Chapter 18

The Digestive System

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Functions of the GI Tract

Motility:

Movement of of food through the GI tract.

Ingestion:

Taking food into the mouth. Chewing the food and mixing it with saliva. Swallowing the food. Rhythmic wave-like contractions that move food through GI tract.

Mastication:

Deglutition:

Peristalsis:

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Functions of the GI Tract

(continued)

Secretion:

Includes both exocrine and endocrine secretions.

Exocrine:

HCl, H20, HC03-, bile, lipase, pepsin, amylase, trypsin, elastase, and histamine are secreted into the lumen of the GI tract. Stomach and small intestine secrete hormones to help regulate the GI system.

Endocrine:

Gastrin, secretin, CCK, GIP, GLP-1, guanylin, VIP, and somatostatin.

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Functions of the GI Tract

(continued)

Digestion:

Breakdown of food particles into subunits (chemical structure change). Process of the passage of digestion (chemical subunits) into the blood or lymph. Temporary storage and elimination of indigestible food.

Absorption:

Storage and elimination:

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Digestive System (GI)

GI tract divided into:

Insert fig. 18.2

Alimentary canal. Accessory digestive organs.

GI tract is 30 ft long and extends from mouth to anus.

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Layers of GI Tract

Composed of 4 tunics:

Mucosa. Submucosa.

Muscularis. Serosa.

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Mucosa

Lines the lumen of GI tract.

Consists of simple columnar epithelium. Thin layer of connective tissue containing lymph nodules. Thin layer of smooth muscle responsible for the folds.

Lamina propria:

Muscularis mucosae:

Folds increase surface area for absorption.

Goblet cells:

Secrete mucus.

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Submucosa

Thick, highly vascular layer of connective tissue. Absorbed molecules enter the blood and lymphatic vessels. Submucosal plexus (Meissners plexus):

Provide autonomic nerve supply to the muscularis mucosae.

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Muscularis

Responsible for segmental contractions and peristaltic movement through the GI tract.

Inner circular layer of smooth muscle. Outer longitudinal layer of smooth muscle.

Contractions of these layers move food through the tract; pulverize and mix the food. Myenteric plexus located between the 2 muscle layers. Major nerve supply to GI tract.

Fibers and ganglia from both sympathetic and parasympathetic nervous systems.

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Serosa

Binding and protective outer layer. Consists of areolar connective tissue covered with simple squamous epithelium.

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Regulation of the GI Tract

Extrinsic innervation: Parasympathetic nervous system:

Vagus and spinal nerves: Stimulate motility and GI secretions. Postganglionic sympathetic fibers that pass through submucosal and myenteric plexuses and innervate GI tract: Reduce peristalsis and secretory activity.

Sympathetic nervous system:

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Regulation of the GI Tract

(continued)

Enteric nervous system:

Sites where parasympathetic fibers synapse with postganglionic neurons that innervate smooth muscle. Local regulation of the GI tract. Molecules acting locally. Secreted by the mucosa.

Submucosal and myenteric plexuses:

Paracrine secretion:

Hormonal secretion:

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

From Mouth to Stomach

Mastication (chewing):

Mixes food with saliva which contains salivary amylase.

Enzyme that can catalyze the partial digestion of starch.

Deglutition (swallowing):

Begins as a voluntary activity. Involves 3 phases:

Oral phase is voluntary. Pharyngeal and esophageal phases are involuntary.

Cannot be stopped.

Larynx is raised. Epiglottis covers the entrance to respiratory tract.

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

From Mouth to Stomach

(continued)

Involuntary muscular contractions and relaxations in the mouth, pharynx, larynx, and esophagus are coordinated by the swallowing center in the medulla. Esophagus:

Connects pharynx to the stomach.

Upper third contains skeletal muscle. Middle third contains a mixture of skeletal and smooth muscle. Terminal portion contains only smooth muscle.

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Esophagus

Peristalsis:

Produced by a series of localized reflexes in response to distention of wall by bolus.

Insert 18.4a

Wave-like muscular contractions:

Circular smooth muscle contract behind, relaxes in front of the bolus. Followed by longitudinal contraction (shortening) of smooth muscle.

Rate of 2-4 cm/sec.

After food passes into stomach, LES constricts.

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Stomach

Most distensible part of GI tract.

Empties into the duodenum.

Functions of the stomach: Stores food. Initiates digestion of proteins. Kills bacteria. Moves food (chyme) into intestine.

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Stomach

(continued)

Contractions of the stomach churn chyme.

Insert fig. 18.5

Mix chyme with gastric secretions. Push food into intestine.

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Stomach

(continued)

Gastric mucosa has gastric pits in the folds. Cells that line the folds deeper in the mucosa, are gastric glands.

Insert fig. 18.7

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Gastric Glands

Secrete gastric juice:

Goblet cells: mucus. Parietal cells: HCl and intrinsic factor. Chief cells: pepsinogen. Enterochromaffin-like cells (ECL): histamine and serotonin. G cells: gastrin. D cells: somatostatin. Stomach: ghrelin.

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

HCl Production

Parietal cells secrete H+ into gastric lumen by primary active transport, through H+/ K+ ATPase pump. Parietal cells basolateral membrane takes in Cl- against its electrochemical gradient, by coupling its transport with HC03-.

Insert fig. 18.8

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

HCl Production

(continued)

HCl production is stimulated:

Indirectly by gastrin. Indirectly by ACh.

ACh and gastrin stimulate release of histamine.

Histamine:

Stimulates parietal cells to secrete HCl.

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

HCl Functions

Makes gastric juice very acidic.

Denatures ingested proteins (alter tertiary structure) so become more digestible.

Insert fig. 18.9

Activates pepsinogen to pepsin.

Pepsin is more active at pH of 2.0.

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Digestion and Absorption in the Stomach

Proteins partially digested by pepsin. Carbohydrate digestion by salivary amylase is soon inactivated by acidity. Alcohol and aspirin are the only commonly ingested substances absorbed.

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Gastric and Peptic Ulcers

Peptic ulcers:

Erosions of the mucous membranes of the stomach or duodenum produced by action of HCl.
Ulcers of the duodenum are produced by excessive gastric acid secretions. Bacterium that resides in GI tract that may produce ulcers. Histamine released by tissue damage and inflammation stimulate further acid secretion.

Zollinger-Ellison syndrome:

Helicobacter pylori:

Acute gastritis:

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Protective Mechanisms of Stomach

Parietal and chief cells impermeable to HCl. Alkaline mucus contains HC03-. Tight junctions between adjacent epithelial cells. Rapid rate of cell division (entire epithelium replaced in 3 days). Prostaglandins inhibit gastric secretions.

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Small Intestine

Each villus is a fold in the mucosa. Covered with columnar epithelial cells interspersed with goblet cells. Epithelial cells at the tips of villi are exfoliated and replaced by mitosis in crypt of Lieberkuhn. Lamina propria contain lymphocytes, capillaries, and central lacteal.

Insert fig. 18.12

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Absorption in Small Intestine

Duodenum and jejunum:

Carbohydrates, amino acids, lipids, iron, and Ca2+. Bile salts, vitamin B12, electrolytes, and H20.

Ileum:

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Intestinal Enzymes

Microvilli contain brush border enzymes that are not secreted into the lumen.

Brush border enzymes remain attached to the cell membrane with their active sites exposed to the chyme.

Absorption requires both brush border enzymes and pancreatic enzymes.

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Intestinal Contractions and Motility

2 major types of contractions occur in the small intestine:

Insert fig. 18.14

Peristalsis:

Slow movement. Pressure at the pyloric end of small intestine is greater than at the distal end.

Segmentation:

Major contractile activity of the small intestine. Contraction of circular smooth muscle.

Mix chyme.

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Contractions of Intestinal Smooth Muscles

Occur automatically in response to endogenous pacemaker activity. Rhythm of contractions is paced by graded depolarizations called slow waves.

Insert fig. 18.15

Slow waves produced by interstitial cells of Cajal. Slow waves spread from 1 smooth muscle cell to another through nexuses.

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Contractions of Intestinal Smooth Muscles

When slow waves above threshold, it triggers APs by opening of VG Ca2+ channels. Inward flow of Ca2+:

Produces the upward depolarization phase. Stimulates contraction of smooth muscle. VG K+ channels open.

Repolarization:

Slow waves decrease in amplitude as they are conducted.

May stimulate contraction in proportion to the magnitude of depolarization.

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Cells and Electrical Events in the Muscularis

Insert fig. 18.16

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Large Intestine

Outer surface bulges outward to form haustra. Little absorptive function.

Absorbs H20, electrolytes, several vitamin B complexes, vitamin K, and folic acid.

Intestinal microbiota produce significant amounts of folic acid and vitamin K. Bacteria ferment indigestible molecules to produce short-chain fatty acids.

Does not contain villi.

Secretes H20, via active transport of NaCl into intestinal lumen.

Guanylin stimulates secretion of Cl- and H20, and inhibits absorption of Na+ (minor pathway).

Membrane contains Na+/K+ pumps.

Minor pathway.

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Fluid and Electrolyte Absorption in the Intestine

Small intestine:

Most of the fluid and electrolytes are absorbed by small intestine.

Absorbs about 90% of the remaining volume.

Absorption of H20 occurs passively as a result of the osmotic gradient created by active transport.

Aldosterone stimulates NaCl and H20 absorption in the ileum.

Large intestine:

Absorbs about 90% of the remaining volume.

Absorption of H20 occurs passively as a result of the osmotic gradient created by active transport of Na+ and Cl-.

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Defecation

Waste material passes to the rectum. Occurs when rectal pressure rises and external anal sphincter relaxes. Defecation reflex:

Longitudinal rectal muscles contract to increase rectal pressure.

Relaxation of internal anal sphincter.

Excretion is aided by contractions of abdominal and pelvic skeletal muscles.

Push feces from the rectum.

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Structure of Liver

Liver largest internal organ.

Hepatocytes form hepatic plates that are 12 cells thick. Arranged into functional units called lobules. More permeable than other capillaries.

Plates separated by sinusoids.

Contains phagocytic Kupffer cells. Secretes bile into bile canaliculi, which are drained by bile ducts.

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Structure of Liver

(continued)

Insert fig. 18.20

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Hepatic Portal System

Products of digestion that are absorbed are delivered to the liver. Capillaries drain into the hepatic portal vein, which carries blood to liver.

blood is deoxygenated. Hepatic vein drains liver.

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Enterohepatic Circulation

Compounds that recirculate between liver and intestine.

Many compounds can be absorbed through small intestine and enter hepatic portal blood. Variety of exogenous compounds are secreted by the liver into the bile ducts.

Insert fig. 18.22

Can excrete these compounds into the intestine with the bile.

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Major Categories of Liver Function

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Bile Production and Secretion

The liver produces and secretes 2501500 ml of bile/day. Bile pigment (bilirubin) is produced in spleen, bone marrow, and liver.

Derivative of the heme groups (without iron) from hemoglobin.

Free bilirubin combines with glucuronic acid and forms conjugated bilirubin.

Secreted into bile. Urobilogen is absorbed by intestine and enters the hepatic vein.

Converted by bacteria in intestine to urobilinogen.

Recycled, or filtered by kidneys and excreted in urine.

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Metabolism of Heme and Bilirubin

Insert fig. 18.23

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Bile Production and Secretion

(continued)

Bile acids are derivatives of cholesterol.

Major pathway of cholesterol breakdown in the body. Cholic acid. Chenodeoxycholic acid.

Insert fig. 18.25

Principal bile acids are:

Combine with glycine or taurine to form bile salts.

Bile salts aggregate as micelles.

95% of bile acids are absorbed by ileum.

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Detoxification of the Blood

Liver can remove hormones, drugs, and other biologically active molecules from the blood by:

Excretion into the bile. Phagocytosis by Kupffer cells. Chemical alteration of the molecules.

Ammonia is produced by deamination of amino acids in the liver. Liver converts it into urea.

Excreted in urine.

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Detoxification of the Blood

(continued)

Inactivation of steroid hormones and drugs.

Conjugation of steroid hormones and xenobiotics make them anionic.

Can be transported into bile by multispecific organic anion transport carriers.

Steroid and xenobiotic receptors stimulate production of cytochrome P450 enzymes.

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Secretion of Glucose, Triglycerides and Ketones

Liver helps regulate blood glucose concentration by:

Glycogenesis and lipogenesis. Glycogenolysis and gluconeogenesis.

Contains enzymes required to convert free fatty acids into ketone bodies.

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Production of Plasma Proteins

Albumin and most of the plasma globulins (except immunoglobulins) are produced by the liver. Albumin:

Constitutes 70% of the total plasma protein.

Contributes most to the colloid osmotic pressure in the blood.

Globulins:

Transport cholesterol and hormones. Inhibit trypsin. Produce blood clotting factors I, II, III, V, VII, IX, XI.

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Gallbladder

Sac-like organ attached to the inferior surface of the liver. Stores and concentrates bile. When gallbladder fills with bile, it expands.

Contraction of the muscularis layer of the gallbladder, ejects bile into the common bile duct into duodenum.

When small intestine is empty, sphincter of Oddi closes.

Bile is forced up to the cystic duct to gallbladder.

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Pancreas

Exocrine:

Acini:

Insert fig. 18.26

Secrete pancreatic juice.

Endocrine:

Islets of Langerhans:

Secrete insulin and glucagon.

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Pancreatic Juice

Contains H20, HC03- and digestive enzymes.

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Pancreatic Juice

Complete digestion of food requires action of both pancreatic and brush border enzymes.

Most pancreatic enzymes are produced as zymogens. Trypsin (when activated by enterokinase) triggers the activation of other pancreatic enzymes.

Fig. 18.29

Pancreatic trypsin inhibitor attaches to trypsin.

Inhibits its activity in the pancreas.

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Neural and Endocrine Regulation

Neural and endocrine mechanisms modify the activity of the GI system. GI tract is both an endocrine gland, and a target for the action of hormones.

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Regulation of Gastric Function

Gastric motility and secretion are automatic. Waves of contraction are initiated spontaneously by pacesetter cells. Extrinsic control of gastric function is divided into 3 phases:

Cephalic phase. Gastric phase. Intestinal phase.

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Cephalic Phase

Stimulated by sight, smell, and taste of food. Activation of vagus: Stimulates chief cells to secrete pepsinogen. Directly stimulates G cells to secrete gastrin. Directly stimulates ECL cells to secrete histamine. Indirectly stimulates parietal cells to secrete HCl.

Continues into the 1st 30 min. of a meal.

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Gastric Phase

Arrival of food in stomach stimulates the gastric phase. Gastric secretion stimulated by:

Distension. Chemical nature of chyme (amino acids and short polypeptides). Stimulates G cells to secrete gastrin. Stimulates chief cells to secrete pepsinogen. Stimulates ECL cells to secrete histamine. Histamine stimulates secretin of HCl. Positive feedback effect.

As more HCl and pepsinogen are secreted, more polypeptides and amino acids are released.

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Gastric Phase

(continued)

Secretion of HCl is also regulated by a negative feedback effect:

Insert. Fig. 18.30

HCl secretion decreases if pH < 2.5. At pH of 1.0, gastrin secretion ceases. D cells stimulate secretion of somatostatin. Paracrine regulator to inhibit secretion of gastrin.

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Intestinal Phase

Inhibits gastric activity when chyme enters the small intestine. Arrival of chyme increases osmolality and distension.

Activates sensory neurons of vagus and produces an inhibitory neural reflex:

Inhibits gastric motility and secretion. In the presence of fat, enterogasterone inhibits gastric motility and secretion.

Hormone secretion:

Inhibit gastric activity:

Somatostatin, CCK, and GLP-1.

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Enteric Nervous System

Submucosal and myenteric plexuses contain 100 million neurons. Include preganglionic parasympathetic axons, ganglion cell bodies, postganglionic sympathetic axons; and afferent intrinsic and extrinsic sensory neurons.

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Enteric Nervous System

(continued)

Peristalsis: ACh and substance P stimulate smooth muscle contraction above the bolus. NO, VIP, and ATP stimulate smooth muscle relaxation below the bolus.

Insert fig. 18.31

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Paracrine Regulators of the Intestine

Serotonin (5-HT):

Stimulates intrinsic afferents, which send impulses into intrinsic nervous system; and activates motor neurons. Stimulates contraction of the duodenum and stomach antrum. Activates guanylate cyclase, stimulating the production of cGMP.

Motilin:

Guanylin:

cGMP stimulates the intestinal cells to secrete Cl- and H20.

Inhibits the absorption of Na+.

Uroguanylin:

May stimulate kidneys to secrete salt in urine.

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Intestinal Reflexes

Intrinsic and extrinsic regulation controlled by intrinsic and paracrine regulators. Gastroileal reflex:

Increased gastric activity causes increased motility of ileum and movement of chyme through ileocecal sphincter. Distension of ileum, decreases gastric motility. Overdistension in 1 segment, causes relaxation throughout the rest of intestine.

Ileogastric reflex:

Intestino-intestinal reflex:

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Secretion of Pancreatic Juice

Secretion of pancreatic juice and bile is stimulated by: Secretin: Occurs in response to duodenal pH < 4.5. Stimulates production of HC03 by pancreas. Stimulates the liver to secrete HC03 into the bile. CCK: Occurs in response to fat and protein content of chyme in duodenum. Stimulates the production of pancreatic enzymes. Enhances secretin. Stimulates contraction of the sphincter of Oddi.

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Digestion and Absorption of Carbohydrates

Salivary amylase:

Begins starch digestion. Digests starch to oligosaccharides. Oligosaccharides hydrolyzed by brush border enzymes.

Insert fig. 18.32

Pancreatic amylase:

Glucose is transported by secondary active transport with Na+ into the capillaries.

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Digestion and Absorption of Protein

Digestion begins in the stomach when pepsin digests proteins to form polypeptides. In the duodenum and jejunum:

Endopeptidases cleave peptide bonds in the interior of the polypeptide: Trypsin. Chymotrypsin. Elastase. Exopeptidases cleave peptide bonds from the ends of the polypeptide: Carboxypeptidase. Aminopeptidase.

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Digestion and Absorption of Protein

(continued)

Free amino acids absorbed by cotransport with Na+. Dipeptides and tripeptides transported by secondary active transport using a H+ gradient to transport them into the cytoplasm. Hydrolyzed into free amino acids and then secreted into the blood.

Insert fig. 18.33

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Digestion and Absorption of Lipids

Arrival of lipids in the duodenum serves as a stimulus for secretion of bile. Emulsification:

Bile salt micelles are secreted into duodenum to break up fat droplets.

Pancreatic lipase and colipase hydrolyze triglycerides to free fatty acids and monglycerides.

Colipase coats the emulsification droplets and anchors the lipase enzyme to them. Form micelles and move to brush border.

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Digestion and Absorption of Lipids

(continued)

Free fatty acids, monoglycerides, and lysolecithin leave micelles and enter into epithelial cells.

Resynthesize triglycerides and phospholipids within cell.

Combine with a protein to form chylomicrons.

Secreted into central lacteals.

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Transport of Lipids

In blood, lipoprotein lipase hydrolyzes triglycerides to free fatty acids and glycerol for use in cells. Remnants containing cholesterol are taken to the liver.

Form VLDLs which take triglycerides to cells. Once triglycerides are removed, VLDLs are converted to LDLs.

LDLs transport cholesterol to organs and blood vessels.

HDLs transport excess cholesterol back to liver.

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Absorption of Fat

Insert fig. 18.36