GI Physiology V:The Liver and

PancreasIDP/DPT GI System, Fall 2011

Jerome W. Breslin, Ph.D.LSUHSC-NO Department of

PhysiologyMEB 7208 (1901 Perdido St.)

568-2669jbresl@lsuhsc.edu

Liver & Pancreas Lecture Outline.

•Introduction

•Exocrine Pancreas

•GIP, Glucose, & Insulin Secretion

•Pancreatic Juice Composition

•Cellular Basis of Secretion

•Secretion and Phases of Digestion

•Liver

•Bile Secretion

•Gall Bladder Function

Required Reading

•Barrett, Gastrointestinal Physiology

•Chapter 4 - sections on Pancreas

•Chapter 10 - overview and section on enterohepatic circulation

•Chapter 11

•Chapter 12

Exocrine Pancreas

•Enzymes are produced and secreted in excess.

•However, nutrition problems will arise if production of pancreatic enzymes falls by as little as 10%, or if outflow of pancreatic juice is obstructed.

The exocrine cells in the pancreas play a central role in the production of digestive enzymes; the endocrine functions of the pancreas will be discussed at length in Chapter 16.

Figure 15-25

PANCREATIC JUICE FORMATION

Acinar CellsRespond to CCK, VIP, GRP & Acetylcholine

Ductule CellsRespond to Secretin& Acetylcholine

Na+ K+

Cl- HCO3-

Acinar cells secrete proteins into lumen; water & salts follow from blood by a paracellular route.Ductal cells modify secretions of the Acinar cells – add HCO3

-

[HCO3-] increases during elevated pancreatic secretion.

Berne & LevyFig. 32-19

orBarrett,Fig. 4-4

pH = 7.2 pH = 8.0

Secretin stimulates HCO3- secretion

in the pancreatic ducts when S cells detect that acid is present

in the duodenum.

Barrett, Fig. 4-5

Also see Fig. 4-7

for secretion mechanismSecretin Receptors are Densely Expressed

on Pancreatic Ductular Cells in Humans.

Stimuli and Second Messengers that mediate elevated

secretion by Pancreatic Acinar Cells

Barrett, Fig. 4-7

Notes:Both calcium and

cAMP are important, but

increasing calcium is more

significant than cAMP.

It is not yet clear whether

Secretin modulates secretion from acinar cells in humans, although it does so in rats. Secretin

receptors may be present on some

subpopulations of acinar cells.

INDUCTION OF FLUID SECRETIONINDUCTION OF FLUID SECRETIONIN PANCREATIC ACINAR CELLSIN PANCREATIC ACINAR CELLS

PANCREATIC SECRETIONPANCREATIC SECRETIONIN CEPHALIC & GASTRIC IN CEPHALIC & GASTRIC PHASES OF DIGESTIONPHASES OF DIGESTION

PANCREATIC SECRETIONPANCREATIC SECRETIONIN THE INTESTINAL PHASEIN THE INTESTINAL PHASE

Liver: Bile Secretion•Bile is produced in the

liver

•Bile is stored in the gallbladder.

•Bile is secreted into the small intestine.

•Bile salts are absorbed in the small intestine and recycled.

Bile formation by cells in the liver includes 6 components:

bile salts, lecithin, bicarbonate ions, cholesterol, bile pigments, and trace metals.

The bile is funneled into the gallbladder and then deliveredinto the duodenum upon stimulation from CCK.

Figure 15-29

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(“I cells”).

Bile Acid Structure

Primary bile acids are

synthesized in the liver.Secondary bile acids are

produced in the colon by bacterial enzymes

(ursodeoxycholic acid is used as cholesterol-

lowering drug).

Up to 95% of the cholesterol-based bile salts are “recycled” by reabsorption along the intestine.

Figure 15-30

Berne & Levy Fig.

32-28

Formation of cannicular bile in the liver sinusoids:

NTCP = Na-dependent taurocholate transporter, OATP = organic ion transport protein, OCT = organic cation transporter, BSEP = bile salt export protein, MDR = multidrug resistance protein,

MRP = MDR related protein.

Water

Mechanism of bile concentration by gallbladder epithelium

Fig. 12-3

Changes in Bile Composition during gallbladder storage

Fig. 12-2,Barrett

Why? Osmolality is based on the number of particles in solution, whether they be ions, molecules, or micelles. Bile acids form micelles, and essentially the number of particles in solution remains the same because free bile acids incorporate into the micelles as the concentration goes up.

Neurohormonal control of gallbladder contraction and

biliary secretion.

Fig. 12-1

Gallstones•Estimated that 20 million people in USA have gallstones.

•Deposition of cholesterol or bilirubin in the gallbladder or in common biliary duct. Cholesterol stones are the common type in Western countries.

•About 1/3 of patients will get episodes of pain in the epigastric region.

•Treatment is cholecystectomy (gall bladder removal) or sometimes endoscopic approaches to remove stones from common biliary duct or sphincter of Oddi.

•Consequence of gall baldder removal is inability to concentrate bile, which affects fat absorption, and fatty meals may need to be avoided.

Summary

•Liver: Bile Production

•Enterohepatic circulation - recycling

•Gallbladder: Bile Concentration and controls release

•CCK is a major regulator

Summary of Factors that regulate CCK release:

Fig. 4-3

Summary of CCK action on duodenal cluster unit

Barrett, Fig. 4-2