GI Physiology IV: Early Intestinal Phase of Digestion

1. GI Physiology IV:Early Intestinal Phase of Digestion • IDP/DPT GI Course, Fall 2011 • Jerome W. Breslin, Ph.D. • LSUHSC-NO Department of Physiology • MEB 7208 (1901 Perdido St.) • 568-2669 • jbresl@lsuhsc.edu

2. Required Reading • Kim Barrett, Gastrointestinal Physiology • Chapter 5 - section on cellular basis of transport • Chapter 9 • Chapter 15 • Chapter 16

3. Outline - Lecture 4 • Quick review of some things from lecture 3 • The Small Intestine & Early Intestinal Phase of Digestion • Regulation: Secretin and Cholecystokinin • Motility of the Small Intestine • Intestinal Digestion and Absorption • Proteins, Carbohydrates, Lipids • Water Soluble Vitamins • Water and Electrolytes

4. Figure 15-34 Video endoscopy has greatly enhanced our understanding of normal processes in the gut, and reveals complications resulting from disease.

6. Intestinal Phase • Initiated by entry of chyme from the stomach into the duodenum. • Reflex response to distention, low pH, osmolarity, and various digestive products. • Responses: • Modification of osmolarity of chyme. • Modification of luminal pH. • Secretion of enzymes. • Secretion of emulsifying agents. • Regulated patterns of motility.

7. Figure 15-24 (CCK, Secretin) Delivery of acid and nutrients into the small intestine initiates signaling that slows gastric motility and secretion which allows adequate time for digestion and absorption in the duodenum.

8. The Small Intestine • GI section between pyloric sphincter and ileal-cecal valve. • 3 sections – duodenum, jejunum & ileum. • Digestion, secretion and absorption all occur here. • Final site of digestion. • Neuro-hormonal regulation of both secretion and motility.

9. Figure 15-7 nutrients By projecting into the lumen, the villi increases the surface area for absorption of nutrients. Microvilli [aka brush border] fringe the villi to further increase surface area.

12. Figure 15-27 Secretin’s receptors are found in the pancreas, which responds with additional bicarbonate delivery: gastric motility and secretion are inhibited. Secretin is secreted by the S Cells in the Crypts of Lieberkühn.

14. Figure 15-31 Cholecystokinin (CCK) stimulates the gallbladder, which responds by contracting and delivering more bile to the duodenum through the sphincter of Oddi, which relaxes (opens) in response to CCK. CCK is secreted by the intestinal mucosa.

16. Figure 15-28 • Cholecystokinin’s receptors are located: • in the pancreas, which • responds with additional • enzyme delivery • in the gallbladder, which • contracts to deliver more • bile • in the sphincter • of Oddi, which relaxes to • facilitate delivery of the enzymes and bile salts

23. Intestinal Motility • Intestinal motility is coordinated by the enteric nervous system and modified by long and short reflexes and hormones. • During and shortly after a meal, intestinal contents are mixed by segmenting movements of the intestinal wall. • After food is digested and absorbed, segmentation is replaced by peristalsis moving undigested material from small intestine into large intestine.

24. Fig 9-4 Barrett

25. Small Intestinal Motility • SEGMENTATION/MIXING • stationary contraction/relaxation cycles • subdivision and mixing of chyme • pacemaker cells generate basic electrical rhythm • BER decreases along length of intestine • duodenum 10-12/min • Ileum 7-9/min • slow migration toward large intestine

26. Small Intestinal Motility (continued) • MIGRATING MYOELECTRIC COMPLEX • Peristaltic activity that replaces segmentation at completion of absorption • Repeated waves traveling about 2 feet • Migrates down small intestine taking about 2 hr to reach large intestine • Process repeated from beginning • candidate hormone: motilin

27. Fasting Motor Pattern: “Migrating Myoelectric Complex” (MMC) From Stomach to the Ileum ~100 minute cycle: Phase I (~50 min) = quiescent Phase II (~40 min) = irregular contractions Phase III (5-10 min) = forward contractions

28. Regulation of MMCs is poorly understood: 1. Independent of vagus and splanchnic innervation 2. Phase III of the MMC is related to elevated plasma Motilin (secreted by M cells).

34. Just before vomiting, BER is suspended. Then, rapid burst of electrical activity moving in the oral direction.

35. Laxatives (Cathartics) cause increased spike potentials, and more forward contractions. In the above example, castor oil can act as a laxative vs. a control oil (triolein).

36. Intestinal Digestion • Chyme mixed with secretions from pancreas, liver & duodenum. • Secretions modify the pH, osmolarity, and continue the digestive process to make the digested material ready for absorption into the intestinal blood or lymphatic system. • Type and volume of secretions depend on the constitution of the chyme.

37. Digestion in the Gut 3 SUB-PHASES OF INTESTINAL DIGESTION • LUMINAL • Mixing of chyme with enzymes • BRUSH BORDER • Specific enzymes present on the luminal surface of the enterocytes • CYTOSOLIC/INTRACELLULAR • Intracellular digestion in the enterocytes

39. Digestion in the Gut • Proteins: • All 3 phases, luminal, brush border and cytosolic digestion may be involved • Carbohydrates: • Only luminal and brush border digestion – no intracellular digestion by the enterocyte • Lipids: • All digestion is luminal; triglyceride is re-formed in the enterocyte!

40. Figure 15-26 Were digestive enzymes synthesized in their active form, they would digest the very cells that make them. Hence, inactive precursors (e.g., trypsinogen) become activated (trypsin).

42. Absorption in the Gut • Proteins: • Active transport of amino acids and small peptides (< 5 amino acids). • Carbohydrates: • Uptake of monomers only • Active transport of glucose; facilitated diffusion for other sugars. • Lipids: • Uptake of free fatty acids and glycerol. • Mechanism of uptake by the enterocytes is probably diffusion.

43. Three sites of protein digestion: 1. Lumen 2. Brush Border 3. Cytoplasm PepT1

44. Short peptide uptake coupled to proton transport Barrett Fig. 15-8

45. Activation of Proteases in the Small Intestine Fig. 15-6

46. Protein Digestion • Proteases stored in inactive form in pancreas & secreted in response to neurohormonal stimulation. • Pancreatic trypsinogen converted to active form by duodenal brush-border enterokinase. • Trypsin activates all other luminal peptidases. • Digestion of oligopeptides in lumen and small peptides at brush border. • Uptake of free amino acids, di- and tri-peptides by active transport mechanisms. • Cytosolic degradation of di- and tri-peptides.

47. Amino Acids, Dipeptides, and Tripeptides are Absorbed by Specific Transporters. Cytoplasmic Peptidases Barrett, Fig. 15-8 There are also many brush border transporters for individual amino acids.

49. Carbohydrate • Polysaccharides digested in duodenal lumen by pancreatic amylase to produce oligosaccharides and disaccharides. • Brush border digestion of polymers by specific amylases and disaccharidases forms monosaccharides. • Simple sugars taken up by active transport processes into enterocytes. • NO uptake of disaccharides or oligosaccharides!

50. Carbohydrate Digestion & Absorption (continued) • Sugars enter blood stream by facilitated diffusion or active transport mechanisms. • Glucose in the intestinal lumen stimulates the release of GIP (Glucose dependent insulinotropic peptide or gastrointestinal inhibitory peptide). • GIP stimulates the release of insulin from the pancreas in anticipation of glucose in the portal blood. • GIP inhibits gastric motility to facilitate digestion and absorption from the GI tract.