Lecture 4

Exocrine pancreas

Simon A. Lewis
23397
MRB 143C
slewis@utmb.edu
 EXOCRINE PANCREAS
• Structure
• Composition of fluid secretion
• Sites of secretion
• Mechanism of secretion
• Regulation of secretion
Exocrine Pancreas
Intercalated
Acini duct
Individual pancreatic
lobule

Extralobular duct

Lobules

Intralobular
ducts
Extralobular ducts

Main collecting duct

 Ionic Composition of Pancreatic
Secretion
180
Ionic Concentration (meq/L)

160
140
120
100
Na+
80
60
40
20
0
0 5 10 15 20 25

Rate of Secretion (ml/min)

 Ionic Composition of Pancreatic
Secretion
180
Ionic Concentration (meq/L)

160
140
120
100 Na+
80 K+
60
40
20
0
0 5 10 15 20 25

Rate of Secretion (ml/min)

 Ionic Composition of Pancreatic
Secretion
180
Ionic Concentration (meq/L)

160
140
120
Na+
100
K+
80
HCO3-
60
40
20
0
0 5 10 15 20 25

Rate of Secretion (ml/min)

 Ionic Composition of Pancreatic
Secretion
180
Ionic Concentration (meq/L)

160
140
120 K+
100 Na+
80 Cl-
60 HCO3-
40
20
0
0 5 10 15 20 25

Rate of Secretion (ml/min)

 Acinar fluid
Acinus NaCl rich fluid

Lobules of acinar
and ductal
parenchyma

Intralobular
ductal system

Extralobular
ductal system

Main collecting duct

 Acinar fluid
Acinus NaCl rich fluid

Lobules of acinar
and ductal
parenchyma
Na+
K+ Secretin-stimulated
Intralobular HCO3- secretion
ductal system Cl- (higher [HCO3-])

Extralobular
ductal system

Main collecting duct

 Acinar fluid
Acinus NaCl rich fluid

Lobules of acinar
and ductal
parenchyma
Na+
K+ Secretin-stimulated
Intralobular HCO3- secretion
ductal system Cl- (higher [HCO3-])

Na+
Secretin-stimulated
Extralobular K+
HCO3- secretion
ductal system (higher [HCO3-])
Cl-

Main collecting duct

 Acinar fluid
Acinus NaCl rich fluid

Lobules of acinar
and ductal
parenchyma
Na+
K+ Secretin-stimulated
Intralobular HCO3- secretion
ductal system Cl- (higher [HCO3-])

Na+
Secretin-stimulated
Extralobular K+
HCO3- secretion
ductal system (higher [HCO3-])
Cl-

Main collecting duct Na+

Secretin-stimulated
K+
HCO3- secretion
Cl- (higher [HCO3-])
 Pancreatic Zymogen Secretion

Increase
turnover
Acetylcholine phosphatidyl
inositol

CCK, gastrin Release

cellular
calcium Increase
enzyme
GRP secretion

Increase
Secretin, VIP
cellular
cyclic AMP
Mechanism of Chloride Secretion of
Acinus
Na+

ATP
ADP

K+
. K+
Ca++

Cl- Na+
Acinar
2 Cl-
lumen
K+
Ca++
cAMP
Mechanism of Chloride Secretion of
Acinus
Na+

ATP
ADP

K+
. K+
Ca++

Cl- Na+
Acinar
2 Cl-
lumen
K+
Ca++
cAMP
Na+
Na+
Mechanism of Bicarbonate Secretion
Intralobular, Extralobular, Main Duct

K+
Tubovesicles
ATP

HCO3- Na+
HCO3- + H+
H+ H+ + HCO3-

Cl- H2CO3 Na+

Cl - H2CO3
CA

H2O + CO2 CO2 + H2O

K +

Duct
lumen
Duct cell
Mechanism of Bicarbonate Secretion
Intralobular, Extralobular, Main Duct

K+
Tubovesicles
ATP

HCO3- Na+
HCO3- + H+
H+ H+ + HCO3-

Cl- H2CO3 Na+

Cl - H2CO3
CA
Na +

K+ H2O + CO2 CO2

K +

Duct
lumen Na+
Duct cell

K+
Cephalic Phase of Pancreatic
Secretion
Conditioned Stimuli:
•smell, taste
•chewing Vagus nerve
•swallowing
•hypoglycemia

Gastrin

H2O and
NaHCO3

Ac
Ach h
Acinar cells
Duct
Enzymes cells
Monitor peptide
Gastrin
 Intestinal Phase of Pancreatic
Secretion
Vagus nerve
(vagovagal reflex)
Parietal cell

Fat
protein
H+
1 cells

CCK Peptides + amino acids

Fat
S cells
H+

Duct Ach
H2 O cells
Secretin Ach Acinar
NaHCO3 cells

Enzymes
Monitor peptide
Secretin

CCK
 CCK-Releasing Factor
• Released from duodenal and jejunal cells
into intestinal lumen
• stimulated by fats and amino acids
• stimulates CCK release from duodenum and
jejunum into the blood
• CCK-RF is trypsin sensitive
 Interdigestive Phase
• CCK-RF is quickly hydrolyzed by trypsin

• Products of CCK-RF hydrolysis do not

stimulate CCK release

• Zymogen secretion is reduced

 Digestive Phase
• Presence of proteins and peptides in the
intestinal lumen reduces hydrolysis of
CCK-RF

• Higher concentration of CCK-RF stimulates

CCK release and thus zymogen secretion

• CCK-RF is part of negative feedback

system to control zymogen secretion
 Monitor Peptide
• Released by pancreatic acinar cells into the
lumen of the acinus
• Ach and GRP stimulate pancreatic release
during cephalic phase and intestinal phase.
• Stimulates CCK release from I cells.
• CCK stimulates monitor peptide release.
• Trypsin hydrolysis inactivates monitor
peptide
 ZYMOGEN GRANULES
• Proteases: trypsinogen, chymotrypsinogen,
proelastase, procarboxypeptidase A and B
• Amylase
• Lipases: lipase, esterases,
prophospholipase A2
• Procolipase
• Monitor peptide
• Nucleases: deoxyribonuclease, ribonuclease
Trypsinogen Trypsin

enterokinase

Procarboxypeptidase A
Trypsinogen Trypsin

enterokinase

Procarboxypeptidase A carboxypeptidase A
Procarboxypeptidase B
Trypsinogen Trypsin

enterokinase

Procarboxypeptidase A carboxypeptidase A
Procarboxypeptidase B carboxypeptidase B

Proelastase
Trypsinogen Trypsin

enterokinase

Procarboxypeptidase A carboxypeptidase A
Procarboxypeptidase B carboxypeptidase B

Proelastase elastase

Chymotrypsinogen
Trypsinogen Trypsin

enterokinase

Procarboxypeptidase A carboxypeptidase A
Procarboxypeptidase B carboxypeptidase B

Proelastase elastase

Chymotrypsinogen chymotrypsin
Products of Starch Hydrolysis by
α-amylase
Maltose Limit dextrin Maltotriose

1:6 link 1:4 link

 Starch
Luminal Digestion

Salivary Amylase

Partially Converted Starch

Pancreatic Amylase

Lactose α-Dextrins Maltotriose Maltose Trehalose Sucrose

Membrane Digestion

Maltase 5 25 25
Sucrase 25 25 100

α-Dextrinase 95 50 50
Trehalase 100
Lactase 100

Glucose + + + + + +
Products

Galactose +
Fructose +
Lipid hydrolysis
Site of Lipid hydrolysis
Micelle structure
 CYSTIC FIBROSIS:
Exocrine Gland Disease
• Pancreas
• Sweat ducts
• Parotid gland
• Submaxillary glands
• Small salivary glands
• Intestinal glands
• Intrahepatic bile duct
• Gallbladder
• Tracheobronchial glands
• Brunners glands
• Predominately a Caucasian disease.
• 1 in 2400 Americans
 Clinical Findings
• Salty skin
• Meconium plug (obstruction of the small
and large intestine with thick mucus plug)
• Malnutrition (inadequate weight gain)
• Steatorrhea (oily, foul smelling stool)
• Respiratory complications
 Exocrine Pancreas:
• Pancreatic ducts blocked by protein rich
plug.
• Dilated pancreatic ducts.
• Tissue destruction with fibrosis and fat
deposits.
 Autosomal recessive trait
• Chromosome 7q
• Mutation in CFTR cystic fibrosis
transmembrane conductance regulator.
• CFTR is thought to be a Chloride channel.
• Delta F508 is the most common mutation
(70%).
• Mutated channel does not get trafficked to
the apical membrane.
 Why does the absence of a chloride
channel have such wide spread
effects.
• Sweat ducts?
• Salivary glands?
• Intestine?
• Respiratory system?
• Pancreas?