) Stimulates insulin release. In the presence of an oral glucose load, GIP causes the release of insulin from the pancreas. Thus, oral glucose is more effective than intravenous glucose in causing insulin release and, therefore, glucose utilization. (2) Inhibits H+ secretion by gastric parietal cells. b. Stimuli for the release of GIP GIP is secreted by the duodenum and jejunum. GIP is the only GI hormone that is released in response to fat, protein, and carbohydrate. GIP secretion is stimulated by fatty acids, amino acids, and orally administered glucose. 12 13  III. GASTROINTESTINAL MOTILITY Contractile tissue of the GI tract is almost exclusively unitary smooth muscle, with the exception of the pharynx, upper one-third of the esophagus, and external anal sphincter, all of which are striated muscle. Depolarization of circular muscle leads to contraction of a ring of smooth muscle and a decrease in diameter of that segment of the GI tract. Depolarization of longitudinal muscle leads to contraction in the longitudinal direction and a decrease in length of that segment of the GI tract. 14 ASTROINTESTINAL MOTILITY….. (Cont’d) B. Chewing, swallowing, and esophageal peristalsis 1. Chewing lubricates food by mixing it with saliva. decreases the size of food particles to facilitate swallowing and to begin the digestive process. 2. Swallowing The swallowing reflex is coordinated in the medulla. Fibers in the vagus and glossopharyngeal nerves carry information between the GI tract and the medulla. The following sequence of events is involved in swallowing: a. The nasopharynx closes and, at the same time, breathing is inhibited. b. The laryngeal muscles contract to close the glottis and elevate the larynx. c. Peristalsis begins in the pharynx to propel the food bolus toward the esophagus. Simultaneously, the upper esophageal sphincter relaxes to permit the food bolus to enter the esophagus. 15 ASTROINTESTINAL MOTILITY….. (Cont’d) 3. Esophageal motility The esophagus propels the swallowed food into the stomach. Sphincters at either end of the esophagus prevent air from entering the upper esophagus and gastric acid from entering the lower esophagus.. 16 ASTROINTESTINAL MOTILITY….. (Cont’d) Clinical correlations of esophageal motility a. Gastroesophageal reflux (heartburn) may occur if the tone of the lower esophageal sphincter is decreased and gastric contents reflux into the esophagus. b. Achalasia may occur if the lower esophageal sphincter does not relax during swallowing and food accumulates in the esophagus. 17 TROINTESTINAL MOTILITY….. (Cont’d) 1. “Receptive relaxation” The orad region of the stomach relaxes to accommodate the ingested meal. CCK participates in “receptive relaxation” by increasing the distensibility of the orad stomach. 18 TROINTESTINAL MOTILITY….. (Cont’d) 3. Gastric emptying The caudad region of the stomach contracts to propel food into the duodenum. a. The rate of gastric emptying is fastest when the stomach contents are isotonic. If the stomach contents are hypertonic or hypotonic, gastric emptying is slowed. b. Fat inhibits gastric emptying 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 19 ASTROINTESTINAL MOTILITY….. (Cont’d) D. Small intestinal motility The small intestine functions in the digestion and absorption of nutrients. The small intestine mixes nutrients with digestive enzymes, exposes the digested nutrients to the absorptive mucosa, and then propels any non absorbed material to the large intestine. As in the stomach, slow waves set the basic electrical rhythm, which occurs at a frequency of 12 waves/min. Action potentials occur on top of the slow waves and lead to contractions. Parasympathetic stimulation increases intestinal smooth muscle contraction; sympathetic stimulation decreases it. 20 ASTROINTESTINAL MOTILITY….. (Cont’d) Peristaltic contractions are highly coordinated and propel the chyme through the small intestine toward the large intestine. Ideally, peristalsis occurs after digestion and absorption have taken place. Contraction behind the bolus and, simultaneously, relaxation in front of the bolus cause the chyme to be propelled caudally. The peristaltic reflex is coordinated by the enteric nervous system. 21 ASTROINTESTINAL MOTILITY….. (Cont’d) Segmentation contractions mix the intestinal contents. A section of small intestine contracts, sending the intestinal contents (chyme) in both orad and caudad directions. That section of small intestine then relaxes, and the contents move back into the segment. This back-and-forth movement produced by segmentation contractions causes mixing without any net forward movement of the chyme. 22 ASTROINTESTINAL MOTILITY….. (Cont’d) Gastroileal reflex is mediated by the extrinsic ANS and possibly by gastrin. The presence of food in the stomach triggers increased peristalsis in the ileum and relaxation of the ileocecal sphincter. As a result, the intestinal contents are delivered to the large intestine. 23  Ileocecal Valve is between Ileum and Colon Ascending colon Ileocecal sphincter New Gastrin meal Ileum Pushes valve Pushes closed and valve open contracts Ileocecal and relaxes sphincter valve sphincter Cecum Appendix 24 Fig. 16-19, p. ASTROINTESTINAL MOTILITY….. (Cont’d) E. Large intestinal motility Fecal material moves from the cecum to the colon (i.e., through the ascending, transverse, descending, and sigmoid colons), to the rectum, and then to the anal canal. Haustra, or saclike segments, appear after contractions of the large intestine. 1. Cecum and proximal colon When the proximal colon is distended with fecal material, the ileocecal sphincter contracts to prevent reflux into the ileum. a. Segmentation contractions in the proximal colon mix the contents and are responsible for the appearance of haustra. b. Mass movements occur 1 to 3 times/day and cause the colonic contents to move distally for long distances (e.g., from the transverse colon to the sigmoid colon). 2. Distal colon Because most colonic water absorption occurs in the proximal colon, fecal material in the distal colon becomes semisolid and moves slowly. Mass movements propel it into the rectum. 25 Figure 25.16a The TRANSVERSE Large COLON Left colic Intestine Right colic (splenic) (hepatic) flexure flexure DESCENDING COLON ASCENDING COLON Haustra Ileocecal valve Ileu Cecum m Taenia coli Appendix Sigmoid flexure SIGMOID COLON Rectu m 26 ASTROINTESTINAL MOTILITY….. (Cont’d) 3. Rectum, anal canal, and defecation The sequence of events for defecation is as follows: a. As the rectum fills with fecal material, it contracts and the internal anal sphincter relaxes (recto sphincteric reflex). b. Once the rectum is filled to about 25% of its capacity, there is an urge to defecate. However, defecation is prevented because the external anal sphincter is tonically contracted. c. When it is convenient to defecate, the external anal sphincter is relaxed voluntarily. The smooth muscle of the rectum contracts, forcing the feces out of the body. Intra-abdominal pressure is increased by expiring against a closed glottis (Valsalva maneuver). 4. Gastrocolic reflex The presence of food in the stomach increases the motility of the colon and increases the frequency of mass movements. a. The gastrocolic reflex has a rapid parasympathetic component that is initiated when the stomach is stretched by food. b. A slower, hormonal component is mediated by CCK and gastrin. 27 Defecation Reflex 28 ASTROINTESTINAL MOTILITY….. (Cont’d) F. Vomiting A wave of reverse peristalsis begins in the small intestine, moving the GI contents in the orad direction. The gastric contents are eventually pushed into the esophagus. If the upper esophageal sphincter remains closed, retching occurs. If the pressure in the esophagus becomes high enough to open the upper esophageal sphincter, vomiting occurs. The vomiting center in the medulla is stimulated by tickling the back of the throat, gastric distention, and vestibular stimulation (motion sickness). The chemoreceptor trigger zone in the fourth ventricle is activated by emetics, radiation, and vestibular stimulation. 29  IV. GASTROINTESTINAL SECRETION A. Salivary secretion 1. Functions of saliva a. Initial starch digestion by α-amylase (ptyalin) and initial triglyceride digestion by lingual lipase 30 31 TROINTESTINAL SECRETION….(Cont’d) b. Lubrication of ingested food by mucus c. Protection of the mouth and esophagus by dilution and buffering of ingested foods 2. Composition of saliva a. Saliva is characterized by: (1) High volume (relative to the small size of the salivary glands) (2) High K + and HCO3– concentrations (3) Low Na+ and Cl– concentrations (4) Hypotonicity (5) Presence of α-amylase, lingual lipase, and kallikrein b. The composition of saliva varies with the salivary flow rate (Figure 6-4). 32 TROINTESTINAL SECRETION….(Cont’d) 3. Formation of saliva Saliva is formed by three major glands—the Parotid glands Submandibular gland sublingual gland 33 TROINTESTINAL SECRETION….(Cont’d) 4. Regulation of saliva production Saliva production is controlled by the parasympathetic and sympathetic nervous systems (not by GI hormones). Saliva production is unique in that it is increased by both parasympathetic and sympathetic activity. Parasympathetic activity is more important. 34 TROINTESTINAL SECRETION….(Cont’d) B. Gastric secretion 1. Gastric cell types and their secretions Parietal cells, located in the body, secrete HCl and intrinsic factor. Chief cells, located in the body, secrete pepsinogen. G cells, located in the antrum, secrete gastrin. 2. Mechanism of gastric H+ secretion Parietal cells secrete HCl into the lumen of the stomach and, concurrently, absorb HCO3– into the bloodstream as follows: a. In the parietal cells, CO2 and H2O are converted to H+ and HCO3–, catalyzed by carbonic anhydrase. 35 TROINTESTINAL SECRETION….(Cont’d) 36 TROINTESTINAL SECRETION….(Cont’d) 37 ROINTESTINAL SECRETION….(Cont’d) Bile duct from liver Stomach Duodenum Hormones (insulin, glucagon) Blood Endocrine portion Duct cells Acinar cells of pancreas (islets of Langerhans) Exocrine portion To pancreatic duct of pancreas NaHCO3– and duodenum Duct cells (secrete aqueous NaHCO3– solution) Zymogen granules Enzymes Acinar cells (secrete digestive 38 enzymes) Fig. 16-11, p. 608 ROINTESTINAL SECRETION….(Cont’d) Bile secretion and gallbladder function 1. Composition and function of bile Bile contains bile salts, phospholipids, cholesterol, and bile pigments (bilirubin). a. Bile salts are amphipathic molecules because they have both hydrophilic and hydrophobic portions. In aqueous solution, bile salts orient themselves around droplets of lipid and keep the lipid droplets dispersed (emulsification). aid in the intestinal digestion and absorption of lipids by emulsifying and solubilizing them in micelles. b. Micelles Free fatty acids and monoglycerides are present in the inside of the micelle, essentially “solubilized” for subsequent absorption. 39  DIGESTION AND ABSORPTION Carbohydrates, proteins, and lipids are digested and absorbed in the small intestine. The surface area for absorption in the small intestine is greatly increased by the presence of the brush border. A. Carbohydrates 1. Digestion of carbohydrates Only monosaccharides are absorbed. Carbohydrates must be digested to glucose, galactose, and fructose for absorption to proceed. a. Amylases (salivary and pancreatic) hydrolyze 1,4-glycosidic bonds in starch, yielding maltose, maltotriose, and α-limit dextrins. b. Maltase, dextrinase, and sucrase in the intestinal brush border then hydrolyze the oligosaccharides to glucose. c. Lactase, trehalase, and sucrase degrade their respective disaccharides to monosaccharides. 40 ESTION AND ABSORPTION…..(Cont’d) 41 GESTION AND ABSORPTION…..(Cont’d) Lactase degrades lactose to glucose and galactose. Trehalase degrades trehalose to glucose. Sucrase degrades sucrose to glucose and fructose. 2. Absorption of carbohydrates a. Glucose and galactose are transported from the intestinal lumen into the cells by a Na+-dependent cotransport (SGLT 1) in the luminal membrane. The sugar is transported “uphill” and Na+ is transported “downhill.” are then transported from cell to blood by facilitated diffusion (GLUT 2). The Na+–K+ pump in the basolateral membrane keeps the intracellular [Na+] low, thus maintaining the Na+ gradient across the luminal membrane. Poisoning the Na+–K+ pump inhibits glucose and galactose absorption by dissipating the Na+ gradient. b. Fructose is transported exclusively by facilitated diffusion; therefore, it cannot be absorbed against a concentration gradient. 42 ESTION AND ABSORPTION…..(Cont’d) 43 GESTION AND ABSORPTION…..(Cont’d) 3. Clinical disorders of carbohydrate absorption Lactose intolerance results from the absence of brush border lactase and, thus, the inability to hydrolyze lactose to glucose and galactose for absorption. Nonabsorbed lactose and H2O remain in the lumen of the GI tract and cause osmotic diarrhea. 44 GESTION AND ABSORPTION…..(Cont’d) B. Proteins 1. Digestion of proteins a. Endopeptidases degrade proteins by hydrolyzing interior peptide bonds. b. Exopeptidases hydrolyze one amino acid at a time from the C terminus of proteins and peptides. c. Pepsin is not essential for protein digestion. is secreted as pepsinogen by the chief cells of the stomach. Pepsinogen is activated to pepsin by gastric H+. The optimum pH for pepsin is between 1 and 3. When the pH is >5, pepsin is denatured. Thus, in the intestine, as HCO3– is secreted in pancreatic fluids, duodenal pH increases and pepsin is inactivated. 45 GESTION AND ABSORPTION…..(Cont’d) 46 GESTION AND ABSORPTION…..(Cont’d) d. Pancreatic proteases include trypsin, chymotrypsin, elastase, carboxypeptidase are secreted in inactive forms that are activated in the small intestine as follows: (1) Trypsinogen is activated to trypsin by a brush border enzyme, enterokinase. (2) Trypsin then converts Chymotrypsinogen to chymotrypsin, Proelastase to elastase, and procarboxypeptidase to carboxypeptidase trypsinogen to more trypsin (3) After their digestive work is complete, the pancreatic proteases degrade each other and are absorbed along with dietary proteins. 47 GESTION AND ABSORPTION…..(Cont’d) 2. Absorption of proteins Digestive products of protein can be absorbed as amino acids, dipeptides, and tripeptides (in contrast to carbohydrates, which can only be absorbed as monosaccharides). a. Free amino acids Na+-dependent amino acid cotransport occurs in the luminal membrane. It is analogous to the cotransporter for glucose and galactose. The amino acids are then transported from cell to blood by facilitated diffusion. 48 GESTION AND ABSORPTION…..(Cont’d) b. Dipeptides and tripeptides are absorbed faster than free amino acids. H+-dependent cotransport of dipeptides and tripeptides also occurs in the luminal membrane. After the dipeptides and tripeptides are transported into the intestinal cells, cytoplasmic peptidases hydrolyze them to amino acids. The amino acids are then transported from cell to blood by facilitated diffusion. 49 GESTION AND ABSORPTION…..(Cont’d) 50 GESTION AND ABSORPTION…..(Cont’d) C. Lipids 1. Digestion of lipids a. Stomach (1) In the stomach, mixing breaks lipids into droplets to increase the surface area for digestion by pancreatic enzymes. (2) Lingual lipases digest some of the ingested triglycerides to monoglycerides and fatty acids. However, most of the ingested lipids are digested in the intestine by pancreatic lipases. (3) CCK slows gastric emptying. Thus, delivery of lipids from the stomach to the duodenum is slowed to allow adequate time for digestion and absorption in the intestine. 51 GESTION AND ABSORPTION…..(Cont’d) 52 GESTION AND ABSORPTION…..(Cont’d) 53 GESTION AND ABSORPTION…..(Cont’d) b. Small intestine (1) Bile acids emulsify lipids in the small intestine, increasing the surface area for digestion. (2) Pancreatic lipases hydrolyze lipids to fatty acids, monoglycerides, cholesterol, and lysolecithin. The enzymes are pancreatic lipase, cholesterol ester hydrolase, and phospholipase A2. (3) The hydrophobic products of lipid digestion are solubilized in micelles by bile acids. 54 GESTION AND ABSORPTION…..(Cont’d) 2. Absorption of lipids a. Micelles bring the products of lipid digestion into contact with the absorptive surface of the intestinal cells. Then, fatty acids, monoglycerides, and cholesterol diffuse across the luminal membrane into the cells. Glycerol is hydrophilic and is not contained in the micelles. b. In the intestinal cells, the products of lipid digestion are re- esterified to triglycerides, cholesterol ester, and phospholipids and, with apoproteins, form chylomicrons. 55 GESTION AND ABSORPTION…..(Cont’d) D. Absorption and secretion of electrolytes and water Electrolytes and H2O may cross intestinal epithelial cells by either cellular or paracellular (between cells) routes. Tight junctions attach the epithelial cells to one another at the luminal membrane. The permeability of the tight junctions varies with the type of epithelium. A “tight” (impermeable) epithelium is the colon. “Leaky” (permeable) epithelia are the small intestine and gallbladder. 56 GESTION AND ABSORPTION…..(Cont’d) 1. Absorption of NaCl a. Na+ moves into the intestinal cells, across the luminal membrane, and down its electrochemical gradient by the following mechanisms: (1) Passive diffusion (through Na+ channels) (2) Na+–glucose or Na+–amino acid cotransport (3) Na+–Cl– cotransport (4) Na+–H+ exchange In the small intestine, Na+–glucose cotransport, Na+–amino acid cotransport, and Na+–H+ exchange mechanisms are most important. These cotransport and exchange mechanisms are similar to those in the renal proximal tubule. In the colon, passive diffusion via Na+ channels is most important. The Na+ channels of the colon are similar to those in the renal distal tubule and are stimulated by aldosterone. 57 GESTION AND ABSORPTION…..(Cont’d) b. Na+ is pumped out of the cell against its electrochemical gradient by the Na+–K+ pump in the basolateral membranes. c. Cl– absorption accompanies Na+ absorption throughout the GI tract by the following mechanisms: (1) Passive diffusion by a paracellular route (2) Na+–Cl– cotransport (3) Cl––HCO3– exchange 58 GESTION AND ABSORPTION…..(Cont’d) 2. Absorption and secretion of K+ a. Dietary K+ is absorbed in the small intestine by passive diffusion via a paracellular route. b. K+ is actively secreted in the colon by a mechanism similar to that for K+ secretion in the renal distal tubule. As in the distal tubule, K+ secretion in the colon is stimulated by aldosterone. In diarrhea, K+ secretion by the colon is increased because of a flow rate– dependent mechanism similar to that in the renal distal tubule. Excessive loss of K+ in diarrheal fluid causes hypokalemia. 59 GESTION AND ABSORPTION…..(Cont’d) 3. Absorption of H2O is secondary to solute absorption. is isosmotic in the small intestine and gallbladder. The mechanism for coupling solute and water absorption in these epithelia is the same as that in the renal proximal tubule. In the colon, H2O permeability is much lower than in the small intestine, and feces may be hypertonic. 60 GESTION AND ABSORPTION…..(Cont’d) 4. Secretion of electrolytes and H2O by the intestine The GI tract also secretes electrolytes from blood to lumen. The secretory mechanisms are located in the crypts. The absorptive mechanisms are located in the villi. a. Cl– is the primary ion secreted into the intestinal lumen. It is transported through Cl– channels in the luminal membrane that are regulated by cAMP. b. Na+ is secreted into the lumen by passively following Cl–. H2O follows NaCl to maintain isosmotic conditions. c. Vibrio cholerae (cholera toxin) causes diarrhea by stimulating Cl– secretion. Na+ and H2O follow Cl– into the lumen and lead to secretory diarrhea. 61 GESTION AND ABSORPTION…..(Cont’d) E. Absorption of other substances 1. Vitamins a. Fat-soluble vitamins (A, D, E, and K) are incorporated into micelles and absorbed along with other lipids. b. Most water-soluble vitamins are absorbed by Na+-dependent cotransport mechanisms. c. Vitamin B 12 is absorbed in the ileum and requires intrinsic factor. The vitamin B 12–intrinsic factor complex binds to a receptor on the ileal cells and is absorbed. Gastrectomy results in the loss of gastric parietal cells, which are the source of intrinsic factor. Injection of vitamin B12 is required to prevent pernicious anemia. 62 GESTION AND ABSORPTION…..(Cont’d) 2. Calcium absorption in the small intestine depends on the presence of adequate amounts of the active form of vitamin D, 1,25-dihydroxycholecalciferol, which is produced in the kidney. 1,25-dihydroxycholecalciferol induces the synthesis of an intestinal Ca2+-binding protein, calbindin. Vitamin D deficiency or chronic renal failure results in inadequate intestinal Ca2+ absorption, causing rickets in children and osteomalacia in adults. 63 GESTION AND ABSORPTION…..(Cont’d) 3. Iron is absorbed as heme iron (iron bound to hemoglobin or myoglobin) or as free Fe2+. In the intestinal cells, “heme iron” is degraded and free Fe2+ is released. The free Fe2+ binds to apoferritin and is transported into the blood. Free Fe2+ circulates in the blood bound to transferrin, which transports it from the small intestine to its storage sites in the liver, and from the liver to the bone marrow for the synthesis of hemoglobin. Iron deficiency is the most common cause of anemia. 64 65  VI. LIVER PHYSIOLOGY A. Bile formation and secretion B. Bilirubin production and excretion C. Metabolic functions of the liver 1. Carbohydrate metabolism Performs gluconeogenesis, stores glucose as glycogen, and releases stored glucose into the circulation. 66 LIVER PHYSIOLOGY-----Cont’d) 2. Protein metabolism Synthesizes nonessential amino acids e.g alanine, arginine, asparagine..etc Synthesizes plasma proteins 3. Lipid metabolism Participates in fatty acid oxidation Synthesizes lipoproteins, cholesterol, and phospholipids 67 LIVER PHYSIOLOGY-----Cont’d) D. Detoxification Potentially toxic substances are presented to the liver via the portal circulation. Liver modifies these substances in “first pass metabolism.” Phase I reactions are catalyzed by cytochrome P-450 enzymes, which are followed by phase II reactions that conjugate the substances. 68 The End 69