GI Physiology V:
The Liver and
Pancreas
IDP/DPT GI System, Fall 2011
Jerome W. Breslin, Ph.D.
LSUHSC-NO Department of Physiology
MEB 7208 (1901 Perdido St.)
568-2669
jbresl@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.
Figure 15-25
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.
PANCREATIC JUICE
FORMATION
Acinar cells secrete proteins into lumen; water & salts follow from
blood by a paracellular route.
Ductal cells modify secretions of the Acinar cells – add HCO3Acinar Cells
Respond to CCK, VIP, GRP & Acetylcholine
Na+
K+
Cl-
HCO3-
Ductule Cells
Respond to Secretin
& Acetylcholine
[HCO3-] increases during elevated pancreatic
secretion.
pH = 7.2
pH = 8.0
Berne & Levy
Fig. 32-19
or
Barrett,
Fig. 4-4
HCO3
Secretin stimulates
secretion in the
pancreatic ducts when S cells detect that acid
is present in the duodenum.
Barrett, Fig. 45
Also see Fig.
4-7 for
secretion
mechanism
Secretin Receptors are Densely Expressed on
Pancreatic Ductular Cells in Humans.
Stimuli and Second Messengers that
mediate elevated secretion by Pancreatic
Notes:
Acinar Cells
Both calcium and cAMP
are important, but
increasing calcium is
more significant than
cAMP.
Barrett, Fig. 4-7
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 SECRETION
IN PANCREATIC ACINAR CELLS
PANCREATIC SECRETION
IN CEPHALIC & GASTRIC
PHASES OF DIGESTION
PANCREATIC SECRETION
IN 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.
Figure 15-29
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 delivered
into the duodenum upon stimulation from CCK.
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
(“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 cholesterollowering drug).
Figure 15-30
Up to 95% of the
cholesterol-based bile
salts are “recycled” by
reabsorption along
the intestine.
Formation of cannicular bile in the liver sinusoids:
Water
Berne & Levy
Fig. 32-28
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.
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
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