1. Chapter 18
The Digestive System

2. Functions of the GI Tract
Motility:
Movement of of food through the GI tract.
Ingestion:
Taking food into the mouth.
Mastication:
Chewing the food and mixing it with saliva.
Deglutition:
Swallowing the food.
Peristalsis:
Rhythmic wave-like contractions that move food through GI tract.

3. Functions of the GI Tract
Secretion:
Includes both exocrine and endocrine secretions.
Exocrine:
HCl, H20, HC03-, bile, lipase, pepsin, amylase, trypsin, elastase,and histamine, etc. are secreted into the lumen of the GI tract.
Endocrine:
Stomach and small intestine secrete hormones to help regulate the GI system.
Gastrin, secretin, CCK, GIP, GLP-1, guanylin, VIP, and somatostatin, etc.

4. Functions of the GI Tract
Digestion:
Breakdown of food particles into subunits (chemical structure change).
Absorption:
Process of the passage of digestion (chemical subunits) into the blood or lymph.
Storage and elimination:
Temporary storage and elimination of indigestible food.

5. Digestive System GI tract divided into:
Alimentary canal.
Accessory digestive organs.
GI tract is 30 ft long and extends from mouth to anus.

6. Layers of GI Tract
Mucosa
Submucosa
Muscularis
Serosa

7. Mucosa Lines the lumen of GI tract.
Consists of simple columnar epithelium.
Lamina propria: Thin layer of connective tissue containing lymph nodes.
Muscularis mucosae:
Thin layer of smooth muscle responsible for the folds.
Increase surface area.
Goblet cells:
Secrete mucus.

8. Submucosa Thick, highly vascular layer of connective tissue.
Absorbed molecules enter the blood and lymph vessels in this layer.
Submucosal plexuses:
Provide autonomic nerve supply to the muscularis mucosae.

9. Muscularis
Responsible for segmental contractions and peristaltic movement through the GI tract.
Inner circular smooth muscle.
Outer longitudinal smooth muscle.
Contractions of these layers move food through the tract and pulverize the food.
Myenteric plexus located between 2 muscle layers.
Major nerve supply to GI tract.

10. Serosa Binding and protective outer layer.
Consists of connective tissue.

11. Regulation of the GI Tract
Extrinsic innervation:
Parasympathetic Nervous System:
Stimulate motility.
Sympathetic Nervous System:
Reduce peristalsis and secretory activity.
Enteric Nervous System:
Submucosal plexus and myenteric plexus:
Local regulation of the GI tract.
Paracrine secretion:
Molecules acting locally.
Hormonal secretion:
Secreted by the mucosa.

12. Esophagus Deglutition begins as a voluntary activity.
Larynx is raised.
Epiglottis covers the entrance to the respiratory tract.
Involuntary muscular contractions and relaxations in the esophagus follow.

13. Esophagus Connects pharynx to the stomach.
Upper third contain skeletal muscle.
Middle third contains a mixture of skeletal and smooth muscle.
Terminal portion contains only smooth muscle.

14. Esophagus Peristalsis:
Produced by a series of localized reflexes in response to distention of wall by bolus.
Wave-like 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.

15. Stomach Most distensible part of GI tract. Empties into the duodenum.
Functions of the stomach:
Store food.
Initiate digestion of proteins.
Kill bacteria.
Move food (chyme) into intestine.

16. Stomach Contractions of the stomach churn chyme.
Mix chyme with gastric secretions.
Push food into intestine.

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

18. Gastric Glands Gastric Juice: Goblet cells: mucus.
Parietal cells: HCl and intrinsic factor.
Chief cells: pepsinogen.
Enterochramaffin-like cells (ECL): histamine and serotonin.
G cells: gastrin.
D cells: somatostatin.

19. HCl Production
Parietal cells secrete H+ into gastric lumen by primary active transport trough H+ / K+ ATPase pump.
Parietal cell’s basolateral membrane couples Cl- against its electrochemical gradient by coupling its transport with HC03-.

20. HCl Production HCL production is stimulated:
Indirectly by gastrin.
Indirectly by ACh.
ACh and gastrin stimulate release of histamine.
Histamine:
Stimulates parietal cells to secrete HCL.

21. HCL Functions Makes gastric juice very acidic.
Optimum pH of of stomach is 2.0.
Denatures ingested proteins (alter tertiary structure) so become more digestible.
Activates pepsinogen to pepsin.

22. 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.

23. Protective Mechanisms of Stomach
Parietal and chief cells impermeable to HCL.
Alkaline mucus contains HC03-.
Tight junctions between adjacent cells.
Rapid rate of cell division (3 days).
Prostaglandins which inhibit gastric secretions.

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

25. Absorption in Small Intestine
Duodenum and jejunum:
Carbohydrates, amino acids, lipids, Ca++, and Fe++.
Ileum:
Bile salts, vitamin B12, electrolytes, and H20.

26. 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.

27. Intestinal Contractions and Motility
2 major types of contractions occur in the small intestine:
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.

28. Contractions of Intestinal Smooth Muscles
Occur automatically in response to endogenous pacemaker activity.
Rhythm of contractions is paced by graded depolarizations.
Slow waves produced by interstitial cells of Cajal.
Slow waves spread from 1 smooth muscle cell to another through nexuses.

29. Contractions of Intestinal Smooth Muscles
Slow waves decrease in amplitude as they are conducted.
May stimulate contraction in proportion to the magnitude of depolarization.
When slow waves above threshold, it triggers APs by opening of VG Ca++ channels.

30. Smooth Muscle Action Potentials
At threshold, VG Ca++ channels open.
Repolarization: VG K+ channels open.
Stimulates contraction.
Parasympathetic NS, stretch and gastrin increase the amplitude of slow waves.
Stimulate APs.
SNS decrease APs.

32. Large Intestine
Aid absorption of H20, electrolytes, vitamin B complex vitamins, vitamin K, and folic acid.
Secrete H20, via active transport of NaCl.
Guanylin stimulates secretion of Cl- and H20 and inhibits absorption of Na+.
Contains lymphocytes, lymph nodes, goblet cells.

33. 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 in the ileum.
Large intestine:
Absorption of H20 occurs passively as a result of the osmotic gradient created by active transport of Na+ and Cl-.

34. Defecation Waste material passes to the rectum. Defecation reflex:
Longitudinal rectal muscle contract to increase rectal pressure.
Relaxation of of internal anal sphincter.
Excretion is aided by contractions of abdominal and pelvic skeletal muscles.
Push feces from the rectum.

35. Structure of Liver Liver largest internal organ.
Hepatocytes form hepatic plates that are 1 – 2 cells thick.
Plates separated by sinusoids.
More permeable than other capillaries.
Contain phagocytic Kupffer cells.

36. Hepatic Portal System
Products of digestion that are absorbed are delivered to the liver.
Drain into the hepatic portal vein.
¾ blood is deoxygenated.
Hepatic vein drains liver.

37. Enterohepatic Circulation
Variety of exogenous compounds are secreted by the liver into the bile ducts.
Can excrete these compounds into the intestine with the bile.
Eliminated in the feces.

38. Table 18.4 Major Categories of Liver Function
Functional Category Actions
Detoxication of Blood Phagocytosis by Kupffer cells
Chemical alteration of biologically active molecules (hormones and drugs)
Production of urea, uric acid, and other molecules that are less toxic than parent compounds
Excretion of molecules in bile
Carbohydrate Metabolism Conversion of blood glucose to glycogen and fat
Production of glucose from liver glycogen and from other molecules (amino acids, lactic acid) by gluconeogenesis
Secretion of glucose into the blood
Lipid Metabolism Synthesis of triglyceride and cholesterol
Excretion of cholesterol in bile
Production of ketone bodies from fatty acids
Protein Synthesis Production of albumin
Production of plasma transport proteins
Production of clotting factors (fibrinogen, prothrombin, and others)
Secretion of Bile Synthesis of bile salts
Conjugation and excretion of bile pigment (bilirubin)

39. Bile Production and Secretion
The liver produces and secreted 250 – 1500 ml of bile/day.
Bile pigment (bilirubin) 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.

40. Bile Production and Secretion
Converted by bacteria in intestine to urobilinogen.
Urobilogen is absorbed by intestine and enters the hepatic vein.
Recycled in bile or general circulation.
Filtered by kidneys into the urine.
Produces amber color.

41. Bile Production and Secretion
Bile acids are derivatives of cholesterol.
Major pathway of cholesterol breakdown in the body.
Principal bile acids are:
Cholic acid.
Chenodeoxycholic acid.
Combine with glycine or taurine to form bile salts.
Bile salts aggregate as micelles.
95% of bile acids are absorbed by ileum.

42. 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.

44. 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 ketones.

45. 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 and blood clotting.

46. 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.

47. Pancreas Exocrine: Endocrine: Acini: secrete pancreatic juice.
Secrete insulin and glucagon.

48. Pancreatic Juice Contain H20 , HC03- and digestive enzymes.
Enzyme Zymogen Activator Action
Trypsin Trypsinogen Enterokinase Cleaves internal peptide bonds
Chymotrypsin Chymotrypsinogen Trypsin Cleaves internal peptide bonds
Elastase Proelastase Trypsin Cleaves internal peptide bonds
Carboxypeptidase Procarboxypeptidase Trypsin Cleaves last amino acid from carboxyl-terminal end of polypeptide
Phospholipase Prophospholipase Trypsin Cleaves fatty acids from phospholipids such as lecithin
Lipase None None Cleaves fatty acids from glycerol
Amylase None None Digests starch to maltose and short chains of glucose molecules
Cholesterolesterase None None Releases cholesterol from its bonds with other molecules
Ribonuclease None None Cleaves RNA to form short chains
Deoxyribonuclease None None Cleaves DNA to form short chains

49. 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.

50. 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.

51. 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.

52. Cephalic Phase Sight, smell, and taste of food. Activation of vagus:
Stimulate chief cells to secrete pepsinogen.
Directly stimulate G cells to secrete gastrin.
Directly stimulate ECL cells to secrete histamine.
Indirectly stimulate parietal cells to secrete HCl.

53. Gastric Phase Arrival of food in stomach stimulates the gastric phase.
Gastric secretion stimulated by:
Distension.
Chemical nature of chyme (amino acids and peptides).
Activation of vagus:
Stimulate G cells to secrete gastrin.
Stimulate chief cells to secrete pepsinogen.
Stimulates ECL cells to secrete histamine.
Histamine stimulates secretin of HCl.
Positive feedback effect.

54. Gastric Phase
Secretion of HCl is also regulated by a negative feedback effect:
HCl secretion decreases if pH < 2.5.
At pH of 1.0, gastrin secretion ceases.
D cells stimulate secretion of somatostatin.
Inhibits secretion of gastrin.

55. Intestinal Phase
Inhibits gastric activity when chyme enters the small intestine.
Arrival of chyme increases osmolality and distension.
Activate sensory neurons of vagus and produce an inhibitory neural reflex.
In the presence of fat, enterogasterone inhibits gastric motility and secretion.

56. Intestinal Phase Hormone secretion: Inhibit gastric activity:
Somatostatin.
CCK.
GLP-1.

57. Enteric Nervous System
Submucosal and myenteric plexuses contain 100 million neurons.
Include preganglionic parasympathetic axons, ganglion cell bodies, postganglionic sympathetic axons, and sensory neurons.

58. Enteric Nervous System
Peristalsis:
ACh and substance P stimulate smooth muscle contraction.
NO, VIP, and ATP stimulate smooth muscle relaxation.

59. Paracrine Regulators of the Intestine
Serotonin:
Stimulates intrinsic afferents which send impulses into intrinsic nervous system and activate motor neurons.
Motilin:
Stimulates contraction of the duodenum and stomach antrum.
Guanylin:
Activates cGMP which stimulates the intestinal cells to secrete Cl- and H20.
Inhibits the absorption of Na+.

60. Intestinal Reflexes Gastroileal reflex: Ileogastric reflex:
Increased gastric activity causes increased motility of ileum and movement of chyme.
Movement through ileocecal sphincter.
Ileogastric reflex:
Distension of ileum causes decreased gastric motility.
Intestino-intestinal reflex:
Overdistension in 1 segment, causes relaxation of rest of intestine.

61. Secretion of Bile
Secretion of pancreatic juice and bile is stimulated by:
Secretin:
Occurs in response to duodenal pH < 4.5.
Stimulates the liver to secrete HC03- into the bile.
CCK:
Occurs in response to fat and protein.
Enhances secretin.
Stimulates contraction of the sphincter of Oddi.

62. Digestion and Absorption of Carbohydrates
Salivary amylase:
Begins starch digestion.
Pancreatic amylase:
Digest starch to oligosaccharides
Oligosaccharides hydrolyzed by brush border enzymes.
Transported by secondary active transport with Na+.

63. Digestion and Absorption of Protein
Digestion begins in the stomach when pepsin digestion 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.

64. Digestion and Absorption of Protein
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.

65. Digestion and Absorption of Lipids
Arrival of lipids in the duodenum serves as a stimulus for secretion of bile.
Emulsification:
Bile salts 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.

66. Digestion and Absorption of Lipids
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.

67. Transport of Lipids
In blood, lipoprotein lipase hydrolyzes triglycerides to free fatty acids and glycerol for use in cells.
Remnants taken to liver.
Form VLDL which take triglycerides to cells, and converted to LDLs.
LDLs transport cholesterol to organs and blood vessels.
HDLs transport excess cholesterol back to liver.