1. Definitions Digestion:
Breakdown of ingested nutrients into forms which can be absorbed
Absorption:
Transport of small molecules from the GI tract into the blood
Motility:
Patterns of GI contraction and relaxation; tone of sphincters
Secretion:
Control of secretion of digestive enzymes & regulatory hormones

2. Gastrointestinal functions
fig 15-2
Digestion: mouth, stomach, small intestine Absorption: small intestine
Secretion: mouth, stomach, small intestine Motility: entire GI tract

3. GI functions: mouth, esophagus, stomach, pancreas
fig 15-3a

4. GI functions: biliary system, small intestine, large intestine
fig 15-3b

5. Fluid exchanges Oral intake: 1200 ml/day Secretions: 7000 ml/day
Absorption: 8100 ml/day
Feces: 100 ml/day
Significance:
potential for  fluid loss if absorption compromised
fig 15-5

6. Microanatomy of GI tract
Mucosa: absorptive epithelium, endocrine/exocrine cells, muscularis mucosa
Submucosa: blood/lymph vessels, submucosal nerve plexus
Muscularis externa: circular muscle, myenteric nerve plexus, longitudinal muscle
Serosa, mesentery
fig 15-6

7. Intestinal structure: villi
fig 15-7
Surface area: “tennis court”, villi, microvilli (next)
Life cycle: ~5 day life cycle, generated at base of villi, shed from top

8. The intestinal cell
fig 15-8
Surface enzymes: released into intestine as cells released
Microvilli = “brush border”

9. Carbohydrate digestion & absorption
Source:
~ half of daily caloric intake
~ 70% as starch (potatoes, pasta, rice, bread), ~ 30% as sucrose, lactose
cellulose:  glucose links not digestible, forms “bulk” of diet
Starch:  14, 16 links hydrolyzed by salivary & pancreatic amylase  maltose, maltotriose
Intestinal disaccharidases:
maltase: hydrolyses maltose, maltotriose  glucose
sucrase: hydrolyses sucrose  glucose + fructose
lactase: hydrolyses lactose  glucose + galactose
Absorption: from small intestine into blood capillaries
Glucose, galactose by Na+ linked cotransport at luminal border
Fructose by facilitated diffusion at luminal border
Glucose, galactose, fructose by facilitated diffusion at basolateral surface

10. Protein digestion & absorption
Source:
~ 20% of daily caloric intake
Digestion:
gastric *pepsin (endopeptidase, acid pH optimum)
pancreatic *trypsin & *chymotrypsin (endopeptidase, alkaline pH optimum)
pancreatic carboxypeptidase (exopeptidase)
intestinal aminopeptidase (exopeptidase)
Absorption:
small intestine, into blood capillaries
aminoacids by Na+ linked cotransport, di- & tri-peptides by H+ linked cotransport at luminal border
peptides hydrolyzed in intestinal cell
aminoacids by facilitated diffusion at basolateral membrane
* secreted as inactive precursor (next slide)

11. Pepsin, trypsin, chymotrypsin activation
fig 15-21
fig 15-26

12. Lipid digestion & absorption
Source:
Triglyceride, ~30% of daily caloric intake
Digestion:
pancreatic lipase (triglyceride  2-monoglyceride + 2 fatty acids)
lipases act at fat water interfaces & depend on fat surface area
Emulsification:
mechanical disruption (chewing, motility of stomach & small intestine
amphipathic emulsifiers (bile salts, bile phospholipid)

13. Anatomy of bile & pancreatic ducts
Bile: produced in liver, stored in gall bladder
Composition: bile salts, phospholipids, cholesterol, bicarbonate, bile pigments (heme metabolism), drug metabolites & trace metals
fig 15-4

14. Bile salt actions Bile: produced in liver, stored in gall bladder
fig 15-10
fig 15-9
Bile: produced in liver, stored in gall bladder
Emulsification in duodenum & upper intestine

15. Triglyceride digestion
Colipase:
from pancreas, binds lipase to emulsion droplet
Micelles:
4-7 nm diameter
store of fatty acids & monoglycerides for transport into epithelial cells
fig 15-11

16. Triglyceride absorption
Resynthesis:
2 FA + MG  TG
on smooth endoplasmic reticulum
Chylomicrons:
80-90% triglyceride + phospholipid + cholesterol, coated with amphipathic proteins
released by exocytosis into lacteal
metabolized by fat & liver
fig 15-12

17. Vitamins, water absorption
passively absorbed down osmotic gradient
GI wall permeable, therefore GI contents isosmotic
mostly from small intestine
Vitamins:
lipid soluble (vit A, D, E, K) with lipids (micelles, diffusion, chylomicrons)
water soluble (vit B, vit C) diffusion, mediated transport
vit B12 with intrinsic factor (from stomach parietal cells), endocytosis

18. Regulation of secretion: general
Luminal stimuli:
1. distension of wall (volume stimulates mechanoreceptors)
2. osmolality of chyme (osmoreceptors)
3. acidity of chyme (chemoreceptors)
4. chyme concentration of digestive products: monosaccharides, fatty acids, peptides, aminoacids (chemoreceptors)

19. Neural regulation Long reflexes: mostly parasympathetic
Short reflexes:
enteric nervous system, myenteric & submucosal plexuses, conduct impulses up & down GI tract
fig 15-13

20. Hormonal regulation (simplification of table 15-4)
Gastrin
Cholecystokinin
Secretin
GIP
Structure
peptide
Source
G cells in stomach
small intestine epithelium
Release stimulus
Parasymp NS, stomach AA’s, peptides
( pH inhibits)
FA’s, AA’s in small intestine;
 osmolality
 pH in small intestine
 glucose, AA’s in small intestine
Actions
 stomach enzymes, H+, motility
 secretion of bile, pancreatic enzymes, relaxes sphincter of Oddi
 secretion of bile & pancreatic HCO3-
 insulin secretion
GIP = glucose insulinotropic peptide (gastric inhibitory peptide)
Cholecystokinin & secretin potentiate each others’ actions

21. Saliva Composition: fluid, mucus, amylase Functions:
moistening food, preventing tooth decay (lysozyme, IgA), starting starch digestion
Regulation of release:
parasympathetic NS  (responding to sight, smell, thought of food)
sympathetic NS  (transient); ( saliva flow,  blood flow)
acidic fruit juices, mechanical contact

22. Gastric secretion
fig 15-17
fig 15-16
Structure: fundus, body, antrum; lower esophageal & pyloric sphincters
Goblet cells  mucus, Parietal cells  HCl & intrinsic factor,
Chief cells  pepsinogen, G cells  gastrin

23. HCl secretion by parietal cells
fig 15-18
As HCl is secreted, HCO3- is returned to the GI blood (“alkaline tide”)
Function of HCl: not digestive, kills potential parasites: bacteria etc.

24. Regulation of HCl secretion
fig 15-20
HCl secretion increased by:
parasympathetic NS stimulation (cephalic phase)
gastrin (direct & via histamine from mast cells) (gastric phase)
HCl secretion inhibited by somatostatin

25. Phases of gastric secretion of pepsinogen & HCl
Cephalic phase:
stimulus: sight, smell, thought of food, chewing
mechanism:  parasympathetic NS  secretion & motility
Gastric phase:
stimulus: aminoacids, peptides in stomach, distension,  pH as food enters
mechanism: short/long loop reflexes, gastrin  secretion & motility
Intestinal phase:
stimulus: intestinal distension,  pH,  osmolality, digestive products
mechanism: short/long loop reflexes, secretin, CCK, GIP

26. Pancreatic secretion Enzymes (a reminder):
trypsin, chymotrypsin, (elastase), carboxypeptidase
amylase, lipase, (phospholipases, nucleases)
Bicarbonate
fig 15-25

27. Regulation of pancreatic secretion
Stimulus: fatty acids, glucose,  osmolality, distension in small intestine
Mediator: cholecystokinin
Response:
relaxation of sphincter of Oddi, contraction of gall bladder
secretion of pancreatic enzymes, potentiation of secretin actions
Stimulus:  pH in small intestine
Mediator: secretin
Response: secretion of bicarbonate in pancreatic juice & bile
Stimulus: glucose in small intestine
Mediator: glucose insulinotropic peptide (GIP)
Response: secretion of insulin, inhibition of gastric secretion

28. Regulation of pancreatic secretion
fig 15-27
fig 15-28

29. Bile
Source:
produced in liver, stored & concentrated in the gall bladder
Composition:
bile salts, phospholipids, cholesterol (emulsify fats)
bicarbonate (neutralizes HCl)
bile pigments (heme metabolism), drug metabolites & trace metals
Regulation of secretion:
intestinal fatty acids  cholecystokinin  gall bladder contraction
Enterohepatic circulation:
next screen

30. Regulation of bile secretion
fig 15-31

31. Bile enterohepatic circulation
Bile salts circulate
2-3x per meal
fig 15-30

32. Gastrointestinal motility omitted
Omit objectives 16-20

33. Liver functions 1. exocrine function: bile salts, bicarbonate
2. plasma proteins: albumin, binding proteins, angiotensinogen
3. metabolism: gluconeogenesis, urea, ketoacids, lipoproteins
4. cholesterol synthesis, secretion in bile
5. excretion: bile pigments, trace metals, drug metabolites