Gastrointestinal Secretions

1
Chapter 32 Gastrointestinal Secretions
2
Exocrine of the GI tract

• Composition
• Function
• Digest food
• Dilute the food into iso-osmotic fluid
• Provide a favorable pH for the digestive enzymes
• 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
Bile 0.5 l/d pH 7.8-8.0
Small intestine absorbs 8.5 l/d
Pancreatic juice 1.5 ml/d pH 8.0-8.4
Intestinal secretion 1.5 l/d pH 7.8-8.0
Colon absorbs 0.4-1 l/d
0.1 l/d water excreted
3
I. Salivary secretion
4
Salivary gland
5
Secretion
Saliva water, ions, mucus, enzymes
Acinar Cells ????
6
Functions of secretion

• 1. Moisten food
• 2. Begin chemical digestion (a amylase, ???)
• 3. Adjust appetite
• 4. Bacteriostatic action (????) (bacteriolysin,
  ???)

7
Control of salivary secretion
Fear Sleep Tired Dehydration
Nausea

• Secretion rate depends entirely on neural control
  
• both parasympathetic (Ach, M receptor) (water
  secretion)
• and sympathetic (NA, ß receptor) (enzyme)
• lead to increased secretion

PNS(IP3)
SNS (cAMP)
Secretion Vasodilation Cell contraction Metabolism
8
II. Gastric secretion
9
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)

10
Oesophagus
Lower Oesophageal Sphincter
Fundus
Duodenum
Pylorus
Body
Antrum
11
Functional Anatomy of Stomach
Oesophagus
Fundus
Lower Oesophageal
Sphincter
Fundus

• Storage

Body

• Storage
• Mucus
• HCl
• Pepsinogen
• Intrinsic factor

Duodenum
Pylorus
Body
Antrum
Antrum

• Mixing/Grinding
• Gastrin

12
II.1 Gastric gland cells

• 1. Oxyntic gland (???)
• Parietal cell
• Chief cell
• Mucous neck cell
• 2. Pyloric gland
• Mucus cell
• 3. Cardiac gland
• Mucus cell
• 4. Endocrine cells (G, D, ECL)
• ECLenterochromaffin-like cell

13
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.
14
Structure of Stomach Wall
15
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 small
  intestine

16
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

17
HCl secretion
????
??
18
HCl secretion
19
HCl secretion
20
pHlt2
Stomach Lumen
Carbonic Anhydrase
CO2 H2O
CO2
pHgt7.4
Blood
21
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 lt 3.5
Cells
22

• Physical/chemical barrier to attack by gastric
  juice
• Stimulated by
• Ach
• Mechanical Stim
• Chemicals (ethanol)
• If breached e.g. hypersecretion of acid -
  ulceration

23
Gastric Mucus-Bicarbonate Barrier
24

• 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,

25
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
26
II.3 Regulation of Secretion
27
Control of Gastric Acid Secretion

• Gastric acid secretion is controlled by three
  mechanisms
• Neurocrine (vagus/local reflexes)
• Endocrine (gastrin)
• Paracrine (histamine)

28
Endocrine gland cells of gastric pits
Stimulates acid secretion

• Inhibits
• acid secretion
• gastrin and pepsin release
• pancreatic exocrine secretions

Stimulates acid secretion
29
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.As
• Stimulates G-cells

• Acids
• Stimulate D cells

30
Endogenous substances regulating gastric secretion
????
31
GASTRIN
ACETYLCHOLINE
HISTAMINE
H

K
32
Gastric secretion during digesting food
33
Mechanisms Stimulating Gastric Acid Secretion in
Cephasic Phase
Cephalic Phase
GRP
34
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

35

• 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

36
Gastric Phase
Distension of stomach (arrival of food)
Peptides in lumen
Gastrin/ACh
37

• 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)

38

• 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

39

• 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

40

• 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

41
Regulation of Gastric Secretions occurs via 3
phases
42
Mechanisms Inhibiting Gastric Acid Secretion
Cephalic Phase
Gastric Phase
Intestinal Phase
Acid in duodenum
Fat in duodenum
43
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)

44
Regulation of gastric secretion
Mechanical stimulation Entero-oxyntin
Hyperosmotic solution
Fatty acids
HCl
Secretion of Ach or other transmitters by nerve
endings
D
Gastric gland
45
III. Secretion of the pancreas
46
Secretion of the pancreas
Endocrine - insulin glucagon Exocrine - enzymes
and bicarbonate essential for digestion almost
under separate hormonal control
47
Gall bladder
Sphincter of Oddi
48
Anatomy and secretion
49
Islet of Langerhans (secrete insulin)
Acinus
Capillary
Acinar cells (secrete enzymes)
Intercalated duct
Duct cells (secrete HCO3)
To pancreatic duct
50
Exocrine Pancreas
Responsible for digestive function of pancreas

• Function
• Secretion of bicarbonate by duct cells
• Secretion of digestive enzymes by acinar cells

51
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

52
Categories of Pancreatic Enzymes
Proteases Nucleases Elastases Phospholipases Lipas
es Amylase
Cleave peptide bonds Hydrolyze DNA/RNA Collagen
digestion Phospholipids to fatty
acids Triglycerides to fatty acids
glycerol Starch to maltose glucose
53
Activation of pancreatic proteases
54
Bicarbonate secretion
Blood
Lumen
H2O
55
Bicarbonate function
Function 1. Neutralize gastric acid
emptied into the duodenum 2. Provide a
favorable alkaline environment for optimal
activity of pancreatic enzymes
56
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

57
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
58
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
59
Cholecystokinin
stomach
duodenum
I cells
Peptides Amino acids, Fatty Acid H
Vagus afferent nerve vagovagal reflex
CCK release peptide
Fat
pancreas
5-HT
Enzymes
60
Secretin
H
Fat
Peptides
S cells
61
Control of Pancreatic Function
62
Intestinal phase of secretion
Peptides Amino acids Fat, H
63
IV Biliary secretion

64
Structure/Function of Liver
Liver lobule
Central vein
Bile canaliculus
Hepatic artery
Hepatic portal vein
Portal triad
65
(No Transcript)
66
Secretion and storage of bile
Constituents of bile Liver
Gallbladder Water 98 92 Bile
salts 1 6 Bilirubin(???) 0.04 0.3 Chole
sterol(???) 0.1 0.3-0.9 Fatty
acids 0.12 0.3-1.2 Lecithin(???) 0.04 0.
3 Na, K, Ca, Cl, HCO3
67
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,???)

68
(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.
69
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 re-aggregation.
emulsification
70
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.
71
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.)

72
In fasting state Bile stored in gall bladder
concentrated
Liver
Sphincter of Oddi (closed)
73
Digestion - fat in duodenum stimulates CCK
release from I cells
FAT
CCK
74
The enterohepatic circulation
Liver - secretion
Portal vein
Gallbladder-storage concentration
Common bile duct
Duodenum-digestion emulsification
Ileum - absorption of bile acids
75
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.
76
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

77
Small Intestine secretion

78
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 )
79
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