Human Physiology

1. Human Physiology The Digestive System

2. GI-introduction The gastrointestinal (GI) system consists of the digestive tract: mouth, esophagus, stomach, small intestine, large intestine, rectum, and anus; and associated glands: salivary glands, pancreas, and liver.

3. GI functions GI functions include ingestion and transport, digestion, and absorption of nutrients and excretory functions.

4. GI-introduction • Inside gastrointestinal (GI) tract, food is broken down by hydrolysis into molecular monomers • Absorption of monomers occurs in small intestine

5. Segments of the GI tract (1) • Mouth • Pharynx • Esophagus • Stomach

6. Segments of the GI tract (2) • Small intestine is a tube about 4 centimeters in diameter and 6 to 7 meters long. It is composed of the duodenum (about 25 centimeters), the jejunum (about 2.5 meters) and the ileum (about 3.5 meters) • Large intestine (colon is about 1.25 meters long. It consists of the cecum, the ascending colon, the transverse colon, the descending colon, the rectum, and the anus • Sphincters between segments

7. Segments of the GI tract (3)

8. Layers of the GI tract From esophagus to anus, the tube consists of concentrically arranged layers of muscle, nervous, and mucosal tissue. The tissue layers of the GI tract are, from serosal to luminal side: • Serosa • Longitudinal muscle • Myenteric plexus • Circular muscle • Submucosa • Submucosal plexus • Muscularis mucosae • Mucosa

9. Layers of the GI tract

10. Layer: Myenteric Plexus The myenteric plexus (Auerbach's plexus) is a plexus of nerve cells lyingbetween the muscle coats.

11. Layer: Submucosal Plexus The submucosal plexus (Meissner's plexus) is a plexus of nerve cells lying in the submucosa.

12. Layer: Mucosa The surface of the mucosa layer communicates with the lumen of the GI tract. The mucosa contains epithelial cells that have endocrine, exocrine, secretory, and absorptive functions. It has a large surface area across which materials are exchanged. This area is greatly increased by the finger-like extensions of the epithelium that form the villi and invaginations that form the crypts.

13. Segment: Mouth In the mouth, food is chewed, reduced to small particles, mixed with saliva, and formed into a bolus in preparation for swallowing. Salivary enzymes (amylase and lingual lipase) initiate digestion.

14. Segment: Stomach Stomach mixes the food contents with the gastric exocrine secretions. Gastric secretions include HCl and pepsin, which initiate protein digestion.

15. Stomach Secretory cellsSecretion product• surface mucous cells, mucous neck cells mucus, HCO3-• oxyntic (= parietal) cells HCl, intrinsic factor• chief (= peptic) cells pepsinogen, gastric lipase• neuroendocrine cells G cells gastrin D cells somatostatin

16. Stomach Digestive functions • digestive enzymes: pepsinogen (endopeptidase) gastric lipase • HCl secretion (parietal cells): acidic environment for pH optimum (1.8-3.5) of digestive enzyme pepsin (activated from pepsinogen) and lingual lipase (pH optimum 4). HCl softens food • Intrinsic factor: binds Vit B12 and protects from gastric and intestinal digestion Protective functions • gastric acidity: antibacterial • mucus and HCO3-: protective layer against damage of gastric mucosa by low pH

17. The Intestine

18. Segment: Small Intestine In the small intestine (duodenum, jejunum, ileum), contractile activity servesto mix the chyme with the alkaline exocrine secretions of the intestine, pancreas, and liver. These secretions contain a number of digestive enzymes, including proteases, amylases, and lipases. Protein, lipids, carbohydrate, vitamins, water, and electrolytes.

19. Segment: Large Intestine In the large intestine (cecum, colon, rectum, anal canal), colonic contractile activity transports chyme slowly and mixes it thoroughly, exposing it to the absorptive surface where most of the remaining fluid is absorbed.

20. Segment: Large Intestine

21. Segment: Sphincters • Sphincters, or regions with sphincter-like activity serve to regulate the flow of GI contents and to prevent back flux of material from the more distal segments. • Fecal continence is controlled by the internal and external anal sphincters.

22. Other Organs of the GI System • The following structures also play an important role in GI function: • Liver: synthesis and secretion of bile. • Gall Bladder: storage, concentration, and expulsion of bile. • Pancreas: synthesis and secretion of digestive enzymes and alkaline fluid

23. Regulation of GI Function The functions of the GI tract are regulated by both: • humoral mechanisms(peptides secreted by the endocrine cells of the GI tract) • neural mechanisms submucosal plexus-Meissner's and myenteric plexus (Auerbach's) • extrinsic nervous control (sympathetic and parasympatheticis division)

24. The GI peptides fall into two families basedon similarities of their amino acid sequences. These are: • gastrin-cholecystokinin family • and the secretin family

25. Gastrin (1) Gastrin is secreted by the G cells, which are present in the antrum of the stomach and in the duodenum. Its plasma concentration rises during the digestive phase.

26. Gastrin (2) Gastrin is released by G cells after: - vagal stimulation, - distention of the stomach, - presence of protein digestion products in the stomach.

27. Gastrin (3) Gastrin release is inhibited by somatostatin (SS), increasing in response to acidification of the stomach contents. Gastrin is the only GI hormone known to be released by direct neural stimulation.

28. Actions of Gastrin Gastrin has two major physiologic actions: - stimulates hydrochloric acid secretion by the parietalcells - trophic effect on gastric and intestinal mucosa.

29. Cholecystokinin (1) CCK is synthesized in the cells of the duodenal and jejunal mucosa. The principal stimuli for CCK release in the smallintestine are: • products of fat digestion • products of protein digestion in the small intestine.

30. Cholecystokinin (2) CCK has five physiologic actions: stimulus for pancreatic enzyme secretion stimulates pancreatic fluid and bicarbonate secretion stimulus for bile expulsion from the gallbladder inhibits gastric emptying trophic action on the pancreas • Secretin • Secretin is a 27-amino acid peptide with a helical configuration. • It has some amino acid sequences that are the same as those found in VIP, glucagon, and GIP. The entire molecule is required for full biologic activity.

31. Cholecystokinin (3)

32. Secretin (1) • stimulates pancreatic fluid and bicarbonate secretion • stimulates hepatic ducts to secrete bicarbonate • stimulates trophic action on the pancreas • inhibits gastric acid secretion, ( inhibiting both gastrin release and gastrin-stimulated acid secretion )

33. Secretin (2)

34. Gastric Inhibitory Peptide GIP Gastric Inhibitory Peptide (GIP) is secreted by endocrine cells in the duodenum and jejunum. It is a linear peptide with 42 amino acid residues and is a member of the same peptide family as secretin.

35. Important actions of GI hormones Action Gastrin CCK Secretin GIP Acid secretion S I I Pancreatic HCO3- secretion S S Pancreatic enzyme secretion S Bile HCO3- S Gallbladder contraction S Gastric emptying I Mucosal growth S Pancreatic growth S S S = stimulates; I = inhibits

36. Additional GI hormones Hormones are produced by enteroendocrine cells in the GI tract in stomach, small and large intestine Motilin Serotonin Substance P Vasoactive intestinal peptide (VIP) Neurotensin increases intestinal motility increases intestinal motility increases intestinal motility neurotransmitter for intestinal smooth muscle stimulates secretion of water and ions decreases intestinal motility increases blood flow to ileum 16

37. Additional GI hormones (cont.) stimulate hepatic glycogenolysis stimulates hepatic glycogenolysis local inhibition of other endocrine cells (e.g. G-cells) inhibits secretion of HCl increases epithelial growth increases secretion of HCl Glucagon Entero-glucagon Glicentin (glucagon-like substance) Somatostatin Urogastrone (Epidermal Growth Factor) Histamine

38. Pancreatic Hormones Pancreatic hormones:insulin glucagon somatostatin produced and secreted (endocrine pancreatic secretion) by the islets of Langerhans essential for the regulation of metabolism

39. Digestion The food we eat must first be hydrolyzed to products of smaller size that can be absorbed by the mucosa of the small intestine; this process is known as digestion.

40. Carbohydrates (1) Dietary intake of carbohydrates consists of: - starch (polymer of glucose and fructose) -60% - sucrose (glucose and fructose unites)-30% - lactose (galactose and glucose units)-10 %

41. Carbohydrates (2) Dietary intake of carbohydrates- total of about 350 to 450 grams of carbohydrates per day. Starch digestion begins in the mouth with the action of salivary amylase. Most of the starch digestion takes place in the lumen of the small intestine, using pancreatic amylase.

42. Carbohydrates (3) The average diet also contains a small amount of unavailable carbohydrates, including indigestible oligosaccharides (eg, raffinose) and dietary fiber (cellulose and hemicellulose). These carbohydrates are not digested in the small intestine. They pass to the colon, where they arefermented by bacterial enzymes. Fermentation products include: -acetic acid, - propionic acid, -butyric acid

43. Proteins and Peptides(1) The initial phase of protein digestion occurs in the stomach (gastric phase) and is carried out by pepsin. Pepsin is secreted by chief cells in an inactive form called pepsinogen.

44. Proteins and Peptides (2) Peptide digestion occurs in the small intestine. It is complicated because there is peptidase activity both at brush borders and within the cytoplasm of intestinal mucosa cells. Aminopeptides must be absorbed by specific amino acid and peptide transport systems. Intracellular peptidases hydrolyze the absorbed peptides.

45. Lipids Dietary fat is present mostly as triglycerides and is insoluble in water. Fat is converted into water-soluble material after triglycerides are digested to fatty acids and monoglycerides, and by the formation of micelles with bile acids.

46. Lingual Lipase Is secreted by glands located at the root of the tongue and the parotid glands. It is more specific for medium fatty acids and therefore is more important in the digestion of milk fat in the newborn.

47. Gastric Lipase Cells of the stomach secrete a gastric lipase that is the main preduodenal lipase in the adult. The preduodenal lipases appear to be especially important during the neonatal period. During this time pancreatic lipase is not yet very active and milk fat must be digested.

48. Pancreatic Lipase Is secreted in active form into the duodenum Is almost completely inactivated by bile acid colipase, a protein present in the pancreatic juice, is activated by trypsin and prevents the inactivation of lipase.

49. Absorption (1) Absorption is the transport of solute and water from the gut lumen, across the intestinal epithelium, into the lymph or venous blood. Most absorption takes place in the small intestine.

50. Absorption (2) Daily absorption : 200 to 300 grams of carbohydrates 100 grams of amino acids 100 grams of fat 100 grams of electrolytes, 7 or 8 liters of water. ( 10 times more foods and three times more water could be absorbed per day in the small intestine. Also, the colon is able to absorb great quantities of water and ions ).