Download Gastrointestinal Secretions

Chapter 32
Gastrointestinal Secretions
1
Exocrine of the GI tract
Composition
Function
A. Digest food
B. Dilute the food into isoosmotic fluid
C. Provide a favorable pH for
the digestive enzymes
D. Provide mucus for
lubrication and protection
of all parts of the
alimentary tract
Regulation
Ingest 2 l/d
water
Saliva 1.5 l/d
pH 6.8-7.0
Gastric secretion 2
l/d, pH 1.5-3
Small
intestine
absorbs
8.5 l/d
Colon
absorbs 0.41 l/d
Bile 0.5 l/d pH
7.8-8.0
Pancreatic juice
1.5 ml/d pH 8.0-8.4
Intestinal secretion 1.5
l/d pH 7.8-8.0
0.1 l/d water2
excreted
I. Salivary secretion
3
Salivary gland
4
Secretion
Saliva: water, ions, mucus, enzymes
Acinar Cells: 腺
泡细胞
5
Functions of secretion
1. Moisten food
2. Begin chemical digestion (a amylase, 淀
粉酶)
3. Adjust appetite
4. Bacteriostatic action （抑菌作用)
(bacteriolysin, 溶菌素)
6
Control of salivary secretion
Secretion rate depends
entirely on neural control
Fear
Sleep
Tired
Dehydration
Nausea
both parasympathetic (Ach,
M receptor) (water
secretion)
and sympathetic (NA, β
receptor) (enzyme)
lead to increased
secretion
SNS (cAMP)
PNS(IP3)
Secretion
Vasodilation
Cell contraction
Metabolism
7
II. Gastric secretion
8
Functions of Stomach
• Temporary store of ingested material
• Dissolve food particles and initiate
digestive process
• Control delivery of contents to small
intestine
• Sterilise ingested material
• Produce intrinsic factor (Vitamin B12
absorption)
9
Oesophagus
Lower Oesophageal
Sphincter
Fundus
Duodenum
Pylorus
Body
Antrum
10
Functional Anatomy of Stomach
Fundus
Body
Antrum
• Storage
•
•
•
•
•
Oesophagus
Lower Oesophageal
Sphincter
Storage
Duodenum
Pylorus
Mucus
HCl
Pepsinogen
Intrinsic factor
• Mixing/Grinding
• Gastrin
Fundus
Body
Antrum
11
II.1 Gastric gland cells
1. Oxyntic gland (泌酸
腺）
Parietal cell
Chief cell
Mucous neck cell
2. Pyloric gland
Mucus cell
3. Cardiac gland
Mucus cell
4. Endocrine cells (G, D,
ECL)
ECL:enterochromaffin-like cell
12
Exocrine gland cells of gastric pits
Produce alkaline
mucus that covers
mucosa layer
Synthesize and
secrete the protease
precursor known as
pepsinogen.
Synthesize and
secrete the HCl acid
responsible for the
acidic pH in the
gastric lumen.
13
Structure of Stomach Wall
14
II.2 Composition and function
of gastric secretions
1. HCl
 converts pepsinogen to pepsin for chemical
digestion
 provides optimal pH environment for pepsin
 destroys some bacteria
 stimulates the small intestinal mucosa to release
secretinand CCK
 promotes the absorption of Ca2+ and Fe2+ in
15
small intestine
Composition and function of
gastric secretions
2. Pepsinogen (precursor of pepsin)
 digestion of proteins
3. Mucus
 forms a protective barrier: Mucus-bicarbonate
barrier
4. Intrinsic factor
 combines with vitamin B12 to make it
absorbable
16
HCl secretion
光面管泡
微管
17
HCl secretion
18
HCl secretion
19
K
H2O
Stomach
Lumen
~
Cl
pH<2
Carbonic
Anhydrase
H
H2CO3
CO2 + H2O
HCO3
Cl
CO2
Blood
pH>7.4
20
Inactive precursor of pepsin
which initiates protein digestion
Cells
Is not necessary for complete
digestion of dietray protein –
pancretic enzymes are sufficient
Active only when the pH < 3.5
21
Physical/chemical barrier
to attack by gastric juice
Stimulated by:
• Ach
• Mechanical Stim
• Chemicals (ethanol)
If breached e.g.
hypersecretion of acid 22
ulceration
Gastric Mucus-Bicarbonate Barrier
23
Gastric Mucus-bicarbonate barrier
The insoluble mucus and bicarbonate
construct a barrier
prevent hydrogen ions from diffusing to
the mucosal layer
protect the stomach mucosa from injury
by hydrochloric acid and pepsin,
24
Intrinsic Factor
Only gastric secretion that is Essential for health
Secreted from parietal cells in humans, chif cells in
other species
Forms a complex with vitamin B12 in the gut
The complex is resistant to digestion and therefore
enables absorption of vitamin B12
Lack of intrinsic factor causes Vit B12 deficiency
(pernicious anaemia) – as all the Vit B12 is digested
and therefore can not be absorbed
25
II.3 Regulation of Secretion
26
Control of Gastric Acid Secretion
Gastric acid secretion is controlled by three
mechanisms:
• Neurocrine (vagus/local reflexes)
• Endocrine (gastrin)
• Paracrine (histamine)
27
Endocrine gland cells of gastric pits
Stimulates acid
secretion
Inhibits
• acid secretion
• gastrin and pepsin
release
• pancreatic exocrine
secretions
Stimulates acid
secretion
28
Regulation of Gastric Secretions
The important stimulatory signals
Autonomic nerves
• Release ACh
• Stimulates smooth muscle contraction
• Also stimulates Chief , Parietal , ELC and G cells
Gastrin
• Stimulates Chief , Parietal , ELC cells
Histamin
• Stimulates Parietal cells
Protein products such as peptides, A.A’s
• Stimulates G-cells
Acids
• Stimulate D cells
29
Endogenous substances regulating
gastric secretion
协同作用
30
GASTRIN
HISTAMINE
ACETYLCHOLINE
GS AC
Ca
ATP
cAMP
Ca
PROTEIN
KINASES
H
K
~
31
Gastric secretion
during digesting food
32
Mechanisms Stimulating Gastric Acid
Secretion in Cephasic Phase
Cephalic Phase
Sight, smell,
taste of food
Vagus
nerve
GRP
Gastrin/ACh
+
ACh
G cells
ECL
cells
Parietal
cells
+
+
Gastrin
Histamine
33
Cephalic Phase
1. Cephalic phase
Occurs before food enters the stomach;
initiated by smell, taste, sight Impulses from
olfactory, chemical and other receptors activate the
vagal nuclei in the medulla (via Hypothalamus)
This triggers motor impulses to travel via the
vagus nerve to the parasympathetic enteric ganglia
Enteric ganglia in turn stimulate stomach glands
34
Cephalic Phase
Unconditioned and conditioned reflex
Only occurs when we want food
depression dampens this reflex
Account for 10% - 15% total volume of secretion
Large amount of HL and pepsinogen, high digestive
ability
35
Gastric Phase
Distension
of stomach
(arrival of food)
Peptides
in lumen
Gastrin/ACh
Vagal/
Enteric
reflexes
G cells
ECL
cells
ACh
Gastrin
Parietal
cells
Histamine
36
 Starts when food reaches the stomach
 Provides 2/3 of the juice released
 There are two parts (neural and chemical) to this phase
• Neural part
 Activated by stretch receptors
 Initiates both local neural reflexes as well as the longer
vago-vagal reflex
 Both reflexes result in release of ACh at stomach synapses
which stimulates secretory cells
 This branch is inhibited by Sympathetic action (emotional
upset)
37
Chemical part
An increase in pH (thus, ‘less’ acidity), presence of peptides,
caffeine activate the G-cells
This results in Gastrin being released
Gastrin acts on Parietal cells that start secreting HCl
Gastrin also stimulates Histamine release, which in turn
stimulates Parietal cells
The increase in HCl promotes pepsin production and protein
degradation
38
Chemical part
The release of Gastrin is partly regulated by acidity
Increased acidity inhibits the G-cells
Increased presence of proteins in a meal tends to buffer
proton
This in turn keeps the pH from becoming too acidic
and allows more gastrin to be released
39
Intestinal Phase
Account for about 5% of secretion
Primarily hormonal – denervated stomach will
be stimulated to secrete acid by protein in
duodenum
Hormone still unknown
Very smalll number of G-cells in duodenum
also release gastrin in response to amino acids
40
Regulation of Gastric Secretions occurs via 3 phases
41
Mechanisms Inhibiting Gastric Acid Secretion
Cephalic Phase
Stopping eating
Gastric Phase
pH ( [HCl])
Vagal activity
Gastrin
Intestinal Phase
Enterogastric
Acid in
(splanchnic) reflex
duodenum
Fat in
duodenum
Gastrin secrn
Gastrin stimn
of parietal
Secretin release
cells
GIP release
Gastrin secrn
42 n
Parietal HCl secr
Enterogastrones
• Hormones released from gland cells in duodenal
mucosa - secretin, cholecystokinin (CCK), GIP
• Released in response to acid, hypertonic
solutions, fatty acids or monoglycerides in
duodenum
• Act collectively to prevent further acid build up
in duodenum
• Two strategies:
• inhibit gastric acid secretion
• reduce gastric emptying (inhibit
motility/contract pyloric sphincter)
43
Regulation of gastric secretion
Hyperosmotic solution
Mechanical
stimulation
Entero-oxyntin
Fatty acids
HCl
Secretion of Ach or other transmitters
by nerve endings
D
Gastric gland
44
III. Secretion of the pancreas
45
Secretion of the pancreas
Endocrine - insulin & glucagon
Exocrine - enzymes and bicarbonate
essential for digestion
almost under separate hormonal control
46
Gall bladder
Sphincter of Oddi
47
Anatomy and secretion
48
Islet of Langerhans
(secrete insulin)
Acinus
Capillary
Acinar cells
(secrete enzymes)
Intercalated duct
Duct cells
(secrete HCO3)
49
To pancreatic duct
Exocrine Pancreas
Responsible for digestive function of pancreas
• Anatomical Structure
Acini
Ducts
Pancreatic Duct
• Function
Secretion of bicarbonate by duct cells
Secretion of digestive enzymes by acinar cells
50
Zymogens
• Acinar cells contain digestive enzymes stored as
inactive zymogen granules
• Prevents autodigestion of pancreas
• Enterokinase (bound to brush border of duodenal
enterocytes) converts trypsinogen to trypsin
• Trypsin converts all other zymogens to active
forms
Duodenum
51
Categories of Pancreatic Enzymes
Proteases
Cleave peptide bonds
Nucleases
Hydrolyze DNA/RNA
Elastases
Collagen digestion
Phospholipases
Phospholipids
Lipases
Triglycerides to fatty acids+
glycerol
Amylase
Starch to maltose + glucose
to fatty acids
52
Activation of pancreatic proteases
Enterokinase
Trypsinogen
Trypsin
Trypsinogen
Chymotrypsinogen
Proelastase
Procarboxypeptidase
Trypsin
Chymotrypsin
Elastase
Carboxypeptidase
53
Bicarbonate secretion
Blood
Lumen
CO2
H 2O
CO2
H2CO3
HCO3-
HCO3-
H+
H+
ClNa+
H 2O
ATP
ClNa+
Na+
H2O
54
Bicarbonate function
Function
1. Neutralize gastric
acid emptied into the
duodenum
2. Provide a favorable
alkaline environment
for optimal activity of
pancreatic enzymes
55
Control of Pancreatic Function
•
Bicarbonate secretion stimulated by secretin
•
Secretin released in response to acid in
duodenum
• Zymogen secretion stimulated by
cholecystokinin (CCK)
• CCK released in response to fat/amino acids in
duodenum
• Also under neural control (vagal/local reflexes)
- triggered by arrival of organic nutrients in
duodenum
56
Control of pancreatic secretion
- secretion in 3 phases
Cephalic phase - only 10-15% of total secretion
Activation of vagal efferent 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 and
neuronal reflex
Results in maximal enzyme and bicarbonate
release
57
Control of pancreatic secretion
Key hormones in stimulation of secretion
are:
Cholecystokinin (CCK) and Secretin (
released from the small intestine)
Inhibiting factors: SS, PP, glucagon
58
Cholecystokinin
stomach
duodenum
CCK
I cells
Peptides Amino
Vagus afferent
CCK
release peptide
+
nerve – acids, Fatty Acid H
pancreas
vagovagal
Fat
reflex
5-HT
Enzymes
59
Secretin
H+
Fat
Peptides
S cells
HCO3-
Secretin
60
Control of Pancreatic Function
61
Intestinal phase of secretion
VAGUS
CCK
Peptides
Amino acids
Fat, H+
Secretin
HCO3-
ACh
Enzymes
62
IV Biliary secretion
63
Structure/Function of Liver
Liver lobule
Central
vein
Central
vein
Blood
Bile
Bile
canaliculus
Hepatic
artery
Portal triad
Hepatic
portal vein
Portal
triad
64
65
Secretion and storage of bile
Constituents of bile
Liver
Gallbladder
Water
98%
92%
Bile salts
1%
6%
Bilirubin(胆红素）
0.04%
0.3%
Cholesterol（胆固醇）
0.1%
0.3-0.9%
Fatty acids
0.12%
0.3-1.2%
Lecithin（卵磷脂）
0.04%
0.3%
Na, K, Ca, Cl, HCO3
66
Functions of bile
Emulsification of fats
Increased absorption of lipids into
enterocytes (include vitamin A, D, E, K)
Increased synthesis and secretion of bile
Cholesterol excretion (only route)
Excretion of breakdown products of
haemoglobin (bilirubin，胆红素)
67
(a)
A molecular model of a
bile salt, with the
cholesterol-derived “core”
in yellow.
(b)
A space-filling model of a
bile salt.
The non-polar surface
helps emulsify fats,
The polar surface
promotes water solubility.
68
Of the 6 components present in
bile, only Bile salts and
phospholipids aid in digestive
processes.
Bile salts and phospholipids
convert large fat globules into
smaller pieces with polar
surfaces that inhibit reaggregation.
emulsification
69
Emulsified fat globules are small
enough
that lipase enzymes gain access
to degrade triglycerides to
monoglycerides and fatty acids,
Monoglycerides and fatty acids
enter the absorptive cells by simple
diffusion
or aggregate to form loosely held
micelles, which readily break
down.
70
Regulation of bile secretion and empty of
gallbladder
1. Nervous regulation: Vagus-vagus reflex
2. Humoral regulation: CCK , Gastrin, Secretin, SS
3. Bile salt: Enteroheptic circulation (Def.)
71
In fasting state
Bile stored in gall bladder&
concentrated
Liver
HCO3-
Aqueous secretion
from duct epithelium
rich in HCO3- and
stim. by secretin
HCO3-
ClNa+
H 2O
Fluid & electrolytes
absorbed by active
transport of Na+
Sphincter of Oddi
(closed)
72
Digestion - fat in
duodenum stimulates
CCK release from I
cells
FAT
CCK
Gall bladder
contraction
BILE
73
Sphincter of Oddi relaxes
Liver secretion
The enterohepatic
circulation
Portal vein
GallbladderCommon
bile duct
storage &
concentration
Duodenumdigestion &
emulsification
Ileum absorption of
74
bile acids
Up to 95% of the
cholesterol-based bile salts
are “recycled” by
reabsorption along the
intestine.
Inhibition of reabsorption
results in synthesis of new
bile acids and lowering of
cholesterol levels.
Increasing dietary fiber
could trap a greater
percentage of the bile in the
fibrous feces.
75
Regulation of Bile Release
• Acidic, fatty chyme causes the duodenum to release:
• Cholecystokinin (CCK) and secretin into the
bloodstream
• Bile salts and secretin transported in blood stimulate
the liver to produce bile
• Vagal stimulation causes weak contractions of the
gallbladder
• Cholecystokinin causes:
• The gallbladder to contract
• The sphincter of Oddi to relax
76
• As a result, bile enters the duodenum
Small Intestine secretion
77
Composition and function
Digestive enzymes not secreted from small intestine from pancreas or found on enterocytes
except enterokinase secreted from duodenal
mucosa
Mucus/alkali secretions - mucosal protection
Aqueous secretions
Function
Lubricate and protect intestinal surface (Ig A)
Dilute digestive products
Digest specific food substances
(enzymes in enterocytes: peptidase, sucrase, etc )
78
Regulation of small intestinal
secretion
Local stimuli
The presence of chyme in the intestine
Hormonal regulation
Secretin
CCK
Neuronal regulation
Vagus nerve – excitatory
Sympathetic nerve - inhibitory
79