1

Composition
Function
A.
B.
C.
D.
Ingest 2 l/d water
Digest food
Dilute the food into isoosmotic fluid
Provide a favorable pH for
Small the digestive enzymes intestine absorbs
Provide mucus for
8.5 l/d lubrication and protection of all parts of the alimentary tract
Colon absorbs 0.4-
1 l/d
Regulation
Saliva 1.5 l/d pH 6.8-7.0
Gastric secretion 2 l/d, pH 1.5-3
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
excreted

3

4

Acinar Cells: 腺
泡细胞
5

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

Secretion rate depends entirely on neural control both parasympathetic (Ach,
M receptor) (water secretion) and sympathetic (NA, β receptor) (enzyme) lead to increased secretion
Fear
Sleep
Tired
Dehydration
SNS (cAMP)
Secretion
Vasodilation
Cell contraction
Metabolism
Nausea
PNS(IP3)
7

8

• 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 B
12 absorption)
9

Oesophagus
Lower Oesophageal
Sphincter
Fundus
Duodenum
Pylorus
Body
Antrum
10

Fundus
Oesophagus
Lower Oesophageal
Sphincter
Fundus
• Storage
Body
• Storage
• Mucus
• HCl
• Pepsinogen
Duodenum
Pylorus
• Intrinsic factor
Body
Antrum
Antrum
• Mixing/Grinding
• Gastrin
11

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

14

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 Ca 2+ and Fe 2+ in small intestine
15

2. Pepsinogen (precursor of pepsin)
 digestion of proteins
3. Mucus
 forms a protective barrier: Mucus-bicarbonate barrier
4. Intrinsic factor
 combines with vitamin B
12 absorbable to make it
16

光面管泡
微管
17

HCl secretion
18

19

H
2
O
Cl
K
Stomach
Lumen
~
H
H
2
CO
3
Carbonic
Anhydrase
CO
2
+ H
2
O
HCO
3
Cl
CO
2
Blood pH<2

Cells
Inactive precursor of pepsin which initiates protein digestion
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 ulceration
22

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

Only gastric secretion that is Essential for health
Secreted from parietal cells in humans, chif cells in other species
Forms a complex with vitamin B
12 in the gut
The complex is resistant to digestion and therefore enables absorption of vitamin B
12
Lack of intrinsic factor causes Vit B
12 and therefore can not be absorbed deficiency
(pernicious anaemia) – as all the Vit B
12 is digested
25

26

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

协同作用
30

GASTRIN
HISTAMINE
Ca
ACETYLCHOLINE
G
S AC
ATP cAMP
K
PROTEIN
KINASES
H
~
Ca
31

Gastric secretion during digesting food
32

Mechanisms Stimulating Gastric Acid
Secretion in Cephasic Phase
Sight, smell, taste of food
Cephalic Phase
Vagus nerve
+
ACh
Parietal cells
GRP
G cells
+
Gastrin
+
Gastrin/ACh
ECL cells
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

Distension of stomach
(arrival of food)
Gastric Phase
Vagal/
Enteric reflexes
ACh
Peptides in lumen
Gastrin/ACh
G cells
Gastrin
Parietal cells
ECL 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


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
Acid in duodenum
Enterogastric
(splanchnic) reflex
Fat in duodenum
Secretin release
GIP release
Gastrin secr n
Gastrin stim n of parietal cells
Gastrin secr n
Parietal HCl secr n

• 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

45

Endocrine - insulin & glucagon
Exocrine - enzymes and bicarbonate essential for digestion almost under separate hormonal control
46

Gall bladder
Sphincter of Oddi
47

48

Islet of Langerhans
(secrete insulin)
Acinus
Capillary
Acinar cells
(secrete enzymes)
Intercalated duct
Duct cells
(secrete HCO
3
)

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
51
Duodenum

Categories of Pancreatic Enzymes
Proteases
Nucleases
Elastases
Phospholipases
Lipases
Amylase
Cleave peptide bonds
Hydrolyze DNA/RNA
Collagen digestion
Phospholipids to fatty acids
Triglycerides to fatty acids+ glycerol
Starch to maltose + glucose
52

Activation of pancreatic proteases
Trypsinogen
Enterokinase
Trypsin
Trypsinogen
Chymotrypsinogen
Proelastase
Procarboxypeptidase
Trypsin
Chymotrypsin
Elastase
Carboxypeptidase
53

Lumen
Blood
H
2
O CO
2
CO
2
H
2
CO
3
HCO
3
-
HCO
3
-
H + H +
ATP
Cl -
Na +
Cl -
Na + Na +
H
2
O
H
2
O
54

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

- 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

Key hormones in stimulation of secretion are:
Cholecystokinin (CCK) and Secretin ( released from the small intestine)
Inhibiting factors: SS, PP, glucagon
58

CCK duodenum
I cells
Peptides Amino
Vagus afferent nerve – acids, Fatty Acid H + vagovagal Fat reflex
5-HT stomach pancreas
Enzymes
59

H +
Fat
Peptides
S cells
Secretin
HCO
3
-
60

Control of Pancreatic Function
61

Intestinal phase of secretion
CCK
Peptides
Amino acids
Fat, H +
Secretin HCO
3
-
Enzymes
VAGUS
ACh
62

63

Structure/Function of Liver
Liver lobule
Central vein
Central vein
Blood
Bile
Bile canaliculus
Portal triad
Hepatic artery
Hepatic portal vein
Portal triad 64

65

Secretion and storage of bile
Constituents of bile
Water
Liver
98%
Bile salts
Bilirubin( 胆红素）
1%
0.04%
Cholesterol （胆固醇） 0.1%
Fatty acids
Lecithin （卵磷脂）
0.12%
0.04%
Na, K, Ca, Cl, HCO3
Gallbladder
92%
6%
0.3%
0.3-0.9%
0.3-1.2%
0.3%
66


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

Liver
HCO
3
-
Cl -
Na +
HCO
3
-
In fasting state
Bile stored in gall bladder& concentrated
Aqueous secretion from duct epithelium rich in HCO
3
and stim. by secretin
H
2
O
Fluid & electrolytes absorbed by active transport of Na+
Sphincter of Oddi
(closed)
72

Gall bladder contraction
BILE
Digestion - fat in duodenum stimulates
CCK release from I cells
CCK
FAT

Liver secretion
The enterohepatic circulation
Portal vein
Gallbladderstorage & concentration
Common bile duct
Duodenumdigestion & emulsification
Ileum absorption of bile acids 74

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
•
As a result, bile enters the duodenum
76

77

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

Local stimuli
The presence of chyme in the intestine
Hormonal regulation
Secretin
CCK
Neuronal regulation
Vagus nerve – excitatory
Sympathetic nerve - inhibitory
79