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PANCREAS
Dr. Zainab H.H.
Dept. of physiology
College of medicine
Al-Nahrain University
 Learning objectives
 Describe the pancreatic secretion
 Describe the function of cystic fibrosis
transmembrane conductance regulator (CFTR)
 Describe the regulatory mechanisms of
pancreatic secretion
 List the enzymatic components of pancreatic
secretion
PANCREAS
-is present outside GI but connected to it by a duct.
-has two components
– Exocrine 90%: produces several digestive
enzymes
– ducts will secret an electrolyte solution that
contain large amounts of water & bicarbonate
ions
–
Endocrine 2%: produces hormones such as insulin
Composition of the pancreatic juice:
– The volume is 1-1.5 liter per day.
– PH is 8
– It contains water and different electrolyte CATIONS (Na⁺, K⁺, Ca⁺⁺, Mg⁺⁺)
- ANIONS (HCO3⁻, Cl⁻, SO4⁼, HPO4⁼)
– neutralizing acid chyme emptied by stomach
– organic constituents: different digestive enzymes
for digestion of protein, fat and CHO.
Acinar cells …….produce:
 hydrolytic enzymes
aid in digestion of fats, proteins, carbohydrates, and
nucleic acids
 secretagogues,
- In apical region of acinar cells
- is secretory granules
- stimulate pancreatic enzyme secretion.
- causing an increase in cytosolic Ca2+Concentration.
- they are :
A-acetylcholine,
secreted from vagal efferents,
B-cholecystokinin;
PANCREATIC DUCT…. Secretion:
Centroacinar and ductal cells produce the initial aqueous
secretion, which is isotonic and contains Na, K , Cl, and HCO3
 This initial secretion is then modified by transport processes in
the ductal epithelial cells as follows:
 The apical membrane of ductal cells contains a Cl –HCO3
exchanger, and the basolateral membrane contains Na –K
ATPase and an Na –H exchanger.
 In the presence of carbonic anhydrase, CO2 and H2O combine
in the cells to form H2CO3. H2CO3 dissociates into H and
HCO3.
 The HCO3 is secreted into pancreatic juice by the Cl-HCO3
exchanger in the apical membrane.
 The H is transported into the blood by the Na –H exchanger in
the basolateral membrane.

The net result, or sum, of these transport processes is
net secretion of HCO3 into pancreatic ductal juice and
net absorption of H ; absorption of H causes
acidification of pancreatic venous blood
 The Na and K concentrations are the same as their
concentrations in plasma, but the Cl and HCO3
concentrations vary with pancreatic flow rate.
 Cl− is recycled by Cl− channel from cell to lumen via:
cystic fibrosis transmembrane conductance regulator
(CFTR)
■ Na+ secretion :

is secreted into duct lumen following HCO3 − secretion;

water :
 follows by osmosis
 produce fluid secretion.
Which of the following is true about the
secretion from the exocrine pancreas?
(A) It has a higher Cl– concentration than
does plasma
(B) It is stimulated by the presence of HCO3
– in the duodenum
(C) Pancreatic HCO3– secretion is increased by
gastrin
(D) Pancreatic enzyme secretion is increased
by cholecystokinin (CCK)
(E) It is hypotonic

Effect of Flow Rate on Composition
of Pancreatic Juice
At the highest pancreatic flow rates (more than
30 mL/min), the HCO3 concentration of
pancreatic juice is highest (and much higher
than plasma HCO3), and the Cl concentration is
lowest.
 At the lowest flow rates, HCO3 is lowest and Cl
is highest
 The Na and K concentrations in pancreatic juice
remain constant.

Regulation of Pancreatic
Secretion
Pancreatic secretion has two functions:
(1) to secrete the enzymes necessary for
digestion of carbohydrates, proteins, and lipids;
the enzymatic portion of pancreatic secretion
performs these digestive functions;

(2) to neutralize H in the chyme delivered to the
duodenum from the stomach
The enzymatic and aqueous portions are
regulated separately:
 The aqueous secretion is stimulated by the
arrival of H in the duodenum,


The enzymatic secretion is stimulated by
products of digestion (small peptides, amino
acids, and fatty acids).
REGULATION OF PANCREATIC SECRETION:
1. Nervous by vagus.
2. Hormonal
a- Cholecystokinin-pancreozymin CCK.
b- Secretin.
PHASES OF PANCREATIC SECRETION:
1. Cephalic and Gastric phase:
-acetylcholine released by vagal nerve.
-secretion is rich in enzymes and poor in water &
bicarbonate.
-accounts for 20% of total secretion of pancreatic
enzymes after a meal.
2. The intestinal phase is the most important phase
and accounts for approximately 80% of the
pancreatic secretion
Acinar cells (enzymatic secretion) have :
1. receptors for CCK (CCK-A receptors)
2. muscarinic receptors for ACh.
 During the intestinal phase, CCK is the most
important stimulant for the enzymatic
secretion.
 The I cells of intestinal mucosa are stimulated
to secrete CCK by the presence of amino acids,
small peptides, and fatty acids in the intestinal
lumen.
 ACh stimulates enzyme secretion and
potentiates the action of CCK by vagovagal
reflexes


Ductal cells

have receptors for:
CCK, ACh, and secretin.

Secretin, which is secreted by the S cells of the duodenum, is
the major stimulant of the aqueous HCO3 -rich secretion.

Secretin is secreted in response to H in the lumen of the
intestine, which signals the arrival of acidic chyme from the
stomach.
To ensure that pancreatic lipases will be active (since they are
inactivated at low pH), the acidic chyme requires rapid
neutralization by the HCO3 -containing pancreatic juice.


(aqueous secretion of Na+, HCO3-, and H2O).
The effects of secretin are potentiated by both CCK and ACh
Secretion of which of the following substances
is inhibited by low pH?
(A) Secretin
(B) Gastrin
(C) Cholecystokinin (CCK)
(D) Vasoactive intestinal peptide (VIP)
(E) Gastric inhibitory peptide (GIP)


Enzymatic component of pancreatic secretion (acinar
cells).
Protein digesting enzymes:
1.
2.
3.
4.
Trypsin.
Chymotrypsin.
Elastase.
Carboxypeptidase.
are secreted from pancreas in an inactive form:
1.
2.
3.
4.
trypsinogen,
chymotrypsinogen,
proelastase, &
Procarboxypeptidase.
– activated after secreted into intestinal tract (not in
pancreas).
Trypsinogen :
 is activated by an enzyme called enterokinase or
enteropeptidase
 secreted by intestinal mucosa when chyme comes in
contact with mucosa. .
 Enterokinase :convert inactive trypsinogen into
Trypsin.
 trypsin can activate: trypsinogen …into ………trypsin.
 once trypsin is formed :
it cause autocatalytic chain reaction by which more
trypsinogen is activated into ……..trypsin.
also activate:
 chymotrypsinogen ……into ……..chymotrypsin,
 procarboxypeptidase ..into ….carboxypeptidase,
 proelastase ……………..into ………elastase.
Trypsin and chymotrypsin
will digest whole or partially digested protein into peptide level.
Carboxypeptidase :
will digest peptides into amino acids.
Enzymes for the digestion of nucleic acids:
1.
2.
Ribonuclease: which acts on RNA.
Deoxyribonuclease: which acts on DNA.
Enzymes for digestion of carbohydrates:
α-amylase:
similar to that of salivary secretion.
It splits starches and glycogen into disaccharides such as maltose and isomaltose.
Fat splitting enzymes
Fat splitting enzymes:
1. Lipase.
2. Procolipase (colipase):
secreted as procolipse (inactive form)
activated into active form by trypsin.
Colipase
 is a protein that binds to surface of fat
droplet
 displacing emulsifying agents and
anchoring lipase to droplet,.
lipase :
 not act on fat droplets covered by
emulsifying agents without colipase.
3-Phospholipase A2
–
–
secreted as inactive form (prophospholipase A2) &
activated by trypsin into phospholipase A2,
phospholipase A2 acts on lecithin
In acute pancreatitis
prophospholipase A2 is activated inside pancreas and
cause partial digestion of lecithin into lysolecithin and a
fatty acid.
Lysolecithin causes damage of pancreatic tissue.
4-Trypsin inhibitor:
is secreted by cells that secrete proteolytic enzymes
It surrounds the enzyme granules and prevents its
activation both inside acini or the ducts of pancreas.
Why Pancreas does not digest itself
1- enzymes are secreted in an inactive
form.
2- Trypsin inhibitor.
3- Flow (no stagnation).
amount of enzyme secreted will flow.
DEFICIENCY OF PANCREATIC ENZYMES:
Caused by chronic pancreatitis or damage to
pancreas.
–fat digestion:
It affects mainly
–Protein digestion
Will be affected
protein loss will be significant.
–carbohydrates digestion
is little affected.
deficiency of lipase:
result in deficiency in digestion of fat lead to steatorrhoea.
(stool bulky, pale, greasy and of bad odour and floats
on water).
SECRETIN:
-is secreted by the S cells of the duodenum
-it’s secreted when chyme enters intestine.
-important factor that causes release of secretin is:
ACID → hydrochloric acid → causes release of
secretin → absorbed by blood → to pancreas.
- The secretion is a watery, alkaline juice poor in
enzymes and chloride.
Importance of secretin mechanism:
1. neutralize the acid in the duodenum.
2. bicarbonate ions will provide a suitable PH for the
action of the pancreatic enzymes.
3. provide the fluid medium to wash out enzymes that
are secreted into acini.
CHOLECYSTOKININ-PANCREOZYMIN (CCK):
-released from mucosa of upper s. intestine (I cells) in
response to fat and partial byproducts of protein digestion.
– CCK when released will be absorbed by the blood and then
will go to pancreas to cause secretion of pancreatic juice
-rich in enzymes but poor in water and bicarbonate.
-similar to vagal stimulation but not blocked by atropine.
-accounts for about 70-80% of total secretion of pancreatic
digestive enzymes after a meal.
Cholecystokinin (CCK) inhibits
(A) gastric emptying
(B) pancreatic HCO3– secretion
(C) pancreatic enzyme secretion
(D) contraction of the gallbladder
(E) relaxation of the sphincter of Oddi
