Secretions of the small intestine, pancreas and liver

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Secretions of the small intestine, pancreas and
liver
Small intestine many villi on surface of
intestine crypts/glands of Lieberkuhn between
villi epithelial cells have brush
border Secretions are from cells within the
crypts of Lieberkuhn and fall into two
groups secretions into the lumen (from
enterocytes) secretions into the blood (from
endocrine cells)
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Intestinal secretions
Small intestine Mucus/alkali secretions - mucosal
protection Aqueous secretions under local
nervous control some minor hormonal
control (secretin, CCK)
Large intestine Secretion primarily consists of
mucus. Can also secrete water in response to
irritation
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Villus
Mucous cells (simple goblet cells)
Enterocytes (absorptive cells with brush border)
Endocrine cells (secrete hormones for control of
gut function)
Paneth cell (have secretory granules)
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Secretions into the lumen- aqueous
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Bicarbonate secretion
Blood
Lumen
H2O
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Secretions from the intestines - enzymes and
hormones
Digestive enzymes not secreted from small
intestine - from pancreas or found on
enterocytes except enterokinase secreted from
duodenal mucosa
Hormones - secreted from endocrine cells in
mucosa Stimulated by activation of chemoreceptors
in response to constiutuents of food and act to
stimulate production of digestive secretions from
other organs Gastrin - duodenum ?
stomach Cholescystokinin - SI ?
pancreas Secretin - SI ? pancreas
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Secretions into the lumen - mucus

• Brunners glands- compound mucus glands,
  secreting
• alkali
• mucus

First protection for duodenum from acid
Secretion stimulated by para-sympathetics Inhibite
d by sympathetics ?stress related ulceration
Pancreas
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Effect of cholera toxin
Blood
Lumen
Na
Na
K
K
Cl-
Cl-
Cl-
Na
Na
ATP
cAMP?
K
K
Na
Na
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Pancreatic secretion
- secretion in 3 phases Cephalic phase - only
10-15 of total secretion activation of vagal
efferents stimulates enzyme release Gastric
phase - only present in some species NOT
SIGNIFICANT IN HUMANS Intestinal phase - majority
of secretion combination of hormones CCK and
secretin results in maximal enzyme and
bicarbonate release
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Pancreatic secretions
Endocrine - insulin glucagon Exocrine - enzymes
and bicarbonate essential for digestion almost
under separate hormonal control
Key hormones in stimulation of secretion
are Cholecystokinin (CCK) Secretin Both released
from the small intestine
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Cholecystokinin
stomach
duodenum
I cells
Peptides Amino acids,H
Fat
pancreas
Enzymes
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Secretin
Fat
H
S cells
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Intestinal phase of secretion
Peptides Amino acids Fat, H
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Functions of bile
- emulsification of fats - increased absorption
of lipids into enterocytes - cholesterol
excretion (only route) - excretion of breakdown
products of haemoglobin (bilirubin)
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Secretion and storage of bile
Constituents of bile. Liver Gallbladder Wate
r 98 92 Bile salts 1 6 Bilirubin 0.
04 0.3 Cholesterol 0.1 0.3-0.9 Fatty
acids 0.12 0.3-1.2 Lecithin 0.04 0.3
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Bile production and storage
Bile canaliculi
hepatocyte
Canal of Hering
Bile duct
lined with cuboid epithelium
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In fasting state Bile stored in gall bladder
concentrated
Liver
Sphincter of Oddi (closed)
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Digestion - fat in duodenum stimulates CCK
release from I cells
FAT
CCK
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Function and fate of bile acids - the
enterohepatic circulation
Liver - secretion
Bile acids almost totally reabsorbed in terminal
illeum. 20 excreted daily. Inhibition of
reabsorption results in synthesis of new bile
acids and lowering of cholesterol levels.
Portal vein
Gallbladder-storage concentration
Common bile duct
Duodenum-digestion emulsification
Ileum - absorption of bile acids
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Secretions of the intestine, pancreas and liver-
summary
Small intestine - mucus and fluid - involved
in protection and absorption - hormones -
control of pancreatic and bile secretions Pancre
atic secretions - bicarbonate for neutralisation
of acids, optimises conditions for enzyme
action - enzymes for digestion Liver - bile for
emulsification of fat
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Bicarbonate secretion
Blood
Lumen
H2O
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Secretions into the lumen- aqueous
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Intestinal Secretin Secretion
Secretin pmol/g
73 7
324
5.5
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Secretin
Fat
H
S cells
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Cholecystokinin (pancreozymin)

• Release of digestive enzymes from the pancreas
  into the duodenum. Older literature refers to
  cholecystokinin as pancreozymin, a term coined to
  describe this effect.
• Contraction of the gallbladder to deliver bile
  into the duodenum. The name cholecystokinin (to
  "move the gallbladder") was given to describe
  this effect. Cholecystokinin is also known to
  stimulate secretion of bile salts into the
  biliary system

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Cholecystokinin
stomach
duodenum
I cells
Peptides Amino acids,H
Fat
pancreas
Enzymes
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Intestinal CCK Secretion
CCK pmol/g
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Pre-procholecystokinin
R
RK
K
R
RR
Signal
1
25
50-51
61
75
85-86
95
CCK is a classic gut hormone produced within
endocrine I-cells. The CCK gene is also
expressed in large quantities in cerebral and
peripheral neurons where shorter, cleavage
peptides are potent neurotransmitters and
modulators.
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Pre-procholecystokinin
R
RK
K
R
RR
Signal
1
25
50-51
61
75
85-86
95
Mammalian pro-CCK has several endoproteolytic
processing sites where cleavage is known to
occur. The processing tissue specific and the
pattern of bioactive CCK peptides in the
intestine and brain are markedly different.
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Pre-procholecystokinin
R
RK
K
R
RR
Signal
1
25
50-51
61
75
85-86
95
CCK-83
CCK-58
CCK-33
Plasma
CCK-22
Neuronal
CCK-8
CCK-5
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Pre-procholecystokinin
R
RK
K
R
RR
Signal
1
25
50-51
61
75
85-86
95
Why the tissue specific expression patterns ? 1.
Long lived neurons, more complete processing,
short lived mucosal cells are shed into the gut
before maximal post-translational processing
occurs.
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Pre-procholecystokinin
R
RK
K
R
RR
Signal
1
25
50-51
61
75
85-86
95
Why the tissue specific expression patterns ? 2.
Intermediate CCK peptides (CCK-58,33,22) have
slower clearance from the plasma than CCK-8,
hence longer stimulatory effect over the course
of the complete digestive process.
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Gastrin
CCK
Phenylalanine Aspartic Acid Methionine Tryptophan
Phenylalanine Aspartic Acid Methionine Tryptophan
Glycine Methionine Tyrosine-SO3
Glycine Tyrosine R11 a.a.
R26 a.a.
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• Two receptors that bind cholecystokinin have been
  identified. The CCKA receptor is found on
  pancreatic acinar cells, the CCKB receptor, which
  also functions as the GASTRIN receptor, is the
  predominant form in brain and stomach. Both
  receptors are have seven transmembrane domains
  typical of G protein-coupled receptors.