GI Physiology IV:

Early Intestinal Phase of Digestion

IDP/DPT GI Course, Fall 2011Jerome W. Breslin, Ph.D.LSUHSC-NO Department of

PhysiologyMEB 7208 (1901 Perdido St.)

568-2669jbresl@lsuhsc.edu

Required Reading

•Kim Barrett, Gastrointestinal Physiology

•Chapter 5 - section on cellular basis of transport

•Chapter 9

•Chapter 15

•Chapter 16

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

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

Figure 15-34

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.

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.

Figure 15-24

(CCK, Secretin)

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.

By projectinginto the lumen, the villi increases the surface area for absorption of nutrients.

Microvilli [aka brushborder] fringe thevilli to further increase surface area.

nutrients

Figure 15-7

Secretin’s receptors are found in the pancreas, which responds with additional bicarbonate delivery: gastric motility and secretion are inhibited.

Figure 15-27

Secretin is secreted by the S Cells in the Crypts of Lieberkühn.

Cholecystokinin (CCK) stimulates the gallbladder, which responds by contracting and delivering morebile to the duodenumthrough the sphincterof Oddi, which relaxes (opens) in response to CCK.

Figure 15-31

CCK is secreted by the intestinal mucosa.

Cholecystokinin’s receptors are located:• in the pancreas, which responds with additional enzyme delivery• in the gallbladder, which contracts to deliver morebile• in the sphincterof Oddi, which relaxes tofacilitate delivery of the enzymes and bile salts

Figure 15-28

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.

Fig 9-4Barrett

• 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

Small Intestinal Motility

• 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

Small Intestinal Motility (continued)

Fasting Motor Pattern:“Migrating Myoelectric Complex” (MMC)From Stomach to the Ileum

~100 minute cycle: Phase I (~50 min) = quiescentPhase II (~40 min) = irregular contractionsPhase III (5-10 min) = forward contractions

Regulation of MMCs is poorly understood:1. Independent of vagus and splanchnic innervation2. Phase III of the MMC is related to elevated plasma Motilin (secreted by M cells).

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

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).

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.

Digestion in the Gut

•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

3 SUB-PHASES OF INTESTINAL DIGESTION

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!

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).

Figure 15-26

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.

Three sites of protein digestion:

1. Lumen

2. Brush Border

3. Cytoplasm

PepT1

Short peptide uptake coupled to proton

transport

BarrettFig. 15-8

Activation of Proteases in the Small Intestine

Fig. 15-6

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.

Amino Acids, Dipeptides, and Tripeptides are Absorbed by

Specific Transporters.

Barrett, Fig. 15-8

There are also many brush border transporters for individual amino acids.

CytoplasmicPeptidases

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!

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.

Digestion of Carbohydrates Occurs in the Intestinal

Lumen & at the Brush Border

Berne & Levy Fig. 33-2

Monosaccharides are absorbed by specific transporters on the

brush border membrane.

Berne & Levy Fig. 33-2

1. Sodium gradient for SGLT1 driven by Na+/K+ ATPase.2. Basolateral GLUT2 transports monosaccharides to the blood.

Berne & Levy Fig. 33-4

Lipid Digestion & Absorption•Lipid digestion in luminal phase only.

•Digestion requires bile salts, pancreatic lipase, co-lipase and phospholipids.

•Lipids emulsified by bile salts and phospholipids.

•Triglyceride digested to form free fatty acids and a monoglyceride.

•Digestion productions taken up by diffusion

A molecular modelof a bile salt, with the cholesterol-derived “core” in yellow.

A space-filling modelof a bile salt. Thenon-polar surfacehelps emulsify fats, andthe polar surfacepromotes water solubility.

Figure 15-9

Bile salts and phospholipids convert large fat globules into smaller pieces with polar surfaces that inhibit reaggregation.

Figure 15-10

Big Droplets of Fat

Small Droplets of Fat

Micelles

Fatty Acids andMonoglycerides

Chylomicron Assembly

Distribution and Processing

Figure 15-12

Emulsified fat globules are small enough that lipase enzymes gain access todegrade triglyceridesto monoglycerides andfatty acids, which enterthe absorptive cells by simple diffusion or aggregate to form loosely held micelles, which readily break down.

Figure 15-11

Lipid Absorption•Free fatty acids and monoglycerides reformed into

triglycerides inside the enterocytes.

•Triglycerides packaged together with cholesterol and apo-lipoprotein molecules to form very large lipoproteins – CHYLOMICRONS.

•Chylomicrons secreted into lacteals – terminal of lymphatic system - enters systemic circulation in neck.

Water Soluble Vitamins

•Each has specific transporters (too many to mention)

•Vitamin B12: Requires Intrinsic Factor secreted by parietal cells in stomach.

•Pernicious Anemia: Caused by Vitamin B12 deficiency secondary to Atrophic gastritis (chronic inflammation of stomach mucosa), or more specifically loss of parietal cells.

Intrinsic Factor is

required for vitamin B12 (cobalamin)

uptake.

Absorption is in terminal

ileum.

Fig. 15-9, Barrett

Water and Electrolyte Absorption in the Small

Intestine•Sodium absorption generally coupled to nutrient absorption (e.g. SGLT1, PEPT1).

•Electrogenic: forces anions (mainly chloride) to passively follow the sodium transport by paracellular route.

•Water transported passively, following osmotic gradients (favoring absorption).

Water balance in

the GI tract.

Barrett, Fig. 5-1

Chloride secretion in small intestine and

colon.

Barrett,Fig. 5-8

Cholera toxin binds and activates the Gs G-protein, causing elevated cAMP and

increased Cl- secretion. Leads to secretory diarrhea. Fig. 5-9: cAMP regulates CFTR

Fig. 5-4: Balance between absorption and secretion in

health and secretory diarrhea.

Immature cells in Crypts of Lieberkuhn

Bicarbonate secretion in the duodenum

Fig. 5-10 in Barrett

Neutralization of HCl from the

stomach.

CFTR

Cl- H2O

Na+

Na+

Na+Na+

K+

K+

2Cl-

2Cl-

ATP

Na+

GUT LUMEN

K+

K+

BASOLATERAL AREA

IMMATURE CELLS INCRYPTS OF LIEBERKUHN

Na+

K+

ATP

Na+

H+ HCO3-

Cl-

Cl-

H2CO3 H2O + CO2

CO2

CO2K+

MATURE ENTEROCYTES