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

Digestion: mouth, stomach, small intestine Absorption: small intestine

Secretion: mouth, stomach, small intestine Motility: entire GI tract

fig 15-2

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

fig 15-5

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

6

Microanatomy of GI tract

fig 15-6

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

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: 14, 16 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

pepsin

trypsin, chymotrypsin

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

fig 15-9 fig 15-10

Bile: produced in liver, stored in gall bladderEmulsification in duodenum & upper intestine

15

Triglyceride digestion

fig 15-11

Colipase:

from pancreas, binds lipase to emulsion droplet

Micelles:

4-7 nm diameter

store of fatty acids & monoglycerides for transport into epithelial cells

16

Triglyceride absorption

fig 15-12

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

17

Vitamins, water absorption

Water:

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

fig 15-13

Long reflexes: mostly parasympathetic

Short reflexes: enteric nervous system, myenteric & submucosal plexuses, conduct impulses up & down GI tract

20

Hormonal regulation (simplification of table 15-4)

Gastrin Cholecystokinin Secretin GIP

Structure peptide peptide peptide peptide

Source G cells in stomach

small intestine epithelium

small intestine epithelium

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

Structure: fundus, body, antrum; lower esophageal & pyloric sphincters

Goblet cells mucus, Parietal cells HCl & intrinsic factor,

Chief cells pepsinogen, G cells gastrin

fig 15-16

fig 15-17

23

HCl secretion by parietal cells

As HCl is secreted, HCO3- is returned to the GI blood (“alkaline tide”)

Function of HCl: not digestive, kills potential parasites: bacteria etc.

fig 15-18

24

Regulation of HCl secretion

HCl secretion increased by:

parasympathetic NS stimulation (cephalic phase)gastrin (direct & via histamine from mast cells) (gastric phase)

HCl secretion inhibited by somatostatin

fig 15-20

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), carboxypeptidaseamylase, 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 bladdersecretion 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 15-28 fig 15-27

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

fig 15-30

Bile salts circulate 2-3x per meal

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